Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 61 Records) |
Query Trace: Ester M[original query] |
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Patterns of urinary organophosphate ester metabolite trajectories in children: the HOME Study
Yang W , Braun JM , Vuong AM , Percy Z , Xu Y , Xie C , Deka R , Calafat AM , Ospina M , Yolton K , Cecil KM , Lanphear BP , Chen A . J Expo Sci Environ Epidemiol 2023 BACKGROUND: Organophosphate esters (OPEs) have replaced flame retardant polybrominated diphenyl ethers as flame retardants in consumer products, but few longitudinal studies have characterized childhood OPE exposure. OBJECTIVE: We aimed to examine the exposure pattern of urinary OPE metabolites in children. METHODS: We quantified three urinary OPE metabolites five times in children (1, 2, 3, 5, 8 years) from 312 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA. We examined the associations of average maternal OPE metabolite concentrations with OPE metabolite concentrations in childhood, characterized childhood OPE trajectories with latent class growth analysis (LCGA), and examined factors related to trajectory membership. RESULTS: Bis(2-chloroethyl) phosphate (BCEP) had the lowest median concentrations over time (0.66-0.97 mg/L) while the median concentrations of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) increased with age (1.44-3.80 mg/L). The median concentrations of diphenyl phosphate (DPHP) fluctuated between 1.96 and 2.69 mg/L. Intraclass correlation coefficients for urinary metabolites measured at five time points indicated high variability within individuals (0.13-0.24). Average maternal urinary BCEP and BDCIPP were associated with concentrations in early childhood. Maternal education, the birth year of the child, and having a carpet in the main activity room were associated with BCEP and BDCIPP trajectory while none of the factors were associated with DPHP trajectory. SIGNIFICANCE: The trajectory analysis showed different patterns of urinary OPE metabolite concentrations, suggesting the need to collect multiple samples to adequately reflect OPE exposure. IMPACT STATEMENT: In this well-established cohort, we evaluated the patterns of urinary OPE metabolites in children ages 1-8 years. The number of repeated measures over childhood has not been achieved in prior studies. Our results suggested the high variability of urinary OPE metabolites within individuals. Maternal metabolite concentrations during pregnancy were related to child concentrations at ages 1-3 years. BCEP, BDCIPP, and DPHP demonstrated different trajectories in children, which suggests that multiple samples may be required to capture OPE exposure patterns in childhood. |
Temporal trends and predictors of gestational exposure to organophosphate ester flame retardants and plasticizers
Bommarito PA , Friedman A , Welch BM , Cantonwine DE , Ospina M , Calafat AM , Meeker JD , McElrath TF , Ferguson KK . Environ Int 2023 180 108194 BACKGROUND: Organophosphate esters (OPEs), used as flame retardants and plasticizers, are chemicals of concern for maternal and infant health. Prior studies examining temporal trends and predictors of OPE exposure are primarily limited by small sample sizes. OBJECTIVES: Characterize temporal trends and predictors of OPE exposure biomarkers. METHODS: We determined urinary concentrations of eight biomarkers of OPE exposure at three timepoints during pregnancy for participants in the LIFECODES Fetal Growth Study (n = 900), a nested case-cohort recruited between 2007 and 2018. We examined biomarker concentrations, their variability during pregnancy, and temporal trends over the study period. In addition, we identified sociodemographic and pregnancy characteristics associated with biomarker concentrations. Analyses were conducted using both the within-subject pregnancy geometric means and biomarker concentrations measured at individual study visits. RESULTS: Five OPE biomarkers were detected in at least 60% of the study participants. Biomarkers were not strongly correlated with one another and intraclass correlation coefficients, measuring within-subject variability during pregnancy, ranged from 0.27 to 0.51. Biomarkers exhibited varying temporal trends across study years. For example, bis(1-chloro-2-propyl) phosphate (BCIPP) increased monotonically, whereas bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), displayed non-monotonic trends with concentrations that peaked between 2011 and 2014. We observed associations between sociodemographic characteristics and OPE biomarkers. In general, concentrations of most OPE biomarkers were higher among participants from racial and ethnic minority populations, participants who were younger, had higher pre-pregnancy body mass index (BMI), and less than a college degree. We observed consistent results using either averaged or visit-specific biomarker concentrations. SIGNIFICANCE: We observed widespread exposure to several OPEs and OPE biomarkers displayed varying temporal trends in pregnant people from 2007 to 2018. Concentrations of most OPE biomarkers varied according to sociodemographic factors, suggesting higher burdens of exposure among participants with higher pre-pregnancy BMI, those belonging to racial and ethnic minority populations, and lower educational attainment. |
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemic, epidemic and bat coronavirus (preprint)
Sheahan TP , Sims AC , Zhou S , Graham RL , Hill CS , Leist SR , Schafer A , Dinnon KH 3rd , Montgomery SA , Agostini ML , Pruijssers AJ , Chappell JD , Brown AJ , Bluemling GR , Natchus MG , Saindane M , Kolykhalov AA , Painter G , Harcourt J , Tamin A , Thornburg NJ , Swanstrom R , Denison MR , Baric RS . bioRxiv 2020 2020.03.19.997890 Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV 2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to another nucleoside analog inhibitor. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (b-D-N4-hydroxycytidine-5’-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses. |
Temporal trends in urinary concentrations of phenols, phthalate metabolites and phthalate replacements between 2000 and 2017 in Boston, MA
