Article

Scientific Opinion on the Risks to Public Health Related to the Presence of Bisphenol A (BPA) in Foodstuffs: Part I - Exposure Assessment

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Abstract

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.

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... Widespread human exposure is mainly due to leaching from food contact materials, but also to consumers' products such as thermal papers. The European Food Safety Authority (EFSA) has recently estimated the average total exposure to BPA from food and nonfood sources in 152 and 146 ng kg À1 body weight (bw) day À1 , respectively for women and men (EFSA, 2015a). The continuous exposure is confirmed by biomonitoring studies that detected measurable levels of BPA in 95% samples of the general population, with urinary average values ranging between 1.1 and 3.6 ng ml À1 , and serum values up to 3.8 ng ml À1 (EFSA, 2015a). ...
... 26 and the OECD Principles on Good Laboratory Practice. Dose levels were selected according to two EFSA Opinions (EFSA, 2006(EFSA, , 2015a, namely, the high-dose level of 50 mg kg À1 bw day À1 represents the LOAEL of the three-generation study in rat, thus corresponding to a dose level likely inducing reproductive/developmental effects (EFSA, 2006); the lower BPA dose level of 0.5 mg kg À1 bw day À1 corresponds to 4.4-fold the conservative oral human equivalent dose (HED) of 113 μg kg À1 bw, recently used by EFSA to define the new temporary TDI (EFSA, 2015a). CD-1 female mice (10 in control and five in treatment groups, 30-35 g bw) were purchased from Harlan (San Pietro al Natisone, Italy) and kept under standard laboratory conditions (22 ± 0.5°C, 50-60% relative humidity, 12 h dark-light alternation with 12-14 air changes h À1 ) with water and food (4RF25 GLP "Top Certificate" diet; Mucedola, Milan, Italy) available ad libitum. ...
Article
Bisphenol A (BPA) is a widespread endocrine disrupter mainly used in food contact plastics. Much evidence supports the adverse effects of BPA, particularly on susceptible groups such as pregnant women. The present study considered placental development - relevant for pregnancy outcomes and fetal nutrition/programming - as a potential target of BPA. Pregnant CD-1 mice were administered per os with vehicle, 0.5 (BPA05) or 50 mg kg(-1) (BPA50) body weight day(-1) of BPA, from gestational day (GD) 1 to GD11. At GD12, BPA50 induced significant degeneration and necrosis of giant cells, increased vacuolization in the junctional zone in the absence of glycogen accumulation and reduction of the spongiotrophoblast layer. In addition, BPA05 induced glycogen depletion as well as significant nuclear accumulation of β-catenin in trophoblasts of labyrinthine and spongiotrophoblast layers, supporting the activation of the Wnt/β-catenin pathway. Transcriptomic analysis indicated that BPA05 promoted and BPA50 inhibited blood vessel development and branching; morphologically, maternal vessels were narrower in BPA05 placentas, whereas embryonic and maternal vessels were irregularly dilated in the labyrinth of BPA50 placentas. Quantitative polymerase chain reaction evidenced an estrogen receptor β induction by BPA50, which did not correspond to downstream genes activation; indeed, the transcription factor binding sites analysis supported the AhR/Arnt complex as regulator of BPA50-modulated genes. Conversely, Creb appeared as the main transcription factor regulating BPA05-modulated genes. Embryonic structures (head, forelimb) showed divergent perturbations upon BPA05 or BPA50 exposure, potentially related to unbalanced embryonic nutrition and/or to modulation of genes involved in embryo development. Our findings support placenta as an important target of BPA, even at environmentally relevant dose levels. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
... Im Erdboden scheint BPA lediglich in der Lage zu sein sich in oberflächliche Erd-oder Sedimentschichten (≤ 30 cm) abzusetzen und wird primär über aerobe Abbauprozesse zersetzt (Xu et al. 2009;EFSA 2015a). ...
... Es wird direkt vor Ort sowie alternativ in der Leber metabolisiert. Dabei wird die Chemikalie vornehmlich mit Hilfe des Enzyms UDP-Glucuronyltransferase an Glucuronsäure gebunden (Biotransformation: Phase-II-Reaktion).Alternativ bindet BPA in geringerem Maße mit Hilfe von Sulfotransferasen auch an Sulfat(Völkel et al. 2002;Hanioka et al. 2008;EFSA 2015a). Durch die Bindung (Konjugation) wird das BPA biologisch inaktiv und verliert seine endokrine Wirkung im Körper(Matthews et al. 2001). ...
