Faculty Bibliography

Neonicotinoids (NEOs) are insecticides that are widely used around the world. Following exposure, NEOs get metabolized in human bodies. The biomarkers to assess human NEO exposure are not well described because of the lack of information on the metabolites of NEOs (m-NEOs). In this study, five m-NEOs including N-desmethyl-acetamiprid (N-dm-ACE), 5-hydroxy-imidacloprid (5-OH-IMI), olefin-imidacloprid (Of-IMI), 1-methyl-3-(tetrahydro-3-furylmethyl) guanidine (DIN-G), and 1-methyl-3-(tetrahydro-3-furylmethyl) (DIN-U) were measured in 275 urine samples collected from 10 cities in China. All of the m-NEOs were frequently detected in urine samples with the median concentrations ranging from 0.42 (DIN-G) to 1.02 (5-OH-IMI) ng/mL. The urinary concentrations of N-dm-ACE and 5-OH-IMI measured in China were higher than those reported from Japan and the USA. In comparison to the parent NEO (i.e., acetamiprid, ACE; imidacloprid, IMI; and dinotefuran, DIN) concentrations reported in the same set of samples by our research group, the median ratios of m-NEO to the corresponding parent NEO (m-NEO/NEO) ranged from 4.95 (DIN-G/DIN) to 37.7 (N-dm-ACE/ACE), indicating that NEOs are mainly present as metabolites rather than the parent forms. Furthermore, the ratio of Σm-NEOs/ΣNEOs was significantly (p < 0.01) higher in females than in males, suggesting that NEOs are more readily metabolized in females or females are more highly exposed to m-NEOs. To our knowledge, this is the first study to measure Of-IMI, DIN-G, and DIN-U levels in urine samples from China. We recommend biomonitoring studies to include N-dm-ACE, 5-OH-IMI, and DIN-U (and DIN-G) for clear understanding of human exposure to ACE, IMI, and DIN, respectively.

BACKGROUND:Exposure to bisphenols and phthalates might influence bone health. We hypothesized that exposure to bisphenols and phthalates during fetal life has persistent effects on bone development. OBJECTIVES/OBJECTIVE:To analyze the associations of fetal exposure to bisphenols and phthalates with bone health in school-aged children. METHODS:Among 1,362 mother-child pairs participating in a population-based cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at first, second and third trimester with high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Total body bone mineral density (BMD) and bone area (BA) were measured using dual-energy X-ray absorptiometry (DXA) at 6 and 10 years, and were both used to calculate bone mineral content (BMC) and area-adjusted BMC (aBMC, a measure of volumetric BMD). RESULTS:and -0.12 (95% CI, -0.20 to -0.04) g). Maternal third trimester low molecular weight (LMW) phthalate concentrations were associated with higher aBMC at 6 years whereas, maternal third trimester di-n-octylphthalate (DNOP) concentrations were associated with lower aBMC at 10 years. However, these associations did not remain statistically significant after multiple testing correction. DISCUSSION/CONCLUSIONS:Maternal first trimester BPS concentrations are associated with lower BMD and aBMC in school-aged children. These findings should be considered as hypothesis generating and need further replication and exploration of potential underlying mechanisms.

Developmental exposure to bisphenol A (BPA) is associated with liver dysfunction and diseases in adulthood. The aims of this study were to assess the effects of prenatal BPA exposure on the hepatic transcriptome and proteome in female and male offspring and to understand adverse outcome pathways (AOPs) to observed phenotypic effects. Pregnant Wistar rats were exposed to 50 or 5000 μg BPA/kg bw/day, or 17β-estradiol (E2, 50 μg/kg bw/day) from embryonic day 3 to 18. The liver transcriptome and proteome profiles were analyzed in the newborn (postnatal day 1; PND1) and weaning (PND21) rat offspring. Based on the differentially expressed genes/proteins derived from transcriptome and proteome profiles, we performed pathway, transcription factor, and disease enrichment analyses. A principal component analysis of transcriptome data demonstrated that prenatal BPA exposure caused masculinization of the hepatic transcriptome in females. Both of transcriptomic and proteomic data showed that prenatal BPA exposure led to the disruption of cell cycle, lipid homeostasis, and hormone balance in offspring. Most of the effects at the transcript level were extended from newborn to weaning in males, but were moderated until weaning in females. The alterations at the transcript and protein levels were accordant with the observation of increases in body weight and anogenital distance and changes in hepatosomatic index in the offspring. Collectively, we constructed AOPs with evidence of sex- and age-specific actions of prenatal BPA exposure in the offspring.

