Free Bisphenol A Research Articles

Chromatographic methods for the determination of free bisphenol A in technical and food products

The article provides a brief overview of chromatographic methods for the determination of free bisphenol A in technical and food products. Bisphenol A (BPA) is used as a monomer in the production of some plastics and epoxy resins. Free BPA may be present in quantities exceeding acceptable levels in plastic food containers and in food products packaged in these containers. Maximum permissible concentration (MPC) of BPA in the air of the working area is 5 mg/m3, which in terms of liquid is 5 µg/dm3. Maximum permissible concentration for the content of BPA in water, in water bodies for domestic, drinking and community water use is 0.1 mg/dm3. In European countries for plastics in contact with food, the BPA migration value is 0.6 mg/kg. Despite the relatively low toxicity of BPA, it can accumulate in the human body and cause harmful effects. To determine BPA in plastic, food products, and biological fluids, gas chromatography with preliminary derivatization by silylation or acylation of the analyte is most often used. Gas chromatographic techniques for direct chromatography on heat-resistant columns have also been developed. A fluorometric detector and a mass spectrometric detector are used as detection devices, along with a flame ionization detector. An alternative method for determination of BPA is HPLC with optical and mass spectrometric detection methods. The TLC method was also developed for the determination of BPA. For the preparation of BPA samples, solid-phase extraction (SPE), liquid-liquid extraction (LLE), dispersive liquid-liquid microextraction (DLLME), combined extraction method with acetonitrile separation (QuEChERS) are used.

Importance of relative binding of bisphenol A and bisphenol S to plasma proteins for predicting their in vivo potencies

Many studies suggest that the potential impact of bisphenol S (BPS) as an endocrine disruptor is comparable to that of bisphenol A (BPA). However, in vitro-to-in vivo and from animal to human extrapolations require knowledge of the plasma free fraction of the active endocrine compounds. The present study aimed to characterise BPA and BPS binding to plasma proteins both in humans and different animal species. The plasma protein binding of BPA and BPS was assessed by equilibrium dialysis in plasma from adult female mice, rats, monkeys, early and late pregnant women as well as paired cord blood, early and late pregnant sheep and foetal sheep.The fraction of free BPA was independent of plasma concentrations and ranged between 4% and 7% in adults. This fraction was 2 to 3.5 times lower than that of BPS in all species except sheep, ranging from 3% to 20%. Plasma binding of BPA and BPS was not affected by the stage of pregnancy, BPA and BPS free fractions representing about 4% and 9% during early and late human pregnancy, respectively. These fractions were lower than the free fractions of BPA (7%) and BPS (12%) in cord blood.Our results suggest that similarly to BPA, BPS is extensively bound to proteins, mainly albumin. The higher fraction of free BPS compared to BPA may have implications for human exposure assessment since BPS free plasma concentrations are expected to be 2 to 3.5 times higher than that of BPA for similar plasma concentration.

Plastic bottle feeding produces changes in biochemical parameters in human infants - A pilot study.

Background Plastic bottles are widely used by people to feed their infants when breastfeeding is not possible. Bisphenol A (BPA), an endocrine disruptor is widely used in the manufacturing of plastic wares and is leached out from these plastic wares on exposure to high temperature, changed pH, or cleaning the plastic wares by harsh detergents.Purpose Feeding through plastic bottles over prolong duration is expected to expose the infants to leached BPA. Hence the present study was taken up to compare the effects of breastfeeding and plastic bottle feeding on biochemical parameters in infants and also detect for the presence of free BPA or its metabolite in the infants.Methods Biochemical tests like lipid profile, liver function tests, creatine-kinase–MB (CK-MB), serum urea, serum electrolytes were performed on blood samples obtained from infants who were breastfed and plastic bottle fed. Further, plasma and urine samples of the infants were subjected to Liquid chromatography-mass spectrometry analysis for detecting free BPA and BPA glucuronide.Results Biochemical changes in form of raised triglycerides, cholesterol, low-density lipoproteins, very low-density lipoproteins and increase in CK-MB, serum urea were observed in plastic bottle fed infants. BPA glucuronide was also detected in the urine of these infants. Free BPA was not detected in plasma or urine samples of the infants except in one plasma sample from bottle-fed group.Conclusion Plastic bottle feeding may lead to toxic changes in the functioning of organs which manifest as altered biochemical parameters.

