Exposure to bisphenol A in European women from 2007 to 2014 using human biomonitoring data - The European Joint Programme HBM4EU.

BACKGROUND: Bisphenol A (BPA; or 4,4'-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. OBJECTIVE: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18-73 years (n = 4,226) and its determinants. METHODS: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. RESULTS: Total BPA was quantified in 85-100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA's BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. CONCLUSION: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.

Association between Bisphenol A and Prostate-Specific Antigen (PSA) among U.S. Older Males: National Health and Nutrition Examination Survey (NHANES), 2003-2012.

BACKGROUND: There is growing evidence indicating that environmental endocrine disruptors may influence the development of prostate cancer. Despite this, the connection between BPA and PSA levels is still not fully understood and appears intricate. In this study, we aimed to assess the link between BPA exposure and PSA levels using data from the NHANES database. METHODS: We conducted a weighted linear regression, logistic regression analysis, natural cubic spline (NCS), subgroup analysis, and interaction analysis on 2768 participants. Urinary BPA was considered the independent variable, while PSA was the dependent variable. RESULTS: In the study, the average age of the participants selected was 62.70 years (±12.93). Age was negatively correlated with BPA, while PSA and BMI were positively correlated with BPA concentration (all of the p-value < 0.05). In the fully adjusted model, the weighted linear and logistic regression results showed that BPA was positively correlated with PSA and prostate cancer. NCS analysis results show that BPA and PSA have a non-linear relationship. Sensitivity and subgroup analyses showed similar results. In addition, there were interactions between BPA and age, PIR, education, HbA1c, high-density lipoprotein, smoking status, and Diabetes. CONCLUSIONS: There was a positive correlation between urinary BPA and PSA in older American males, especially when the BPA concentration was higher than 4.46 ng/mL. In future practical applications of prostate cancer screening, it is crucial to focus on individuals aged 75 years and older, as well as those with a PIR between 0 and 1, non-Hispanic black, and other risk groups to provide reference values for the primary and secondary prevention of prostate cancer.

Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts.

BACKGROUND: There is limited epidemiological evidence on the association of prenatal exposure to phthalates and synthetic phenols with altered pubertal timing. OBJECTIVE: To examine the association of prenatal exposure to phthalates, bisphenol A (BPA), parabens, benzophenone 3 (BP-3), and triclosan (TCS) with pubertal development in girls and boys from three European cohorts. METHODS: Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP), BPA, methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), and butyl-paraben (BuPB), BP-3, and TCS were quantified in one or two (1st and 3rd trimester) urine samples collected during pregnancy (1999-2008) from mothers in three birth cohorts: INMA (Spain), EDEN (France), and MoBa (Norway). Pubertal development of their children was assessed at a single visit at age 7-12 years (579 girls, 644 boys) using the parent-reported Pubertal Development Scale (PDS). Mixed-effect Poisson and g-computation and Bayesian Kernel Machine Regression (BKMR) were employed to examine associations of individual and combined prenatal chemical exposure, respectively, with the probability of overall pubertal onset, adrenarche, and gonadarche (stage 2+) in girls and boys. Effect modification by child body mass index (BMI) was also assessed. RESULTS: Maternal concentrations of the molar sum of DEHP and of DiNP metabolites were associated with a slightly higher probability of having started puberty in boys (relative risk, RR [95% CI] = 1.13 [0.98-1.30] and 1.20 [1.06-1.34], respectively, for a two-fold increase in concentrations), with a stronger association for DiNP in boys with overweight or obesity. In contrast, BPA, BuPB, EtPB, and PrPB were associated with a lower probability of pubertal onset, adrenarche, and/or gonadarche in all boys (e.g. overall puberty, BPA: RR [95% CI] = 0.93 [0.85-1.01] and BuPB: 0.95 [0.90-1.00], respectively), and the association with BPA was stronger in boys with underweight/normal weight. In girls, MEHP and BPA were associated with delayed gonadarche in those with underweight/normal weight (RR [95% CI] = 0.86 [0.77-0.95] and 0.90 [0.84-0.97], respectively). Most of these associations were trimester specific. However, the chemical mixture was not associated with any pubertal outcome in boys or girls. CONCLUSIONS: Prenatal exposure to certain phthalates and synthetic phenols such as BPA may impact the pubertal development of boys, and weight status may modify this effect. BPA may also alter the pubertal development of girls.

