Faculty Bibliography

Abstract Secretoglobins are a superfamily of secreted proteins thought to participate in inflammation, tissue repair, and tumorigenesis. Secretoglobin family 2A member 1 (Scgb2a1) is a component of prostatein, a major androgen-binding protein secreted by the rat prostate. Using a rat model for developmental reprogramming of susceptibility to prostate carcinogenesis, we identified, by RNA-seq, that Scgb2a1 is significantly upregulated (>100-fold) in the prostate of adult rats neonatally exposed to bisphenol A (BPA), with increased gene expression confirmed by quantitative RT-PCR and chromatin immunoprecipitation for histone H3 lysine 9 acetylation. Bisulfite analysis of two CpG islands located within 10 kb of the Scgb2a1 promoter identified significant hypomethylation of the CpG island upstream of the transcription start site of this gene in the reprogrammed prostate. These data suggest that expression of Scgb2a1 in the adult prostate could be epigenetically reprogrammed by BPA exposure during prostate development, with potential implications for cancer risk and response to chemotherapeutics associated with prostatein binding.

Extracts of wastewater collected from 4 sewage treatment plants (STPs) receiving effluents from different sources in South India were investigated for their levels of transcription factor-mediated gene induction in primary cultured rat hepatocytes. In addition, the relation between gene induction levels and the prevalence of antimicrobial-resistant Escherichia coli (E. coli) in wastewater was examined. STP-3, which treats only hospital wastewater, exhibited significantly greater induction potency of all 6 drug metabolizing cytochrome P450 (CYP) genes examined, CYP1A1, 1A2, 1B1, 2B15, 3A1, and 3A2, whereas the wastewater at STP-1, which exclusively receives domestic sewage, showed significantly diminished levels of induction of 3 CYP genes when compared to the levels of CYP induction at STP-2, which receives mixed wastewater. Samples collected during the monsoon season showed a significantly altered gene induction capacity compared to that of samples from the pre-monsoon period. The data suggest that the toxicity of wastewater in STPs was not significantly diminished during the treatment process. The chemical-gene interaction data predicted that a vast number of chemicals present in the wastewater would stimulate the genes studied in the rat hepatocytes. The multivariable logistic regression analysis demonstrated that the prevalence of isolates resistant to cefotaxime, imipenem and streptomycin was significantly correlated with the levels of induction of at least three CYP-isozymes in STP wastewater. In addition, the resistance of isolates in treatment plants was not altered by the treatment steps, whereas the sampling season did have an impact on the resistance to specific antimicrobials. The identification of receptor-mediated gene regulation capacities offers important data not limited to the (synergistic) physiological role of chemicals in biological systems but may provide new insight into the link between the effects of known/unknown drugs and prevalence of antimicrobial-resistant bacteria in wastewater.

OBJECTIVE:Endocrine-disrupting chemicals (EDCs) adversely affect human health. Our objective was to determine the association of EDC exposure with earlier age of menopause. METHODS:Cross-sectional survey using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 (n = 31,575 females). Eligible participants included: menopausal women >30 years of age; not currently pregnant, breastfeeding, using hormonal contraception; no history of bilateral oophorectomy or hysterectomy. Exposures, defined by serum lipid and urine creatinine-adjusted measures of EDCs, data were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models considered complex survey design characteristics and adjusted for age, race/ethnicity, smoking, body mass index. EDCs were stratified into long (>1 year), short, and unknown half-lives; principle analyses were performed on those with long half-lives as well as phthalates, known reproductive toxicants. Secondary analysis determined whether the odds of being menopausal increased with EDC exposure among women aged 45-55 years. FINDINGS/RESULTS:This analysis examined 111 EDCs and focused on known reproductive toxicants or chemicals with half-lives >1 year. Women with high levels of β-hexachlorocyclohexane, mirex, p,p'-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners -70, -99, -105, -118, -138, -153, -156, -170, and -183 had mean ages of menopause 1.9 to 3.8 years earlier than women with lower levels of these chemicals. EDC-exposed women were up to 6 times more likely to be menopausal than non-exposed women. CONCLUSIONS:This study of a representative sample of US women documents an association between EDCs and earlier age at menopause. We identified 15 EDCs that warrant closer evaluation because of their persistence and potential detrimental effects on ovarian function. Earlier menopause can alter the quantity and quality of a woman's life and has profound implications for fertility, human reproduction, and our global society.

