Ferguson et al., 2019
Ferguson, K. K., Rosario, Z., McElrath, T. F., Velez Vega, C., Cordero, J. F., Alshawabkeh, A., & Meeker, J. D.; “Demographic risk factors for adverse birth outcomes in Puerto Rico in the PROTECT cohort;” Plos One, 2019, 14(6), e0217770; DOI: 10.1371/journal.pone.0217770.
ABSTRACT:
Preterm birth is a major public health problem, especially in Puerto Rico where the rates are among the highest observed worldwide, reaching 18% in 2011. The Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) study is an ongoing investigation of environmental factors that contribute to this condition. In the present analysis, we sought to examine common risk factors for preterm birth and other adverse birth outcomes which have not been characterized previously in this unique population. Pregnant women from the PROTECT cohort are recruited from the heavily contaminated Northern coast of the island of Puerto Rico and are free of pre-existing conditions like diabetes. We examined associations between basic demographic, behavioral (e.g., tobacco and alcohol use), and pregnancy (e.g., season and year of delivery) characteristics as well as municipality of residence in relation to preterm birth (<37 weeks gestation), postterm birth (>/=41 weeks gestation), and small and large for gestational age in univariate and multivariate logistic regression models. Between 2011 and 2017, 1028 live singleton births were delivered as part of the PROTECT cohort. Of these, 107 (10%) were preterm. Preterm birth rates were higher among women with low socioeconomic status, as indicated by education level and income, and among women with high pre-pregnancy body mass index (BMI). Odds ratios of small for gestational age delivery were higher for women who reported tobacco use in pregnancy and lower for women who delivered in the hurricane and dengue season (July-October). Overall, in pregnant women residing in Puerto Rico, socioeconomic status was associated with preterm birth but few other factors were associated with this or other adverse outcomes of pregnancy. Research to understand environmental factors that could be contributing to the preterm birth epidemic in Puerto Rico is necessary. FULL TEXT
Silver et al., 2021
Silver, M. K., Fernandez, J., Tang, J., McDade, A., Sabino, J., Rosario, Z., Velez Vega, C., Alshawabkeh, A., Cordero, J. F., & Meeker, J. D.; “Prenatal Exposure to Glyphosate and Its Environmental Degradate, Aminomethylphosphonic Acid (AMPA), and Preterm Birth: A Nested Case-Control Study in the PROTECT Cohort (Puerto Rico);” Environmental Health Perspectives, 2021, 129(5), 57011; DOI: 10.1289/EHP7295.
ABSTRACT:
BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide in the world. Despite nearly ubiquitous exposure, few studies have examined prenatal GLY exposure and potentially adverse pregnancy outcomes. Preterm birth (PTB) is a risk factor for neonatal mortality and adverse health effects in childhood.
OBJECTIVES: We examined prenatal exposure to GLY and a highly persistent environmental degradate of GLY, aminomethylphosphonic acid (AMPA), and odds of PTB in a nested case-control study within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort in northern Puerto Rico.
METHODS: GLY and AMPA in urine samples collected at 18+/-2 (Visit 1) and 26+/-2 (Visit 3) wk gestation (53 cases/194 randomly selected controls) were measured using gas chromatography tandem mass spectrometry. Multivariable logistic regression was used to estimate associations with PTB (delivery <37wk completed gestation).
RESULTS: Detection rates in controls were 77.4% and 77.5% for GLY and 52.8% and 47.7% for AMPA, and geometric means (geometric standard deviations) were 0.44 (2.50) and 0.41 (2.56) mug/L for GLY and 0.25 (3.06) and 0.20 (2.87) mug/L for AMPA, for Visits 1 and 3, respectively. PTB was significantly associated with specific gravity-corrected urinary GLY and AMPA at Visit 3, whereas associations with levels at Visit 1 and the Visits 1-3 average were largely null or inconsistent. Adjusted odds ratios (ORs) for an interquartile range increase in exposure at Visit 3 were 1.35 (95% CI: 0.99, 1.83) and 1.67 (95% CI: 1.26, 2.20) for GLY and AMPA, respectively. ORs for Visit 1 and the visit average were closer to the null.
