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Abstract Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorder among females of reproductive age. Many emerging contaminants in personal care products have been confirmed with endocrine disruptive effects. We performed a case-control study to explore the association between the concentrations of certain emerging contaminants (organic UV filters, bisphenol A, and triclosan) and the risk of PCOS. Urine samples were collected from 40 women with PCOS (case group) and 83 healthy women (control group). No significant differences were found in detection rate or total concentrations of analytes in women with PCOS and controls (p > 0.05). In addition, no association was found between certain emerging contaminants and PCOS either in an unadjusted binary logistic regression model or in a model adjusted for potential confounders. However, with stratification according to body mass index, one organic UV filter - octocrylene(OC) was significantly associated with PCOS in women with BMI ≥ 24 (adjusted OR = 1.512, 95% CI: 1.043, 2.191). It's the first time to investigate the association between exposure of organic UV filters and PCOS risk. We conclude that there is positive association between OC and PCOS risk in obese and overweight women. Highlights • We investigated the association between certain PCPs concentrations and PCOS risk. • BP-3, HMS and OC were present in 61.0%, 27.6% and 70.7% of subjects' urine samples. • Urinary OC concentrations were positively correlated to PCOS in women with BMI≥ 24. [ABSTRACT FROM AUTHOR]

Abstract We evaluated whether bisphenol-A (BPA) could be quantified in breast adipose tissue samples provided by 36 breast cancer mastectomy patients and 14 reduction mammoplasty patients. Samples of breast adipose tissue were collected and BPA concentration was quantified using HPLC-ESI-MS/MS. BPA was detectable above the limit of quantitation of 0.38 ng/g in 30.6% of samples. BPA concentrations varied within- and between breasts and were similar between cases and controls (0.39 vs 0.41 ng/g, p = 0.74). Highlights • BPA was detected in breast adipose tissue of breast cancer cases and controls. • Mean BPA concentrations were similar between cases and controls. • BPA concentrations were highly variable within- and between-breasts from a single patient. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) and Di-(2-ethylhexyl) phthalate (DEHP) are two wide spread chemicals classified as endocrine disruptors (ED). The present study aims to estimate the non-dietary (dermal, non-dietary ingestion and inhalation) exposure to BPA and DEHP for a pregnant women cohort. In addition, to assess the prenatal exposure for the fetus, a physiologically based pharmacokinetic (PBPK) model was used. It was adapted for pregnancy in order to assess the internal dosimetry levels of EDs (BPA and DEHP) in the fetus. Estimates of exposure to BPA and DEHP from all pathways along with their relative importance were provided in order to establish which proportion of the total exposure came from diet and which came from non-dietary exposures. In this study, the different oral dosing scenarios (dietary and non-dietary) were considered keeping inhalation as a continuous exposure case. Total non-dietary mean values were 0.002 µg/kg bw /day (0.000; 0.004 µg/kg bw /day for 5th and 95th percentile, respectively) for BPA and 0.597 µg/kg bw /day (0.116 µg/kg bw /day and 1.506 µg/kg bw /day for 5th and 95th percentile, respectively) for DEHP. Indoor environments and especially dust ingestion were the main non-dietary contributors to the total exposure of BPA and DEHP with 60% and 81%. However, as expected, diet showed the higher contribution to total exposure with > 99.9% for BPA and 63% for DEHP. Although diet was considered the primary source of exposure to BPA and phthalates, it must be taken into account that with non-dietary sources the first-pass metabolism is lacking, so these may be of equal or even higher toxicological relevance than dietary sources. The present study is in the framework of “Health and environmental-wide associations based on large population surveys” (HEALS) project (FP7–603946). [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a chemical toxicant that has deleterious effects on human. BPA causes oxidative stress in tissues, including the liver. Diphenyl diselenide (PhSe) 2 improves the antioxidant response via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein (keap 1) pathway in macrophage cells. In the present study, we investigated whether (PhSe) 2 counteracts hepatic oxidative stress induced by BPA in male and female Swiss mice. Three-week-old mice received by the intragastric (i.g.) route BPA (5 mg/kg) from 21st to 60th postnatal day (PND). At PND 61, the mice were treated with (PhSe) 2 (1 mg/kg, i.g.) for seven days. Parameters of hepatic damage and oxidative stress were determined in male and female mice. The results show that BPA increased the activity of aspartate aminotransferase in female mice, and in male mice the activity of alanine aminotranseferase was increased. Male and female mice had an increase in fat mass accumulation. Male mice showed an increase in hepatic oxidative damage of proteins and a decrease in non-enzymatic (ascorbic acid and non-protein thiol) and enzymatic (superoxide dismutase) defenses, which are consistent with oxidative stress status. Male mice were more susceptible than female mice to hepatic oxidative stress induced by BPA. BPA decreased Nrf2/Keap1 protein content in male mice. (PhSe) 2 reduced hepatic oxidative stress induced by BPA in male mice. Our results demonstrate that male mice were more susceptible to hepatic oxidative stress induced by BPA than female mice. (PhSe) 2 regulated Nrf2/Keap-1 signaling pathway and countered hepatic oxidative stress induced by BPA in male mice. [ABSTRACT FROM AUTHOR]