Environmental and occupational exposure to bisphenol compounds in Finland.

The aim of the study was to assess non-occupational and occupational exposure to bisphenol compounds in Finland. The participants were 151 non-occupationally exposed volunteers and 15 potentially exposed employees of a sewage-pipe relining company and a floor-coating company. The following chemicals were measured in the urine samples: bisphenol A (BPA), bisphenol F (BPF), bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), and the metabolites of the latter two [bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE·H2O), bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE·2 H2O), bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) ether (BADGE·HCl·H2O), bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE·HCl), and bisphenol A bis(3-chloro-2-hydroxypropyl) ether (BADGE·2HCl) and bisphenol F bis(2,3-dihydroxypropyl) ether (BFDGE·2 H2O), and bisphenol F bis(3-chloro-2-hydroxypropyl) ether (BFDGE·2HCl)]. BADGE and BFDGE were also measured in breathing zone air samples and hand-wipe samples of the sewage-pipe relining and floor-coating workers. Non-occupational exposure to BPA has decreased in Finland. The BPF level of the non-occupationally exposed was higher than the respective levels reported in the recent literature. BPA and BPF concentrations in the workers' urine samples were in the same range as those in the corresponding concentrations of the non-occupationally exposed population. Higher concentrations of BADGE and BFDGE metabolites were found in some of the workers' urine samples. Elevated urine concentrations were also observed in the samples collected the next morning. Some of the urinary BADGE and BFDGE metabolite results correlated with the hand-wipe results. The results show that occupational exposure to BADGE and BFDGE may occur in sewage-pipe relining and floor-coating work. They also indicate that dermal contamination plays a role in total exposure. Although the measured urinary levels indicate that the absorption of these bisphenol compounds are unlikely to pose a systemic health risk, the risk of dermal sensitization remains.

Exploring the relationships between exposure levels of bisphenols and phthalates and prostate cancer occurrence.

We established an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously analyzing the metabolites of bisphenols and phthalates in urine to identify the associations between these exposure levels and prostate cancer (PCa) based on a case-control study. After purifying urine samples with SPE, 18 metabolites were separated on a C18 column, and MS detection was performed. The UPLC-MS/MS method has been proven effective at evaluating bisphenol and phthalate exposure (0.020-0.20 µg/L of the limits of detection, 71.8 %∼119.4 % of recoveries, 0.4 %∼8.2 % of precision). Logistic regression explored the association between exposure level and PCa in 187 PCa cases and 151 controls. The detection rates of bisphenol A (BPA) and most phthalate metabolites were 100 % ranging from 0.06-46.74 and 0.12-899.92 µg/g creatinine, respectively, while the detection rates of other bisphenols and mono-benzyl phthalate (MBzP) are low, ranging from 0 % to 21.85 %. Correlation analysis of the metabolite levels indicated that the exposure sources of BPA, di-ethyl phthalate (DEP), and di(2-ethylhexyl) phthalate (DEHP) were different, and that the exposure sources of di-n-butyl phthalate (DnBP) and di-isobutyl phthalate (DiBP) may differ between two groups. Logistic regression analysis revealed that BPA (OR<0.45 vs ≥1.43 =10.02) and DEHP exposure (OR<21.75 vs ≥45.42 =48.26) increased the risk of PCa.

Endocrine disrupting chemicals in children's and their parents' urine: Is the exposure related to the Chinese and Western lifestyle?