Jiang VS , Calafat AM , Williams PL , Chavarro JE , Ford JB , Souter I , Hauser R , Mínguez-Alarcón L . Sci Total Environ 2023 898 165353 Endocrine disrupting chemicals (EDCs) can adversely affect human health and are ubiquitously found in everyday products. We examined temporal trends in urinary concentrations of EDCs and their replacements. Urinary concentrations of 11 environmental phenols, 15 phthalate metabolites, phthalate replacements such as two di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) metabolites, and triclocarban were quantified using isotope-dilution tandem mass spectrometry. This prospective ecological study included 996 male and 819 female patients who were predominantly White/Caucasian (83 %) with an average age of 35 years and a BMI of 25.5 kg/m(2) seeking fertility treatment in Boston, MA, USA. Patients provided a total of 6483 urine samples (median = 2, range = 1-30 samples per patient) between 2000 and 2017. Over the study period, we observed significant decreases (% per year) in urinary concentrations of traditional phenols, parabens, and phthalates such as bisphenol A (β: -6.3, 95 % CI: -7.2, -5.4), benzophenone-3 (β: -6.5, 95 % CI: -1.1, -18.9), parabens ((β range:-5.4 to -14.2), triclosan (β: -18.8, 95 % CI: -24, -13.6), dichlorophenols (2.4-dichlorophenol β: -6.6, 95 % CI: -8.8, -4.3); 2,5-dichlorophenol β: -13.6, 95 % CI: -17, -10.3), di(2-ethylhexyl) phthalate metabolites (β range: -11.9 to -22.0), and other phthalate metabolites including mono-ethyl, mono-n-butyl, and mono-methyl phthalate (β range: -0.3 to -11.5). In contrast, we found significant increases in urinary concentrations of environmental phenol replacements including bisphenol S (β: 3.9, 95 % CI: 2.7, 7.6) and bisphenol F (β: 6, 95 % CI: 1.8, 10.3), DINCH metabolites (cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester [MHiNCH] β: 20, 95 % CI: 17.8, 22.2; monocarboxyisooctyl phthalate [MCOCH] β: 16.2, 95 % CI: 14, 18.4), and newer phthalate replacements such as mono-3-carboxypropyl phthalate, monobenzyl phthalate, mono-2-ethyl-5-carboxypentyl phthalate and di-isobutyl phthalate metabolites (β range = 5.3 to 45.1), over time. Urinary MHBP concentrations remained stable over the study period. While the majority of biomarkers measured declined over time, concentrations of several increased, particularly replacement chemicals that are studied. |
Stability of lipids in plasma and serum: Effects of temperature-related storage conditions on the human lipidome
Reis GB , Rees JC , Ivanova AA , Kuklenyik Z , Drew NM , Pirkle JL , Barr JR . J Mass Spectrom Adv Clin Lab 2021 22 34-42 Large epidemiological studies often require sample transportation and storage, presenting unique considerations when applying advanced lipidomics techniques. The goal of this study was to acquire lipidomics data on plasma and serum samples stored at potential preanalytical conditions (e.g., thawing, extracting, evaporating), systematically monitoring lipid species for a period of one month. Split aliquots of 10 plasma samples and 10 serum samples from healthy individuals were kept in three temperature-related environments: refrigerator, laboratory benchtop, or heated incubator. Samples were analyzed at six different time points over 28 days using a Bligh & Dyer lipid extraction protocol followed by direct infusion into a lipidomics platform using differential mobility with tandem mass spectrometry. The observed concentration changes over time were evaluated relative to method and inter-individual biological variability. In addition, to evaluate the effect of lipase enzyme levels on concentration changes during storage, we compared corresponding fasting and post-prandial plasma samples collected from 5 individuals. Based on our data, a series of low abundance free fatty acid (FFA), diacylglycerol (DAG), and cholesteryl ester (CE) species were identified as potential analytical markers for degradation. These FFA and DAG species are typically produced by endogenous lipases from numerous triacylglycerols (TAGs), and certain high abundance phosphatidylcholines (PCs). The low concentration CEs, which appeared to increase several fold, were likely mass-isobars from oxidation of other high concentration CEs. Although the concentration changes of the high abundant TAG, PC, and CE precursors remained within method variability, the concentration trends of FFA, DAG, and oxidized CE products should be systematically monitored over time to inform analysts about possible pre-analytical biases due to degradation in the study sample sets. |
Predictors of urinary biomarker concentrations of phthalates and some of their replacements in children in the Project Viva cohort
Kalloo G , Janis JA , Seshasayee SM , Rifas SL , Calafat AM , Botelho JC , Hauser R , James-Todd T , Oken E , Fleisch AF . J Expo Sci Environ Epidemiol 2022 33 (2) 255-263 BACKGROUND: Some phthalates are still widely used in food packaging, toys, and personal care products, and links to adverse health have motivated substitution with replacement chemicals. Few studies have examined patterns and predictors of phthalate replacement biomarkers in children. OBJECTIVE: To examine associations of sociodemographic, dietary, and urine collection characteristics with urinary concentrations of biomarkers of select phthalates and their replacements in mid-childhood. METHODS: We studied 830 children ages 6-10 years in 2007-2010 in a Boston-area cohort. We quantified urinary metabolites and summed their concentrations to calculate biomarkers of the concentrations of ten parent phthalates/replacements. We used linear regression to examine mutually adjusted associations of each predictor with each phthalate biomarker. We used logistic regression to examine predictors of 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) biomarker detectability. RESULTS: Predictor characteristics explained 25-48% of urinary biomarker variability. Di-2-ethylhexyl terephthalate (DEHTP) biomarker was higher in females (18.7% [95% CI: 0.7, 39.9]), children who consumed more meat and dairy, and samples collected from later years. DINCH biomarker was more detectable in females (odds ratio [OR] 2.1 [95% CI: 1.5, 3.0]) and samples from later years. SIGNIFICANCE: Populations of children with increased urinary concentrations of phthalate and replacement biomarkers can be targeted for future study of sources of exposure, and identifying dietary predictors of biomarkers will directly guide future interventions. IMPACT: Our study uses data from a large cohort that is one of the first to measure DINCH, DEHTP, and metabolites of di-isononyl phthalate and di-isodecyl phthalate. Additionally, we evaluate predictors during mid-childhood when biomarkers might be highest. As the use of replacement phthalates increases, our study is one of the first to examine biomarker patterns and predictors among children. |
Early life organophosphate ester exposures and bone health at age 12years: The Health Outcomes and Measures of the Environment (HOME) study