Background Bisphenol A (BPA) is associated with dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity in rodents, but evidence in humans is lacking. Objective To determine whether BPA exposure during pregnancy is associated with dysregulation of the HPA-axis, we examined the association between urinary BPA concentrations and diurnal salivary cortisol in pregnant women. Secondary analyses investigated whether the association between BPA and cortisol was dependent on fetal sex. Methods Diurnal salivary cortisol and urinary BPA were collected during pregnancy from 174 women in a longitudinal cohort study, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Associations between BPA and daytime cortisol and the cortisol awakening response (CAR) were estimated using mixed models after adjusting for covariates. Results Higher concentrations of total BPA uncorrected for urinary creatinine were associated with dysregulation of the daytime cortisol pattern, including reduced cortisol at waking, β=−.055, 95% CI (−.100, −.010) and a flatter daytime pattern, β=.014, 95% CI (.006, .022) and β=−.0007 95% CI (−.001, −.0002) for the linear and quadratic slopes, respectively. Effect sizes in creatinine corrected BPA models were slightly smaller. None of the interactions between fetal sex and BPA were significant (all 95% CI's include zero). Conclusions These findings provide the first human evidence suggesting that BPA exposure is associated with dysregulation of HPA-axis function during pregnancy. [ABSTRACT FROM AUTHOR]

For the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5–12 y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300 mg/L or above 3000 mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named “European reference values”. After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the “European reference values” by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87–2.24) µg/L and 1.88 (1.71–2.07) µg/L for children ( n =653) and mothers ( n =639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers ( r =0.265, p <0.001), which may suggest a possible common environmental/dietary factor that influences the biomarker level in each pair. Exposure of the general European population was well below the current health-based guidance values and no participant had BPA values higher than the health-based guidance values. [ABSTRACT FROM AUTHOR]

We evaluated the within-person variability of urinary BPA levels over two samples collected three years apart in 90 Women's Health Initiative participants. The intraclass correlation coefficient was 0.09 (95% CI 0.01–0.44), indicating high within-participant variability relative to the between-person variation. Concordance of BPA quartile over time was low (31.7%) and was unrelated to demographic, behavioral, or dietary factors. A single, or even several, measurements of BPA may not adequately classify long-term exposure in human studies. [ABSTRACT FROM AUTHOR]

As part of the second Flemish Environment and Health Study (FLEHS II), bisphenol-A (BPA) and different phthalate metabolites were analyzed, for the first time, in the urine of 210 adolescents in Flanders, Belgium. All chemicals had a detection frequency above 90%. For all compounds, except the sum of DEHP, highest levels were detected during spring. Average values for the Flemish adolescents were in an agreement with concentrations found in different international studies, all confirming the ubiquity of BPA and phthalate exposure. There was a significant correlation between BPA and the different phthalate metabolites ( r between 0.26 and 0.39; p <0.01). Shared sources of exposure to BPA and phthalates, such as food packaging, were suggested to be responsible for this positive correlation. Different determinants of exposure were evaluated in relation to the urinary concentrations of these chemicals. For BPA, a significant association was observed with household income class, smoking and exposure to environmental tobacco smoke. For phthalates, the following significant associations were observed: age (MBzP), educational level of the adolescent (MBzP), equivalent household income (MnBP), use of personal care products (MnBP and MBzP), wall paper in house (MnBP and MBzP) and use of local vegetables (MnBP and MBzP). [ABSTRACT FROM AUTHOR]

