Serum Bisphenol A Concentrations Research Articles

The evaluation of serum bisphenol A in patients with preeclampsia.

High bisphenol A (BPA) concentration may compromise normal placental development. The aim of this study was to determine maternal serum BPA concentrations in pregnant women with complicated preeclampsia (PE) and normal pregnant women, to compare BPA concentrations, and to examine pregnancy outcomes. This prospective case-control study was conducted between March 2021 and October 2021. Serum BPA levels of preeclamptic pregnancy and normal pregnancy were statistically evaluated. In addition, the PE group was divided into three subgroups according to the course of pregnancy. Group 1: patients with non-severe PE who delivered at 37 weeks or later, Group 2: patients with severe PE who delivered at less than 34 weeks, Group 3: patients with severe PE who delivered between 34 and 37 weeks. The association between BPA levels and pregnancy outcome was investigated. Forty-six cases in the PE group were compared with 46 cases of normal pregnancies. The median BPA level was 19.46 ng/mL in the PE group and 16.36 ng/mL in the control group. The median BPA levels in the PE group were significantly higher than those in the control group (p=0.007). Serum BPA levels were significantly lower in women who delivered at 37 weeks or later than in women who delivered at less than 34 weeks due to severe PE (p ≤ 0.018). Our study highlights the association between elevated maternal serum levels of BPA and PE. Moreover, knowledge of BPA levels in women with PE may provide information about the prognosis of pregnancy.

Physiologically based modelling of dermal absorption and kinetics of consumer-relevant chemicals: A case study with exposure to bisphenol A from thermal paper

Bisphenol A (BPA) is one of the best studied industrial chemicals in terms of exposure, toxicity, and toxicokinetics. This renders it an ideal candidate to exploit the recent advancements in physiologically based pharmacokinetic (PBPK) modelling to support risk assessment of BPA specifically, and of other consumer-relevant hazardous chemicals in general. Using the exposure from thermal paper as a case scenario, this study employed the multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA) model available in the Simcyp® Simulator to simulate the dermal toxicokinetics of BPA at local and systemic levels. Sensitivity analysis helped to identify physicochemical and physiological factors influencing the systemic exposure to BPA. The iterative modelling process was as follows: (i) development of compound files for BPA and its conjugates, (ii) setting-up of a PBPK model for intravenous administration, (iii) extension for oral administration, and (iv) extension for exposure via skin (i.e., hand) contact. A toxicokinetic study involving hand contact to BPA-containing paper was used for model refinement. Cumulative urinary excretion of total BPA had to be employed for dose reconstruction. PBPK model performance was verified using the observed serum BPA concentrations. The predicted distribution across the skin compartments revealed a depot of BPA in the stratum corneum (SC). These findings shed light on the role of the SC to act as temporary reservoir for lipophilic chemicals prior to systemic absorption, which inter alia is relevant for the interpretation of human biomonitoring data and for establishing the relationship between external and internal measures of exposure.

Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility

Serum and urinary bisphenol A (BPA) concentrations have been associated negatively with the number of retrieved oocytes after in vitro fertilization (IVF). The impact of BPA upon women with polycystic ovary syndrome (PCOS) and women with tubal factor infertility (TFI), following IVF, was investigated. To this purpose, associations among serum and urinary and follicular fluid (FF) BPA concentrations and the number of retrieved and fertilized oocytes and comparisons between pregnancy rates were evaluated. This was a cross-sectional study conducted at a university-affiliated assisted conception unit between January and November 2019, including 93 women of reproductive age (PCOS: 45; TFI: 48) following IVF. Unconjugated FF and serum BPA concentrations and total urinary BPA concentration were measured using a novel gas chromatography-mass spectrometry method. The number of retrieved and fertilized oocytes and pregnancy rate were documented and evaluated. The number of oocytes retrieved from PCOS women was greater than that of 21 TFI women, independently of BMI. Lower FF BPA concentrations were found in all PCOS women and in overweight/obese PCOS compared to TFI women (0.50, 0.38, and 1.13ng/mL, respectively). In TFI women, FF BPA concentrations correlated negatively with the number of retrieved oocytes. Serum and FF and urinary BPA concentrations did not significantly affect the number of fertilized oocytes and pregnancy rate in both groups. FF BPA concentrations were lower in all PCOS women and in overweight/obese PCOS than in TFI women. In TFI women, FF BPA concentrations correlated negatively with retrieved oocytes. Confirmation of these findings might lead to moderation of use of BPA-containing products by women undergoing IVF.