Bisphenol A Exposure in Exclusively Breastfed Infants and Lactating Women: An Observational Cross-sectional Study

Objective:Bisphenol A (BPA) is a known endocrine disruptor and free BPA will interact with estrogen. BPA is also fat soluble and will therefore contaminate breast milk. The European Food Safety Authority has set a limit for temporary tolerable daily intake of 4 μg/kg body weight/day in breastfeeding infants. The aim of this study was to measure human milk BPA concentrations in Turkish women and thus exclusively breastfed infants’ exposure to BPA.Methods:Healthy, postnatal, exclusively breastfeeding women were recruited and breast milk samples were collected. Free BPA concentration was analyzed in the milk samples using competitive enzyme-linked immunosorbent assay. Participants’ demographic characteristics and nutritional habits were investigated through face-to-face interviews using a detailed questionnaire.Results:Eighty women participated. Median milk free BPA level was 0.63 μg/L. There was no statistically significant association between maternal body mass index, birth type, parity, infant birth week, infant birth weight, and human milk BPA concentration. Nevertheless, there was a significant association between human milk BPA level and consumption of fast-food and carbonated drinks (p=0.022 and p=0.018, respectively). Exclusively breastfed infants’ mean BPA exposure was 0.0099±0.0079 μg/kg bw/day. There was a moderate negative significant correlation between infant BPA exposure and infant current body weight (r=0.327, p=0.003).Conclusion:BPA exposure in exclusively breastfed infants was within accepted limits and the current dietary exposure level of infants in this cohort was safe.

Human biomonitoring initiative (HBM4EU): Human biomonitoring guidance values (HBM-GVs) derived for bisphenol A

The “European Human Biomonitoring Initiative” (HBM4EU) derives human biomonitoring guidance values (HBM-GVs) for the general population (HBM-GVGenPop) and/or for occupationally exposed adults (HBM-GVWorker) for several priority substances and substance groups as identified by policy makers, scientists and stakeholders at EU and national level, including bisphenol A (BPA).Human exposure to BPA is widespread and of particular concern because of its known endocrine-disrupting properties. Unlike the conjugated forms of BPA circulating in the body, free BPA is known to interact with the nuclear estrogen receptors. Because free BPA is considered to be more toxicologically active than the conjugated forms (e.g. BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S)), its measurement in blood provides the superior surrogate of the biologically effective dose. However, considering the difficulty of implementing blood sampling in large HBM cohorts, as well as the current analytical capacities complying with the quality assurance (QA)/quality control (QC) schemes, total BPA in urine (i.e. the sum of free and conjugated forms of BPA measured after an hydrolysis of phase II metabolites) was retained as the relevant exposure biomarker for BPA.HBM-GVGenPop for total BPA in urine of 230 µg/L and 135 µg/L for adults and children, respectively, were developed on the basis of toxicological data. To derive these values, the concentrations of urinary total BPA consistent with a steady-state exposure to the temporary Tolerable Daily Intake (t-TDI) of 4 µg/kg bw/day set in 2015 by the European Food Safety Authority (EFSA) were estimated. The BPA human physiologically-based pharmacokinetic (PBPK) model developed by Karrer et al. (2018) was used, assuming an oral exposure to BPA at the t-TDI level averaged over 24 h. Dermal uptake of BPA is suspected to contribute substantially to the total BPA body burden, which in comparison with the oral route, is generating a higher ratio of free BPA to total BPA in blood. Therefore, an alternative approach for calculating the HBM-GVGenPop according to the estimated relative contributions of both the oral and dermal routes to the global BPA exposure is also discussed.Regarding BPA exposure at the workplace, the steady-state concentration of urinary total BPA was estimated after a dermal uptake of BPA that would generate the same concentration of free BPA in plasma (considered as the bioactive form) as would a 24 h-averaged intake to the European Chemicals Agency (ECHA)’s oral DNEL of 8 µg BPA/kg bw/day set for workers. The predicted concentration of urinary total BPA at steady-state is equivalent to, or exceeds the 95th percentile of total BPA in urine measured in different European HBM studies conducted in the general population. Thus, no HBM-GVWorker was proposed, as the high background level of BPA coming from environmental exposure - mostly through food intake - is making the discrimination with the occupational exposure to BPA difficult.

