Faculty Bibliography

Onondaga Lake in central New York State was listed as a Superfund site in 1994 due to industrial disposal of pollutants. A biomonitoring program was conducted to assess exposure to over 70 legacy contaminants and contaminants of emerging concern in populations disproportionately at risk for exposure residing near Onondaga Lake and to educate these communities on how to reduce exposures. The populations of focus were refugees from Burma and Bhutan and low-income, primarily African American, anglers (urban anglers). These communities consume locally caught fish for economic as well as cultural reasons and therefore may be at higher risk of exposure. This study focuses on assessment of exposure to per- and polyfluoroalkyl substances (PFAS) and associations with local fish consumption. Using respondent driven sampling, 311 refugees and 89 urban anglers were enrolled in the study. Following informed consent, study participants provided blood and urine specimens and completed a questionnaire. Percentiles of locally caught fish meals in the past 12 months by race/ethnicity groups showed that the Burmese participants of Karen ethnicity were the highest consumers, with a median of 135 meals compared to 103 meals for the other Burmese participants, 70 meals for the urban anglers, and 44 meals for the Bhutanese participants. Compared to the National Health and Nutrition Examination Survey (NHANES) 2015-16 sample of the general U.S. population, the Karen participants had markedly elevated perfluorooctane sulfonic acid (PFOS) and perfluorodecanoic acid (PFDA) levels with median serum concentrations 9.5 times greater (41.6 ng/mL vs. 4.4 ng/mL) and 26.9 times greater (2.69 ng/mL vs. 0.10 ng/mL), respectively; the other Burmese participants had moderately elevated levels of PFOS and PFDA with median serum concentrations 3.0 times greater (13.3 ng/mL vs. 4.4 ng/mL) and 7.3 greater times greater (0.73 ng/mL vs. 0.10 ng/mL), respectively; and, PFAS levels were not elevated in the Bhutanese or urban angler cohorts. Male gender was consistently the strongest predictor of PFAS exposure among all study cohorts. A positive association between local fish consumption was indicated only for PFOS among urban anglers. An association between local fish consumption and PFAS was not statistically significant among the refugee cohorts, perhaps due to the lack of 'lower-end' exposure or exposure variability. Community events were held by the program staff to present the biomonitoring results and distribute community outreach materials with visual aids specific for the study populations to promote safe fish eating.

Single-use or disposable facemasks have been widely used by the public for personal protection against the spread of COVID-19. The majority of disposable facemasks are made of synthetic polymers such as polypropylene, polyethylene terephthalate (as polyester), and polystyrene, and could therefore be a source of human exposure to plasticizers that are incorporated into these polymers during production. Little is known, however, about the occurrence of plasticizers in facemasks. In this study, we determined the concentrations of nine phthalate diesters and six non-phthalate plasticizers in 66 facemasks purchased in the United States. Among phthalate diesters, dibutyl phthalate, di(2-ethylhexyl)phthalate, di-iso-butyl phthalate, and butyl benzyl phthalate were found in all facemask samples, at median concentrations of 486, 397, 254, and 92 ng/g, respectively. Among non-phthalate plasticizers, dibutyl sebacate (median: 3390 ng/g) and di(2-ethylhexyl)adipate (352 ng/g) were found at notable concentrations. Inhalation exposure to select phthalate and non-phthalate plasticizers from the use of facemasks was estimated to range from 0.1 to 3.1 and 3.5 to 151 ng/kg-bw/d, respectively. To our knowledge, this is the first study to report the occurrence of phthalate and non-phthalate plasticizers in facemasks collected from the United States.

Contamination levels and distribution patterns of ten typical phthalic acid esters (PAEs) were investigated in various types of water samples collected from Hanoi metropolitan area in Vietnam. Concentrations of 10 PAEs in bottled water, tap water, lake water, and wastewater samples were measured in the ranges of 1640-15,700 ng/L (mean/median: 6400/5820 ng/L), 2100-18,000 ng/L (mean/median: 11,200/9270 ng/L), 19,600-127,000 ng/L (mean/median: 51,800/49,300 ng/L), and 20,700-405,000 ng/L (mean/median: 121,000/115,000 ng/L), respectively. Among PAEs, di-(2-ethylhexyl) phthalate (DEHP) accounted for a major proportion of total concentrations (45%) in wastewater, followed by diisobutyl phthalate (DiBP, 10.3%), and dibutyl phthalate (DBP, 9.53%). Concentrations of PAEs in wastewater decreased significantly with distance from the wastewater treatment plants (WWTPs). Concentrations of PAEs in surface water samples did not vary greatly between locations. PAEs were found in bottled water in the following order: DBP (22.4%), DiBP (22.3%), benzylbutyl phthalate (BzBP, 20.1%), and DEHP (15.5%). The estimated mean exposure doses of 10 PAEs through consumption of drinking water for adults and children in Vietnam were 254 and 256 ng/kg-bw/day, respectively. Capsule: Highest concentrations of PAEs were measured in wastewater, followed by lake water, tap water, and bottled water.

