Faculty Bibliography

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.

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.

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.

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.

Phthalates have been associated with reproductive toxicity and precocious puberty in females, but the occurrence of these toxicants in feminine hygiene products is rarely reported. In this study, eight phthalates were determined in 120 feminine hygiene products (56 feminine care products and 64 sanitary napkins) collected from China. Phthalates were found in 86% and 98% of feminine care products and sanitary napkins, respectively, with the total concentrations varying between not detectable and 813 μg/g (median: 0.26 μg/g) and 0.25 and 8.76 μg/g (1.43 μg/g), respectively. Diethyl phthalate, dibutyl phthalate, and bis(2-ethylhexyl)phthalate were the major compounds, accounting for >60% of the total concentrations. The plastic materials used on the top and bottom layers and the hot melt adhesive used during the manufacturing process are the potential sources of phthalates in sanitary napkins. The range of daily exposure doses of phthalates in women from the use of feminine care products and sanitary napkins was <0.001-0.156 μg/kg-bw/day and <0.001-0.731 μg/kg-bw/day, respectively. Sanitary napkins contributed to 8.2% of the total exposure, and the levels of exposure to several phthalates from sanitary napkins were much higher than those reported from indoor dust ingestion but were lower than those of dietary intakes. Our study confirmed a new source of women's exposure to phthalates, sanitary napkins.

Bisphenol A (BPA) and its alternatives are suspected endocrine disruptors. However, prenatal exposure and transplacental transfer of bisphenols (BPs is still limited. Therefore, BPA and its six alternatives in maternal serum (MS), maternal urine (MU), cord serum (CS), and amniotic fluid (AF) samples collected from 106 maternal-fetal pairs in an e-waste dismantling site in Southern China were determined. Bisphenol AF (BPAF) and bisphenol S (BPS) were the dominant BPA alternatives observed in MS and CS, and the geometric mean (GM) concentration of BPAF (0.013 ng/mL in MS, 0.097 ng/mL in CS) and BPS (0.01 ng/mL in MS, 0.03 ng/mL in CS) in MS and CS was lower than that of BPA (0.5 ng/mL in MS, 1.2 ng/mL in CS). The ratios of BPA concentrations between MU and MS (MU:MS ratio) were over three times higher than those of AF and CS (AF:CS ratio), thereby suggesting low biotransformation/metabolism of BPA in fetuses. The placental transfer rates of BPs (i.e., CS:MS ratio) were compound-specific (BPAF 3.26, BPA 1.94, BPS 1.11). Results suggest that BPA and its alternatives can pass through the placental barrier. The placental transfer rates of BPs are positively related to molecular weight or log K_ow values. This finding indicates that an active transport is responsible for the placental transfer of BPs.

Organophosphate (OP) esters are emerging environmental contaminants, but little is known about their occurrence in dust. In this study, 19 OP triesters and their 11 diester degradation products were measured in indoor dust and outdoor dust collected from China. ∑OP triester concentrations in indoor dust (median: 2380 ng/g dry weight [dw]) were an order of magnitude higher than those in outdoor dust (446 ng/g dw). The median concentrations of ∑OP diesters in indoor and outdoor dust were 260 and 96.8 ng/g dw, respectively. Dust samples collected from eastern and southern China contained higher concentrations of ∑OP di- and tri-esters than those from the other regions. Dust from the most urbanized areas in China including Beijing, Shanghai, and Guangzhou exhibited the highest concentrations of ∑OP di- (>1000 ng/g dw) and triesters (>4000 ng/g dw). We also found notable concentrations of emerging aryl-OP triesters in dust (3.85-10.6 ng/g dw). Significant correlations existed between the concentrations of bis(2-ethylhexyl) phosphate (BEHP) and tris(2-ethylhexyl) phosphate (TEHP) (rho = 0.672-0.691, p < 0.01), as well as DPHP and triphenyl phosphate (TPHP) (rho = 0.537-0.766, p < 0.01) in dust samples, indicating that OP diesters originated from the degradation of triesters. High molar concentration ratios of DEP to triethyl phosphate (TEP) and DPHP to TPHP/ethylhexyl diphenyl phosphate (EHDPP) suggested that these OP triesters degrade readily. Significant correlations were found between the concentrations of ∑OP di- (R²â€¯= 0.390, p < 0.05) and tri-esters (R²â€¯= 0.475, p < 0.01) in paired indoor-outdoor dust samples, which suggested that indoor dust was the source of OP esters to the outdoor environment. The estimated daily intake (EDI) of ∑OP diesters through dust ingestion was 0.21 ng/kg bw/d for adults and 2.59 ng/kg bw/d for children. The exposure levels of OP diesters, DEP and DPHP, were comparable to those of their parent triester compounds.

Feminine hygiene products, a category of daily necessities, can be a source of exposure to plasticizers and antimicrobial agents in women. Nevertheless, studies on the occurrence of chemicals in feminine hygiene products have received little attention. In this study, 24 endocrine-disrupting chemicals (EDCs), comprising nine phthalates, six parabens, eight bisphenols, and triclocarban (TCC) were measured in seven categories of feminine hygiene products (i.e., pads, panty liners, tampons, wipes, bactericidal creams and solutions, and deodorant sprays and powders; N = 77) collected in the Albany area of New York State in the United States. Dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), di-iso-butyl phthalate (DIBP), di(2-ethylhexyl) phthalate (DEHP), methyl paraben (MeP), and ethyl paraben (EtP) were found in all pad, panty liner, and tampon samples. Panty liners contained the highest concentrations of DMP (median: 249 ng/g), DEP (386 ng/g), DBP (393 ng/g), and DIBP (299 ng/g) and tampons contained the highest concentrations of DEHP (267 ng/g). MeP, EtP, and propyl paraben (PrP) were the major parabens found in feminine hygiene products. Bactericidal creams and solutions contained median concentrations of MeP, EtP and PrP at 2840, 734, and 278 ng/g, respectively. The estimated exposure doses of phthalates, parabens, and bisphenols through the dermal absorption pathway from the use of pads, panty liners, and tampons were significant. In comparison with the exposure doses reported previously from other sources and pathways, the significance of feminine hygiene products as sources of EDC exposure was delineated. The dermal absorption doses from the use of feminine hygiene products, under different exposure scenarios, were 0.19-27.9% and 0.01-6.2% of the total exposure doses of phthalates and bisphenols, respectively. This is the first study to report the occurrence of phthalates, parabens, bisphenols, and TCC in feminine hygiene products from the United States.