Bisphenol A leaching from epoxy resins in the drinking water distribution networks as human health risk determinant

Monitoring and management of drinking water distribution networks (DWDNs), including possible leaching from materials in contact with drinking water, have been stressed as crucial to avoid re-contamination of drinking water leading to a potential increase of human health risk. Recent scientific studies and regulations clearly highlighted the leaching of bisphenol A (BPA) from plastic materials used to renovate DWDNs pipelines as one of the major hazardous source, resulting in severe consequences for human health. In this study, lab migration tests were performed on three commercial epoxy resins, designed with the Design of Experiments (DoE) method in order to build a BPA migration model as a function of water chemical stability, evaluated as aggressivity index (AI), and residual chlorine concentration. Tests lasted about 170 days to account for both short and long-term leaching. BPA migration over time was well described by a combination of two 1st-order kinetic models with an initial peak of leaching, a decrease and, then, a second increase due to resins' deterioration. Initial BPA concentration in the contact water and BPA integral migration over time showed inverse proportionality with both chlorine concentration and AI values. However, measurements of free BPA content in epoxy resins proved that this is due to BPA transformation, not to a reduced leaching. The validated BPA migration model was combined with the hydraulic model of the DWDN in an urban area, through EPANET-MSX software. The model allowed to simulate the propagation of BPA in the DWDN, after the execution of a relining intervention, identifying the most vulnerable areas and permitting to customize a site-specific monitoring and intervention plan to minimize the health risk for final consumers.

A rapid analysis of Bisphenol A using MISPE coupled with HPLC-FLD in tissues of food-producing animals

Bisphenol A (BPA) is a highly-produced organic compound of anthropogenic origin with a wide-range use and is ubiquitously present in both living organisms and the environment. A previously published analytical method for testing of the free (aglycone) BPA in foodstuffs was simplified and optimized for sheep muscle tissue, kidney and liver, by using only a single MISPE purification step allied with HPLC-FLD analysis. The recovery rates and RSD values over a concentration range of 1–10 µg/kg were in the range of 67‒86% and 3‒34%, respectively, while linearity in the matrix, represented by the r2, was ≥0.999. LOD values were 0.5‒1 µg/kg and LOQ values were 1 µg/kg. The analytical method used is a contribution to the field of veterinary toxicology and food testing and also proved to be applicable for other food-producing animal species, e.g. pigs, poultry and freshwater fish. The MISPE sorbent material for testing of BPA was reusable, with up to five re-use cycles without significant loss in performance characteristics.•The paper reports on a rapid determination of free (aglycone) BPA in tissues of food-producing animals by HPLC-FLD and presents a substantial improvement of analytical performance with regard to time- and cost-savings, as well as environmental protection.•MISPE is an advanced analytical technology, and the results proved that in a single and simplified SPE step it had good performance characteristics such as selectivity, recovery and precision, allied with low LOD and LOQ values.•It was proved that MISPE BPA cartridges could be used at least five times without significant loss of methodological recovery and precision.

