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Determination of bisphenol A and bisphenol S concentrations and assessment of estrogen- and anti-androgen-like activities in thermal paper receipts from Brazil, France, and Spain
Abstract
Bisphenol A (BPA) is a high-production-volume chemical with endocrine disrupting properties commonly used as color developer in thermal paper. Concerns about the potential hazards of human BPA exposure have led to the increasing utilization of alternatives such as bisphenol S (BPS) and bisphenol F (BPF). This study was designed to assess: (i) BPA, BPS, and BPF concentrations in 112 thermal paper receipts from Brazil, France, and Spain by liquid chromatography coupled to mass spectrometry (LC-MS); and (ii) hormone-like activities of these receipts using two receptor-specific bioassays, the E-Screen for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity. BPA was present in 95.3% of receipts from Spain, 90.9% of those from Brazil, and 51.1% of those from France at concentrations up to 20.27 mg/g of paper. Only two samples from Brazil, two from Spain, and ten from France had a BPS concentration ranging from 6.46 to 13.29 mg/g; no BPA or BPS was detected in 27.7% of French samples. No BPF was detected in any receipt. Estrogenic activity was observed in all samples from Brazil and Spain and in 74.5% of those from France. Anti-androgenic activity was observed in > 90% of samples from Brazil and Spain and in 53.2% of those from France. Only 25.5% of French samples were negative for both estrogenic and anti-androgenic activity. Estrogenic and anti-androgenic activities per gram of paper were up to 1.411 µM estradiol (E2) equivalent units (E2eq) and up to 359.5 mM procymidone equivalent units (Proceq), respectively. BPA but not BPS concentrations were positively correlated with both estrogenic and anti-androgenic activities. BPA still dominates the thermal paper market in Brazil and Spain, and BPS appears to be one of the main alternatives in France. There is an urgent need to evaluate the safety of alternatives proposed to replace BPA as developer in thermal printing. The large proportion of samples with hormonal activity calls for the adoption of preventive measures.
... Bisphenol A (BPA) is a synthetic high production monomer used in polycarbonate plastics and epoXy resins in a wide range of consumer products. These include for instance canned food and beverages, plastic bottles, food containers, toys, thermal receipts, and medical equipment among many other applications (Calafat et al., 2009;Cao et al., 2009;Carwile et al., 2009;Ehrlich et al., 2014;Fleisch et al., 2010;Iribarne-Durán et al., 2019;Molina-Molina et al., 2019;Vandenberg et al., 2007). More recently, BPA has even been detected in infants' socks, highlighting the novel role of textiles as potential source of bisphenol exposure (Freire et al., 2019). ...
... These include for instance canned food and beverages, plastic bottles, food containers, toys, thermal receipts, and medical equipment among many other applications (Calafat et al., 2009;Cao et al., 2009;Carwile et al., 2009;Ehrlich et al., 2014;Fleisch et al., 2010;Iribarne-Durán et al., 2019;Molina-Molina et al., 2019;Vandenberg et al., 2007). More recently, BPA has even been detected in infants' socks, highlighting the novel role of textiles as potential source of bisphenol exposure (Freire et al., 2019). Although diet is one of the predominant sources of BPA exposure in the general population due to the leaching of BPA from packaging materials and can liners into food and beverages (Buckley et al., 2019;Vandenberg et al., 2010), other sources and routes also contribute to human exposure (Freire et al., 2019;Molina-Molina et al., 2019;Morgan et al., 2018). ...
... More recently, BPA has even been detected in infants' socks, highlighting the novel role of textiles as potential source of bisphenol exposure (Freire et al., 2019). Although diet is one of the predominant sources of BPA exposure in the general population due to the leaching of BPA from packaging materials and can liners into food and beverages (Buckley et al., 2019;Vandenberg et al., 2010), other sources and routes also contribute to human exposure (Freire et al., 2019;Molina-Molina et al., 2019;Morgan et al., 2018). Indeed, non-dietary sources (e.g. ...
The main purpose of the present doctoral thesis was to select, describe, test, and implement effect biomarkers for the assessment of exposure-health associations during critical windows of human development, related to cognitive and behavioral alterations. For this goal, the following specific objectives were proposed: Objective 1: To identify and prioritize existing biomarkers of effect for BPA, metals, pesticides, and complex mixtures of chemicals. Objective 2: To provide relevant mechanistic and adverse outcome pathway (AOP) information in order to cover knowledge gaps and better interpret effect biomarker data. Objective 3: To investigate the effects of chemical exposure with cognitive domains, intelligence quotient (IQ), and behavioral function among Spanish adolescent males from the INMA-Granada cohort.
El objetivo principal de la presente tesis doctoral fue seleccionar, describir, probar e implementar biomarcadores de efecto para la evaluación de asociaciones exposiciónsalud durante ventanas críticas del desarrollo humano, relacionadas con alteraciones cognitivas y conductuales. Para este fin, se propusieron los siguientes objetivos específicos: Objetivo 1: Identificar y priorizar los biomarcadores de efecto existentes para BPA, metales, pesticidas y mezclas complejas de productos químicos. Objetivo 2: Proporcionar información relevante sobre mecanismos y vías del efecto adverso (AOP) para cubrir las lagunas de conocimiento y mejorar la interpretación de los biomarcadores de efecto. Objetivo 3: Investigar los efectos de la exposición a contaminantes ambientales sobre la función cognitiva, el cociente intelectual (CI) y la función conductual en adolescentes varones españoles de la cohorte INMA-Granada.
... Businesses such as restaurant, banks, movie theaters, and other stores generally use thermal printed receipts and tickets that thermal receipt papers are prepared by a color developer, like BPA which consists of acidic compound being able to promote the ring-opening reaction of fluoran dyes (Gontani et al. 2017;Olaon 2018). Due to the wide use of BPA in consumer products, the releases of BPA to environment and human are an inevitable and it is gaining significant public attention because of its adverse effects, especially significant negative impacts on reproductive abilities as an endocrine disruptor even at low concentrations (U.S. Environmental Protection Agency 2010; Kinch et al. 2015;Michałowicz 2014;Molina-Molina et al. 2019;Rubin 2011;Wu et al. 2018). As a result of BPA concern increases in globally, Canada was the first country in the world to ban the use of BPA in baby bottles and to restrict BPA in all food and beverage stored in cans or reusable plastic containers since 2010; unfortunately, it has still been reported about the 9 out of 10 Canadians have BPA in their bodies according to the latest survey results of Government of Canada due to the increased daily exposure of BPA via thermal paper receipts (Health Canada 2017; Canada Environmental Defence 2019). ...
... In particular, a study has reported the BPA concentration up to 42,600 µg/g in thermal paper cash register receipts (Babu et al. 2015). Recent scientific studies have demonstrated that BPA concentrations were at least 250-to 1000-fold higher than findings in food-related matrices (Molina-Molina et al. 2019) and those results may show another potential source as a major contributor to our daily exposure to BPA (Biedermann et al. 2010;Canada Environmental Defence 2019;Hormann et al. 2014). Consistently, a few studies have showed significant evidences that thermal receipt paper is one of the main sources of BPA for consumers or workers exposure due to the high levels of bioactive BPA in human serum and in urine (Hormann et al. 2014;Liu and Martin 2017). ...
... In addition, handling thermal receipt papers is directly shown to the human exposure of BPS (Liao et al. 2012b) that may be suspected to more easily penetrate skin than BPA and be potent in the same order or more of toxic effects than BPA (Eladak et al. 2015;Usman and Ahmad 2016). Similarity to several observations on the toxicity of BPA, it has been widely reported negative effects of BPS causing endocrine disruption, cytotoxicity, mutagenicity, and altering reproductive system (Björnsdotter et al. 2017;Eladak et al. 2015;Molina-Molina et al. 2019;Qiu et al. 2016;Ullah et al. 2016;Usman and Ahmad 2016;Wu et al. 2018;Žalmanová et al. 2016); however, some studies demonstrated that BPS was less potent estrogenic activity than BPA (Molina-Molina et al. 2013;Rochester and Bolden 2015). A recent study has investigated the presence of BPS in human urine samples to analyze the level of BPS in several countries and showed the concentrations ranging from 0.03 (n = 33) in Korea to 4.92 ng/mL (n = 130) in Saudi Arabia (Wu et al. 2018). ...
Bisphenol A (BPA) has been widely used in thermal receipt papers as a color developer; however, it has been substituted with alternative chemicals such as bisphenol S (BPS) due to the global restriction and regulations about the BPA in thermal receipt papers as a result of negative effects on human and environmental health. Little is known about the current changes of BPA or BPS in thermal receipt papers and its implication to human exposure. This study investigated the concentrations of BPA and BPS in thermal receipt papers collected from 14 business sites (n = 18); juice bar, bakery store, wholesale marts, bank, theater, clothe store, fast-food restaurant, coffee shop, cosmetic shop, bookstore, post office, and convenience store. Among 18 samples, BPA concentrations in 13 receipt samples from 9 public facilities were in range of 1.4 µg/g in a bookstore to 10,353.3 µg/g in a theater. In case of BPS, it was detected in 8 receipt samples from 8 public facilities in range of 4182.4 µg/g in a theater (before printing) to 11,946.3 µg/g in a post office (before printing). The estimated daily intake (EDI) of BPA and BPS by dermal absorption was evaluated on the basis of average concentrations in terms of contact frequencies between general individual and occupational individual. For the general individual, the EDI of BPA and BPS ranged from 0.08 ng/d in a bookstore to 602 ng/d in a theater (after printing) and ranged from 243 ng/d in a box office (before printing) and 694 ng/d in a post office, respectively. For the occupational individual, the EDI of BPA and BPS ranged from 6.1 ng/d in a bookstore to 45,123 ng/d in a theater (after printing) and ranged from 18,228 ng/d in a box office (before printing) to 52,065 ng/d in a post office, respectively. This study shows the current changes of BPA and BPS in thermal receipt papers and emerging concerns by BPS as much as concerns by BPA that needs further investigation about adverse effects on human health.
... BPA is a compound used as a monomer in the fabrication of polycarbonate plastics and in epoxy resins to coat the inner lining of cans and beverages among many other applications [1]. BPA is incorporated into the human body mainly through its presence in food packaging products [2], but alternatives routes exist including dust ingestion/inhalation, thermal receipts handling or even through clothing [3,4]. The main effects of BPA are thought to be attributable to its oestrogenic capacity [5]. ...
... The authors of that study suggested that oestrogens induce MN through interference with the kinase signalling that controls the spindle checkpoint [9]. In addition, it has been shown that the amount of copy number variations (CNVs) in chromosomes 3,4,11,22, and X was higher in BPAtreated neuronal progenitor cells (NPCs) than in control cells. It was suggested that BPA exposure could cause genomic instability in cultured NPCs through the reduction of DNA methyltransferase activity, leading to increased genetic instability [10]. ...
Objective
To assess the genetic and epigenetic effects promoted by Bisphenol A (BPA) exposure in adolescent males from the Spanish INMA-Granada birth cohort, and in human cells.
Methods
DNA methylation was analysed using MEDIP. Repeat number variation in genomic DNA was evaluated, along with the analysis of H3K4me3 by using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Analyses were performed with material extracted from whole blood of the adolescents, complemented by in vitro assessments of human (HeLa) cells exposed to 10 nM BPA, specifically, immunofluorescence evaluation of protein levels, gene expression analysis and ChIP‒qPCR analysis.
Results
Adolescents in the high urinary BPA levels group presented a higher level of Satellite A (SATA) repetitive region copy numbers compared to those in the low BPA group and a tendency towards increase in telomere length. We also observed decreased DNA methylation at the promoters of the imprinted genes H19, KCNQ1, and IGF2 ; at LINE1 retroelements; and at the ARID2, EGFR and ESRRA and TERT genes. Genome-wide sequencing revealed increased H3K4me3 occupancy at the promoters of genes encoding histone acetyltransferases, telomeric DNA binding factors and DNA repair genes. Results were supported in HeLa cells exposed to 10 nM BPA in vitro. In accordance with the data obtained in blood samples, we observed higher H3K4me3 occupancy and lower DNA methylation at some specific targets in HeLa cells. In exposed cells, changes in the expression of genes encoding DNA repair factors ( ATM, ARID2, TRP53 ) were observed, and increased expression of several genes encoding telomeric DNA binding factors ( SMG7, TERT, TEN1, UPF1, ZBTB48 ) were also found. Furthermore, an increase in ESR1/ERa was observed in the nuclei of HeLa cells along with increased binding of ESR1 to KAT5, KMT2E and TERF2IP promoters and decreased ESR1 binding at the RARA promoter. The DNA damage marker p53/TP53 was also increased.
Conclusion
In this pilot study, genome-wide analysis of histone trimethylation in adolescent males exposed to BPA revealed a global impact on the expression of genes encoding telomeric binding proteins and histone acetyltransferase factors with similar results in HeLa cells. Nevertheless, larger studies should confirm our findings.
... This has prompted many regulatory agencies, including Health Canada (2009), the US Food and Drug Administration (2010), and the European Union (EC regulation 321/2011) to restrict or even ban its production, import, and use, particularly in manufacturing polycarbonate infant feeding bottles, food and/or beverage packaging materials (Chen et al., 2016;Huang et al., 2012). The next step taken by European Commission (EC) was the prohibition of BPA usage in thermal paper products at concentrations above 0.02% from January 2020 onward, which consequently fueled the increased utilization of bisphenol S (BPS) in these products (European Commission, 2006;Molina-Molina et al., 2019). Tightening the regulations accompanied by the public concern stimulated the development and production of BPA alternatives to replace it in countless applications. ...
... In comparison to BPA, BPS is more resistant to biodegradation making it more amenable to accumulate and persist in the environment Wu et al., 2018). Traces of BPS have been detected in various environmental matrices, including surface water (Yamazaki et al., 2015;Zhao et al., 2019), sediments (Jin and Zhu, 2016), sewage sludge (Song et al., 2014;Yu et al., 2015), paper products (Goldinger et al., 2015;Molina-Molina et al., 2019;Rocha et al., 2015), indoor dust and air , some food items (Liao and Kannan, 2013;Yang et al., 2014b;Zhou et al., 2019), and consumer products (Liao et al., 2012b;Pivnenko et al., 2015). Moreover, there is a growing body of literature reporting the widespread occurrence of BPS in human urine (Ghayda et al., 2019;Liao et al., 2012a), serum Wan et al., 2018b), blood (Jin et al., 2018;Yang et al., 2014a), placental tissue and breast milk (Deceuninck et al., 2015;Dualde et al., 2019;Pan et al., 2020), maternal and cord sera blood serum (Liu et al., 2017), and semen (Ghayda et al., 2019), revealing an increasing risk of human exposure to this contaminant. ...
