Faculty Bibliography

Endometriosis is a hormone-responsive gynecologic disease, signifying its connotations across a woman's life span. Previous studies suggested that endocrine disrupting chemicals were risk factors for endometriosis. Nevertheless, little is known on exposure to organophosphate, pyrethroid and phenoxy acid pesticides on endometriosis diagnosis. In this study, we determined the concentrations of 11 pesticides, metabolites of organophosphate and pyrethroid insecticides, and phenoxy herbicides, in urine collected from 619 reproductive-age women in Utah and California, using liquid chromatography-tandem mass spectrometry. The association of urinary concentrations of pesticides with an increase in the odds of endometriosis diagnosis was examined in 594 women who underwent laparoscopy/laparotomy (operative cohort: n = 471) or pelvic magnetic resonance imaging (population cohort: n = 123), during 2007-2009. 2-Isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), malathion dicarboxylic acid (MDA), para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPY), 3-phenoxybenzoic acid (3-PBA), and 2,4-dichlorophenoxyacetic acid (2,4-D) were detected in ≥95% of the urine samples analyzed. Urinary concentrations of IMPY, MDA, PNP, 3-PBA and 2,4-D tended to be higher in younger, non-Hispanic black, nulliparous and less affluent women. IMPY was the most dominant compound in urine followed by PNP and TCPY. When women in the 4th quartile of IMPY and the 2nd quartile of TCPY concentrations (μg/g creatinine) were compared with women in the 1st quartile, the odds ratios (ORs) for diagnosis of endometriosis increased significantly in unadjusted models (IMPY OR = 1.89, 95% confidence interval (Cl) = 1.12-3.20; TCPY OR = 1.65, 95% Cl = 1.02-2.69) for the operative (n = 471) and entire data set (n = 594), respectively. Our results suggest that exposure to elevated concentrations of diazinon (the parent compound of IMPY) and chlorpyrifos and chlorpyrifos-methyl (parent compounds of TCPY) may be associated with endometriosis.

Human exposure to per- and polyfluoroalkyl substances (PFASs) continues to be a concern. Little is known about their toxicokinetics, particularly with regard to fecal excretion of PFASs. Because pets are sentinels of human exposure to environmental contaminants, analysis of PFASs in pet feces can provide information about rates of excretion of these chemicals. In this study, 15 PFASs were measured in cat and dog feces collected from the Albany area of New York State. All PFASs except perfluorodecanesulfonate and perfluoroheptanoic acid were found in cat and dog feces. The sum concentrations of 13 PFASs (∑PFAS) varied between 21.6 and 474 (mean: 85.4 ± 94.5) ng/g dry weight for dogs, which were slightly higher than those found for cats (range: 18.0-165 ng/g dry weight, mean: 54.7 ± 26.9 ng/g dry weight). Long-chain perfluorocarboxylic acids with 9-12 carbons (perfluorononanoic acid, perfluorodecanoic acid, perfluoroundecanoic acid, and perfluorododecanoic acid) were predominant in pet feces. Perfluorooctanesulfonate and its precursors were found at low concentrations. Fecal excretion rates of PFASs in cats and dogs were found to be similar. The estimated daily fecal excretion suggested that both dogs and cats are exposed to some PFASs at doses above the provisional minimum risk level recommended for humans.

Poly- and per-fluoroalkyl substances (PFAS) were reported to be used in food packaging to impart water and oil repellency. Little is known, however, with regard to the occurrence of PFAS in pet food packaging. In this study, 37 pet food packaging and 11 pet foods were analyzed for the determination of 13 perfluoroalkyl acids (PFAA), including nine perfluoroalkyl carboxylic acids (PFCA; C4-C12) and four perfluoroalkyl sulfonic acids (PFSA; C4-C10). Furthermore, samples were extracted in organic solvents (methanol and ethyl acetate) and an aliquot of the extract was analyzed using total oxidizable precursor (TOP) assay to determine the occurrence of PFAS precursors that may be present in packaging. PFSA concentrations were below their respective limits of detection. Plastic food packaging samples contained ∑PFCA (sum of 9 PFCAs) concentrations an order of magnitude higher (range: <LOD-60.0 ng/g; mean: 11.8 ng/g), following oxidation of extracts by the TOP assay, than those measured prior to oxidation (range: <LOD-10.3 ng/g; mean: 1.28 ng/g). Similarly, pet food contained approximately an order of magnitude higher ∑PFCA concentrations (range: 0.600"“14.3 ng/g; mean: 5.71 ng/g) following oxidation than those measured prior to oxidation (range: <LOD-3.67 ng/g; mean: 0.89 ng/g). Higher ∑PFCA concentrations following the TOP assay suggested the occurrence of PFAA precursors in food packaging. Fluorotelomer alcohols were suspected to contribute to higher PFCA concentrations measured following the oxidation of extracts of food packaging.