The Development of a Photothermal Immunochromatographic Lateral Flow Strip for Rapid and Sensitive Detection of Bisphenol A in Food Samples

A novel quantitative photothermal-sensing immunochromatographic assay (PT-ICA) with high sensitivity was developed for the detection of bisphenol A (BPA). Gold acid chloride trihydrate (HAuCl4·3H2O) was first reduced by citric acid trisodium salt (C6H5Na3O7) to form Au nanoparticles and adsorbed on the surface of black phosphorus nanosheets to form a black phosphorus-Au (BP-Au) complex. The antibody against BPA was then coupled to the BP-Au complex to form the black phosphorus-Au-antibody (BP-Au-Ab) photothermal probe for capturing BPA in samples. During the detection, the precoated antigen BPA-bovine serum albumin (BPA-BSA) on the T line and free BPA molecules in the sample would competitively bind to the limited BP-Au-Ab photothermal probes. After that, the exothermic process under an 808-nm laser was recorded using an infrared thermal imager, which represented the concentration of BPA in the samples. The PT-ICA demonstrated high sensitivity with a limit detection of 0.24 ng/mL, which was 6.25 times lower than that of the visual-ICA. In addition, the assays were highly specific, only minor cross-sensitivity occurred between BPA and 4-cumylphenol. The optimized assay was applied in the detection of BPA in different food samples with recoveries ranging from 75.91 to 119.59%. Finally, the PT-ICA was verified using a commercial enzyme-linked immunosorbent assay (ELISA) kit. The results of the developed assay showed good agreement with that of the ELISA kit. The optimized PT-ICA required a shorter detection time (approximately 30 min) than the ELISA kit (approximately 2 h), which has potential applications in the detection field.

A novel method for rapid and quantitative detection of bisphenol A in urine.

Bisphenol A (BPA) is classified as an endocrine disruptor (ED) and it can interact with variety of hormone receptors leading to hormonal disruption and increased risk of various adverse health effects. Reducing human exposure to BPA is one of the main challenges of public health, as it is constantly present in daily life. A low-cost and commonly applied method to enable determination of BPA in the patient's body has yet to be developed. Currently available techniques are expensive, time-consuming, and require access to highly equipped analytical chemistry laboratories. Here we describe a fast and cheap engineered lateral flow assay of our design, to detect of BPA in urine samples. The technology not only provides an opportunity to perform rapid medical diagnostics without the need for an access to the central laboratory but also a means for self-diagnosis by the patient. The addition of β-glucuronidase improves the sensitivity of detection as it releases the free BPA from glucuronide complexes in urine. This invention may become a demonstrated analytical means for lowering human exposure to BPA and probably also to other EDs and consequently, may be useful in decrease of the risk for several lifestyle diseases.

Determination of free and total bisphenol A in the urine and feces of orally and subcutaneously dosed sheep by high-performance liquid chromatography with fluorescence detection

An analytical procedure has been introduced to enable a study of the excretion of free bisphenol A (BPA), total BPA and its main metabolite bisphenol A glucuronide (BPA–GLUC). In the experiment, in which 100 μg/kg b. w. BPA was administered daily to one Istrian Pramenka sheep for 5 days with consecutive urine and feces samples being taken, BPA and total BPA were determined in samples using high-performance liquid chromatography (HPLC) with fluorescence detection. Because of their good recovery, precision, and sensitivity, the methods have also proved applicable to further ecotoxicological studies of free BPA, BPA–GLUC and total BPA. The results were subsequently compared with reported field studies of BPA in livestock excreta.

Assessment of Bisphenol A Levels in Preschool Children: Results of a Human Biomonitoring Study in Ankara, Turkey

Objective:There is general concern regarding environmental chemical exposure and the impact it may have on human health. This is particularly important for vulnerable populations such as infants and children during critical periods of development. Bisphenol A (BPA) is an endocrine disrupting chemical used worldwide over the last 30 years in many consumer products. Evidence points to widespread human exposure to BPA. The aim of this study was to evaluate the exposure of Turkish preschool children to BPA.Methods:This study was conducted as a preliminary investigation of BPA in urine, collected from 3-6 year old children living in Ankara. After spot urine samples were taken from preschool children, free BPA, β-D-glucuronide and total BPA were determined using high-performance liquid chromatography tandem mass spectrometry and adjusted by creatinine concentration.Results:Preschool children from Ankara (n=125; males n=70, females n=55; mean age: 4.50±1.26) were recruited. BPA was detected in 76.8% of children from Ankara city, with urinary concentrations ranging from < limit of quantification to 18.36 μg/g creatinine. Total BPA levels were not statistically different between boys (1.26 μg/g creatinine) and girls (2.24 μg/g creatinine) (p>0.05).Conclusion:This study is an important contribution to the limited information about childhood exposure to BPA. The estimated daily BPA intake in this study is substantially lower than the European Food Safety Authority derived tolerable daily intake of 4 μg/kg BW/day.