Children are known to be more vulnerable to exposure to endocrine-disrupting chemicals (EDCs) compared to adults, but evaluating the exposure pathways can be challenging. This research employed target and non-target analysis (NTA) to examine the exposure characteristics of EDCs in spot urine samples collected from 46 children's (aged 3-12 years) and their parents in Hong Kong (Chinese/Western lifestyle) and Guangzhou (mainly Chinese lifestyle). The results revealed that the geometric mean concentrations of phthalate esters metabolites (mPAEs) and bisphenols (BPs) in children's urine were 127.3 µg/gcrea and 2.5 µg/gcrea in Guangzhou, and 93.7 µg/gcrea and 2.9 µg/gcrea in Hong Kong, respectively, which were consistent with global levels. NTA identified a total of 1069 compounds, including 106 EDCs, commonly detected in food, cosmetics, and drugs. Notable regional differences were observed between Guangzhou and Hong Kong with potential sources of EDCs including dietary and cosmetic additives, toys, flooring and dust, as well as differences in lifestyles, diet, and living environment. However, age was found to significantly impact EDC exposure. The quantified EDCs (mPAEs and BPs) posed possible health risks to 60% of the children. Moreover, the presence of caffeine in children's urine, which exhibited higher detection rates in children from Hong Kong (95.6%) and Guangzhou (44.4%), warrants further attention. The sources of EDCs exposure in these regions need to be fully confirmed.

Bisphenol A and polycystic ovary syndrome in human: A systematic review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain and one of the hypotheses is that environmental factors, such as the bisphenol A (BPA) endocrine disruptor, may be involved. OBJECTIVE: To investigate the association between exposure to BPA and PCOS. SEARCH STRATEGY: Research was conducted focusing on studies published in English, Portuguese, and Spanish from January 2001 to March 2023 and available in Embase, Medline/PubMed, Rima, Lilacs, Scielo, Google academic, and SCI databases. SELECTION CRITERIA: Studies in humans that evaluated the association between exposure to BPA and a diagnosis of PCOS. DATA COLLECTION AND ANALYSIS: Following PRISMA guidelines, study characteristics and relevant data were extracted. MAIN RESULTS: Selection of 15 case-control and 7 cross-sectional studies with a total of 1682 PCOS patients. The studies were carried out in China, Poland, Turkey, Japan, Greece, Italy, the USA, Iran, Iraq, Egypt, India, Czechia, and Slovakia. A positive relationship between exposure to BPA and PCOS was described in19 studies (1391 [82.70%] of the PCOS patients). The fluids used in the studies were serum, urine, plasma, and follicular fluid. BPA was measured by ELISA and by chromatography (HPLC, HPLC-MS/MS, GC-MS, and GC-MS/MS). Diagnosis of PCOS used Rotterdam criteria in 15, NIH 1999 in 3, AE&PCOS Society in 2, similar to the Rotterdam criteria in 1, and criteria not informed in 1. Androgens were measured in 16 studies; in 12, hyperandrogenism was positively associated with BPA. BPA level was related to body mass index (BMI) in studies. In 15 studies independently of BMI, women with PCOS had higher BPA levels. Carbohydrate metabolism disorders were evaluated in 12 studies and in 6 a positive correlation was found with BPA levels. Lipid profile was evaluated in seven studies and in only one the correlation between lipid profile and BPA levels was present. CONCLUSIONS: Exposure to BPA is positively associated with PCOS, mainly with the hyperandrogenism.

Mitigating the impact of bisphenol A exposure on mortality: Is diet the key? A cohort study based on NHANES.

Bisphenol A (BPA) is a widespread environmental pollutant linked to detrimental effects on human health and reduced life expectancy following chronic exposure. This prospective cohort study aimed to examine the association between BPA exposure and mortality in American adults and to explore the potential mitigating effects of dietary quality on BPA-related mortality. This study utilized data from 8761 American adults in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). Urinary BPA levels were employed to assess BPA exposure, and dietary quality was evaluated using the Healthy Eating Index-2015 (HEI-2015). All-cause, cardiovascular disease (CVD), and cancer mortality statuses were determined until December 31, 2019, resulting in a cumulative follow-up of 80,564 person-years. The results showed that the highest tertile of urinary BPA levels corresponded to a 36% increase in all-cause mortality and a 62% increase in CVD mortality compared to the lowest tertile. In contrast, the highest tertile of HEI-2015 scores was associated with a 29% reduction in all-cause mortality relative to the lowest tertile. Although no significant interaction was found between HEI-2015 scores and urinary BPA levels concerning mortality, the association between HEI-2015 scores and both all-cause and CVD mortality was statistically significant at low urinary BPA levels. Continuous monitoring of BPA exposure is crucial for evaluating its long-term adverse health effects. Improving dietary quality can lower all-cause mortality and decrease the risk of all-cause and CVD mortality at low BPA exposure levels. However, due to the limited protective effect of dietary quality against BPA exposure, minimizing BPA exposure remains a vital goal.

