Analytical Methods - HH-RA.org

Bibliography Tag: analytical methods

Arnold et al., 2015

Arnold, S. M., Morriss, A., Velovitch, J., Juberg, D., Burns, C. J., Bartels, M., Aggarwal, M., Poet, T., Hays, S., & Price, P.; “Derivation of human Biomonitoring Guidance Values for chlorpyrifos using a physiologically based pharmacokinetic and pharmacodynamic model of cholinesterase inhibition;” Regulatory Toxicology and Pharmacology, 2015, 71(2), 235-243; DOI: 10.1016/j.yrtph.2014.12.013.

ABSTRACT:

A number of biomonitoring surveys have been performed for chlorpyrifos (CPF) and its metabolite (3,5,6-trichloro-2-pyridinol, TCPy); however, there is no available guidance on how to interpret these data in a health risk assessment context. To address this gap, Biomonitoring Guidance Values (BGVs) are developed using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model. The PBPK/PD model is used to predict the impact of age and human variability on the relationship between an early marker of cholinesterase (ChE) inhibition in the peripheral and central nervous systems [10% red blood cell (RBC) ChE inhibition] and levels of systemic biomarkers. Since the PBPK/PD model characterizes variation of sensitivity to CPF in humans, interspecies and intraspecies uncertainty factors are not needed. Derived BGVs represent the concentration of blood CPF and urinary TCPy associated with 95% of the population having less than or equal to 10% RBC ChE inhibition. Blood BGV values for CPF in adults and infants are 6100 ng/L and 4200 ng/L, respectively. Urinary TCPy BGVs for adults and infants are 2100 mug/L and 520 mug/L, respectively. The reported biomonitoring data are more than 150-fold lower than the BGVs suggesting that current US population exposures to CPF are well below levels associated with any adverse health effect. FULL TEXT

McDermott et al., 2019

McDermott, S., Hailer, M. K., & Lead, J. R.; “Meconium identifies high levels of metals in newborns from a mining community in the U.S;” Science of the Total Environment, 2019, 135528; DOI: 10.1016/j.scitotenv.2019.135528.

ABSTRACT:

BACKGROUND: This pilot study was conducted to determine if we could identify intrauterine exposure to metals in meconium, as a measure of exposure for mother-child pairs living in proximity to a mining operation.

OBJECTIVES: We used meconium as a means to measure metal exposure in utero. We set out to quantify the exposure to selected metals that are currently being mined and also are found in the Superfund site in Butte, Montana, and to compare it to that of Columbia, South Carolina, US, where mining is not occurring.

METHODS: This cross-sectional study was conducted between May and November 2018. We received Institutional Review Board approval and we consented women following the birth of their newborns, and collected meconium within 24 h of birth, without any identifiers. Each laboratory used the same protocol for collection, transport, and storage; and the same laboratory protocol was used for the analysis of all samples. Samples were digested using standard acid/peroxide digestion methods and measured by inductively coupled plasma mass spectroscopy.

RESULTS: We collected meconium specimens from 17 infants in Columbia, South Carolina and 15 infants in Butte, Montana. The concentrations found in Columbia were in the low mug kg(-1) range (or less) and were similar to the low levels that have been identified in other studies of meconium. The magnitude of the differences in concentrations found in Butte compared to Columbia was 1792 times higher for Cu, 1650 times higher for Mn, and 1883 times higher for Zn.

CONCLUSION: Using meconium to measure exposure of newborns has implications for risk assessment in a mining-exposed population. This approach was inexpensive and thorough. The magnitude of the differences in the metal levels identified from the two study sites suggests there is an urgent need for further research to learn if there are health consequences to these highly exposed infants. FULL TEXT

Ostrea et al., 2006

Ostrea, E. M., Bielawski, D. M., & Posecion Jr., N C; “Meconium analysis to detect fetal exposure to neurotoxicants;” Archives of Disease in Childhood, 2006, 91(8), 628-629; DOI: 10.1136/adc.2006.097956.

ABSTRACT:

Not Available.

