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Eskenazi et al., 2004

Brenda Eskenazi, Kim Harley, Asa Bradman, Erin Weltzien, Nicholas P. Jewell, Dana B. Barr, Clement E. Furlong, and Nina T. Holland, “Association of in Utero Organophosphate Pesticide Exposure and Fetal Growth and Length of Gestation in an Agricultural Population,” Environmental Health Perspecitives, 112:10, 2004, DOI: 10.1289/ehp.6789

ABSTRACT:

Although pesticide use is widespread, little is known about potential adverse health effects of in utero exposure. We investigated the effects of organophosphate pesticide exposure during pregnancy on fetal growth and gestational duration in a cohort of low-income, Latina women living in an agricultural community in the Salinas Valley, California. We measured nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4-nitrophenol) in maternal urine collected twice during pregnancy. We also measured levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in maternal and umbilical cord blood. We failed to demonstrate an adverse relationship between fetal growth and any measure of in utero organophosphate pesticide exposure. In fact, we found increases in body length and head circumference associated with some exposure measures.
However, we did find decreases in gestational duration associated with two measures of in utero pesticide exposure: urinary dimethyl phosphate metabolites [βadjusted = –0.41 weeks per log10 unit increase; 95% confidence interval (CI), –0.75––0.02; p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as malathion, and umbilical cord cholinesterase (βadjusted = 0.34 weeks per unit increase; 95% CI, 0.13–0.55; p = 0.001). Shortened gestational duration was most clearly related to increasing exposure levels in the latter part of pregnancy. These associations with gestational age may be biologically plausible given that organophosphate pesticides depress cholinesterase and acetylcholine stimulates contraction of the uterus. However, despite these observed associations, the rate of preterm delivery in this population (6.4%) was lower than in a U.S. reference population. FULL TEXT

Ranjbar et al., 2015

Mahsa Ranjbar, Michael A. Rotondi, Chris I. Ardern, and Jennifer L. Kuk, “The Influence of Urinary Concentrations of Organophosphate Metabolites on the Relationship between BMI and Cardiometabolic Health Risk,” Journal of Obesity, 2015, DOI: 10.1155/2015/687914

ABSTRACT:

The objective was to determine whether detectable levels of OP metabolites influence the relationship between BMI and cardiometabolic health. This cross-sectional study was conducted using 2227 adults from the 1999–2008 NHANES datasets. Urinary concentrations of six dialkyl phosphate metabolites were dichotomized to above and below the detection limit. Weighted multiple regression analysis was performed adjusting for confounding variables. Independent of BMI, individuals with detectable metabolites had higher diastolic blood pressure (for dimethylphosphate, diethylphosphate, and diethyldithiophosphate; ???? < 0.05), lower HDL (for diethyldithiophosphate; ???? = 0.02), and higher triglyceride (for dimethyldithiophosphate; ???? = 0.05) than those below detection. Contrarily, those with detectable dimethylthiophosphate had better LDL, HDL, and total cholesterol, independent of BMI. Individuals at a higher BMI range who had detectable diethylphosphate (interaction: ???? = 0.03) and diethylthiophosphate (interaction: ???? = 0.02) exhibited lower HDL, while little difference existed between OP metabolite detection statuses at lower BMIs. Similarly, individuals with high BMIs and detectable diethylphosphate had higher triglyceride than those without detectable levels, while minimal differences between diethylphosphate detection statuses were observed at lower BMIs (interaction: ???? = 0.02). Thus, cardiometabolic health outcome differs depending on the specific OP metabolite being examined, with higher BMIs amplifying health risk. FULL TEXT

Tsao et al., 2016

Yun-Chen Tsao, Yung-Chun Lai, Hsiu-Chuan Liu, Ray H. Liu, and Dong-Liang Lin, “Simultaneous Determination and Quantitation of Paraquat, Diquat, Glufosinate and Glyphosate,in Postmortem Blood and Urine by LC–MS-MS,” Journal of Analytical Toxicology, 40, 2016, DOI: 10.1093/jat/bkw042

ABSTRACT:

A simple method, incorporating protein-precipitation/organic backwashing and liquid chromatography–tandem mass spectrometry (LC–MS-MS), has been successfully developed for the simultaneous analysis of four highly water-soluble and less volatile herbicides (paraquat, diquat, glufosinate and glyphosate) in ante- and postmortem blood, urine and gastric content samples. Respective isotopically labeled analogs of these analytes were adopted as internal standards. Acetonitrile and dichloromethane were used for protein precipitation and organic solvent backwashing, respectively, followed by injecting the upper aqueous phase into the LC–MS-MS system. Chromatographic separation was achieved using an Agilent Zorbax SB-Aq analytical column, with gradient elution of 15 mM heptafluorobutyric acid and acetonitrile. Mass spectrometric analysis was performed under electrospray ionization in positive-ion multiple reaction
monitoring mode. The precursor ions and the two transition ions (m/z) adopted for each of these four analytes were paraquat (185; 169 and 115), diquat (183; 157 and 78), glufosinate (182; 136 and 119) and glyphosate (170; 88 and 60), respectively. Analyte-free blood and urine samples, fortified with the analytes of interest, were used for method development/validation and yielded acceptable recoveries of the analytes; interday and intraday precision and accuracy data; calibration linearity and limits of detection and quantitation. This method was successfully incorporated into an overall analytical scheme, designed for the analysis of a broad range of compounds present in postmortem samples, helpful to medical examiners’ efforts to determine victims’ causes of death. FULL TEXT

