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
Ingaramo et al., 2016
Ingaramo, P. I., Varayoud, J., Milesi, M. M., Schimpf, M. G., Munoz-de-Toro, M., & Luque, E. H., “Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction,” Reproduction, 2016, 152(5), 403-415. DOI: 10.1530/REP-16-0171.
ABSTRACT:
In this study, we investigated whether neonatal exposure to a glyphosate-based herbicide (GBH) alters the reproductive performance and the molecular mechanisms involved in the decidualization process in adult rats. Newborn female rats received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate (i) the reproductive performance on gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology, endometrial cell proliferation, apoptosis and cell cycle regulators, and endocrine pathways that regulate uterine decidualization (steroid receptors/COUP-TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group showed a significant increase in the number of resorption sites on GD19, associated with an altered decidualization response. In fact, on GD9, the GBH-treated rats showed morphological changes at the IS, associated with a decreased expression of estrogen and progesterone receptors, a downregulation of COUP-TFII (Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss. FULL TEXT
Hernández-Plata et al., 2015
Hernández-Plata, Isela, Giordano, Magda, Díaz-Muñoz, Mauricio, & Rodríguez, Verónica M., “The herbicide glyphosate causes behavioral changes and alterations in dopaminergic markers in male Sprague-Dawley rat,” NeuroToxicology, 2015, 46, 79-91. DOI: 10.1016/j.neuro.2014.12.001.
ABSTRACT:
Glyphosate (Glyph) is the active ingredient of several herbicide formulations. Reports of Glyph exposure in humans and animal models suggest that it may be neurotoxic. To evaluate the effects of Glyph on the nervous system, male Sprague-Dawley rats were given six intraperitoneal injections of 50, 100, or 150mg Glyph/kg BW over 2 weeks (three injections/week). We assessed dopaminergic markers and their association with locomotor activity. Repeated exposure to Glyph caused hypoactivity immediately after each injection, and it was also apparent 2 days after the last injection in rats exposed to the highest dose. Glyph did not decrease monoamines, tyrosine hydroxylase (TH), or mesencephalic TH+ cells when measured 2 or 16 days after the last Glyph injection. In contrast, Glyph decreased specific binding to D1 dopamine (DA) receptors in the nucleus accumbens (NAcc) when measured 2 days after the last Glyph injection. Microdialysis experiments showed that a systemic injection of 150mg Glyph/kg BW decreased basal extracellular DA levels and high-potassium-induced DA release in striatum. Glyph did not affect the extracellular concentrations of 3,4-dihydroxyphenylacetic acid or homovanillic acid. These results indicate that repeated Glyph exposure results in hypoactivity accompanied by decreases in specific binding to D1-DA receptors in the NAcc, and that acute exposure to Glyph has evident effects on striatal DA levels. Additional experiments are necessary in order to unveil the specific targets of Glyph on dopaminergic system, and whether Glyph could be affecting other neurotransmitter systems involved in motor control.
Donahue et al., 2010
Donahue, S. M., Kleinman, K. P., Gillman, M. W., & Oken, E., “Trends in birth weight and gestational length among singleton term births in the United States: 1990-2005,” Obstetrics and Gynecology, 2010, 115(2 Pt 1), 357-364. DOI: 10.1097/AOG.0b013e3181cbd5f5.
ABSTRACT:
OBJECTIVE: To estimate changes over time in birth weight for gestational age and in gestational length among term singleton neonates born from 1990 to 2005.
METHODS: We used data from the U.S. National Center for Health Statistics for 36,827,828 singleton neonates born at 37-41 weeks of gestation, 1990-2005. We examined trends in birth weight, birth weight for gestational age, large and small for gestational age, and gestational length in the overall population and in a low-risk subgroup defined by maternal age, race or ethnicity, education, marital status, smoking, gestational weight gain, delivery route, and obstetric care characteristics.