A descriptive analysis of first trimester urinary concentrations of 14 bisphenol analogues in the MIREC Canadian pregnancy cohort.

BACKGROUND: Concern over the health effects of BPA, particularly for the developing fetus, has led to an increasing use of bisphenol analogues in industrial and consumer products, which may be as hormonally active as BPA. Biomonitoring data for many bisphenol analogues, especially in pregnant populations, are limited. METHODS: We measured concentrations of 14 bisphenol analogues in 1st trimester urine samples (n = 1851) from the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort (2008-2011). We examined patterns of exposure according to sociodemographic and sampling characteristics as well as occupation and frequency of consumption of canned fish within the previous 3 months. RESULTS: BPA was detected in 89% of participants with a specific gravity standardized geometric mean concentration of 0.990 µg/L. Biphenol 4,4' (BP 4,4'), 4,4'-dihydroxydiphenyl ether (DHDPE), and bisphenol E (BPE) were detected in >97% of participants. Bisphenol F (BPF) and bisphenol S (BPS) were detected in >60% of participants. Specific gravity standardized geometric mean concentrations of these 5 compounds ranged from 0.024 to 0.564 µg/L. Nine bisphenol analogues were detected in <9% of participants. Concentrations of BP 4,4', DHDPE, and BPE were higher in younger women and those with higher pre-pregnancy BMI, lower household income, lower education, and among smokers. We found a similar pattern of differences in BPF for age, education, and smoking status while BPS similarly differed across categories of pre-pregnancy BMI. Participants who were unemployed or working in the service industry had higher molar sum of 7 bisphenol analogues than those working in healthcare, education, or an office setting. Canned fish consumption was not related to bisphenol analogue concentrations. CONCLUSION: BP 4,4', DHDPE, BPE, BPF, and BPS were highly detected in 1st trimester urine samples in this large pan-Canadian pregnancy cohort. This suggests widespread exposure to these analogues around 2008-2011 and warrants further investigation into associations with health outcomes.

A large-scale nationwide study of urinary phenols in the Chinese population.

Bisphenol A (BPA), tetrabromobisphenol A (TBBPA), and their substitutes are commonly used in everyday products. However, large-scale internal exposure levels of them in China, the factors influencing on them, and the associated health risks were not systematically investigated still. In the present study, there were 1157 morning urine samples collected from residents of 26 provincial capitals in China for the measurement of BPA and seven bisphenol analogues, as well as TBBPA and its substitutes, i.e., tetrachlorobisphenol A and 4,4'-sulphonylbis(2,6-dibromophenol). The concentrations of Σ8bisphenols and Σ3TBBPAs ranged from

Urinary phthalates, phenols, and parabens in relation to sleep health markers among a cohort of Mexican adolescents.

INTRODUCTION: Emerging research has shed light on the potential impact of environmental toxicants on sleep health, however, it remains unclear if these associations exist during adolescence and whether associations differ by sex. This study aimed to examine associations between phthalates, parabens, and phenols on adolescent sleep health using cross-sectional data from 470 participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study. MATERIAL AND METHODS: In 2015, spot urine samples were analyzed for exposure biomarkers of 14 phthalate metabolites, seven phenol, and four paraben analytes. Over seven consecutive days, sleep duration, midpoint, and fragmentation were assessed with wrist-actigraphy. We examined associations between summary phthalates, individual phthalate metabolites, and phenol and paraben analytes with mean weekday sleep duration, midpoint, and fragmentation using linear regression models adjusted for specific-gravity and sex, age, pubertal status, smoking and alcohol behavior, physical activity, and screen time. RESULTS: Mean (SD) age was 13.8 (2.1) years; 53.5 % were female. Σ Plastic - summary measure for toxicants from plastic sources - and Σ DEHP and its metabolites, were associated with longer sleep duration in the unstratified sample. To illustrate, every 1-unit log increase in Σ DEHP was associated with 7.7 min (95 % CI: 0.32, 15.1; p < 0.05) longer duration. Summary measures of toxicants from plastic sources, personal care products, anti-androgenic toxicants, and multiple individual phthalates, phenols, and parabens were associated with later midpoint. The midpoint associations were largely female-specific. There were no associations with sleep fragmentation. CONCLUSIONS: Higher EDC exposure may be related to longer sleep duration and later sleep timing during adolescence, and associations may vary by toxicant and according to sex.