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McEwen et al., 2019

McEwen, L. M., O’Donnell, K. J., McGill, M. G., Edgar, R. D., Jones, M. J., MacIsaac, J. L., Lin, D. T. S., Ramadori, K., Morin, A., Gladish, N., Garg, E., Unternaehrer, E., Pokhvisneva, I., Karnani, N., Kee, M. Z. L., Klengel, T., Adler, N. E., Barr, R. G., Letourneau, N., Giesbrecht, G. F., Reynolds, J. N., Czamara, D., Armstrong, J. M., Essex, M. J., de Weerth, C., Beijers, R., Tollenaar, M. S., Bradley, B., Jovanovic, T., Ressler, K. J., Steiner, M., Entringer, S., Wadhwa, P. D., Buss, C., Bush, N. R., Binder, E. B., Boyce, W. T., Meaney, M. J., Horvath, S., & Kobor, M. S.; “The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells;” Proceedings of the National Academy of Sciences, 2019; DOI: 10.1073/pnas.1820843116.

ABSTRACT:

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease. FULL TEXT

Jusko et al., 2012

Jusko, T. A., Klebanoff, M. A., Brock, J. W., & Longnecker, M. P.; “In-utero exposure to dichlorodiphenyltrichloroethane and cognitive development among infants and school-aged children;” Epidemiology, 2012, 23(5), 689-698; DOI: 10.1097/EDE.0b013e31825fb61d.

ABSTRACT:

BACKGROUND: Dichlorodiphenyltrichloroethane (DDT) continues to be used for control of infectious diseases in several countries. In-utero exposure to DDT and dichlorodiphenyldichloroethylene (DDE) has been associated with developmental and cognitive impairment among children. We examined this association in an historical cohort in which the level of exposure was greater than in previous studies.

METHODS: The association of in-utero DDT and DDE exposure with infant and child neurodevelopment was examined in 1100 subjects in the Collaborative Perinatal Project, a prospective birth cohort enrolling pregnant women from 12 study centers in the United States from 1959 to 1965. Maternal DDT and DDE concentrations were measured in archived serum specimens. Infant mental and motor development was assessed at age 8 months using the Bayley Scales of Infant Development, and child cognitive development was assessed at age 7 years, using the Wechsler Intelligence Scale for Children.

RESULTS: Although levels of DDT and DDE were relatively high in this population (median DDT concentration, 8.9 mug/L; DDE, 24.5 mug/L), neither were related to Mental or Psychomotor Development scores on the Bayley Scales nor to Full-Scale Intelligence Quotient at 7 years of age. Categorical analyses showed no evidence of dose- response for either maternal DDT or DDE, and estimates of the association between continuous measures of exposure and neurodevelopment were indistinguishable from 0.

CONCLUSIONS: Adverse associations were not observed between maternal serum DDT and DDE concentrations and offspring neurodevelopment at 8 months or 7 years in this cohort. FULL TEXT

Duty et al., 2003

Duty, S. M., Singh, N. P., Silva, M. J., Barr, D. B., Brock, J. W., Ryan, L., Herrick, R. F., Christiani, D. C., & Hauser, R.; “The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay;” Environmental Health Perspectives, 2003, 111(9), 1164-1169; DOI: 10.1289/ehp.5756.

ABSTRACT:

Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine sample. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry; data were corrected for urine dilution by adjusting for specific gravity. The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers); percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail; and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 micro m [95% confidence interval (95% CI), 0.74-6.47]; the TDM also increased 1.2 micro m (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm. FULL TEXT

Wenzel et al., 2018

Wenzel, A. G., Brock, J. W., Cruze, L., Newman, R. B., Unal, E. R., Wolf, B. J., Somerville, S. E., & Kucklick, J. R.; “Prevalence and predictors of phthalate exposure in pregnant women in Charleston, SC;” Chemosphere, 2018, 193, 394-402; DOI: 10.1016/j.chemosphere.2017.11.019. https://www.ncbi.nlm.nih.gov/pubmed/29154114.