Calafat AM , Ospina M . Sci Total Environ 2022 851 158246 BACKGROUND: No human studies have evaluated early life organophosphate ester (OPE) exposures with bone health outcomes, despite evidence of osteotoxicity. OBJECTIVES: We assessed associations of urinary OPE metabolites measured across early life with areal bone mineral density (aBMD) and bone mineral content (BMC) at age 12 years. METHODS: Among 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study, we quantified concentrations of bis-2-chloroethyl phosphate (BCEP), bis-(1,3-dichloro-2-propyl) (BDCIPP), di-n-butyl phosphate (DnBP), and diphenyl phosphate (DPHP) in urine collected from mothers during pregnancy and children at ages 1, 2, 3, 5, and 8 years. At age 12 years, we performed dual energy x-ray absorptiometry and calculated aBMD and BMC z-scores at six skeletal sites. We estimated overall and sex-stratified BMD/BMC z-score differences per interquartile range (IQR) increase in OPE concentrations at multiple exposure timepoints: gestation (average) and 1-3 (average), 5, and 8 years. RESULTS: In adjusted models, overall associations of BCEP and BDCIPP with total hip and 1/3rd distal radius aBMD and BMC varied significantly by exposure timepoint, as did BDCIPP with whole body aBMD. For example, differences (95 % CI) in total hip aBMD z-score per IQR increase in BDCIPP were 0.33 (0.01, 0.64), -0.10 (-0.34, 0.14), -0.18 (-0.40, 0.05), and 0.14 (-0.09, 0.38) for concentrations during gestation and at 1-3, 5, and 8 years, respectively. Overall DnBP and DPHP associations were generally null at all timepoints. We observed sex-specific associations for some timepoints and skeletal sites. For example, an IQR increase in 8-year DPHP was associated with a 0.21 (0.05, 0.38) greater total hip aBMD z-score among females but -0.19 (-0.43, 0.05) lower z-score among males. DISCUSSION: Early life OPE exposures may be associated with sex- and exposure period-dependent alterations in early adolescent bone mineral accrual and strength. |
Maternal urinary organophosphate ester metabolite concentrations and glucose tolerance during pregnancy: The HOME Study
Yang W , Braun JM , Vuong AM , Percy Z , Xu Y , Xie C , Deka R , Calafat AM , Ospina M , Yolton K , Cecil KM , Lanphear BP , Chen A . Int J Hyg Environ Health 2022 245 114026 BACKGROUND: Endocrine-disrupting chemicals may alter glucose homeostasis, especially during pregnancy. Biomonitoring studies suggest ubiquitous human exposure to organophosphate esters (OPEs), chemicals with endocrine-disrupting capabilities. Few studies have examined the association between maternal exposure to OPEs and blood glucose during pregnancy. METHODS: With data from 301 pregnant women in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA, we examined whether OPE concentrations were associated with changes in blood glucose. We quantified four OPE metabolites in maternal spot urine samples collected at 16- and 26-weeks pregnancy. We extracted results from the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) via medical chart review. Women with GCT ≥ 140 mg/dL or any abnormal values in OGTT (≥ 95 mg/dL fasting glucose, ≥ 180 mg/dL 1-h glucose, ≥ 155 mg/dL 2-h glucose, ≥ 140 mg/dL 3-h glucose) were defined as having elevated glucose levels. We used linear regression and Bayesian Kernel Machine Regression (BKMR) to estimate the associations of individual OPE metabolites and OPE mixtures with blood glucose levels during pregnancy. We used modified Poisson regression to estimate the associations of OPE metabolite concentrations with elevated glucose levels. We further examined effect measure modification by maternal characteristics (age, pre-pregnancy body mass index [BMI], and race/ethnicity). RESULTS: Diphenyl phosphate (DPHP) had the highest geometric mean concentration of the urinary OPE metabolites (1.83 μg/L at 16 weeks, 1.24 μg/L at 26 weeks). Thirty women (10.0%) had elevated glucose levels. Individual OPE metabolites or their mixtures were not significantly associated with continuous GCT results. We did not observe effect measure modification by maternal age, pre-pregnancy BMI categories, or race/ethnicity. Compared with women in the 1st tertile of average DPHP of 16- and 26 weeks of pregnancy, women in the 3rd tertile tended to have a reduced risk of elevated glucose levels (RR = 0.41, 95% CI = 0.16-1.06, p for trend = 0.06). CONCLUSION: In this cohort, maternal urinary OPE metabolite concentrations were weakly associated with blood glucose levels during pregnancy. |
Phthalate and DINCH urinary concentrations across pregnancy and risk of preterm birth
Yland JJ , Zhang Y , Williams PL , Mustieles V , Vagios S , Souter I , Calafat AM , Hauser R , Messerlian C . Environ Pollut 2021 292 118476 Preconception and prenatal exposure to phthalates has been associated with an increased risk of preterm birth. However, it is unclear whether there are periods of heightened susceptibility during pregnancy. This prospective cohort study included 386 women undergoing fertility treatment who gave birth to a singleton infant during 2005 through 2018. Eleven phthalate metabolites were measured in spot urine samples collected at each trimester. In approximately 50% of participants, two metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), a phthalate substitute, were also measured. The molar sum of four di(2-ethylhexyl) phthalate metabolites (∑DEHP) was calculated. We evaluated the associations of mean maternal biomarker concentrations with risk of preterm birth using modified log-binomial models and utilized multiple informant models to compare trimester-specific associations. We examined the relative biomarker concentration across gestation comparing women with preterm birth to women with term delivery using quadratic mixed model. The risk ratio for preterm birth associated with a one-unit increase in the natural log-transformed urinary concentrations of ∑DEHP (mean during pregnancy) was 1.21 (95% confidence interval (CI): 0.84, 1.72). In multiple informant models, these associations were strongest in the third trimester (RR = 1.51; 95% CI: 1.17, 1.95). Estimated mean ∑DEHP concentrations were higher among women with preterm than term delivery, especially late in gestation. Associations with preterm birth were also observed for each of the four individual DEHP metabolites. Detection of cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), a metabolite of DINCH, appeared to be positively related to preterm birth. In this prospective cohort of subfertile couples, maternal ∑DEHP metabolite concentrations during pregnancy were associated with an increased risk of preterm birth, particularly during late gestation. |
Influenza vaccine effectiveness within prospective cohorts of healthcare personnel in Israel and Peru 2016-2019
Thompson MG , Soto G , Perez A , Newes-Adeyim G , Yoo YM , Hirsch A , Katz M , Tinoco Y , Shemer Avni Y , Ticona E , Malosh R , Martin E , Matos E , Reynolds S , Wesley M , Ferdinands J , Cheung A , Levine M , Bravo E , Arriola CS , Ester Castillo M , Carlos Castro J , Dawood F , Goldberg D , Manuel Neyra Quijandría J , Azziz-Baumgartner E , Monto A , Balicer R . Vaccine 2021 39 (47) 6956-6967 BACKGROUND: There are limited data on influenza vaccine effectiveness (IVE) in preventing laboratory-confirmed influenza illness among healthcare personnel (HCP). METHODS: HCP with direct patient contact working full-time in hospitals were followed during three influenza seasons in Israel (2016-2017 to 2018-2019) and Peru (2016 to 2018). Trivalent influenza vaccines were available at all sites, except during 2018-2019 when Israel used quadrivalent vaccines; vaccination was documented by electronic medical records, vaccine registries, and/or self-report (for vaccinations outside the hospital). Twice-weekly active surveillance identified acute respiratory symptoms or febrile illness (ARFI); self-collected respiratory specimens were tested by real-time reverse transcription polymerase chain reaction (PCR) assay. IVE was 100 × 1-hazard ratio (adjusted for sex, age, occupation, and hospital). RESULTS: Among 5,489 HCP who contributed 10,041 person-seasons, influenza vaccination coverage was 47% in Israel and 32% in Peru. Of 3,056 ARFIs in Israel and 3,538 in Peru, A or B influenza virus infections were identified in 205 (7%) in Israel and 87 (2.5%) in Peru. IVE against all viruses across seasons was 1% (95% confidence interval [CI] = -30%, 25%) in Israel and 12% (95% CI = -61%, 52%) in Peru. CONCLUSION: Estimates of IVE were null using person-time models during six study seasons in Israel and Peru. |