BACKGROUND:Fetal exposure to bisphenols is associated with altered fetal growth, adverse birth outcomes and childhood cardio-metabolic risk factors. Metabolomics may serve as a tool to identify the mechanisms underlying these associations. We examined the associations of maternal bisphenol urinary concentrations in pregnancy with neonatal metabolite profiles from cord blood. METHODS:In a population-based prospective cohort study among 225 mother-child pairs, maternal urinary bisphenol A, S and F concentrations in first, second and third trimester were measured. LC-MS/MS was used to determine neonatal concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL), and carnitines in cord blood. RESULTS:No associations of maternal total bisphenol concentrations with neonatal metabolite profiles were present. Higher maternal average BPA concentrations were associated with higher neonatal mono-unsaturated alkyl-lysophosphatidylcholine concentrations, whereas higher maternal average BPS was associated with lower neonatal overall and saturated alkyl-lysophosphatidylcholine (p-values < 0.05).Trimester-specific analyses showed that higher maternal BPA, BPS and BPF were associated with alterations in neonatal NEFA, diacyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines, alkyl-lysophosphatidylcholine, sphingomyelines and acyl-carnitines, with the strongest effects for third trimester maternal bisphenol and neonatal diacyl-phosphatidylcholine, sphingomyeline and acyl-carnitine metabolites (p-values < 0.05). Associations were not explained by maternal socio-demographic and lifestyle characteristics or birth characteristics. DISCUSSION/CONCLUSIONS:Higher maternal bisphenol A, F and S concentrations in pregnancy are associated with alterations in neonatal metabolite profile, mainly in NEFA, PL and carnitines concentrations. These findings provide novel insight into potential mechanisms underlying associations of maternal bisphenol exposure during pregnancy with adverse offspring outcomes but need to be replicated among larger, diverse populations.

Background/UNASSIGNED:The metabolic pathways can be affected by dysregulation in thyroid hormone levels which in turn can arise from environmental chemical exposure. This study investigated the association of selected trace elements with thyroid disorders in a Saudi population. Methods/UNASSIGNED:Urine samples collected from 100 participants (50 thyroid disorder patients and 50 controls) were analyzed to determine trace elements using inductively coupled plasma-mass spectrometer. Non-parametric Mann-Whitney Test, were used to examine the association between socio-demographic as well as clinical characteristics of thyroid profile levels (T3, T4 and TSH) and urinary trace element concentrations. Results/UNASSIGNED:Urine from patients with thyroid disorders had significantly higher concentrations of Ni, Cu, and Cd (p-values <0.0005). In contrast, urinary Cr and Zn (p-values <0.013 and 0.005) were low in thyroid patients compared to the control. Conclusion/UNASSIGNED:First study to report urinary trace element levels showed a possible link between thyroid disorders and trace element exposure which reflect the environmental pollution..

BACKGROUND:Phthalates are commonly used endocrine-disrupting chemicals that are ubiquitous in the general population. Prenatal phthalate exposure may alter placental physiology and fetal development, leading to adverse perinatal and childhood health outcomes. OBJECTIVE:We examined associations between prenatal phthalate exposure in the second and third trimesters and the placental transcriptome at birth, including genes and long noncoding RNAs (lncRNAs), to gain insight into potential mechanisms of action during fetal development. METHODS: RESULTS:was associated with multiple phthalate metabolites. Third-trimester MCIOP and mono-isobutyl phthalate concentrations were significantly associated with placental expression of 18 genes and two genes, respectively. Expression of genes within 27 biological pathways was associated with mono-methyl phthalate, MCIOP, and monoethyl phthalate concentrations. DISCUSSION/CONCLUSIONS:by phthalate exposure. https://doi.org/10.1289/EHP8973.

Although primary aromatic amines (AAs) are widely used in consumer products, little is known about their occurrence in indoor dust. A liquid chromatography - tandem mass spectrometry (LC-MS/MS) method was applied for the determination of 29 AAs and two tobacco smoke markers (nicotine and cotinine) in 256 house dust samples collected from 10 countries. Of the 29 AAs analyzed, p-anisidine, o-anisidine, 2,6-dimethylaniline (2,6-DMA), p-cresidine (p-CD), p-toluidine (p-TD), 4,4'-methylenedianiline (4,4'-MDA), ortho/meta-toluidine (o/m-TD), 4-chloroaniline (4-CA), 2,4-diaminotoluene (2,4-DAT), aniline, and 2-naphthylamine (2-NA) as well as nicotine and cotinine, were found prevalent in house dust samples. Sum median concentrations of AAs and tobacco smoke markers varied from 29.6 to 576 ng/g (overall median: 200 ng/g) and 10.8 to 2920 ng/g (415 ng/g), respectively. Among AAs, aniline was the abundant contaminant, found at median concentrations ranging from 19.6 ng/g (Colombia) to 334 ng/g (South Korea). Nicotine was detected in all indoor samples at median concentrations ranging from 9.92 ng/g (Colombia) to 2790 ng/g (India) ng/g. Concentrations of AAs in indoor dust were significantly correlated with those of nicotine. Estimated daily intake (EDI) of select AAs through the ingestion of house dust was in the range of 0.019-3.03 ng/kg-bw/day, which was five orders of magnitude below the tolerance limits.