Glucuronidated Metabolites of Bisphenols A and S Alter the Properties of Normal Urothelial and Bladder Cancer Cells.

Bisphenol A (BPA) and bisphenol S (BPS) are synthetic chemicals used to produce plastics which can be released in food and water. Once ingested, BPA and BPS are metabolized by the liver, mainly as glucuronidated metabolites, and are excreted through urine. Since urine can be stored for many hours, the bladder is chronically exposed to BP metabolites, and studies have shown that these metabolites can remain active in the organism. Therefore, the effect of physiological concentrations of glucuronidated BPs was evaluated on the bioenergetics (glycolysis and mitochondrial respiration), migration and proliferation of normal urothelial cells, and non-invasive and invasive bladder cancer cells. The results demonstrated that an exposure of 72 h to glucuronidated BPA or BPS decreased the bioenergetics and activity of normal urothelial cells, while increasing these parameters for bladder cancer cells. These findings suggest that BP metabolites are not as inactive as initially believed, and their ubiquitous presence in the urine could promote bladder cancer progression.

Association of environmental phenols with endometriosis and uterine leiomyoma: An analysis of NHANES, 2003-2006.

Exposure to phenols is widespread since they are found in many everyday products. Given that phenols are considered endocrine disrupting chemicals with the potential to interfere with hormonal activities, they could have adverse effects on female reproductive health. We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), 2003-2006 to examine the association between phenols and endometriosis and uterine leiomyoma (fibroids). Levels of bisphenol A (BPA), benzophenone-3, and triclosan were measured using urine samples, and information on endometriosis and fibroids diagnoses as well as other relevant characteristics were ascertained using self-reported questionnaires. Multivariate logistic regression with odds ratios (ORs) and 95 % confidence intervals (CIs) were used to quantify the association between each phenol and female gynecologic condition. Our study included 700 women, of which 53 women had endometriosis and 107 women had fibroids. We found exposure to BPA to be statistically significantly positively associated with endometriosis (p = 0.05); women in the highest exposure quartile had over the three times the odds of having endometriosis relative to women in the lowest quartile (OR=3.58, 95 % CI 1.00-12.89). None of the phenols considered were significantly associated with fibroids. Overall, exposure to BPA increased the odds of having endometriosis, and there appeared to be a dose-response relationship. This suggests that BPA may play a role in the pathogenesis of endometriosis although the cross-sectional nature of NHANES data is a methodological limitation. Additional research on the impact of endocrine disrupting chemicals, like phenols, on female reproductive health should be conducted.

Gestational exposure to bisphenol analogues and kisspeptin levels in pregnant women and their children: A pregnancy-birth cohort study.

Gestational exposure to bisphenol analogues (BPs)，especially bisphenol A (BPA), has been associated with adverse pregnancy-related outcomes and altered reproductive development of offspring, but the underlying mechanisms are not well documented. Kisspeptin, a key regulator of reproductive health, could be the potential target for endocrine disrupting compounds like BPs. Among 528 mother-child pairs, we investigated the associations of gestational BPs exposure with kisspeptin levels in two critical life stages, pregnancy and pre-puberty. Maternal BPs and kisspeptin concentrations were measured in urine samples collected in the third trimester. Children's urine samples were collected at 6-year visit and analyzed for kisspeptin levels. Associations were observed between BPA and its alternatives and lower kisspeptin in pregnant women but higher kisspeptin in their children. In contrast, TCBPA was suggestively associated with higher kisspeptin in pregnant women but lower kisspeptin in children. Our study provides the first epidemiologic evidence that gestational exposure to selected BPs may be associated with altered kisspeptin system in both pregnant women and their children, sheds some light on the potential mechanisms underlying the various reproductive health outcomes following gestational BPA exposure, and suggests potential reproductive toxicities of other BPs in humans.

Urinary Concentrations of Triclosan, Bisphenol A, and Brominated Flame Retardants and the Association of Triclosan with Demographic Characteristics and Body Fatness among Women with Newly Diagnosed Breast Cancer.

