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We examined the patterns, variability, and predictors of urinary bisphenol A (BPA) concentrations in 337 children from the Cincinnati, Ohio HOME Study. From 2003 to 2014, we collected two urine samples from women at 16 and 26 weeks of pregnancy and six urine samples from children at 1-5 and 8 years of age. We used linear mixed models to calculate intraclass correlation coefficients (ICCs) as a measure of within-person BPA variability and to identify sociodemographic and environmental predictors. For the 8-year visit, we used multivariable linear regression to explore associations between urinary BPA concentrations and exposure-related factors. We calculated daily intakes using equations estimating creatinine excretion rates and creatinine-standardized BPA concentrations. Urinary BPA concentrations, which decreased over childhood, had a low degree of reproducibility (ICC < 0.2). Estimated daily intakes decreased with age and were below the reference dose of 50 µg/kg body weight/day. BPA concentrations were positively associated with consuming food stored or heated in plastic, consuming canned food and beverages, and handling cash register receipts. Our results suggest that there are multiple sources of BPA exposure in young children. Etiological studies should collect serial urine samples to accurately classify BPA exposure and consider sociodemographic and environmental factors as possible confounders. [ABSTRACT FROM AUTHOR]

Numerous studies have investigated the environmental occurrence, human exposure, and toxicity of bisphenol A (BPA). Following stringent regulations on the production and usage of BPA, several bisphenol analogues have been produced as a replacement for BPA in various applications. The present review outlines the current state of knowledge on the occurrence of bisphenol analogues (other than BPA) in the environment, consumer products and foodstuffs, human exposure and biomonitoring, and toxicity. Whereas BPA was still the major bisphenol analogue found in most environmental monitoring studies, BPF and BPS were also frequently detected. Elevated concentrations of BPAF, BPF, and BPS (i.e., similar to or greater than that of BPA) have been reported in the abiotic environment and human urine from some regions. Many analogues exhibit endocrine disrupting effects, cytotoxicity, genotoxicity, reproductive toxicity, dioxin-like effects, and neurotoxicity in laboratory studies. BPAF, BPB, BPF, and BPS have been shown to exhibit estrogenic and/or antiandrogenic activities similar to or even greater than that of BPA. Knowledge gaps and research needs have been identified, which include the elucidation of environmental occurrences, persistence, and fate of bisphenol analogues (other than BPA), sources and pathways for human exposure, effects on reproductive systems and the mammary gland, mechanisms of toxicity from coexposure to multiple analogues, metabolic pathways and products, and the impact of metabolic modification on toxicity. [ABSTRACT FROM AUTHOR]

Phenols and parabens are used in a multitude of consumer products resulting in ubiquitous human exposure. Animal and in vitro studies suggest that exposure to these compounds may be related to a number of adverse health outcomes, as well as potential mediators such as oxidative stress and inflammation. We examined urinary phenol (bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP)) and paraben (butyl paraben (B-PB), methyl paraben (M-PB), propyl paraben (P-PB)) concentrations measured three times during pregnancy in relation to markers of oxidative stress and inflammation among participants in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) project. Serum markers of inflammation (c-reactive protein (CRP), IL-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α)) were measured twice during pregnancy ( n = 105 subjects, 187 measurements) and urinary markers of oxidative stress (8-hydroxydeoxyguanosine (OHdG) and isoprostane) were measured three times during pregnancy ( n = 54 subjects, 146 measurements). We used linear mixed models to assess relationships between natural log-transformed exposure and outcome biomarkers while accounting for within individual correlation across study visits. After adjustment for urinary specific gravity, study visit, maternal pre-pregnancy BMI, and maternal education, an interquartile range (IQR) increase in urinary BPA was associated with 21% higher OHdG ( p = 0.001) and 29% higher isoprostane ( p = 0.0002), indicating increased oxidative stress. The adjusted increase in isoprostane per IQR increase in marker of exposure was 17% for BP-3, 27% for B-PB, and 20% for P-PB (all p < 0.05). An IQR increase in triclosan (TCS) was associated with 31% higher serum concentrations of IL-6 ( p = 0.007), a pro-inflammatory cytokine. In contrast, IQR increases in BP-3 and B-PB were significantly associated with 16% and 18% lower CRP, a measure of systemic inflammation. Our findings suggest that exposure to BPA, select parabens, and TCS during pregnancy may be related to oxidative stress and inflammation, potential mechanisms by which exposure to these compounds may influence birth outcomes and other adverse health effects, but additional research is needed. [ABSTRACT FROM AUTHOR]