Association of endocrine disrupting chemicals levels in serum, environmental risk factors, and hepatic function among 5- to 14-year-old children

Endocrine-disrupting chemicals (EDCs) might increase the risk of childhood diseases by disrupting hormone-mediated processes that are critical for growth and development during childhood, however, the association among the exposure level of EDCs such as Nonylphenol (NP), Bisphenol A (BPA), Dimethyl phthalate (DMP) in children and environmental risk factors, as well as hepatic function has not been elaborated. This study aimed to discuss this interesting relationship among NP, BPA, DMP concentrations in serum, environmental risk factors, hepatic function of 5- to 14-year-old children in industrial zone, residential zone and suburb in northern district of Guizhou Province, China. In Zunyi city, 1006 children participated in cross-sectional health assessments from July to August 2018, and their parents completed identical questionnaires on the environmental risk factors of EDCs exposure to mothers and children. Serum NP, BPA and DMP concentrations were measured by high performance liquid chromatography (HPLC). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were detected with automatic biochemical analyzer. The median concentrations of serum NP, BPA, and DMP in the participants were 45.85 ng/mL, 26.31 ng/mL and 31.62 ng/mL, respectively, which were higher than the environmental concentration limits of the U.S. National Environmental Protection Agency (EPA). Hair gels used during pregnancy, types of domestic drinking water, nail polish and cosmetics used by children were significantly positive correlated with serum NP concentration (P < 0.05). Gender, feeding pattern, plastic water cup used during pregnancy, hair spray and perfume use for children, duration of children birth, materials for baby bottle or cup and ways to plastic products were significantly positively correlated with serum BPA concentration (P < 0.05). Gender, perms used during pregnancy, hair spray and perfume use for children, using plastic lunch box during pregnancy, duration of children birth, exposure to pesticides, parents’ occupations were significantly positively correlated with serum DMP concentrations (P < 0.05). Serum NP (β = 0.296, P = 0.036) and DMP (β = 0.316, P = 0.026) concentrations and TBIL level were significantly positively correlated. Serum NP concentration and the levels of IBIL (β = 0.382, P = 0.006) are significantly positively correlated. Cosmetics used during pregnancy significantly increased AST level (β = 2.641, P = 0.021). There was a positive correlation between the frequency of hair spray and perfume use for children and the AST (β = 4.241, P = 0.022). NP, BPA and DMP, which were commonly detected in the serum of children aged 5−14 years old in Zunyi City, Northern Guizhou Province, China, were closely related to the environmental risk factors of exposure environment during pregnancy, infancy and school age. Exposure to NP, BPA and DMP would have negative effects on hepatic function, and these effects showed differences in gender and geographical location. Notably,The relationships were more evident in girls than in boys.

Prenatal Bisphenol A Exposure and Early Childhood Behavior and Cognitive Function: A Chinese Birth Cohort Study

Introduction: Biomonitoring of bisphenol A (BPA) in human blood is still scarce, although already noticeable. We aimed to examine the associations between prenatal serum BPA concentrations and behavior and cognitive function in preschool children. Methods: A total of 1,782 mother-child pairs with complete demographic information, blood samples, and psychological measurements were included from the China-Anhui Birth Cohort (C-ABCS). We detected serum BPA concentrations and assessed children’s neurodevelopment using a set of psychometric scales. Results: The median prenatal maternal serum BPA concentration was 0.23 (P25, P75: 0.07, 0.52) ng/mL, with a detection frequency of 85.19%. Compared with the girls with the lowest concentrations, those with highest BPA concentrations had increased risks of inhibitory self-control impairment [relative risk (RR) = 3.66, 95% confidence interval (CI): 1.53, 7.58], emergent metacognition impairment (RR = 1.70, 95% CI: 1.07, 2.78), conduct problem (RR = 1.68, 95% CI: 1.12, 2.39), peer relationship problem (RR = 2.57, 95% CI: 1.33, 4.47), higher total difficulties score (RR = 1.76, 95% CI: 1.12, 2.67), and higher impact factor score (RR = 1.52, 95% CI: 1.11, 2.05), while the boys with the highest prenatal BPA concentrations had an increased risk of conduct problem compared with those with the lowest concentrations (RR = 1.59, 95% CI: 1.09, 2.24) (P-interaction = 0.011). After stratification by age, high prenatal BPA concentrations were associated with increased ADHD (RR = 4.44, 95% CI: 1.54, 10.85) among children aged 3 years, not among children aged 4 years. Conclusion: Our study revealed the sex-specific and age-specific impacts of prenatal BPA exposure on preschool children’s cognitive and behavioral development.

