Rocheleau et al., 2015
Rocheleau CM, Bertke SJ, Lawson CC, Romitti PA, Sanderson WT, Malik S, Lupo PJ, Desrosiers TA, Bell E, Druschel C, Correa A, Reefhuis J, “Maternal occupational pesticide exposure and risk of congenital heart defects in the National Birth Defects Prevention Study,” Birth Defects Research Part A, Clinical and Molecular Teratololgy, 2015, 103:10, DOI: 10.1002/bdra.23351.
ABSTRACT:
BACKGROUND: Congenital heart defects (CHDs) are common birth defects, affecting approximately 1% of live births. Pesticide exposure has been suggested as an etiologic factor for CHDs, but previous results were inconsistent.
METHODS: We examined maternal occupational exposure to fungicides, insecticides, and herbicides for 3328 infants with CHDs and 2988 unaffected control infants of employed mothers using data for 1997 through 2002 births from the National Birth Defects Prevention Study, a population-based multisite case-control study. Potential pesticide exposure from 1 month before conception through the first trimester of pregnancy was assigned by an expert-guided task-exposure matrix and job history details self-reported by mothers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression.
RESULTS: Maternal occupational exposure to pesticides was not associated with CHDs overall. In examining specific CHD subtypes compared with controls, some novel associations were observed with higher estimated pesticide exposure: insecticides only and secundum atrial septal defect (OR = 1.8; 95% CI, 1.3-2.7, 40 exposed cases); both insecticides and herbicides and hypoplastic left heart syndrome (OR = 5.1; 95% CI, 1.7-15.3, 4 exposed cases), as well as pulmonary valve stenosis (OR = 3.6; 95% CI, 1.3-10.1, 5 exposed cases); and insecticides, herbicides, and fungicides and tetralogy of Fallot (TOF) (OR = 2.2; 95% CI, 1.2-4.0, 13 exposed cases).
CONCLUSION: Broad pesticide exposure categories were not associated with CHDs overall, but examining specific CHD subtypes revealed some increased odds ratios. These results highlight the importance of examining specific CHDs separately. Because of multiple comparisons, additional work is needed to verify these associations. FULL TEXT
Rissman and Adli, 2014
Rissman EF, Adli M, “Minireview: transgenerational epigenetic inheritance: focus on endocrine disrupting compounds,” Endocrinology, 2014, 155:8, DOI: 10.1210/en.2014-1123.
ABSTRACT: The idea that what we eat, feel, and experience influences our physical and mental state and can be transmitted to our offspring and even to subsequent generations has been in the popular realm for a long time. In addition to classic gene mutations, we now recognize that some mechanisms for inheritance do not require changes in DNA. The field of epigenetics has provided a new appreciation for the variety of ways biological traits can be transmitted to subsequent generations. Thus, transgenerational epigenetic inheritance has emerged as a new area of research. We have four goals for this minireview. First, we describe the topic and some of the nomenclature used in the literature. Second, we explain the major epigenetic mechanisms implicated in transgenerational inheritance. Next, we examine some of the best examples of transgenerational epigenetic inheritance, with an emphasis on those produced by exposing the parental generation to endocrine-disrupting compounds (EDCs). Finally, we discuss how whole-genome profiling approaches can be used to identify aberrant epigenomic features and gain insight into the mechanism of EDC-mediated transgenerational epigenetic inheritance. Our goal is to educate readers about the range of possible epigenetic mechanisms that exist and encourage researchers to think broadly and apply multiple genomic and epigenomic technologies to their work. FULL TEXT
Richard et al., 2005
Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE, “Differential effects of glyphosate and roundup on human placental cells and aromatase, ” Environmental Health Perspectives, 2005, 113:6.
ABSTRACT:
Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation. FULL TEXT
Rappazzo et al., 2016
Rappazzo KM, Warren JL, Meyer RE, Herring AH, Sanders AP, Brownstein NC, Luben TJ, “Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort,” Birth Defects Research Part A, Clinical and Molecular Teratolology, 2016, 106:4, DOI: 10.1002/bdra.23479.
ABSTRACT:
BACKGROUND: Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects.
METHODS: We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (<10(th) , 10-50(th) , 50-90(th) , and >90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status.
RESULTS: We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]).
CONCLUSION: Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes.
Omoike et al., 2015
Omoike OE, Lewis RC, Meeker JD, “Association between urinary biomarkers of exposure to organophosphate insecticides and serum reproductive hormones in men from NHANES 1999-2002,” Reproductive Toxicology, 2015, 53, DOI: 10.1016/j.reprotox.2015.04.005.