The normal brain development and function are delicately driven by an ever-changing milieu of steroid hormones arising from fetal, placental, and maternal origins. This reliance on the neuroendocrine system sets the stage for the exquisite sensitivity of the central nervous system to the adverse effects of endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA) is one of the most common EDCs which has been a particular focus of environmental concern for decades due to its widespread nature and formidable threat to human and animal health. The heightened regulatory actions and the scientific and public concern over the adverse health effects of BPA have led to its replacement with a suite of structurally similar but less known alternative chemicals. Bisphenol S (BPS) is the main substitute for BPA that is increasingly being used in a wide array of consumer and industrial products. Although it was considered to be a safe BPA alternative, mounting evidence points to the deleterious effects of BPS on a wide range of neuroendocrine functions in animals. In addition to its reproductive toxicity, recent experimental efforts indicate that BPS has a considerable potential to induce neurotoxicity and behavioral dysfunction. This review analyzes the current state of knowledge regarding the neurobehavioral effects of BPS and discusses its potential mode of actions on several aspects of the neuroendocrine system. We summarize the role of certain hormones and their signaling pathways in the regulation of brain and behavior and discuss how BPS induces neurotoxicity through interactions with these pathways. Finally, we review potential links between BPS exposure and aberrant neurobehavioral functions in animals and identify key knowledge gaps and hypotheses for future research.
... Bisphenol A (BPA) is a synthetic high production monomer used in polycarbonate plastics and epoxy resins in a wide range of consumer products. These include for instance canned food and beverages, plastic bottles, food containers, toys, thermal receipts, and medical equipment among many other applications (Calafat et al., 2009;Cao et al., 2009;Carwile et al., 2009;Ehrlich et al., 2014;Fleisch et al., 2010;Iribarne-Durán et al., 2019;Molina-Molina et al., 2019;Vandenberg et al., 2007). More recently, BPA has even been detected in infants' socks, highlighting the novel role of textiles as potential source of bisphenol exposure . ...
... More recently, BPA has even been detected in infants' socks, highlighting the novel role of textiles as potential source of bisphenol exposure . Although diet is one of the predominant sources of BPA exposure in the general population due to the leaching of BPA from packaging materials and can liners into food and beverages (Buckley et al., 2019;Vandenberg et al., 2010), other sources and routes also contribute to human exposure Molina-Molina et al., 2019;Morgan et al., 2018). Indeed, non-dietary sources (e.g. ...
Human biomonitoring (HBM) studies have demonstrated widespread and daily exposure to bisphenol A (BPA). Moreover, BPA structural analogues (e.g. BPS, BPF, BPAF), used as BPA replacements, are being increasingly detected in human biological matrices. BPA and some of its analogues are classified as endocrine disruptors suspected of contributing to adverse health outcomes such as altered reproduction and neurodevelopment, obesity, and metabolic disorders among other developmental and chronic impairments. One of the aims of the H2020 European Human Biomonitoring Initiative (HBM4EU) is the implementation of effect biomarkers at large scales in future HBM studies in a systematic and standardized way, in order to complement exposure data with mechanistically-based biomarkers of early adverse effects. This review aimed to identify and prioritize existing biomarkers of effect for BPA, as well as to provide relevant mechanistic and adverse outcome pathway (AOP) information in order to cover knowledge gaps and better interpret effect biomarker data. A comprehensive literature search was performed in PubMed to identify all the epidemiologic studies published in the last 10 years addressing the potential relationship between bisphenols exposure and alterations in biological parameters. A total of 5716 references were screened, out of which, 119 full-text articles were analyzed and tabulated in detail. This work provides first an overview of all epigenetics, gene transcription, oxidative stress, reproductive, glucocorticoid and thyroid hormones, metabolic and allergy/immune biomarkers previously studied. Then, promising effect biomarkers related to altered neurodevelopmental and reproductive outcomes including brain-derived neurotrophic factor (BDNF), kisspeptin (KiSS), and gene expression of nuclear receptors are prioritized, providing mechanistic insights based on in vitro, animal studies and AOP information. Finally, the potential of omics technologies for biomarker discovery and its implications for risk assessment are discussed. To the best of our knowledge, this is the first effort to comprehensively identify bisphenol-related biomarkers of effect for HBM purposes.
... Results showed that BPA concentrations in 22% of investigated samples exceeded the EU BPA limit of 0.2 mg/g. Another study conducted by Molina-Molina et al. [10] to explore BPA and Bisphenol S (BPS) concentrations in thermal papers (n = 112) from Brazil, France, and Spain revealed that BPA was found in 95.3% of receipts from Spain, 90.9% from Brazil, and 51.1% from France at concentrations up to 20.3 mg/g of paper. Wong et al. [11] investigated the presence of BPA in 30 thermal paper receipt samples collected from various stores in British Columbia, Canada; thirteen (13) samples contained BPA levels between 0.124-871.17 ...
Bisphenol A (BPA) is an industrial chemical that is widely used in various industrial applications. It has concerns in its use as a color developer in thermal paper receipts since it is identified as an endocrine disruptor and causes hormonal disturbances. In this study, thirty thermal paper receipt samples were randomly collected from various locations in Sharjah, United Arab Emirates and analyzed using high performance liquid chromatography–mass spectrometry. Sixty percent (60%) of receipt samples showed BPA levels above the acceptable limit (200 ng/mg) set by the European Union (EU) for thermal papers. On the other hand, 40% of the samples reported very low BPA levels (< 0.02 ng/mg). However, estimated weight adjusted daily intakes (EDI) ranged between 8.22 ×10 ⁻¹¹ and 0.000812 μg/kg bw/day for the general population, and between 7.89×10 ⁻⁹ and 0.0681 μg/kg bw/day for the occupationally exposed cashiers. Thus, all calculated EDIs were below the European Food Safety Authority Tolerable Daily Intake (4 μg/kg·bw/day) and the provisional Health Canada Tolerable Daily Intake (25 ug/kg bw/day) under varying paper-to-skin transfer coefficients and absorption fractions. Nevertheless, due to its health effects and recent legal restrictions by EU, the occurrence of co-exposure to dietary and non-dietary sources should be considered in the health risk assessment of Bisphenol A, mainly for people with frequent occupational exposure to thermal paper, and especially with the increased use of sanitizers. The current study is a first within the UAE context in relation to BPA in thermal paper receipts, thus its significance especially with the recent EU enforcement of BPA limits in paper receipts. The study highlights that proper policies as well as education and awareness may assist in limiting transdermal BPA exposure for the general and occupationally exposed populations.
... Among them, Bisphenol A (BPA), one of the plasticisers used in many daily consumer products, such as food packaging [5], paper products [6] and dental sealants [7], is now a recognised endocrine disruptor. Thus, in several countries, including Canada, France, and Switzerland, it has been banned from the food industry [8]. ...
Background
Ovarian granulosa cells (GC) are essential for the development and maturation of a proper oocyte. GC are sensitive to endocrine disruptors, including bisphenol A (BPA) and its analogue bisphenol S (BPS), plasticisers present in everyday consumer products. BPA exhibits greater binding affinity for the membrane oestrogen receptor (GPER) than for the nuclear oestrogen receptors (ERα and ERβ). Here, we analysed the effects of BPA and BPS on the steroidogenesis of ovine GC in vitro, as well as their early mechanisms of action, the ovine being a relevant model to study human reproductive impairment. Disruption of GC steroidogenesis might alter oocyte quality and consequently fertility rate. In addition, we compared the effects of a specific GPER agonist (G-1) and antagonist (G-15) to those of BPA and BPS. Ewe GC were cultured with BPA or BPS (10 or 50 µM) or G-1 (1 µM) and/or G-15 (10 µM) for 48 h to study steroidogenesis.
Results
Both BPA and BPS (10 µM) altered the secretion of progesterone, however, only BPS (10 µM) affected oestradiol secretion. RNA-seq was performed on GC after 1 h of culture with BPA or BPS (50 µM) or G-1 (10 µM), followed by real-time PCR analyses of differentially expressed genes after 12, 24 and 48 h of culture. The absence of induced GPER target genes showed that BPA and BPS did not activate GPER in GC after 1 h of treatment. These molecules exhibited mainly independent early mechanisms of action. Gene ontology analysis showed that after 1 h of treatment, BPA mainly disrupted the expression of the genes involved in metabolism and transcription, while BPS had a smaller effect and impaired cellular communications. BPA had a transient effect on the expression of CHAC1 (NOTCH signalling and oxidative balance), JUN (linked to MAPK pathway), NR4A1 (oestradiol secretion inhibition), ARRDC4 (endocytose of GPCR) and KLF10 (cell growth, differentiation and apoptosis), while expression changes were maintained over time for the genes LSMEM1 (linked to MAPK pathway), TXNIP (oxidative stress) and LIF (cell cycle regulation) after 12 and 48 h, respectively.
Conclusion
In conclusion, although they exhibited similar effects, BPA and BPS impaired different molecular pathways in GC in vitro. New investigations will be necessary to follow the temporal changes of these genes over time, as well as the biological processes involved.
... Recognising the observation that in some cases a banned chemical is substituted by another with similar or even unknown properties through regrettable substitution, HBM4EU tackled chemicals in groups (Blum et al., 2019;Buekers et al., 2021;Carvaillo et al., 2019;Lemke et al., 2021;Molina-Molina et al., 2019;Rugard et al., 2020;Sackmann et al., 2018;Trasande, 2017). Grouping of substances is advocated under the chemical strategy as a means of speeding up the risk assessment and management process, for example with per-and polyfluoroalkyl substances (PFAS). ...
One of the major goals of the European Human Biomonitoring Initiative (HBM4EU) was to bridge the gap between science and policy by consulting both policy makers and national scientists and generating evidence of the actual exposure of residents to chemicals and whether that exposure would be suggest a potential health risk. Residents' perspectives on chemical exposure and risk were also investigated. HBM4EU's research was designed to answer specific short-term and long-term policy questions at national and European levels, and for its results to directly support regulatory action on chemicals. A strategy was established to prioritise chemicals for analysis in human matrices, with a total of 18 substances/substance groups chosen to be investigated throughout the five-and a -half-year project. HBM4EU produced new evidence of human exposure levels, developed reference values for exposure, investigated determinants of exposure and derived health-based guidance values for those substances. In addition, HBM4EU promoted the use of human biomonitoring data in chemical risk assessment and developed innovative tools and methods linking chemicals to possible health impacts, such as effect biomarkers. Furthermore, HBM4EU advanced understand of effects from combined exposures and methods to identify emerging chemicals. With the aim of supporting policy implementation, science-to-policy workshops were organised, providing opportunities for joint reflection and dialogue on research results. I, and indicators were developed to assess temporal and spatial patterns in the exposure of European population. A sustainable human biomonitoring monitoring framework, producing comparable quality assured data would allow: the evaluation of time trends; the exploration of spatial trends: the evaluation of the influence of socio-economic conditions on chemical exposure. Therefore, such a framework should be included in the European Chemicals' Strategy for Sustainability and the data would support the Zero Pollution Action Plan.
... The compound called Bisphenol A (BPA) is defined as a synthetic high production monomer utilized in polycarbonate plastics and the resins of epoxy in consumer products. These products are used in canned beverages and food, bottles made of plastic, plastic food containers, thermal receipts, plastic medical equipment, and various plastic consumer products used in other applications (1)(2)(3)(4)(5)(6)(7). Regarding the health effect, BPA leads to hepatotoxic effects, mutagenic features for DNA, carcinogenic effects, and direct effects on the reproductive system (8)(9)(10). ...
Bisphenol A (BPA) is a synthetic compound with alterations in the liver, antioxidant enzymes, and reproductive hormones. The therapeutic potential of Moringa oleifera extract has recently been considered. The present study aimed to estimate the leaf extract of M. oleifera against hepatotoxicity induced by BPA. In total, 44 adult male rats were used in this study, and the experiment was conducted on 11 groups (4 animals per group). The rats were administrated (orally) with 5 and 10 mg/kg BPA and treated (orally) with 100, 200, 300, and 400 mg/kg of the aqueous extract of M. oleifera. After 28 days of challenge, liver enzymes, including aspartate transaminase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), as well as a pathological study using the liver tissue sections were determined. The findings showed a significant (P≤0.05) increase in the AST, ALT, and ALP in the BPA groups with different histological changes that included the sclerosis of the bile duct surrounded by fibrocytes and lymphocytes infiltration. After treatment with M. oleifera, the liver enzymes and tissue returned to a normal state and showed non-significant (P≤0.05) differences, compared to the control group. According to the results, it can be concluded that the aqueous extract of M. oleifera has a great potential to prevent and improve liver damage of BPA.
... Bisphenol A [2, 2-bis (4-hydroxyphenyl) propane] is a diphenylmethane derivate of two hydroxyphenol groups. It has been in use as an industrial plasticizer and a component of epoxy resin used in the manufacture of plastic infant feeding bottles, food containers, storage vessels, dinnerware, paints, and as a developer in thermal papers for the last many decades ( Ehrlich et al., 2014 ;Geens et al., 2012 ;Iribarne-Durán et al., 2019 ;Liao and Kannan, 2013 ;Molina-Molina et al., 2019 ;Xue et al., 2018 ). However, the toxicity issues of BPA are a matter of concern from a long time. ...
Bisphenol A (BPA) is an industrial chemical used in plastics, resin-based food packaging, and thermal papers etc. BPA is reported as an endocrine disruptor and implicated in many disorders including infertility, diabetes, neurological, obesity, and cancer. The populace comes in contact with BPA through oral, inhalation, and dermal routes as it leaches out of the finished products. The present study is aimed to determine the levels of absorption through the skin as well as the penetration rate of BPA into the circulation following dermal exposure in Swiss albino mice. We used ultra-performance liquid chromatography with fluorescence detector to quantify the unconjugated BPA in the serum and skin samples collected at 6 h, 12 h, 24 h, 48 h, 72 h, and 168 h from Swiss albino mice exposed to 250 mg/kg bw BPA through a single dermal application. Mean serum unconjugated BPA Cmax of 745 ng/mL was observed at 24 h. Unconjugated BPA appeared in serum 562 ng/mL within 6 h and was detected till 72 h at concentrations near the LOD (3.9 ng/mL) while those in skin samples unconjugated BPA is detectable at all the time points and displayed a gradual decrease in BPA concentration with progressing duration post dermal exposure. Our study showed a slow absorption rate of BPA through the skin into the circulation and greater bioavailability of unconjugated BPA as it bypasses the first-pass metabolism, resulting in prolonged retention in the system with delayed elimination on dermal exposure.
