Faculty Bibliography

Organophosphate esters (OPEs) are ubiquitous contaminants in the environment, but little is known about their occurrence in foodstuffs, an important source of human exposure. In this study, 15 OPEs were measured in foodstuffs and food-packing materials collected from local markets in Albany, New York, United States, for the first time. Among the foodstuffs analyzed, median concentrations of ∑OPEs (sum of 15 OPEs) in meat (6.76 ng/g wet weight; ww) and fish/seafood (7.11 ng/g ww) were higher than those in other food categories. ∑OPEs were found in food packaging at a median concentration of 132 ng/g. The estimated daily dietary intakes (EDIs) of OPE were of 37.9, 135, 56.6, 32.2, and 25.1 ng/kg body weight (bw)/day for infants, toddlers, children, teenagers, and adults, respectively. Meat was a major source (47%) of dietary OPEs exposure in adults, whereas dairy products accounted for 52% of OPE exposures in toddlers.

Perfluoroalkyl substances (PFAS) may have been released during the collapse of the World Trade Center (WTC) on 9/11. Evidence suggests PFAS can cross the placental barrier in humans and cause harm to the developing fetus; however, no studies have measured PFAS in mothers exposed to the WTC disaster during pregnancy. We measured PFAS in maternal plasma (n = 48) or cord blood (n = 231) from pregnant women in the Columbia University WTC birth cohort, enrolled between December 13, 2001 and June 26, 2002 at one of three hospitals located near the WTC site. In order to maximize sample size, we used a linear regression to transform the 48 maternal plasma samples to cord blood equivalents in our study; cord blood and transformed maternal plasma-to-cord blood samples were then analyzed together. We evaluated the association between WTC exposure and PFAS concentrations using three exposure variables: 1) living/working within two miles of WTC; 2) living within two miles of WTC regardless of work location; and 3) working but not living within two miles of WTC. Exposure was compared with those not living/working within two miles of WTC (reference group). Living/working within two miles of WTC was associated with 13% higher perfluorooctanoic acid (PFOA) concentrations compared with the reference group [GMR (95% CI): 1.13 (1.01, 1.27)]. The association was stronger when comparing only those who lived within two miles of WTC to the reference group [GMR (95% CI): 1.17 (1.03, 1.33)], regardless of work location. Our results provide evidence that exposure to the WTC disaster during pregnancy resulted in increases in PFAS concentrations, specifically PFOA. This work identifies a potentially vulnerable and overlooked population, children exposed to the WTC disaster in utero, and highlights the importance of future longitudinal studies in this cohort to investigate later life effects resulting from these early life exposures.

Organophosphate esters (OPs) are substitutes for polybrominated diphenyl ether (PBDE) flame retardants. China is the largest producer of OPs globally, with the production rate increasing at 15% annually. Since some OPs are neurodevelopmental and/or carcinogenic toxicants, human exposure is a concern. In this study, concentrations of eight OP metabolites (mOPs) were measured in human urine samples collected from 13 cities located in Northern, Eastern, Southern, and Southwestern China. All target mOPs were frequently detected with detection rates of 50% to 100%, indicating widespread human exposure to OPs. Bis(2-chloroethyl) phosphate (BCEP; median: 0.68 ng/mL), bis(1-chloro-2-propyl) phosphate (BCIPP; 0.30 ng/mL), diphenyl phosphate (DPHP; 0.30 ng/mL), and dibutyl phosphate (DBP; 0.29 ng/mL) were the dominant mOPs across all participants. Regional differences in concentrations (ΣmOPs varied from 0.86 to 3.7 ng/mL) and composition profiles (contribution of chlorinated mOPs to ΣmOPs varied from 35% to 95%) of mOPs were observed within China. In comparison to the concentrations reported worldwide, urinary DPHP and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) levels in China were lower, whereas BCEP and DBP levels were comparable or higher. The total daily intake (TDI) of tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) were estimated from daily urine excretion rate and the fraction of OP metabolized in human liver microsomes (TDI_HLM) or S9 fraction (TDI_S9). The intake estimates showed that Chinese residents were exposed to TCEP from 96.9 to 46,700 (or 52.2 to 25,200) ng/kg bw/day. Depending on the reference dose, we found that approximately 5% of the individuals exceeded the limit (i.e., 2200 ng/kg bw/day) for TCEP intake. To our knowledge, this is the first nationwide baseline survey to determine urinary levels of mOPs in Chinese residents.

