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Bibliography Index

Kubsad et al., 2019

Kubsad, D., Nilsson, E. E., King, S. E., Sadler-Riggleman, I., Beck, D., & Skinner, M. K.; “Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology;” Scientific Reports, 2019, 9(1), 6372; DOI: 10.1038/s41598-019-42860-0.

ABSTRACT:

Ancestral environmental exposures to a variety of factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. One of the most widely used agricultural pesticides worldwide is the herbicide glyphosate (N-(phosphonomethyl)glycine), commonly known as Roundup. There are an increasing number of conflicting reports regarding the direct exposure toxicity (risk) of glyphosate, but no rigorous investigations on the generational actions. The current study using a transient exposure of gestating F0 generation female rats found negligible impacts of glyphosate on the directly exposed F0 generation, or F1 generation offspring pathology. In contrast, dramatic increases in pathologies in the F2 generation grand-offspring, and F3 transgenerational great-grand-offspring were observed. The transgenerational pathologies observed include prostate disease, obesity, kidney disease, ovarian disease, and parturition (birth) abnormalities. Epigenetic analysis of the F1, F2 and F3 generation sperm identified differential DNA methylation regions (DMRs). A number of DMR associated genes were identified and previously shown to be involved in pathologies. Therefore, we propose glyphosate can induce the transgenerational inheritance of disease and germline (e.g. sperm) epimutations. Observations suggest the generational toxicology of glyphosate needs to be considered in the disease etiology of future generations. FULL TEXT

Ford and Schust, 2009

Ford, Holly B., & Schust, Danny J.; “Recurrent pregnancy loss: etiology, diagnosis, and therapy;” Reviews in Obstetrics & Gynecology, 2009, 2(2), 76-83.

ABSTRACT:

Spontaneous pregnancy loss is a surprisingly common occurrence, with approximately 15% of all clinically recognized pregnancies resulting in pregnancy failure. Recurrent pregnancy loss (RPL) has been inconsistently defined. When defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period, it affects approximately 1% to 2% of women. This review highlights the current understanding of the various etiologies implicated in RPL, including factors known to be causative, as well as those implicated as possible causative agents. The appropriate diagnostic evaluation, therapy, and prognosis are also addressed. FULL TEXT

Sacala & Roszak, 2019

Sacała, Elżbieta, & Roszak, Michał, “Mitigation of glyphosate-based herbicide toxicity in maize (Zea mays L.) seedlings by ascorbic acid,” Toxicological & Environmental Chemistry, 2019, 100(5-7), 550-559. DOI: 10.1080/02772248.2019.1567731.

ABSTRACT:

The toxicity of glyphosate at 3.6 mg L−1 to maize seedlings raised from un-treated seeds and the effectiveness of seed pretreatment by soaking in 0.25 mmol L−1 ascorbic acid (AsA) solution for mitigation of toxicity were evaluated in hydroponic culture. Glyphosate dramatically reduced the growth of roots and photosynthetic pigments in the leaves but increased protein content in the leaves. Superoxide dismutase activity and AsA concentration in the roots were increased, and guaiacol peroxidase (GPOX) activity was unaffected. Pretreatment with AsA improved the dry mass of the roots and shoots, increased the protein content in roots and leaves, and significantly decreased the activity of GPOX in roots. The positive effect of AsA treatment was not associated with more efficient functioning of the antioxidative system. FULL TEXT

Winchester et al., 2019

Winchester, Paul, Reiter, Jill L., Proctor, Cathy, Gerona, Roy R., Avery, Kayleigh D., Bromm, Jennifer R., Elsahy, Deena A, Hadley, Emily A., McGraw, Sara N., & Jones, Dana D., “Glyphosate in 1st Trimester of Pregnancy: Herbicides in the Womb,” 2019, Presented at the Pediatric Academic Societies (PAS) Meeting 2019, 4/24-5/1/2019, Baltimore, MD.