... Results showed that BPA concentrations in 22% of investigated samples exceeded the EU BPA limit of 0.2 mg/g. Another study conducted by Molina-Molina et al. [10] to explore BPA and Bisphenol S (BPS) concentrations in thermal papers (n = 112) from Brazil, France, and Spain revealed that BPA was found in 95.3% of receipts from Spain, 90.9% from Brazil, and 51.1% from France at concentrations up to 20.3 mg/g of paper. Wong et al. [11] investigated the presence of BPA in 30 thermal paper receipt samples collected from various stores in British Columbia, Canada; thirteen (13) samples contained BPA levels between 0.124-871.17 ...
... Therefore, development of efficient, sensitive and rapid high-throughput screening methods for detecting endocrine-disrupting effects of pollutants has become an essential link in the research field of EDCs [13]. To date, the existing screening methods used to evaluate effects on estrogen and thyroxine of EDCs include E-screen based on MCF-7 mammalian cell proliferation and T-screen relying on GH3 mammalian cell proliferation experiments [14,15]. In addition, H295R cells were applied as an ideal in vitro model to evaluate the effect of EDCs on the synthesis of steroid hormones through non-receptor pathways [16,17]. ...
Bisphenol A (BPA) and its analogues have been classified as endocrine disruptors via binding to nuclear receptors. Two novel bioassays, BLYrARS and BLYrPRS, were developed for rapid detection of agonistic and antagonistic activities of BPA and five of its analogues binding rat androgen receptor (rAR) and rat progesterone receptor (rPR). The reporter bioassay was based on two autonomously bioluminescent strains of the yeast Saccharomyces cerevisiae, recombined with a bacterial luciferase reporter gene cassette (lux) that can produce autofluorescence, regulated by the corresponding hormone response element acting as the responsive promoter. The bioluminescent signal is autonomous and continuous without cell lysis or addition of exogenous reagents. The AR agonist R1881 could be detected at 4 h with a half-maximal effective concentration (EC50) of ~9.4 nM. The PR agonist progesterone could be determined at 4 h with an EC50 of ~2.74 nM. None of the sixteen bisphenols presented agonistic activities against rAR and rPR. However, thirteen BPs were rAR antagonists and eleven BPs acted as rPR antagonists with different potency. The BLYrARS and BLYrPRS bioassay characterized by automated signal acquisition without additional manipulations or cost can be applied for simple and rapid detection of agonistic and antagonistic activities of BPs and other compounds acting as agonists or antagonists of rAR and rPR. Based on data derived by use of this bioassay endocrine-disrupting activities of some BPA analogues are more potent than BPA.
... This substitution mostly involves the use of other bisphenols, which have a structure similar to that of BPA. One of the most widely used bisphenols is bisphenol S (BPS), in particular as a developer for thermal paper (Molina-Molina et al., 2019). Use of BPS has increased continually, even accelerating after the definitive ban on BPA in thermal paper, as shown by the 153% increase in a single year between 2018 and 2019 (ECHA, 2020). ...
The close structural analogy of bisphenol (BP) S with BPA, a recognized endocrine-disrupting chemical and a substance of very high concern in the European Union, highlights the need to assess the extent of similarities between the two compounds and carefully scrutinize BPS potential toxicity for human health. This analysis aimed to investigate human health toxicity data regarding BPS, to find a point of departure for the derivation of human guidance values.
A systematic and transparent methodology was applied to determine whether European or international reference values have been established for BPS. In the absence of such values, the scientific literature on human health effects was evaluated by focusing on human epidemiological and animal experimental studies. The results were analyzed by target organ/system: male and female reproduction, mammary gland, neurobehavior, and metabolism/obesity. Academic experimental studies were analyzed and compared to regulatory data including subchronic studies and an extended one-generation and reproduction study. In contrast to the regulatory studies, which were performed at dose levels in the mg/kg bw/day range, the academic dataset on specific target organs or systems showed adverse effects for BPS at much lower doses (0.5–10 μg/kg bw/day). A large disparity between the lowest-observed-adverse-effect levels (LOAELs) derived from regulatory and academic studies was observed for BPS, as for BPA. Toxicokinetic data on BPS from animal and human studies were also analyzed and showed a 100-fold higher oral bioavailability compared to BPA in a pig model. The similarities and differences between the two bisphenols, in particular the higher bioavailability of BPS in its active (non-conjugated) form and its potential impact on human health, are discussed. Based on the available experimental data, and for a better human protection, we propose to derive human reference values for exposure to BPS from the N(L)OAELs determined in academic studies.
... Bisphenol A (BPA) is a highly produced synthetic monomer used in polycarbonate plastics and epoxy resins. Among many consumer products, BPA is found in the inner lining of cans and tins (Cao et al., 2009;González et al., 2020;Kim et al., 2020), polycarbonate plastic bottles (Carwile et al., 2009), thermal receipts (Ehrlich et al., 2014Molina-Molina et al., 2019), medical equipment (Iribarne-Durán et al., 2019), and textiles . Human BPA exposure is ubiquitous and more than 90% of the European population still has detectable concentrations in their urine (Covaci et al., 2015;Tschersich et al., 2021), despite the fact that BPA analogues have been recently introduced as replacements (Wu et al., 2018). ...
Background
Bisphenol A (BPA) exposure has been linked to altered behavior in children. Within the European Human Biomonitoring Initiative (HBM4EU), an adverse outcome pathway (AOP) network was constructed supporting the mechanistic link between BPA exposure and brain-derived neurotrophic factor (BDNF).
Objective
To test this toxicologically-based hypothesis in the prospective INMA-Granada birth cohort (Spain).
Methods
BPA concentrations were quantified by LC-MS/MS in spot urine samples from boys aged 9–11 years, normalized by creatinine and log-2 transformed. At adolescence (15–17 years), blood and urine specimens were collected, and serum and urinary BDNF protein levels were measured using immunoassays. DNA methylation levels at 6 CpGs in Exon IV of the BDNF gene were also assessed in peripheral blood using bisulfite-pyrosequencing. Adolescent's behavior was parent-rated using the Child Behavior Checklist (CBCL/6-18) in 148 boys. Adjusted linear regression and mediation models were fit.
Results
Childhood urinary BPA concentrations were longitudinally and positively associated with thought problems (β = 0.76; 95% CI: 0.02, 1.49) and somatic complaints (β = 0.80; 95% CI: −0.16, 1.75) at adolescence. BPA concentrations were positively associated with BDNF DNA methylation at CpG6 (β = 0.21; 95% CI: 0.06, 0.36) and mean CpG methylation (β = 0.10; 95% CI: 0.01, 0.18), but not with total serum or urinary BDNF protein levels. When independent variables were categorized in tertiles, positive dose-response associations were observed between BPA-thought problems (p-trend = 0.08), BPA-CpG6 (p-trend ≤ 0.01), and CpG6-thought problems (p-trend ≤ 0.01). A significant mediated effect by CpG6 DNA methylation was observed (β = 0.23; 95% CI: 0.01, 0.57), accounting for up to 34% of the BPA-thought problems association.
Conclusions
In line with toxicological studies, BPA exposure was longitudinally associated with increased BDNF DNA methylation, supporting the biological plausibility of BPA-behavior relationships previously described in the epidemiological literature. Given its novelty and preliminary nature, this effect biomarker approach should be replicated in larger birth cohorts.
... Bisphenol A (BPA) is an ubiquitous environmental chemical pollutant with endocrine disruption and potential reproductive toxicity [1], which can be detected in body fluids and tissues (blood, urine, placenta, breast milk, etc.) due to its leaching from food packaging and can liners, indicating the internal exposure of fetuses to BPA [2][3][4]. China has become the world's largest producer and consumer of BPA, accounting for about 20% of the world's total production, while little is known about its neurotoxicity in the Chinese population [5]. ...
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.
... Parabens and bisphenols have been frequently reported in human urine (Moos et al. 2016;Zhang et al. 2013Zhang et al. , 2020bZhao et al. 2018), blood (Li et al. 2019;Zhang et al. 2020a), milk (Ranvir et al. 2015; Thomsen et al. 2010), and fat tissues (Wang et al. 2015a). The sources of human exposure to these chemicals have been reported as indoor dust (Liu et al. 2019;Wang et al. 2012;Zhang et al. 2020b), indoor air (Rudel et al. 2010), personal care products (Adeyemi et al. 2020;Guo and Kannan 2013;Guo et al. 2014), food (Gonzalez et al. 2020;Ji et al. 2014;Liao and Kannan 2014;Liao et al. 2013c), cloth (Lopez-Ramon et al. 2019;Luongo et al. 2016), and paper products (Castro et al. 2019;Molina-Molina et al. 2019;Neves et al. 2009), but other potential sources are still left unnoticed including pharmaceuticals, especially over-thecounter (OTC) medicines that are available easily to the patients. A recent study has reported that the concentrations of parabens in human urine were significantly increased during the first hour of administration of paraben-containing pharmaceuticals (Moos et al. 2016). ...
Pharmaceuticals, such as over-the-counter (OTC) medicines, may be an important source of human exposure to several endocrine disruptors, though unnoticed to date. In the present study, we investigated the presence of six parabens and nine bisphenol A (BPA) and its analogues in OTC medicines manufactured in China. Parabens and bisphenols were present in more than 90% of the samples. The total measured concentrations of parabens and bisphenols were in the range of non-detectable (ND) to 213 ng/g and ND to 415 ng/g, respectively. Regarding parabens, methyl paraben (MeP) was the predominant analog, accounting for 43 ± 36% of the total amount, followed by ethyl paraben (EtP) (39 ± 35%), and others (< 10%). Bisphenol F and BPA were the predominant bisphenols, accounting for 24 ± 28% and 22 ± 26% of the total amount, respectively. The median values of estimated daily intakes (EDIs) of parabens and bisphenols were the highest for infants (2.96 and 3.14 ng/kg_bw/day, respectively) and the lowest for adults (0.69 and 0.25 ng/kg_bw/day, respectively); moreover, the EDIs of parabens and bisphenols were higher in Chinese patent medicines than in western pediatric medicines. The hazard quotient (HQ) for sum of MeP and EtP (∑(MeP + EtP)) and BPA in three age groups were within the safe zone (HQ < 0.0004). Monte Carlo simulation was applied to predict the human exposure risk of parabens and bisphenols. The predicted ranges of EDIs of parabens and bisphenols were much wider, and the extreme predicted values were observed in all four age groups, which were higher than the acceptable daily intake. The extreme predicted values of ∑(MeP + EtP) and BPA were indicative of carcinogenic risk in toddlers. These results implied potential risks for the Chinese people existed. Considering the huge export of Chinese traditional medicines and western medicines worldwide, and easy access to OTC medicines for the general population, the presence of parabens, bisphenols, and other environmental contaminants in medicines still need to be monitored.
... Recent comparative investigations using different animal models such as C. elegans, zebrafish, and rodents proved that BPF and BPA analogues have greater or equivalent neuroendocrine disruptive effects comparable to BPA [14,88,[90][91][92]. Another study has shown that BPA, BPF, and BPS possess equivalent potential to activate human ESR1 and ESR2 [23,93], which are known to have a wide range of endocrine physiological networks [29] including upregulation of postsynaptic density protein, synaptophysin, and αamino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors expression in glutamatergic neurons [94]. A human post-mortem study using the hypothalamic and white matter of the brain from obese and normal weight individuals showed that low concentrations of BPF (2.2 ng/g) and BPA (1.2 ng/g) in the hypothalamus and BPF (2.3 ng/g), and BPA (1.0 ng/g) in white matter, were linked to their obese conditions [29]. ...
Bisphenol A (BPA) is considered as one of the most extensively synthesized and used chemicals for industrial and consumer products. Previous investigations have established that exposure to BPA has been linked to developmental, reproductive, cardiovascular, immune, and metabolic effects. Several jurisdictions have imposed restrictions and/or have banned the use of BPA in packaging material and other consumer goods. Hence, manufacturers have replaced BPA with its analogues that have a similar chemical structure. Some of these analogues have shown similar endocrine effects as BPA, while others have not been assessed. In this investigation, we compared the neurodevelopmental effects of BPA and its major replacement Bisphenol F (BPF) on rat fetal neural stem cells (rNSCs). rNSCs were exposed to cell-specific differentiation media with non-cytotoxic doses of BPA or BPF at the range of 0.05 M to 100 M concentrations and measured the degree of cell proliferation, differentiation, and morphometric parameters. Both of these compounds increased cell proliferation and impacted the differentiation rates of oligodendrocytes and neurons, in a concentration-dependent manner. Further, there were concentration-dependent decreases in the maturation of oligodendrocytes and neurons, with a concomitant increase in immature oligodendrocytes and neurons. In contrast, neither BPA nor BPF had any overall effect on cellular proliferation or the cytotoxicity of astrocytes. However, there was a concentration-dependent increase in astrocyte differentiation and morphological changes. Morphometric analysis for the astrocytes, oligodendrocytes, and neurons showed a reduction in the arborization. These data show that fetal rNSCs exposed to either BPA or BPF lead to comparable changes in the cellular differentiation, proliferation, and arborization processes.
... Both however appeared to have antiandrogenic properties (Pelch et al., 2019). Beside its antiandrogenic activity, BPA appears to disrupt the expression of the steroidogenic enzymes (Molina-Molina et al., 2019). Due to the differences in the study protocols and between the laboratories it is however difficult to compare the available data on the effects of BPA and its analogues on androgen receptors (ARs) and ERs. ...
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]: 0.14 ng/mL [0.10; 1.17] vs. 0.08 ng/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.
... Bisphenols are chemicals produced in large quantities in the manufacturing of polycarbonate plastics and epoxy resins, thermal paper and as internal coating in a lot of consumer products (Gingrich et al. 2019;Molina-Molina et al. 2019;Vandenberg et al. 2007Vandenberg et al. , 2009). In the last decades, one of the most widely used compounds of this group has been bisphenol A (BPA); however, concerns about its detrimental effects on human health have led to the prohibition or limitation of this compound (ECHA 2017;EU 2011EU , 2016USEPA 2014) and its replacement by structural analogues with similar physicochemical properties. ...