Evaluation of enhanced darkfield microscopy and hyperspectral imaging for rapid screening of TiO(2) and SiO(2) nanoscale particles captured on filter media
Neu-Baker NM , Dozier AK , Eastlake AC , Brenner SA . Microsc Res Tech 2021 84 (12) 2968-2976 Here we report on initial efforts to evaluate enhanced darkfield microscopy (EDFM) and light scattering Vis-NIR hyperspectral imaging (HSI) as a rapid screening tool for the offline analysis of mixed cellulose ester (MCE) filter media used to collect airborne nanoparticulate from work environments. For this study, the materials of interest were nanoscale titanium dioxide (TiO(2) ) and silicon dioxide (SiO(2) ; silica), chosen for their frequent use in consumer products. TiO(2) and SiO(2) nanoscale particles (NPs) were collected on MCE filter media and were imaged and analyzed via EDFM-HSI. When visualized by EDFM, TiO(2) and SiO(2) NPs were readily apparent as bright spherical structures against a dark background. Moreover, TiO(2) and SiO(2) NPs were identified in hyperspectral images. EDFM-HSI images and data were compared to scanning transmission electron microscopy (STEM), a NIST-traceable technique for particle size analysis, and the current gold standard for offline analysis of filter media. As expected, STEM provided more accurate sizing and morphology data when compared to EDFM-HSI, but is not ideal for rapid screening of the presence of NPs of interest since it is a costly, low-throughput technique. In this study, we demonstrate the utility of EDFM-HSI in rapidly visualizing and identifying TiO(2) and SiO(2) NPs on MCE filters. This screening method may prove useful in expediting time-to-knowledge compared to electron microscopy. Future work will expand this evaluation to other industrially relevant NPs, other filter media types, and real-world filter samples from occupational exposure assessments. |
Additive Manufacturing for Occupational Hygiene: A Comprehensive Review of Processes, Emissions, & Exposures
Stefaniak AB , Du Preez S , Du Plessis JL . J Toxicol Environ Health B Crit Rev 2021 1-50 This comprehensive review introduces occupational (industrial) hygienists and toxicologists to the seven basic additive manufacturing (AM) process categories. Forty-six articles were identified that reported real-world measurements for all AM processes, except sheet lamination. Particles released from powder bed fusion (PBF), material jetting (MJ), material extrusion (ME), and directed energy deposition (DED) processes exhibited nanoscale to submicron scale; real-time particle number (mobility sizers, condensation nuclei counters, miniDiSC, electrical diffusion batteries) and surface area monitors (diffusion chargers) were generally sufficient for these processes. Binder jetting (BJ) machines released particles up to 8.5 µm; optical particle sizers (number) and laser scattering photometers (mass) were sufficient for this process. PBF and DED processes (powdered metallic feedstocks) released particles that contained respiratory irritants (chromium, molybdenum), central nervous system toxicants (manganese), and carcinogens (nickel). All process categories, except those that use metallic feedstocks, released organic gases, including (but not limited to), respiratory irritants (toluene, xylenes), asthmagens (methyl methacrylate, styrene), and carcinogens (benzene, formaldehyde, acetaldehyde). Real-time photoionization detectors for total volatile organics provided useful information for processes that utilize polymer feedstock materials. More research is needed to understand 1) facility-, machine-, and feedstock-related factors that influence emissions and exposures, 2) dermal exposure and biological burden, and 3) task-based exposures. Harmonized emissions monitoring and exposure assessment approaches are needed to facilitate inter-comparison of study results. Improved understanding of AM process emissions and exposures is needed for hygienists to ensure appropriate health and safety conditions for workers and for toxicologists to design experimental protocols that accurately mimic real-world exposure conditions.ABBREVIATIONS ABS : acrylonitrile butadiene styrene; ACGIH® TLV® : American Conference of Governmental Industrial Hygienists Threshold Limit Value; ACH : air change per hour; AM : additive manufacturing; ASA : acrylonitrile styrene acrylate; AVP : acetone vapor polishing; BJ : binder jetting; CAM-LEM : computer-aided manufacturing of laminated engineering materials; CNF : carbon nanofiber; CNT : carbon nanotube; CP : co-polyester; CNC : condensation nuclei counter; CVP : chloroform vapor polishing; DED : directed energy deposition; DLP : digital light processing; EBM : electron beam melting; EELS : electron energy loss spectrometry; EDB : electrical diffusion batteries; EDX : energy dispersive x-ray analyzer; ER : emission rate; FDM™ : fused deposition modeling; FFF : fused filament fabrication; IAQ : indoor air quality; LSP : laser scattering photometer; LCD : liquid crystal display; LDSA : lung deposited particle surface area; LOD : limit of detection; LOM : laminated object manufacturing; LOQ : limit of quantitation; MCE : mixed cellulose ester filter; ME : material extrusion; MJ : material jetting; OEL : occupational exposure limit; OPS : optical particle sizer; PBF : powder bed fusion; PBZ : personal breathing zone; PC : polycarbonate; PEEK : poly ether ether ketone; PET : polyethylene terephthalate; PETG : Polyethylene terephthalate glycol; PID : photoionization detector; PLA : polylactic acid; PM(1) : particulate matter with aerodynamic diameter less than 1 µm; PM(2.5) : particulate matter with aerodynamic diameter less than 2.5 µm; PM(10) : particulate matter with aerodynamic diameter less than 10 µm; PSL : plastic sheet lamination; PVA : polyvinyl alcohol; REL : recommended exposure limit; SDL : selective deposition lamination; SDS : safety data sheet; SEM : scanning electron microscopy; SL : sheet lamination; SLA : stereolithography; SLM : selective laser melting; SMPS : scanning mobility particle sizer; SVOC : semi-volatile organic compound; TEM : transmission electron microscopy; TGA : thermal gravimetric analysis; TPU : thermo polyurethane; UAM : ultrasonic additive manufacturing; UC : ultrasonic consolidation; TVOC : total volatile organic compounds; TWA : time-weighted average; VOC : volatile organic compound; VP : vat photopolymerization. |
Global birth defects app: An innovative tool for describing and coding congenital anomalies at birth in low resource settings.