Per- and polyfluoroalkyl substances (PFASs) are used in specialty/functional textiles to impart oil, water, and stain repellency. Little is known, however, with regard to the occurrence of PFASs in textiles including infant clothing. In this study, 13 perfluoroalkyl acids (PFAAs), comprising four perfluoroalkyl sulfonic acids (PFSAs; C4-C10) and nine perfluoroalkyl carboxylic acids (PFCAs; C4-C12) were determined in 160 textile samples collected from the United States. Two extraction methods, one involving a simple solvent extraction (i.e., before oxidation) and the other with an oxidative treatment (i.e., after oxidation) of textile extracts, were used. The sum concentrations of 13 PFAAs (i.e., ∑PFAA) in textile extracts before oxidation ranged from <LOD to 63.7 μg/m² (<LOD-285 ng/g), with a mean value of 3.18 μg/m² (14.2 ng/g). ∑PFAA concentrations were the highest in flame retarded textiles (n = 23; mean: 13.3 μg/m²; 59.4 ng/g), followed by water repellent textiles (n = 56; 2.88 μg/m²; 12.9 ng/g) and infant clothes (n = 81; 0.521 μg/m²; 2.33 ng/g). C4-C10 PFCAs accounted for at least three-quarters of the ∑PFAA content in our textile samples. Textile extracts analyzed after oxidative treatment exhibited ∑PFAA concentrations 10-fold higher than those in extracts analyzed prior to oxidation, which suggested that PFAA precursors are used in textiles. Precursors that generated C4-C5 PFCAs, upon oxidation, were more prevalent than those that yielded PFOA. The calculated dermal exposure doses in infants of PFAAs present in clothes were at least 1-2 orders of magnitude below the reference doses proposed by the United States Environmental Protection Agency. This is the first time that the oxidative treatment was applied in the analysis of PFASs in textiles, and our results suggest the existence of PFCA precursors in textiles.

Objective/UNASSIGNED:(rs7975232) with osteoporosis risk in the Saudi population. Methods/UNASSIGNED:< 0.05 considered as significant. Results/UNASSIGNED:= 0.01, respectively). Conclusion/UNASSIGNED:were found to be significantly determinant risk factors for osteoporosis progression in the Saudi population.

