Andreotti et al., 2015
Andreotti, G., Hoppin, J. A., Hou, L., Koutros, S., Gadalla, S. M., Savage, S. A., Lubin, J., Blair, A., Hoxha, M., Baccarelli, A., Sandler, D., Alavanja, M., & Beane Freeman, L. E.; “Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health Study;” Plos One, 2015, 10(7), e0133382; DOI: 10.1371/journal.pone.0133382.
ABSTRACT:
Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected between 2006 and 2008. Self-reported information, including pesticide use, was collected at three time points: enrollment (1993-1997) and two follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated cumulative use (using data from all three questionnaires), and more recent use (using data from the last follow-up questionnaire). Multivariable linear regression was used to examine the associations between pesticide use (ever, lifetime days, intensity-weighted lifetime days (lifetime days*intensity score)) and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57 pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p-trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were significantly associated with shorter RTL, while increasing lifetime days of alachlor was significantly associated with longer RTL (p-trend=0.03). Only the association with 2,4-D was significant after adjustment for multiple comparisons. Of the 40 pesticides evaluated for recent use, malathion was associated with shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest that leukocyte TL may be impacted by cumulative use and recent use of certain pesticides.
An et al., 2019
An, Xuehua, Liu, Xinju, Jiang, Jinhua, Lv, Lu, Wang, Feidi, Wu, Shenggan, & Zhao, Xueping; “Exposure risks to pesticide applicators posed by the use of electric backpack sprayers and stretcher-mounted sprayers in orchards;” Human and Ecological Risk Assessment: An International Journal, 2019, 26(8), 2288-2301; DOI: 10.1080/10807039.2019.1675493.
ABSTRACT:
he introduction of the pesticide registration system in pesticide risk assessments has promoted the scientific and safe use of pesticides, and the assessment of occupational exposure risk. In the present study, we performed an experiment in a citrus orchard subject to normal orchard management practices. By measuring the exposure of applicators’ (farmers and technicians) body parts to 45% malathion emulsifiable concentrate during its application using electric backpack sprayers (0.25KPa) and stretcher-mounted sprayers (1.5 KPa), the unit exposure (UE) was determined. The risks of exposure for pesticide applicators who adopted five different protective measures (A: no personal protective equipment (PPE), i.e., no clothes, no gloves, no caps, and no socks; B: short-sleeved top and shorts; C: short-sleeved top, shorts, and a single pair of gloves; D: short-sleeved top, shorts, a single pair of gloves, and a cap; E: long-sleeved top, long pants, a single pair of gloves, and a cap) were also assessed. The results were as follows: 1) The total levels of exposure for pesticide applicators using electric backpack sprayers and stretchermounted sprayers were 3613.63 mg and 5654.28mg, respectively. When electric backpack sprayers were used, the body parts that had the highest exposure were the head (13.8%), hands (19.9%) and back (14.0%), and when stretcher-mounted sprayers were used, the hands (32.5%) and lower legs (21.1%) had the highest level of exposure; 2) In the absence of PPE, the UE values for farmers who used electric backpack sprayers and farmers who used stretcher-mounted sprayers were significantly different. However, when PPE was used, the difference in UE values between the farmers using the two different types of sprayers was not significant; 3) When protective measure A was adopted, the risk quotient (RQ) values of the farmers and technicians who used electric backpack sprayers for the application of malathion were 1.44 and 0.54, respectively; the corresponding RQ values when protective measure B was adopted were 0.97 and 0.28, respectively. When stretcher-mounted sprayers were used for the application of chlorpyrifos, the RQ value of the farmers who adopted protective measure E was 0.43 while other types of PPE use resulted in RQ values greater than 1. In contrast, the RQ value for technicians was 1.62 when protective measure A was used and 1.02 when protective measure B was adopted, whereas other types of PPE use resulted in RQ values less than 1. Therefore, besides increasing the awareness of personal protection among pesticide applicators, improvement in the management of pesticide use and the enhancement of standard operations are of practical significance for controlling occupational exposure to pesticides.
Alexander et al., 2007
Alexander, B. H., Mandel, J. S., Baker, B. A., Burns, C. J., Bartels, M. J., Acquavella, J. F., & Gustin, C.; “Biomonitoring of 2,4-dichlorophenoxyacetic acid exposure and dose in farm families;” Environmental Health Perspectives, 2007, 115(3), 370-376; DOI: 10.1289/ehp.8869.
