Faculty Bibliography

BACKGROUND:Insufficient or excessive gestational weight gain are associated with increased risks of adverse birth and childhood outcomes. Increasing evidence suggests that exposure to bisphenols and phthalates may disrupt hormonal pathways and thereby influence gestational weight gain. OBJECTIVE:To examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with gestational weight gain. METHODS:In a population-based prospective cohort study among 1,213 pregnant women, we measured early and mid-pregnancy bisphenol and phthalate urine concentrations. Maternal anthropometrics before pregnancy were obtained by questionnaire and repeatedly measured at our research center during pregnancy. We used linear and logistic regressions to evaluate the associations of bisphenols and phthalates with total and period-specific gestational weight gain. RESULTS:Higher maternal total bisphenols and bisphenol S were associated with a lower total gestational weight gain at nominal level. Stratification by body mass index group showed that higher total bisphenols and bisphenol S were associated with lower total gestational weight gain specifically in normal weight women (respectively -509 g [95% CI -819, -198] and -398 g [95% CI -627, -169]). Each log unit increase in early pregnancy total bisphenol and bisphenol A urine concentrations were associated with lower mid- to late pregnancy gestational weight gain in the whole group (effect estimates -218 g/log unit increase [95% CI -334, -102] and -132 g/log unit increase [95% CI -231, -34], respectively). These associations were independent of mid-pregnancy compounds. Mid-pregnancy bisphenols and phthalates concentrations were not associated with gestational weight gain. DISCUSSION/CONCLUSIONS:Higher maternal bisphenol urine concentrations in early pregnancy may lead to reduced gestational weight in second half of pregnancy. Further research is needed to assess the effects of maternal bisphenols and phthalates urine concentrations on placental and fetal growth and development.

Temporal trends in plasma concentrations of per- and polyfluoroalkyl substances (PFAS) in free-ranging bottlenose dolphins (Tursiops truncatus) inhabiting two geographic areas: Indian River Lagoon, Florida over the years 2003-2015 and the waters surrounding Charleston, South Carolina over 2003-2013, were examined. Nine PFAS met the inclusion criteria for analysis based on percent of values below level of detection and sampling years. Proportionate percentiles parametric quantile regression assuming lognormal distributions was used to estimate the average ratio of PFAS concentrations per year for each chemical. Plasma concentrations decreased over time for perfluorodecanoate (PFDA), perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluoroundecanoate (PFUnDA) in both locations. Perfluorononanoate (PFNA) decreased with time in Indian River Lagoon dolphins. Perfluorododecanoate (PFDoDA) concentrations significantly increased over time among female Indian River Lagoon dolphins. Regulation and phaseout of specific PFAS groups may have led to the decreasing levels of those PFAS and increasing levels of other replacement PFAS.

The extensive use of melamine and its three derivatives (i.e., ammeline, ammelide, and cyanuric acid) resulted in their widespread occurrence in the environment. Nevertheless, limited information is available on their distribution in the aquatic environment. In this study, concentrations and profiles of melamine and its derivatives were determined in 223 water samples, comprising river water, lake water, seawater, tap water, bottled water, rain water, wastewater, and swimming pool water, collected from New York State, USA. The sum concentrations of melamine and its derivatives (∑₄MELs) decreased in the following order: swimming pool water (median: 1.5 × 10⁷ ng/L) ≫ wastewater (1240) > precipitation (739) > tap water (512) > river water (370) > lake water (347) > seawater (186) > bottled water (98). Cyanuric acid was the major compound, accounting for 60-100% of ∑₄MELs concentrations in swimming pool water, wastewater, precipitation, tap water, seawater, and bottled water, whereas melamine dominated in river and lake water (54-64% of ∑₄MELs). Significant positive correlations (0.499 < R < 0.703, p < 0.002) were found between the concentrations of melamine and atrazine (a triazine herbicide) in surface waters. The geographic distribution in the concentrations of ∑₄MELs in river, lake, and tap water corresponded with the degree of urbanization, suggesting that human activities contribute to the sources melamine and cyanuric acid in the aquatic environments. A preliminary hazard assessment of melamine and cyanuric acid in waters suggested that their ecological or human health risks were minimal. This is the first study to document the occurrence and spatial distribution of melamine and its derivatives in waters from the United States.

BACKGROUND:The National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns. OBJECTIVES:Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research. METHODS:We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring. RESULTS:assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring. DISCUSSION:The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals. https://doi.org/10.1289/EHP5133.

The New York State Department of Health conducted the Healthy Fishing Communities Program in collaboration with the Agency for Toxic Substances and Disease Registry to assess human exposure to contaminants common to Lake Ontario, Lake Erie and surrounding rivers and waterways among populations in western New York State who eat locally caught fish. The program enrolled licensed anglers and Burmese refugees and immigrants, living near four designated Great Lakes Areas of Concern: Buffalo River, Niagara River, Eighteenmile Creek, and the Rochester Embayment. These target populations were sampled and enrolled independently into the program between February and October of 2013. A core set of contaminants were measured in blood and urine of 409 licensed anglers and 206 Burmese refugees and immigrants which included lead, cadmium, mercury, PCBs, PBDEs, organochlorine pesticides (hexachlorobenzene, mirex, DDT, DDE, and chlordane and its metabolites oxychlordane and trans-Nonachlor), and PFOS and PFOA. Biomonitoring results showed that both groups had higher geometric means for blood lead, total blood mercury, and serum PFOS compared to the 2013-2014 NHANES reference levels. The Burmese refugee group also showed higher geometric means for creatinine-adjusted urine mercury and lipid-adjusted serum DDE compared to national levels. Licensed angler participants reported eating a median of 16 locally caught fish meals in the past year. Burmese participants consumed local fish throughout the year, and most frequently in the summer (median 39 fish meals or 3 times a week). The study results provide valuable information on populations at high risk of exposure to contaminants in the Great Lakes Basin of western New York. The results provide the foundation for developing and implementing public health actions to reduce potential exposures to Great Lakes pollutants.