Exposure assessment of bisphenol A by drinking coffee from plastic cups.

Human exposure to plastic and Bisphenol-A (BPA) is very wide in food or beverage containers and baby bottles that have contacted polycarbonate and epoxy resin. Currently a traditional beverage in Arabian culture is served in plastic cups instead of glass cups in different occasions. To evaluate the possible BPA leach from the grade 5 drinking coffee plastic cups into the coffee and whether the use of plastic cups instead of glass ones to serve hot Arabian coffee poses a health risk. Oral administration of such coffee to three different groups of rats were undertaken. Each group consisted of 10 males and 10 females. The first group (G1) was gavaged 1.5 ml of hot water in glass cups. The second group (G2) was gavaged 1.5 ml of hot water in plastic cups while the third one (G3) was gavaged 1.5 ml of Arabian coffee in plastic cups. Serum concentrations of Bisphenol-A were measured 4 weeks later. Complete postmortem examination was conducted and representative tissue samples were subjected to histopathological evaluation. In the control group receiving water kept in a glass cup had 24 ± 2 μg/L serum concentration and the second group was 36 ± 4 μg/L while in the third group was 29 ± 6 μg/L. No significant postmortem changes or histopathological findings were present in the studied animals. Bisphenol-A can be leached from food-grade plastic cups into hot drinks within short period of time, posing a significant impact to public health.

Associations of serum bisphenol A levels with incident chronic kidney disease risk

Associations of bisphenol A (BPA) levels with renal disease are inconsistent. The present prospective study aims to evaluate the association of serum BPA levels with chronic kidney disease (CKD) in a Chinese middle-aged and elderly population. At baseline 1370 participants (mean age 61.7 years, 58.8% females) free of kidney disease and cancer were followed up nearly 10 years. Baseline serum BPA concentration was measured with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Multivariable logistic regression model was used to investigate relationship between serum BPA levels and incident CKD risk. During a 10-year follow-up, 246 individuals developed CKD. Baseline serum BPA concentration was 2.92 (1.00, 5.27) ng/mL. At baseline, after adjustment for multiple covariates serum BPA levels were negatively correlated with eGFR levels (β = −0.068, P = 0.009). Compared to those with low levels of serum BPA, participants with high levels had a significant negative association with CKD [ORs (95% CI) = 0.35 (0.25, 0.50), P < 0.001], and this association was not modified by conventional risk factors. The negative associations remained in females but not in males (P for interaction = 0.016). Significant interaction between baseline eGFR and serum BPA levels on CKD risk was also found (P for interaction = 0.027), Except subjects with 60–70 mL/min/1.73 m2 eGFR at baseline, inverse association robustly existed between serum BPA levels and incident CKD risk in the other eGFR subgroups. Further studies are needed to validate our findings.

Risk assessment of predicted serum concentrations of bisphenol A in children and adults following treatment with dental composite restoratives, dental sealants, or orthodontic adhesives using physiologically based pharmacokinetic modeling

Bisphenol A (BPA) is a chemical used to manufacture bisphenol A glycidyl methacrylate (BisGMA). BisGMA has been used for decades in dental composite restoratives, sealants, and adhesives. Based on published studies, exposure to low concentrations of BPA are possible from dental and orthodontic devices. The serum BPA concentrations arising from such devices and oral doses were predicted using a PBPK model in children and adult females based on 1) published extraction data for cured and uncured 3M ESPE Filtek Supreme Ultra Flowable, 3M ESPE Filtek Bulk Fill Restorative, and 3M ESPE Clinpro Sealant and 2) published 20% ethanol/water and water rinsate data following orthodontic application with 3M ESPE Transbond MIP Primer and 3M ESPE Transbond XT Adhesive. Predicted oral exposure to BPA arising from these dental and orthodontic devices is low (median <10 ng/treatment) and predicted serum BPA concentrations were also low (<10−4 nM). Even the maximum predicted exposure in this study (533.2 ng/treatment) yields a margin of exposure of 7.5 relative to the EFSA t-TDI (4 μg/kg-day) and is only 2.8% of the daily BPA exposure for the US population in a 58-kg woman (15,660 ng/day). Therefore, the exposure to BPA arising from the 3M ESPE dental and orthodontic devices evaluated in this study is negligible relative to daily BPA exposure in the general population and these potential BPA sources do not constitute a risk to patients.

Serum bisphenol A analogues in women diagnosed with the polycystic ovary syndrome - is there an association?