Abstract: The Children''s Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) study investigated the potential exposures of 257 preschool children, ages , and their primary adult caregivers to more than 50 anthropogenic chemicals. Field sampling took place in selected counties in North Carolina (NC) and Ohio (OH) in 2000–2001. Over a 48-h period in each child''s daycare center and/or home, food, beverages, indoor air, outdoor air, house dust, soil, participants’ hand surfaces and urine were sampled. Additional samples—transferable residues, food preparation surface wipes, and hard floor surface wipes—were collected in the approximately 13% of the homes that had pesticide applications within the 7 days prior to field sampling. Three phenols were among the measured chemicals: pentachlorophenol (PCP), bisphenol-A [2,2-bis(4-hydroxyphenyl)propane], and nonylphenol (4-n-nonylphenol). Nonylphenol (NP) was detected in less than 11% of the samples in any medium. Among samples that were collected at all participants’ homes and daycare centers, PCP was detected in >50% of indoor air, outdoor air, house dust, and urine samples; bisphenol-A (BPA) was detected in >50% of indoor air, hand wipe, solid food, and liquid food samples. The concentrations of the phenols in the sampled media were measured, and the children''s potential exposures and potential absorbed doses resulting from intake through the inhalation, dietary ingestion, and indirect ingestion routes of exposure were estimated. The children''s potential exposures to PCP were predominantly through inhalation: 78% in NC and 90% in OH. In contrast, their potential exposures to BPA were predominantly through dietary ingestion: 99%, for children in both states. The children''s estimated exposures to PCP, calculated from the amounts excreted in their urine, exceeded their estimated maximum potential intake, calculated from the multimedia PCP concentrations, by a factor greater than 10. This inconsistency for PCP highlights the need for further research on the environmental pathways and routes of PCP exposure, investigation of possible exposures to other compounds that could be metabolized to PCP, and on the human absorption, metabolism, and excretion of this phenol over time periods longer than 48h. [Copyright &y& Elsevier]

Abstract: Bisphenol-A (BPA) shows proliferative actions in uterus and mammary glands and may influence the development of male and female reproductive tracts in utero or during early postnatal life. Because of its ability to function as an estrogen receptor (ER) agonist, BPA has the potential to disrupt normal endocrine signaling through regulation of ER target genes. Some genes are regulated by both estradiol (E2) and BPA, but those exclusive to either agent have not been described. Using a yeast strain incorporating a vitellogenin A2 ERE-LacZ reporter gene into the genome, we found that BPA induced expression of the reporter in colonies transformed with the ERα expression plasmid, illustrating BPA-mediated regulation within a chromatin context. Additionally, a reporter gene transiently transfected into the endometrial cancer (Ishikawa) cell line also showed BPA activity, although at 100-fold less potency than E2. To compare global gene expression in response to BPA and E2, we used a variant of the MCF-7 breast cancer cell line stably expressing HA-tagged ERα. Cultures were treated for 3h with an ethanol vehicle, E2 (10−8 M), or BPA (10−6 M), followed by isolation of RNA and microarray analysis with the human U95A probe array (Affymetrix, Santa Clara, CA, USA). More than 300 genes were changed 2-fold or more by either or both agents, with roughly half being up-regulated and half down-regulated. A number of growth- and development-related genes, such as HOXC1 and C6, Wnt5A, Frizzled, TGFβ-2, and STAT inhibitor 2, were found to be affected exclusively by BPA. We used quantitative real-time PCR to verify regulation of the HOXC6 gene, which showed decreased expression of approximately 2.5-fold by BPA. These results reveal novel effects by BPA and E2, raising interesting possibilities regarding the role of endocrine disruptors in sexual development. [Copyright &y& Elsevier]