DISCUSSION: Urine GLY and AMPA levels in samples collected near the 26th week of pregnancy were associated with increased odds of PTB in this modestly sized nested case-control study. Given the widespread use of GLY, multiple potential sources of AMPA, and AMPA’s persistence in the environment, as well as the potential for long-term adverse health effects in preterm infants, further investigation in other populations is warranted.
Kogevinas, 2021
Kogevinas, M.; “Glyphosate Exposure during Pregnancy and Preterm Birth (More Research Is Needed);” Environmental Health Perspectives, 2021, 129(5), 51301; DOI: 10.1289/EHP9428.
ABSTRACT:
Not Available
Ganesan and Keating, 2020
Ganesan, S., & Keating, A. F.; “Ovarian mitochondrial and oxidative stress proteins are altered by glyphosate exposure in mice;” Toxicology and Applied Pharmacology, 2020, 402, 115116; DOI: 10.1016/j.taap.2020.115116.
ABSTRACT:
Glyphosate (GLY) usage for weed control is extensive. To investigate ovarian impacts of chronic GLY exposure, female C57BL6 mice were orally administered saline as vehicle control (CT) or GLY at 0.25 (G0.25), 0.5 (G0.5), 1.0 (G1.0), 1.5 (G1.5), or 2 (G2.0) mg/kg for five days per wk. for 20 wks. Feed intake increased (P < .05) in G1.5 and G2.0 mice and body weight increased (P < .05) in G1.0 mice. There was no impact of GLY on estrous cyclicity, nor did GLY affect circulating levels of 17beta-estradiol or progesterone. Exposure to GLY did not impact heart, liver, spleen, kidney or uterus weight. Both ovarian weight and follicle number were increased (P < .05) by G2.0 but not affected at lower GLY concentrations. There were no detectable effects of GLY on ovarian protein abundance of pAKT, AKT, pAKT:AKT, gammaH2AX, STAR, CYP11A1, HSD3B, CYP19A, ERA or ERB. Increased (P < .05) abundance of ATM protein was observed at G0.25 but not higher GLY doses. A dose-dependent effect (P < .10) of GLY exposure on ovarian protein abundance as quantified by LC-MS/MS was observed (G0.25-4 increased, 19 decreased; G0.5-5 increased, 25 decreased; G1.0-65 increased, 7 decreased; G1.5-145 increased, 2 decreased; G2.0-159 increased, 4 decreased). Pathway analysis was performed using DAVID and identified glutathione metabolism, metabolic and proteasome pathways as GLY exposure targets. These data indicate that chronic low-level exposure to GLY alters the ovarian proteome and may ultimately impact ovarian function. FULL TEXT
Franke et al., 2021
Franke, Adrian A., Li, Xingnan, Shvetsov, Yurii B., & Lai, Jennifer F.; “Pilot study on the urinary excretion of the glyphosate metabolite aminomethylphosphonic acid and breast cancer risk: The Multiethnic Cohort study;” Environmental Pollution, 2021, 277, 116848; DOI: https://doi.org/10.1016/j.envpol.2021.116848.