Due to the endocrine disrupting effects of bisphenol A (BPA) several governmental authorities have banned its use and the manufacturers had to find alternative substances with similar chemical properties. This led to the increase in the use of so-called BPA analogues, which however also turn out to possess mild estrogenic and ani-androgenic properties and thus, may cause fertility problems and sex-hormone dependent endocrinopathies. The aim of this study was to evaluate the potential association between the exposure to BPA and its two analogues: BPS and BPF, with the diagnosis of the polycystic ovary syndrome (PCOS), which remains the most common female endocrinopathy. Serum concentrations of BPA, BPS and BPF were measured using high performance liquid chromatography method with tandem mass spectrometry (HPLC-MS/MS) among 199 women with PCOS and 158 control subjects. In women with PCOS serum BPS concentrations were significantly higher compared to the control subjects (geometric mean [95% CI]: 0.14ng/mL [0.10; 1.17] vs. 0.08ng/mL [0.06; 0.09], P=0.023). Serum BPA and BPF concentrations did not differ between the studied groups. There was however a negative correlation between serum BPA and HOMA-IR (r=- 0.233, P=0.001) and TST (r=- 0.203, P=0.006) in women with PCOS. No correlations were found between the serum BPs and other metabolic parameters such as serum lipids, insulin, DHEA-S, androstenedione and FAI. When studying the association between serum BPA analogues and PCOS it turned out that women whose serum BPS concentrations were in the first tertile were more likely to be diagnosed with this endocrinopathy (OR [95% CI]: 1.21 [1.04; 3.46], P=0.017). This association was also statistically significant when adjusted for age, education, BMI, smoking, income, and alcohol consumption (adjusted OR [95% CI]: 1.12 [1.03; 3.71], P=0.029). These results point to the potential association between the exposure to BPS and the diagnosis of PCOS. The role of BPA is not clear and warrants further studies.

Elevated Serum Bisphenol A Levels Are Linked to Intracerebral Hemorrhage Risk in Young Patients

Background: Bisphenol A (BPA) is a widely used industrial chemical and is associated with many diseases. Here, we investigated the relationship between serum BPA concentration and endocrine function, cytokines, and ambulatory blood pressure indicators in young patients with unexplained intracerebral hemorrhage (YUICH). Methods: 380 YUICH patients and normal control subjects (n = 380) were recruited from Changzhi People's Hospital affiliated to Shanxi Medical University and Changzhi Heping Hospital affiliated to Changzhi Medical College. The serum BPA, insulin-like growth factor-1 (IGF-1), N-terminal brain natriuretic peptide (NT pro-BNP), matrix metalloproteinase 9 (MMP-9) and TOLL-like receptor 4 ( TLR-4) level. Radioimmunoassay was used to detect the serum levels of S100B protein (S100B), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), total testosterone (TT) and free testosterone (FT). Observe the variability of blood pressure levels through 24-hour ambulatory blood pressure monitoring, and use cerebrovascular computed tomography and magnetic resonance imaging for routine measurement. Findings: The following parameters of YUICH patients increased significantly compared with the normal control group. Serum BPA (0.85±0.15 vs 0.535±0.11 pg/ml), MMP-9 (104±10 vs 53±8.1 pg/ml), S100B (0.105±0.024 vs. 0.098±0.02μg/L), IL-1β (0.60±0.04 vs. 0.19±0.03 ng/ml), TNFα (1.29±0.13vs0.66±0.09 ng/L), TLR-4 (12.04±1.14vs 5.69±144 ), NT pro-BNP (1464±97 vs. 353), TPO-Ab (81.55±16.7 vs 8.7±2.7 IU/l). The following parameters were significantly reduced compared with the control group, IGF-1 (65.2±10.4 vs 105±9.5 ng/l), P <0.01.The FT4 of male patients with YUICH was higher than that of the control group (45±10.2 vs 26±9.2 nmol/l), and the TSH level of female patients with YUICH was higher than that of the control group (9±2.3 vs 2.1±0.4 ng/l, P<0.01). The serum free testosterone level of male patients with YUICH was lower compared with the control group (0.18±0.03 vs 0.21±0.02 nmol/l). Serum BPA is positively correlated with TPO-Ab, NT-pro BNP, FT4, MMP-9, IL-1β, S100B, and TNF-α (r = 0.47), (r = 0.50), (r = 0.42), (R = 0.43) (r = 0.44), (r = 0.46), both P <0.01 and (r = 0.38, P <0.05); serum BPA is negatively correlated with IGF-1 and free testosterone (r =- 0.49), (r = -0.46), P <0.01; while serum S100B is positively correlated with 24hSBPCV, MMP-9 (r = 0.45), (r = 0.51), MMP-9 is positively correlated with nDBPCV (r = 0.51) TLR -4 is positively correlated with IL-1β (r = 0.52) P<0.01. Interpretation: Thus, BPA exposure will destroy a variety of hormone systems, and the production of cytokines and the variability of ambulatory blood pressure may be involved in the pathophysiological process and pathogenesis of YUICH. Trial Registration: Chinese Clinical Trial Registry A Primary Registry of International Clinical Trial Registry Platform, World Health Organization. Clinical trials.gov. Chi CTR1900023626. Funding Statement: This work was supported by the Natural Science Foundation of Shanxi Province (grant nos. 2010011055-1 and 201701D121177); Shanxi Provincial Science and Technology Department of the Project Fund (grant no. 2011099); and Spark Planning Project of Changzhi City of Shanxin Province (grant no. 200704009). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All patients provided written, informed consent prior to participation in the study. The protocol was approved by Changzhi People’s Hospital and the Ethics Committee of Shanxi Medical University Affiliated Hospital (approval no.2013093).confirming that all experiments were performed in accordance with relevant guidelines and regulations.