RESULTS: In 2005, compared with 1990, we observed decreases in birth weight (-52 g in the overall population, -79 g in a homogenous low-risk subgroup) and large for gestational age birth (-1.4% overall, -2.2% in the homogenous subgroup) that were steeper after 1999 and persisted in regression analyses adjusted for maternal and neonate characteristics, gestational length, cesarean delivery, and induction of labor. Decreases in mean gestational length (-0.34 weeks overall) were similar regardless of route of delivery or induction of labor.
CONCLUSION: Recent decreases in fetal growth among U.S., term, singleton neonates were not explained by trends in maternal and neonatal characteristics, changes in obstetric practices, or concurrent decreases in gestational length.
LEVEL OF EVIDENCE: III.
ATSDR, 2019
Agency for Toxic Substances and Disease Registry, “Toxicological Profile for Glyphosate: Draft for Public Comment,” United States Department of Health and Human Services, 2019.
SUMMARY:
This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary.
The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for these toxic substances described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a substance’s toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced.
The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile begins with a relevance to public health discussion which would allow a public health professional to make a real-time determination of whether the presence of a particular substance in the environment poses a potential threat to human health. The adequacy of information to determine a substance’s health effects is described in a health effects summary. Data needs that are of significance to the protection of public health are identified by ATSDR and EPA.
Each profile includes the following:
(A) The examination, summary, and interpretation of available toxicologic information and epidemiologic evaluations on a toxic substance to ascertain the levels of significant human exposure for the substance and the associated acute, intermediate, and chronic health effects;
(B) A determination of whether adequate information on the health effects of each substance is available or in the process of development to determine the levels of exposure that present a significant risk to human health due to acute, intermediate, and chronic duration exposures; and
(C) Where appropriate, identification of toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans.
Chang et al., 2018
Chang, S., Nazem, T. G., Gounko, D., Lee, J., Bar-Chama, N., Shamonki, J. M., Antonelli, C., & Copperman, A. B., “Eleven year longitudinal study of U.S. sperm donors demonstrates declining sperm count and motility,” Fertility and Sterility, 2018, 110(4), e54-e55. DOI: 10.1016/j.fertnstert.2018.07.170.
ABSTRACT:
OBJECTIVE: Physicians and public health experts have been investigating whether there is evidence of deterioration in semen quality.1-3 Investigators who believe in a decline point to the concomitant increase in the incidence of genitourinary abnormalities.3-5 Others have focused on increased exposure to environmental endocrine disruptors and changes in diet and BMI. One obstacle to understanding male fertility is possible geographic variations in semen quality, which may be due to differences in climate, pollution, occupational exposure, lifestyle, and social habits. This study sought to evaluate semen quality in geographically diverse US sperm donors.
DESIGN: Retrospective.
MATERIALS AND METHODS: Semen analyses (SA) from 2007-2017 were examined. The sperm donors (ages 19-38) originated from Los Angeles, Palo Alto, Houston, Boston, Indianapolis and New York City. Total sperm count, average concentration and total motile count were analyzed as a whole and by region. Data was analyzed using a general estimate equation model with an exchangeable working correlation structure.
RESULTS: A total of 124,107 SA specimens were analyzed. Controlling for BMI, there was a decline in total sperm count (b¼-2.9, p<0.01), concentration (b¼-1.76, p<0.01) and total motile sperm count (b¼-2.45, p<0.01) over the 11-year study. There were decreases in SA parameters in all regions except New York City, which showed no change in total sperm count, concentration or total motile sperm count. Boston showed a decline in concentration and total motile sperm count but no difference in total sperm count.
CONCLUSIONS: Changes in our modern environment—chemical exposures or increasingly sedentary lifestyles—may negatively affect spermatogenesis. We demonstrated a time-related decline in semen quality. Given that donors have higher than average sperm counts, these trends would likely be magnified in the general population. If confirmed, these findings would serve as a public health warning, particularly with the simultaneous increase in other male disorders, including testicular cancer.5 The magnitude of semen quality decline varied by region, with only samples from New York City consistent throughout the study. To further investigate geographical differences, future prospective studies should investigate potential causes for this decline. Identifying modifiable risk factors is the first step in determining how to reverse these trend.