ABSTRACT:
OBJECTIVE: We estimated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure and systemic dose in farm family members following an application of 2,4-D on their farm.
METHODS: Farm families were recruited from licensed applicators in Minnesota and South Carolina. Eligible family members collected all urine during five 24-hr intervals, 1 day before through 3 days after an application of 2,4-D. Exposure profiles were characterized with 24-hr urine 2,4-D concentrations, which then were related to potential predictors of exposure. Systemic dose was estimated using the urine collections from the application day through the third day after application.
RESULTS: Median urine 2,4-D concentrations at baseline and day after application were 2.1 and 73.1 microg/L for applicators, below the limit of detection, and 1.2 microg/L for spouses, and 1.5 and 2.9 microg/L for children. The younger children (4-11 years of age) had higher median post-application concentrations than the older children (> or = 12 years of age) (6.5 vs. 1.9 microg/L). The geometric mean systemic doses (micrograms per kilogram body weight) were 2.46 (applicators), 0.8 (spouses), 0.22 (all children), 0.32 (children 4-11 years of age), and 0.12 (children > or = 12 years of age). Exposure to the spouses and children was primarily determined by direct contact with the application process and the number of acres treated. Multivariate models identified glove use, repairing equipment, and number of acres treated as predictors of exposure in the applicators.
CONCLUSIONS: We observed considerable heterogeneity of 2,4-D exposure among farm family members, primarily attributable to level of contact with the application process. Awareness of this variability and the actual magnitude of exposures are important for developing exposure and risk characterizations in 2,4-D-exposed agricultural populations.
Agency for Toxic Substances and Disease Registry, 2020b
Agency for Toxic Substances and Disease Registry, “Toxicological Profile for Glyphosate,” 2020.
Agency for Toxic Substances and Disease Registry, 2020
Agency for Toxic Substances and Disease Registry, “Toxicological Profile for 2,4-Dichlorophenoxyacetic Acid (2,4-D),” 2020.
Cosemans et al., 2021
Cosemans, C., Van Larebeke, N., Janssen, B. G., Martens, D. S., Baeyens, W., Bruckers, L., Den Hond, E., Coertjens, D., Nelen, V., Schoeters, G., Hoppe, H. W., Wolfs, E., Smeets, K., Nawrot, T. S., & Plusquin, M.; “Glyphosate and AMPA exposure in relation to markers of biological aging in an adult population-based study;” International Journal of Hygiene and Environmental Health, 2021, 240, 113895; DOI: 10.1016/j.ijheh.2021.113895.
ABSTRACT:
BACKGROUND/AIM: Glyphosate, a broad-spectrum herbicide, and its main metabolite aminomethylphosphonic acid (AMPA) are persistent in the environment. Studies showed associations between glyphosate or AMPA exposure and several adverse cellular processes, including metabolic alterations and oxidative stress.
OBJECTIVE: To determine the association between glyphosate and AMPA exposure and biomarkers of biological aging.
METHODS: We examined glyphosate and AMPA exposure, mtDNA content and leukocyte telomere length in 181 adults, included in the third cycle of the Flemish Environment and Health Study (FLEHSIII). DNA was isolated from leukocytes and the relative mtDNA content and telomere length were determined using qPCR. Urinary glyphosate and AMPA concentrations were measured by Gas Chromatography-Tandem Mass Spectrometry (GC-MS-MS). We used multiple linear regression models to associate mtDNA content and leukocyte telomere length with glyphosate or AMPA exposure while adjusting for confounding variables.
RESULTS: A doubling in urinary AMPA concentration was associated with 5.19% (95% CI: 0.oth49 to 10.11; p = 0.03) longer leukocyte telomere length, while no association was observed with urinary glyphosate concentration. No association between mtDNA content and urinary glyphosate nor AMPA levels was observed.
CONCLUSIONS: This study showed that AMPA exposure may be associated with telomere biology in adults.
Mesnage et al., 2021D
Robin Mesnage, Mariam Ibragim, Daniele Mandrioli, Laura Falcioni, Eva Tibaldi, Fiorella Belpoggi, Inger Brandsma, Emma Bourne, Emanuel Savage, Charles A Mein, Michael N Antoniou; “Comparative Toxicogenomics of Glyphosate and Roundup Herbicides by Mammalian Stem Cell-Based Genotoxicity Assays and Molecular Profiling in Sprague-Dawley Rats”, Toxicological Sciences, 2021; DOI: 10.1093/toxsci/kfab143.