Serum Bisphenol A, glucose homeostasis, and gestational diabetes mellitus in Chinese pregnant women: a prospective study.

Lab studies have suggested that exposure to Bisphenol A (BPA) could disturb glucose homeostasis, but epidemiologic studies are limited and show inconsistent results for pregnant women. For this, 535 pregnant women were selected from a pregnant women cohort established in Tangshan City in North China between 2013 and 2014. Serum concentrations of BPA were measured in the early term of pregnancy, and fasting glucose and insulin levels were repeatedly measured in each of three terms of pregnancy (early, middle, and late). Gestational diabetes mellitus (GDM) were examined by Oral Glucose Tolerance Test (OGTT) in the middle and late terms of pregnancy. BPA was detected in 97.5% of pregnant women with a median of 6.50ng/ml. Natural log-transformed BPA (Ln BPA) was positively associated with fasting glucose level (β (95% CI): 0.038 (0.015~0.061)), fasting insulin level (0.195 (0.069~0.321)), and homeostasis model insulin resistance index (HOMA-IR) (0.226 (0.087~0.364)) in the middle term of pregnancy by multiple linear regression model after adjusting for potential confounders. After serum BPA levels were divided into three groups (low, middle, and high), BPA showed a positive dose-response relationship with blood glucose, insulin, and HOMA-IR in the middle term of pregnancy. Increased BPA concentration tended to increase the RR of GDM although not statistically significant (risk ratio: 2.51 (95% CI: 0.68~9.30) for high vs low tertile of BPA concentrations). These findings suggested that exposure to BPA might affect glucose homeostasis and the middle term of pregnancy was a potentially sensitive period.

Bisphenol A exposure and risk of ischemic heart disease in the Spanish European Prospective Investigation into cancer and nutrition study

BackgroundCardiovascular disease, particularly ischemic heart disease (IHD), is the leading cause of mortality worldwide. Bisphenol A (BPA) is considered an endocrine disruptor and obesogen, present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident IHD in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). MethodsWe designed a case-cohort study within the EPIC-Spain cohort. The population consisted of 4636 participants from 4 EPIC-Spain centers (946 IHD cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Follow-up was performed by linking with national and regional databases and reviewing patients’ clinical records. Cox Proportional Hazards Models were used for the statistical analyses. ResultsMedian follow-up time was 16 years and 70% of the participants showed detectable BPA values (>0.2 ng/ml). Geometric mean (GM) values of cases and sub-cohort were 1.22 ng/ml vs 1.19 ng/ml respectively (p = 0.90). Cox regression models showed no significant association of BPA serum levels and IHD, acute myocardial infarction or angina pectoris risk. ConclusionsWe evidenced a similar percentage of detection of BPA among cases and sub-cohort participants from our population, and no clear association with IHD risk was observed. However, further investigation is needed to understand the influence of BPA on IHD risk.

Serum concentration of bisphenol A in elderly cats and its association with clinicopathological findings.