Experimental studies suggest that prenatal exposure to endocrine disrupting chemicals interferes with developmental processes in the fetal brain. Yet, epidemiological evidence is inconclusive. In a birth cohort (2008-2010, upstate New York), we quantified concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and bisphenol A (BPA) in stored newborn dried blood spots using liquid chromatography/tandem mass spectrometry. Mothers reported on children's behavior using the Strengths and Difficulties Questionnaire at age 7 (650 singletons and 138 twins). Difficulties in total behavior (i.e., emotional, conduct, hyperactivity, and peer problems) and prosocial behavior were classified using validated cut-offs. We used logistic regression with generalized estimating equations to estimate the odds of having difficulties per exposure category. In total, 111 children (12.1%) had total behavioral difficulties and 60 (6.5%) had difficulties in prosocial behavior. The median (interquartile range) of PFOS, PFOA, and BPA were 1.74 ng/ml (1.33), 1.12 ng/ml (0.96), and 7.93 ng/ml (10.79), respectively. Higher PFOS levels were associated with increased odds of having behavioral difficulties (OR per SD of log PFOS = 1.30, 95%CI: 1.03-1.65). We observed associations between PFOS in the highest relative to the lowest quartile and behavioral difficulties (OR for PFOS_1.14-1.74 = 1.65, 95%CI: 0.84-3.34; PFOS_1.75-2.47 = 1.73, 95%CI: 0.87-3.43; and PFOS_>2.47 = 2.47, 95%CI: 1.29-4.72 compared to PFOS_<1.41). The associations between higher concentrations of PFOS and behavioral difficulties at age 7 years were driven by problems in conduct and emotional symptoms. Higher PFOA levels were associated with difficulties in prosocial behavior (OR = 1.35, 95%CI: 1.03-1.75). There was an inverse association between BPA concentrations and difficulties in prosocial behavior but only in the 2nd and 4th quartiles. We found no interactions between sex and chemical concentrations. Increasing prenatal exposure to PFOS and PFOA, as reflected in neonatal concentrations, may pose risk for child behavioral difficulties.

BACKGROUND:Novel methodologies to quantify infant exposures to endocrine disrupting chemicals (EDCs) for population-based studies are needed. OBJECTIVES:We used newborn dried blood spots to quantify three EDCs and their associations with infant outcomes in the Upstate KIDS Cohort. METHODS:We measured bisphenol A (BPA), perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in 2071 singleton and 1040 twin infants born to mothers in New York State. We log transformed concentrations after rescaling by their standard deviations and modeled each in relation to gestational age, birthweight, length, head circumference and Ponderal Index (PI) using linear regression techniques. All models were adjusted for maternal age, body mass index, education, infertility treatment and parity. Generalized estimating equations with robust standard errors were used to assess the associations for twins. RESULTS:Chemicals were largely quantified above the limits of detection (>99% for PFOS and PFOA; 90% for BPA). Overall, we observed no significant associations between PFASs and birth size irrespective of plurality of birth. However, among twins, BPA was associated with decreases in gestational age (adjusted β = -0.09 weeks; 95% Confidence Interval (CI): -0.16, -0.02) and birthweight (adjusted β = -32.52 g; 95% CI: -60.99, -4.05), head circumference (adjusted β = -0.18 cm; 95% CI: -0.38, -0.02) and increased PI in singletons (adjusted β = 0.02 cm; 95% CI: 0.004, 0.04). CONCLUSION:We observed negative associations between BPA and birth size in twins. Our findings demonstrate the feasibility of newborn dried blood spots for quantifying neonatal exposure at the population level.