Brändli et al., 2012

Dirk Brändli and Sandra Reinacher, “Herbicides found in Human Urine,” Ithaka Journal, 1/2012, 2012

SUMMARY:

Glyphosate is the main active substance used in most commercial herbicides. It poisons not only plants, but also animals and humans. When testing for glyphosate contamination in an urban population, a German university found significant contamination in all urine samples with levels 5 to 20 times above the legal limit for drinking water. Glyphosate background info, health risks, and reasons for contamination are discussed. FULL TEXT

Curwin et al., 2007

Brian Curwin, Misty Hein, Wayne Sanderson, Cynthia Striley, Dick Heederik, Hans Kromhout, Stephen Reynolds, Michael Alavanja, “Urinary Pesticide Concentrations Among Children, Mothers and Fathers Living in Farm and Non-Farm Households in Iowa,” The Annals of Occupational Hygiene, 51:1, January 2007, DOI: 10.1093/annhyg/mel062

ABSTRACT:

In the spring and summer of 2001, 47 fathers, 48 mothers and 117 children of Iowa farm and non-farm households were recruited to participate in a study investigating take-home pesticide exposure. On two occasions ∼1 month apart, urine samples from each participant and dust samples from various rooms were collected from each household and were analyzed for atrazine, metolachlor, glyphosate and chlorpyrifos or their metabolites. The adjusted geometric mean (GM) level of the urine metabolite of atrazine was significantly higher in fathers, mothers and children from farm households compared with those from non-farm households (P ≤ 0.0001). Urine metabolites of chlorpyrifos were significantly higher in farm fathers (P = 0.02) and marginally higher in farm mothers (P = 0.05) when compared with non-farm fathers and mothers, but metolachlor and glyphosate levels were similar between the two groups. GM levels of the urinary metabolites for chlorpyrifos, metolachlor and glyphosate were not significantly different between farm children and non-farm children. Farm children had significantly higher urinary atrazine and chlorpyrifos levels (P = 0.03 and P = 0.03 respectively) when these pesticides were applied by their fathers prior to sample collection than those of farm children where these pesticides were not recently applied. Urinary metabolite concentration was positively associated with pesticide dust concentration in the homes for all pesticides except atrazine in farm mothers; however, the associations were generally not significant. There were generally good correlations for urinary metabolite levels among members of the same family. FULL TEXT

Rull et al., 2006

Rudolph P. Rull Beate Ritz Gary M. Shaw, “Neural Tube Defects and Maternal Residential Proximity to Agricultural Pesticide Applications,” American Journal of Epidemiology, 163:8, 15 April 2006, DOI: 10.1093/aje/kwj101

ABSTRACT:

Residential proximity to applications of agricultural pesticides may be an important source of exposure to agents that have been classified as developmental toxins. Data on two case-control study populations of infants with neural tube defects (NTDs) and nonmalformed controls delivered in California between 1987 and 1991 were pooled to investigate whether maternal residential proximity to applications of specific pesticides or physicochemical groups of pesticides during early gestation increases the risk of these malformations. Maternal residential proximity within 1,000 m of pesticide applications was ascertained by linking mothers’ addresses with agricultural pesticide use reports and crop maps. Odds ratios were computed by using conventional single- and multiplepesticide and hierarchical multiple-pesticide logistic regression. In single-pesticide models, several pesticides were associated with NTDs after adjustment for study population, maternal ethnicity, educational level, cigarette smoking, and vitamin use. In a hierarchical multiple-pesticide model, effect estimates for only benomyl and methomyl suggested a possible association. Elevated risks of NTDs and anencephaly or spina bifida subtypes were also associated with exposures to chemicals classified as amide, benzimidazole, methyl carbamate, or organophosphorus pesticides and with increasing numbers of pesticides. These results suggest that ambient exposure to certain categories of agricultural pesticides may increase the risk of NTDs. FULL TEXT

Bolognesi et al., 1997

Claudia Bolognesi, Stefania Bonatti, Paolo Degan, Elena Gallerani, Marco Peluso, Roberta Rabboni, Paola Roggieri, and Angelo Abbondandolo, “Genotoxic Activity of Glyphosate and Its Technical Formulation Roundup,” Journal of Agricultural and Food Chemistry, 45, 1997, DOI: 10.1021/jf9606518