Thesis
Zielsetzung Ziel dieser Studie war der qualitative und quantitative Nachweis einer Freisetzung von BPA ins Abwasser beim Beschleifen von dentalen Kompositfüllungsmaterialien sowie die Untersuchung drei verschiedener Filtermaterialien zur Reduktion des BPA-Gehalts. Methode Es wurden vier moderne Füllungsmaterialien ausgewählt (Ceram X mono, Filtek Supreme XTE, Filtek Silorane und Core X Flow). Für jedes Komposit wurde eine identische Anzahl an Materialproben (5x2mm, n=10) nach Herstellerangaben ausgehärtet (20s). Diese wurden anschließend von Hand mit einem wassergekühlten Bohrer, an einer vom Wasserkreislauf getrennten Dentaleinheit, beschliffen (200.000 U/min; 90s). Das entstandene Abwasser wurde in Glasflaschen aufgefangen und für sechs Monate bei 7°C gelagert. Die angewandte Studienmethode bestand aus einer Aufkonzentrierung mittels SPE-Verfahren sowie einer chemischen Analyse mit Hilfe von Hochleistungsflüssigkeits-chromatographie und Fluoreszenzdetektion (HPLC-FLD). Drei Filtergranulate (Zeosorb, Katalox Light und Catalytic Carbon) wurden auf ihr Potenzial untersucht BPA aus einem wässrigen Medium zu entfernen. Dafür wurden jeweils gleiche Volumen mit bekannter BPA-Konzentration durch befüllte Filterapparaturen durchlaufen gelassen. Die chemische Analyse des Wasser erfolgte vor und nach Durchlauf mit der identischen Methode der Wasserproben. Ergebnisse Beim Beschleifen aller untersuchten Kompositmaterialien ließ sich BPA im Abwasser qualitativ nachweisen. Die Konzentrationen lagen insgesamt in einem Bereich von < LOD-0,192 μg/ml. Ceram X mono und Filtek Supreme XTE zeigten vergleichbare Konzentrationen (p > 0,05), die im Vergleich zu Filtek Silorane und Core X Flow jeweils signifikant erhöht waren (p < 0,05). Bei der Filtereffizienz zeigte Catalytic Carbon die mit Abstand höchste Filtereffizienz (99,38%) vor Zeosorb (7,91%) und Katalox Light). Lediglich Aktivkohle führte zu einer klinisch signifikanten Reduktion des BPA-Gehalts (p < 0,05). Fazit BPA kann durch das Beschleifen von dentalen Kompositfüllungen in das Abwasser gelangen. Die Freisetzungmenge erscheint dabei abhängig vom jeweiligen Material zu sein. Unter allen getesteten Filtermaterialien erscheint Aktivkohle bei der Reduktion von BPA im Abwasser besonders effizient zu sein.
... Since 2006, the European Food Safety Authority (EFSA) has conducted several scientific assessments on BPA. The last scientific opinion, published in January 2015, consists of three separate documents, namely Executive Summary [79]; Part I-Exposure assessment [96] and Part II-Toxicological assessment and risk characterization [80]. In this opinion, the EFSA Panel on Food Contact Materials, Enzymes, Flavorings and Processing Aids has established a temporary Tolerable Daily Intake (t-TDI) of 4 mg kg À1 body weight per day and it has concluded that there is no consumer health risk from BPA exposure. ...
... Nevertheless, bans on the use of BPA for food packaging intended for young children (zero to three years old) have been proposed by several EU Member States (viz. Denmark, Sweden, France, Belgium and Austria) [96]. The U.S. Environmental Protection Agency (EPA) and U.S. Food and Drug Administration (FDA) have chosen not to regulate BPA due to insufficient scientific evidence of adverse human health effects at low-levels of exposure [97,98], despite provisions for its elimination from some products such as baby bottles [98]. ...
