Faculty Bibliography

Oxidative stress has been recognized as one of the most important contributors to infertility in both males and females. Exposure to many environmental chemicals, such as phthalates, has been shown to induce oxidative stress. In a longitudinal study designed to assess exposure to environmental chemicals and fecundity in couples who were planning pregnancy, 894 urine samples were collected from 469 couples from Michigan and Texas during 2005-2009. The concentrations of 14 phthalate metabolites and a marker of oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG), were determined in these samples. Concentrations, profiles, and estimated daily intakes (DIs) of phthalates were positively associated with 8-OHdG. The median concentrations of monomethyl phthalate (mMP), monoethyl phthalate (mEP), mono(3-carboxypropyl) phthalate (mCPP), mono-n-butyl phthalate (mBP), mono(2-isobutyl) phthalate (miBP), monobenzyl phthalate (mBzP), Σ5mEHP (sum of five metabolites of di(2-ethylhexyl) phthalate (DEHP)) and Σ14phthalates (sum of 14 urinary phthalate metabolites) were 0.48, 85.2, 4.50, 7.66, 4.36, 3.80, 54.8, and 249 μg/g creatinine, respectively. The estimated DI values for DEHP in 39 individuals were above the U.S. Environmental Protection Agency's (EPA) reference dose (RfD) of 20 μg/kg-bw/day. The mean and median concentrations of 8-OHdG were 6.02 and 3.13 μg/g creatinine, respectively, which were significantly higher in females than in males. Statistically significant associations were found between 8-OHdG and urinary concentrations of mEP, and Σ5mEHP for females. Similarly, a significant association was found between 8-OHdG and DIs estimated for select phthalates. Our results suggested that phthalate exposure increases oxidative stress, which can be a mechanism for the diminished fertility observed in couples who were highly exposed to select phthalates.

Dried blood spots (DBS) collected from infants shortly after birth for the newborn screening program (NSP) in the United States are valuable resources for the assessment of exposure to environmental chemicals in newborns. The NSP was debuted as a public health program in the United States in the 1960s; and the DBS samples collected over a period of time can be used in tracking temporal trends in exposure to environmental chemicals by newborns. In this study, polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were measured in DBS samples collected from newborns in Upstate New York from 1997 to 2011 by gas chromatography-high resolution mass spectrometry (GC-HRMS). Twelve PCBs and two OCPs were found in DBS samples at a detection rate above 50% (n=51). The mean whole blood concentration of ΣPCBs (sum of 12 congeners) over the 15-year period was 1.06 ng/mL, followed by p,p'-DDE (0.421 ng/mL) and HCB (0.065 ng/mL). The measured concentrations of PCBs and p,p'-DDE in infants'blood were comparable to those reported in cord blood, suggesting maternal/trans-placental transfer of these compounds from mothers to fetuses. The concentrations of ΣPCBs and p,p'-DDE in blood samples of infants decreased significantly between 1997 and 2001, and no significant reduction was found thereafter. This observation is consistent with the trends reported for these chemicals in other human tissues in the United States.