Dolk H , Leke AZ , Whitfield P , Moore R , Karnell K , Barišić I , Barlow-Mosha L , Botto LD , Garne E , Guatibonza P , Godfred-Cato S , Halleux CM , Holmes LB , Moore CA , Orioli I , Raina N , Valencia D . Birth Defects Res 2021 113 (14) 1057-1073 BACKGROUND: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. METHODS: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The "basic" version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The "surveillance" version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. RESULTS: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The "basic" version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The "surveillance" version is currently being field-tested. CONCLUSION: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care. |
Evaluation of classification methods for identifying multiwalled carbon nanotubes collected on mixed cellulose ester filter media
Smith D , Neu-Baker NM , Eastlake AC , Zurbenko IG , Brenner SA . J Microsc 2021 283 (2) 102-116 Enhanced darkfield microscopy (EDFM) and hyperspectral imaging (HSI) are being evaluated as a potential rapid screening modality to reduce the time-to-knowledge for direct visualization and analysis of filter media used to sample nanoparticulate from work environments, as compared to the current analytical gold standard of transmission electron microscopy (TEM). Here, we compare accuracy, specificity, and sensitivity of several hyperspectral classification models and data pre-processing techniques to determine how to most effectively identify multi-walled carbon nanotubes (MWCNTs) in hyperspectral images. Several classification schemes were identified that are capable of classifying pixels as MWCNT(+) or MWCNT(-) in hyperspectral images with specificity and sensitivity over 99% on the test dataset. Functional principal component analysis (FPCA) was identified as an appropriate data pre-processing technique, testing optimally when coupled with a quadratic discriminant analysis (QDA) model with forward stepwise variable selection and with a support vector machines (SVM) model. The success of these methods suggests that EDFM-HSI may be reliably employed to assess filter media exposed to MWCNTs. Future work will evaluate the ability of EDFM-HSI to quantify MWCNTs collected on filter media using this classification algorithm framework using the best-performing model identified here - quadratic discriminant analysis with forward stepwise selection on functional principal component data - on an expanded sample set. This article is protected by copyright. All rights reserved. |
Incidence of uterine leiomyoma in relation to urinary concentrations of phthalate and phthalate alternative biomarkers: A prospective ultrasound study
Fruh V , Claus Henn B , Weuve J , Wesselink AK , Orta OR , Heeren T , Hauser R , Calafat AM , Williams PL , Baird DD , Wise LA . Environ Int 2020 147 106218 BACKGROUND: Numerous studies suggest that some phthalates have adverse reproductive effects. However, literature on the association between phthalates and incidence of uterine leiomyomata (UL) is limited and inconsistent, with no existing prospective studies. OBJECTIVES: We examined the association of urinary concentrations of phthalate and phthalate alternative biomarkers with UL incidence. METHODS: We conducted a case-cohort analysis within a subgroup of 754 participants in the Study of the Environment, Lifestyle, and Fibroids (SELF), a prospective cohort of premenopausal Black women aged 23-35 years who were recruited during 2010-2012. We quantified fourteen phthalates and two phthalate alternative [1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH)] biomarkers in urine collected at baseline, 20 months, and 40 months. Transvaginal ultrasounds identified UL at baseline and every 20 months during 60 months of follow-up. We evaluated the individual biomarkers, molar sum of di(2-ethylhexyl) phthalate [ΣDEHP] and potency-weighted sum of anti-androgenic [WΣAA] biomarkers. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between biomarkers and UL incidence. We then used quantile g-computation to examine joint associations of multiple phthalate biomarkers with UL incidence. RESULTS: Most individual biomarkers showed weak-to-moderate inverse associations with UL incidence. HRs comparing highest vs. lowest quartiles of mono-isobutyl phthalate (MiBP) and mono-hydroxyisobutyl phthalate (MHiBP) concentrations were 0.63 (95% CI: 0.40, 1.01) and 0.61 (95% CI: 0.38, 0.96), respectively. Inverse associations for specific phthalates were stronger among women with BMI ≥ 30 kg/m(2). HRs comparing detectable vs. nondetectable concentrations of DINCH biomarkers were 0.92 (95% CI: 0.62, 1.35) for cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl ester (MHNCH) and 0.68 (95% CI: 0.38, 1.18) for cyclohexane-1,2-dicarboxylic acid mono carboxyisoocytl ester (MCOCH). For the DEHP metabolite of mono(2-ethylhexyl) phthalate (MEHP), we observed weak-to-moderate positive associations. HRs comparing highest vs. lowest quartiles for MEHP and ΣDEHP were 1.29 (95% CI: 0.82, 2.06) and 0.96 (95% CI: 0.61, 1.50), respectively. In the mixtures analysis, the HR for a joint quartile increase in phthalate biomarker concentrations was 0.90 (95% CI: 0.73, 1.08). DISCUSSION: In this prospective ultrasound study of reproductive-aged Black women, urinary concentrations of phthalate and DINCH biomarkers were not appreciably associated with higher risk of UL, either individually or jointly. |
Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island
Crawford KA , Hawley N , Calafat AM , Jayatilaka NK , Froehlich RJ , Has P , Gallagher LG , Savitz DA , Braun JM , Werner EF , Romano ME . Environ Health 2020 19 (1) 97 BACKGROUND: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors. METHODS: We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log(2)-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex. RESULTS: We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (β = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (β = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (β = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (β = - 0.50 cm, 95%CI = - 0.86, - 0.14) and female weight (β = - 0.19 kg, 95%CI = - 0.36, - 0.02), but positively associated with weekly growth in iliac skinfold thickness (β = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (β = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (β = 0.14 mm, 95%CI = 0.002, 0.28). CONCLUSIONS: Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP. |
Association of parental preconception exposure to phthalates and phthalate substitutes with preterm birth
Zhang Y , Mustieles V , Yland J , Braun JM , Williams PL , Attaman JA , Ford JB , Calafat AM , Hauser R , Messerlian C . JAMA Netw Open 2020 3 (4) e202159 Importance: Although phthalate exposure during pregnancy has been associated with preterm birth, the association of preconception exposure in either parent with preterm birth constitutes a knowledge gap. Objective: To examine the association of paternal and maternal preconception urinary concentrations of biomarkers of phthalates and phthalate substitutes with singleton preterm birth. Design, Setting, and Participants: This study, conducted at an academic fertility center in Boston, Massachusetts, included a prospective preconception cohort of subfertile couples comprising 419 mothers and 229 fathers and their 420 live-born singleton offspring born between January 1, 2005, and December 31, 2018. Statistical analysis was performed from August 1 to October 31, 2019. Exposures: Urinary concentrations of metabolites of phthalates and phthalate substitutes obtained before conception. Main Outcomes and Measures: Gestational age was abstracted from delivery records and validated using the American College of Obstetricians and Gynecologists guidelines for births after medically assisted reproduction. The risk ratio (RR) of preterm birth (live birth before 37 completed weeks' gestation) was estimated in association with urinary concentrations of 11 individual phthalate metabolites, the molar sum of 4 di-(2-ethylhexyl) phthalate (SigmaDEHP) metabolites, and 2 metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH, a nonphthalate plasticizer substitute) using modified Poisson regression models adjusted for covariates. Results: The mean (SD) age of the 419 mothers was 34.7 (4.0) years, the mean (SD) age of the 229 fathers was 36.0 (4.5) years, and the mean (SD) gestational age of the 420 singleton children (217 boys) was 39.3 (1.7) weeks, with 34 (8%) born preterm. In adjusted models, maternal preconception SigmaDEHP concentrations (RR, 1.50; 95% CI, 1.09-2.06; P = .01) and cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH, a metabolite of DINCH) concentrations (RR, 1.70; 95% CI, 0.89-3.24; P = .11) were associated with an increased risk of preterm birth. After additional adjustment for prenatal SigmaDEHP or MHiNCH concentrations, the association of maternal preconception exposure to SigmaDEHP and preterm birth remained robust (RR, 1.69; 95% CI, 1.17-2.44; P = .006), while the association of maternal preconception exposure to MHiNCH and preterm birth was attenuated (RR, 1.17; 95% CI, 0.49-2.81; P = .72). The remaining urinary metabolites examined in either parent showed no association with preterm birth. Conclusions and Relevance: In this prospective cohort of subfertile couples, maternal preconception exposure to SigmaDEHP metabolites was associated with an increased risk of preterm birth. The results suggest that female exposure to select phthalate plasticizers during the preconception period may be a potential risk factor for adverse pregnancy outcomes, which may need to be considered in preconception care strategies. |
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice.