Article
Bisphenol A (BPA) is ubiquitous in humans and the environment. Its potential adverse effects through genomic and non-genomic pathways have fostered BPA replacement by bisphenol analogs that, unfortunately, exert similar adverse effects. Many of these analogs, as well as their derivatives, have already found in humans and the environment and major concerns have arisen over their low dose- and mixture-related effects. This review aims to discuss the characteristics of the main analytical methods reported so far for the determination of mixtures of bisphenol analogs and/or derivatives in human and environmental exposure sources and biological fluids. Approaches followed for removal of background contamination, sample preparation and separation and detection of mixtures of bisphenols and derivatives are critically discussed. Sample treatment is matrix-dependent and common steps include analyte isolation, removal of interferences, evaporation of the extracts and solvent reconstitution. Separation and quantification has been almost exclusively carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS) or gas chromatography mass spectrometry (GC–MS), in the last case prior derivatization, but LC-fluorescence detection has also found some applications. Main characteristics, advantages and drawbacks of these methods will be comparatively discussed. Although at an early stage, some approaches for the assessment of the risk to mixtures of bisphenols, mainly based on the combination of chemical target analysis and toxicity evaluation, have been already applied and they will be here presented. Current knowledge gaps hindering a reliable assessment of human and environmental risk to mixtures of bisphenols and derivatives will be outlined.
... Bununla birlikte, bu etki EFSA'nın belirsizlik analizine dahil edilmiştir. 45 Ayrıca bazı hayvan çalışmalarında ise, düşük doz BPA maruziyetinin insülin direnciyle ilişkili olduğunu belirtilmiştir. 44 Yakın tarihli değerlendirmesinde EFSA (European Food Safety Authority), t-TDI' nın bir Benchmark doz (karşılaştırma dozu) modelleme yaklaşımının türetilmesi için kullanılmış ve farelerde genel bir toksisite çalışmasında böbrek üzerindeki etkilere dayanılarak 8960 μg/kgbw/gün bir BMDL10 (lower confidence limit on the bench-mark dose-%10 tepkiyle ilişkili olan karşılaştırma dozu) değeri türetilmiştir. ...
... 44 Yakın tarihli değerlendirmesinde EFSA (European Food Safety Authority), t-TDI' nın bir Benchmark doz (karşılaştırma dozu) modelleme yaklaşımının türetilmesi için kullanılmış ve farelerde genel bir toksisite çalışmasında böbrek üzerindeki etkilere dayanılarak 8960 μg/kgbw/gün bir BMDL10 (lower confidence limit on the bench-mark dose-%10 tepkiyle ilişkili olan karşılaştırma dozu) değeri türetilmiştir. 45 Hem düşük doz hem de iki yüksek doz içeren sıçanlardaki çalışmalardan elde edilen son bir raporda toksisite sadece yüksek doz gruplarında gözlenirken NOAEL'in 5 mg/kg bw/gün (75 ppm, oral maruz kalma) dozunda toksisite oluşturmadığı belirtilmiştir. 51 BPA'nın dental ve diğer literatürlerde çok çalışılan bir konu olması, onun endokrin bozucu bir kimyasal olabileceği düşüncesinden kaynaklanmaktadır. ...
... That means a nonlinear relationship between dose and effect, where the slope of the curve changes sign somewhere within the range of doses examined [15,16]. In January 2015, the European Food Safety Authorities (EFSA) published its latest comprehensive re-evaluation of BPA exposure and toxicity, and concluded no risks at actual exposure levels [17]. However, a lower Tolerable Daily Intake (TDI) has been set at 4 g/kg bw/day (ie 12.5 times less than the previous TDI). ...
... Anyway, this amount remains very far below the TDI set at 4 g/kg bw/day and also far below the highest mean exposure estimated by EFSA for children older than 3 years at 0.7 g/kg bw/day (i.e. 21 g/day for a 30-kg child) [17]. In vivo exposure to BPA from orthodontic resin would be therefore extremely low, more than 42 000 times lower than the TDI for a 30-kg-child, thus negligible. ...
