Bibliography Tag: biomonitoring

Bibliography Index

Panzacchi et al., 2018

Panzacchi, S., Mandrioli, D., Manservisi, F., Bua, L., Falcioni, L., Spinaci, M., Galeati, G., Dinelli, G., Miglio, R., Mantovani, A., Lorenzetti, S., Hu, J., Chen, J., Perry, M. J., Landrigan, P. J., & Belpoggi, F. “The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation,” Environmental Health, 17(1), 52, 2018.  doi:10.1186/s12940-018-0393-y.

ABSTRACT:

BACKGROUND: Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine.

METHODS: We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA.

RESULTS: Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA.

CONCLUSIONS: Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model. FULL TEXT

Shaw, 2017

William Shaw, PhD, “Elevated Urinary Glyphosate and Clostridia Metabolites With Altered Dopamine Metabolism in Triplets With Autistic Spectrum Disorder or Suspected Seizure Disorder: A Case Study,” Integrative Medicine, 2017, 16:1.

CONTEXT: Autism is a neurodevelopmental disorder for which a number of genetic, environmental, and nutritional causes have been proposed. Glyphosate is used widely as a crop desiccant and as an herbicide in fields of genetically modified foods that are glyphosate resistant. Several researchers have proposed that it may be a cause of autism, based on epidemiological data that correlates increased usage of glyphosate with an increased autism rate.

OBJECTIVE:  The current study was intended to determine if excessive glyphosate was present in the triplets and their parents and to evaluate biochemical findings for the family to determine the potential effects of its presence.

DESIGN: The author performed a case study with the cooperation of the parents and the attending physician.

SETTING: The study took place at The Great Plains Laboratory, Inc (Lenexa, KS, USA).

PARTICIPANTS: Participants were triplets, 2 male children and 1 female, and their parents. The 2 male children had autism, whereas the female had a possible seizure disorder. All 3 had elevated urinary glyphosate, and all of the triplets and their mother had elevated values of succinic acid or tiglylglycine, which are indicators of mitochondrial dysfunction.

INTERVENTION:
The participants received a diet of organic food only.

OUTCOME MEASURES:
The study performed organic acids, glyphosate, toxic chemicals and tiglylglycine, and creatinine testing of the participants’ urine.

RESULTS:
The 2 male triplets with autism had abnormalities on at least 1 organic acids test, including elevated phenolic compounds such as 4-cresol, 3-[3-hydroxyphenyl]-3-hydroxypropionic acid and 4-hydroxyphenylacetic acid, which have been previously associated with Clostridia bacteria and autism. The female, who was suspected of having a seizure disorder but not autism, did not have elevated phenolic compounds but did have a significantly elevated value of the metabolite tiglylglycine, a marker for mitochondrial dysfunction and/or mutations. One male triplet was retested postintervention and was found to have a markedly lower amount of glyphosate in his urine.

CONCLUSIONS:
The pattern of metabolites in the urine samples of the males with autism are consistent with a recent theory of autism that connects widespread glyphosate use with alteration of animal and human gastrointestinal flora. That theory is that the normally beneficial bacteria species that are sensitive to glyphosate are diminished and harmful bacteria species, such as Clostridia, that are insensitive to glyphosate, are increased following exposure to glyphosate. Excessive dopamine, caused by inhibition of dopamine-beta-hydroxylase by Clostridia metabolites, in turn, produces oxidative species that damage neuronal Krebs cycle enzymes, neuronal mitochondria, and neuronal structural elements such as the neurofibrils.  FULL TEXT

Lerro et al., 2017

Catherine C. Lerro, Laura E. Beane Freeman, Lützen Portengen, Daehee Kang, Kyoungho Lee, Aaron Blair, Charles F. Lynch, Berit Bakke, Anneclaire J. De Roos, and Roel C.H. Vermeulen, “A longitudinal study of atrazine and 2,4-D exposure and oxidative stress markers among Iowa corn farmers,” Environmental and Molecular Mutagenesis, 2017, 58, DOI: 10.1002/em.22069

ABSTRACT:

Reactive oxygen species, potentially formed through environmental exposures, can overwhelm an organism’s antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases. Pesticide exposures have been shown to cause oxidative stress in vivo. We utilized a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to the widely used herbicides atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. 225 urine samples were collected during five agricultural time periods (pre-planting, planting, growing, harvest, off-season) for 30 farmers who applied pesticides occupationally and 10 controls who did not; all were non-smoking men ages 40–60. Atrazine mercapturate (atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2′-deoxyguanosine [8-OHdG], and 8-isoprostaglandin-F2α [8-isoPGF]) were measured in urine. We calculated β estimates and 95% confidence intervals (95%CI) for each pesticide-oxidative stress marker combination using multivariate linear mixed-effect models for repeated measures. Farmers had higher urinary atrazine mercapturate and 2,4-D levels compared to controls. In regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (β=0.066, 95%CI=0.008–0.124) and 8-isoPGF (β=0.088, 95%CI=0.004–0.172). 2,4-D may be associated with oxidative stress because of modest increases in 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation, with recent 2,4-D exposure. Future studies should investigate the role of 2,4-D-induced oxidative stress in the pathogenesis of human diseases.  FULL TEXT

Bouchard et al., 2011

Bouchard MF, Chevrier J, Harley KG, Kogut K, Vedar M, Calderon N, Trujillo C, Johnson C, Bradman A, Barr DB, Eskenazi B., “Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children.,” Environmental Health Perspectives, 2011, 119:8, DOI: 10.1289/ehp.1003185.

ABSTRACT:
CONTEXT: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development.

OBJECTIVE: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children.

METHODS: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment.

RESULTS: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores.

CONCLUSIONS: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population. FULL TEXT

Koureas et al., 2012

Koureas M, Tsakalof A, Tsatsakis A, Hadjichristodoulou C., “Systematic review of biomonitoring studies to determine the association between exposure to organophosphorus and pyrethroid insecticides and human health outcomes,” Toxicology Letters,  2012, 210:2, DOI: 10.1016/j.toxlet.2011.10.007.

ABSTRACT:

For the appropriate protection of human health it is necessary to accurately estimate the health effects of human exposure to toxic compounds. In the present  review, epidemiological studies on the health effects of human exposure to organophosphorus  (OP) and pyrethroid (PYR) insecticides have been critically assessed. This review is focused on studies where the exposure assessment was based on quantification of specific biomarkers in urine or plasma. The 49 studies reviewed used different epidemiological approaches and analytical methods as well as different exposure assessment methodologies. With regard to OP pesticides, the studies reviewed suggested negative effects of prenatal exposure to these pesticides on neurodevelopment and male reproduction. Neurologic effects on adults, DNA damage and adverse birth outcomes were also associated with exposure to OP pesticides. With regard to exposure to PYR pesticides, there are currently few studies investigating the adverse health outcomes due to these pesticides. The effects studied in relation to PYR exposure were mainly male reproductive effects (sperm quality, sperm DNA damage and reproductive hormone disorders). Studies’ findings provided evidence to support the hypothesis that PYR exposure is adversely associated with effects on the male reproductive system. The validity of these epidemiological studies is strongly enhanced by exposure assessment based on biomarker quantification. However, for valid and reliable results and conclusions, attention should also be focused on the validity of the analytical methods used, study designs and the measured toxicants characteristics.

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

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

Parvez et al., 2018

S. Parvez, R. R. Gerona, C. Proctor, M. Friesen, J. L. Ashby, J. L. Reiter, Z. Lui, and P. D. Winchester, “Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study,” Environmental Health, 17:23, March 9, 2018, DOI: 10.1186/s12940-018-0367-0.

ABSTRACT:

BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length.

METHOD: Urine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. GLY measurements were performed using liquid chromatography-tandem mass spectrometry. Demographic and survey information relating to food and water consumption, stress, and residence were obtained by questionnaire. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length.

RESULTS: The mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5–7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths (r = − 0.28, p = 0.02).

CONCLUSIONS: This is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further  investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized. FULL TEXT

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