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.
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.
Nishioka et al., 2001
Nishioka, M. G., Lewis, R. G., Brinkman, M. C., Burkholder, H. M., Hines, C. E., & Menkedick, J. R.; “Distribution of 2,4-D in air and on surfaces inside residences after lawn applications: comparing exposure estimates from various media for young children;” Environmental Health Perspectives, 2001, 109(11), 1185-1191; DOI: 10.1289/ehp.011091185.
ABSTRACT:
We collected indoor air, surface wipes (floors, table tops, and window sills), and floor dust samples at multiple locations within 11 occupied and two unoccupied homes both before and after lawn application of the herbicide 2,4-D. We measured residues 1 week before and after application. We used collected samples to determine transport routes of 2,4-D from the lawn into the homes, its subsequent distribution between the indoor surfaces, and air concentration as a function of airborne particle size. We used residue measurements to estimate potential exposures within these homes. After lawn application, 2,4-D was detected in indoor air and on all surfaces throughout all homes. Track-in by an active dog and by the homeowner applicator were the most significant factors for intrusion. Resuspension of floor dust was the major source of 2,4-D in indoor air, with highest levels of 2,4-D found in the particle size range of 2.5-10 microm. Resuspended floor dust was also a major source of 2,4-D on tables and window sills. Estimated post application indoor exposure levels for young children from nondietary ingestion may be 1-10 microg/day from contact with floors, and 0.2-30 microg/day from contact with table tops. These are estimated to be about 10 times higher than the preapplication exposures. By comparison, dietary ingestion of 2,4-D is approximately 1.3 microg/day. FULL TEXT