Article
Objectives: First, to analyse the in vitro release of BPA and Bis-GMA from an orthodontic resin composite (Transbond XT, 3M Unitek), stored in various conditions, by gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS); then to extrapolate the data to the clinical situation. Secondly, to explore the thermal stability of Bis-GMA. Methods: Cylinders of resin composite were prepared and stored according to 3 different protocols: (1) they were light-cured 20s, then placed in artificial saliva; (2) they were light-cured 2s, then placed in acetonitrile; (3) they were light-cured 2s, then placed in methanol. For each group, BPA and Bis-GMA release were determined with GC/MS and/or LC/MS at least after one week. Besides, 120 brackets (10 of each type) were bonded over metal teeth, then debonded, and the weight and the surface of resin composite residues were measured. BPA and Bis-GMA release of adhesive residues were extrapolated from the data obtained with the cylinders. Besides, BPA release from a heated Bis-GMA solution was measured. Results: With GC/MC, BPA was detected in all samples. With LC/MS, BPA was detected only from samples immersed in MeOH; Bis-GMA was detected, in varying amount according to the extraction media and the light-curing time. BPA was found after heating of the Bis-GMA solution. Significance: Contamination risk and the heat applied in GC/MS may overestimate the BPA release from resin composite. Based on the LC/MS results, the risk of BPA release after orthodontic bonding would be more than 42000 times lower than the TDI for a 30-kg child.
... Bununla birlikte, bu etki EFSA'nın belirsizlik analizine dahil edilmiştir. 45 Ayrıca bazı hayvan çalışmalarında ise, düşük doz BPA maruziyetinin insülin direnciyle ilişkili olduğunu belirtilmiştir. 44 Yakın tarihli değerlendirmesinde EFSA (European Food Safety Authority), t-TDI' nın bir Benchmark doz (karşılaştırma dozu) modelleme yaklaşımının türetilmesi için kullanılmış ve farelerde genel bir toksisite çalışmasında böbrek üzerindeki etkilere dayanılarak 8960 μg/kgbw/gün bir BMDL10 (lower confidence limit on the bench-mark dose-%10 tepkiyle ilişkili olan karşılaştırma dozu) değeri türetilmiştir. ...
... 44 Yakın tarihli değerlendirmesinde EFSA (European Food Safety Authority), t-TDI' nın bir Benchmark doz (karşılaştırma dozu) modelleme yaklaşımının türetilmesi için kullanılmış ve farelerde genel bir toksisite çalışmasında böbrek üzerindeki etkilere dayanılarak 8960 μg/kgbw/gün bir BMDL10 (lower confidence limit on the bench-mark dose-%10 tepkiyle ilişkili olan karşılaştırma dozu) değeri türetilmiştir. 45 Hem düşük doz hem de iki yüksek doz içeren sıçanlardaki çalışmalardan elde edilen son bir raporda toksisite sadece yüksek doz gruplarında gözlenirken NOAEL'in 5 mg/kg bw/gün (75 ppm, oral maruz kalma) dozunda toksisite oluşturmadığı belirtilmiştir. 51 BPA'nın dental ve diğer literatürlerde çok çalışılan bir konu olması, onun endokrin bozucu bir kimyasal olabileceği düşüncesinden kaynaklanmaktadır. ...
Article
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ÖZET Bisfenol A (BPA), diş hekimliğinde kullanılan kompozit rezinlerin temelinde olduğu bili- nen bir molekül olan bisfenol A glisidilmetakrilatın (Bis-GMA veya "Bowen reçinesi") önemli bir bileşenidir. Uluslararası diş hekimliği literatüründe, BPA ve/veya türevlerinin etken madde üre- tebilen dozlarda kompozit dolgu ve fissür örtücülerden ağız boşluğuna salınabileceği savunul- maktadır. Aynı zamanda BPA bileşiğinin; zayıf östrojenik özelliklere sahip olduğu düşünülmekte, düşük dozlarının bile nörolojik rahatsızlıklara neden olabileceği varsayımıyla sağlığa zararlı ol- duğu öne sürülmektedir. Bu makalede BPA’nın sadece östrojenik aktivitesi ile ilgili değil diğer sis- temik etkileri üzerinde de durularak, dental materyallerden salınan BPA’nın en aza indirgenmesi için alınması gereken önlemlerin vurgulanması amaçlanmaktadır. Anahtar Kelimeler: Bisfenol A; restoratif materyaller; diş hekimliği ABSTRACT Bisphenol A (BPA) is a significant compound of bisphenol A glysidilmetacrylate (Bis- GMA or Bowen’s resin) which known to be a molecule in the bases of composite resins used in dentistry. In the international literature of dentistry, it has been asserted that BPA and/or its de- rivatives can be released from composite fillings or fissure sealants into the oral cavity. At the same time, BPA is thought to be having weak estrogenic compounds and it is proposed to be haz- ardous for health by assuming that it can lead to neurologic disorders even at the low dosages of human exposure. The aim of this article is to emphasize the importance of the measures to be taken for minimizing BPA that is released from resin based dental materials, by accentuating not only the estrogenic activities of BPA but also its other systemic effects. Keywords: Bisphenol A; restorative materials; dentistry
... The print surface of thermal paper is coated with milligrams of free BPA per gram paper as a heat-activated print developer[6], and it appears that free BPA is readily transferred to other materials that the thermal paper contacts[7]. While small lipophilic compounds such as BPA (logP = 3.4; molecular weight 228 Da) can pass through skin[8,9], regulatory agencies have assumed that this route of human BPA exposure should not be significant in spite of the lack of data and acknowledged ''significant uncertainties'' around the issue of human exposure to BPA from thermal paper[10]. However, a factor that has not been considered in estimating transdermal exposure to BPA from thermal paper is that hand sanitizers are now commonly used, particularly in fast-food restaurants where people may handle thermal receipts before eating or ordering food. ...