Cattani et al., 2017
Cattani, D., Cesconetto, P. A., Tavares, M. K., Parisotto, E. B., De Oliveira, P. A., Rieg, C. E. H., Leite, M. C., Prediger, R. D. S., Wendt, N. C., Razzera, G., Filho, D. W., & Zamoner, A., “Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: Implication of glutamate excitotoxicity and oxidative stress,” Toxicology, 2017, 387, 67-80. DOI: 10.1016/j.tox.2017.06.001.
ABSTRACT:
We have previously demonstrated that maternal exposure to glyphosate-based herbicide (GBH) leads to glutamate excitotoxicity in 15-day-old rat hippocampus. The present study was conducted in order to investigate the effects of subchronic exposure to GBH on some neurochemical and behavioral parameters in immature and adult offspring. Rats were exposed to 1% GBH in drinking water (corresponding to 0.36% of glyphosate) from gestational day 5 until postnatal day (PND)-15 or PND60. Results showed that GBH exposure during both prenatal and postnatal periods causes oxidative stress, affects cholinergic and glutamatergic neurotransmission in offspring hippocampus from immature and adult rats. The subchronic exposure to the pesticide decreased L-[(14)C]-glutamate uptake and increased (45)Ca(2+) influx in 60-day-old rat hippocampus, suggesting a persistent glutamate excitotoxicity from developmental period (PND15) to adulthood (PND60). Moreover, GBH exposure alters the serum levels of the astrocytic protein S100B. The effects of GBH exposure were associated with oxidative stress and depressive-like behavior in offspring on PND60, as demonstrated by the prolonged immobility time and decreased time of climbing observed in forced swimming test. The mechanisms underlying the GBH-induced neurotoxicity involve the NMDA receptor activation, impairment of cholinergic transmission, astrocyte dysfunction, ERK1/2 overactivation, decreased p65 NF-kappaB phosphorylation, which are associated with oxidative stress and glutamate excitotoxicity. These neurochemical events may contribute, at least in part, to the depressive-like behavior observed in adult offspring. FULL TEXT
Catov et al., 2016
Catov, J. M., Lee, M., Roberts, J. M., Xu, J., & Simhan, H. N., “Race Disparities and Decreasing Birth Weight: Are All Babies Getting Smaller?,” American Journal of Epidemiology, 2016, 183(1), 15-23. DOI: 10.1093/aje/kwv194.
ABSTRACT:
The mean infant birth weight in the United States increased for decades, but it might now be decreasing. Given race disparities in fetal growth, we explored race-specific trends in birth weight at Magee-Womens Hospital, Pittsburgh, Pennsylvania, from 1997 to 2011. Among singleton births delivered at 37-41 weeks (n = 70,607), we evaluated the proportions who were small for gestational age and large for gestational age and changes in mean birth weights over time. Results were stratified by maternal race/ethnicity. Since 1997, the number of infants born small for their gestational ages increased (8.7%-9.9%), whereas the number born large for their gestational ages decreased (8.9%-7.7%). After adjustment for gestational week at birth, maternal characteristics, and pregnancy conditions, birth weight decreased by 2.20 g per year (P < 0.0001). Decreases were greater for spontaneous births. Reductions were significantly greater in infants born to African-American women than in those born to white women (-3.78 vs. -1.88 per year; P for interaction = 0.010). Quantile regression models indicated that birth weight decreased across the entire distribution, but reductions among infants born to African-American women were limited to those in the upper quartile after accounting for maternal factors. Limiting the analysis to low-risk women eliminated birth weight reductions. Birth weight has decreased in recent years, and reductions were greater in infants born to African-American women. These trends might be explained by accumulation of risk factors such as hypertension and prepregnancy obesity that disproportionately affect African-American women. Our results raise the possibility of worsening race disparities in fetal growth. FULL TEXT
Cai et al., 2017
Cai, Wenyan, Ji, Ying, Song, Xianping, Guo, Haoran, Han, Lei, Zhang, Feng, Liu, Xin, Zhang, Hengdong, Zhu, Baoli, & Xu, Ming, “Effects of glyphosate exposure on sperm concentration in rodents: A systematic review and meta-analysis,” Environmental Toxicology and Pharmacology, 2017, 55, 148-155. DOI: 10.1016/j.etap.2017.07.015.
