Faculty Bibliography

An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information.

Seven parabens including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), iso-propylparaben (iPrP), butylparaben (BuP), benzylparaben (BzP), and heptylparaben (HepP) were determined in bottled water, tap water, river water, lake water, and wastewater samples collected from Hanoi, Vietnam, using solid phase extraction (SPE) followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The highest total concentration of parabens were measured in wastewater (range, 27.3-1050 ng/L; mean/median, 268/175 ng/L), followed by lake water (range, 18.0-254 ng/L; mean/median, 51.7/58.5 ng/L), river water (range, 16.5-52.1 ng/L; mean/median, 32.1/42.6 ng/L), tap water (range, 5.01-54.3 ng/L; mean/median, 28.6/41.1 ng/L), and bottled water (range, 1.56-39.9 ng/L; mean/median, 6.92/9.19 ng/L). Methylparaben and propylparaben were the predominant compounds found in all samples. The mean estimated human exposure dose of parabens through drinking bottled water was 0.27 ng/kg-bw/day, which is 6 orders of magnitude below the safety threshold recommended by the Joint FAO/WHO Expert Committee on Food Additive in 1974 (10 mg/kg-bw/day). Concentrations of parabens measured in river water, lake water, and wastewater samples were assessed to pose low to moderate ecological risks to aquatic organisms (0.1 < RQ < 1). Methyl, ethyl, and propyl parabens exhibited significant correlations in water samples.

Background/UNASSIGNED:Air pollution, which results in the formation of polycyclic aromatic hydrocarbons (PAHs), has been identified as a cause of renal function decline and a contributor to CKD. However, the results of cross-sectional studies investigating personal, integrated biomarkers of PAHs have been mixed. Longitudinal studies may be better suited to evaluate environmental drivers of kidney decline. The purpose of this study was to examine associations of serially measured urinary PAH metabolites with clinical and subclinical measures of kidney function over time among children with CKD. Methods/UNASSIGNED:-isoprostane) were assayed in urine samples. Results/UNASSIGNED:Children were followed over an average (SD) of 3.0 (1.6) years and 2469 study visits (mean±SD, 4.0±1.6). Hydroxynaphthalene (NAP) or hydroxyphenanthrene (PHEN) metabolites were detected in >99% of samples and NAP concentrations were greater than PHEN concentrations. PHEN metabolites, driven by 3-PHEN, were associated with increased eGFR and reduced proteinuria, diastolic BP z-score, and NGAL concentrations over time. However, PAH metabolites were consistently associated with increased KIM-1 and 8-OHdG concentrations. Conclusions/UNASSIGNED:Among children with CKD, these findings provoke the potential explanation of reverse causation, where renal function affects measured biomarker concentrations, even in the setting of a longitudinal study. Additional work is needed to determine if elevated KIM-1 and 8-OHdG excretion reflects site-specific injury to the proximal tubule mediated by low-grade oxidant stress.

BACKGROUND:Studies suggest associations between exposure to individual polybrominated diphenyl ethers (PBDEs) with preterm birth (PTB) and shorter gestational age. Little is known about exposure to PBDE mixtures and these outcomes. We evaluated associations of multiple PBDEs in early pregnancy with gestational age at delivery and PTB. METHODS:Data were collected from 2046 women without obesity and 396 women with obesity from the NICHD Fetal Growth Studies, who had early pregnancy plasma PBDEs concentrations and gestational age at delivery. PTB was defined as < 37 weeks of gestation at delivery and further categorized into subtypes (late or very early/moderate; spontaneous or medically indicated). We applied (1) generalized linear models (GLM); (2) principal component analysis (PCA); and (3) Bayesian Kernel Machine Regression (BKMR) to evaluate the individual and joint associations of log-transformed PBDE concentrations with gestational age at delivery and PTB, adjusting for potential confounders and evaluating effect modifiers. RESULTS:, and women who were ≥35 years old among those without obesity. In BKMR analyses, a suggestive inverse association between PBDE 153 and gestational age at delivery, and an inverse U-shaped association between PBDE 154 and gestational age at delivery were observed in women without obesity. No statistically significant association of PBDEs and gestational age or PTB was observed among women with obesity. CONCLUSIONS:PBDEs, specifically PBDE 153, were associated with shorter gestation and higher risk of certain PTB subtypes among pregnant women without obesity.