Article
Full-text available
Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone's urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults.
... While the primary source of BPA effects789. exposure is through food, there is uncertainty with regard BPA reportedly have the potential to produce to the amount of exposure that can also occur dermally widespread adverse effects through their endocrine and through air [2,17181920. However, recent evidence also disrupting activity, such as carcinogenicity, neurotoxicity, indicates that exposure may occur through dermal contact immunotoxicity, interference with the cardiovascular with thermal paper, used widely in cash register receipts toxicity and so on [8,10]. ...
Article
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Bisphenol-A (BPA) is an organic compound with two phenol functional groups. Bisphenol-A (BPA) is a widely used industrial plasticizer with known estrogenic properties. It is used in the manufacture of epoxy resins and polycarbonate plastics. This study was designed to evaluate and assess the possible teratogenicity of BPA administrated to pregnant rats. Sixty pregnant Wistar albino rats (10 RAT/group) were administrated oral doses of Bisphenol-A (300 & 600 mg/kg /day) from 6 up to both 15 and 19 days (GD15 & GD19) of th th th gestation. While, control groups received Olive oil only. The obtained data revealed that, pregnant rats treated with Bisphenol-A showed states of instability, nervousness, twitching of head, agitation, hazy movement and marked reduction in food intake as well as reduction in the body weight. Uteri were removed and dissected to evaluate the intrauterine growth retardations as well as skeletal malformation. BPA doses induced reduction in implantation sites, foetal body weight, with a symmetrical distribution of embryos in both uterine horns. Increase in both mortality and resorption rates were reported. BPA also induced decrease in the embryonic crown rump values and induced severe skeletal anomalies on both 15 and 19 days of gestation. In conclusion, th th this study shaded more light on the teratogenicity of BPA on embryonic development and the adverse effects on the pregnant female rats.
... and flame retardants. There is growing concern over the implication of BPA as a causative agent in some chronic human diseases, including diabetes, obesity, cardiovascular disease, reproductive disorders, birth defects, chronic respiratory and kidney diseases, and breast cancer [3,4]. 17␣-ethinylestradiol (EE2) is a synthetic estrogen used in contraceptive pills. ...
Article
In recent years, there has been an increase in efforts to improve wastewater treatment as the concentration of dangerous pollutants, such as endocrine disrupting chemicals, in wastewater increases. These compounds, which mimic the effect of hormones, have a negative impact on human health and are not easily removed from water. One way to effectively eliminate these pollutants is to use enzymatically activated materials. In this study, we report on the use of laccase from the white rot fungus Trametes versicolor immobilized onto polyamide 6/chitosan (PA6/CHIT) nanofibers modified using two different spacers (bovine serum albumin and hexamethylenediamine). We then tested the ability of the PA6/CHIT-laccase biocatalysts to eliminate a mixture containing 50 μM of two endocrine disrupting chemicals: bisphenol A and 17α-ethinylestradiol. The PA6/CHIT nanofiber matrix used in this study not only proved to be a suitable carrier for immobilized and modified laccase but was also efficient in the removal of a mixture of endocrine disrupting chemicals in three treatment cycles.