Among UV-filters, benzophenones are one of the most abundantly used and detected groups in the environment. Bisphenols are also one of the most widely used chemicals in plastics, but their demonstrated deleterious effects on several organisms and humans have led to the production of alternative analogues. However, few comparative studies on the ecotoxicological effects of these derivatives or analogues have been carried out. The present study aimed to investigate the effects of two benzophenones (BP-3 and BP-4) and two bisphenols (BPA and BPS) in a short-term exposure of the freshwater endobenthic bivalve Corbicula fluminea. Clams were exposed for 96 h to several concentrations of the four pollutants: BP-3 (0.63; 1.25; 2.5; 5 mg l −1), BP-4 (4.75; 9.5; 19; 38 mg l −1), BPA (3.75; 7.5; 15; 30 mg l −1), and BPS (2.5; 5; 10; 20 mg l −1). The comparative acute toxicity of these pollutants was evaluated by the analysis of the post-exposure filtering capacity of clams, lipid peroxidation (LP) levels and the activity of the antioxidant enzymes catalase (CAT) and glutathione reductase (GR). After the exposure period, except for BP-4, the chemicals tested seemed to be detected by clams and provoked valve closure, decreasing filter-feeding in a concentration-dependent manner. Furthermore, C. fluminea exposed to the highest concentrations of BP-3, BP-4 and BPA showed a significant increase in LP, CAT and GR activities with respect to their controls. BP-3 and BPA were the most toxic compounds showing significant differences in all the parameters analysed at the highest concentrations assayed. However, clams exposed to BPS showed only significant alterations in filtration parameters and in GR activity, in the two highest concentrations tested, indicating that this compound was the least toxic to clams. Obtained results highlight the importance of investigating the effects that emerging pollutants have on aquatic organisms.
... bisphenol A, phthalates, and/or perfluorinated chemicals, to which the majority of the human population is continuously exposed (Boberg et al., 2018;Rosenmai et al., 2016). However, employing classical approaches such as targeted analysis to characterize the chemical composition of FCMs and successively testing single compounds for biological activities is an inadequate and cumbersome strategy (Lopez-Espinosa et al., 2007;Molina-Molina et al., 2019). This procedure will neither provide information on compounds that are not explicitly known to be present in the FCMs, nor account for the total, integrated biological activities of all the compounds present in the product (i.e. the mixture effect). ...
Humans are exposed to a large number of chemicals from sources such as the environment, food, and consumer products. There is growing concern that human exposure to chemical mixtures, especially during critical periods of development, increases the risk of adverse health effects in newborns or later in life. Historically, the one-chemical-at-a-time approach has been applied both for exposure assessment and hazard characterisation, leading to insufficient knowledge about human health effects caused by exposure to mixtures of chemicals that have the same target. To circumvent this challenge researchers can apply in vitro assays to analyse both exposure to and human health effects of chemical mixtures in biological samples. The advantages of using in vitro assays are: (i) that an integrated effect is measured, taking combined mixture effects into account and (ii) that in vitro assays can reduce complexity in identification of Chemicals of Emerging Concern (CECs) in human tissues.
We have reviewed the state-of-the-art on the use of receptor-based in vitro assays to assess human exposure to chemical mixtures and related health impacts. A total of 43 studies were identified, in which endpoints for the arylhydrocarbon receptor (AhR), the estrogen receptor (ER), and the androgen receptor (AR) were used. The majority of studies reported biological activities that could be associated with breast cancer incidence, male reproductive health effects, developmental toxicities, human demographic characteristics or lifestyle factors such as dietary patterns. A few studies used the bioactivities to check the coverage of the chemical analyses of the human samples, whereas in vitro assays have so far not regularly been used for identifying CECs in human samples, but rather in environmental matrices or food packaging materials.
A huge field of novel applications using receptor-based in vitro assays for mixture toxicity assessment on human samples and effect-directed analysis (EDA) using high resolution mass spectrometry (HRMS) for identification of toxic compounds waits for exploration. In the future this could lead to a paradigm shift in the way we unravel adverse human health effects caused by chemical mixtures.
... The results showed that BPA exposure could decrease the spinous synaptic density of hippocampus in ovariectomized female rats, but BPA combined with estrogen could not. Studies showed that BPA concentrations were positively correlated with both estrogenic and anti-androgenic activities and BPA embryonic exposure increased the expression of estrogen receptor [23,24]. In our opinion all of these were inferred that the effect of BPA was related to the content of estrogen. ...
Bisphenol A (BPA) is widely used in industrial production. It is closely related to the growth and development of the nervous system, and can enter the fetal circulation through the placental barrier, and can be secreted through breast milk. The development of nervous system is very important in fetus and neonatal period. The purpose of this study is to investigate the effects of different doses of BPA on learning and memory function of nervous system in rats. Pregnant rats were randomly divided into three treatment groups (control group, 5 mg/kg/d, 50 mg/kg/d). All animals received BPA from the discovery of pregnancy to 21 days after birth. Results had shown that after high concentration BPA exposure, the increase of PS amplitude and f-EPSP slope in hippocampal CA1 area of male offspring was lower than that of control group. High concentration of BPA could inhibit Nestin, Cyclin D1, bcl-2 and Rac1 in male offspring rats and the expression of bax and RhoA was promoted by BPA. In summary, our study indicated that BPA exposure during pregnancy and lactation could impair the hippocampal function of male offspring by affecting the growth and apoptosis of hippocampal neurons, which might be due to the abnormal regulation of RhoA and Rac1.
... BPA will therefore need to be replaced by alternatives. As a substitute for BPA, a structural analogue, bisphenol S (BPS), is already commonly used in thermal papers used for till receipts (Liao et al., 2012;Goldinger et al., 2015;Rocha et al., 2015;Bj€ ornsdotter et al., 2017aBj€ ornsdotter et al., , 2017bEckardt and Simat, 2017;Molina-Molina et al., 2019;Vervliet et al., 2019). Because of its physicochemical properties and its low cost compared to other current potential alternatives, BPS should quickly replace BPA. ...
Bisphenol A (BPA) is widely used in industrial products. Due to the toxicity of this compound, and to comply with restrictions and regulations, manufacturers have progressively replaced it by substitutes. One of the main substitutes used is bisphenol S (BPS). Despite increasing use in many products, the effects of BPS on human health have been little investigated, and studies on percutaneous BPS absorption and particularly toxicokinetic data are lacking. However, the endocrine-disrupting activity of BPA and BPS appears comparable. Dermal contact is a significant source of occupational exposure and is the main route during handling of bisphenol-containing receipts by cashiers. Here, percutaneous BPS absorption was investigated and compared to that of BPA. Experiments were performed according to OECD guidelines. Test compounds dissolved in a vehicle - acetone, artificial sebum or water – were applied in vitro to fresh human skin samples in static Franz diffusion cells. Flux, cumulative absorbed dose and distribution of dose recovered were measured. BPA absorption was vehicle-dependent - ranging from 3% with sebum to 41% with water. BPS absorption was much lower than BPA absorption whatever the vehicle tested (less than 1% of applied dose). However, depending on the vehicle 20%–47% of the applied BPS dose remained in the skin, and was consequently potentially absorbable. Both BPA and BPS were mainly absorbed without biotransformation. Taken together, these results indicate that workers may be exposed to BPS through skin when handling products containing it. This exposure is of concern as its toxicity is currently incompletely understood.
... Moreover, it has been demonstrated that acute or chronic exposure to BPA, impaired functional recovery after myocardial infarction due to a reduced ability to induce macrophage polarization from proinflammatory to a reparative state 12,13 . Indeed, there is an increasing concern about BPA higher bioaccumulation in developing organisms and special vulnerable populations such as patients exposed to BPA leaching from medical devices, people handling thermal paper receipts, or plastic industry workers 4,13,14 . ...
Epidemiological studies link long term exposure to xenoestrogen Bisphenol-A to adverse cardiovascular effects. Our previous results show that BPA induces hypertension by a mechanism involving CamKII activation and increased redox stress caused by eNOS uncoupling. Recently, CamKII sustained activation has been recognized as a central mediator of programmed cell death in cardiovascular diseases, including necroptosis. However, the role of necroptosis in cardiac response to BPA had not yet been explored. Mice exposed to BPA for 16 weeks showed altered heart function, electrical conduction, and increased blood pressure. Besides, a stress test showed ST-segment depression, indicative of cardiac ischemia. The hearts exhibited cardiac hypertrophy and reduced vascularization, interstitial edema, and large hemorrhagic foci accompanied by fibrinogen deposits. BPA initiated a cardiac inflammatory response, up-regulation of M1 macrophage polarization, and increased oxidative stress, coinciding with the increased expression of CamKII and the necroptotic effector RIP3. In addition, cell death was especially evident in coronary endothelial cells within hemorrhagic areas, and Evans blue extravasation indicated a vascular leak in response to Bisphenol-A. Consistent with the in vivo findings, BPA increased the necroptosis/apoptosis ratio, the expression of RIP3, and CamKII activation in endothelial cells. Necrostatin-1, an inhibitor of necroptosis, alleviated BPA induced cardiac dysfunction and prevented the inflammatory and hemorrhagic response in mice. Mechanistically, silencing of RIP3 reversed BPA-induced necroptosis and CamKII activation in endothelial cells, while inhibition of CamKII activation by KN-93 had no effect on RIP3 expression but decreased necroptotic cell death suggesting that BPA induced necroptosis is mediated by a RIP 3/CamKII dependent pathway. Our results reveal a novel pathogenic role of BPA on the coronary circulation. BPA induces endothelial cell necroptosis, promotes the weakening of coronary vascular wall, which caused internal ventricular hemorrhages, delaying the reparative process and ultimately leading to cardiac dysfunction.
... However, most replacements are structural analogs such as bisphenol S (BPS), which are also hormonally active (Rochester and Bolden, 2015) and are suspected of having similar adverse effects in experimental animals (Carvaillo et al., 2019). BPA to BPS replacement is a concern in many countries (Kataria et al., 2017;Molina-Molina et al., 2019;Ye et al., 2015), with the speed of substitution being relatively faster in the United States market compared to other countries . Other phenolic EDCs such as parabens and triclosan are frequently used in personal care products, food additives, and pharmaceuticals to prevent microbial growth Giulivo et al., 2016), while benzophenone-3 is used as an ultraviolet filter in sunscreens, body lotions, and make-up, among other uses (Liao and Kannan, 2014). ...
Background
Phenol exposure during pregnancy has been associated with preterm birth, but the potential effect of preconception exposure in either parent is unknown. There is a growing body of evidence to suggest that the preconception period is a critical window of vulnerability for adverse pregnancy outcomes.
Objective
We examined whether maternal and paternal preconception urinary concentrations of select phenols were associated with the risk of preterm birth among couples attending fertility care.
Methods
The analysis included 417 female and 229 male participants of the Environment and Reproductive Health (EARTH) Study who gave birth to 418 singleton infants between 2005 and 2018 and for whom we had phenol biomarkers quantified in at least one urine sample collected before conception. Mothers and fathers provided an average of 4 and 3 urine samples during the preconception period, respectively. We calculated the geometric mean of bisphenol A (BPA), bisphenol S (BPS), benzophenone-3, triclosan, and the molar sum of parabens (ΣParabens) urinary concentrations to estimate each participant’s preconception exposure. Risk ratios (RRs) of preterm birth (live birth before 37 completed weeks’ gestation) were estimated using modified Poisson regression models adjusted for covariates.
Results
The mean (SD) gestational age among singletons was 39.3 (1.7) weeks with 8% born preterm. A natural log-unit increase in maternal preconception BPA (RR 1.94; 95% CI: 1.20, 3.14) and BPS (RR 2.42; 95% CI: 1.01, 5.77) concentration was associated with an increased risk of preterm birth. These associations remained after further adjustment for maternal prenatal and paternal preconception biomarker concentrations. Paternal preconception ΣParabens concentrations showed a possible elevated risk of preterm birth (RR 1.36; 95% CI: 0.94, 1.96). No consistent pattern of association was observed for benzophenone-3 or triclosan biomarkers in either parent.
Discussion
Maternal preconception urinary BPA and BPS concentrations, as well as paternal preconception urinary parabens concentrations were prospectively associated with a higher risk of preterm birth. Subfertile couples’ exposure to select phenols during the preconception period may be an unrecognized risk factor for adverse pregnancy outcomes.
... The global volume of BPA consumption was estimated at 7.7 million metric tons in 2015 and is expected to reach 10.6 million metric tons in 2022 [11]. The leaching of BPA from these materials into food is considered mainly responsible for human exposure to BPA [12], although there have been recent reports on exposure from other sources, including personal care products [13], clothes [14][15][16], and thermal paper [17]. It is suspected that human exposure to BPA may be associated with the development of estrogen-dependent diseases, given its xenoestrogenic properties [18,19]. ...
Aim: The aim of this study was to explore associations of urinary concentrations of bisphenols A (BPA), S (BPS), and F (BPF) and of thiobarbituric acid reactive substances (TBARS) with the risk of endometriosis in women of childbearing age. Methods: This case–control study enrolled 124 women between January 2018 and July 2019: 35 women with endometriosis (cases) and 89 women without endometriosis undergoing abdominal surgery for other reasons (controls). Endometriosis was diagnosed (cases) or ruled out (controls) by laparoscopic inspection of the pelvis and the biopsy of suspected lesions (histological diagnosis). Fasting urine samples were collected before surgery to determine concentrations of BPA, BPS, BPF, and TBARS. Associations of bisphenol and TBARS concentrations with endometriosis risk were explored with multivariate logistic and linear regression analyses. Results: After adjustment for urinary creatinine, age, BMI, parity, and residence, endometriosis risk was increased with each 1 log unit of BPA [OR 1.5; 95%CI 1.0–2.3] and Σbisphenols [OR 1.5; 95%CI 0.9–2.3] but was not associated with the presence of BPS and BPF. Classification of the women by tertiles of exposure revealed statistically significant associations between endometriosis risk and the second tertile of exposure to BPA [OR 3.7; 95%CI 1.3–10.3] and Σbisphenols [OR 5.4; 95%CI 1.9–15.6]. In addition, TBARS concentrations showed a close-to-significant relationship with increased endometriosis risk [OR 1.6; 95%CI 1.0–2.8], and classification by TBARS concentration tertile revealed that the association between endometriosis risk and concentrations of BPA [OR 2.0; 95%CI 1.0–4.1] and Σbisphenols [OR 2.2; 95%CI 1.0–4.6] was only statistically significant for women in the highest TBARS tertile (>4.23 μM). Conclusion: Exposure to bisphenols may increase the risk of endometriosis, and oxidative stress may play a crucial role in this association. Further studies are warranted to verify these findings.
... In contrast, levels of urinary BPS were higher in low-income participants. Because BPS is found in cleaning and corrosion inhibiting products as well as in thermal print papers, it is probable that individuals with a low socioeconomic status might be more likely to be exposed to BPS due to occupational exposures Molina-Molina et al., 2019). Consistent with previously reported associations of BPS with obesity in animal models (Meng et al., 2019), urinary BPS levels were higher in obese participants. ...
Background:
Bisphenols F (BPF) and S (BPS) are bisphenol A (BPA) analogs used as substitutes in consumer products. Despite previous reports of BPA's association with asthma, no studies have examined its structural analogs in relation to asthma and allergy outcomes.
Objective:
To examine the association of urinary BPF, BPS, and BPA with asthma and hay fever in a US representative sample.