ABSTRACT:

Phthalates are plasticizers commonly detected in human urine due to widespread exposure from PVC plastics, food packaging, and personal care products. Several phthalates are known antiandrogenic endocrine disruptors, which raises concern for prenatal exposure during critical windows of fetal development. While phthalate exposure is ubiquitous, certain demographics are subject to greater or lesser exposure. We sampled urine from 378 pregnant women during the second trimester of gestation living in Charleston, SC, and measured eight urinary phthalate metabolites as biomarkers of phthalate exposure: monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and monomethyl phthalate (MMP). Demographic data was collected from questionnaires administered at the time of specimen collection. All phthalate metabolites were detected in over 93% of urine samples. On average, concentrations were highest for MEP (median = 47.0 ng/mL) and lowest for MMP (median = 1.92 ng/mL). Sociodemographic characteristics associated with elevated phthalate concentrations included being unmarried, less educated, having a low income, high body mass index (BMI), and/or being African American. After racial stratification, age, BMI, education, and income were significantly associated with phthalate concentrations in African American women. Marital status was associated with phthalate concentrations in Caucasian women only, with greater concentrations of MBP, MEHHP, MiBP, and MMP in unmarried versus married women. Results of this cross-sectional study provide evidence for significant racial and demographic variations in phthalate exposure. FULL TEXT

Silva et al., 2003

Silva, M. J., Malek, N. A., Hodge, C. C., Reidy, J. A., Kato, K., Barr, D. B., Needham, L. L., & Brock, J. W.; “Improved quantitative detection of 11 urinary phthalate metabolites in humans using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry;” Journal of Chromatography Part B: Analytical Technologies in the Biomedical and Life Sciences, 2003, 789(2), 393-404.

ABSTRACT:

Phthalates are widely used as industrial solvents and plasticizers, with global use exceeding four million tons per year. We improved our previously developed high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometric (HPLC-APCI-MS/MS) method to measure urinary phthalate metabolites by increasing the selectivity and the sensitivity by better resolving them from the solvent front, adding three more phthalate metabolites, monomethyl phthalate (mMP), mono-(2-ethyl-5-oxohexyl)phthalate (mEOHP) and mono-(2-ethyl-5-hydroxyhexyl)phthalate (mEHHP); increasing the sample throughput; and reducing the solvent usage. Furthermore, this improved method enabled us to analyze free un-conjugated mono-2-ethylhexyl phthalate (mEHP) by eliminating interferences derived from coelution of the glucuronide-bound, or conjugated form, of the mEHP on measurements of the free mEHP. This method for measuring phthalate metabolites in urine involves solid-phase extraction followed by reversed-phase HPLC-APCI-MS/MS using isotope dilution with (13)C(4) internal standards. We further evaluated the ruggedness and the reliability of the method by comparing measurements made by multiple analysts at different extraction settings on multiple instruments. We observed mMP, monoethyl phthalate (mEP), mono-n-butyl phthalate (mBP), monobenzyl phthalate (mBzP), mEHP, mEHHP and mEOHP in the majority of urine specimens analyzed with DEHP-metabolites mEHHP and mEOHP present in significantly higher amounts than mEHP.

Aris and Leblanc, 2011

Aris, Aziz, & Leblanc, Samuel; “Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada.;” Reproductive Toxicology, 2011, 31, 528-533; DOI: 10.1016/j.reprotox.2011.02.004.

ABSTRACT:

Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. FULL TEXT

Ford et al., 2017

Ford, B., Bateman, L. A., Gutierrez-Palominos, L., Park, R., & Nomura, D. K.; “Mapping Proteome-wide Targets of Glyphosate in Mice;” Cell Chemical Biology, 2017, 24(2), 133-140; DOI: 10.1016/j.chembiol.2016.12.013.

ABSTRACT:

Glyphosate, the active ingredient in the herbicide Roundup, is one of the most widely used pesticides in agriculture and home garden use. Whether glyphosate causes any mammalian toxicity remains highly controversial. While many studies have associated glyphosate with numerous adverse health effects, the mechanisms underlying glyphosate toxicity in mammals remain poorly understood. Here, we used activity-based protein profiling to map glyphosate targets in mice. We show that glyphosate at high doses can be metabolized in vivo to reactive metabolites such as glyoxylate and react with cysteines across many proteins in mouse liver. We show that glyoxylate inhibits liver fatty acid oxidation enzymes and glyphosate treatment in mice increases the levels of triglycerides and cholesteryl esters, likely resulting from diversion of fatty acids away from oxidation and toward other lipid pathways. Our study highlights the utility of using chemoproteomics to identify novel toxicological mechanisms of environmental chemicals such as glyphosate. FULL TEXT

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