Blue mussels (Mytilus edulis) and sediments collected from 1991 to 2005 from New Bedford Harbor (NBH), MA, were analyzed for two polycyclic musks (HHCB or Galaxolide® and AHTN or Tonalide®), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs). HHCB and AHTN were found in mussel tissues at mean concentrations of 836 and 376 ng/g lipid weight (lw), respectively, which were two- to seven-fold higher than those found at a reference site. Mean concentrations of HHCB and AHTN in NBH sediments were 12 and 6.3 ng/g dry weight (dw), respectively. Four- and five-ringed PAHs, such as phenanthrene, anthracene, fluoranthene, and pyrene, collectively accounted for 61 % of the ∑PAHs concentrations in mussels from NBH. Mean ΣPCB concentrations in mussels from upper and lower NBH were 942 and 182 μg/g lw, respectively, and were dominated by tetra- and penta-chlorobiphenyl congeners, collectively accounting for 61 % of the ΣPCB concentrations. The mean concentration of ∑PBDEs in mussels from NBH was 277 ng/g lw, and no significant difference existed in the concentrations between upper and lower NBH. DDTs were the major OCP found in mussels, found at a mean concentration of 778 ng/g lw. The concentrations of HHCB, AHTN, ΣPBDEs, ΣPAHs, and DDTs in mussels decreased significantly (r (2) ≥ 0.56, p ≤ 0.052) from 1991 to 2005. The concentrations of PCBs and chlordanes did not exhibit a decreasing trend in mussel tissues (r (2) < 0.50; p > 0.076) from 1991 to 2005. Based on the temporal trends in the concentrations of HHCB, AHTN, ∑PAHs, and ∑PBDEs found in mussels from NBH, it was estimated that between 5.5 and 12 years were required for the concentrations of these compounds to decrease by half (i.e., environmental halving time) of the levels found in 1991.

BACKGROUND:Polybrominated diphenyl ethers (PBDE) have been used widely in consumer products and are currently found at detectable levels in the blood of humans and animals across the globe. In stark contrast to this widespread exposure to PBDEs, there is relatively little research on potential adverse health effects of exposure of children to these chemicals. OBJECTIVES/OBJECTIVE:We performed this cross-sectional study to determine if blood PBDE levels (for 4 congeners) are associated with cardiovascular stress responses and psychological states in children. METHODS:Levels of 4 PBDE congeners (BDE-28, -47, -99, and -100) in whole blood were measured in children (N=43). These levels were analyzed in relation to cardiovascular disease risk factors, including cardiovascular responses to acute stress and relevant psychological variables, namely, hostility and depression. RESULTS:Higher levels of blood PBDEs were associated with significantly greater sympathetic activation during acute psychological stress and greater anger, as evidenced by significant associations with 3 different measures of this psychological variable. CONCLUSIONS:This study suggests an association between PBDE exposure and children's cardiovascular responses to stress as well as parental and self-reported anger in the child. These variables are particularly important as they may be of potential relevance to the future development of cardiovascular disease (CVD). Although intriguing, there is a need for further investigation and replication with a larger sample of children.

Perchlorate (ClO4 (-)) and thiocyanate (SCN(-)) interfere with iodide (I(-)) uptake by the sodium/iodide symporter, and thereby these anions may affect the production of thyroid hormones (THs) in the thyroid gland. Although human exposure to perchlorate and thiocyanate has been studied in the United States and Europe, few investigations have been performed in Asian countries. In this study, we determined concentrations of perchlorate, thiocyanate, and iodide in 131 serum samples collected from 2 locations in Northern Vietnam, Bui Dau (BD; electrical and electronic waste [e-waste] recycling site) and Doung Quang (DQ; rural site) and examined the association between serum levels of these anions with levels of THs. The median concentrations of perchlorate, thiocyanate, and iodide detected in the serum of Vietnamese subjects were 0.104, 2020, and 3.11 ng mL(-1), respectively. Perchlorate levels were significantly greater in serum of the BD population (median 0.116 ng mL(-1)) than those in the DQ population (median 0.086 ng mL(-1)), which indicated greater exposure from e-waste recycling operations by the former. Serum concentrations of thiocyanate were not significantly different between the BD and DQ populations, but increased levels of this anion were observed among smokers. Iodide was a significant positive predictor of serum levels of FT3 and TT3 and a significant negative predictor of thyroid-stimulating hormone in males. When the association between serum levels of perchlorate or thiocyanate and THs was assessed using a stepwise multiple linear regression model, no significant correlations were found. In addition to greater concentrations of perchlorate detected in the e-waste recycling population, however, given that lower concentrations of iodide were observed in the serum of Vietnamese females, detailed risk assessments on TH homeostasis for females inhabiting e-waste recycling sites, especially for pregnant women and their neonates, are required.