Quantification of eight bisphenol analogues in blood and urine samples of workers in a hazardous waste incinerator

Bisphenol A (BPA) has been widely used in the manufacture of polycarbonate plastic and epoxy resins. In recent years, producers have started replacing BPA by other chemical analogues, such as bisphenol -S (BPS) and -F (BPF), all of them under the label “BPA-free”. However, despite bisphenol (BP) analogues have a very similar structure, their endocrine-disrupting properties could differ from those of BPA. Unfortunately, information regarding human exposure to BP analogues is very limited, not only as single substances, but also as chemical mixtures. The aim of this study was to determine the levels of 8 BP analogues (A, S, F, B, AF, Z, E, and AP) in biological samples from a controlled cohort of workers in a hazardous waste incinerator (HWI) located in Constantí (Catalonia, Spain). Firstly, a chemical method to analyze a mixture of those 8 analogues in total blood and urine was optimized, being samples quantified by means of gas chromatography coupled to mass spectrometry (GC-MS). Furthermore, a biomonitoring study was performed by collecting samples of total blood and urine of 29 people working in the HWI. Among the 8 BP analogues assessed, BPA presented the highest levels in both biological samples, with mean total (free + conjugated) BPA concentrations of 0.58 and 0.86 μg/L in blood and urine, respectively. Free vs. total BPA levels presented a mean percentage of 79% in blood and 19% in urine. Beyond BPA, traces of BPB were also found in a single sample of blood. Furthermore, none of the remaining BP analogues was detected in blood or urine. Despite BPA has been regulated, it is still very present in the environment, being human exposure to this chemical still an issue of concern for the public health.

Comparison of Bisphenol A and Bisphenol S Percutaneous Absorption and Biotransformation.

Background:Bisphenol S (BPS) has been widely substituted for bisphenol A (BPA) on thermal papers, but little is known about its skin absorption.Objectives:We compared the percutaneous absorption and biotransformation of BPS and BPA in vitro and in a controlled human trial.Methods:Absorption and biotransformation of BPS and BPA were monitored across reconstructed human epidermis at two environmentally relevant doses over 25 h. In the human trial, five male participants handled thermal receipts containing BPS and washed their hands after 2 h. Urine (0–48 h) and serum (0–7.5h) were analyzed for target bisphenols, and one participant repeated the experiment with extended monitoring. BPS data were compared with published data for isotope-labeled BPA () in the same participants.Results:At doses of 1.5 and applied to reconstructed human epidermis, the permeability coefficient of BPS (0.009 and , respectively) was significantly lower than for BPA (0.036 and , respectively), and metabolism of both bisphenols was negligible. In participants handling thermal receipts, the quantities of BPS and on hands was significantly correlated with maximum urinary event flux (), but the slope was lower for BPS than BPA ( and 1.1, respectively). As a proportion of total urinary bisphenol, free BPS [: ] was higher than for free BPA (). Postexposure maximum urinary BPS concentrations (0.93 to ; ) were in the 93–98th percentile range of BPS in background Canadians (; ).Conclusion:Both the in vitro and human studies suggested lower percutaneous absorption of BPS compared with BPA, but a lower biotransformation efficiency of BPS should also be considered in its evaluation as a BPA substitute. https://doi.org/10.1289/EHP5044

Determination of Bisphenol A (BPA) in Commercially Packaged Ready-to-Consume Carbonated and Noncarbonated Water and Nonalcoholic Beverages: A Single-Laboratory Validation Study, First Action 2017.15.