ABSTRACT:
Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remain controversial. As GBHs are more cytotoxic than glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo. First, glyphosate was compared with representative GBHs, namely MON 52276 (European Union), MON 76473 (United Kingdom), and MON 76207 (United States) using the mammalian stem cell-based ToxTracker system. Here, MON 52276 and MON 76473, but not glyphosate and MON 76207, activated oxidative stress and unfolded protein responses. Second, molecular profiling of liver was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (at 0.5, 50, and 175 mg/kg bw/day glyphosate) for 90 days. MON 52276 but not glyphosate increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation by DNA damage and circadian rhythm regulation. Genes most affected in liver were similarly altered in kidneys. Small RNA profiling in liver showed decreased amounts of miR-22 and miR-17 from MON 52276 ingestion. Glyphosate decreased miR-30, whereas miR-10 levels were increased. DNA methylation profiling of liver revealed 5727 and 4496 differentially methylated CpG sites between the control and glyphosate and MON 52276 exposed animals, respectively. Apurinic/apyrimidinic DNA damage formation in liver was increased with glyphosate exposure. Altogether, our results show that Roundup formulations cause more biological changes linked with carcinogenesis than glyphosate. FULL TEXT
Rauh et al., 2012
Rauh, V. A., Perera, F. P., Horton, M. K., Whyatt, R. M., Bansal, R., Hao, X., Liu, J., Barr, D. B., Slotkin, T. A., & Peterson, B. S.; “Brain anomalies in children exposed prenatally to a common organophosphate pesticide;” Proceedings of the National Academy of Sciences, 2012, 109(20), 7871-7876; DOI: 10.1073/pnas.1203396109. https://www.ncbi.nlm.nih.gov/pubmed/22547821.
ABSTRACT:
Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9-11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure x IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose-response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain. FULL TEXT
Rauh et al., 2012
Rauh, V. A., Perera, F. P., Horton, M. K., Whyatt, R. M., Bansal, R., Hao, X., Liu, J., Barr, D. B., Slotkin, T. A., & Peterson, B. S.; “Brain anomalies in children exposed prenatally to a common organophosphate pesticide;” Proceedings of the National Academy of Sciences, 2012, 109(20), 7871-7876; DOI: 10.1073/pnas.1203396109. https://www.ncbi.nlm.nih.gov/pubmed/22547821.
ABSTRACT:
Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9-11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure x IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose-response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain. FULL TEXT
Rauh et al., 2011
Rauh, Virginia, Arunajadai, Srikesh, Horton, Megan, Perera, Frederica, Hoepner, Lori, Barr, Dana B, & Whyatt, Robin; “Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide;” Environmental Health Perspectives, 2011, 119(8), 1196-1201; DOI: 10.1289/ehp.1003160.
ABSTRACT:
BACKGROUND: In a longitudinal birth cohort study of inner-city mothers and children (Columbia Center for Children’s Environmental Health), we have previously reported that prenatal exposure to chlorpyrifos (CPF) was associated with neurodevelopmental problems at 3 years of age.
OBJECTIVE: The goal of the study was to estimate the relationship between prenatal CPF exposure and neurodevelopment among cohort children at 7 years of age.
METHODS: In a sample of 265 children, participants in a prospective study of air pollution, we measured prenatal CPF exposure using umbilical cord blood plasma (picograms/gram plasma) and 7-year neurodevelopment using the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Linear regression models were used to estimate associations, with covariate selection based on two alternate approaches.
RESULTS: On average, for each standard deviation increase in CPF exposure (4.61 pg/g), Full-Scale intelligence quotient (IQ) declined by 1.4% and Working Memory declined by 2.8%. Final covariates included maternal educational level, maternal IQ, and quality of the home environment. We found no significant interactions between CPF and any covariates, including the other chemical exposures measured during the prenatal period (environmental tobacco smoke and polycyclic aromatic hydrocarbons).
CONCLUSIONS: We report evidence of deficits in Working Memory Index and Full-Scale IQ as a function of prenatal CPF exposure at 7 years of age. These findings are important in light of continued widespread use of CPF in agricultural settings and possible longer-term educational implications of early cognitive deficits.