Sheahan TP , Sims AC , Zhou S , Graham RL , Pruijssers AJ , Agostini ML , Leist SR , Schafer A , Dinnon KH 3rd , Stevens LJ , Chappell JD , Lu X , Hughes TM , George AS , Hill CS , Montgomery SA , Brown AJ , Bluemling GR , Natchus MG , Saindane M , Kolykhalov AA , Painter G , Harcourt J , Tamin A , Thornburg NJ , Swanstrom R , Denison MR , Baric RS . Sci Transl Med 2020 12 (541) Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog beta-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (beta-D-N(4)-hydroxycytidine-5'-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses. |
CoMPARA: Collaborative Modeling Project for Androgen Receptor Activity.
Mansouri K , Kleinstreuer N , Abdelaziz AM , Alberga D , Alves VM , Andersson PL , Andrade CH , Bai F , Balabin I , Ballabio D , Benfenati E , Bhhatarai B , Boyer S , Chen J , Consonni V , Farag S , Fourches D , Garcia-Sosa AT , Gramatica P , Grisoni F , Grulke CM , Hong H , Horvath D , Hu X , Huang R , Jeliazkova N , Li J , Li X , Liu H , Manganelli S , Mangiatordi GF , Maran U , Marcou G , Martin T , Muratov E , Nguyen DT , Nicolotti O , Nikolov NG , Norinder U , Papa E , Petitjean M , Piir G , Pogodin P , Poroikov V , Qiao X , Richard AM , Roncaglioni A , Ruiz P , Rupakheti C , Sakkiah S , Sangion A , Schramm KW , Selvaraj C , Shah I , Sild S , Sun L , Taboureau O , Tang Y , Tetko IV , Todeschini R , Tong W , Trisciuzzi D , Tropsha A , Van Den Driessche G , Varnek A , Wang Z , Wedebye EB , Williams AJ , Xie H , Zakharov AV , Zheng Z , Judson RS . Environ Health Perspect 2020 128 (2) 27002 BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling. OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP). METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast/Tox21 HTS in vitro assays. RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set. DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of approximately 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment. https://doi.org/10.1289/EHP5580. |
Composition-function analysis of HDL subpopulations: Influence of lipid composition on particle functionality
Niisuke K , Kuklenyik Z , Horvath KV , Gardner MS , Toth CA , Asztalos BF . J Lipid Res 2020 61 (3) 306-315 The composition-function relationship of HDL particles and its effects on the mechanisms driving coronary heart disease (CHD) is poorly understood. We tested the hypothesis that the functionality of HDL particles is significantly influenced by their lipid composition. Using a novel 3D-separation method, we isolated five different-sized HDL subpopulations from CHD patients who had low prebeta-1 functionality (ABCA1-dependent cholesterol-efflux normalized for prebeta-1 concentration) and controls who had either low or high prebeta-1 functionality. Molecular numbers of apoA-I, apoA-II, and eight major lipid classes were determined in each subpopulation by LC/MS. The average number of lipid molecules decreased from 422 in the large spherical alpha-1 particles to 57 in the small discoid prebeta-1 particles. With decreasing particle size, the relative concentration of free cholesterol (FC) decreased in alpha-mobility but not in prebeta-1 particles. Prebeta-1 particles contained more lipids than predicted; 30% of which were neutral lipids (cholesteryl ester and TG) indicating that these particles were mainly remodeled from larger particles not newly synthesized. There were significant correlations between HDL-particle functionality and the concentrations of several lipids. Unexpectedly, the phospholipid:FC ratio was significantly correlated with large-HDL-particle functionality but not with prebeta-1 functionality. There was significant positive correlation between particle functionality and total lipids in high-F controls indicating that the lipid-binding capacity of apoA-I plays a major role in the cholesterol efflux capacity of HDL particles. Functionality and lipid composition of HDL particles are significantly correlated and probably both are influenced by the lipid-binding capacity of apoA-I. |
An exploratory analysis of urinary organophosphate ester metabolites and oxidative stress among pregnant women in Puerto Rico
Ingle ME , Watkins D , Rosario Z , VelezVega CM , Calafat AM , Ospina M , Ferguson KK , Cordero JF , Alshawabkeh A , Meeker JD . Sci Total Environ 2019 703 134798 BACKGROUND: Organophosphate esters (OPEs) are used as flame retardants and plasticizers. Oxidative stress, the imbalance of reactive oxygen species and antioxidants, measured prenatally has been associated with adverse birth outcomes including preeclampsia and preterm birth. We are the first study to investigate the relationship between OPEs and oxidative stress among pregnant women. METHODS: Pregnant women 18-40 yrs. were recruited in Northern Puerto Rico (n=47) between 2011 and 2015. OPE concentrations of: bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), dibutyl phosphate (DNBP), and diphenyl phosphate (DPHP) and biomarkers for oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine up to three times during pregnancy. Associations between oxidative stress biomarkers and OPEs were assessed using linear mixed models adjusted for specific gravity, age, BMI, and income. RESULTS: Metabolites BCEtP, BDCPP, and DPHP were frequently detected (>97%). OPE metabolite concentrations remained stable over time (Intraclass correlation coefficients (ICCs): 0.51-0.60). Metabolites BCEtP, BCPP, and DPHP were associated with an increase in 8-isoprostane and OHdG. An interquartile range (IQR) increase in BDCPP was associated with a 21% increase in 8-isoprostane (p<0.01), while and IQR increase in DPHP and BCPP was associated with a 12% increase (p=0.04, p=0.08, respectively). IQR increases in BDCPP and DPHP were also associated with an 18 and 19% increase in OHdG, respectively (p<0.01). CONCLUSION: OPE metabolites were frequently detected and our results suggest that exposure to OPEs is associated with higher levels of oxidative stress. Further investigation into these relationships and birth outcomes is warranted. |
The association of urinary organophosphate ester metabolites and self-reported personal care and household product use among pregnant women in Puerto Rico
Ingle ME , Watkins D , Rosario Z , Velez Vega CM , Huerta-Montanez G , Calafat AM , Ospina M , Cordero JF , Alshawabkeh A , Meeker JD . Environ Res 2019 179 108756 BACKGROUND: Organophosphate esters (OPEs) are widely detected among U.S. pregnant women. OPEs, some of which are present in nail polish, have been associated with adverse reproductive health outcomes. More research is needed to investigate associations with OPEs and personal care products (PCP) use. METHODS: Pregnant women (18-40 years) were recruited from two hospitals and five prenatal clinics in Northern Puerto Rico (n=148 women) between 2011 and 2015. Concentrations of bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-n-butyl phosphate (DNBP), di-benzyl phosphate (DBzP), di-cresyl phosphate (DCP), DPHP, and 2,3,4,5-tetrabromobenzoic acid (TBBA) were measured twice during pregnancy. Participants completed questionnaires on PCP and household products (HP) use. Associations among products and metabolite concentrations (n=296 observations) were assessed using linear mixed models. RESULTS: BCEtP, BCPP, BDCPP and DPHP were detected frequently (>/=77%). Correlations among metabolites (0.16</=r</=0.35) and Intraclass correlation coefficients (ICCs) (0.03</=ICC</=0.34) were weak-to-moderate. Suntan lotion was associated with a 110% increase in BDCPP. DPHP increased with perfume (51%) and nail polish (49%) use. BCPP increased 46% with pesticide use in home. CONCLUSION: Biomarkers of OPEs were often detected among pregnant women. Associations with PCP and HP use suggest OPEs may be used in such products, specifically in perfume and nail polish. Further investigation into these products is warranted. |