Background: Bisphenol A (BPA) is an endocrine-disrupting compound that could migrate to beverages from packaging materials. AOAC INTERNATIONAL issued a call for methods for determination of free BPA in beverages based on the AOAC Standard Method Performance Requirement (SMPR®) 2017.018. Objective: The objective of the single-laboratory validation (SLV) study was to validate a method for the analysis of BPA in relevant beverages and evaluate its performance characteristics against the AOAC SMPR 2017.18. Methods: The analytical method involves extraction of a beverage sample (10 mL) using 10 mL 1% acetic acid in acetonitrile after the addition of isotopically labeled internal standard. Sodium chloride is added to salt out BPA into the acetonitrile phase. After centrifugation, a freeze-out step is used to remove coextracted lipids. An aliquot of the supernatant upper layer is then analyzed using high-pressure LC coupled to tandem mass spectrometry in electrospray negative ionization mode. Results: Accuracy, repeatability, and intermediate precision were determined by spiking 10 representative nonalcoholic beverage matrixes at three concentration levels. Individual percent recoveries ranged between 76.5 and 113.2%, 86.2 and 114.8%, and 90.9 and 109.3% for the spike levels of 0.3, 1.5, and 20 μg/L, respectively. The repeatability and intermediate precision results were in the range of 0.2-11.3% and 1.8-11.1%, respectively. The LOD was estimated at ≤0.1 μg/L and LOQ was validated at 0.3 μg/L. Conclusions: The validated method performance characteristics met the requirements stated in the AOAC SMPR 2017.018. This method was approved AOAC First Action Official MethodsSM 2017.15. Highlights: SLV study evaluating free BPA at three concentration levels (0.3, 1.5, and 20 μg/L) in 10 types of commercially packaged nonalcoholic beverages (as recommended for the method validation in the AOAC SMPR 2017.018). Validated method performance characteristics (LOD, LOQ, analytical range, accuracy, and precision) met the AOAC SMPR 2017.018. Method approved as the AOAC First Action Official Method 2017.15.

Free bisphenol A (BPA), BPA-Glucuronide (BPA-G), and total BPA concentrations in maternal serum and urine during pregnancy and umbilical cord blood at delivery

Abstract While adult exposure to total bisphenol A (BPA) has been well documented, developmental exposure to BPA and fetal exposure to the bioactive form (free BPA) remains poorly defined. Therefore, pregnant women (n = 199) between 28 and 35 weeks of pregnancy were invited to participate in this study. Maternal serum free of hemolysis (n = 189) and urine (n = 112) were collected at third trimester and delivery along with umbilical cord blood (UCB) at delivery. Free BPA, BPA mono-glucuronide (BPA-G) and total BPA concentrations were measured using gas chromatography coupled with tandem mass spectrometry. Circulating concentrations of free BPA were quantifiable above the method detection limit (MDL = 0.026 ng/mL) in approximately 34% of serum samples in the third trimester and 21% of samples at delivery whereas BPA-G and total BPA were quantified in 43 and 70% of third trimester and delivery samples, respectively. The geometric mean of free BPA, BPA-G and total BPA concentrations in maternal serum during the third trimester and at delivery were 0.62 ng/L and

Risk characterization of bisphenol-A in the Slovenian population starting from human biomonitoring data