Methods:
We analyzed data from 3,538 participants aged 12 years or older in the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Children aged 6-11 years (N = 738), who did not have all covariate data available, were analyzed separately. Covariate-adjusted logistic regression was used to assess the association of the exposures with the outcomes.
Results:
BPF, BPS, and BPA were detected in 57.1%, 88.4%, and 94.8% of the urine samples, respectively. Urinary BPF detection was positively associated with current asthma (odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.16-2.04) and hay fever (OR: 1.66, 95% CI: 1.12-2.46). Urinary BPS was associated with increased odds of current asthma in men (OR: 1.64, 95% CI: 1.13-2.40) and urinary BPA was associated with increased odds of asthma without hay fever in children aged 6-11 years (OR: 2.65, 95% CI: 1.05-6.68).
Conclusion:
Our nationally-representative findings document that BPF and BPS exposure is common in the US and that exposure to these BPA analogs is associated with asthma and/or hay fever. Our results suggest that BPF and BPS may not be safe alternatives to BPA; however, prospective studies should be conducted to confirm these results.
Numerous techniques and technologies have been proposed for the detection and identification of hazardous chemicals that can harm the
lungs and respiratory system as well as the central nervous system and kidneys when inhaled. Most practical techniques can be carried out
by extraordinary professionals in well-equipped facilities. A reliable, simple, highly sensitive, and feasible sensing technique is still required.
A potential sensor for these harmful chemicals is the photonic crystal fiber (PCF), which achieves several unique properties. A square-core
PCF sensor is proposed in this work for the detection of detrimental gases (tetra-chloro silane, tetra-chloro methane, turpentine, and tin
terra-chloride) in the THz region. The cladding region is divided into three rings, and each ring has rectangular and square air holes.
Within the operating region, we have found a relatively high sensitivity of 96.185% along with 95.407% core power fraction, 0.2211 numerical
aperture, and a low effective area of 154 470 μm2 at 1.9 THz frequency. Ignorable confinement loss of 3.071 × 10−14 cm−1 and effective
material loss of 0.007 72 cm−1 have been also found. Additionally, the current manufacturing techniques guarantee the viability of the proposed
PCF sensor’s manufacture. These obtained results demonstrate that the proposed sensor can be effectively employed for applications
involving hazardous chemical compounds, gases, and biosensing.
The increased usage of bisphenol S (BPS) results in wide distribution in pregnant women. In this study, pregnant mice were given multiple-dose BPS during gestation. Results showed that prenatal BPS exposure (50 μg/kg/day) induced increased weight gain, dyslipidemia, higher liver triglyceride (TG), adipocyte hypertrophy, and hepatic lipid deposition in male offspring. Exosomes play important roles in regulating lipid metabolism. Here, serum exosomes and adipose miRNA sequencing of male offspring indicated a remarkable decrease in miR-29a-3p expression. To clarify whether adipocyte-derived exosomes mediate hepatic lipid deposition, exosomes were extracted from BPS-treated adipocytes and co-cultured with hepatocytes. These exosomes could be taken up by hepatocytes and promoted lipid deposition, and notably, exosomal miR-29a-3p was downregulated. Furthermore, miR-29a-3p knockdown in adipocyte-derived exosomes promoted hepatocyte lipid deposition, whereas overexpression led to the opposite effect. Also, the role of miR-29a-3p was demonstrated in hepatocytes by overexpressing or knocking it down. Subsequent studies have shown that miR-29a-3p can promote lipid deposition by directly targeting Col4a1. Taken together, prenatal BPS exposure could lead to lower miR-29a-3p yield in adipocyte-derived exosomes and decrease miR-29a-3p content transported to hepatocytes, which further negatively regulate Col4a1 and promote hepatic lipid deposition. Our findings provided clues to maternal environmental exposure-induced liver metabolic diseases.
Various chemicals are known to impact biological systems disrupting normal homeostasis, especially the endocrine system, called endocrine disrupting chemicals. Endocrine disrupting chemicals are universal in the environment, and a low concentration (µg/L to ng/L) severely impacts human health and wildlife due to transgenerational and multigenerational effects. The present review analyzed original research articles (109), review articles (76), short communication (20), article report (1), monograph (1), and scientific reports (2) via PubChem, science direct, National Center for Biotechnology Information, web of science on the source and fate of endocrine disrupting chemicals in the environment which are a prime concern to public health. A thorough investigation of the fate of these contaminants in environmental matrices such as air, water, soil, and biota is prioritized to form a clear link between the exposure and its effect on humans and biota. Environmental guidelines for these chemicals in environmental matrices and their treatment methods are also discussed in the review.Graphical abstract
Bisphenol A (BPA) is a synthetic chemical widely employed to synthesize epoxy resins, polymer materials, and polycarbonate plastics. BPA is abundant in the environment, i.e., in food containers, water bottles, thermal papers, toys, medical devices, etc., and is incorporated into soil/water through leaching. Being a potent endocrine disrupter, and has the potential to alter several body mechanisms. Studies confirmed its anti-androgen action and estrogen-like effects, which impart many negative health impacts, especially on the immune system, neuroendocrine process, and reproductive mechanism. Moreover, it can also induce mutagenesis and carcinogenesis, as per recent scientific research. This review focuses on BPA's presence and concentrations in different environments, food sources and the basic mechanisms of BPA-induced toxicity and health disruptions. It is a unique review of its type because it focuses on the association of cancer, hormonal disruption, immunosuppression, and infertility with BPA. These issues are widespread today, and BPA significantly contributes to their incidence because of its wide usage in daily life utensils and other accessories. The review also discusses researched-based measures to cope with the toxic chemical.
Objective: To assess the genetic and epigenetic effects promoted by Bisphenol A(BPA) exposure in adolescent males from the Spanish INMA-Granada birth cohort, as well as in human cells.
Methods: DNA methylation was analysed using MEDIP. Repeat number variation in genomic DNA was evaluated, along with the analysis of H3K4me3 by using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). All experiments were performed with material extracted from whole blood of adolescents from INMA. The epidemiological study was complemented by in vitro assessments of human (HeLa) cells exposed to BPA, specifically, immunofluorescence evaluation of histone modification levels, gene expression analysis and ChIP‒qPCR analysis.
Results: Adolescents in the high urinary BPA group presented higher genetic instability of Satellite A (SATA) repetitive region compared to those in the low BPA group. We also observed decreased DNA methylation at the promoters of the imprinted genes H19, KCNQ1, and IGF2; at LINE1 retroelements; and at the ARID2, EGFR1 and ESRRA genes. Genome-wide sequencing revealed increased H3K4me3 occupancy at the promoters of genes encoding histone acetyltransferases, telomeric DNA binding factors and DNA repair genes. These results were supported by studying HeLa cells exposed to 10 nMBPA in vitro. Exposure of cells to BPA caused a global increase in histone H4 acetylation and a decrease in H3K9me3 levels. In exposed cells, changes in the expression of genes encoding DNA repair factors (ATM, ARID2) were observed, and the expression of several genesencoding telomeric DNA binding factors (SMG7, TERT, TEN1, UPF1, ZBTB48) increased. Moreover, increased binding of ESR1 to KAT5, KMT2E and TERF2IP promoters and decreased ESR1 binding at the RARA promoter were observed.
Conclusion: Genome-wide analysis of histone trimethylation and BPA exposure in the in adolescents from the INMA cohort revealed a global impact of BPA on the expression of genes encoding telomeric binding proteins and histone acetyltransferase factors, which showed parallels with HeLa cells exposed to a human-relevant dose.
As plastic consumption has increased, environmental problems associated with the accumulation of plastic wastes have started to emerge. These include the non-degradability of plastic and its disintegration into sub-micron particles. Although some biodegradable plastic products have been developed to relieve the landfill and leakage burden, a significant portion of discarded plastics are inevitably still incinerated. The concern here is that incinerating plastics may result in the emission of toxic volatile organic compounds (VOCs). Moreover, lack of policy and the limited market share contributes to the indiscriminate discarding of biodegradable plastics, whereby it is mixed and subsequently incinerated with non-degradable plastics. The aim of this study was therefore to qualitatively and quantitatively analyze the VOCs emitted from both non-degradable and biodegradable plastics during combustion employing gas chromatography mass spectrometry. Here, non-degradable poly(vinyl chloride) and poly(ethylene terephthalate) emitted 10–115 and 6–22 ppmv of VOCs, respectively. These emission levels were more than 100 times higher than the VOC concentrations of 0.1–0.5 and 0.1–1.8 ppmv obtained for biodegradable polyhydroxyalkanoate and polylactic acid, respectively. Notably, due to the presence of a repeating butylene group in both non-degradable and biodegradable plastics, 1,3-butadiene accounted for the highest concentration among the VOCs identified, with concentrations of 6–116 ppmv and 0.5–558 ppmv obtained, respectively. During the evaluation of gas barrier films employed for food packaging purposes, non-degradable aluminum-coated multilayered films emitted 9–515 ppmv of VOCs, compared to the 2–41 ppmv VOCs emitted by biodegradable nanocellulose/nanochitin-coated films. Despite the significantly lower levels of VOCs emitted during the incineration of biodegradable plastics, this does not represent suitable waste treatment solution because VOCs are still emitted during incomplete combustion. This study aims to encourage further research into diverse combustion conditions for plastics and stimulate discussions on the fate of discarded plastics.
Background
Human breast milk is considered the optimal source of nutrition for infants. Milk from breast milk banks offers an alternative to infant formulas for vulnerable hospitalized neonates most likely to benefit from exclusive human milk feeding. However, breast milk can also be a source of exposure to environmental contaminants, including endocrine-disrupting chemicals (EDCs).
Aim
To evaluate concentrations of phenolic EDCs, including bisphenols, parabens (PBs), and benzophenones (BPs), in samples from a human milk bank in Granada, Southern Spain and to explore sociodemographic, reproductive, and lifestyle factors related to their concentrations in the milk.
Methods
Concentrations of three bisphenols [bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS)], four PBs [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP), and butyl-paraben (n-BuP)], and six BPs [BP-1, BP-2, BP-3, BP-6, BP-8, and 4-hydroxy-BP] were determined in milk samples from 83 donors. Information on potential explanatory variables was gathered using the milk bank donor form and an ad hoc questionnaire. Multiple linear and logistic regression models were fitted.
Results
Detectable concentrations were found of at least one of the analyzed compounds in all donor breast milk samples and at least five compounds in one-fifth of them. The most frequently detected compounds were MeP (90.5%), BP-3 (75.0%), EtP (51.2%), n-PrP (46.4%), and BPA (41.7%). Median concentrations ranged between <0.10 ng/mL (n-PrP, n-BuP, BP-1) and 0.59 ng/mL (BP-3). No sample contained detectable concentrations of BPF, BPS, or most BPs (BP-2, BP-6, BP-8, and 4- hydroxy-BP). Breast milk phenol concentrations were associated with parity, the utilization of deodorants, mouthwash, skin care products, and cosmetics, and the intake of nutritional supplements.
Conclusions
Results reveal the widespread presence of BPA, PBs, and BP-3 in donor breast milk samples, highlighting the need for preventive measures to enhance the benefits of breast milk from milk banks and from breastfeeding women in general.
The objective of this work was to evaluate thermal paper (TP) tickets used in Argentina as a potential source of bisphenol A (BPA) that could impact humans and the environment. BPA in TP was measured by HPLC ranging from 11.1 to 30.5 mg BPAg⁻¹. In order to estimate the impact on humans, dermal BPA estimated daily intake was calculated as being 79.3 ± 19.5 μgd⁻¹ for workers and 1.6 ± 0.4 μgd⁻¹ for the general population. To evaluate TP’s impact on the environment, BPA migration from TP to water and soil was studied. In the case of water, 99.6% of the BPA tickets content migrated in 30 h, while 78.0% moved into the soil in 96 h. BPA degradation kinetics in soil and water were also carried out; while in soil 61.9% of BPA degraded in 120 h, no degradation was observed up to 120 h in tap or river water.
Additionally, ecotoxicological effects of BPA on the earthworm Eisenia andrei, a representative terrestrial indicator, were studied performing bioassays on lethality, avoidance, and reproductive and enzymatic activity. BPA showed to be very toxic to E. andrei (LC50 value in contact paper test of 17 μgcm⁻², 95% confidence interval 6–46 μgcm⁻², 24 h exposure) and also caused an increase of total cocoons for earthworms exposed to 10 and 50 mg BPA kg⁻¹ soil. Evasion response was observed at a concentration of 50 mg BPA kg⁻¹ soil, while no effect was observed on cholinesterases, carboxylesterases, and glutathione S-transferases activities (1, 10, and 50 mg BPA kg⁻¹ soil). Finally, a simple BPA degradation technology using water peroxide and radish (Raphanus sativus) tissue as catalyst was explored as a simple and domestic potential treatment to avoid BPA migration to the environment.
Graphical abstract
In this study, we investigated for the first time the suitability of supramolecular solvent (SUPRAS)-based microextraction probe for the development of generic and fast sample treatment prior to qualitative analysis by ambient mass spectrometry (AMS) based on ASAP (atmospheric solids analysis probe). SUPRAS are nanostructured liquids formed by the self-assembly of amphiphilic aggregates with multiple binding sites and microenvironments of different polarity for the efficient extraction of multiple compounds. Different types of SUPRAS were evaluated as a simple and single step sample treatment for ASAP. The method was applied to the screening of bisphenol A and structural analogues in thermal paper. Optimal results were achieved with SUPRAS synthesized with 1-decanol in mixtures of ethanol:water. SUPRAS (1.1-2 μL) were loaded onto glass probes and placed in contact with samples for 10 seconds before ASAP analysis. AMS signal peaks (width: 0.2-0.5 min) were easily integrated and normalized with internal standards (RSD: 2-25%). The method was applied to 62 samples of thermal paper. BPA and BPS were the most widely used, this highlighting the progressive industrial replacement of BPA by BPS.
A square cored PCF (SC-PCF) sensor is proposed in this paper for the purpose of detecting detrimental chemical analytes (DEHP, BPA, and BPS) that are generally found in different plastic products. This SC-PCF sensor is capable of operating in the 1–2 THz regimes. Within this operable range, we found a relatively higher sensitivity of 96.5% along with 95.73% core power fraction, 0.225 numerical aperture, and a lower Aeff of 1.48 × 10⁵ μm² at 1.9 THz frequency. A tiny confinement loss of 2.68 × 10⁻¹³ cm⁻¹ and effective material loss of 0.008 cm⁻¹ are also evaluated. Besides the present fabrication techniques ensures the feasibility of fabrication for this proposed SC-PCF sensor. These estimated results evinced that our proposed sensor can efficiently be used in terms of the noxious chemical compounds, gas, and bio-sensing applications.