ABSTRACT:
Breast cancer is the most commonly diagnosed female cancer and the second leading cause of death in women in the US, including Hawaii. Accumulating evidence suggests that aminomethylphosphonic acid (AMPA), the primary metabolite of the herbicide glyphosate—a probable human carcinogen, may itself be carcinogenic. However, the relationship between urinary AMPA excretion and breast cancer risk in women is unknown. In this pilot study, we investigated the association between pre-diagnostic urinary AMPA excretion and breast cancer risk in a case-control study of 250 predominantly postmenopausal women: 124 cases and 126 healthy controls (individually matched on age, race/ethnicity, urine type, date of urine collection, and fasting status) nested within the Hawaii biospecimen subcohort of the Multiethnic Cohort. AMPA was detected in 90% of cases and 84% of controls. The geometric mean of urinary AMPA excretion was nearly 38% higher among cases vs. controls (0.087 vs 0.063 ng AMPA/mg creatinine) after adjusting for race/ethnicity, age and BMI. A 4.5-fold higher risk of developing breast cancer in the highest vs. lowest quintile of AMPA excretion was observed (ORQ5 vs. Q1: 4.49; 95% CI: 1.46–13.77; ptrend = 0.029). To our knowledge, this is the first study to prospectively examine associations between urinary AMPA excretion and breast cancer risk. Our preliminary findings suggest that AMPA exposure may be associated with increased breast cancer risk; however, these results require confirmation in a larger population to increase study power and permit careful examinations of race/ethnicity differences.
Coullery et al., 2020
Coullery, R., Pacchioni, A. M., & Rosso, S. B.; “Exposure to glyphosate during pregnancy induces neurobehavioral alterations and downregulation of Wnt5a-CaMKII pathway;” Reproductive Toxicology, 2020, 96, 390-398; DOI: 10.1016/j.reprotox.2020.08.006.
ABSTRACT:
Glyphosate-based formulations are the most popular herbicide used around the world. These herbicides are widely applied in agriculture to control weeds on genetically modified crops. Although there is much evidence showing that glyphosate-based herbicides induce toxic effect on reproductive and hepatic systems, and also cause oxidative damage on cells, studies from recent years revealed that the nervous system may represent a key target for their toxicity. In the present work, we evaluated the effect of glyphosate (without adjuvants) in neonate rats after gestational exposure. Particularly, we examined whether glyphosate during gestation affected the nervous system function at early development. Pregnant Wistar rats were treated with 24 or 35mg/kg of pure glyphosate every 48h and neurobehavioral studies were performed. Our results indicated that gestational exposure to glyphosate induced changes in reflexes development, motor activity and cognitive function, in a dose-dependent manner. To go further, we evaluated whether prenatal exposure to glyphosate affected the Ca(+2)-mediated Wnt non-canonical signaling pathway. Results indicated that embryos exposed to glyphosate showed an inhibition of Wnt5a-CaMKII signaling pathway, an essential cascade controlling the formation and integration of neural circuits. Taken together, these findings suggest that gestational exposure to glyphosate leads to a downregulation of Wnt/Ca(+2) pathway that could induce a developmental neurotoxicity evidenced by deficits at behavioral and cognitive levels in rat pups. FULL TEXT
Toda et al., 2021
Toda, Mitsuru, Beer, Karlyn D., Kuivila, Kathryn M., Chiller, Tom M., & Jackson, Brendan R.; “Trends in Agricultural Triazole Fungicide Use in the United States, 1992–2016 and Possible Implications for Antifungal-Resistant Fungi in Human Disease;” Environmental Health Perspectives, 2021, 129(5); DOI: 10.1289/ehp7484.
ABSTRACT:
BACKGROUND: The fungus Aspergillus fumigatus (A. fumigatus) is the leading cause of invasive mold infections, which cause severe disease and death in immunocompromised people. Use of triazole antifungal medications in recent decades has improved patient survival; however, triazole-resistant infections have become common in parts of Europe and are emerging in the United States. Triazoles are also a class of fungicides used in plant agriculture, and certain triazole-resistant A. fumigatus strains found causing disease in humans have been linked to environmental fungicide use.
OBJECTIVES: We examined U.S. temporal and geographic trends in the use of triazole fungicides using U.S. Geological Survey agricultural pesticide use estimates.