ABSTRACT:

BACKGROUND: Our previous study demonstrated that >90% of pregnant Midwest women had detectable glyphosate (GLY) in their urine. Most glyphosate exposure occurs through food & certain beverages but not through drinking water. Shorter pregnancies, rural address and caffeinated beverages were associated with higher GLY levels. The cohort was small and predominantly Caucasian. The current study was needed to confirm high rates of GLY detection in a racially more diverse high risk population.
OBJECTIVE: Will GLY be detected in a majority of pregnancies regardless of race/ethnicity? Are GLY levels associated with adverse pregnancy outcomes? Do GLY levels vary by season of collection in pregnancy?
DESIGN/METHODS: Prospective observation study. Discarded urine from 1st trimester pregnancies were collected prospectively from a high risk University obstetrical clinic. All pregnancy outcomes and neonatal outcomes were abstracted. Urines were frozen, shipped to analytical lab (USCF, RG) for analysis. Urine GLY (Glyphosate (N(phosphomethyl) glycine) was analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS), limit of quantification of 0.1 ng/mL. GLY measured as independent variable was compared to multiple variables using bivariate analysis.
RESULTS: GLY was detected in 99% (186 of 187) pregnancies. Levels varied from 1.004 to 10.31ng/mL with geometric mean 3.264ng/mL. Mean maternal age was 30, with 69% white, 4.2% Hispanic, 12% Black, 3.7% Asian and one “other”. GLY levels did not differ significantly by racial/ethnic group. GLY levels were not significantly difference between preterm and term outcomes, multiple/singleton or between fetal loss and live births. GLY levels were higher with increasing gestation at enrollment with 4-8 weeks GLY 2.73 vs 9-13 weeks 3.51(p=.0098). Significantly higher GLY levels were found in April-July pregnancies vs other months(3.64 vs 3.07 p=.03). NICU admission rates were 85% for preterm and 35% for term. Birth defect rate was12% and 37% had intrauterine drug exposure or NAS. Preterm birth rate was 31%. CONCLUSIONS: Glyphosate was found in virtually all of these high risk pregnancies in the first trimester regardless of race/ethnicity, plurality, fetal loss or gestation at birth. GLY levels rose with increasing gestation in the first trimester suggesting that gestation at measurement impacts GLY levels. Dietary sources contribute to GLY but we did find April-July are associated with higher GLY levels than other months. The fetal epigenetic consequences of 1st trimester GLY exposure remains unknown. FULL TEXT

Presutti et al., 2016

Presutti, R., Harris, S. A., Kachuri, L., Spinelli, J. J., Pahwa, M., Blair, A., Zahm, S. H., Cantor, K. P., Weisenburger, D. D., Pahwa, P., McLaughlin, J. R., Dosman, J. A., & Freeman, L. B., “Pesticide exposures and the risk of multiple myeloma in men: An analysis of the North American Pooled Project,” International Journal of Cancer, 2016, 139(8), 1703-1714. DOI: 10.1002/ijc.30218.

ABSTRACT:

Multiple myeloma (MM) has been consistently linked with agricultural activities, including farming and pesticide exposures. Three case-control studies in the United States and Canada were pooled to create the North American Pooled Project (NAPP) to investigate associations between pesticide use and haematological cancer risk. This analysis used data from 547 MM cases and 2700 controls. Pesticide use was evaluated as follows: ever/never use; duration of use (years); and cumulative lifetime-days (LD) (days/year handled x years of use). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusted for age, province/state of residence, use of proxy respondents and selected medical conditions. Increased MM risk was observed for ever use of carbaryl (OR = 2.02, 95% CI = 1.28-3.21), captan (OR = 1.98, 95% CI = 1.04-3.77) and DDT (OR = 1.44, 95% CI = 1.05-1.97). Using the Canadian subset of NAPP data, we observed a more than threefold increase in MM risk (OR = 3.18, 95% CI = 1.40-7.23) for </=10 cumulative LD of carbaryl use. The association was attenuated but remained significant for >10 LD of carbaryl use (OR = 2.44; 95% CI = 1.05-5.64; ptrend = 0.01). For captan, </=17.5 LD of exposure was also associated with a more than threefold increase in risk (OR = 3.52, 95% CI = 1.32-9.34), but this association was attenuated in the highest exposure category of >17.5 LD (OR = 2.29, 95% CI = 0.81-6.43; ptrend = 0.01). An increasing trend (ptrend = 0.04) was observed for LD of DDT use (LD > 22; OR = 1.92, 95% CI = 0.95-3.88). In this large North American study of MM and pesticide use, we observed significant increases in MM risk for use of carbaryl, captan and DDT. FULL TEXT

Nordstrom et al., 1998

Nordstrom, M., Hardell, L., Magnuson, A., Hagberg, H., & Rask-Anderson, A., “Occupational exposures, animal exposure and smoking as risk factors for hairy cell leukaemia evaluated in a case-control study,” British Journal of Cancer, 1998, 77(11), 2048-2052.