... Monomers, exerting the estrogenic activity, can seep into the water or food following breakdown of polymers. 13 The EFSA considers diet as the major source of BPA exposure. 14 Exposure to BPA is nearly ubiquitous with concentration in human serum ranging from 0.2 to 1.6 ng/ml and it accumulates in fat. ...
Article
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Epidemiologic and experimental studies have associated changes of blood glucose homeostasis to Bisphenol A (BPA) exposure. We took a toxicogenomic approach to investigate the mechanisms of low-dose (1 × 10(-9 )M) BPA toxicity in ex vivo cultures of primary murine pancreatic islets and hepatocytes. Twenty-nine inhibited genes were identified in islets and none in exposed hepatocytes. Although their expression was slightly altered, their impaired cellular level, as a whole, resulted in specific phenotypic changes. Damage of mitochondrial function and metabolism, as predicted by bioinformatics analyses, was observed: BPA exposure led to a time-dependent decrease in mitochondrial membrane potential, to an increase of ROS cellular levels and, finally, to an induction of apoptosis, attributable to the bigger Bax/Bcl-2 ratio owing to activation of NF-κB pathway. Our data suggest a multifactorial mechanism for BPA toxicity in pancreatic islets with emphasis to mitochondria dysfunction and NF-κB activation. Finally, we assessed in vitro the viability of BPA-treated islets in stressing condition, as exposure to high glucose, evidencing a reduced ability of the exposed islets to respond to further damages. The result was confirmed in vivo evaluating the reduction of glycemia in hyperglycemic mice transplanted with control and BPA-treated pancreatic islets. The reported findings identify the pancreatic islet as the main target of BPA toxicity in impairing the glycemia. They suggest that the BPA exposure can weaken the response of the pancreatic islets to damages. The last observation could represent a broader concept whose consideration should lead to the development of experimental plans better reproducing the multiple exposure conditions.
... Currently, estimates and predictions of human exposure to substances in food can involve the use of conservative default assumptions. The conservative nature of the default assumptions can be seen from the increasing evidence that direct measurements (biomonitoring) in humans usually demonstrate much lower exposures than those derived from exposure estimates, as has been shown for example, for phthalates and bisphenol A (Qian, Chen, Kransler, & Zaleski, 2014;EFSA, 2015). While conservative default assumptions build in a high degree of safety in any risk-based approach, they may also result in unnecessary actions when overestimated exposures exceed health-based guidance values. ...
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Background: Food legislation in the European Union and elsewhere includes both hazard- and risk-based approaches for ensuring safety. In hazard-based approaches, simply the presence of a potentially harmful agent at a detectable level in food is used as a basis for legislation and/or risk management action. Risk-based approaches allow consideration of exposure in assessing whether there may be unacceptable risks to health. Scope and approach: The advantages and disadvantages of hazard- and risk-based approaches for ensuring the safety of food chemicals, allergens, ingredients and microorganisms were explored at an ILSI Europe workshop. Key findings and conclusions: It was concluded that both types of approach have their place, depending on the context. However, problems can arise when both types of approach are used in regulation by separate agencies that address different aspects of the same agent/substance present in food. This separation of decision-making can result in hazard-based restrictions on marketing and use, whereas risk-based assessments for those exposed show there is reasonable certainty no harm will result. This in turn can lead to contradictory, confusing and ultimately unnecessary actions. Use of hazard-based approaches for foods also means that comparisons with benefits for nutrition and food security cannot be undertaken. This has the potential to lead to bias in the overall conclusions of regulators and risk managers, who may not have been presented with the benefits of particular foods. The value of risk-based approaches is becoming increasingly recognised.
... If bisphenol A is used as an example of an additive, this mussel portion would contain 0.28 lg of bisphenol A. In a conservative scenario we could assume that bisphenol A would be completely released from the microplastic. EFSA estimated an average bisphenol A exposure of adults from dietary and non-dietary sources of 0.19-0.20 lg/kg bw per day (EFSA CEF Panel, 2015). So a 70-kg adult would ingest on average about 14 lg bisphenol A per day. ...