DISCUSSION: Based on our analysis, overall tonnage of triazole fungicide use nationwide was relatively constant during 1992–2005 but increased >4-fold during 2006–2016 to 2:9 million kg in 2016. During 1992–2005, triazole fungicide use occurred mostly in orchards and grapes, wheat, and other crops, but recent increases in use have occurred primarily in wheat, corn, soybeans, and other crops, particularly in Midwest and Southeast states. We conclude that, given the chemical similarities between triazole fungicides and triazole antifungal drugs used in human medicine, increased monitoring for environmental and clinical triazole resistance in A. fumigatus would improve overall understanding of these interactions, as well as help identify strategies to mitigate development and spread of resistance. FULL TEXT
Mesnage et al., 2021B
Mesnage, R., Teixeira, M., Mandrioli, D., Falcioni, L., Ibragim, M., Ducarmon, Q. R., Zwittink, R. D., Amiel, C., Panoff, J. M., Bourne, E., Savage, E., Mein, C. A., Belpoggi, F., & Antoniou, M. N.; “Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats;” Communications Biology, 2021, 4(1), 471; DOI: 10.1038/s42003-021-01990-w.
ABSTRACT:
Health effects of pesticides are not always accurately detected using the current battery of regulatory toxicity tests. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in a subchronic toxicity test of a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole) in Sprague-Dawley rats. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little effect. Contrastingly, serum and caecum metabolomics revealed that nicotinamide and tryptophan metabolism were affected, which suggested activation of an oxidative stress response. This was not reflected by gut microbial community composition changes evaluated by shotgun metagenomics. Transcriptomics of the liver showed that 257 genes had their expression changed. Gene functions affected included the regulation of response to steroid hormones and the activation of stress response pathways. Genome-wide DNA methylation analysis of the same liver samples showed that 4,255 CpG sites were differentially methylated. Overall, we demonstrated that in-depth molecular profiling in laboratory animals exposed to low concentrations of pesticides allows the detection of metabolic perturbations that would remain undetected by standard regulatory biochemical measures and which could thus improve the predictability of health risks from exposure to chemical pollutants. FULL TEXT
Alavanja et al., 2004
Alavanja, M. C., Hoppin, J. A., & Kamel, F.; “Health effects of chronic pesticide exposure: cancer and neurotoxicity;” Annual review of public health, 2004, 25, 155-197; DOI: 10.1146/annurev.publhealth.25.101802.123020.
ABSTRACT:
Pesticides are widely used in agricultural and other settings, resulting in continuing human exposure. Epidemiologic studies indicate that, despite premarket animal testing, current exposures are associated with risks to human health. In this review, we describe the routes of pesticide exposures occurring today, and summarize and evaluate the epidemiologic studies of pesticide-related carcinogenicity and neurotoxicity in adults. Better understanding of the patterns of exposure, the underlying variability within the human population, and the links between the animal toxicology data and human health effects will improve the evaluation of the risks to human health posed by pesticides. Improving epidemiology studies and integrating this information with toxicology data will allow the human health risks of pesticide exposure to be more accurately judged by public health policy makers. FULL TEXT
Blair et al., 1985
Blair, A., Malker, H., Cantor, K. P., Burmeister, L., & Wiklund, K.; “Cancer among farmers. A review;” Scandinavian Journal of Work, Environment, & Health, 1985, 11(6), 397-407; DOI: 10.5271/sjweh.2208.
ABSTRACT:
During the performance of routine tasks farmers may come in contact with a variety of substances, including pesticides, solvents, oils and fuels, dusts, paints, welding fumes, zoonotic viruses, microbes, and fungi. Because some of these substances are known or suspected carcinogens, the epidemiologic literature regarding cancer risks concerning farmers has been reviewed. Farmers had consistent deficits for cancers of the colon, rectum, liver, and nose. The deficits for cancer of the lung and bladder were particularly striking, presumably due to less frequent use of tobacco among farmers than among people in many other occupational groups. Malignancies frequently showing excesses among farmers included Hodgkin’s disease, leukemia, non-Hodgkin’s lymphoma, multiple myeloma, and cancers of the lip, stomach, prostate, skin (nonmelanotic), brain, and connective tissues. The etiologic factors that may contribute to these excesses in the agricultural environment have not been identified. Detailed, analytic epidemiologic studies that incorporate environmental and biochemical monitoring are needed to clarify these associations. FULL TEXT