Faculty Bibliography

Perfluoroalkyl substances (PFAS) were among various persistent organic pollutants suspected to have been released during the collapse of the World Trade Center (WTC) on 9/11. Evidence on the association between prenatal PFAS exposure and child neurodevelopment is limited and inconsistent. This study evaluated the association between prenatal PFAS exposure and child cognitive outcomes measured at 5 different time points in a population prenatally exposed to the WTC disaster. The study population included 302 pregnant women in the Columbia University WTC birth cohort enrolled between December 13, 2001 and June 26, 2002 at three hospitals located near the WTC site: Beth Israel, St. Vincent's, and New York University Downtown. We evaluated the association between prenatal exposure to four PFAS (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA)) and child neurodevelopment measured using the Bayley Scales of Infant Development (BSID-II) at approximately 1, 2 and 3 years of age and using The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at approximately 4 and 6 years of age. Geometric mean (range) concentrations of PFAS were 6.03 (1.05, 33.7), 2.31 (0.18, 8.14), 0.43 (<LOQ, 10.3) and 0.67 (<LOQ, 15.8) ng/mL for PFOS, PFOA, PFNA and PFHxS, respectively. Several PFAS were associated with increases in cognitive outcomes in females and overall (males and females combined). Child sex modified the association between PFOS and the mental development index measured using BSID-II, with the observed relationship being positive for females and negative for males. Through principal component analyses, we observed a negative relationship between PFNA and the psychomotor development index measured using BSID-II and the verbal IQ measured using WPPSI. Our results suggest a sex- and compound-specific relationship between prenatal PFAS exposures and childhood neurodevelopment.

The aim of the study was to evaluate the influence of the application of increasing proportions (0%, 10%, 25%, 50%, 75%, and 100%) of an admixture of PCB-contaminated Hudson River sediment collected from the Upper Hudson River, near Waterford, Saratoga county (New York, USA) on soil properties, phytotoxicity, and biometric and physiological responses of cucumber (Cucumis sativus L. cv 'Wisconsin SMR 58') and zucchini (Cucurbita pepo L. cv 'Black Beauty') grown as potential phyto- and rhizoremediators. The experiment was performed for 4 weeks in a growth chamber under controlled conditions. Amendment of Hudson River sediment to soil led to a gradual increase in PCB content of the substratum from 13.7 μg/kg (with 10% sediment) to 255 μg/kg (with 100% sediment). Sediment amendment showed no phytotoxic effects during the initial stages, even Lepidium sativum root growth was stimulated; however, this positive response diminished following a 4-week growth period, with the greatest inhibition observed in unplanted soil and zucchini-planted soil. The stimulatory effect remained high for cucumber treatments. The sediment admixture also increased cucurbit fresh biomass as compared to control samples, especially at lower doses of sediment admixture, even though PCB content of the soil amended with sediment increased. Cucurbits' leaf surface area, in turn, demonstrated an increase for zucchini, however only for 50% and 75% sediment admixture, while cucumber showed no changes when lower doses were applied and decrease for 75% and 100% sediment admixture. Chlorophyll a + b decreased significantly in sediment-amended soils, with greater inhibition observed for cucumber than zucchini. Our results suggest that admixture of riverine sediment from relatively less-contaminated locations may be used as soil amendments under controlled conditions; however, further detailed investigation on the fate of pollutants is required, especially in terms of the bioaccumulation and biomagnification properties of PCBs, before contaminated sediment can be applied in an open environment.

The aim of this study was to assess the potential for application of Hudson River sediment as a plant growth medium by mixing with various proportions of soil. The growth medium obtained by the admixture of soil and Hudson River sediment was characterized by optimal pH, reduced salinity, and presence of macro- (K, Mg) and micronutrients (Fe, Mn). Apart from beneficial nutrients and organic matter, the riverine sediment also contained toxic metals (Zn 86 mg; Cu 17.8 mg; Ni 16.6 mg; Cr 20.7 mg; Cd 0.46 mg; Pb 20.7 mg/kg, at concentrations below the threshold effect concentration) and PCBs (total concentration 254 ng/g), which can have a negative impact on soil ecosystems. The results ecological risk assessment of six trace elements and PCBs in sediment suggested medium/moderate risk (PECq = 0.21) and the need for ecotoxicological tests prior to its use as a growth medium. However, ecotoxicity tests of the soil/sediment admixture indicated that it was non-toxic or less-toxic to crustacean Heterocypris incongruens (PE = - 8-38%) and bacteria Aliivibrio fischeri (PE = - 20-38). For Sinapis alba L. and Lepidium sativum L., the germination index (GI) indicated the dominance of inhibitory effect on plant growth; whereas for the Sorghum saccharatum L., the GI value showed the stimulatory effect. Based on the above physicochemical and ecotoxicological analyses, the sediment was found suitable for use as a growth medium, for non-edible plants. It is worth to underline that this sediment was collected from relatively less contaminated location of the river and therefore the results may not represent sediments from entire stretch of the Hudson River.