BACKGROUND/UNASSIGNED:The obesity increased incidence of diabetes, hypertension and atherosclerosis and rate of morbidity and mortality. The main cause of atherosclerosis is endothelial dysfunction and formation of foam cells and macrophage that lead to unfavorable complications. This study evaluated specific biomarkers for endothelial dysfunction as sensitive indices for early predication of atherosclerosis in obese subjects. STUDY DESIGN/UNASSIGNED:One hundred fifty male age and sex matching were included in the current study divided into three groups according to body mass index (BMI): Control (BMI ≤ 22), obese (BMI> 28) and obese with atherosclerosis (BMI> 28). Fasting serum was subjected for determination of adhesion molecules, sICAM-1, sVCAM-1, E-selectin, oxo-LDL and 8-iso-PGF2α by ELISA technique. RESULTS/UNASSIGNED:Data obtained showed that, a significant elevation of serum inflammatory markers CRP, IL-6 and TNF-α and adhesion molecules sICAM-1 (p<0.001) with sensitivity 96%, sVCAM-1 (p <0.01) with sensitivity 92%, E-selectin (p<0.001) with sensitivity 94%, oxo-LDL (p <0.05) and 8-iso-PGF2α (p < 0.001) with sensitivity 97% in obese with atherosclerosis compared with obese and control. CONCLUSION/UNASSIGNED:The levels of serum adhesion molecules contributed in the pathogenesis of endothelial dysfunction can be used as sensitive biomarkers for early prediction of atherosclerosis in obese subjects.

Perfluoroalkyl sulfonates (PFSAs), perfluoroalkyl carboxylates (PFCAs), and emerging alternatives and precursors of these compounds were determined in tissues of finless porpoise (Neophocaena asiaeorientalis sunameri) collected from East China Sea in 2009-2010 and 2018-2019. The median hepatic concentrations of emerging poly- and perfluoroalkyl substances (PFASs), including 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), 2,3,3,3-tetrafluoro-2-propanoate (HFPO-DA), and 4,8-dioxa-3H-perfluorononanoate (ADONA) were 16.2, 2.16, < LOQ (limit of quantification) and < LOQ ng/g ww (wet weight), respectively. The concentrations of legacy substances, perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA), were 86.9 and 1.95 ng/g ww, respectively. The liver concentrations of 6:2 Cl-PFESA, HFPO-DA, and perfluorohexanesulfonate (PFHxS) increased with time between 2009-2010 and 2018-2019. Further, concentrations of PFOA showed a declining trend in finless porpoise, whereas PFOS and its precursor (i.e., perfluorooctane sulfonamide [FOSA]) showed an increasing trend with time between 2009-2010 and 2018-2019. Analysis of PFASs in nine different tissues/organs of finless porpoise (i.e., liver, heart, intestine, spleen, kidney, stomach, lung, muscle, and skin) revealed a similar distribution pattern between 6:2 Cl-PFESA and PFOS; however, the tissue distribution patterns differed between HFPO-DA and PFOA. The concentrations of PFAS alternatives in kidney were similar or lower than the prototype compounds PFOS and PFOA (i.e., 8:2 Cl-PFESA < 6:2 Cl-PFESA ≈ PFOS; HFPO-DA < PFOA), implying slow renal excretion of PFAS alternatives as that of legacy PFASs. The estimates of body burdens of PFASs in porpoises suggested comparable accumulation of PFAS alternatives and legacy PFSAs and PFCAs. This study provides novel information on temporal trends and tissue distribution of emerging PFASs in marine mammals in China.