In recent years, the occurrence of organic UV-filters (UVFs) and bisphenol derivatives (BPs) in the marine environment has raised high concerns all over the world, due to the potentially adverse impacts on marine organism and, indirectly on human health. This paper reports, for the first time in Romania, the occurrence, distribution pattern and environmental risk assessment of UVFs, BPs and their metabolites in seawater, sediment and algae collected from the Romania Black Sea coastal region. BP-3 (2-hydroxy-4-methoxy-benzophenone) was the most abundant contaminant in seawater samples, with detection frequency of 100%. Sediment samples were dominated by ES (Ethylhexyl salicylate), with concentration values up to 5823 ng/g d.w., while for algae, concentrations of several hundreds of ng/g d.w. were determined for BP-3, BS (Benzyl salicylate) and BPE (Bisphenol E). Environmental risk assessment revealed that some UVFs and BPs detected in seawater samples were hazardous to the marine organism of the Black Sea.
Due to its widespread applications and its ubiquitous occurrence in the environment, bisphenol A (BPA) and its alternatives have gained increasing attention, especially in terms of human safety. Like BPA, alternatives such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) have also been identified to be endocrine-disrupting chemicals (EDCs). Hence, in this study, we reviewed the literature of BPA and its alternatives mainly published between the period 2018–2020, including their occurrences in the environment, human exposure, and adverse health effects. The review shows that bisphenols are prevalent in the environment with BPA, BPS, and BPF being the most ubiquitous in the environment worldwide, though BPA remains the most abundant bisphenol. However, the levels of BPS and BPF in different environmental media have been constantly increasing and their fates and health risks are being evaluated. The studies show that humans and animals are exposed to bisphenols in many different ways through inhalation and ingestion and the exposure can have serious health effects. Urinary bisphenols (BPs) levels were frequently reported to be positively associated with different health problems such as cancer, infertility, cardiovascular diseases, diabetes and neurodegenerative diseases. Our literature study also shows that BPs generate reactive oxygen species and disrupt various signalling pathways, which could lead to the development of chronic diseases. Activated carbon-based and chitosan-based sorbents have been widely utilized in the removal of BPA in aqueous solutions. In addition, enzymes and microorganisms have also been getting much attention due to their high removal efficiencies.
A multilayered iron oxide/reduced graphene oxide (ION-RGO) nanocomposite electrode is reported for the voltammetric sensing of bisphenol-A (BPA). Structural characterizations reveal the nanocomposite features RGO sheets decorated with nanometric spherical ION in a mixture of maghemite and magnetite phases. ITO substrate modified with the ION-RGO multilayered film exhibits strong electrocatalytic effect toward BPA oxidation, which is made possible by Fe(III) catalysts generated at the ION's surface after scanning the electrode potential from below 0 V (vs Ag/AgCl) and followed by the RGO phase conducting the transferred electrons. Under optimized differential pulse voltammetry conditions, the proposed sensor shows three linear working ranges 0.09–1.17 (r² = 0.999), 1.17–3.81 (r² = 0.995) and 3.81–8.20 (r² = 0.998), with the highest sensitivity equaling 7.76 μA cm⁻²/μmol L⁻¹ and the lowest limit of detection of 15 nmol L⁻¹. A single electrode can be used for at least twenty consecutive runs loosing less than 15% of sensitivity, whereas electrodes fabricated in different bacthes exhibit almost identical perfomances. Determination of BPA in a thermal paper sample shows no difference (at 95% confidence level) between the proposed sensor and HPLC/UV. The sensor is neither influenced by the matrix composition nor by other emerging contaminants.
Animal-derived food plays an important role in human exposure to bisphenol compounds (BPs), potentially as a result of the presence of BPs in animal feed. Even so, there have been few studies regarding the source of BPs in animal feed. The objective of the present study was to assess both the occurrence of BPs in animal feed packaging and the migration of BPs from feed packaging into animal feed. Thirteen BPs were monitored in 30 used animal feed plastic packaging samples previously employed for different animal feedstuffs and made of polypropylene (PP) or polyethylene (PE). Six and two BPs were found in PP-based woven bags and PE-based films, respectively. Bisphenol A (BPA) was the predominant analogue with a wide range of concentrations in both the PP- and PE-based packaging. A migration experiment was performed and provided the first-ever confirmation that BPA is able to migrate from plastic packaging into solid feed. Both contact time and the initial BP concentration affected the extent of migration. These results expand our knowledge regarding the origin of BPs in the food chain and suggest that further study of the bioaccumulation of BPs in animals is warranted.
Background
Bisphenol S (BPS) is a structural analogue of bisphenol A (BPA) that is found in the environment. BPS may accumulate in anuric patients due to decreased urinary excretion. The toxicity and health effects of BPS are poorly characterized.
Methods
A cross-over study was performed using polynephron (PN) or polysulphone (PS) dialysers for a short (1 week each, 14 patients) or long (3 months each, 20 patients) period on each dialyser. Plasma BPA, BPS and hippuric acid were assessed by SRM mass spectrometry (SRM-MS). The biological significance of the BPS concentrations found was explored in cultured kidney tubular cells.
Results
In haemodiafiltration (HDF) patients, plasma BPS was 10-fold higher than in healthy subjects (0.53 ± 0.52 versus 0.05 ± 0.01 ng/mL; P = 0.0015), while BPA levels were 35-fold higher (13.23 ± 14.65 versus 0.37 ± 0.12 ng/mL; P = 0.007). Plasma hippuric acid decreased after an HDF session, while BPS and BPA did not. After 3 months of HDF with the same membranes, the BPS concentration was 1.01 ± 0.87 ng/mL for PN users and 0.62 ± 0.21 ng/mL for PS users (P non-statistically significant). In vitro, BPS and BPA leaked from dialysers containing them. In cultured tubular cells, no biological impact (cytotoxicity, inflammatory and oxidative stress gene expression) was observed for BPS up to 200 µM, while BPA was toxic at concentrations ≥100 µM.
Conclusions
BPS may be released from dialysis membranes, and dialysis patients display high BPS concentrations. However, BPS concentrations are lower than BPA concentrations and no BPS toxicity was observed at concentrations found in patient plasma.
The environmental contaminant bisphenol S (BPS) was determined by a kinetic fluorimetric method combined with Fenton process in the presence of rhodamine B (RhB). In acidic solution, the fluorescent RhB was oxidized by hydroxyl radical generated in Fenton process and produced fluorescence quenching, which was obviously accelerated by BPS added into the system. The decrease in fluorescence intensity (ΔF) was proportional to the concentration of BPS with the maximum excitation and emission wavelengths of 554 nm and 578 nm, respectively. Under the optimal conditions, the ΔF was good linear with the concentration of BPS over the range of 0.004–2.0 mg/L with a correlation coefficient of 0.9991. The detection limit of 0.73 μg/L was obtained for the determination of BPS by the proposed method. The general coexisting substances did not interfere to the reactions of BPS with Fenton reagent and RhB. The proposed method has been successfully applied to determine BPS migrated from plastic package with satisfactory results. This new method is environmentally friendly and easy to popularize.
Bisphenol A (BPA) is a high production volume chemical that has wide industrial applications, especially as a color developer in thermal papers. The present study focused on the determination of levels of BPA in thermal receipts collected from different locations in Akure, Nigeria, and the estimation of daily intake of BPA through dermal absorption. Thermal receipts were collected from different locations, and the levels of extracted BPA were determined using fluorescence spectroscopy. The daily intake of BPA was estimated, and the amount was compared with the reference value. BPA was detected in all the samples analyzed with levels ranging from 1.50 to 3.16 mg/g. These values were lower than the values detected in thermal receipts obtained from other countries. The estimated mean daily intakes of BPA by dermal absorption due to handling of thermal receipts were 0.20 and 9.89 μg/day for the general population and the occupationally exposed individuals, respectively, and were much lower than the reference value of 50 μg/kg bw/day provided by the European Food Safety Authority. This indicates that dermal exposure to BPA is not a serious health risk to the population.
Musa estuary and its tributaries, located northwest of the Persian Gulf, host many industrial complexes, high-density ports, and urban areas along their coastal regions and are, therefore, constantly threatened by chemical contamination. The present study is the first to have investigated the surface sediments in six stations of the Musa estuary tributaries. The mean variations in BPA concentrations in the dry sediments of these stations ranged from 2.22 to 16.71 ng/g. Fairly high levels of BPA were found in Durragh station and its neighboring industrial sites. The lowest BPA level (2.22 ng/g) was observed in the station at the mouth of the Persian Gulf. Based on the EU risk-assessment system, the concentration levels of BPA in the sediments are in the low-risk range. Only in certain areas of the estuary were the sediments of moderate risk, and prolonged contact between ecological populations and them could cause toxicity in aquatic organisms.
Background:
Newborns in neonatal intensive care units (NICUs) are in contact with a variety of medical products whose production might include synthetic chemicals with hormonal activity.
Objectives:
Our aim was to assess the content of bisphenol A (BPA) and parabens (PBs) and the hormone-like activities of a subset of medical products commonly used in NICUs in prolonged intimate contact with NICU newborns.
Methods:
Fifty-two NICU items were analyzed, determining the concentrations of BPA and PBs [methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butylparaben (BuP)] and using the E-Screen and PALM-luciferase assays to measure the in vitro (anti-)estrogenic and (anti-)androgenic activity, respectively, of the extracts. Items found to have elevated BPA/PB content or hormone-like activities were further extracted using leaching methodologies.
Results:
BPA was found in three-fifths and PBs in four-fifths of tested NICU items, and
∼
25
%
and
∼
10
%
of extracts evidenced estrogenic and anti-androgenic activity, respectively. The highest BPA content was found in the three-way stopcock (
>
7.000
ng
/
g
), followed by patterned transparent film dressing, gastro-duodenal feeding tubes, sterile gloves, single-lumen umbilical catheters, and intravenous (IV) infusion extension sets (concentrations ranged from 100 to
700
ng
/
g
BPA). A total PB concentration (
∑
PBs
)
>
100
ng
/
g
was observed in several items, including light therapy protection glasses, patterned transparent film dressing, winged IV catheters, IV infusion extension sets, and textile tape. The highest estrogenic activity [
>
450
pM
estradiol equivalent (
E
2
eq
)] was found in small dummy nipples, three-way stopcocks, and patterned transparent film dressing and the highest anti-androgenic activity [
>
5
mM
procymidone equivalent units per gram (
Proceq
/
g
)] in small dummy nipples and three-way stopcocks.
Discussion:
According to these findings, neonates might be exposed to multiple sources of BPA and PBs in NICUs via inhalation, dermal, oral, and IV/parenteral routes. There is a need to address the future health implications for these extremely vulnerable patients and to adopt precautionary preventive measures as a matter of urgency. https://doi.org/10.1289/EHP-embargotest.
Background:
Newborns in neonatal intensive care units (NICUs) are in contact with a variety of medical products whose production might include synthetic chemicals with hormonal activity.
Objectives:
Our aim was to assess the content of bisphenol A (BPA) and parabens (PBs) and the hormone-like activities of a subset of medical products commonly used in NICUs in prolonged intimate contact with NICU newborns.
Methods:
Fifty-two NICU items were analyzed, determining the concentrations of BPA and PBs [methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butylparaben (BuP)] and using the E-Screen and PALM-luciferase assays to measure the in vitro (anti-)estrogenic and (anti-)androgenic activity, respectively, of the extracts. Items found to have elevated BPA/PB content or hormone-like activities were further extracted using leaching methodologies.
Results:
BPA was found in three-fifths and PBs in four-fifths of tested NICU items, and
∼
25
%
and
∼
10
%
of extracts evidenced estrogenic and anti-androgenic activity, respectively. The highest BPA content was found in the three-way stopcock (
>
7.000
ng
/
g
), followed by patterned transparent film dressing, gastro-duodenal feeding tubes, sterile gloves, single-lumen umbilical catheters, and intravenous (IV) infusion extension sets (concentrations ranged from 100 to
700
ng
/
g
BPA). A total PB concentration (
∑
PBs
)
>
100
ng
/
g
was observed in several items, including light therapy protection glasses, patterned transparent film dressing, winged IV catheters, IV infusion extension sets, and textile tape. The highest estrogenic activity [
>
450
pM
estradiol equivalent (
E
2
eq
)] was found in small dummy nipples, three-way stopcocks, and patterned transparent film dressing and the highest anti-androgenic activity [
>
5
mM
procymidone equivalent units per gram (
Proceq
/
g
)] in small dummy nipples and three-way stopcocks.
Discussion:
According to these findings, neonates might be exposed to multiple sources of BPA and PBs in NICUs via inhalation, dermal, oral, and IV/parenteral routes. There is a need to address the future health implications for these extremely vulnerable patients and to adopt precautionary preventive measures as a matter of urgency. https://doi.org/10.1289/EHP5564.
Bisphenols are the environmental pollution of a highly harmful, but different in their magnitude, influence on the living organisms. Among various aspects of the toxicity of these compounds their effect on the red blood cells is intensively investigated. The aim of this work was to compare the effect of bisphenol A (BPA), bisphenol S (BPS) and bisphenol F (BPF) on model erythrocyte membranes and to get insight into the origin of the differences in the harmful effect of these substances on cells. Thus, the influence of bisphenols on multicomponent Langmuir films imitating the outer leaflet of erythrocyte membrane was thoroughly analyzed. An important step of the experiments were the studies on the effect of bisphenols on the films composed from particular erythrocyte membrane lipids. It was confirmed that both BPA and BPF affect model lipid systems more strongly than BPS, by changing their condensation, ordering, stability and morphology. However, the most essential conclusion was that BPA acts on the erythrocyte lipids more selectively than BPS and BPF and the influence exerted by this molecule is more strongly determined by the membrane composition. It was also suggested that cholesterol may act as the molecule of a decisive role from the point of view of the magnitude of the incorporation and the effect of BPA and BPF on membrane. Thus, the level of bisphenols toxicity to erythrocytes may depend on the concentration of cholesterol in their membranes.
Dangers from various chemical compounds in polycarbonate plastics that are exposed to the human body are a matter of great apprehension nowadays. Research has been going on and many analytical and electrochemical analysis methods have been developed to detect these harmful compounds. But in most cases, these analyses are very time consuming, require certain laboratory settings, a lot of pre-preparation and overpriced equipment. For these, an optical analysis technique employing a dodecagonal photonic crystal fiber (PCF) structure having a floral pattern in the first cladding layer is considered in this work. Among the most detrimental chemical compounds of plastic, bisphenol A (BPA), bisphenol S (BPS) and di (2-ethylhexyl) phthalate (DEHP), these three are considered and sensitivity of these compounds are measured individually. As a result, the relative sensitivity of 94.9%, 97.6% and 94.9% respectively for BPA, BPS, and DEHP is obtained. It is to be mentioned that these concerned compounds are sensed by PCF for the first time to the best of our knowledge. Furthermore, confinement loss and nonlinearity are also analyzed for the same proposed structure altering the three compounds which also results in a satisfactory outcome showing low confinement loss and very high nonlinearity. Thus, the proposed dodecagonal floral structure can be employed in various applications including chemical and biochemical sensing, nonlinear optics, supercontinuum generation, and many others.