Phthalates and phthalate alternatives have diverse associations with oxidative stress and inflammation in pregnant women
van TErve TJ , Rosen EM , Barrett ES , Nguyen RHN , Sathyanarayana S , Milne GL , Calafat AM , Swan SH , Ferguson KK . Environ Sci Technol 2019 53 (6) 3258-3267 Exposure to environmental chemicals such as phthalates has been linked to numerous adverse pregnancy outcomes, potentially through an oxidative stress mediated mechanism. Most research examined urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) as the oxidative stress biomarker. However, 8-iso-PGF2alpha also originates from enzymatic sources linked to inflammation. Therefore, associations between phthalates and 8-iso-PGF2alpha could have been misinterpreted. To clarify this, the 8-iso-PGF2alpha/prostaglandin F2alpha ratio approach was used to quantitatively distinguish between inflammation or oxidative stress derived 8-iso-PGF2alpha and estimate their associations with phthalate metabolites in a cohort of 758 pregnant women from The Infant Development and Environment Study (TIDES). Most urinary phthalate metabolites were associated with a significant increase in 8-iso-PGF2alpha. For example, a 22.4% higher 8-iso-PGF2alpha concentration (95% confidence interval = 14.4, 30.9) was observed with an interquartile range increase in mono- n-butyl phthalate. For most metabolites, associations were observed solely with oxidative stress derived 8-iso-PGF2alpha. In contrast, monocarboxy-isononyl phthalate and monoisononyl phthalate (MNP) were associated with both sources of 8-iso-PGF2alpha. Metabolites of the phthalate alternative 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH), were only associated with inflammation-derived 8-iso-PGF2alpha, which is interesting because DINCH metabolites and MNP have structural similarities.In conclusion, phthalates metabolites are not exclusively associated with oxidative stress derived 8-iso-PGF2alpha. Depending on the metabolite structure, some are also associated with inflammation derived sources, which provides interesting insights in the toxicology of phthalates. |
Sample preparation method for visualization of nanoparticulate captured on mixed cellulose ester filter media by enhanced darkfield microscopy and hyperspectral imaging
Neu-Baker NM , Eastlake AC , Brenner SA . Microsc Res Tech 2019 82 (6) 878-883 A significant hurdle in conducting effective health and safety hazard analysis and risk assessment for the nanotechnology workforce is the lack of a rapid method for the direct visualization and analysis of filter media used to sample nanomaterials from work environments that represent potential worker exposure. Current best-known methods include transmission electron microscopy (TEM) coupled with energy dispersive x-ray spectroscopy (EDS) for elemental identification. TEM-EDS is considerably time-, cost-, and resource-intensive, which may prevent timely health and safety recommendations and corrective actions. A rapid screening method is currently being explored using enhanced darkfield microscopy with hyperspectral imaging (EDFM-HSI). For this approach to be effective, rapid, and easy, sample preparation that is amenable to the analytical technique is needed. Here, we compare the sample preparation steps for mixed cellulose ester (MCE) filter media specified in NIOSH Method 7400-Asbestos and Other Fibers by Phase Contrast Microscopy (PCM)-against a new method, which involves saturation of the filter media with acetone. NIOSH Method 7400 was chosen as a starting point since it is an established technique for preparing transparent MCE filters for optical microscopy. Limitations in this method led to the development and comparison of a new method. The new method was faster, easier, and rendered filters more transparent, resulting in improved visualization and analysis of nanomaterials via EDFM-HSI. This new method is suitable for a rapid screening protocol due to its speed, ease of use, and the improvement in image acquisition and analysis. |
Cetp inhibition improves HDL function but leads to fatty liver and insulin resistance in CETP-expressing transgenic mice on a high-fat diet
Zhu L , Luu T , Emfinger CH , Parks BA , Shi J , Trefts E , Zeng F , Kuklenyik Z , Harris RC , Wasserman DH , Fazio S , Stafford JM . Diabetes 2018 67 (12) 2494-2506 In clinical trials inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels but doesn't robustly improve cardiovascular outcomes. About 2/3 of trial participants were obese. Lower plasma CETP activity is associated with increased cardiovascular risk in human studies, and protective aspects of CETP have been observed in mice fed a high-fat diet (HFD) with regard to metabolic outcomes. To define if CETP inhibition has different effects depending on the presence of obesity, we performed short-term anacetrapib treatment in chow- and HFD-fed CETP-transgenic mice. Anacetrapib raised HDL cholesterol and improved aspects of HDL functionality including reverse cholesterol transport and HDL's anti-oxidative capacity in HFD-fed mice better than in chow-fed mice. Anacetrapib worsened the anti-inflammatory capacity of HDL in HFD-fed mice. The HDL proteome was markedly different with anacetrapib treatment in HFD-fed vs. chow-fed mice. Despite benefits on HDL, anacetrapib led to liver triglyceride accumulation and insulin resistance in HFD-fed mice. Overall, our results support a physiologic importance of CETP in protecting from fatty liver, and demonstrate a context-selectivity of CETP inhibition that might be important in obese subjects. |
Urinary concentrations of phthalate metabolites, bisphenols and personal care product chemical biomarkers in pregnant women in Israel
Machtinger R , Berman T , Adir M , Mansur A , Baccarelli AA , Racowsky C , Calafat AM , Hauser R , Nahum R . Environ Int 2018 116 319-325 Mounting evidence suggests possible adverse effects of intrauterine exposure to certain phenols and phthalates, two classes of endocrine disruptor chemicals, on the developing fetus, with consequences into later life. These findings have contributed to the replacement of some chemicals, such as di2ethylhexyl phthalate (DEHP) and bisphenol A (BPA), in consumer products. For the current study we quantified urinary concentrations of biomarkers of exposure among 50 pregnant women in Israel to several phthalates, bisphenols and personal care product chemicals, as well as DEHP and BPA alternatives. We detected 14 of the 31 biomarkers in more than 90% of the women. We detected biomarkers of 1,2cyclohexane dicarboxylic acid, diisononyl ester (DINCH), bisphenol S, and bisphenol F not as frequently (27-56%). This study is the first to evaluate exposure to triclosan, bisphenols, parabens, and phthalates and BPA alternatives among Israeli pregnant women. |
Impact of enzymatic hydrolysis on the quantification of total urinary concentrations of chemical biomarkers