ABSTRACT:

To evaluate occupational exposures as risk factors for hairy cell leukaemia (HCL), a population-based case-control study on 121 male HCL patients and 484 controls matched for age and sex was conducted. Elevated odds ratio (OR) was found for exposure to farm animals in general: OR 2.0, 95% confidence interval (Cl) 1.2-3.2. The ORs were elevated for exposure to cattle, horse, hog, poultry and sheep. Exposure to herbicides (OR 2.9, Cl 1.4-5.9), insecticides (OR 2.0, Cl 1.1-3.5), fungicides (OR 3.8, Cl 1.4-9.9) and impregnating agents (OR 2.4, Cl 1.3-4.6) also showed increased risk. Certain findings suggested that recall bias may have affected the results for farm animals, herbicides and insecticides. Exposure to organic solvents yielded elevated risk (OR 1.5, Cl 0.99-2.3), as did exposure to exhaust fumes (OR 2.1, Cl 1.3-3.3). In an additional multivariate model, the ORs remained elevated for all these exposures with the exception of insecticides. We found a reduced risk for smokers with OR 0.6 (Cl 0.4-1.1) because of an effect among non-farmers.  FULL TEXT

Lang and Nuevo-Chiquero, 2012

Lang, K., & Nuevo-Chiquero, A., “Trends in self-reported spontaneous abortions: 1970-2000,” Demography, 2012, 49(3), 989-1009. DOI: 10.1007/s13524-012-0113-0.

ABSTRACT:

Little is known about how the miscarriage rate has changed over the past few decades in the United States. Data from Cycles IV to VI of the National Survey of Family Growth (NSFG) were used to examine trends from 1970 to 2000. After accounting for abortion availability and the characteristics of pregnant women, the rate of reported miscarriages increased by about 1.0% per year. This upward trend is strongest in the first seven weeks and absent after 12 weeks of pregnancy. African American and Hispanic women report lower rates of early miscarriage than do whites. The probability of reporting a miscarriage rises by about 5% per year of completed schooling. The upward trend, especially in early miscarriages, suggests awareness of pregnancy rather than prenatal care to be a key factor in explaining the evolution of self-reported miscarriages. Any beneficial effects of prenatal care on early miscarriage are obscured by this factor. Differences in adoption of early-awareness technology, such as home pregnancy tests, should be taken into account when analyzing results from self-reports or clinical trials relying on awareness of pregnancy in its early weeks. FULL TEXT

Lamure et al., 2019

Lamure, S., Carles, C., Aquereburu, Q., Quittet, P., Tchernonog, E., Paul, F., Jourdan, E., Waultier, A., Defez, C., Belhadj, I., Sanhes, L., Burcheri, S., Donadio, D., Exbrayat, C., Saad, A., Labourey, J. L., Baldi, I., Cartron, G., & Fabbro-Peray, P., “Association of Occupational Pesticide Exposure With Immunochemotherapy Response and Survival Among Patients With Diffuse Large B-Cell Lymphoma,” JAMA Network Open, 2019, 2(4), e192093. DOI: 10.1001/ jamanetworkopen.2019.2093.

ABSTRACT:

IMPORTANCE: Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds might hinder chemotherapy efficiency in patients with lymphoma.

OBJECTIVE: To examine the association of occupational exposure to pesticides with immunochemotherapy response and survival among patients treated for diffuse large B-cell lymphoma.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed patients treated from July 1, 2010, to May 31, 2015, for diffuse large B-cell lymphoma, with a 2-year follow-up. The study took place at 6 university and nonuniversity hospitals in Languedoc-Roussillon, France. A total of 404 patients with newly diagnosed diffuse large B-cell lymphoma treated with anthracycline-based immunochemotherapy were included before the study began. Occupational history was reconstructed for 244 patients and analyzed with the PESTIPOP French job-exposure matrix to determine likelihood of occupational exposure to pesticides. Analysis of the data was performed from July 15, 2017, to July 15, 2018.

MAIN OUTCOMES AND MEASURES: Treatment failure (ie, partial response, stable disease, disease progression, or interruption for toxic effects) rate, 2-year event-free survival, and overall survival between exposed and nonexposed patients after adjustment for confounding factors.