The current study aims to characterize exposure and risk associated to bisphenol-A (BPA) exposure in Slovenia, starting from biomonitoring data. Based on the urinary data, daily intake for the individuals was back-calculated using a physiology based biokinetic (PBBK) model properly parameterized for BPA, coupled with an exposure reconstruction algorithm. Re-running the PBBK model in forward mode allowed the estimation of biologically effective dose (free plasma BPA) and the respective daily area under the curve (AUC). Finally, risk characterization ratio was derived using both external and internal dose metrics. The urinary BPA levels were found low, with GM of 0.79, 1.51 and 0.20 μg/g creatinine for mothers, children and fathers respectively, similar to the levels of other European countries. Based on the above and accounting for the dynamics of exposure and biokinetics, daily intake was estimated, median exposure levels have been estimated equal to 0.019, 0.035 and 0.005 μg/kg_bw/d for mothers, fathers and children respectively. The highest estimated intake level was found in a child, equal to 0.87 μg/kg_bw/d, while the maximum intake for mothers and fathers were 0.7 and 0.8 μg/kg_bw/d respectively. The respective RCR levels using the EFSA t-TDI of 4 μg/kg_bw/d were 2 magnitudes of order lower below 1, independently of the selected method. It has to be noted that had daily intake been estimated solely based on the urinary concentrations mass balance, the estimated intake would be lower, as a result of the oversimplification on exposure and elimination time dynamics. This highlights the importance for using PBBK modelling based exposure reconstruction schemes for rapidly metabolized and excreted compounds such as BPA, as well as the study design of efficient sampling for rapidly metabolized compounds.

Exposure and dietary sources of bisphenol A (BPA) and BPA-alternatives among mothers in the APrON cohort study

Diet is regarded as the main source of bisphenol A (BPA) exposure, but comparatively little is known about dietary sources of BPA-alternatives. Here we measured exposure of BPA and BPA-alternatives among pregnant women in Canada, estimated their 24-h intakes and examined the importance of various dietary sources. Free and total BPA, bisphenol S (BPS) and bisphenol F (BPF) were measured in 467 second trimester maternal urine samples, and in 455 paired samples collected at three months postpartum. Linear regression was used to evaluate associations between urinary concentrations of bisphenols and 24-h dietary recall data. The geometric means of total BPA in second trimester and postpartum urine (1.2 and 0.95 ng/mL, respectively) were 5–7 times higher than corresponding total BPS (0.16 and 0.17 ng/mL). The detection frequency of BPF was only 9% (i.e. >1.0 ng/mL). However, at both time points 95th percentiles of total BPF (7.3 and 4.2 ng/mL, respectively) were similar to total BPA (8.2 and 5.0 ng/mL). Free BPS and BPF were detected in <2% of samples, but were detectable when total BPS or BPF concentrations were highest, always at <1% of the total concentration. The tolerable daily intake for total BPA (i.e. 18 nmol/kg BW/d) was not exceeded, but for BPS the estimated 24-h intake was as high as 14 nmol/kg BW/d (95th percentile: 0.12 nmol/kg BW/d), and for BPF was even higher among the highest centile of exposure (maximum and 95th percentile: 30, 0.81 nmol/kg BW/d). Canned food consumption was associated with higher total BPA, but was not associated with BPS. For BPF, mustard consumption may be an important exposure source, particularly among the highest exposed. Relatively high exposure to BPS and BPF in a minority of pregnant women highlights the need to better understand the associated health risks and exposure sources of BPA-alternatives.

Evaluation of Bisphenol A influence on endocannabinoid system in pregnant women

Bisphenol A (BPA) is a synthetic chemical widely used in the industry, which may potentially evoke negative effects on human health, especially on reproductive processes and fetal development. BPA has been reported to act on estrogen, estrogen-related, androgen, thyroid hormone, pregnane X, peroxisome proliferation-activated, and aryl hydrocarbon receptors. However, other potential mechanisms of BPA action on pregnancy cannot be excluded. Comprehensive evaluation of BPA effect on pregnant women can be performed by use of metabolomics. In the present study LC-MS-based plasma metabolomics was performed in the group of pregnant women with known concentrations of free, conjugated and total BPA. Significant positive correlations were observed between several endocannabinoids (fatty acid amides) and free (r = 0.307–0.557, p-value = 0.05–0.00002) and total (r = 0.413–0.519, p-value = 0.008–0.00006) BPA concentrations. Palmitoleamide was positively correlated with conjugated (r = 0.348, p-value = 0.05) while lysophosphatidylethanolamine 18:0 with free (r = 0.519, p-value = 0.00006) BPA concentration. The docking calculations of BPA and fatty acid amide hydrolase (enzyme degrading endocannabinoids, FAAH) indicated that it can act as a competitive inhibitor by blocking FAAH catalytic residues. In vitro study showed that BPA moderately inhibits FAAH activity (15% decrease for 200 ng mL-1 and almost 50% for 200 μg mL-1 of BPA). In the present study for the first time inhibitory potential of BPA on FAAH hydrolase is reported. Inhibition of FAAH may lead to a rise of plasma endocannabinoids level. BPA exposure and increased level of endocannabinoids are miscarriage risk factors. Based on obtained results it can be hypothesized that BPA may induce adverse pregnancy outcomes by acting on endocannabinoid system.