Organophosphate esters (OPEs) are used as flame retardants and plasticizers in many consumer products. Owing to OPEs' toxicity, exposure of organisms in aquatic ecosystems is a concern. Information that pertains to the occurrence and distribution of OPEs in marine aquatic environment, however, is scarce. In this study, concentrations and profiles of 14 OPE triesters were determined in sediment collected in coastal waters (Bohai Sea and East China Sea) of northern China. The total concentrations of OPEs (ΣOPEs) in surface sediment were in the range of 1.76-49.9 (median: 9.13) ng/g dry weight (dw), which were comparable to or lower than the range of concentrations reported for surface sediments worldwide. Tris(2-chloro-propyl) phosphate (TCIPP), tris(2-chloroethyl) phosphate (TCEP), tri-isobutyl phosphate (TiBP), and tri-n-butyl phosphate (TnBP) were the predominant OPEs found in surface sediment, collectively accounting for 81% of the total concentrations. ΣOPE concentrations in sediment core (range: 8.58-169, median: 31.6 ng/g dw) were generally higher than those found in surface sediment. The vertical distribution of OPEs in sediment core showed a gradual increasing trend in concentrations during the past decade.

Polar bear (Ursus maritimus) populations accumulate dioxins and related compounds (DRCs) at levels that are of health concern. The toxicities of DRCs are primarily mediated via aryl hydrocarbon receptor (AHR) signaling pathway. To evaluate the sensitivity and responses to DRCs in polar bears, we assessed the activation potencies of polar bear-specific AHR (pbAHR) by DRCs through in vitro and in silico approaches. In vitro assays showed that the pbAHR was as sensitive to DRCs as C3H/lpr mouse AHR, which is well-known to be highly sensitive to DRCs. Comparison of pbAHR transactivation potencies indicated that TCDF, 2,3,4,7,8-PeCDF, and BaP exhibited high induction equivalency factors (IEFs). Considering the accumulation levels of DRCs in polar bears, PCB126 was found to be the most active inducer of pbAHR. The in vitro transactivation potencies of ligands of pbAHR showed a significant relationship with in silico ligand docking energies in a pbAHR homology model. The protein ligand interaction fingerprint (PLIF) analysis showed different interaction patterns depending on the ligands. Several amino acids which are highly conserved among mammals may be involved in species-specific responses via backbone interactions with neighboring amino acid residues which are specific to pbAHR. We document high susceptibility of polar bears to DRCs, through a mechanistic approach, for the first time.