We developed a fast, selective and sensitive on-line LC/LC–MS/MS method for the simultaneous determination of nine parabens and seven environmental phenols in urine. Parabens are widely used as antimicrobial preservatives. Bisphenol A, triclosan, triclocarban, 2-phenylphenol, and benzophenones are used inter alia in disinfectants, sunscreens and in polymers. Some of these substances are suspected endocrine disruptors. Limits of quantification and analytical quality criteria fully met the needs for determining exposure levels occurring in the general population. We analyzed 157 spot urine samples from the general German population (59 females, 39 males and 59 children). For the parabens, we found methyl, ethyl and n -propyl paraben with high detection rates (77–98%), followed by n -butyl (36%), iso -butyl (17%), iso -propyl (3%) and benzyl paraben (3%). We detected no pentyl and heptyl paraben. Urinary concentrations were highest for methyl paraben (median 24.5 μg/L; 95th percentile 379 μg/L) followed by ethyl (1.4 μg/L; 35.2 μg/L) and n -propyl paraben (1.2 μg/L; 68.1 μg/L). Other environmental phenols with high detection rates were BPA (95%), triclosan (45%) and benzophenone 1 and 3 (26%). For most of the parabens/environmental phenols we found higher urinary levels in females than in males or children, probably due to differences in (personal care) product use. However, high levels (in the mg/L range) were also observed in children. Exposure to the above substances is occurring worldwide. Differences between countries do seem to exist and might be caused by different product compositions or different use habits. Human metabolism data is urgently needed to extrapolate from urinary biomarker levels to doses actually taken up. [ABSTRACT FROM AUTHOR]

We present a sensitive method for simultaneous determination of bisphenol A (BPA), benzophenone-3 (BP-3), 4-tert-octylphenol (t-OP),ortho-phenylphenol (OPP), four parabens (methyl, ethyl, propyl, butyl parabens) and five chlorophenols (2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), 2,4,5-trichlorophenol (2,4,5-triclorophenol), 2,4,6-trichlorophenol (2,4,6-TCP), and triclosan (TCS)), in human urine by high-pressure liquid chromatography (HPLC) mass spectrometry (MS). Samples were processed using enzymatic deconjugation of glucuronides followed by solid phase extraction (SPE) on a C18 cartridge and the eluate was concentrated. Analytes were separated by reversed-phase HPLC and then detected by atmospheric pressure chemical ionisation (APCI) MS and quantified by isotope dilution method. We describe details for optimisation of each step of the procedure. The sample treatment steps are straightforward and not labour-intensive and, therefore, permit a high sample throughput with excellent prospects for automation. This method shows low inter-day variation, and detection limits for most of the compounds are below 1 ng/mL in 1 mL of urine. The method accuracy was also verified by the analysis of proficiency testing urine samples. [ABSTRACT FROM AUTHOR]

Abstract: Bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), dichoro- and phenyl phenols are industrial chemicals present in numerous consumer products such as polycarbonate plastics, preservatives in personal care products, sun screens, pesticides and fungicides, respectively, and they are all suspected endocrine disrupters. In this study the urinary excretion of eight phenols in Danish children recruited from the general population were investigated. One 24h urine and two consecutive first morning samples were collected from each of 129 healthy Danish children and adolescents (6–21 years). The concentrations of urinary phenols were analyzed by a new on-line TurboFlow-liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Most of the analyzed phenols were detectable in more than 80% of the 24h urine samples and the median concentration of BPA, TCS, BP-3, 2,4-dichorophenol and 2,5-dichorophenol (analyzed as ∑DCP), 2-phenylphenol and 4-phenylphenol were 1.37, 1.45, 1.41, 0.65, 0.36 and 0.53ng/mL, respectively. The ranges of the excreted TCS and BP-3 were wide; from below limit of detection to maximum levels of 955ng/mL and 162ng/mL, respectively, while the other phenols were excreted in a more narrow range with maximum levels below 25ng/mL. Concentrations in first morning urine were in general higher than in 24h urine and comprised 30–47% of the absolute amount excreted during 24h. The youngest children aged 6–10 years had a significantly higher urinary BPA concentration (ng/mL) and also a relatively higher daily BPA excretion (ng/kg bw/24h) than the older children and adolescents. The opposite pattern was observed for TCS, BP-3 and ∑DCP for which urinary levels increased significantly with age. No gender difference or associations to pubertal development were observed. In conclusion, our study showed that Danish children were exposed to multiple phenols simultaneously. Small children were relatively more exposed to BPA than older children, while higher exposures to TCS, BP-3 and ∑DCP were seen among adolescents. [Copyright &y& Elsevier]

Abstract: Bisphenol A (BPA) is a high production-volume chemical used in the manufacture of a wide variety of consumer products. However it is also a ubiquitous contaminant that can interfere with endocrine systems of wildlife and humans. China is the “world factory” and the Pearl River Delta is the major manufacturing center and is consequently polluted. Concentrations of BPA in meats of marketable fish had not been previously reported for this region. In the study upon which we report here concentrations of BPA were determined in 20 common species of freshwater and marine fish, collected from markets in Hong Kong, SAR, China. A comprehensive analytical method based on SPE extraction and liquid chromatography electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) was developed, validated and applied. The method limit of detection (LOD) and limit of quantification (LOQ) were 0.5 and 1.25ngg−1 dw, respectively. BPA was detected in 19 species of fish at concentrations, ranging from 0.5 to 2.0ngg−1 ww. Average daily BPA intake per person ranged from 1.1×102 ngd−1 for marine fish and 2.2×102 ngd−1 for freshwater fish. Concentrations of BPA in fish from Hong Kong markets unlikely would be causing adverse population-level effects in humans. [Copyright &y& Elsevier]