Background: Triclosan, bisphenol A (BPA), and brominated flame retardants are environmental estrogenic endocrine-disrupting compounds that may influence the prognosis of breast cancer. We examined the urinary concentrations of these compounds and their associations with demographic characteristics and body fatness in a population of women with newly diagnosed breast cancer. Methods: Overnight urine collection and anthropometric measures were obtained from 302 participants. Triclosan, BPA, tetrabromobisphenol A (TBBPA), and tetrabromobenzoic acid (TBBA) concentrations were determined using ultra-performance liquid chromatography−tandem mass spectrometry. Regression analyses were conducted to examine associations of urinary compound concentration with age, menopause, race, ethnicity, educational level, estrogen receptor status, body size, and body composition. Results: Triclosan, BPA, and TBBA were detected in urine samples from 98.3%, 6.0%, and 0.3% of patients, respectively; TBBPA was undetectable. Among patients with quantifiable values, the geometric mean concentrations were 20.74 µg/L (27.04 µg/g creatinine) for triclosan and 0.82 µg/L (1.08 µg/g creatinine) for BPA. Body mass index ≥ 30 vs. <25 kg/m2 was associated with lower creatinine-corrected urinary concentrations of triclosan (−40.00, 95% confidence interval [CI] = −77.19 to −2.81; p = 0.0351). The observed association was predominantly in postmenopausal women (−66.57; 95% CI: −109.18% to −23.96%). Consistent results were found for associations between triclosan levels and fat mass variables. Conclusion: In this study population, women with newly diagnosed breast cancer had triclosan exposure. Assessments of the implications of urinary concentrations of triclosan for women should consider body fatness and menopausal status.

Bisphenol-A in biological samples of breast cancer mastectomy and mammoplasty patients and correlation with levels measured in urine and tissue.

Endocrine disrupting chemicals (EDCs) are organic compounds that have estrogenic activity and can interfere with the endocrine system. Bisphenol-A (BPA) is one of these compounds which possess a potential risk for breast cancer. The aim of this research was to evaluate BPA concentration in both the urine and breast adipose tissue samples of breast cancer mastectomy and mammoplasty patients and study correlations of BPA levels in breast adipose tissue with urine samples in the both groups. Urine and breast adipose tissue samples from 41 breast cancer mastectomy and 11 mammoplasty patients were taken. BPA concentrations were detected using an ELISA assay. Urinary BPA concentrations were significantly higher in cancerous patients (2.12 ± 1.48 ng/ml; P < 0.01) compared to non-cancerous (0.91 ± 0.42 ng/ml). Likewise, tissue BPA concentrations in cancerous patients (4.20 ± 2.40 ng/g tissue; P < 0.01) were significantly higher than non- cancerous (1.80 ± 1.05 ng/g tissue). Urinary BPA concentrations were positively correlated with breast adipose tissue BPA in the case group (P < 0.001, R = 0.896). We showed that BPA was present in urine and breast adipose tissue samples of the studied populations. With regard to higher BPA mean concentration in cancerous patients than non-cancerous individuals in this study, BPA might increase the risk of breast cancer incidence.

Human-Biomonitoring derived exposure and Daily Intakes of Bisphenol A and their associations with neurodevelopmental outcomes among children of the Polish Mother and Child Cohort Study.

BACKGROUND: Bisphenol A (BPA) is an industrial chemical mostly used in the manufacture of plastics, resins and thermal paper. Several studies have reported adverse health effects with BPA exposures, namely metabolic disorders and altered neurodevelopment in children, among others. The aim of this study was to explore BPA exposure, its socio-demographic and life-style related determinants, and its association with neurodevelopmental outcomes in early school age children from Poland. METHODS: A total of 250 urine samples of 7 year-old children from the Polish Mother and Child Cohort Study (REPRO_PL) were analyzed for BPA concentrations using high performance liquid chromatography with online sample clean-up coupled to tandem mass spectrometry (online-SPE-LC-MS/MS). Socio-demographic and lifestyle-related data was collected by questionnaires or additional biomarker measurements. Emotional and behavioral symptoms in children were assessed using mother-reported Strengths and Difficulties Questionnaire (SDQ). Cognitive and psychomotor development was evaluated by Polish adaptation of the Intelligence and Development Scales (IDS) performed by trained psychologists. RESULTS: Urinary BPA concentrations and back-calculated daily intakes (medians of 1.8 µg/l and 46.3 ng/kg bw/day, respectively) were similar to other European studies. Urinary cotinine levels and body mass index, together with maternal educational level and socio-economic status, were the main determinants of BPA levels in Polish children. After adjusting for confounding factors, BPA has been found to be positively associated with emotional symptoms (ß: 0.14, 95% CI: 0.022; 0.27). Cognitive and psychomotor development were not found to be related to BPA levels. CONCLUSIONS: This study represents the first report of BPA levels and their determinants in school age children in Poland. The exposure level was found to be related to child emotional condition, which can have long-term consequences including social functioning and scholastic achievements. Further monitoring of this population in terms of overall chemical exposure is required.