Concentrations of 26 brominated flame retardants (BFRs), including 19 polybrominated diphenyl ethers congeners (PBDEs), 3 isomers of hexabromocyclododecanes (HBCDs), and 4 alternative BFRs (alt-BFRs; hexabromobenzene, pentabromotoluene, 1,2-bis(2,4,6-tribromphenoxy)ethane, and decabromodiphenylethane) were determined in outdoor settled dust and pine needles collected across mainland China. BFRs were extensively found in the two matrices, with mean total concentrations at 4090 and 314 ng/g dry weight (dw), in dust and pine needles, respectively. The total BFRs concentrations in dust significantly varied among three mixed-land-use categories, with mean concentrations of 74.3, 1284, and 25,525 ng/g dw in rural, urban, and point source areas, respectively. For PBDE congeners, dust samples contained predominantly BDE-209 (69.2% of the total BFRs), whereas lower brominated PBDEs such as BDE-28 (19.7%), -47 (11.0%), and -99 (12.2%) accounted for higher proportions in pine needles. Spatial distribution of BFRs showed distinct geographical signatures with the highest levels found in South Central China. Application of McLachlan's framework to our data suggested that the uptake of BFRs in pine needles was controlled primarily by kinetically limited gaseous deposition and by particle-bound deposition. Assessment on human exposure to BFRs through outdoor dust ingestion revealed a low risk for Chinese adults and toddlers.

Concentrations of nine metabolites of organophosphate and pyrethroid insecticides, as well as two phenoxy herbicides, were determined in 322 urine samples collected from eight countries during 2006-2014 by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The target pesticides were found ubiquitously, indicating widespread exposure of humans to pesticides in these countries. The highest sum concentrations of 11 pesticides were found in urine collected from Vietnam (median, 28.9 ng/mL), followed in decreasing order by samples from India (14.2 ng/mL), China (13.6 ng/mL), Korea (12.5 ng/mL), Greece (12.3 ng/mL), Saudi Arabia (11.3 ng/mL), the USA (7.9 ng/mL), and Japan (7.1 ng/mL). Organophosphorus compounds accounted for 62-77% of the total urinary pesticide concentrations. Para-nitrophenol (metabolite of parathion and methyl parathion) and 3,5,6-trichloro-2-pyridinol (metabolite of chlorpyrifos and chlorpyrifos-methyl) were the major metabolites, especially in India (72%), China (69%), and Greece (66%). Differences in urinary pesticide concentrations between genders (male vs. female), age groups (categorized as ≤20, 21-49, and ≥50 years), and cities (Guangzhou, Shanghai, and Qiqihar) were examined. On the basis of the concentrations measured in urine, total daily intakes (DIs) of pesticides were estimated. The DIs of chlorpyrifos were found to be higher for populations in Vietnam, Greece, India, China, and Korea (≥9.6 μg/day) than those estimated for the other countries (<5 μg/day). The DIs of parathion (≥9.6 μg/day) in populations of China, India, and Korea were higher than those estimated for the other countries (5.7-9.3 μg/day). This is the first study to establish baseline levels of exposure of a variety of pesticides in several Asian countries.

Melamine and its derivatives (i.e., ammeline, ammelide, and cyanuric acid) are extensively used in household products, such as furniture, dinnerware, and food utensils. Nevertheless, limited information is available on human exposures, other than dietary sources, to melamine and its derivatives. In this study, the occurrence of melamine and its derivatives was determined, for the first time, in 341 samples of indoor dust, collected from 12 countries. All of the dust samples contained target analytes, with global median concentrations of 1800, 1100, 48, and 45 ng/g for melamine, cyanuric acid, ammelide, and ammeline, respectively. The total concentrations of melamine and its derivatives varied among countries in the following decreasing order: United States (median: 17 000 ng/g) > Japan (8400) > China (8000) > South Korea (7300) > Saudi Arabia (4400) > Romania (4300) > Greece (3400) > Kuwait (2400) > Vietnam (2300) > Colombia (1300) > Pakistan (820) > India (430). Correlation analysis indicated the existence of multiple and varied sources for melamine and cyanuric acid. Estimated daily intakes of melamine via indoor dust ingestion were at least 2 orders of magnitude below the current tolerable daily intake.

