Faculty Bibliography

In both human and animals, in utero exposure to bisphenol A (BPA), an endocrine-disrupting chemical used in the production of plastics and epoxy resins, has been shown to affect offspring reproductive and metabolic health during adult life. We hypothesized that the effect of prenatal exposure to environmentally relevant doses of BPA will be evident during fetal organogenesis and fetal/postnatal growth trajectory. Pregnant ewes were administered BPA subcutaneously from 30 to 90 days of gestation (term 147 days). Fetal organ weight, anthropometric measures, maternal/fetal hormones and postnatal growth trajectory were measured in both sexes. Gestational BPA administration resulted in higher accumulation in male than female fetuses only at fetal day 65, with minimal impact on fetal/maternal steroid milieu in both sexes at both time points. BPA-treated male fetuses were heavier than BPA-treated female fetuses at fetal day 90 whereas this sex difference was not evident in the control group. At the organ level, liver weight was reduced in prenatal BPA-treated female fetuses, while heart and thyroid gland weights were increased in BPA-treated male fetuses relative to their sex-matched control groups. Prenatal BPA treatment also altered the postnatal growth trajectory in a sex-specific manner. Males grew slower during the early postnatal period and caught up later. Females, in contrast, demonstrated the opposite growth trend. Prenatal BPA-induced changes in fetal organ differentiation and early life growth strongly implicate translational relevance of in utero contributions to reproductive and metabolic defects previously reported in adult female offspring.

Neonicotinoid insecticides (NEOs) are emerging pesticides of concern due to their potential toxicity to non-target species (e.g., bees, fish and birds). China is an important producer and user of NEOs in the world. Studies on human exposure to NEOs in China are very limited. In this study, urinary levels of six NEOs, namely acetamiprid (ACE), clothianidin (CLO), dinotefuran (DIN), imidacloprid (IMI), thiacloprid (THD), and thiamethoxam (THM) were determined in 324 individuals from 13 cities in China. Across all sampling locations, total NEO concentrations (ΣNEOs; sum of six NEOs) were dominated by CLO (median: 0.24 ng/mL), IMI (0.21 ng/mL), THM (0.15 ng/mL) and DIN (0.14 ng/mL) collectively accounting for 98% of the concentrations. Urinary concentrations of each NEO varied depending on the sampling location with the median values ranged from 0.057 to 1.2 ng/mL for CLO, from 0.036 to 0.83 ng/mL for DIN, from 0.069 to 3.2 ng/mL for IMI, and from 0.062 to 0.45 ng/mL for THM. Sex-related differences in IMI, ACE and ΣNEOs concentrations were observed with males presenting significantly higher urinary levels than did females. All six NEOs were significantly positively correlated (r = 0.135 to 0.661, p < 0.05) with each other, suggesting that the exposure sources of NEOs are common or related. On the basis of urinary IMI levels, we calculated the median daily intake (DI; mean and range) of IMI to be 1.6 (4.1, <0.02-55) μg/day, or 0.034 (0.11, <0.0003-2.1) μg/kg bw/day. To our knowledge, this is the first study to document the ubiquitous occurrence of and human exposure to NEOs in China.

BACKGROUND:The exposome is a novel research paradigm offering promise for understanding the complexity of human exposures, including endocrine-disrupting chemicals (EDCs) and pregnancy outcomes. The physiologically active state of pregnancy requires understanding temporal changes in EDCs to better inform the application of the exposome research paradigm and serve as the impetus for study. METHODS:We randomly selected 50 healthy pregnant women with uncomplicated pregnancies from a pregnancy cohort who had available serum/urine samples in each trimester for measuring 144 persistent and 48 nonpersistent EDCs. We used unsupervised machine-learning techniques capable of handling hierarchical clustering of exposures to identify EDC patterns across pregnancy, and linear mixed-effects modeling with false-discovery rate correction to identify those that change over pregnancy trimesters. We estimated the percent variation in chemical concentrations accounted for by time (pregnancy trimester) using Akaike Information Criterion-based R methods. RESULTS:Four chemical clusters comprising 80 compounds, of which six consistently increased, 63 consistently decreased, and 11 reflected inconsistent patterns over pregnancy. Overall, concentrations tended to decrease over pregnancy for persistent EDCs; a reverse pattern was seen for many nonpersistent chemicals. Explained variance was highest for five persistent chemicals: polybrominated diphenyl ethers #191 (51%) and #126 (47%), hexachlorobenzene (46%), p,p'-dichloro-diphenyl-dichloroethylene (46%), and o,p'-dichloro-diphenyl-dichloroethane (36%). CONCLUSIONS:Concentrations of many EDCs are not stable across pregnancy and reflect varying patterns depending on their persistency underscoring the importance of timed biospecimen collection. Analytic techniques are available for assessing temporal patterns of EDCs during pregnancy apart from physiologic changes.