Urinary bisphenol A in women with polycystic ovary syndrome - a possible suppressive effect on steroidogenesis?

OBJECTIVES: There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. METHODS: Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. RESULTS: PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. CONCLUSIONS: PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.

Risk of breast cancer and prediagnostic urinary excretion of bisphenol A, triclosan and parabens: The Multiethnic Cohort Study.

Exposure to bisphenol A (BPA), triclosan and parabens is widespread but their impact on breast cancer risk remains unclear. This nested case-control study investigated endocrine-disrupting chemicals (EDCs) and breast cancer risk within the Multiethnic Cohort (MEC). We measured prediagnostic urinary BPA, triclosan and parabens in 1032 postmenopausal women with breast cancer (48 African American, 77 Latino, 155 Native Hawaiian, 478 Japanese American and 274 White) and 1030 individually matched controls, using a sensitive and validated liquid chromatography mass spectrometry assay. Conditional logistic regression was used to examine risk with these EDCs with adjustment for creatinine and potential confounders. In all women, breast cancer risk was not associated with BPA (Ptrend  = 0.53) and was inversely associated with triclosan (ORT3 vs T1  = 0.83, 95% CI: 0.66-1.04, Ptrend  = 0.045) and total parabens (ORT3 vs T1  = 0.77, 95% CI: 0.62-0.97, Ptrend  = 0.03). While risk of hormone receptor positive (HR+) cancer was 20% to 23% lower among women in the upper two tertiles of paraben exposure (Ptrend  = 0.02), risk of HR negative (HR-) was reduced 27% but only among those in the upper tertile of exposure. Although risk associations did not differ significantly by ethnicity or by body mass index (BMI), the inverse association with triclosan was observed mainly among overweight/obese women (ORT3 vs T1  = 0.76, 95% CI: 0.56-1.02, Ptrend  = 0.02). In summary, breast cancer risk in a multiethnic population was unrelated to BPA and was weakly inversely associated with triclosan and paraben exposures. Studies with multiple urine samples collected before breast cancer diagnosis are needed to further investigate these EDCs and breast cancer risk.

Exposure of bisphenol A in breast cancer patients-quantitatively assessed by sensitivity-enhanced high-performance liquid chromatography coupled with fluorescence detection: A case-control study.

A simple, reproducible and sensitive liquid chromatography (HPLC) method has been developed and validated for estimation of bisphenol A (BPA) in human urine. A simple liquid-liquid extraction technique was used in BPA sample preparation. The analyte was chromatographed on a Shimadzu Prominence HPLC system using isocratic mobile phase conditions at a flow rate of 0.500 ml/min and a Hypersil Gold C18 column maintained at 40°C. Quantification was performed on a fluorescence detector set at excitation 275 nm, emission 313 nm and bisphenol B was used as internal standard. The total run time was 8 min. The method was found to have acceptable sensitivity, selectivity, accuracy (98.82-103.64%), precision (1.17-5.36) and stability in the validation experiment carried out as per the USFDA guidelines. The method sensitivity was as low as 0.50 ng/ml. The applicability of the validated analytical method was established in human patient urine samples. The mean human urine BPA concentrations were 1.18 ± 2.11 ng/ml in the control group and 5.76 ± 6.00 ng/ml in the patient group (P < 0.001). Therefore, this method could be considered as an alternative for routine bio-monitoring of BPA which is less expensive and feasible in resource-poor settings.