Bisphenol A (BPA) is an endocrine disruptor frequently detected in human biofluids. Dermal absorption of BPA from thermal paper receipts occurs but BPA pharmacokinetics following dermal exposure is not understood. To compare the pharmacokinetics of dermal and dietary BPA exposure, six male participants handled simulated receipts containing relevant levels of BPA (isotope-labeled BPA-d16) for 5 min, followed by hand-washing 2 hrs later. Urine (0-48 hrs) and serum (0-7.5 hrs) were monitored for free and total BPA-d16. One week later, participants returned for a dietary administration with monitoring as above. One participant repeated the dermal administration with extended monitoring of urine (9 days) and serum (2 days). After dietary exposure, urine total BPA-d16 peaked within 5 hrs and quickly cleared within 24 hrs. After dermal exposure, cumulative excretion increased linearly for 2 days, and half the participants still had detectable urinary total BPA-d16 after 1 week. The participant repeating the dermal exposure had detectable BPA-d16 in urine for 9 days, showed linear cumulative excretion over 5 days, and had detectable free BPA-d16 in serum. Proportions of free BPA-d16 in urine following dermal exposure (0.71% - 8.3% of total BPA-d16) were generally higher than following the dietary exposure (0.29% - 1.4%). Compared to dietary BPA exposure, dermal absorption of BPA leads to prolonged exposure and may lead to higher proportions of unconjugated BPA in systemic circulation.
Purpose:
As an essential component of polycarbonate plastics and epoxy resins, Bisphenol A (BPA) is found in numerous industrial and consumer products. BPA may cause adverse health effects because of its endocrine activity. General population exposure to this compound mainly through diet is well documented. Thermal paper was also identified as a source of BPA through dermal intake. In this study, we investigated whether frequent contact with thermal paper is associated with an increase in urinary BPA excretion.
Methods:
We evaluated the exposure to BPA in cashiers and in non-occupationally exposed workers from several workplaces. Urinary BPA was quantified in free (unconjugated) and total (unconjugated plus conjugated) forms in 24-h and spot urine samples using LC-MS/MS. BPA concentration in thermal paper was also measured from each workplace. In addition, participants provided information on job, food and drink, tobacco consumption and hands wash during the sampling period through a questionnaire.
Results:
Urine samples were collected from 90 cashiers and 44 controls. Free and total BPA were detected in all samples. The median urinary total BPA concentration was 3.54 µg/L (2.89 µg/g creatinine) for controls and 8.92 µg/L (6.76 µg/g creatinine) for cashiers. For the free BPA, the median urinary concentration was 0.20 µg/L (0.21 µg/g creatinine) for controls and 0.28 µg/L (0.22 µg/g creatinine) for cashiers. Any correlation was found between the urinary concentration levels and the number of thermal receipts handled. Hand washes frequency, age, job length of service and tobacco consumption had also no effect on the BPA excretions.
Conclusion:
A significant increase in urinary total BPA concentration was observed for cashiers handling daily thermal paper receipts. However, no significant increase was observed in urinary free BPA concentration. These findings are particularly interesting for risk assessment since all available data on occupational exposure to BPA through thermal paper were obtained from models or from simulated experiments.
Bisphenol A (BPA) is a high production volume chemical associated with a wide range of health outcomes in animal and human studies. BPA is used as a developer in thermal paper products including cash register receipt paper; however little is known about exposure of cashiers to BPA and alternative compounds in receipt paper.
To determine if handling receipt paper results in measurable absorption of BPA or the BPA alternatives, bisphenol S (BPS) and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP).
Cashiers (n = 77) and non-cashiers (n=25) were recruited from the Raleigh-Durham-Chapel Hill region of North Carolina during 2011-2013. Receipts were analysed for the presence of BPA or alternatives considered for use in thermal paper. In cashiers, total urine and serum BPA, BPS, and BPSIP levels in post-shift samples (collected ≤ 2h after completing a shift) were compared with pre-shift samples (collected ≥ 24 hours after a work shift). Urine levels in cashiers were compared to levels from non-cashiers.
Each receipt contained 1-2% by weight of the paper of BPA, BPS, or BPSIP. The post-shift geometric mean total urinary BPS concentration was significantly higher than the pre-shift mean in 33 cashiers who handled receipts containing BPS. Mean urine BPA concentrations in 31 cashiers who handled BPA receipts were as likely to decrease as increase after a shift, but the mean post-shift concentration was significantly higher than in non-cashiers. BPSIP was detected more frequently in urine of cashiers handling BPSIP receipts compared to non-cashiers. Only a few cashiers had detectable levels of total BPA or BPS in serum, whereas BPSIP tended to be detected more frequently.
Thermal receipt paper is a potential source of occupational exposure to BPA, BPS, and BPSIP.
Increasing concern over bisphenol A (BPA) as an endocrine disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often labeled "BPA-free." Some of the chemical replacements however, are also bisphenols, and may have similar physiological effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA substitutes.
This review was carried out to evaluate the physiological effects and endocrine activities of the BPA substitutes BPS and BPF. Further, we compared the hormonal potency of BPS and BPF to BPA.
We conducted a systematic review, based on the Office of Health Assessment and Translation (OHAT) protocol.
We identified the body of literature-to-date, consisting of 32 studies (25 in vitro only, and seven in vivo). The majority of these studies examined the hormonal activities of BPS and BPF and found their potency to be in the same order of magnitude and of similar action to BPA (estrogenic, anti-estrogenic, androgenic, and anti-androgenic) in vitro and in vivo. BPS also has potencies similar to estradiol in membrane-mediated pathways, which are important for cellular actions like proliferation, differentiation, and death. BPS and BPF also showed other effects in vitro and in vivo, such as altered organ weights, reproductive endpoints, and enzyme expression.
Based on the current literature, BPS and BPF are as hormonally active as BPA, and have endocrine disrupting effects.
Bisphenol A (BPA) is a widely studied typical endocrine-disrupting chemical, and one of the major new issues is the safe replacement of this commonly used compound. Bisphenol S (BPS) and bisphenol F (BPF) are already or are planned to be used as BPA alternatives. With the use of a culture system that we developed (fetal testis assay [FeTA]), we previously showed that 10 nmol/L BPA reduces basal testosterone secretion of human fetal testis explants and that the susceptibility to BPA is at least 100-fold lower in rat and mouse fetal testes. Here, we show that addition of LH in the FeTA system considerably enhances BPA minimum effective concentration in mouse and human but not in rat fetal testes. Then, using the FeTA system without LH (the experimental conditions in which mouse and human fetal testes are most sensitive to BPA), we found that, as for BPA, 10 nmol/L BPS or BPF is sufficient to decrease basal testosterone secretion by human fetal testes with often nonmonotonic dose-response curves. In fetal mouse testes, the dose-response curves were mostly monotonic and the minimum effective concentrations were 1,000 nmol/L for BPA and BPF and 100 nmol/L for BPS. Finally, 10,000 nmol/L BPA, BPS, or BPF reduced Insl3 expression in cultured mouse fetal testes. This is the first report describing BPS and BPF adverse effects on a physiologic function in humans and rodents.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Background:
In 2007, an expert panel reviewed associations between bisphenol A (BPA) exposure and reproductive health outcomes. Since then, new studies have been conducted on the impact of BPA on reproduction.
Objective:
In this review, we summarize data obtained since 2007, focusing on a) findings from human and animal studies, b) the effects of BPA on a variety of reproductive end points, and c) mechanisms of BPA action.
Methods:
We reviewed the literature published from 2007 to 2013 using a PubMed search based on keywords related to BPA and male and female reproduction.
Discussion:
Because BPA has been reported to affect the onset of meiosis in both animal and in vitro models, interfere with germ cell nest breakdown in animal models, accelerate follicle transition in several animal species, alter steroidogenesis in multiple animal models and women, and reduce oocyte quality in animal models and women undergoing in vitro fertilization (IVF), we consider it an ovarian toxicant. In addition, strong evidence suggests that BPA is a uterine toxicant because it impaired uterine endometrial proliferation, decreased uterine receptivity, and increased implantation failure in animal models. BPA exposure may be associated with adverse birth outcomes, hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but additional studies are required to confirm these associations. Studies also suggest that BPA may be a testicular toxicant in animal models, but the data in humans are equivocal. Finally, insufficient evidence exists regarding effects of BPA on the oviduct, the placenta, and pubertal development.
Conclusion:
Based on reports that BPA impacts female reproduction and has the potential to affect male reproductive systems in humans and animals, we conclude that BPA is a reproductive toxicant.
There is growing evidence that bisphenol A (BPA) may adversely affect humans. BPA is an endocrine disruptor that has been shown to be harmful in laboratory animal studies. Until recently, there were relatively few epidemiological studies examining the relationship between BPA and health effects in humans. However, in the last year, the number of these studies has more than doubled. A comprehensive literature search found 91 studies linking BPA to human health; 53 published within the last year. This review outlines this body of literature, showing associations between BPA exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects. These studies encompass both prenatal and postnatal exposures, and include several study designs and population types. While it is difficult to make causal links with epidemiological studies, the growing human literature correlating environmental BPA exposure to adverse effects in humans, along with laboratory studies in many species including primates, provides increasing support that environmental BPA exposure can be harmful to humans, especially in regards to behavioral and other effects in children.
Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic β-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ERβ-/- mice to study whether ERβ is involved in the rapid regulation of K(ATP) channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in β-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K(ATP) channel activity, increased glucose-induced [Ca(2+)](i) signals and insulin release in β-cells from WT mice but not in cells from ERβ-/- mice. The rapid reduction in the K(ATP) channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ERβ and indicate that results obtained with BPA in mouse β-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans.
For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of "the dose makes the poison," because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.
Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two- and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies.
Bisphenol A (BPA) is a monomer used mainly in the synthesis of polycarbonates and epoxy resins. Percutaneous absorption is the second source of exposure, after inhalation, in the work environment. However, studies on this route of absorption are lacking or incomplete. In this study, percutaneous BPA absorption was measured in vivo and ex vivo in the rat, and ex vivo in humans. An approximately 12-fold difference in permeability between rat skin and human skin was found, with permeability being higher in the rat. In addition, inter- and intra-individual variability of up to tenfold was observed in humans. No accumulation of BPA in the skin was found during exposure. The skin clearance rate following exposure was estimated at 0.4 μg/cm²/h. Ex vivo and in vivo percutaneous absorption fluxes of BPA in the rat were in the same range (about 2.0 μg/cm²/h), suggesting that extrapolation to the in vivo situation in humans may be possible. The European tolerable daily intake (TDI) of BPA is 50 μg/kg body weight. However, many research projects have highlighted the significant effects of BPA in rodents at doses lower than 10 μg/kg/day. A 1-h occupational exposure over 2,000 cm² (forearms and hands) may lead to a BPA absorption of 4 μg/kg/day. This is 8% of the European TDI and is very close to the value at which effects have been observed in animals. This absorption must therefore be taken into account when evaluating risks of BPA exposure, at least until more relevant results on the toxicity of BPA in humans are available.
Purpose:
In thermal paper, Bisphenol S (BPS) is one of the alternatives for bisphenol A (BPA). Due to its structural similarity to BPA, concern has been raised about the safety of BPS. Indeed, handling thermal paper receipts could be a source of occupational exposure to BPS among cashiers, as it was previously described for BPA. In this study, we investigated whether frequent contacts with thermal paper are associated with an increase in urinary BPS levels in cashiers.
Method:
Total (unconjugated and conjugated forms) and free (unconjugated) BPS were measured in urine samples from 17 cashiers and 15 controls, using LC-MS/MS. Spot urine samples, including pre-shift and post-sift samples and first morning void were collected from each volunteer. BPS concentration in thermal paper was determined and the number of receipts handled by cashiers was estimated as well.
Results:
The median urinary total BPS concentration was 0.67 μg/L (0.52 μg/g creatinine) for controls and 2.53 μg/L (2.07 μg/g creatinine) for cashiers. Total BPS concentration was significantly higher in cashiers than in controls. Free BPS was detected in less than 20% of urine samples collected from controls and in less than 50% of urine samples collected from cashiers.
Conclusion:
The detectable levels of BPS in urine of controls suggest an exposure to BPS of the general population. In addition, frequent contact with thermal paper could be responsible for an increase in urinary concentration of total BPS in cashiers.
Bisphenol A (BPA) is an important industrial raw material that is widely applied in daily products. BPA is also an endocrine-disrupting chemical that may adversely affect humans. This review thoroughly collected data on BPA concentration in human urine and determined main influencing factors. The average BPA intake of humans across six continents or the average value worldwide was calculated based on a simple model. Results showed that the average BPA intake was ranked from high to low as follows: Oceania, Asia, Europe, and North America in the child population and Oceania, Europe, Asia, and North America in the adult population. The annual trend of the average BPA intake was similar between the adult and child populations. The BPA intake in the two populations evidently decreased from 2000 to 2008 and then slightly increased from 2008 to 2011. The BPA intake in the child population started to decrease again from 2011, whereas the corresponding intake in the adult population continued to increase. The distinct difference likely contributed to the wide prohibition of the use of BPA in food-related products for children in many countries since 2009; the bans effectively decreased the total BPA exposure in the child population.
Background:
Exposure to bisphenols and phthalates in pregnancy may lead to adverse health effects in women themselves and their offspring.
Objective:
To describe first trimester bisphenol and phthalate urine concentrations, including bisphenol and phthalate replacements, and determine nutritional, socio-demographic and lifestyle related determinants.
Methods:
In a population-based prospective cohort of 1396 mothers, we measured first trimester bisphenol, phthalate and creatinine urine concentrations (samples collected in 2004-2005, median gestational age 12.9 weeks [inter-quartile range (IQR) 12.1-14.4]). We examined associations of potential determinants with log-transformed bisphenol and phthalate concentrations. Outcomes were back-transformed. Nutritional analyses were performed in a subgroup of 642 Dutch participants only, as the Food Frequency Questionnaire was aimed at Dutch food patterns.