BACKGROUND:Prenatal exposure to persistent organic pollutants (POPs) may be associated with obesogenic effects in offspring. Our study is the first to investigate associations between concentrations of POPs from newborn dried blood spots (DBS) and birth characteristics. METHODS:Concentrations of 10 polychlorinated biphenyl congeners (PCBs), polybrominated diphenyl ether-47 (PBDE-47), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were measured from DBSs collected at birth from 2,065 singleton infants. DBS samples were pooled in groups of five and assayed together to reach limits of detection. Differences in risk of large for gestational age (LGA, defined as >90th percentile of birth weight for sex and gestational age), small for gestational age (SGA, <10th), and preterm birth (gestational age <37 weeks) were estimated using logistic regression per unit (ng/ml) increase in concentration of each chemical, adjusting for individual-level covariates, including maternal age, race/ethnicity, prepregnancy BMI, education, parity, smoking, and infant sex while assuming a gamma distribution and using multiple imputation to account for pools. RESULTS:There were 215 (11.3%) singletons born LGA, 158 (7.5%) born SGA, and 157 (7.6%) born preterm. Higher concentrations of POPs were positively associated with slightly higher risk of LGA and higher birth weight. CONCLUSIONS:Relationships between POPs measured in newborn DBS and birth size were mixed. Pooled analysis methods using DBS could address challenges in limits of detection and costs for population-based research.

Normal maternal thyroid function during pregnancy is essential for fetal development and depends upon an adequate supply of iodine. Little is known about how iodine status is associated with preterm birth and small for gestational age (SGA) in mildly iodine insufficient populations. Our objective was to evaluate associations of early pregnancy serum iodine, thyroglobulin (Tg), and thyroid-stimulating hormone (TSH) with odds of preterm birth and SGA in a prospective, population-based, nested case-control study from all births in Finland (2012-2013). Cases of preterm birth (n = 208) and SGA (n = 209) were randomly chosen from among all singleton births. Controls were randomly chosen from among singleton births that were not preterm (n = 242) or SGA (n = 241) infants during the same time period. Women provided blood samples at 10-14 weeks' gestation for serum iodide, Tg and TSH measurement. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for preterm birth and SGA. Each log-unit increase in serum iodide was associated with higher odds of preterm birth (adjusted OR = 1.19, 95% CI = 1.02-1.40), but was not associated with SGA (adjusted OR = 1.01, 95% CI = 0.86-1.18). Tg was not associated with preterm birth (OR per 1 log-unit increase = 0.87, 95% CI = 0.73-1.05), but was inversely associated with SGA (OR per log-unit increase = 0.78, 95% CI = 0.65-0.94). Neither high nor low TSH (versus normal) were associated with either outcome. These findings suggest that among Finnish women, iodine status is not related to SGA, but higher serum iodide may be positively associated with preterm birth.

The goal of this study was to assess biomarkers of exposure to glyphosate and assess potential associations with renal function in children. Glyphosate is used ubiquitously in agriculture worldwide. While previous studies have indicated that glyphosate may have nephrotoxic effects, few have examined potential effects on kidney function in children. We leveraged three cohorts across different phases of child development and measured urinary levels of glyphosate. We evaluated associations of glyphosate with three biomarkers of kidney injury: albuminuria (ACR), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury marker 1 (KIM-1). Multivariable regression analyses examined associations of glyphosate with kidney injury biomarkers controlling for covariates. We identified glyphosate in 11.1% of the total participants. The herbicide was detected more frequently in the neonate population (30%). Multivariable regression models failed to identify significant associations of log-transformed glyphosate with any of the kidney injury biomarkers, controlling for covariates age, sex, and maternal education. While we confirm detectability of glyphosate in children's urine at various ages and stages of life, there is no evidence in this study for renal injury in children exposed to low levels of glyphosate. Further studies of larger sample size are indicated to better understand putative deleterious effects of the herbicide after different levels of exposure.

Human exposure to microplastics has been a topic of interest, but measurements of exposure are limited. Pet animals are sentinels of human exposure, as they share a common living environment with humans. In this study, 58 pet (cat and dog) foods and 78 pet feces samples were collected from Albany, NY, USA, for the analysis of polyethylene terephthalate (PET) and polycarbonate (PC) by alkali-assisted thermal depolymerization and liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods. PET was detected at concentrations in the range of <1,500 ng/g to 12,000 ng/g (median: <1,500 ng/g) and <1,500 to 4,600 ng/g (median: <1,500 ng/g) in cat and dog foods, respectively. The concentrations of PET in cat (<2,300-340,000 ng/g, median: 61,000 ng/g) and dog (7700-190,000 ng/g, median: 30,000 ng/g) feces were 1-2 orders of magnitude higher than those in pet food samples. A significant positive correlation was found between the concentrations of the monomers (i.e., TPA and BPA) and the corresponding MPs in cat feces. The calculated mean estimated daily intake of PET and PC (calculated from pet food) was lower than that of the mean cumulative daily intake (calculated from pet feces), which suggested that diet is a minor source of exposure to PET and PC in pets.