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Following a request from the German Federal Institute for Risk Assessment (BfR), the EFSA Panel for Contaminants in the Food Chain was asked to deliver a statement on the presence of microplastics and nanoplastics in food, with particular focus on seafood. Primary microplastics are plastics originally manufactured to be that size, while secondary microplastics originate from fragmentation. Nanoplastics can originate from engineered material or can be produced during fragmentation of microplastic debris. Microplastics range from 0.1 to 5,000 lm and nanoplastics from approximately 1 to 100 nm (0.001–0.1 lm). There is no legislation for microplastics and nanoplastics as contaminants in food. Methods are available for identification and quantification of microplastics in food, including seafood. Occurrence data are limited. In contrast to microplastics no methods or occurrence data in food are available for nanoplastics. Microplastics can contain on average 4% of additives and the plastics can adsorb contaminants. Both additives and contaminants can be of organic as well of inorganic nature. Based on a conservative estimate the presence of microplastics in seafood would have a small effect on the overall exposure to additives or contaminants. Toxicity and toxicokinetic data are lacking for both microplastics and nanoplastics for a human risk assessment. It is recommended that analytical methods should be further developed for microplastics and developed for nanoplastics and standardised, in order to assess their presence, identity and to quantify their amount in food. Furthermore, quality assurance should be in place and demonstrated. For microplastics and nanoplastics, occurrence data in food, including effects of food processing, in particular, for the smaller sized particles (< 150 lm) should be generated. Research on the toxicokinetics and toxicity, including studies on local effects in the gastrointestinal (GI) tract, are needed as is research on the degradation of microplastics and potential formation of nanoplastics in the human GI tract. Acknowledgements: The Panel wishes to thank the members of the Working Group on the presence of microplastics and nanoplastics in food, with particular focus on seafood:
... BPA may also alter brain physiology, reduce immune response to carcinogens, and interfere meiosis (Kitraki et al., 2016;McGinnis and Ostrom, 2014;Vandenberg et al., 2013). Based on a report from European Food Safety Authority (EFSA), diet is known as the major human exposure pathway to BPA (Husøy et al., 2015;Rudel et al., 2011). More importantly, it is shown that even extremely low doses, parts per trillion, can alter cell function (Wetherill et al.). ...
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... While polyethylene terephthalate (PET) bottles for beverages and laminated PET foils represent the largest application field, there are other PES materials that have been developed over the years and which have found their way onto the FCM market. The legal ban in the European Union of bisphenol A (BPA) as a monomer for baby bottles made of polycarbonate (PC) and the legal approaches of countries like Denmark and France to ban BPA from all food contact materials (FCMs) for babies is forcing manufacturers to look for substitute products (EU 2011;EFSA CEF Panel 2015). The copolyester Tritan™ developed by Eastman can be used for kitchen utensils at moderate temperatures and serves as a replacement product for drinking bottles made of PC. ...
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... If bisphenol A is used as an example of an additive, this mussel portion would contain 0.28 lg of bisphenol A. In a conservative scenario we could assume that bisphenol A would be completely released from the microplastic. EFSA estimated an average bisphenol A exposure of adults from dietary and non-dietary sources of 0.19-0.20 lg/kg bw per day (EFSA CEF Panel, 2015). So a 70-kg adult would ingest on average about 14 lg bisphenol A per day. ...
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An ultrasonic‐assisted dispersive liquid–liquid microextraction method for the simultaneous detection of four bisphenols (BPs) in plastic packaging beverages was established. The recoveries of the four BPs of spiked water solution were 89.0%–106.7%. The standard deviations (Ss) (n = 9) were 1.7%–2.0%. The recoveries of the 4 BPs in the real honey sample at three concentration levels ranged from 87.6% to 97.5%, and the Ss (n = 6) ranged from 1.0% to 2.3%. The method was employed to detect the 4 BPs (BPA, BPS, BPF, and BPAF) in plastic packaging drinking water, soda water, and honey samples. In drinking water samples, BPS was found in 8 out of 13 samples with a maximum concentration of 1.36 μg/L; BPA was found in four samples, and the maximum concentration was 1.08 μg/L. In soda samples, BPS was detected in six out of the eight samples with the maximum concentration of 27.44 μg/L; 11.40 μg/L BPA was detected in one sample; BPAF was detected in one sample and the concentration was below the limit of quantification. In 13 honey samples, BPF was detected in 12 samples, and the maximum concentration was 766.7 μg/kg; BPS was detected in six samples and the maximum concentration was 209.0 μg/kg; BPAF was detected in eight samples, and the maximum concentration was 197.7 μg/kg; BPA was detected in two samples, but the concentrations were all below the LOQ. Compared with other methods reported, the established method was simple, effective, and eco‐friendly. According to the process shown in the figure, the method for the rapid and simultaneous determination of the four trace bisphenols (BPS, BPF, BPA, and BPAF) in plastic packaged beverages was established. The method had good selectivity and extraction efficiency for the four BPs in the three types of beverages, and it was efficient, environmentally friendly, and easy to operate.