ABSTRACT:
BACKGROUND: Correlation between exposure to glyphosate and sperm concentrations is important in reproductive toxicity risk assessment for male reproductive functions. Many studies have focused on reproductive toxicity on glyphosate, however, results are still controversial. We conducted a systematic review of epidemiological studies on the association between glyphosate exposure and sperm concentrations of rodents. The aim of this study is to explore the potential adverse effects of glyphosate on reproductive function of male rodents.
METHODS: Systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Embase, WANFANG and CNKI databases with different combinations of glyphosate exposure and sperm concentration. 8 studies were eventually identified and random-effect model was conducted. Heterogeneity among study results was calculated via chi-square tests. Ten independent experimental datasets from these eight studies were acquired to synthesize the random-effect model.
RESULTS: A decrease in sperm concentrations was found with mean difference of sperm concentrations (MDsperm)=−2.774×106/sperm/g/testis(95%CI=−0.969 to −4.579) in random-effect model after glyphosate exposure. There was also a significant decrease after fitting the random-effect model: MDsperm=−1.632×106/sperm/g/testis (95%CI=−0.662 to −2.601).
CONCLUSIONS: The results of meta-analysis support the hypothesis that glyphosate exposure decreased sperm concentration in rodents. Therefore, we conclude that glyphosate is toxic to male rodent’s reproductive system. FULL TEXT
Beranger et al., 2018
Beranger, R., Hardy, E. M., Dexet, C., Guldner, L., Zaros, C., Nougadere, A., Metten, M. A., Chevrier, C., & Appenzeller, B. M. R., “Multiple pesticide analysis in hair samples of pregnant French women: Results from the ELFE national birth cohort,” Environment International, 2018, 120, 43-53. DOI: 10.1016/j.envint.2018.07.023.
ABSTRACT:
BACKGROUND: A growing body of evidence suggests that prenatal exposure to pesticides might impair fetal development. Nonetheless, knowledge about pesticide exposure of pregnant women, especially in Europe, is largely restricted to a limited panel of molecules.
AIM: To characterize the concentration of 140 pesticides and metabolites in hair strands from women in the ELFE French nationwide birth cohort.
METHODS: Among cohort members who gave birth in northeastern and southwestern France in 2011, we selected those with a sufficient available mass of hair (n=311). Bundles of hair 9cm long were collected at delivery. We screened 111 pesticides and 29 metabolites, including 112 selected a priori based on their reported usage or detection in the French environment. The bundles of hair from 47 women were split into three segments to explore the intraindividual variability of the exposure. Intraclass correlation coefficients (ICCs) were computed for the chemicals with a detection frequency >70%.
RESULTS: We detected a median of 43 chemicals per woman (IQR 38-47). Overall, 122 chemicals (>20 chemical families) were detected at least once, including 28 chemicals detected in 70-100% of hair samples. The highest median concentrations were observed for permethrin (median: 37.9pg/mg of hair), p-nitrophenol (13.2pg/mg), and pentachlorophenol (10.0pg/mg). The ICCs for the 28 chemicals studied ranged from 0.59 to 0.94.
CONCLUSION: Pregnant women are exposed to multiple pesticides simultaneously from various chemical families, including chemicals suspected to be reproductive toxicants or endocrine disruptors. The ICCs suggest that the intraindividual variability of pesticide concentrations in hair is lower than its interindividual variability. FULL TEXT