Faculty Bibliography

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.

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.

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: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.

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.

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.

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.