Exposure of humans to environmental phenolic compounds such as bisphenol A (BPA) and alkylphenols is a matter of concern, due to these compounds' ubiquitous occurrence and estrogenic potencies. Little is known about the levels of environmental phenolics in personal care products (PCPs). In this study, nonylphenol, two octylphenols, eight bisphenols (BPA and its analogs), and triclosan (TCS) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in PCP samples (n = 231) collected from China and the United States (U.S.). The concentrations of 4-n-nonylphenol (4-NP), 4-n-octylphenol (4-OP), 4-tert-octylphenol (4-t-OP), and TCS were in the ranges of <0.5-39,100 [geometric mean (GM): 21.5], <0.5-315 (0.680), <1.0-10,100 (2.69), and <0.5-53,900 (3.03) ng/g, respectively. The GM concentrations of individual bisphenols, including BPA, bisphenol S (BPS), and bisphenol F (BPF), were generally at sub-nanogram per gram levels. No significant differences in concentrations of the target compounds were found among various PCP categories or between China and the U.S. The estimated GM daily intakes of 4-NP, ∑OPs (sum of 4-OP and 4-t-OP), ∑BPs (sum of eight bisphenols), and TCS through dermal absorption from the use of PCPs were 0.932, 0.093, 0.072, and 0.016 μg/day, respectively, for adult Chinese women and 0.340, 0.054, 0.120, and 0.068 μg/day, respectively, for adult U.S. women. Body lotions, face creams, and liquid foundations accounted for the majority (>85 %) of the dermal exposure doses of the target phenolics.

Concern over the occurrence of artificial sweeteners (ASWs) as well as pharmaceuticals and personal care products (PPCPs) in the environment is growing, due to their high use and potential adverse effects on non-target organisms. The data for this study are drawn from a nationwide survey of ASWs in sewage sludge from 40 representative wastewater treatment plants (WWTPs) that receive domestic (WWTPD), industrial (WWTPI), or mixed (domestic plus industrial; WWTPM) wastewaters in Korea. Five ASWs (concentrations ranged from 7.08 to 5220 ng/g dry weight [dw]) and ten PPCPs (4.95-6930 ng/g dw) were determined in sludge. Aspartame (concentrations ranged from 28.4 to 5220 ng/g dw) was determined for the first time in sewage sludge. The median concentrations of ASWs and PPCPs in sludge from domestic WWTPs were 0.8-2.5 and 1.0-3.4 times, respectively, the concentrations found in WWTPs that receive combined domestic and industrial wastewaters. Among the five ASWs analyzed, the median environmental emission rates of aspartame through domestic WWTPs (both sludge and effluent discharges combined) were calculated to be 417 μg/capita/day, followed by sucralose (117 μg/capita/day), acesulfame (90 μg/capita/day), and saccharin (66μg/capita/day). The per-capita emission rates of select PPCPs, such as antimicrobials (triclocarban: 158 μg/capita/day) and analgesics (acetaminophen: 59 μg/capita/day), were an order of magnitude higher than those calculated for antimycotic (miconazole) and anthelmintic (thiabendazole) drugs analyzed in this study. Multiple linear regression analysis of measured concentrations of ASWs and PPCPs in sludge revealed that several WWTP parameters, such as treatment capacity, population-served, sludge production rate, and hydraulic retention time could influence the concentrations found in sludge.