RESULTS: A total of 244 patients (mean [SD] age, 61.3 [15.2] years; 153 [62.7%] male) had complete occupational data. Of these patients, 67 (27.4%) had occupational exposure to pesticides, with 38 exposed through agricultural occupations. Occupational exposure was not associated with clinical and biological characteristics at diagnosis. Occupationally exposed patients had a significantly higher treatment failure rate (22.4% vs 11.3%; P = .03; adjusted odds ratio [AOR] for confounding factors, 3.0; 95% CI, 1.3-6.9); this difference was higher among patients with exposing agricultural occupations compared with other patients (29.0% vs 11.7%; AOR, 5.1; 95% CI, 2.0-12.8). Two-year event-free survival was 70% in the occupationally exposed group vs 82% in the unexposed group (adjusted hazard ratio [AHR] for confounding factors, 2.2; 95% CI, 1.3-3.9). Among patients with exposing agricultural occupations compared with other patients, the difference was more pronounced (2-year event-free survival, 56% vs 83%; AHR, 3.5; 95% CI, 1.9-6.5). Similarly, 2-year overall survival was lower in the group of patients with exposing agricultural occupations compared with other patients (81% vs 92%; AHR, 3.9; 95% CI, 1.5-10.0).

CONCLUSIONS AND RELEVANCE: This retrospective study showed that agricultural occupational exposure to pesticides was associated with treatment failure, event-free survival, and overall survival among patients with diffuse large B-cell lymphoma. FULL TEXT

Karunanayake et al., 2008

Karunanayake, C. P., McDuffie, H. H., Dosman, J. A., Spinelli, J. J., & Pahwa, P., “Occupational exposures and non-Hodgkin’s lymphoma: Canadian case-control study,” Environ Health, 2008, 7, 44. DOI: 10.1186/1476-069X-7-44.

ABSTRACT:

BACKGROUND: The objective was to study the association between Non-Hodgkin’s Lymphoma (NHL) and occupational exposures related to long held occupations among males in six provinces of Canada.

METHODS: A population based case-control study was conducted from 1991 to 1994. Males with newly diagnosed NHL (ICD-10) were stratified by province of residence and age group. A total of 513 incident cases and 1506 population based controls were included in the analysis. Conditional logistic regression was conducted to fit statistical models.

RESULTS: Based on conditional logistic regression modeling, the following factors independently increased the risk of NHL: farmer and machinist as long held occupations; constant exposure to diesel exhaust fumes; constant exposure to ionizing radiation (radium); and personal history of another cancer. Men who had worked for 20 years or more as farmer and machinist were the most likely to develop NHL.

CONCLUSION: An increased risk of developing NHL is associated with the following: long held occupations of faer and machinist; exposure to diesel fumes; and exposure to ionizing radiation (radium). The risk of NHL increased with the duration of employment as a farmer or machinist.

FULL TEXT

Jasper et al., 2012

Jasper, R., Locatelli, G. O., Pilati, C., & Locatelli, C., “Evaluation of biochemical, hematological and oxidative parameters in mice exposed to the herbicide glyphosate-Roundup(®),” Interdisciplinary Toxicology, 2012, 5(3), 133-140. DOI: 10.2478/v10102-012-0022-5.

ABSTRACT:

We evaluated the toxicity of hepatic, hematological, and oxidative effects of glyphosate-Roundup® on male and female albino Swiss mice. The animals were treated orally with either 50 or 500 mg/kg body weight of the herbicide, on a daily basis for a period of 15 days. Distilled water was used as control treatment. Samples of blood and hepatic tissue were collected at the end of the treatment. Hepatotoxicity was monitored by quantitative analysis of the serum enzymes ALT, AST, and γ-GT and renal toxicity by urea and creatinine. We also investigated liver tissues histopathologically. Alterations of hematological parameters were monitored by RBC, WBC, hemoglobin, hematocrit, MCV, MCH, and MCHC. TBARS (thiobarbituric acid reactive substances) and NPSH (non-protein thiols) were analyzed in the liver to assess oxidative damage. Significant increases in the levels of hepatic enzymes (ALT, AST, and γ-GT) were observed for both herbicide treatments, but no considerable differences were found by histological analysis. The hematological parameters showed significant alterations (500 mg/kg body weight) with reductions of RBC, hematocrit, and hemoglobin, together with a significant increase of MCV, in both sexes of mice. In males, there was an important increase in lipid peroxidation at both dosage levels, together with an NPSH decrease in the hepatic tissue, whereas in females significant changes in these parameters were observed only at the higher dose rate. The results of this study indicate that glyphosate-Roundup® can promote hematological and hepatic alterations, even at subacute exposure, which could be related to the induction of reactive oxygen species. FULL TEXT

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