Results:
Bisphenol A, bisphenol S, and bisphenol F were detected in 79.2%, 67.8% and 40.2% of the population, respectively. Mono-n-butylphthalate, mono-(2-ethyl-5-hydroxyhexyl)phthalate and monobenzylphthalate were detected in > 90% of the population. Nutritional intake was not associated with bisphenol and phthalate concentrations after correction for multiple testing was applied. Obesity was associated with higher high-molecular-weight phthalate concentrations and the lack of folic acid supplement use with higher di-n-octylphthalate concentrations (respective mean differences were 46.73nmol/l [95% CI 14.56-93.72] and 1.03nmol/l [0.31-2.06]).
Conclusion:
Bisphenol S and F exposure was highly prevalent in pregnant women in the Netherlands as early as 2004-5. Although associations of dietary and other key factors with bisphenol and phthalate concentrations were limited, adverse lifestyle factors including obesity and the lack of folic acid supplement use seem to be associated with higher phthalate concentrations in pregnant women. The major limitation was the availability of only one urine sample per participant. However, since phthalates are reported to be quite stable over time, results concerning determinants of phthalate concentrations are expected to be robust.
Background:
Bisphenol A (BPA) is an endocrine disrupting chemical widely used in the manufacture of polycarbonate plastic and epoxy resin to produce a multitude of consumer products, food and drink containers, and medical devices. BPA is similar to estradiol in structure and thus interferes in steroid signalling with different outcomes on reproductive health depending on doses, life stage, mode, and timing of exposure. In this respect, it has an emerging and controversial role as a "reproductive toxicant" capable of inducing short and long-term effects including the modulation of gene expression through epigenetic modification (i.e. methylation of CpG islands, histone modifications and production of non-coding RNA) with direct and trans-generational effects on exposed organisms and their offspring, respectively.
Objective:
This review provides an overview about BPA effects on reproductive health and aims to summarize the epigenetic effects of BPA in male and female reproduction.
Results:
BPA exerts epigenetic effects in both male and female reproduction. In males, BPA affects spermatogenesis and sperm quality and possible trans-generational effects on the reproductive ability of the offspring. In females, BPA affects ovary, embryo development, and gamete quality for successful in vivo and in vitro fertilization (IVF).
Conclusion:
The exact mechanisms of BPA - mediated effects in reproduction are not fully understood; however, the environmental exposure to BPA - especially in fetal and neonatal period - deserves attention to preserve the reproductive ability in both sexes and to reduce the epigenetic risk for the offspring.
Bisphenol A (BPA) was commonly used as color developer for thermal paper such as cash register receipts, labels or tickets. Therefore, thermal paper was considered by the European Food Safety Authority (EFSA) as the main source of human exposure to BPA beside epoxy based food contact materials. In this study, a German market analysis on the use of BPA and alternative color developers in thermal paper receipts is provided for the years 2015, 2016 and 2017.114 (2015), 98 (2016) and 99 (2017) samples were randomly collected and analyzed by HPLC-DAD. In summary, BPA was still the most frequently found color developer (48.2% in 2015, 46.9% in 2016 and 52.5% in 2017). The most commonly used alternative was the phenol-free substance Pergafast® 201 (34.2%, 33.7%, 40.4%). The bisphenol analogs bisphenol S (BPS; 11.4%, 9.2%, 6.1%) and D8 (6.1%, 7.1%, 1.0%) were less common. Another phenol-free substituent, a urea urethane compound (UU), was also detected (3.1% in 2016). Concentrations of color developers in thermal paper ranged from 1.4 to 32.4 mg/g (median values between 2.5 and 15.9 mg/g). Concentrations of BPA were found to be highest followed by BPS, UU, Pergafast® 201 and D8. In addition, two pharmacologically active substances, dapsone (6.0 mg/g) and tolbutamide (5.5 mg/g), were detected in a non-marketed thermal paper, that was supposed to use ascorbic acid as initial color developer. Different release experiments of the detected color developers were performed. Sensitizers 1,2-diphenoxy-ethane, 1-phenylmethoxy-naphthalene and diphenylsulfone, used frequently in the thermal paper processes, were quantified.
Thermal paper contains potentially toxic additives, such as bisphenol A (BPA), as a common color developer. Because of its known endocrine disrupting effects, structural analogues to BPA, such as bisphenol S (BPS), D-8 and Pergafast 201, have been used as alternatives, but little is known about the presence and toxicological effects of alternatives other than BPS. In this study, thermal paper is screened by direct probe ambient mass spectrometry (rapid pre-screening method not requiring sample preparation) and by liquid chromatography (LC) with high resolution time-of flight (TOF-MS) mass spectrometry. Cash receipts and other thermal paper products (cinema tickets, boarding passes and luggage tags) were analyzed. Besides BPA and BPS, other developers only recently reported (Pergafast 201, D-8) or to the best of our knowledge not reported before (D-90, TGSA, BPS-MAE) were frequently found as well as some related unreported impurities (2,4-BPS that is a BPS related impurity and a TGSA related impurity). To gain some insight into the potential estrogenicity of the detected developers, a selection of extracts was further analyzed using a LC-nanofractionation platform in combination with cell-based bioassay testing. These preliminary results seems to indicate very low or absence of estrogenic activity for Pergafast 201, D-8, D-90, TGSA and BPS-MAE in comparison to BPA and BPS, although further dose-response tests with authentic standards are required to confirm these results. Compounds for which standards were available were also tested for developmental toxicity and neurotoxicity using zebrafish (Danio rerio) embryos. TGSA and D-8 induced similar teratogenic effects as BPA in zebrafish embryos. BPS and 2,4-BPS did not induce any developmental effects but 2,4-BPS did alter the locomotor activity at the tested concentration. Our findings suggest that the alternatives used as alternatives to BPA (except BPS) might not be estrogenic. However, TGSA and D-8 showed abnormal developmental effects similar to BPA.
Thermal paper contains potentially toxic compounds such as bisphenol A (BPA), which is used as a color developer. BPA has been reported in thermal paper in concentrations up to 42,600 μg g⁻¹. The exposure to BPA via dermal transfer has been recently discussed as a significant contribution to the overall human exposure and the estimated daily intake (EDI) has been reported up to 218 μg d⁻¹. BPA has been also detected in recycled paper with concentrations up to 46 μg g⁻¹. Due to the fact that BPA is a known endocrine disruptor and migrates from materials, regulatory restrictions have been established to prevent risks for the human health. As a consequence, structural analogues, such as bisphenol S (BPS) have been introduced into the market. Little is known about the presence and toxicity of these emerging replacements, and concern has risen about them. The present review gives an overview of the occurrence and levels of BPA and replacements in thermal paper. BPA is still the most common color developer found in thermal paper, followed by BPS. The analytical methods used for quantification of BPA and BPA replacements in paper products are also reviewed. BPA is transferred from thermal paper products to the finger pads upon handling it. Paper-skin transfer followed by penetration of BPA depends on conditions (e.g. greasiness of fingers and use of hand cream). It is, however, still debated whether thermal paper as a source for human exposure contributes significantly to the overall internal BPA exposure.
This opinion describes the assessment of the risks to public health associated with bisphenol A (BPA) exposure. Exposure was assessed for various groups of the human population in three different ways: (1) external (by diet, drinking water, inhalation, and dermal contact to cosmetics and thermal paper); (2) internal exposure to total BPA (absorbed dose of BPA, sum of conjugated and unconjugated BPA); and (3) aggregated (from diet, dust, cosmetics and thermal paper), expressed as oral human equivalent dose (HED) referring to unconjugated BPA only. The estimated BPA dietary intake was highest in infants and toddlers (up to 0.875 µg/kg bw per day). Women of childbearing age had dietary exposures comparable to men of the same age (up to 0.388 µg/kg bw per day). The highest aggregated exposure of 1.449 µg/kg bw per day was estimated for adolescents. Biomonitoring data were in line with estimated internal exposure to total BPA from all sources. BPA toxicity was evaluated by a weight of evidence approach. “Likely” adverse effects in animals on kidney and mammary gland underwent benchmark dose (BMDL10) response modelling. A BMDL10 of 8 960 µg/kg bw per day was calculated for changes in the mean relative kidney weight in a two generation toxicity study in mice. No BMDL10 could be calculated for mammary gland effects. Using data on toxicokinetics, this BMDL10 was converted to an HED of 609 µg/kg bw per day. The CEF Panel applied a total uncertainty factor of 150 (for inter- and intra-species differences and uncertainty in mammary gland, reproductive, neurobehavioural, immune and metabolic system effects) to establish a temporary Tolerable Daily Intake (t-TDI) of 4 µg/kg bw per day. By comparing this t-TDI with the exposure estimates, the CEF Panel concluded that there is no health concern for any age group from dietary exposure and low health concern from aggregated exposure. The CEF Panel noted considerable uncertainty in the exposure estimates for non-dietary sources, whilst the uncertainty around dietary estimates was relatively low.
Bisphenol A were removed from consumer products and replaced by chemical substitutes such as Bisphenol S (BPS). Based on their structural similarity, BPS may be obesogen like Bisphenol A in mice. Our objective was to determine the impact of BPS on lipid homeostasis in C57Bl/6 mice after perinatal and chronic exposure. Pregnant mice were exposed to BPS via the drinking water (0.2; 1.5; 50 μg/kg bw/d). Treatment began at gestational day 0 and continued in offspring up to 23-weeks old. Then, offspring mice were fed with a standard or high fat diet. The body weight, food consumption, fat mass and energy expenditure were measured. A lipid load test was performed to check the postprandial triglyceridemia. Plasma parameters and mRNA gene expression in adipose tissues were also analysed. BPS induced overweight in male mice offspring fed with a HFD at the two highest doses. There was no change in food intake and energy expenditure. The overweight was correlated to the fat mass, hyperinsulinemia and hyperleptinemia. The plasma triglyceride clearance was significantly increased with BPS and tyloxapol® (triglyceride clearance inhibitor) reversed this phenomenon. BPS induced alteration in mRNA expression of marker genes involved in adipose tissue homeostasis: hormone sensitive lipase, PPARγ, insulin receptor, SOCS3 and adiponectin. This is the first time that BPS is described as obesogenic at low doses and after perinatal and chronic exposure in male mice. BPS potentiated the obesity induced by a HFD by inducing the lipid storage linked to faster lipid plasma clearance.
Hormonal disturbances caused by environmental pollutants have become one of the most important issues regarding environmental and human health. Bisphenol A (BPA), octylphenol and nonylphenol are three prominent xenobiotic endocrine active compounds (EACs) mimicking natural female sex hormones (estrogens). Since both BPA and alkylphenol polyethoxylate surfactants are used in paper production the contamination of recycled paper products with these compounds can be expected. Therefore, the contamination of wastepaper, toilet paper and cellulose samples with selected EACs has been investigated. With one exception, all xenoestrogens studied were determined in all toilet paper samples at very high concentrations of 2 - 430 mg/kg dry mass (dm). The concentration of BPA in toilet paper amounted to 3.2 mg/kg dm, 45.5 mg/kg dm and 46.1 mg/kg dm. In seven fractions of separately collected municipal wastepaper the concentrations of BPA amounted to 0.093 to 5.1 mg/kg dm. In three types of cellulose the EAC concentrations were below or hardly above the respective limit of quantitation. Toilet paper, thus, was shown being an important source of xenoestrogen emissions to wastewater. Thermal paper again is assessed as being a major source for the contamination of recycled paper products with BPA. Because of the distinct contamination with xenoestrogens, both paper waste and recycled paper products should not be mixed with biological waste e.g. for co-composting or co-fermentation in order to derive organic fertilisers.
Some thermal paper receipts, commonly referred to as cash register receipts, contain high levels of bisphenol A (BPA). The goal of this study is to investigate whether increased contact with thermal paper receipts is associated with an increase in urinary BPA excretion. Individuals from the NHANES 2003-2004 survey were stratified based on occupation to compare urinary BPA excretion levels. The first major finding demonstrates that individuals with potential occupational exposure to thermal paper receipts are more likely to have detectable levels of urinary BPA compared to individuals with unlikely occupational exposure (p-value < 0.001). The second major finding is that females with potential occupational exposure to thermal paper receipts have significantly higher levels of urinary BPA excretion (geometric mean (GM): 5.45 µg/L, 95% CI: (4.02, 7.39)) compared to females with unlikely occupational exposure (GM: 2.16 µg/L, 95% CI: (1.73, 2.70)). This association continues to remain statistically significant when controlling for creatinine, race, body mass index (BMI), and age. Notably, there was no statistically significant association between occupation and urinary BPA excretion among males. These results suggest that exposure to BPA from thermal paper should be considered when determining aggregate BPA exposure.
Bisphenol A (BPA) is an endocrine and metabolic disruptor commonly employed as a color developer in thermal papers. Consequently, BPA derived from thermal papers has been considered an important source of exposure for humans, since this chemical may migrate from paper to skin upon contact. Further, due to recent restrictions on BPA use in some countries, it has been replaced by a new analogue, bisphenol S (BPS). The aim of the present study was to determine levels of BPA and BPS in 190 different thermal receipts, randomly collected from different locations in São Paulo State, Brazil, including receipts from supermarkets, general and fast-food restaurants, gas stations, bus and airplane tickets, and credit card and bank accounts. BPA and/or BPS were detected in 98% of samples at concentrations ranging from below the quantification limit to 4.3% (mg/100 mg paper). The obtained values were higher than amounts previously reported in other countries. The estimated daily intake through dermal absorption from handling of thermal receipt papers was estimated on the basis of concentrations and frequencies of handling of papers by humans in both the general population and occupationally exposed individuals. Fifth percentile, median, and 95th percentile daily intakes by the general population were 0.44, 1.42, and 2 μg/d, respectively, whereas the corresponding values for occupationally exposed population are 21.8, 71 and 101 μg/d. The potential adverse consequences of elevated occupational exposure are currently being examined.
Because of regulatory actions and public concerns, the use of BPA may decrease, while the use of BPA alternatives may increase. Although BPA alternatives are considered safer than BPA, their effects on health are still largely unknown. For risk assessment, understanding exposure to these chemicals is necessary. We measured the urinary concentrations of BPA and three bisphenol analogs, bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in 616 archived samples collected from convenience samplings of U.S. adults at eight time points between 2000 and 2014. We detected BPA at the highest frequency and geometric mean (GM) concentrations (74-99%, 0.36-2.07 µg/L), followed by BPF (42-88%, 0.15-0.54 µg/L) and BPS (19-74%, <0.1-0.25 µg/L); BPAF was rarely detected (<3% of all samples). Although concentrations of BPF were generally lower than for other bisphenols, the 95th percentile concentration of BPF was often comparable or higher than that of BPA. We did not observe obvious exposure trends for BPF. However, the significant changes in GM concentrations of BPA and BPS suggest that exposures may be declining (BPA) or on the rise (BPS). Nationally representative data will be useful to confirm these findings and to allow monitoring future exposure trends to BPA and some of its bisphenol alternatives.