Exposure to bisphenol A during maternal pregnancy and the emotional and behavioral impact on their preschool children

Objective: To explore the long-term effects of maternal pregnancy bisphenol A (BPA) exposure on emotional and behavioral problems appeared in their preschool children. Methods: The study sample was a subset of the China-Anhui Birth Cohort Study (C-ABCS). A unified questionnaire was used to collect basic information on both pregnant women and their children. Free BPA concentration in maternal serum was determined by high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS). The parent-report version of the Strengths and Difficulties Questionnaire (SDQ) was used to estimate the emotional and behavioral problems in preschool children. A total of 1 713 pairs of mothers and children were included in this study. Association between BPA exposure during pregnancy and the emotional and behavioral problems in preschool children was evaluated with multinomial logistic regression model. Results: Prevalence rates in 1 713 preschool children appeared as: 6.48% of emotional problems, 8.11% for conduct problems, 8.35% for hyperactivity/inattention, 2.86% for peer problems, 11.38% for prosocial behaviors and 7.94% for total difficulties. Subjects were divided according to the degrees of exposure and the results showed as: low exposure group (≤0.120 ng/ml), medium exposure group (0.120<BPA<0.400 ng/ml) and high exposure group (≥0.400 ng/ml) according to the serum BPA concentration in tertile. Results from the multivariate logistic regression analysis showed that high level of maternal BPA exposure appeared a risk factor on children's abnormal conducts (OR=1.876, 95% CI: 1.161-3.029), more obvious in boys (OR=2.291, 95%CI: 1.126-4.661). Conclusion: Maternal exposure to high level of BPA during pregnancy might increase the detrimental effects of abnormal conducts in their preschool children, more obviously seen in boys.

A highly sensitive and quantitative detection method for bisphenol A (BPA) by competitive immunoassay based on surface-enhanced Raman spectroscopy

PurposeIn this study, a highly sensitive and quantitative analysis method using surface-enhanced Raman scattering (SERS)-labeled immunoassay is adopted for bisphenol A bisphenol A (BPA) detection in water samples.Design/methodology/approachPrimarily, an excellent SERS immuno-nanoprobe is prepared, which relays on Au/Ag core-shell nanoparticles tagged 4-mercaptobenzoic acid (4MBA) and labeled with specific antibody against BPA. Second, the coating antigen of 4,4-Bis(4-hydroxyphenol) valeric acid (BVA) coupling poly-L-lysine (PLL) conjugate (BVA-PLL) is fastened on the substrate. Based on competitive immunoassay, the antibody labeled on SERS immuno-nanoprobe will bind with the free BPA and BVA-PLL competitively.FindingsA calibration curve was obtained by plotting the intensity of SERS signal of 4MBA at 1007 cm−1 versus the concentration of BPA. The results indicated that the limit of detection (LOD) for BPA is 1 ng/mL and present a great capacity for higher sensitivity. Furthermore, the method was able to quantitatively detect BPA in water samples, which was validated by high performance liquid chromatography (HPLC).Originality/valueThe method was developed based on competitive immunoassay, and the conjugate (BVA-PLL) was chosen as the coating antigen. Au/Ag core-shell nanoparticles played as the SERS active substrate and were labeled with Raman reporter. The value of this paper is supplying a wide potential for analysis of target analytes in the environmental monitoring and food safety.