In the 2000s, nail polish manufacturers started promoting "3-Free" products, phasing out three widely publicized toxic chemicals: toluene, formaldehyde, and dibutyl phthalate (DnBP). However, DnBP was sometimes replaced by another endocrine-disrupting plasticizer, triphenyl phosphate (TPHP). Many new " n-Free" labels have since appeared, without any standardization on which n chemicals are excluded. This study aimed to compare measured plasticizer content against nail polish labels. First, we summarized definitions of labels. Then, we measured 12 phthalate and 10 organophosphate plasticizers in 40 nail polishes from 12 brands selected for popularity and label variety. We found labels ranging from 3- to 13-Free; 10-Free was the most inconsistently defined (six definitions). Our samples contained TPHP and bis(2-ethylhexyl) phthalate (DEHP) at up to 7940 and 331 μg/g, respectively. The 5- to 13-Free samples had lower TPHP levels than unlabeled or 3-Free samples (median <0.002 vs 3730 μg/g, p < 0.001). The samples that did not contain TPHP had higher DEHP levels (median 68.5 vs 1.51 μg/g, p < 0.05). We measured plasticizers above 100 μg/g in five brands that did not disclose them and in two that excluded them in labels. This study highlights inconsistencies in nail polish labels and identifies TPHP and DEHP as ingredient substitutes for DnBP.

BACKGROUND:Melamine and cyanuric acid, which are currently used in a variety of common consumer products and present in foods, have been implicated in the development of urolithiasis and acute kidney injury in Chinese children. To determine whether US children have measurable concentrations of these chemicals in their bodies and whether they are at greater risk of acute kidney injury, we measured melamine and cyanuric acid exposure in a cohort of US children and determined their relationship with markers of kidney injury. METHODS:We measured urinary melamine and cyanuric acid in a convenience sample of 109 children (4 months - 8 years) from Seattle, WA and New York City, NY using liquid chromatography with tandem mass spectrometry. We measured several urinary markers of kidney injury: fatty acid binding protein 3 (FABP3), kidney injury molecule 1 (KIM1), neutrophil gelatinase-associated lipocalin (NGAL) using Luminex xMAP methods, and urine urea was measured using standard laboratory methods. We described urinary melamine and cyanuric acid concentrations and assessed predictors of the exposures. We used multivariable linear regression to assess relationships between melamine/cyanuric acid and kidney injury markers in unadjusted and adjusted (creatinine, age, sex) analyses. RESULTS:Melamine and cyanuric acid were above the limit of detection (LOD) in 78% and 95% of all samples, respectively. The mean concentrations (SD) for melamine and cyanuric acid were 27.4 ng/ml (141.9 ng/ml) and 35.3 ng/ml (42.4 ng/ml). In unadjusted analyses, we observed statistically significant increases in the percentages of FABP3 and KIM1 in relation to a one log unit change in melamine and cyanuric acid, respectively. In adjusted analyses, we observed a 55% (95% CI 0, 141) increase in KIM1 in relation to a one log unit increase in cyanuric acid. CONCLUSIONS:US children have detectable concentrations of melamine and cyanuric acid in urine, and these concentrations are higher than those reported in children from other countries. This is a novel finding that improves upon previous exposure estimates using questionnaires only and suggests widespread exposure in the population. Cyanuric acid is associated with increased KIM 1 concentrations, suggesting kidney injury. Given the potential widespread exposure, future analyses should examine melamine and cyanuric acid in relation to chronic kidney disease and markers of kidney injury in a larger cohort that is representative of the general population.