Concern has arisen about benzophenone (BP) ultraviolet (UV) radiation filters, given their use in sunscreen and personal-care products and their reported estrogenic and antiandrogenic activity. We recruited 501 couples who were discontinuing use of contraceptives in order to become pregnant for the Longitudinal Investigation of Fertility and the Environment (LIFE) Study (Michigan and Texas, 2005-2009). Couples provided urine specimens and completed daily journals until they either achieved pregnancy or had tried for 12 months. Women used fertility monitors to time sexual intercourse and digital pregnancy tests. Urinary concentrations of 5 UV filters (ng/mL) were determined using triple-quadrupole mass spectrometry: 2,4-dihydroxybenzophenone (also called BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2'-dihydroxy-4-methoxybenzophenone (BP-8); and 4-hydroxybenzophenone. Fecundability odds ratios were estimated for each UV filter (dichotomized at the 75th percentile) and adjusted for age, creatinine concentration, body mass index (weight (kg)/height (m)(2)), cotinine concentration, season, and site, while accounting for time off contraception. Separate models were fitted for each UV filter and partner; final models included partners' concentrations. Male partners' concentrations of BP-2 and 4-hydroxybenzophenone were associated with reduced fecundity in adjusted models (fecundability odds ratio (FOR) = 0.69 (95% confidence interval (CI): 0.50, 0.95) and FOR = 0.74 (95% CI: 0.54, 1.00), respectively). In models adjusting for both partners' concentrations, male BP-2 concentration remained associated with reduced fecundity (FOR = 0.69, 95% CI: 0.49, 0.97). These data suggest that male exposure to select UV filters may diminish couples' fecundity, resulting in a longer time to pregnancy.

Very few studies describe the fate of artificial sweeteners (ASWs) in wastewater treatment plants (WWTPs). In this study, mass loadings, removal efficiencies, and environmental emission of sucralose, saccharin, aspartame, and acesulfame were determined based on the concentrations measured in wastewater influent, primary effluent, effluent, suspended particulate matter (SPM), and sludge collected from two WWTPs in the Albany area of New York State, U.S.A. All ASWs were detected at a mean concentration that ranged from 0.13 (aspartame) to 29.4 μg/L (sucralose) in wastewater influent, 0.49 (aspartame) to 27.7 μg/L (sucralose) in primary influent, 0.11 (aspartame) to 29.6 μg/L (sucralose) in effluent, and from 0.08 (aspartame) to 0.65 μg/g dw (sucralose) in sludge. Aspartame was found in 92% of influent SPM samples at a mean concentration of 444 ng/g dw, followed by acesulfame (92 ng/g) and saccharin (49 ng/g). The fraction of the total mass of ASWs sorbed to SPM was in the rank order: aspartame (50.4%) > acesulfame (10.9%) > saccharin and sucralose (0.8%). The sorption coefficients of ASWs ranged from 4.10 (saccharin) to 4540 L/kg (aspartame). Significant removal of aspartame (68.2%) and saccharin (90.3%) was found in WWTPs; however, sucralose and acesulfame were less efficiently removed (<2.0%). The total mass loading of sucralose, saccharin, and acesulfame in the WWTP that served a smaller population (∼15,000) was 1.3-1.5 times lower than that in another WWTP that served a larger population (∼100,000). The average daily loading of sucralose in both WWTPs (18.5 g/d/1000 people) was ∼2 times higher than the average loading of saccharin. The daily discharge of sucralose from the WWTPs was the highest (17.6 g/d/1000 people), followed by acesulfame (1.22 g/d/1000 people), and saccharin (1.07 g/d/1000 people). Approximately, 1180 g of saccharin and 291 g of acesulfame were transformed in or removed daily from the two WWTPs. This is the first study to describe the fate of ASWs, including the fraction found in SPM and in sludge, in addition to the aqueous portion of wastewater in WWTPs.

Ganges River dolphin, Platanista gangetica gangetica, is one of the three obligatory freshwater dolphins in the world and is distributed in the Ganges-Brahmaputra-Meghna and Sangu-Karnaphuli River systems in India, Nepal, and Bangladesh. This species is facing considerable threats to its survival, and its population has dwindled from 4000 to 5000 in the early 1980s to 3500 in 2014 in the distribution range. This article reviews current status of the sub-species, habitat use, and the potential threats that the dolphins face for their survival (details of taxonomic status and genetics, evolutionary adaptations and anatomical peculiarities, physical adaptation, primitive characteristics, biology, behavior, surfacing behavior and dive times, mating and birth, and life span/age have been placed as Electronic Supplementary Materials). Recommendations have been made for the protection and developing strategies for the conservation of this Endangered and endemic sub-species.

Concentrations of nine phthalate diesters in 24-h airborne PM2.5 and PM10 were determined from October 2011 to August 2012 in a suburban area in Shanghai, China. Dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), di-iso-butyl phthalate (DIBP), benzyl butyl phthalate (BzBP), and di(2-ethylhexyl) phthalate (DEHP) were frequently detected in airborne particulate matter at sum concentrations of these six compounds ranging from 13.3 to 186 ng/m(3), with an average value of 59.8 ng/m(3) in PM2.5, and from 10.1 to 445 ng/m(3), with an average value of 132 ng/m(3) in PM10. DEHP, DBP, and DIBP were the major phthalate diesters found in PM samples. DEHP was found predominantly in coarse (size fraction of between PM2.5 and PM10) particles, whereas DMP, DEP, DBP, DIBP, and BzBP were found predominantly in fine (PM2.5) particles. The concentrations of phthalates in PM during warm months (207 ng/m(3) for PM10 and 71.9 ng/m(3) for PM2.5, on average) were significantly higher than those during cold months (76.9 ng/m(3) for PM10 and 50.4 ng/m(3) for PM2.5). Significant positive correlations were found between concentrations of total phthalates, DEHP, and BzBP, with the total mass and organic carbon content of PM. Based on the concentrations of DEHP, incremental lifetime cancer risks (ILCR) from inhalation exposure were estimated using a Monte Carlo simulation. Although the 95% probabilities for the ILCR values for the general population were below the U.S. Environmental Protection Agency (EPA) threshold of 10(-6), our result is an underestimate of the actual health risk because we only considered the outdoor inhalation exposure to DEHP in this study.