Importance/UNASSIGNED:Prenatal exposure to persistent organic pollutants (POPs) has been associated with birth size, but data on fetal growth and among racially/ethnically diverse pregnant women remain scarce. Objectives/UNASSIGNED:To assess the association between maternal plasma POPs in early pregnancy and fetal growth and by infant sex and maternal race/ethnicity. Design, Setting, and Participants/UNASSIGNED:This cohort study used the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort, which recruited nonobese, low-risk pregnant women before 14 weeks' gestation between July 1, 2009, and January 31, 2013, in 12 community-based clinics throughout the United States. Participants self-identified their race/ethnicity, self-reported their behavioral risk factors, and were followed up throughout their pregnancy. Data were analyzed from July 31, 2018, to June 3, 2019. Exposures/UNASSIGNED:Levels of 76 POPs in early gestation plasma were measured: 11 perfluoroalkyl and polyfluoroalkyl substances, 1 polybrominated biphenyl, 9 polybrominated diphenyl ethers (PBDEs), 44 polychlorinated biphenyls (PCBs), and 11 organochlorine pesticides (OCPs). The bayesian kernel machine regression method was used to examine chemical class mixtures, and generalized additive mixed model was used to analyze individual chemicals. Main Outcomes and Measures/UNASSIGNED:Fourteen fetal biometrics were measured, including head circumference, abdominal circumference, and femur length, within 5 ultrasonography appointments. Results/UNASSIGNED:A total of 2284 low-risk pregnant women were included: 606 women (26.5%) self-identified as white with a mean (SD) age of 30.3 (4.4) years, 589 (25.8%) as black with a mean (SD) age of 25.5 (5.5) years, 635 (27.8%) as Hispanic with a mean (SD) age of 27.1 (5.5) years, and 454 (19.9%) as Asian with a mean (SD) age of 30.5 (4.5) years. A comparison between the 75th and 25th percentile of exposure revealed that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% CI, -6.7 to -2.8 mm) in head circumference, 3.5 mm (95% CI, -4.7 to -2.2 mm) in abdominal circumference, and 0.6 mm (95% CI, -1.1 to -0.2 mm) in femur length. Higher exposure to the PBDE mixture was associated with reduced abdominal circumference (-2.4 mm; 95% CI, -4.0 to -0.5 mm) and femur length (-0.5 mm; 95% CI, -1.0 to -0.1 mm), and the dioxin-like PCB mixture was associated with reduced head circumference (-6.4 mm; 95% CI, -8.4 to -4.3 mm) and abdominal circumference (-2.4 mm; 95% CI, -3.9 to -0.8 mm). Associations with individual chemicals were less consistent. There were some interactions by fetal sex, although most of the results did not vary by maternal race/ethnicity. For example, oxychlordane (-0.98 mm; 95% CI, -1.60 to -0.36 mm; P for interaction <.001), trans-nonachlor (-0.31 mm; 95% CI, -0.54 to -0.08 mm; P for interaction = .005), and p,p'-dichlorodiphenyldichloroethylene (-0.19 mm; 95% CI, -0.22 to -0.09 mm; P for interaction = .006) were associated with shorter femur length among boys only. Conclusions and Relevance/UNASSIGNED:This study found that, among pregnant women with low POP levels, a mixture of OCPs was negatively associated with most fetal growth measures and that mixtures of PBDEs and dioxin-like PCBs were associated with reduced abdominal circumference. These findings suggested that, although exposures may be low, associations with fetal growth are apparent.

Human exposure to neonicotinoid insecticides (hereafter "neonics") is a concern. Spot urine samples have been widely used in the assessment of exposure to neonics. Urinary concentrations, however, can vary greatly over time due to variable exposure, potentially leading to exposure misclassification. In this study, within- and between-individual variability of urinary concentrations of 13 neonics and their metabolites collected consecutively for up to 44 days from 19 individuals were examined. We also measured seven oxidative stress biomarkers (OSBs) in repeated urine samples to elucidate their relationship with neonic exposure by mixed regression models. Intraclass correlation coefficients (ICCs, a ratio of between-individual variance to total variance) were used to assess the reproducibility of neonic/metabolite concentrations. Sensitivity and specificity were used to evaluate how well spot urine samples determined an individual's average exposure over 44 days. A fair to good reproducibility was observed for N-desmethyl-acetamiprid (ICC = 0.42), whereas thiamethoxam, imidacloprid, clothianidin, imidaclothiz, 6-chloronicotinic acid, and sulfoxaflor showed poor reproducibility (ICC = 0.02-0.37). Use of single-spot urine samples to classify high (top 33%) exposure showed higher specificities (0.68-0.92) than sensitivities (0.32-0.88). The minimum number of specimens (k) required to estimate participant-specific mean for neonic exposures within 20% of the "true" values ranged from 16 to 172. Significant positive correlations were found between some of neonic and OSB concentrations. The high variability found in the urinary concentrations of most neonics/metabolites suggests that a single measurement can result in exposure misclassification.

