Faculty Bibliography

Bisphenol A (BPA) is a widely produced, endocrine disrupting compound that is pervasive in the environment. Data suggest that developmental exposure to BPA during sexual differentiation of the brain leads to later behavioral consequences in offspring. Outbred deer mice (Peromyscus maniculatus bairdii) are an excellent animal model for such studies as they exhibit well-defined sex- and steroid-dependent behaviors. Here, dams during gestation and lactation were fed with a phytoestrogen-free control diet, the same diet supplemented with either ethinyl estradiol (0.1 ppb), or one of the three doses of BPA (50 mg, 5 mg, 50 μg/kg feed weight). After weaning, the pups were maintained on control diet until they reached sexual maturity and then assessed for both spatial learning capabilities and anxiety-like and exploratory behaviors. Relative to controls, males exposed to the two upper but not the lowest dose of BPA demonstrated similar impairments in spatial learning, increased anxiety and reduced exploratory behaviors as ethinyl estradiol-exposed males, while females exposed to ethinyl estradiol, but not to BPA, consistently exhibited masculinized spatial abilities. We also determined whether dams maintained chronically on the upper dose of BPA contained environmentally relevant concentrations of BPA in their blood. While serum concentrations of unconjugated BPA in controls were below the minimum level of detection, those from dams on the BPA diet were comparable (5.48±2.07 ng/ml) to concentrations that have been observed in humans. Together, these studies demonstrate that developmental exposure to environmentally relevant concentrations of BPA can disrupt adult behaviors in a dose- and sex-dependent manner.

Concern over the occurrence of pharmaceuticals and their metabolites in the environment is mounting due to the potential adverse effects on nontarget organisms. This study draws upon a nationwide survey of psychoactive pharmaceuticals (i.e., antischizophrenics, anxiolytics, and antidepressants) in sludge from 40 representative wastewater treatment plants (WWTPs) that receive domestic, industrial, or mixed (domestic plus industrial) wastewaters in Korea. A total of 16 psychoactive pharmaceuticals (0.12-460 ng/g dry weight) and nine of their metabolites (0.97-276 ng/g dry weight) were determined in sludge. The median concentrations of psychoactive drugs in sludge from domestic WWTPs were 1.2-3.2 times higher than the concentrations found in WWTPs that receive combined domestic and industrial wastewaters. Among the psychoactive drugs analyzed, the median environmental emission rates of alprazolam (APZ) and carbamazepine (CBZ) through domestic WWTPs (both sludge and effluent discharges combined) were calculated to be ≥ 15.5 μg/capita/day, followed by quetiapine (QTP; 8.51 μg/capita/day), citalopram (CLP; 5.45 μg/capita/day), and venlafaxine (VLF; 3.59 μg/capita/day). The per-capita emission rates of some of the metabolites of psychoactive drugs through WWTP discharges were higher than those calculated for parent compounds. Significant correlations (ρ = 0.432-0.780, p < 0.05) were found between the concentrations of typically coprescribed antischizophrenics and antidepressants in sludge. Multiple linear regression analysis of measured concentrations of drugs in sludge revealed that several WWTP parameters such as treatment capacity, population-served, sludge production rate, composition of wastewater (domestic versus industrial), and hydraulic retention time can affect the concentrations of psychoactive drugs in sludge.

Widespread exposure of humans to benzophenone-3 (BP-3) is a concern due to this compound's potential to disrupt endocrine function. BP-3 can be metabolized by phase I and phase II reactions of the human cytochrome P450 system. Urinary measurements of BP-3 have been used as a biomarker of exposure. Nevertheless, metabolic transformation pathway and the transformation products of BP-3 in humans are still less known. In this study, 166 urine samples collected from children and adults in the U.S. and China were analyzed for free and total forms (free plus conjugated) of BP-3 as well as four of its metabolic derivatives, 4-OH-BP, 2,4-diOH-BP, 2,2',4,4'-tetraOH-BP, and 2,2'-diOH-4-MeO-BP, using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). BP-3 was found in almost all urine samples from the U.S. and China. Concentrations of BP-3 in urine from children (GM: 9.97 ng/mL) and adults (15.7 ng/mL) in the U.S. were significantly higher than those in children (0.622 ng/mL) and adults (0.977) from China. A significant positive relationship was found between the concentrations of urinary BP-3 and its derivatives. The profiles of BP derivatives in urine suggested that demethylation was a major route of BP-3 metabolism. The percentage of the free form of BP-3 in urine was used in the determination of efficacy of phase II metabolism among the different population groups studied. A significantly lower percentage of the free form of BP-3 was found in urine from the U.S. population than in the Chinese population.