ABSTRACT: Exposure to organophosphate (OP) insecticides may alter reproductive hormone levels in men and increase the risk for poor reductive health and other adverse health outcomes. However, relevant epidemiology studies in men are limited. We evaluated urinary concentrations of OP metabolites (3,5,6-trichloro-2-pyridinol and six dialkyl phosphates) in relation to serum concentrations of testosterone (T) and estradiol among 356 men aged 20-55 years old from the U.S. National Health and Nutrition Examination Survey. Biomarkers were detected in greater than 50% of the samples, except for diethyldithiophosphate, dimethylphosphate, and dimethyldithiophosphate. In adjusted regression models, we observed a statistically significant inverse relationship between diethyl phosphate (DEP) and T when DEP was modeled as either a continuous or categorical variable. These findings add to the limited evidence that exposure to certain OP insecticides is linked to altered T in men, which may have important implications for male health. FULL TEXT
Nilsson et al., 2012
Nilsson E, Larsen G, Manikkam M, Guerrero-Bosagna C, Savenkova MI, Skinner MK, “Environmentally induced epigenetic transgenerational inheritance of ovarian disease,” PLoS ONE, 2012, 7:5, DOI: 10.1371/journal.pone.0036129.
ABSTRACT: The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology. FULL TEXT
Winchester et al., 2017
Winchester PD, Parvez S, Proctor C, Ying J, Gerona RR, “Fetal Exposure to Glyphosate,” Presentation, Pediatric Academic Societies, May 6-7, 2017, San Francisco, California.
SUMMARY:
Measured glyphosate in pregnant women to estimate fetal exposure and monitor potential adverse effects on pregnancy outcomes. Glyphosate was present in 91% of the urine samples and higher glyphosate levels were correlated with shorter pregnancies and lower birth weights. FULL TEXT
Roberts and Karr, 2012
Roberts JR, Karr CJ, “Pesticide exposure in children,” 2012, Pediatrics, 130:6.
ABSTRACT: This statement presents the position of the American Academy of Pediatrics on pesticides. Pesticides are a collective term for chemicals intended to kill unwanted insects, plants, molds, and rodents. Children encounter pesticides daily and have unique susceptibilities to their potential toxicity. Acute poisoning risks are clear, and understanding of chronic health implications from both acute and chronic exposure are emerging. Epidemiologic evidence demonstrates associations between early life exposure to pesticides and pediatric cancers, decreased cognitive function, and behavioral problems. Related animal toxicology studies provide supportive biological plausibility for these findings. Recognizing and reducing problematic exposures will require attention to current inadequacies in medical training, public health tracking, and regulatory action on pesticides. Ongoing research describing toxicologic vulnerabilities and exposure factors across the life span are needed to inform regulatory needs and appropriate interventions. Policies that promote integrated pest management, comprehensive pesticide labeling, and marketing practices that incorporate child health considerations will enhance safe use. FULL TEXT
Niemann et al., 2015
Niemann L, Sieke C, Pfeil R, Solecki R., “A critical review of glyphosate findings in human urine samples and comparison with the exposure of operators and consumers,” 2015, Journal of Consumer Protection and Food Safety, 10: 3-12, DOI: 10.1007/s00003-014-0927-3.
ABSTRACT: For active substances in plant protection products (PPP) with well defined urinary elimination, no potential for accumulation and virtually no metabolism, measuring of urine levels could be a powerful tool for human biomonitoring. Such data may provide reliable estimates of actual internal human exposure that can be compared to appropriate reference values, such as the ‘acceptable daily intake (ADI)’ or the ‘acceptable operator exposure level (AOEL)’. Traces of the active compound glyphosate were found in human urine samples, probably resulting either from occupational use for plant protection purposes or from dietary intake of residues. A critical review and comparison of data obtained in a total of seven studies from Europe and the US was performed. The conclusion can be drawn that no health concern was revealed because the resulting exposure estimates were by magnitudes lower than the ADI or the AOEL. The expected internal exposure was clearly below the worst-case predictions made in the evaluation of glyphosate as performed for the renewal of its approval within the European Union. However, differences in the extent of exposure with regard to the predominant occupational and dietary exposure routes and between Europe and North America became apparent. FULL TEXT
National Research Council, 1993
National Research Council, Committee on Pesticides in the Diets of Infants and Children, “Pesticides in the Diets of Infants and Children,” 1993, National Academies Press, Washington DC., DOI: 10.17226/2126. Available at: https://www.nap.edu/read/2126/chapter/1.