INTRODUCTION/BACKGROUND:Perfluoroalkyl substances (PFAS) were among various persistent organic pollutants suspected to have been released during the collapse of the World Trade Center (WTC) on 9/11. Evidence suggests PFAS may have cardiometabolic effects, including alterations in lipid profiles. This study evaluated the association between cord PFAS and lipids in a population prenatally exposed to the WTC disaster. STUDY POPULATION/METHODS:222 pregnant women in the Columbia University WTC birth cohort enrolled between December 13, 2001 and June 26, 2002 at hospitals located near the WTC site: Beth Israel, St. Vincent's, and New York University Downtown. METHODS:We evaluated the association between five cord blood PFAS (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecane sulfonate (PFDS)) and cord blood lipids (total lipids, total cholesterol, triglycerides). RESULTS:Median (interquartile range (IQR)) concentrations of PFAS were 6.32 (4.58-8.57), 2.46 (1.77, 3.24), 0.38 (0.25, 0.74), 0.66 (0.48, 0.95) and 0.11 (0.09, 0.16) ng/mL for PFOS, PFOA, PFNA, PFHxS and PFDS, respectively. Median (IQR) for lipids were 59.0 (51.5, 68.5) mg/dL for total cholesterol, 196.5 (170.5, 221.2) mg/dL for total lipids and 33.1 (24.2, 43.9) mg/dL for triglycerides. In fully adjusted models, several PFAS were associated with higher lipid levels, including evidence of a strong linear trend between triglycerides and both PFOA and PFHxS. CONCLUSIONS:Findings support previous evidence of an association between PFAS exposure and altered lipid profiles and add novel information on this relationship in cord blood, as well as for an understudied PFAS, PFDS.

Global marine pollution by microplastics (MPs) has received considerable attention in recent years. Nevertheless, little is known about the occurrence of MPs in indoor environments. A novel analytical method was used to quantitatively determine polyethylene terephthalate (PET)- and polycarbonate (PC)- based MPs in 286 indoor dust samples collected from 12 countries. PET-based MPs were detected in all dust samples at concentrations of 38-120,000 µg/g (median: 5900 µg/g), whereas PC-based MPs were measured at <0.11-1700 µg/g (median: 8.8 µg/g). Significant positive correlations were found between the concentrations of terephthalic acid (a PET monomer) and PET as well as between bisphenol A (a PC monomer) and PC. Based on the concentrations of MPs measured in indoor dust, the median daily intake of PET-based MPs calculated for infants was in the range of 4000-150,000 ng/kg-bw/day.

Exposure to diethylhexyl phthalate (DEHP), the most abundant plasticizer used in the production of polyvinyl-containing plastics, has been associated to adverse reproductive health outcomes in both males and females. While the effects of DEHP on reproductive health have been widely investigated, the molecular mechanisms by which exposure to environmentally-relevant levels of DEHP and its metabolites impact the female germline in the context of a multicellular organism have remained elusive. Using the Caenorhabditis elegans germline as a model for studying reprotoxicity, we show that exposure to environmentally-relevant levels of DEHP and its metabolites results in increased meiotic double-strand breaks (DSBs), altered DSB repair progression, activation of p53/CEP-1-dependent germ cell apoptosis, defects in chromosome remodeling at late prophase I, aberrant chromosome morphology in diakinesis oocytes, increased chromosome non-disjunction and defects during early embryogenesis. Exposure to DEHP results in a subset of nuclei held in a DSB permissive state in mid to late pachytene that exhibit defects in crossover (CO) designation/formation. In addition, these nuclei show reduced Polo-like kinase-1/2 (PLK-1/2)-dependent phosphorylation of SYP-4, a synaptonemal complex (SC) protein. Moreover, DEHP exposure leads to germline-specific change in the expression of prmt-5, which encodes for an arginine methyltransferase, and both increased SC length and altered CO designation levels on the X chromosome. Taken together, our data suggest a model by which impairment of a PLK-1/2-dependent negative feedback loop set in place to shut down meiotic DSBs, together with alterations in chromosome structure, contribute to the formation of an excess number of DSBs and altered CO designation levels, leading to genomic instability.