Despite reports of the occurrence of bisphenol A diglycidyl ether (BADGE) and its derivatives in canned foods and consumer products, biomonitoring studies of human exposure to these compounds are lacking. In this study, 127 urine samples collected from the U.S. and China were analyzed for free and total (free plus conjugated) concentrations of BADGE and its three derivatives, bisphenol A (2,3-dihydroxypropyl) glycidyl ether [BADGE·H(2)O], bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) ether [BADGE·HCl·H(2)O], and bisphenol A bis (2,3-dihydroxypropyl) ether [BADGE·2H(2)O], using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). BADGE and its three derivatives (collectively referred to as BADGEs) were found in 100% of the urine samples analyzed. Total urinary concentrations of BADGEs in the U.S. ranged from 1.24 to 9.03 ng/mL, with a GM concentration of 3 ng/mL. Concentrations of BADGEs in urine from adults (GM: 1.36 ng/mL) and children (1.02 ng/mL) in China were 3-fold lower than the concentrations found in the U.S. Both free and conjugated forms of BADGEs were present in urine, and the proportion of free form was inversely related to the total concentration of BADGEs. Among the four BADGEs measured in urine, BADGE·2H(2)O was the predominant compound, accounting for 45-60% of the total BADGEs concentration, followed by BADGE (17-24%). The distribution of the four BADGEs varied, depending on age, gender, and ethnicity of the adults and children. Daily intake (DI) and effective daily intake (DI(E)) of BADGEs were estimated based on urinary concentrations, and their respective values were 69.4 and 9.16 ng/kg-bw/day for the U.S. population and 28.4 and 5.69 ng/kg-bw/day for the Chinese population. The concentrations of BADGEs in U.S. urine were 3- to 4-fold higher than the corresponding concentrations of bisphenol A.

p-Hydroxybenzoic acid esters (parabens) and bisphenol A diglycidyl ether (BADGE) are widely present in personal care products, food packages, and material coatings. Nevertheless, little is known about the occurrence of these compounds in indoor dust. In this study, we collected 158 indoor dust samples from the U.S., China, Korea, and Japan and determined the concentrations of 11 target chemicals, viz., six parabens and their common hydrolysis product, 4-hydroxybenzoic acid (4-HB), as well as BADGE and its three hydrolysis products (BADGE·H(2)O, BADGE·2H(2)O, and BADGE·HCl·H(2)O). All of the target compounds were found in dust samples from four countries. Concentrations of sum of six parabens in dust were on the order of several hundred to several thousands of nanogram per gram. Geometric mean concentrations of BADGEs in dust ranged from 1300 to 2890 ng/g among four countries. Methyl paraben (MeP), propyl paraben (PrP), BADGE·2H(2)O, and BADGE·HCl·H(2)O were the predominant compounds found in dust samples. This is the first report of BADGE and its hydrolysis products (BADGEs) in indoor dust samples and of parabens in indoor dust from Asian countries. On the basis of the measured concentrations of target chemicals, we estimated the daily intake (EDI) via dust ingestion. The EDIs of parabens via dust ingestion were 5-10 times higher in children than in adults. Among the four countries studied, the EDIs of parabens (5.4 ng/kg-bw/day) and BADGEs (6.5 ng/kg-bw/day) through dust ingestion were the highest for children in Korea and Japan.

Bisphenol analogues are used in the production of polycarbonate plastics and epoxy resins. Despite the widespread use of bisphenols, few studies have reported the occurrence of compounds other than bisphenol A (BPA) in sediment. In this study, concentrations and profiles of eight bisphenol analogues were determined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in sediments collected from several industrialized areas in the United States (U.S.), Japan, and Korea. The total concentrations of bisphenols (ΣBPs; sum of eight bisphenols) in sediment ranged from below the limit of quantitation (LOQ) to 25,300 ng/g dry weight (dw), with a mean value of 201 ng/g dw. Sediment samples from Lake Shihwa, Korea, contained the highest concentrations of both individual and total bisphenols. Among individual bisphenols, BPA and bisphenol F (BPF) were the predominant compounds, accounting for 64% and 30% of the total bisphenol concentrations in sediment. We also examined vertical profiles of concentrations of bisphenol analogues in sediment cores from the U.S. and Japan. Sediment cores from the U.S. showed a gradual decline in the concentrations of bisphenols as compared to the past decade. BPA concentrations were found to decline in a sediment core from Tokyo Bay, but bisphenol S (BPS) was more frequently detected in core sections that represent the most recent decade, which is consistent with the replacement of BPA with BPS in some applications since 2001 in Japan.