Siloxanes are widely used in various industrial applications as well as in personal care products. Despite their widespread use and potential toxic effects, few studies have reported on the occurrence of siloxanes in the environment. In this study, we determined the concentrations of 5 cyclic and 15 linear siloxanes in sludge collected from 40 representative wastewater treatment plants (WWTPs) in Korea. Total concentrations of 20 siloxanes (Σsiloxane) in sludge ranged from 0.05 to 142 (mean: 45.7) μg/g dry weight, similar to the concentrations reported in European countries but higher than those reported in China. The concentrations of siloxanes in sludge from domestic WWTPs were significantly (p<0.01) higher than those from industrial WWTPs, indicating higher consumption of siloxanes in various personal care products (e.g. shampoos and conditioners). The major siloxane compounds found in sludge were decamethylcyclopentasilane (D5), docosamethyldecasiloxane (L10) and dodecamethylcyclohexasilane (D6), which collectively accounted for, on average, 62% of the Σsiloxane concentrations. Non-parametric multidimensional scaling ordination of the profiles of siloxanes indicated the existence of different usage patterns of siloxanes between industrial and household activities. Multiple linear regression analysis of siloxane concentrations and WWTP characteristics suggested that D5, D6 and linear siloxane concentrations in sludge were positively correlated with population served by a WWTP. Environmental emission fluxes of cyclic and linear siloxanes through sludge disposal in Korea were 14,800 and 18,500 kg/year, respectively. This is the first report describing occurrence and environmental emission of siloxanes through sludge in Korea.

Sediment chronologies from inland lakes suggest the influence of local to sub-regional scale sources for mercury (Hg). However, apportionment of sources for Hg using sediment chronologies is difficult due to the mixing of sources and pathways. Mercury and polycyclic aromatic hydrocarbons (PAH) often share common sources and pathways into the environment. Thus, chronologies of PAHs in dated cores of sediments might be a useful tool to infer sources of Hg. Sediment cores from seven inland lakes of Michigan were collected for measurement of PAHs and Hg and dated by use of (210)Pb. PAH concentrations and ratios of kinetic and thermodynamic PAH compounds were used to infer sources of Hg. Ratios indicate the existence of modern combustion sources to each lake and historic combustion sources to lakes near cement kilns and an iron foundry. Coal combustion sources were identified for two lakes near urban centers. Whereas a petroleum combustion source was identified for a lake that has a coal fired power plant along its shoreline. These results have implications for the cycling of Hg on local to regional scales.

Water, sediment, plankton, and blood and liver tissues of crucian carp (Carassius auratus) and mandarin fish (Siniperca scherzeri) were collected from six major rivers and lakes in South Korea (including Namhan River, Bukhan River, Nakdong River, Nam River, Yeongsan River and Sangsa Lake) and analyzed for perfluorinated alkyl substances (PFASs). Perfluorooctane sulfonate (PFOS) was consistently detected at the greatest concentrations in all media surveyed with the maximum concentration in water of 15 ng L(-1) and in biota of 234 ng mL(-1) (fish blood). A general ascending order of PFAS concentration of water<sediment<plankton<crucian carp tissues<mandarin fish tissues was found. Except for the Nakdong River and Yeongsan River, the sum PFAS concentrations in water samples were below 10 ng L(-1). The PFOS and perfluorooctanoic acid (PFOA) concentrations in water did not exceed levels for acute and/or chronic effects in aquatic organisms. High concentrations of long chain perfluorocarboxylates (LCPFCAs) were found in sediment samples. PFOS, perfluoroundecanoic acid (PFUnA), perfluorododecanoic acid (PFDoA) and perfluorodecanoic acid (PFDA) accounted for 94-99% of the total PFASs concentration in fish tissues. The mean ratios of PFAS concentration between fish blood and fish liver were above 2 suggesting higher levels in blood than in liver. Significant positive correlations (r>0.80, p<0.001) were observed between PFOS concentration in blood and liver tissues of both crucian carp and mandarin fish. This result suggests that blood can be used for nonlethal monitoring of PFOS in fish. Overall, the rank order of mean bioconcentration factors (BCFs) of PFOS in biota was; phytoplankton (196 L/kg)<zooplankton (3,233 L/kg)<crucian carp liver (4,567 L/kg)<crucian carp blood (11,167 L/kg)<mandarin liver (24,718 L/kg)<mandarin blood (73,612 L/kg).