BACKGROUND:Cross-sectional studies have linked greater polychlorinated biphenyl (PCB) exposure to adverse neuropsychological effects in older adults, including learning, memory, and depressive symptoms. However, no studies among older adults have evaluated the association over time. OBJECTIVES:To assess the effect of serum PCB levels on neuropsychological function over a 14-year period in a cohort of older men and women from a PCB-contaminated area of New York State. METHODS:In 2000-2002, we assessed serum PCB levels and neuropsychological function (including the California Verbal Learning Test Trial 1 (CVLTT1) for verbal memory and learning, and the Beck Depression Index (BDI) for depressive symptoms) in 253 men and women, ages 55-74 years. A total of 116 (46%) persons repeated the PCB and neuropsychological assessment 14 years later. To assess the association over time, we used generalized estimating equations with clustering variables time, total PCB (∑PCB), and ∑PCB × time, and adjusted for baseline age, sex, smoking, and total serum-lipids. For statistically significant ∑PCB × time interactions, we evaluated the association between PCBs and either verbal memory and learning or depressive symptoms while holding ∑PCB constant at the 10th and 90th percentiles to clarify the direction of the interaction. RESULTS:Over the study period, serum ∑PCB levels (wet-weight) declined by 22%, and were associated with different patterns of change over time for memory (∑PCB × Time β = 0.08 p = 0.009) and depressive symptoms (∑PCB × Time β = -0.16 p = 0.013). Specifically, verbal memory and learning decreased (β = -0.08 p = 0.008) and depressive symptoms increased (β = 0.17 p = 0.008) among persons with low exposure (∑PCB levels at the 10th percentile), while persons with high exposure (90th percentile) showed non-significant improvements. DISCUSSION:In this cohort, declining ∑PCB levels were likely due at least in part to low rates of local fish consumption in recent decades, given the ban since 1976. The decreased verbal memory and learning and increased depressive symptoms over time among persons with low serum ∑PCB levels is consistent with studies of normative aging. However, the small improvements in those outcomes among those with high serum ∑PCB levels was unexpected. Healthy survivor selection bias or uncontrolled confounding may explain this result. It may also indicate that the neurotoxic impacts of PCBs in older adults are not permanent, but future studies are needed to confirm this possibility.

Similar to humans, pet animals are exposed to environmental contaminants through multiple sources and pathways. Although a few studies have demonstrated exposure of cats and dogs to environmental chemicals, little is known about exposure to bisphenols, benzophenone UV filters, and antibacterial agents. In this study, we measured three bisphenols, three benzophenone-type UV filters, triclosan (TCS), and triclocarban (TCC) in dog (n = 50) and cat urine (n = 50) collected from New York State, USA. Among bisphenols, BPS was found at the highest concentrations (mean ± SD: 3.2 ± 8.5 ng/mL in dogs and 8.85 ± 30.0 ng/mL in cats) with detection frequencies of 96% in dogs and 78% in cats. Among benzophenones, BP-3 (oxybenzone) was the dominant compound in pet urine, followed by BP-1 and BP-8. TCS was found at concentrations higher than those of TCC in both cat and dog urine. There were no significant differences in bisphenol concentrations between sexes or age groups, both in dogs and cats. The calculated hazard quotients (HQ) suggested that the current exposure levels of BPS and BP-3 in pets were 2-5 orders of magnitude below the tentative threshold values available for humans.