The need to dispose of dredged sediments and development of appropriate technology for their safe utilization has become a growing problem in recent years. It has been proposed that dredged, fresh sediments can be utilized in agriculture or environment; however there is also growing interest in the use of thermally-treated sediments. Hence, the aim of this study was threefold: 1) to evaluate the effect of two incineration temperatures (300 °C and 600 °C) on the chemical and ecotoxicological properties of sediment; 2) select the appropriate treatment for further phytoremediation experiments with zucchini; and 3) assess the impact of sediment admixture on the physico-chemical parameters of soil, based on the responses of Aliivibrio fischeri and growth of zucchini (Cucurbita pepo L. cv 'Black Beauty'). A range of chemical (inductively-coupled plasma optical emission spectrophotometry for macro- and trace elements; gas chromatography for polychlorinated biphenyls (PCBs)), ecotoxicological (Microtox assay), and plant morphology (biomass measurement) as well as physiological analyses (spectrophotometry for chlorophyll) were applied. River sediments incinerated at 600 °C resulted in better chemical and ecotoxicological properties than incinerated at 300 °C or no incinerated. Incineration at 600 °C removed PCBs from sediment. In culture experiments conducted with zucchini, sediment treated at 300 °C demonstrated a 51-81% reduction in PCB concentrations compared to untreated sediment. After four weeks of growth, the raw sediment showed a significant increase in K, Fe, Cr, Pb, Zn concentrations, whereas the thermally-processed sediment showed a decrease in Ca, Na, P, Cd, Cu, Ni, and Zn concentrations. Both the fresh and thermally-treated sediment types influenced plant growth positively: they demonstrated higher biomass production than plants grown in control soil; however, plants grown on soil with thermally-processed sediment demonstrated lower biomass than those grown in raw sediment. Chlorophyll content was affected negatively by admixtures of soil with treated or untreated sediment, while a lower chlorophyll a/b ratio was observed in plants grown on an admixture of thermally-treated sediment with soil. Our findings suggest that the use of sediments as a growth medium component may be a promising way for their utilization and transformation from waste material to a valuable resource enhancing the benefits to the environment.

Human exposure to pesticides is widespread and has received much attention in recent years because of its link to adverse health outcomes. Measurement of urinary concentrations of pesticides and their metabolites is often used in the assessment of body burdens of these chemicals. However, pesticides and their metabolites can be present in blood circulatory system, although little is known on serum levels of pesticides. In this study, we aimed to examine the occurrence and profile of four organophosphate (OP), five pyrethroid (PYR) insecticides, two phenoxy acid (PA) herbicides, 14 neonicotinoid (neonic) insecticides and six dialkylphosphate metabolites in serum from 25 individuals diagnosed with osteoarthritis in Jeddah, Saudi Arabia. 2-Isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), 3,5,6-trichloro-2-pyridinol (TCPY), 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, 3-phenoxybenzoic acid, N-desmethyl acetamiprid, dimethylphosphate (DMP) and dimethylthiophosphate (DMTP) were detected in ≥80% of the serum samples analyzed. Metabolites of OPs, DMTP (median concentration: 2.14 ng/mL), DMP (1.04 ng/mL) and TCPY (0.84 ng/mL), collectively accounted for 67-83% of the total serum pesticide concentrations. Serum concentrations of pesticides were similar to or lower than those reported in urine. Our preliminary evidence suggests that serum can be used as a matrix for the assessment of exposure to OPs, PYRs, PAs and neonics.

Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.

OBJECTIVES/OBJECTIVE:Fetal exposure to phthalates and bisphenols may lead to vascular developmental adaptations, which program later cardiovascular disease. We examined the associations of fetal exposure to phthalates and bisphenols with childhood blood pressure. METHODS:In a population-based, prospective cohort study among 1,064 mother-child pairs, we measured maternal urine phthalate and bisphenol concentrations in first, second and third trimester of pregnancy. We measured childhood blood pressure at the mean age of 9.7 years (standard deviation 0.2 years) old. Analyses were performed for the total group, and for boys and girls separately. RESULTS:Maternal urine phthalate concentrations were not associated with childhood blood pressure among boys. Higher third trimester maternal urine concentrations of high molecular weight phthalates (HMWP), di-2-ehtylhexylphthalate (DEHP) and di-n-octylphthalate (DNOP) were associated with lower systolic and diastolic blood pressure among girls (p-values < 0.01). Also, higher second trimester maternal urine total bisphenol and bisphenol A concentrations were associated with higher systolic blood pressure among boys (p values < 0.01), but tended to be associated with a lower diastolic blood pressure among girls. CONCLUSIONS:Our results suggest sex-dependent associations of maternal urine phthalate and bisphenol concentrations during pregnancy with childhood blood pressure. Further studies are needed to explore the underlying mechanisms and long term consequences.

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children's health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO's rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children.