BACKGROUND:Environmental chemicals may be associated with endometriosis. No published research has focused on the possible role of perfluorochemicals (PFCs) despite their widespread presence in human tissues. METHODS:We formulated two samples. The first was an operative sample comprising 495 women aged 18-44 years scheduled for laparoscopy/laparotomy at one of 14 participating clinical sites in the Salt Lake City or San Francisco area, 2007-2009. The second was a population-based sample comprising 131 women matched to the operative sample on age and residence within a 50-mile radius of participating clinics. Interviews and anthropometric assessments were conducted at enrollment, along with blood collection for the analysis of nine PFCs, which were quantified using liquid chromatography-tandem mass spectrometry. Endometriosis was defined based on surgical visualization (in the operative sample) or magnetic resonance imaging (in the population sample). Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for each PFC (log-transformed), adjusting for age and body mass index, and then parity. RESULTS:Serum perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17-3.06]) and perfluorononanoic acid (2.20 [1.02-4.75]) were associated with endometriosis in the operative sample; findings were moderately attenuated with parity adjustment (1.62 [0.99-2.66] and 1.99 [0.91-4.33], respectively). Perfluorooctane sulfonic acid (1.86 [1.05-3.30]) and PFOA (2.58 [1.18-5.64]) increased the odds for moderate/severe endometriosis, although the odds were similarly attenuated with parity adjustment (OR = 1.50 and 1.86, respectively). CONCLUSIONS:Select PFCs were associated with an endometriosis diagnosis. These associations await corroboration.

Concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) were determined in surface sediments from Lake Shihwa and from creeks that discharge into this artificial lake. The toxic equivalents (TEQs) in sediments ranged from 1.0 to 1770 pg/g dry weight, which were some of the highest values ever reported so far for coastal sediments on a global basis. The concentrations of PCDD/Fs and DL-PCBs decreased with increasing distance from the creeks to offshore regions of the lake. Based on a multivariate statistical analysis and congener profiles, it was found that high contamination by PCDD/Fs in creek sediments collected around Lake Shihwa was associated with releases from chlor-alkali processes. Significant correlations were found for total organic carbon content and the concentrations of highly chlorinated PCDD/F congeners. This is the first report to document chlor-alkali processes as a significant source of PCDD/F contamination in Korean coastal waters.

Phthalate esters are ubiquitous environmental pollutants and are recognized as environmental endocrine disruptors because of their potential to elicit reproductive and developmental toxicity. Several phthalate esters have been listed by the US Environmental Protection Agency (EPA) as chemicals of concern. Determination of concentrations of phthalate esters in foodstuffs, typically present at sub to low nanogram-per-gram concentrations (between 0.1 and 100 ng g(-1)), is essential for assessment of human dietary exposure. However, phthalate esters are commonly present as contaminants in several laboratory products, including organic solvents, that are used in sample preparation and analysis. Therefore, accurate analysis of phthalates in food samples is a challenging task. In this review, we summarize the methods available for the determination of phthalate esters in foodstuffs and report on concentrations of phthalates in foodstuffs and potential sources of contamination by phthalates in the analysis of foodstuffs. We offer suggestions to eliminate and/or reduce background levels of contamination by phthalates in the analysis of food and other biological samples. We also introduce methods that are suitable for trace analysis of phthalates in a variety of liquid and solid food samples, in particular, a liquid-liquid extraction method for removal of lipids from food samples, because these can substantially reduce background levels of phthalates in the analytical procedure.

Bisphenol-A (BPA) is a commonly used color developer in thermal paper. In this application, BPA is present in its free, unbound form and can be readily released, making thermal paper a potential source for human exposure. In this study, BPA was determined in 44 thermal paper samples collected in Belgium. BPA was detected in all the samples; 73% of the samples had concentrations between 0.9% and 2.1% (between 9 and 21 mg BPA/g paper), while the remaining 27% of the samples had concentrations below 0.01% (0.1mg BPA/g paper). The BPA concentrations measured in thermal paper were comparable with those reported in other international studies. Since thermal paper is a feedstock for paper recycling processes, contamination of other "BPA-free" papers can occur. An estimation of human exposure through thermal paper results in a median intake of 445 ng BPA/day for the general population, which corresponds to an exposure of 6.4 ng/kg bw/day for a person of 70 kg. The exposure of those people who come occupationally in contact with thermal paper can be much higher.