Thyroid hormone receptor β (THRB) is posttranslationally modified by small ubiquitin-like modifier (SUMO). We generated a mouse model with a mutation that disrupted sumoylation at lysine 146 (K146Q) and resulted in desumoylated THRB as the predominant form in tissues. The THRB K146Q mutant mice had normal serum thyroxine (T4), markedly elevated serum thyrotropin-stimulating hormone (TSH; 81-fold above control), and enlargement of both the pituitary and the thyroid gland. The marked elevation in TSH, despite a normal serum T4, indicated blunted feedback regulation of TSH. The THRB K146Q mutation altered the recruitment of transcription factors to the TSHβ gene promoter, compared with WT, in hyperthyroidism and hypothyroidism. Thyroid hormone content (T4, T3, and rT3) in the thyroid gland of the THRB K146Q mice was 10-fold lower (per gram tissue) than control, despite normal TSH bioactivity. The expression of thyroglobulin and dual oxidase 2 genes in the thyroid was reduced and associated with modifications of cAMP response element-binding protein DNA binding and cofactor interactions in the presence of the desumoylated THRB. Therefore, thyroid hormone production had both TSH-dependent and TSH-independent components. We conclude that THRB sumoylation at K146 was required for normal TSH feedback regulation and TH synthesis in the thyroid gland, by a TSH-independent pathway.

Aromatic amines are widely used in personal care products and human exposure to this class of chemicals is widespread. Bioanalytical methods to determine trace levels of aromatic amines in human urine are scarce. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine 39 primary aromatic amines (AAs) along with nicotine and cotinine in human urine. Chromatographic separation of the 41 analytes was achieved on an Ultra Biphenyl (100 mm × 2.1 mm, 5 µm) column. Mass spectrometry was operated in electrospray ionization positive ion multiple reaction monitoring (MRM) mode. The method exhibited excellent linear dynamic range (0.1-50 ng/mL) with correlation coefficients (r) > 0.999 for all analytes. Urine samples (2 mL) were hydrolyzed using 10 M NaOH at 95 °C for 15 h and target analytes were extracted using methyl-tert-butyl ether (MTBE). Addition of 15 µL of 0.25 M HCl to the sample extracts improved the recoveries of several target analytes. The method was validated through the analysis of fortified quality control (QC) samples and a certified standard reference material (SRM). Relative recoveries (%) of target analytes fortified in QC samples were in the range of 75-114% for 37 of the 41 analytes while the other analytes exhibited lower recoveries (16-74%). The limits of detection (LOD) and limits of quantification (LOQ) of target analytes were in the range of 0.025-0.20 ng/mL and 0.1-1.0 ng/mL, respectively. Intra-day and inter-day precision of the method assessed through the analysis of fortified urine QC samples at three different concentrations were < 11.7% and < 15.9% (measured as RSD), respectively. The method was applied in the analysis of urine samples from the general population and known smokers; aniline, para-anisidine, para-toluidine, ortho/meta-toluidine, 3-chloroaniline, 4-chloroaniline, 3,4-dichloroaniline, and 4,4'-methylenedianiline were found in all smoker's urine at sum concentrations ranging from 0.04 to 9.16 ng/mL.

Prior research suggests that severe iodine deficiency in pregnancy may be associated with stillbirth. However, the relationship between mild to moderate iodine insufficiency, which is prevalent even in developed countries, and risk of stillbirth is unclear. We thus examined associations of iodine status and risk of stillbirth in a prospective population-based nested case-control study in Finland, a mild to moderately iodine insufficient population. Stillbirth cases (n = 199) and unaffected controls (n = 249) were randomly selected from among all singleton births in Finland from 2012 to 2013. Serum samples were collected between 10 and 14 weeks gestation and analysed for iodide, thyroglobulin (Tg) and thyroid-stimulating hormone (TSH). Odds ratios (ORs) and 95% confidence intervals (CIs) for stillbirth were estimated using logistic regression. After adjusting for maternal age, prepregnancy body mass index, socio-economic status and other factors, neither high nor low serum iodide was associated with risk of stillbirth (Q1 vs. Q2-Q3 OR = 0.92, 95% CI = 0.78-1.09; Q4 vs. Q2-Q3 OR = 0.78; 95% CI = 0.45-1.33). Tg and TSH were also not associated with risk of stillbirth in adjusted models. Maternal iodine status was not associated with stillbirth risk in this mildly to moderately iodine-deficient population. Tg and TSH, which reflect functional iodine status, were also not associated with stillbirth risk. The lack of associations observed between serum iodide, TSH and Tg and risk of stillbirth is reassuring, given that iodine deficiency in pregnancy is prevalent in developed countries.