Drinking water is an important source of human exposure to bromate, an ubiquitous environmental contaminant and a suspect human carcinogen. Nevertheless, little is known with regard to bromate exposure from water produced by thermal desalination of seawater. The purpose of this study was to determine the occurrence of bromate in desalinated drinking water and groundwater from Kuwait and estimate associated exposure and health risks to consumers. In this study, 194 tap and ground water samples collected from Kuwait were analyzed for the presence of bromate and bromide (reduced form of bromine). Bromate was found in almost all tap water samples with a mean concentration of 19.6 μg/L, which is higher than the maximum acceptable contaminant level (MCL) of 10 μg/L. The mean concentration of bromide in tap water samples was 46.2 μg/L. In bottled water, lower mean bromate concentration was found (2.89 μg/L) with mean bromide levels at 76.1 μg/L. Saline brackish water had bromate concentration at 9.48 μg/L while bromate was not detected in saline groundwater/well water samples. The mean estimated daily intake (EDI) of bromate by the Kuwaiti population through tap water and commonly consumed bottled water was 21.7 μg/d and 3.21 μg/d, respectively. Among the five age groups, 3 to 5-year-old children had the highest EDI of bromate at 15.4 μg/d. The excess cancer risk due to ingestion of bromate in tap water was estimated to be 3.92 × 10^-4, which is approximately one order of magnitude higher than the maximum acceptable level of risk (2× 10^-5). This study highlights the significance of desalinated water as a source of bromate exposure.

Endocrine-disrupting chemicals are ubiquitously present in our environment, but the mechanisms by which they adversely affect human reproductive health and strategies to circumvent their effects remain largely unknown. Here we show in Caenorhabditis elegans, that supplementation with the antioxidant Coenzyme Q10 (CoQ10) rescues the reprotoxicity induced by the widely used plasticizer and endocrine disruptor bisphenol A (BPA) in part by neutralizing DNA damage resulting from oxidative stress. CoQ10 significantly reduces BPA-induced elevated levels of germ cell apoptosis, phosphorylated checkpoint kinase 1 (CHK-1), double-strand breaks (DSBs) and chromosome defects in diakinesis oocytes. BPA-induced oxidative stress, mitochondrial dysfunction, and increased gene expression of antioxidant enzymes in the germline are counteracted by CoQ10. Finally, CoQ10 treatment also reduced the levels of aneuploid embryos and BPA-induced defects observed in early embryonic divisions. We propose that CoQ10 may counteract BPA-induced reprotoxicity through the scavenging of reactive oxygen species and free radicals and that this natural antioxidant could constitute a low-risk and low-cost strategy to attenuate the impact on fertility by BPA.

Six parabens and their four metabolites were measured in paired maternal serum (MS) and cord serum (CS) samples collected from 95 pregnant women to elucidate placental transfer of this class of compounds. Matched maternal urine (MU) and amniotic fluid (AF) collected from 13 of 95 pregnant women were also analyzed to examine partition of these chemicals between maternal and fetal tissues. The placental transfer rates (PTRs; concentration ratio of parabens between CS and MS) of methyl- (MeP), ethyl- (EtP), propyl-parabens (PrP) were 0.81, 0.63, and 0.60, respectively. Furthermore, the PTRs of OH-MeP (0.93) and OH-EtP (1.8) were higher than those of their corresponding parent parabens, which suggested that hydroxylation increased placental transfer rates of parabens. Structure-dependent placental transfer mechanisms were observed. A significant negative correlation between molecular weights (or log K_ow) of MeP, EtP, PrP, and p-hydroxy benzoic acid (4-HB) and PTRs suggested passive diffusion as a mechanism of placental transfer of these chemicals. Nevertheless, other hydroxylated metabolites (OH-EtP, OH-MeP, and 3,4-dihydroxy benzoic acid (3,4-DHB)) showed a positive correlation between molecular weight (or log K_ow) and PTRs, which suggested that the placental transfer is mediated by protein binding of these metabolites. The MU to MS concentration ratios of MeP (MU/MS_MeP) and PrP (MU/MS_PrP) were 71 and 81, respectively, and MU/MS_MeP was two orders of magnitude higher than that found for the metabolite (MU/MS_OH-MeP: 0.35), suggesting that hydroxylation metabolite reduced urinary elimination of parabens. To our knowledge, this is the first time to report the occurrence and distribution of parabens and their metabolites in paired maternal-fetal serum, urine, and AF samples in China. Our results provide novel information on placental transfer of parabens and their metabolites.