ABSTRACT:

Glyphosate (N-phosphonomethylglycine) is an effective herbicide acting on the synthesis of aromatic amino acids in plants. The genotoxic potential of this herbicide has been studied: the results available in the open literature reveal a weak activity of the technical formulation. In this study, the formulated commercial product, Roundup, and its active agent, glyphosate, were tested in the same battery of assays for the induction of DNA damage and chromosomal effects in vivoand in vitro. Swiss CD1 mice were treated intraperitoneally with test substances, and the DNA damage was evaluated by alkaline elution technique and 8-hydroxydeoxyguanosine (8-OHdG) quantification in liver and kidney. The chromosomal damage of the two pesticide preparations was also evaluated in vivo in bone marrow of mice as micronuclei frequency and in vitro in human lymphocyte culture as SCE frequency. A DNA-damaging activity as DNA single-strand breaks and 8-OHdG and a significant increase in chromosomal alterations were observed with both substances in vivo and in vitro. A weak increment of the genotoxic activity was evident using the technical formulation. FULL TEXT

Benachour et al., 2007

N. Benachour, H. Sipahutar, S. Moslemi, C. Gasnier, C. Travert, G. E. Séralini, “Time- and Dose-Dependent Effects of Roundup on Human Embryonic and Placental Cells,” Archives of Environmental Contamination and Toxicology, 53:1, July 2007, DOI: doi.org/10.1007/s00244-006-0154-8

ABSTRACT:

Roundup® is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce®) on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD50) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2–4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1–2%, i.e., with 21–42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1–2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 μM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact. FULL TEXT

Dallegrave et al., 2003

Eliane Dallegrave, Fabiana DiGiorgio Mantese, Ricardo Soares Coelho, Janaı´na Drawans Pereira, Paulo Roberto Dalsenter, Augusto Langeloh, “The teratogenic potential of the herbicide glyphosate-Roundup in Wistar rats,” Toxicology Letters, 142, 2003, DOI: 10.1016/S0378-4274(02)00483-6.

ABSTRACT:

The aim of this study was to assess the teratogenicity of the herbicide glyphosate-Roundup† (as commercialized in Brazil) to Wistar rats. Dams were treated orally with water or 500, 750 or 1000 mg/kg glyphosate from day 6 to 15 of pregnancy. Cesarean sections were performed on day 21 of pregnancy, and number of corpora lutea, implantation sites, living and dead fetuses, and resorptions were recorded. Weight and gender of the fetuses were determined, and fetuses
were examined for external malformations and skeletal alterations. The organs of the dams were removed and weighed. Results showed a 50% mortality rate for dams treated with 1000 mg/kg glyphosate. Skeletal alterations were observed in 15.4, 33.1, 42.0 and 57.3% of fetuses from the control, 500, 750 and 1000 mg/kg glyphosate groups, respectively. We may conclude that glyphosate-Roundup† is toxic to the dams and induces developmental retardation of the fetal
skeleton. FULL TEXT

Robinson et al., 2012

CJ Robinson, M Antoniou, MEM Habib, CV Howard, RC Jennings, C Leifert, RO Nodari, and J Fagan, “Teratogenic Effects of Glyphosate-Based Herbicides: Divergence of Regulatory Decisions from Scientific Evidence,” Environmental and Analytical Toxicology, S:4, 2012, DOI: 10.4172/2161-0525.S4-006.

ABSTRACT:

The publication of a study in 2010, showing that a glyphosate herbicide formulation and glyphosate alone caused malformations in the embryos of Xenopus laevis and chickens through disruption of the retinoic acid signalling pathway, caused scientific and regulatory controversy. Debate centred on the effects of the production and consumption of genetically modified Roundup Ready® soy, which is engineered to tolerate applications of glyphosate herbicide. The study, along with others indicating teratogenic and reproductive effects from glyphosate herbicide exposure, was rebutted by the German Federal Office for Consumer Protection and Food Safety, BVL, as well as in industry-sponsored papers. These rebuttals relied partly on unpublished industry-sponsored studies commissioned for regulatory purposes, which, it was claimed, showed that glyphosate is not a teratogen or reproductive toxin.

However, examination of the German authorities’ draft assessment report on the industry studies, which underlies glyphosate’s EU authorisation, revealed further evidence of glyphosate’s teratogenicity. Many of the malformations found were of the type defined in the scientific literature as associated with retinoic acid teratogenesis. Nevertheless, the German and EU authorities minimized these findings in their assessment and set a potentially unsafe acceptable daily intake (ADI) level for glyphosate. This paper reviews the evidence on the teratogenicity and reproductive toxicity of glyphosate herbicides and concludes that a new and transparent risk assessment needs to be conducted. The new risk assessment must take into account all the data on the toxicity of glyphosate and its commercial formulations, including data generated by independent scientists and published in the peer-reviewed scientific literature, as well as the industry-sponsored studies. FULL TEXT

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