Faculty Bibliography

Owing to their toxicity, phthalate plasticizers are currently being replaced with terephthalates in many consumer products. Nevertheless, data on human exposure to and toxicity of terephthalates are still scarce. In this study, we developed a robust analytical method for the measurement of six terephthalate metabolites (TPhMs) in human urine through their successful separation from phthalate metabolites (PhMs). Target analytes were identified, using commercially available standards, and quantified with isotopically labeled internal standards (IS). The limits of quantification (LOQ) of TPhMs were in the range of 0.12 to 0.4 ng/mL, with the exception of 2.8 ng/mL for terephthalic acid (TPA) and 3.75 ng/mL for mono-(2-ethylhexyl) terephthalate (mEHTP), which were found in procedural blanks at notable levels. The method developed in this study showed excellent accuracy (recoveries: 86-117%) and precision (RSD: 0.6-12.2%) for TPhMs. The method was successfully applied for the analysis of 30 human urine samples collected from individuals with no known history of occupational exposure. The detection frequencies (df %) of TPhMs in urine ranged between 26.6 and 100%. This is one of the first studies that report a method for the analysis of emerging class of environmental chemicals in human specimens.

Many factors affect the variation in the exposome. We examined the influence of shared household and partner's sex in relation to the variation in 128 endocrine disrupting chemical (EDC) exposures among couples. In a cohort comprising of 501 couples trying for pregnancy, we measured 128 (13 chemical classes) persistent and nonpersistent EDCs and estimated 1) sex-specific differences; 2) variance explained by shared household; and 3) Spearman's rank correlation coefficients ( r_s) for females, males, and couples' exposures. Sex was correlated with 8 EDCs including per- and polyfluoroalkyl substances (PFASs) ( p < 0.05). Shared household explained 43% and 41% of the total variance for PFASs and blood metals, respectively, but less than 20% for the remaining 11 EDC classes. Coexposure patterns of the exposome were similar between females and males, with within-class r_s higher for persistent than for nonpersistent chemicals. Median r_ss of polybrominated compounds and urine metalloids were 0.45 and 0.09, respectively, for females (0.41 and 0.08 for males; 0.21 and 0.04 for couples). Our findings suggest that individual, rather than shared environment, could be a major factor influencing the covariation of the exposome. Understanding the correlations of exposures has important analytical and sampling implications for exposomics research.

Industrial facilities can be point sources of per- and polyfluoroalkyl substances (PFASs) emission to the surrounding environment. In this study, 25 neutral and ionizable PFASs were analyzed in 94 multimedia samples including air, rain, outdoor settled dust, soil, plant leaves, river water, surface sediment, and shallow groundwater from two fluorochemical manufacturing parks (FMPs) in Fuxin, China, to elucidate the multimedia distribution and transfer pattern of PFASs from a point source. The concentrations of individual PFASs in air, outdoor settled dust, and surface river water decreased exponentially as the distance increases from the FMPs, whereas the concentrations of short-chain (C2-C4) perfluoroalkyl carboxylic acids (PFCAs) remained high (3000 ng/L) in the surface water 38 km away. At FMPs, air concentrations of fluorotelomer alcohols and iodides were found dominant with levels of up to 7900 pg/m³ and 920 pg/m³, respectively. Trifluoroacetic acid was directly released from FMPs and occurred in all the environmental matrices at levels 1-2 orders of magnitude higher than other PFCAs. Higher air-water concentration ratios of short-chain PFCAs (C2-C4) suggested their transfer tendency from air to water. Both short-chain (C2) and long-chain (>C6) PFCAs have greater sediment-water distribution coefficients and deposit dust-air coefficients, which have great influences on the long-range transport potential of different analogues.

Melamine is a nitrogen-containing organic compound that is used in a wide range of products, including paints, plastics, and paper, as a flame retardant. A few studies have reported the occurrence of melamine and its derivatives in pet food, following a number of deaths of cats and dogs from kidney failure in 2007, which was attributed to melamine contamination in ingredients used in pet food. Nevertheless, studies that report the occurrence of melamine and its derivatives in pet urine are scarce. In this study, we measured melamine and its derivatives (i.e., ammeline, ammelide, and cyanuric acid) in dog (n = 30) and cat (n = 30) urine collected from Albany, New York, USA, during March through July 2017. The mean (±SD) concentrations of melamine, ammeline, ammelide, and cyanuric acid in dog urine were 21.1 ± 51.2, 2.3 ± 3.8, 9.9 ± 1 0.4, and 79.0 ± 105 ng/mL, respectively; the corresponding concentrations in cats were 21.4 ± 26.1, 1.2 ± 2.5, 6.1 ± 3.9, and 105 ± 94.6 ng/mL, respectively. No significant difference was observed in urinary concentrations of melamine derivatives between cats and dogs. Age and gender were important determinants of the concentrations of the target chemicals in cats and dogs. Cumulative daily intake of melamine and its derivatives was calculated on the basis of urinary concentrations and was found to be 10-500-fold below the tolerable daily intake.