A total of 20 organophosphate triesters (OPEs), including seven alkyl-OPEs, three chlorinated (Cl)-OPEs, seven aryl-OPEs, and three oligomeric-OPEs were measured in 341 house dust samples collected from 12 countries during the period 2010-2014. OPEs were ubiquitous in indoor dust, and the total concentrations of OPEs (∑OPEs; sum of 20 OPEs) ranged from 49.4 to 249,000 ng/g dry weight (dw). Generally, Cl-OPEs were the predominant compounds (51% of total) in indoor dust samples, with a median concentration of 800 ng/g, followed by alkyl-OPEs (31%), aryl-OPEs (17%), and oligomeric-OPEs (1%), with median concentrations of 480, 270, and 21.9 ng/g, respectively. ∑OPE concentrations in indoor dust from more industrialized countries (South Korea: median, 31,300; Japan: 29,800; and the United States: 26,500 ng/g dw) were one or two orders of magnitude higher than those from less industrialized countries (Greece: 7140, Saudi Arabia: 5310, Kuwait: 4420, Romania: 4110, Vietnam: 1190, China: 1120, Colombia: 374, India: 276, and Pakistan: 138 ng/g dw). Statistically significant positive correlations (0.114 < r < 0.748, p < 0.05) were found among the concentrations of 16 OPEs in dust samples, indicating similar sources of these compounds. The median estimated daily intakes of ΣOPEs via dust ingestion for children and adults were in the ranges of 0.29-64.8 and 0.07-14.9 ng/kg bw/day, respectively.

Many organohalogen compounds (OHCs) are persistent organic pollutants (POPs) found in appreciable concentrations in marine predators. While production of some POPs has declined or ceased in recent decades, their capacity for global transport and bioaccumulation results in observations of unchanging or increasing concentrations in marine systems. Sea otters (Enhydra lutris) have been advocated as an environmental sentinel for contaminants due to their longevity, site fidelity and prey species that often overlap with human consumption. Using archived (1992-2010) samples of livers from Northern sea otters (n = 50) from Alaska we examine concentrations of chlordanes (CHLs), polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDTs), and polybrominated diphenyl ethers (PBDEs) and associated metabolites. We found some evidence for declining ΣPCBs over the two decades, however for most animals concentrations were low compared to toxicological thresholds. Six animals had relatively high concentrations of ΣPCBs (mean = 262,000 ng/g lipid weight), ΣDDTs (mean = 8,800 ng/g lw), and ΣPBDEs (mean = 4,600 ng/g lw), with four of these six animals experiencing hepatic parasitism or hepatitis. In order to assess whether differences in POP concentrations are associated with feeding ecology, we examined stable isotopes of C and N in archived muscle and whisker samples. In general, there were no significant relationships between ΣPOP concentrations and stable isotope ratios. There were small differences in stable isotope profiles in animals with high POP concentrations, although it was unclear if these differences were due to feeding ecology or disease processes. This study highlights the importance of considering feeding ecology and necropsy (health and disease status) data while conducting contaminant surveys, and confirms some previous reports of trends in OHCs in Alaska marine mammals.

Siloxanes are organo-silicon compounds containing Si-O-Si linkages and methyl branches. Depending on the structure, siloxanes can be divided into cyclic and linear compounds. Methyl siloxanes with small and medium molecular weights (molecular weights less than 500 g mol^-1), are volatile under normal conditions, and hence are referred to as volatile methyl siloxanes (VMSs). VMSs are additive ingredients in many products such as plastics, rubber, personal care products, and household items. This review provides information on the distribution of VMSs in consumer products, indoor air and dust, and their implications for human exposure. VMSs have been used in personal care products and household items at concentrations on the order of hundreds to thousands of micrograms per gram which are the main sources of contamination in the indoor environments. VMSs have been found widely in indoor air and dust. A significant correlation existed between VMS concentrations in indoor air and dust. Among typical VMSs, dodecamethylcylcopentasiloxane (D5) is the major compound found in indoor environments. The human exposure doses to VMSs through dermal absorption, dust ingestion, and inhalation were compiled; Inhalation is a dominant pathway of exposure to VMSs, especially in indoor environments of occupational settings like hair salons. The human exposure doses were higher in children than in adults.

Phthalates are widely used in several consumer products, including plastics, toys, cosmetics, and medical devices. Little is known about phthalate exposure in pet animals, however, even though they share an indoor environment with humans; this is the first study to measure such exposure. We measured 21 phthalate monoester metabolites (PhMs) in the urine of pet cats (n = 50) and dogs (n = 50) collected from New York State, USA. PhMs were widely detected in all samples, and 12 of 21 PhMs had detection frequencies (Dfs) >80%. The median urinary concentrations of total PhMs in pet cats and dogs were 630 ng/mL and 186 ng/mL, respectively. Monoethyl phthalate (mEP) was the most abundant compound in both cats and dogs. Phthalic acid (PA; a non-specific metabolite of phthalates) was found at very high concentrations in cats (median: 520 ng/mL). The estimated daily intake (EDI) and hazard quotient (HQ) for major phthalates in pets showed that DEHP exposures in cats and dogs were only 2-fold less than the US Environmental Protection Agency suggested reference dose (RfD) for humans.

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.