Human exposure to endocrine-disrupting chemicals (EDCs) has aroused considerable public concern over the last three decades. Nevertheless, little is known with regard to the exposure of EDCs in farm animals. In this study, concentrations of 22 phthalate metabolites (PhMs), 15 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs), and 8 bisphenols (BPs) were determined in 183 bovine urine samples collected from China, India, and the United States. The median concentrations of urinary PhMs, OH-PAHs, and BPs in bovines, collectively, were 66, 4.6, and 16 ng/mL, respectively. Mono-n-butyl phthalate (mBP; median, 14 ng/mL) and ∑₄DEHP (four secondary metabolites of di(2-ethylhexyl) phthalate; 13 ng/mL) were the dominant PhMs; hydroxy-fluorene (OH-Fluo; 1.2 ng/mL) and -phenanthrene (OH-Phen; 1 ng/mL) were the dominant OH-PAHs; and 4,4'-di-hydroxydiphenylmethane (BPF; 10 ng/mL) and 2,2-bis(4-hydroxyphenyl) propane (BPA; 6.7 ng/mL) were the dominant BPs. Bovine urine samples from India and China contained the highest concentrations of PhMs and OH-PAHs, whereas those from India and the United States contained the highest concentrations of BPs. PhM and OH-PAH concentrations were significantly higher in the urine of bulls than those of cows; no such difference was found for BPs. Our findings establish baseline exposure information about three classes of EDCs in domestic farm animals.

Organophosphate esters (OPEs) are used in aircraft lubricating oil and hydraulic fluids, and, thus, airplane emissions are thought to be an important source of these chemicals in the environment. In this study, concentrations of 20 OPEs, comprising seven alkyl-OPEs, three chlorinated (Cl)-OPEs, seven aryl-OPEs, and three oligomeric-OPEs, were determined in outdoor air, soil, pine needles, river water, and outdoor dust samples collected around an airport in Albany, New York, in 2018. Elevated ∑OPE concentrations were found in outdoor air, soil, pine needles, outdoor dust, and river water in the ranges of 1320-20,700 pg/m³ (median: 3880), 1.16-73.1 (14.3) ng/g dry weight (dw), 23.2-534 (102) ng/g (dw), 153-2140 (824) ng/g (dw), and 174-24,600 (1250) ng/L, respectively. The total OPE concentrations in air, soil, water, and outdoor dust samples in the study area were dominated by Cl-OPEs, whereas those in pine needles were dominated by aryl-OPEs. The spatial distribution of OPEs in air, soil, and pine needles showed a gradual decreasing trend with increasing distance from the airport. A significant correlation was observed between ∑OPE concentrations in air and soil, and the fugacity ratio showed the flux of OPEs from air to soil. The spatial distribution of OPEs between air and pine needles was similar and highly correlated, suggesting that pine needles are suitable indicators of atmospheric OPE concentrations. In addition to urban activities, aircraft hydraulic/lubricant oils are a major source of OPEs in the vicinity of the airport. The average daily intake of OPEs via air inhalation and outdoor dust ingestion in the vicinity of the airport was up to 1.53 ng/kg bw/day for children and 0.73 ng/kg bw/day for adults.

Despite high production and usage of parabens and bisphenols, little is known about their spatiotemporal distribution in the marine environment. In this study, we determined the concentrations of several parabens and their metabolites as well as bisphenol analogues in sediment collected from coastal areas of northern China. All sediment samples, including surface sediment and sediment cores, contained at least one of the parabens analyzed, and the total concentrations of parabens (ΣPBs; sum of six parabens) ranged from 1.37 to 24.2 ng/g dw (geometric mean: 3.30-6.09 g/g dw), which was comparable to or slightly higher than those found for the total concentrations of five detectable bisphenols (ΣBPAs; geometric mean: 2.18-4.61 ng/g dw). 4-hydroxybenzoic acid, a common metabolite of parabens, was found in all samples at concentrations in the range of 6.85-437 ng/g dw, which was one order of magnitude lower than those found for benzoic acid. Methyl-, ethyl-, and propyl-parabens were the predominant paraben analogues, collectively accounting for >88% of ΣPBs. Bisphenol A and bisphenol F were the two major bisphenols, collectively accounting for >86% of ΣBPAs. We also examined vertical profiles in concentrations of target analytes in sediment cores. The sediment core from the Shandong Peninsula showed a gradual increase in the concentrations of several parent and metabolic parabens as well as bisphenols during the past decade. Relatively higher concentrations of parabens and bisphenols were found in sediment cores collected from industrialized areas. Significant positive correlations were found among the concentrations of parabens in sediment, which suggested the existence of similar sources for these compounds. Overall, our findings suggest that the Bohai Sea coast is moderately contaminated with parabens and bisphenols in comparison to other coastal areas in China or elsewhere.