Bisphenol A (BPA) has been mentioned as a possible factor contributing to feline hyperthyroidism. Nevertheless, there are no previous studies reporting on the concentration of BPA in feline serum and its association with thyroid function. The objectives of this study were to measure serum BPA concentration in cats aged ⩾7 years, considered as healthy by their owners, and to compare the results with clinicopathological findings. Sixty-nine cats aged ⩾7 years considered as healthy by their owners were enrolled in the study. The concentration of BPA in feline serum was measured using liquid chromatography-tandem mass spectrometry. In all cats, signalment, living environment, diet history, and the results of haematological and biochemical analysis, including thyroxine levels, were available. The mean serum BPA concentration in feline serum was 1.06 ± 0.908 ng/ml. Significant correlation was found between BPA concentration and haemoglobin (r = 0.3397; P = 0.0043), haematocrit (r = 0.3245; P = 0.0065) and the number of red blood cells (r = 0.2916; P = 0.0151), concentration of total protein (r = 0.2383; P = 0.0486), concentration of calcium (r = 0.3915; P = 0.0009) and level of bilirubin (r = 0.3848; P = 0.0011). No other significant correlations were found. Significant differences (P <0.01) were found between mature (1.28 ± 0.994 ng/ml) and geriatric cats (0.420 ± 0.240 ng/ml), between strictly indoor cats (1.27 ± 0.992 ng/ml) and cats with outdoor access (0.660 ± 0.529 ng/ml), and between cats fed canned food (1.23 ± 0.935 ng/ml) and cats fed non-canned food (0.774 ± 0.795 ng/ml). Measurable serum BPA levels were found in all examined samples. The age of the cats was revealed as a significant factor affecting BPA concentration and mature cats had the highest levels. A significantly higher concentration of BPA was found in cats living strictly indoors and in cats fed canned food. No association was found between BPA and thyroid function. Further studies are needed that focus on hyperthyroid cats for better evaluation of this relationship.

A birth cohort study of the association between prenatal serum bisphenol A concentration and infant neurobehavior development

Objective: To explore the association between maternal bisphenol A (BPA) exposure during pregnancy and neurobehavioral development in infant. Methods: Participants were from the Ma'anshan Birth Cohort, which was established from October 2008 to October 2010 based on four municipal medical and health institutions in Ma'anshan. High-performance liquid chromatography-tandem mass spectrometry was applied for the determination of serum BPA concentration in 1 783 pregnant women sampled at their first filing, and during 2.97 to 28.1 months age of the infants. Neurobehavioral development were assessed by 0-6-year-old pediatric examination table of neuropsychological development. Generalized linear model was used to analyze the association between serum BPA levels during pregnancy and infants' neurobehavioral development. Results: A total of 931 mother-child pairs had complete data on serum BPA detection during pregnancy and assessment of infants' neurobehavioral development status. The age of pregnant women at their first filing was (26.67±3.45) years old, and the M (P25,P75) of serum BPA concentration (ng/ml) was 0.23 (0.11, 0.52), with a detection rate of 84.1% (783/931). The age of infants was (13.18±5.46) months, and 53.5% (498) were boys. The developmental quotient scores of large motor, fine motor, adaptive ability, language ability and social behaviors of infants were (97.88±16.32), (97.16±15.35), (99.64±15.47), (95.3±16.04) and (98.95±14.76) points, respectively. Generalized linear model showed that after adjusting for factors such as delivery mode, feeding mode, family per capita monthly income, preterm delivery, gender, maternal age, residence, pre-pregnancy body mass index and residence time, serum BPA level in pregnancy was negatively associated with infant's development of social behavior [β (95%CI):-2.42 (-4.71, -0.12)]. The post-stratification analysis by infant age revealed that the serum BPA level in pregnancy was only negatively associated with the development of language and social behavior developmental quotient scores in infants between the ages of 12 and 18 months, with β (95%CI) about -6.66 (-13.06, -0.25) and -7.401 (-12.97, -1.83), respectively. Conclusion: BPA exposure during pregnancy affects language and social behavior development in infants, and the detection window is between 12 and 18 months old of the infant.

Maternal serum concentrations of bisphenol A and propyl paraben in early pregnancy are associated with male infant genital development.

Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10-17weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally? Maternal serum bisphenol A (BPA) concentration at 10-17weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24months of age. Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window. Case-control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10-17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis. Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models. Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log10 μg/l: 2.90, 95% CI 1.31-6.43, P = 0.009) and as quartiles (phet = 0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051-0.433, P = 0.01) from birth to 24months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured. We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity. Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made. This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), Newlife the Charity for Disabled Children, the Mothercare Group Foundation, Mead Johnson Nutrition and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. Visiting Fellowship (J.M.): Regional Programme 'Jiménez de la Espada' for Research Mobility, Cooperation and Internationalization, Seneca Foundation-Science and Technology Agency for the Region of Murcia (No. 20136/EE/17). K.O. is supported by the Medical Research Council (UK) (Unit Programme number: MC_UU_12015/2). The authors declare no conflict of interest.