Prenatal chemical exposures can influence maternal and child health; however, few industrial chemicals are routinely biomonitored. We assessed an extensive panel of contemporary and emerging chemicals in 171 pregnant women across the United States (U.S.) and Puerto Rico in the Environmental influences on Child Health Outcomes (ECHO) Program. We simultaneously measured urinary concentrations of 89 analytes (103 total chemicals representing 73 parent compounds) in nine chemical groups: bactericides, benzophenones, bisphenols, fungicides and herbicides, insecticides, organophosphate esters (OPEs), parabens, phthalates/alternative plasticizers, and polycyclic aromatic hydrocarbons (PAHs). We estimated associations of creatinine-adjusted concentrations with sociodemographic and specimen characteristics. Among our diverse prenatal population (60% non-Hispanic Black or Hispanic), we detected 73 of 89 analytes in ≥1 participant and 36 in >50% of participants. Five analytes not currently included in the U.S. biomonitoring were detected in ≥90% of samples: benzophenone-1, thiamethoxam, mono-2-(propyl-6-carboxy-hexyl) phthalate, monocarboxy isooctyl phthalate, and monohydroxy-iso-decyl phthalate. Many analyte concentrations were higher among women of Hispanic ethnicity compared to those of non-Hispanic White women. Concentrations of certain chemicals decreased with the calendar year, whereas concentrations of their replacements increased. Our largest study to date identified widespread exposures to prevalent and understudied chemicals in a diverse sample of pregnant women in the U.S.

The potential use of growth substrates prepared with an admixture of 10% to 75% Hudson River sediments was evaluated by analysis of changes in microbial activity (measured using Biolog Ecoplates) and molecular markers (presence of degradative tceA1 and bphA genes) as well as potential risks toward humans and the environment (health and environmental risk quotients). The highest microbial activity was found in growth substrate with 25% Hudson River sediments compared to unamended control soil. Significant differences were observed between samples amended with lower (0-10%) and higher (25-75%) proportion of sediment. Microbial activity increased with the proportion of sediment amendment (≥25% sediment); however, this increase in microbial activity was not affected by increasing pollutant concentrations (PCBs, Pb, Cr Ni and Zn) nor decreasing TOC content. The growth substrate amended with Hudson River sediments demonstrated a potential for PCB degradation, as evidenced by the presence of tceA1 and bphA genes responsible, respectively, for reductive dehalogenation and oxidation of a range of aromatic organic compounds including PCBs. An assessment of risk quotients showed that the growth substrates containing lower doses of Hudson River sediments (10-50%) meet the international requirements for use in agriculture/horticulture for the production of non-food crops. Nevertheless, due to the elevated content of some toxic metals and PCBs, the growth substrate prepared with the highest proportion of sediments (75%) was not suitable for agricultural/horticultural use.

Several primary aromatic amines (AAs) are known or suspected carcinogens. Despite this, the exposure of pet animals to this class of chemicals is unknown. In this study, we investigated the occurrence of 30 AAs and two tobacco chemical markers (nicotine and cotinine) in 63 pet urine (42 dog and 21 cat) and 77 pet feces (37 dog and 40 cat) samples collected from the Albany area of New York State. Eight of the 30 AAs (∑₈AAs) were found in > 38% of dog and cat urine samples, at median concentrations of 7.99 (range: 0.42-52.3 ng/mL) and 31.4 (2.63-75.9) ng/mL, respectively. Nine of the 30 AAs (∑₉AAs) were found in > 73% of dog and cat feces samples, at median concentrations of 278 (range: 61.7-613 ng/g) and 240 (55.4-645) ng/g dry wt, respectively. Among the 30 AAs, 2,6-dimethylaniline (2,6-DMA) accounted for the highest median concentrations in both urine and fecal samples. Median concentrations of nicotine and cotinine were below 0.92 ng/mL in urine and below 3.86 ng/g in feces of both dogs and cats. No significant relationship was found between AA concentrations and pet age or gender. The lack of significant Spearman's rank correlation between the concentrations of AA and nicotine in pet urine/feces suggested that sources other than tobacco smoke contributed to AA exposure in pets. Furthermore, the calculated fecal excretion rates of AAs were higher than the intake rates (estimated through reverse dosimetry), which indicates that cats and dogs are exposed to AA precursors such as azo dyes. Concentrations in urine and feces reflected exposure to direct and indirect exposure sources, respectively, of AAs.