Sewage epidemiology is a rapidly expanding field that can provide information on illicit drug usage in communities, based on the measured concentrations in samples from wastewater treatment plants (WWTPs). In this study, select illicit drugs (six drugs and eight metabolites) were determined on a daily basis for a week in wastewater, suspended particulate matter (SPM), and sludge from two WWTPs in the Albany area in New York State. The WWTP that served a larger population (∼100 000, with a flow rate of 83 300 m(3)/d) showed 3.2 (methadone) to 51 (3,4-methylenedioxyamphetamine; MDA) times higher mass flows of illicit drugs than did the WWTP that served a smaller population (∼15 000, with a flow rate of 6850 m(3)/d). The consumption rate of target illicit drugs in the communities served by the two WWTPs was estimated to range from 1.67 to 3510 mg/d/1000 people. Between the dissolved and particulate phases, the fraction of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), amphetamine, and MDA sorbed to SPM ranged from 34.3% to 41.1% of the total mass in the waste stream. The removal efficiencies of illicit drugs from the two WWTPs ranged from 4% (norcocaine) to 99% (cocaine); however, methamphetamine, methadone, and EDDP showed a negative removal in WWTPs. The environmental emission of illicit drugs from WWTP discharges was calculated to range from 0.38 (MDEA) to 67.5 (EDDP) mg/d/1000 people. Other markers such as caffeine, paraxanthine, nicotine, and cotinine were found to predict the concentrations of select illicit drugs in raw wastewater (r(2) = 0.20-0.79; p ≤ 0.029).

It is well known that perfluorooctane sulfonate (PFOS) preferentially accumulates in the plasma of wildlife and humans. Although earlier studies have suggested that this was due to binding of PFOS to a plasma protein, definite characterization of the protein in in vivo exposure studies was not conducted thus far. In this study, we conducted both in vitro and in vivo experiments to identify PFOS binding protein in the plasma of fish. For the in vivo studies, PFOS was administered intraperitoneally to tiger pufferfish, Takifugu rubripes, and the plasma was separated by ammonium sulfate fractionation. High concentrations of PFOS were found in the 65-70 percent ammonium sulfate fraction (190ng/mL). After SDS-PAGE and N-terminal amino acid sequence analysis, the PFOS-binding protein was identified as an apolipoprotein A-I, which was confirmed on the basis of a significant correlation to the PFOS concentration in each fraction. The plasma samples fractionated by ammonium sulfate from untreated pufferfish were subjected to PFOS binding assay by the equilibrium dialysis method. The results further confirmed that the 60-65 percent ammonium sulfate fraction showed a high PFOS-binding ratio, similar to that found from in vivo studies. We demonstrated that PFOS is likely bound to an apolipoprotein A-I in the plasma of tiger pufferfish in in vivo and in vitro studies.

OBJECTIVE:To assess the relationship between environmental chemicals and couple fecundity or time to pregnancy (TTP). DESIGN/METHODS:Prospective cohort. SETTING/METHODS:Communities of targeted populations with reported exposure. PATIENT(S)/METHODS:501 couples recruited upon discontinuing contraception to become pregnant, 2005-2009. INTERVENTION(S)/METHODS:None. MAIN OUTCOME MEASURE(S)/METHODS:Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) estimated for each partner's chemical concentrations adjusted for age, body mass index, cotinine, creatinine, and research site while accounting for time off contraception. RESULT(S)/RESULTS:Couples completed interviews and anthropometric assessments and provided the urine specimens for quantification of bisphenol A (BPA) and 14 phthalate metabolites, which were measured using high-performance liquid chromatography with electrospray triple-quadrupole mass spectrometer. Women recorded menstruation and pregnancy test results in daily journals. Couples were evaluated until a positive human-chorionic gonadotropin pregnancy test or 12 cycles without pregnancy. Neither female nor male BPA concentration was associated with TTP (FOR 0.98; 95% CI, 0.86, 1.13 and FOR 1.04; 95% CI, 0.91, 1.18, respectively). Men's urinary concentrations of monomethyl, mono-n-butyl, and monobenzyl phthalates were associated with a longer TTP (FOR 0.80; 95% CI, 0.70, 0.93; FOR 0.82, 95% CI, 0.70, 0.97; and FOR 0.77, 95% CI, 0.65 0.92, respectively). CONCLUSION(S)/CONCLUSIONS:Select male but not female phthalate exposures were associated with an approximately 20% reduction in fecundity, underscoring the importance of assessing both partners' exposure to minimize erroneous conclusions.