Abstract: Bisphenol A (BPA) is a monomer crucial for the production of polycarbonate (PC). Recently, it has been verified that BPA is able to migrate from PC baby bottles into food simulants and numerous studies indicate that BPA may affect human health. In this work, five different detergents and bleach were tested to verify if they were able increasing the BPA release from the PC. High performance liquid chromatography (HPLC) with fluorescence detection (FLD) and gas chromatography coupled to mass spectrometry (GC–MS) were used to quantify and identify BPA. Of all detergents tested, only with one was not detected a BPA concentration higher than the control. In the worst case, BPA levels detected were about 500 times higher than the control and the concentration kept high even after rinsing the PC samples three times. In the case of bleach, while it was in contact with the PC, the BPA released was not detected. [Copyright &y& Elsevier]

Abstract: We present two approaches to estimate blood concentrations of Bisphenol A (BPA). Simple kinetic principles were applied to calculate steady state plasma concentrations. A physiologically based model was used to simulate the blood concentration time profile in several age groups exploring the influence of not yet fully developed metabolic capacity on the blood concentrations in the newborn. Both approaches gave concordant results and are in excellent agreement with experimental results [Völkel, W., Colnot, T., Csanady, G.A., Filser, J.G., Dekant, W., 2002. Metabolism and kinetics of bisphenol A in humans at low doses following oral administration. Chem. Res. Toxicol. 15, 1281–1287]. The predictions also agree with published results obtained with a different physiologically based model. According to model simulations, BPA is present in the blood of the normal population at concentrations several orders of magnitude lower than most measurements reported in the literature. At the same external exposure level, the newborn is predicted to have 3 times greater blood concentration than the adult. This is due to the not yet fully developed glucuronidation activity in the newborn, not fully compensated by the unimpaired sulfation pathway. For the highest measured external BPA exposure, the predicted blood concentrations of 2.6pg/ml (steady state concentration) and 8.2pg/ml (peak concentration) in the adult are lower than the in vitro concentrations at which inhibiting adiponectin release from human adipocytes and stimulation of β-cell production and secretion were observed. [Copyright &y& Elsevier]

BACKGROUND: Bisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States. OBJECTIVES: We aimed to assess exposure to BPA and tOP in the U.S. general population. METHODS: We measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants ≥ 6 years of age in the 2003-2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. RESULTS: BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p < 0.001), who in turn had higher concentrations than adults (p = 0.003). LSGM concentrations were lowest for participants in the high household income category (> $45,000/year). CONCLUSIONS: Urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Various lines of evidence have shown that bisphenol A [BPA; HO-C6H4-C(CH3)2- C6H4-OH] acts as an endocrine disruptor when present in very low doses. We have recently demonstrated that BPA binds strongly to human estrogen-related receptor-γ (ERR-γ) in a binding assay using [3H]4-hydroxytamoxifen ([3H]4-OHT). We also demonstrated that BPA inhibits the deactivation activity of 4-OHT. OBJECTIVES: In the present study, we intended to obtain direct evidence that BPA interacts with ERR-γ as a strong binder, and also to clarify the structural requirements of BPA for its binding to ERR-γ. METHODS: We examined [3H]BPA in the saturation binding assay using the ligand binding domain of ERR-γ and analyzed the result using Scatchard plot analysis. A number of BPA derivatives were tested in the competitive binding assay using [3H]BPA as a tracer and in the luciferase reporter gene assay. RESULTS: [3H]BPA showed a KD of 5.50 nM at a Bmax of 14.4 nmol/mg. When we examined BPA derivatives to evaluate the structural essentials required for the binding of BPA to ERR-γ, we found that only one of the two phenol-hydroxyl groups was essential for the full binding. The maximal activity was attained when one of the methyl groups was removed. All of the potent BPA derivatives retained a high constitutive basal activity of ERR-γ in the luciferase reporter gene assay and exhibited a distinct inhibitory activity against 4-OHT. CONCLUSION: These results indicate that the phenol derivatives are potent candidates for the endocrine disruptor that binds to ERR-γ. [ABSTRACT FROM AUTHOR]

The article reports on the continuation of the controversy regarding the human health risks of bisphenol A, an estrogen-like chemical used to make plastics. The chemical industry in the U.S. has proclaimed that the verdict of the federal advisory panel confirms its contention that bisphenol A is safe. However, environmentalists say the report has been tainted by the chemical industry and downplays the risks. On a five-point scale of concern ranging from "negligible" to "serious," the panel had "minimal concern" for potential effects on the prostate during development or accelerated puberty and "negligible concern" that bisphenol A is harming adults.