Dwivedi P , Zhou X , Powell TG , Calafat AM , Ye X . Chemosphere 2018 199 256-262 Human exposure to consumer and personal care products chemicals such as phenols, including parabens and other antimicrobial agents, can be assessed through biomonitoring by quantifying urinary concentrations of the parent chemical or its metabolites, often after hydrolysis of phase II conjugates. Developing suitable analytical methods for the concurrent quantification of multiple exposure biomarkers is challenging because optimal conditions for the hydrolysis of such conjugates (e.g., O-glucuronides, N-glucuronides, sulfates) may differ depending on the biomarker. We evaluated the effectiveness of seven commercial hydrolytic enzymes to simultaneously hydrolyze N-glucuronides (using the antibacterial triclocarban as example compound) and other conjugates (using select phenols and parabens as examples) by using on-line solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry. Incubation (30min, 55 degrees C) with a genetically engineered beta-glucuronidase (IMCS, >/=15 units/muL urine) hydrolyzed N-glucuronide triclocarban, but did not fully hydrolyze the conjugates of phenols and parabens. By contrast, incubation (4h, 37 degrees C) with solid beta-glucuronidase (Helix pomatia, Type H-1, >/=30 units/muL urine) or liquid beta-glucuronidase/arylsulfatase (Helix pomatia, 30 units/muL urine [i.e., 30 muL/100muL urine]) in the presence of 100muL methanol for 100muL urine completely hydrolyzed N-glucuronide triclocarban and the conjugates of several phenols and parabens, without cleaving the ester bond of the parabens to form p-hydroxybenzoic acid. These results highlight the relevance of method validation procedures that include optimizing the hydrolysis of phase II urinary conjugates (e.g., enzyme type and amount used, reaction time, temperature) to quantify accurately and concurrently multiple exposure biomarkers for biomonitoring purposes. |
Effects of FAME biodiesel and HVORD on emissions from an older-technology diesel engine
Bugarski AD , Hummer JA , Vanderslice SE . Min Eng 2017 69 (12) 43-49 The results of laboratory evaluations were used to compare the potential of two alternative, biomass-derived fuels as a control strategy to reduce the exposure of underground miners to aerosols and gases emitted by diesel-powered equipment. The effects of fatty acid methyl ester (FAME) biodiesel and hydrotreated vegetable oil renewable diesel (HVORD) on criteria aerosol and gaseous emissions from an older-technology, naturally aspirated, mechanically controlled engine equipped with a diesel oxidation catalytic converter were compared with those of widely used petroleum-derived, ultralow-sulfur diesels (ULSDs). The emissions were characterized for four selected steady-state conditions. When fueled with FAME biodiesel and HVORD, the engine emitted less aerosols by total particulate mass, total carbon mass, elemental carbon mass and total number than when it was fueled with ULSDs. Compared with ULSDs, FAME biodiesel and HVORD produced aerosols that were characterized by single modal distributions, smaller count median diameters, and lower total and peak concentrations. For the majority of test cases, FAME biodiesel and HVORD favorably affected nitric oxide (NO) and adversely affected nitrogen dioxide (NO2) generation. Therefore, the use of these alternative fuels appears to be a viable tool for the underground mining industry to address the issues related to emissions from diesel engines, and to transition toward more universal solutions provided by advanced engines with integrated exhaust aftertreatment technologies. |
Simultaneous quantification of free cholesterol, cholesteryl esters, and triglycerides without ester hydrolysis by UHPLC separation and in-source collision induced dissociation coupled MS/MS
Gardner MS , McWilliams LG , Jones JI , Kuklenyik Z , Pirkle JL , Barr JR . J Am Soc Mass Spectrom 2017 28 (11) 2319-2329 We demonstrate the application of in-source nitrogen collision-induced dissociation (CID) that eliminates the need for ester hydrolysis before simultaneous analysis of esterified cholesterol (EC) and triglycerides (TG) along with free cholesterol (FC) from human serum, using normal phase liquid chromatography (LC) coupled to atmospheric pressure chemical ionization (APCI) tandem mass spectrometry (MS/MS). The analysis requires only 50 muL of 1:100 dilute serum with a high-throughput, precipitation/evaporation/extraction protocol in one pot. Known representative mixtures of EC and TG species were used as calibrators with stable isotope labeled analogs as internal standards. The APCI MS source was operated with nitrogen source gas. Reproducible in-source CID was achieved with the use of optimal cone voltage (declustering potential), generating FC, EC, and TG lipid class-specific precursor fragment ions for multiple reaction monitoring (MRM). Using a representative mixture of purified FC, CE, and TG species as calibrators, the method accuracy was assessed with analysis of five inter-laboratory standardization materials, showing -10% bias for Total-C and -3% for Total-TG. Repeated duplicate analysis of a quality control pool showed intra-day and inter-day variation of 5% and 5.8% for FC, 5.2% and 8.5% for Total-C, and 4.1% and 7.7% for Total-TG. The applicability of the method was demonstrated on 32 serum samples and corresponding lipoprotein sub-fractions collected from normolipidemic, hypercholesterolemic, hypertriglyceridemic, and hyperlipidemic donors. The results show that in-source CID coupled with isotope dilution UHPLC-MS/MS is a viable high precision approach for translational research studies where samples are substantially diluted or the amounts of archived samples are limited. |
Evaluation of personal inhalable aerosol samplers with different filters for use during anthrax responses
Grinshpun SA , Weber AM , Yermakov M , Indugula R , Elmashae Y , Reponen T , Rose L . J Occup Environ Hyg 2017 14 (8) 0 Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person's breathing zone. While a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. The goal of this study was to determine the best sampler-filter combination(s) for the collection and extraction of B. anthracis spores. The study was designed to 1) evaluate the performance of four filter types [one mixed cellulose ester, MCE (pore size = 3 microm), two polytetrafluoroethylene, PTFE (1 and 3 microm), and one polycarbonate, PC (3 microm)], and 2) evaluate the best performing filters in two commercially-available inhalable aerosol samplers (IOM and Button). Bacillus thuringiensis kurstaki [Bt(k)], a simulant for B. anthracis, served as the aerosol challenge. The filters were assessed based on criteria such as ability to maintain low pressure drop over an extended sampling period, filter integrity under various environmental conditions, spore collection and extraction efficiencies, ease of loading and unloading the filters into the samplers, cost, and availability. Three of four tested collection filters - except MCE - were found suitable for efficient collection and recovery of Bt(k) spores sampled from dry and humid as well as dusty and clean air environments for up to 8 h. The PC (3 microm) filter was identified as the best performing filter in this study. The PTFE (3 microm) demonstrated a comparable performance, but it is more costly. Slightly higher concentrations were measured with the IOM inhalable sampler which is the preferred sampler's performance criterion when detecting a highly pathogenic agent with no established "safe" inhalation exposure level. Additional studies are needed to address the effects of environmental conditions and spore concentration. The data obtained in this investigation are crucial for future efforts on the development and optimization of a method for assessing inhalation exposure to B. anthracis. |
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