Bisphenol-A in the European Prospective Investigation into Cancer and Nutrition cohort in Spain: Levels at recruitment and associated dietary factors

Bisphenol A (BPA) is considered an endocrine disruptor and it is present in numerous products of daily use. The aim of this study was to analyze serum BPA concentrations in a subcohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC), as well as to identify potential predictors of the exposure. The population consisted on 3553 subjects from 4 EPIC-Spain centres and BPA levels were measured in serum samples by UHPLC-MS/MS. Almost 70% of the participants showed detectable BPA values (>0.2 ng/ml), with a geometric mean of 1.19 ng/ml (95% CI: 1.12–1.25). By sex, detectable percentages were similar (p = 0.56) but with higher serum levels in men (1.27 vs 1.11 ng/ml, p = 0.01). Based on the adjusted regression models, a 50 g/day increase in the consumption of added fats and oils were associated with 43% lower BPA serum levels, while sugar and confectionary was associated with 25% higher levels of serum BPA. We evidenced differential exposure levels by province, sex and age, but not by anthropometric or lifestyle characteristics. Further investigation is needed to understand the influence of diet in BPA exposure.

Bisphenol A levels among workers in plastic processing industry and their relations to thyroid hormones

Bisphenol A (BPA) is widely used in plastic processing industry. A cross sectional study was conducted to measure BPA levels in the serum of workers as a biomarker of occupational exposure, investigate the thyroid hormone profile among BPA exposed workers, and identify the relation between occupational exposure to BPA and thyroid hormones during. Our data indicates that the studied workers had higher BPA level than that reported for the Egyptian general population, with median serum level of 15.6 ng/ml and ranged from 1.6 - 62.9 ng/ml while the interquartile range was 16.3 ng/ml, the highest concentration was among the workers of recycling followed by squeegees and PVC departments. As regards thyroid hormones, almost one third of the studied workers had abnormal TSH levels and 12.2% had abnormal T4 levels. According to TSH and T4 levels, 64.4% of the studied workers had normal thyroid function and 35.6% was suffering from subclinical hypothyroidism. There was no statistical significant correlation between BPA levels and subclinical hypothyroidism. However, our data reported a significant positive correlation between thyroid hormoneT3 and serum BPA concentrations. As agonist or antagonist, BPA could bind to the thyroid hormone receptors indicating that remarkable endocrine disruption.

Inverse associations of bisphenol A and phthalate metabolites with serum bilirubin levels in Korean population.

Bisphenol A (BPA) and phthalates are endocrine disruptors that can induce oxidative stress. Serum bilirubin has antioxidant properties and may serve as a biomarker of oxidative stress. The objective of this study was to explore the relationship of BPA and phthalates with serum bilirubin levels in a Korean population. Urinary concentrations of BPA and six phthalate [mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono-benzyl phthalate (MBzP)] were measured in 709 participants. Serum concentrations of BPA and three phthalate metabolites [MnBP, MiBP, and mono-(2-ethylhexyl) phthalate (MEHP)] were measured in 752 participants. After excluding missing variables, associations between above chemicals and serum bilirubin levels were analyzed using multivariate linear regression with age, sex, BMI, GGT, GOT, GPT, and alcohol intake adjustment. Participants were further stratified by sex. Among the urinary chemicals, BPA and four phthalate metabolites (MnBP, MEOHP, MEHHP and MECPP) were inversely associated with serum bilirubin levels (BPA: β = -0.071, P < 0.0001; MnBP: β = -0.055, P = 0.025; MEOHP: β = -0.101, P < 0.0001; MEHHP: β = -0.106, P < 0.0001; MECPP: β = -0.052, P = 0.003). In a case of serum chemicals, only MiBP showed significantly positive association (β = 0.036, P = 0.016). After stratification by sex, the associations of urinary BPA remained both in male and female, of which urinary phthalates disappeared in female. The association of serum MiBP was disappeared after stratification. Urinary BPA and phthalate metabolites were inversely associated with serum bilirubin levels, whereas serum MiBP showed positive association with bilirubin. These results could provide clues for understanding the mechanisms of endocrine disruptor from oxidative stress to excretion from our body.