The metabolites of nine organophosphate ester (OPE) flame retardants were measured in 180 urine samples collected from a population (including adults and children) in western Shanghai, China, using liquid chromatography-tandem spectrometry (LC-MS/MS). The total urinary concentrations of nine OPE metabolites ranged 100-23800 pg/mL, with a geometric mean (GM) value of 1450 pg/mL. The concentrations of alkyl-OPE metabolites (879 pg/mL) were approximately an order of magnitude higher than those of aryl-OPE (53.7 pg/mL) and chlorinated-OPE metabolites (52.7 pg/mL). Diphenyl phosphate (DPHP), diethyl phosphate (DEP), di-n-butyl phosphate (DNBP), bis(2-ethylhexyl) phosphate (BEHP), and bis(2-butoxyethyl) phosphate (BBOEP) were the dominant OPE metabolites found in urine. The results showed that an increase in age was associated with a significant decrease in urinary DPHP (r = -0.278, p < 0.01) and DNBP (r = -0.314, p < 0.01) concentrations. The highest concentrations of DPHP (GM = 80.7 pg/mL) and DNBP (GM = 16.9 pg/mL) were found in urine from people living in homes that were less than 10 years old. The urinary DNBP concentration was significantly associated with self-reported symptoms of allergy. Our result establishes baseline value for OPE exposure in a population in China for comparison in future studies.

Human exposure to endocrine disrupting chemicals (EDCs) has received considerable attention over the last three decades. However, little is known about the influence of co-exposure to multiple EDCs on effect-biomarkers such as oxidative stress in Brazilian children. In this study, concentrations of 40 EDCs were determined in urine samples collected from 300 Brazilian children of ages 6-14 years and data were analyzed by advanced data mining techniques. Oxidative DNA damage was evaluated from the urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8OHDG). Fourteen EDCs, including bisphenol A (BPA), methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), 3,4-dihydroxy benzoic acid (3,4-DHB), methyl-protocatechuic acid (OH-MeP), ethyl-protocatechuic acid (OH-EtP), triclosan (TCS), triclocarban (TCC), 2-hydroxy-4-methoxybenzophenone (BP3), 2,4-dihydroxybenzophenone (BP1), bisphenol A bis(2,3-dihydroxypropyl) glycidyl ether (BADGE·2H₂O), 2,4-dichlorophenol (2,4-DCP), and 2,5-dichlorophenol (2,5-DCP) were found in >50% of the urine samples analyzed. The highest geometric mean concentrations were found for MeP (43.1 ng/mL), PrP (3.12 ng/mL), 3,4-DHB (42.2 ng/mL), TCS (8.26 ng/mL), BP3 (3.71 ng/mL), and BP1 (4.85 ng/mL), and exposures to most of which were associated with personal care product (PCP) use. Statistically significant associations were found between urinary concentrations of 8OHDG and BPA, MeP, 3,4-DHB, OH-MeP, OH-EtP, TCS, BP3, 2,4-DCP, and 2,5-DCP. After clustering the data on the basis of i) 14 EDCs (exposure levels), ii) demography (age, gender and geographic location), and iii) 8OHDG (effect), two distinct clusters of samples were identified. 8OHDG concentration was the most critical parameter that differentiated the two clusters, followed by OH-EtP. When 8OHDG was removed from the dataset, predictability of exposure variables increased in the order of: OH-EtP > OH-MeP > 3,4-DHB > BPA > 2,4-DCP > MeP > TCS > EtP > BP1 > 2,5-DCP. Our results showed that co-exposure to OH-EtP, OH-MeP, 3,4-DHB, BPA, 2,4-DCP, MeP, TCS, EtP, BP1, and 2,5-DCP was associated with DNA damage in children. This is the first study to report exposure of Brazilian children to a wide range of EDCs and the data mining approach further strengthened our findings of chemical co-exposures and biomarkers of effect.

The determination of oxidative stress biomarkers (OSBs) is useful for the assessment of health status and progress of diseases in humans. Whereas previous methods for the determination of OSBs in urine were focused on a single marker, in this study, we present a method for simultaneous determination of biomarkers of oxidative damage to lipids, proteins, and DNA. 2,4-Dinitrophenylhydrazine (DNPH) derivatization followed by solid phase extraction (SPE) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) allowed the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), o- o'-dityrosine (diY), malondialdehyde (MDA), and four F₂-isoprostane isomers: 8-iso-prostaglandinF_2α (8-PGF_2α), 11β-prostaglandinF_2α (11-PGF_2α), 15( R)-prostaglandinF_2α (15-PGF_2α), and 8-iso,15( R)-prostaglandinF_2α (8,15-PGF_2α) in urine. Derivatization with DNPH and SPE was optimized to yield greater sensitivity and selectivity for the analysis of target chemicals. The limits of detection of target analytes in urine were below 30 pg mL^-1. The assay intra- and interday variability was below 16% of the relative standard deviation, and the recoveries of target chemicals spiked into synthetic urine were near 100%. The method was applied to the analysis of 21 real urine samples, and the analytes were found at a detection frequency of 85% for 8-PGF_2α and 15-PGF_2α, 71% for 11-PGF_2α, 81% for 8,15-PGF_2α, and 100% for diY, 8-OHdG, and MDA. This method offers simultaneous determination of multiple OSBs of different molecular origin in urine samples selectively with high accuracy and precision.