High Serum Bisphenol-A Level Might Increase the Risk of Young Intracerebral Hemorrhage

Background and Purpose: Bisphenol-A (BP-A) is a widespread industrial chemical used in the synthesis of polycarbonate plastics and epoxy resins. Recent epidemiological investigations have disclosed the associations between BP-A exposure and some diseases. Evidence from experimental animal studies and clinical studies suggests the BP-A can act as an estrogenic endocrine disruptor and impact neurological outcome. The present study aimed to determine serum BP-A concentrations in youth patients with unexplained intracerebral hemorrhage (YUICH) as well as the relationship and the change among serum BP-A levels, thyroid function parameters, thyroid autoimmunity, and insulin-like growth factor-1 (IGF-1) compared to a control group. Methods: Three hundred and sixty-five YUICH patients and three hundred-eighty age and gender-matched healthy controls were included from the Affiliated Changzhi Municipal people's Hospital of Shanxi Medical University and the Affiliated Heping Hospital of Changzhi Medical college. Serum BP-A levels and insulin growth factor-1 (IGF-1) were measured using corresponding ELISA kits. Several hormonal parameters, including: free and total thyroxine (FT4, TT4), or free and total triiodothyronine (FT3, TT3), thyroid stimulating hormone (TSH), antithyrogobulin (TgAb), antithyroperoxidase (TPOAb), and antithyrotrophin receptor (TRAb) antibodies were measured by using electrochemiluminescence immunoassay Kits. Data analysis was performed using the statistical package SPSS version 18.0 (SPSS, Inc). Results: The levels of serum BPA were significantly higher in the total YUICH group compared with that in the controls（0.85±0.15ng/L vs 0.535±0.11ng/L,P＜0.01). Significant difference was also observed in TPO -Ab and IGF-1 between YUICH patients and controls, (12±1.7 ng/L vs 6.7±2.7 IU/L and 65.2±10.4ng/L vs 105±9.5 ng/L, both of P ＜0.01). Similar trends were observed in the male and Female subgroup. Mean FT4 level was higher in male YUICH groups than in the control groups (45±10.2 nmol/L vs 26 ± 9.2 nmol/L,P＜0.01) ,and TSH was higher in female YUICH group than in the control (9±2.3 ng/Lvs2.1±0.4 ng/L, P＜0.01 ). Linear relation and regression analysis have shown that increasing serum BP-A level were statistically positively correlated with TPOA (r=0.47,P＜ 0.01),and significant negatively associated with low IGF-1 level (r = - 0.49, P＜0.01). additionally, Serum BP-A was positively related with serum free- thyroxine for male YUICH groups（r = 0.42, P＜0.01), but was negatively correlated with thyroid stimulating hormone for female YUICH group ( r= - 0.41, P ＜0.01). However, no statistical difference was noted for serum TgAb and TRAb. Conclusion: Our findings firstly demonstrated that BP-A exposure increased in YUICH patients compared with that in healthy controls. While Female is subclinical hypothyroidism and Male is hyperthyroidism ( high T4) and IGF-1 levels decreased. TPOAb presented a positive association with BP-A. It is concluded that hormone disorder induced by BP-A exposure might be an environmental factor in the pathology of YUICH. Funding Statement: Supports from the Natural Science Foundation of Shanxi provincial (2010011055-10; Shanxi Provincial Science and Technology Department of the Project Fund (2011099); Spark Planning Project of Changzhi City of Shanxin Provin (200704009). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All subjects gave their informed consent for inclusion before they participated in the study to be conducted in accordance with the declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Affiliated Changzhi Municipal People's Hospital of Shanxi Medical University (Ethical code: No.2013093).

Serum levels of phthalates and bisphenol-A in patients with primary ovarian insufficiency

Objectives: Phthalates and bisphenol-A (BPA) may pose a risk for human reproduction. Adverse effects of endocrine disturbing chemicals on animal ovaries have been proposed previously. This study was designed to measure the concentrations of phthalate diesters or their metabolites in serum to evaluate their relevance with primary ovarian insufficiency (POI).Methods: This study was designed as a cross sectional and case-control study. The study group consisted of 30 women diagnosed with POI whereas 30 healthy fertile women without any systemic diseases were recruited as a control group. The two groups were matched with respect to age and body mass index and tobacco smoking. Serum phthalate diesters and BPA levels were measured in both groups.Results: The mean serum level of mono-buthyl phthalate (MBP) was statistically significantly higher in POI group than in control group (8.45 ± 4.2 vs. 5.0 ± 3.47 ng/mL, p < .001). Other serum phthalate metabolites and BPA concentrations were similar among the groups.Conclusions: Serum levels of BPA and phthalate metabolites are increased in women diagnosed with POI. However, MBP is the most significant one among them. MBP may be a contributing risk factor in the development of POI.