Distribution of 12 organophosphate flame retardants (OPFRs) was determined in soil and outdoor settled dust samples collected from a multi-waste (electronic, plastic, and rubber wastes and abandoned household-appliances and vehicles) recycling area, that encompassed different modes of operation i.e. open (ORS) and semi-closed recycling (SCRS). Among the twelve OPFRs analyzed, eleven were detected at a frequency of 75%-100% in all soil and dust samples. In soil samples, ΣOPFR concentrations were significantly higher at ORS (122-2100ng/g) than at SCRS (58.5-316ng/g) and nearby farmlands (37.7-156ng/g). The ΣOPFR concentrations in dust samples were higher than those in soil samples with spatial distribution similar to that observed for soil, decreasing from ORS (1390-42,700ng/g) to SCRS (914-7940ng/g). Tris(2-chloroisopropyl) phosphate (TCIPP) was the major OPFRs in both soil (<MDL-1370ng/g) and dust (39.9-16,300ng/g) samples. Chlorinated OPFRs [TCIPP, tris(1,3-dichloroisopropyl) phosphate (TDCIPP) and tris(2-chloroethyl) phosphate (TCEP)] and aryl-OPFRs [triphenyl phosphate (TPHP), tris(methylphenyl) phosphate (TMPP)] exhibited spatial difference between ORS and SCRS. Principle component analysis (PCA) of OPFR concentrations revealed that TCIPP, TDCIPP, TPHP, TMPP originated from similar sources. TMPP was assessed to pose eco-toxicological risk (risk quotient values: RQs) in the soil ecosystem. The median estimated daily intake (EDI) of OPFRs via soil and outdoor settled dust ingestion (based on average ingestion rate) was 3.14×10^-1ng/kgbw/day for adults at ORS. Our results suggest that waste recycling is an important source of chlorinated- and aryl-OPFRs in the environment.

Parabens, esters of para-hydroxybenzoic acid, are commonly used as antimicrobial preservatives in cosmetics and personal care products. Although several studies report exposure of humans to parabens in Western countries, little is known about exposure of humans to parabens in Asian countries. In this study, we determined concentrations of six parabens in spot urine samples collected from nine countries and estimated daily intakes (DI) and potential health risks of parabens. Ethyl-paraben, methyl-paraben, and propyl-paraben were detected frequently at 100, 98.0, and 80.3%, respectively, with representative median concentrations of 0.68, 7.02, and 1.21 ng/mL, respectively, for all nine countries. Urine samples from females (total median concentration: 32.3 ng/mL) contained significantly higher concentrations of parabens than did those from males (5.46 ng/mL). Urine samples from Korea (total median paraben concentration: 227 ng/mL) had the highest concentrations, which were one to two orders of magnitude higher than those found in other countries (3.67-29.1 ng/mL). The estimated DI of parabens (on the basis of concentrations measured in urine) varied widely, and several samples had propyl-paraben exposures above the acceptable DI. Our results suggest that paraben exposure is ubiquitous in Asian countries, and further assessment of potential health risk of these chemicals is needed.

The occurrence and profiles of 14 triester organophosphate flame retardants (OPFRs) and plasticizers were investigated in surface water, tap water, rainwater, and seawater collected from New York State. In total, 150 samples collected from rivers ( n = 35), lakes ( n = 39), tap water ( n = 58), precipitation/rainwater ( n = 15), and seawater ( n = 3) were analyzed for 14 organophosphate esters (OPEs). An additional nine Hudson River water samples were collected periodically to delineate seasonal trends in OPE levels. The total concentrations of OPEs were found at part-per-trillion ranges, with average concentrations that ranged from 0.01 ng/L for tripropyl phosphate (TPP) in river water to 689 ng/L for tris(2-butoxyethyl)phosphate (TBOEP) in lake water. Tris(1-chloro-2-propyl)phosphate (TCIPP) was the most abundant compound among the investigated OPEs in all types of water. The concentrations of OPEs in river-, lake-, and rainwater were similar but >3 times higher than those found in tap water. Chlorinated alkyl OPFRs accounted for a major proportion of total concentrations. TCIPP, TBOEP, and triethyl phosphate (TEP) were found in >90% of the samples analyzed. Wet deposition fluxes for 14 OPFRs were estimated, on the basis of the concentrations measured in rainwater in Albany, New York, and the values were between 440 and 5250 ng/m². Among several surface water bodies analyzed, samples from the Hudson River and Onondaga Lake contained elevated concentrations of OPEs. Estimated daily intake of OPEs via the ingestion of drinking water was up to 9.65 ng/kg body weight/day.