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There is extensive evidence that bisphenol A (BPA) is related to a wide range of adverse health effects based on both human and experimental animal studies. However, a number of regulatory agencies have ignored all hazard findings. Reports of high levels of unconjugated (bioactive) serum BPA in dozens of human biomonitoring studies have also been rejected based on the prediction that the findings are due to assay contamination and that virtually all ingested BPA is rapidly converted to inactive metabolites. NIH and industry-sponsored round robin studies have demonstrated that serum BPA can be accurately assayed without contamination, while the FDA lab has acknowledged uncontrolled assay contamination. In reviewing the published BPA biomonitoring data, we find that assay contamination is, in fact, well controlled in most labs, and cannot be used as the basis for discounting evidence that significant and virtually continuous exposure to BPA must be occurring from multiple sources.
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Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERa, ERb, AR, AhR, PPARg, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARg. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health.
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Nationally representative data on urinary levels of BPA and its metabolites in the United States from the 2003-2004 to 2011-2012 National Health and Nutrition Examination Surveys (NHANES) were used to estimate daily BPA intakes and examine temporal trends. Additionally, NHANES data on lifestyle/demographic/dietary factors previously reported to be associated with BPA exposures were examined to assess the resiliency of the reported associations (whether the association is maintained across the five surveys). Finally, various approaches for addressing issues with the use of BPA concentration data from spot urine samples were examined for their effect on trends and associations. Three approaches were assessed here: (i) use of generic literature-based 24-h urine excretion volumes, (ii) use of creatinine adjustments, and (iii) use of individual urine flow rate data from NHANES. Based on 2011-2012 NHANES urinary BPA data and assumptions described in this paper, the median daily intake for the overall population is approximately 25ng/kg day; median intake estimates were approximately two to three orders of magnitude below current health-based guidance values. Estimates of daily BPA intake have decreased significantly compared to those from the 2003-2004 NHANES. Estimates of associations between lifestyle/demographic/dietary factors and BPA exposure revealed inconsistencies related to both NHANES survey year and the three approaches listed above; these results demonstrate the difficulties in interpreting urinary BPA data, despite efforts to account for urine dilution and translation of spot sample data to 24-h data. The results further underscore the importance of continued research on how to best utilize urinary measures of environmental chemicals in exposure research. Until a consensus is achieved regarding the best biomonitoring approaches for assessing exposures to short-lived chemicals using urine samples, research on factors associated with BPA exposures should include - and report results from - assessments using both volume-based urinary BPA and creatinine-adjusted urinary BPA data. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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Rationale Due to the growing restrictions on the use of bisphenol A (BPA), several other bisphenols are gaining importance as substitutes for BPA in a variety of applications. There is, therefore, a real need for selective and sensitive methods based on mass spectrometry which will allow the human exposure to these new bisphenols to be assessed. Methods Derivatization of BPA and its substitutes with pyridine-3-sulfonyl chloride is used to enhance the detection capability of bisphenols by electrospray ionization mass spectrometry. A multivariate experimental design, Box-Behnken response surface, was used to evaluate the influence of the main variables potentially affecting the derivatization yield. Fragmentation patterns for all the derivatized bisphenols were acquired by high-resolution/accurate-mass Orbitrap mass spectrometry. Results Temperature and pH were identified as the most important factors affecting the derivatization yield of bisphenols. Fragmentation of the protonated molecules produced abundant analyte-specific product ions. Most of the derivatized bisphenols showed significant improvements in their signal-to-noise ratios compared with the underivatized forms. The stability of these derivatives was demonstrated through several freeze/thaw cycles, short-term room temperature and long-term cold storage. Conclusions Derivatization of BPA and its structural analogues with pyridine-3-sulfonyl chloride is proposed as a specific, sensitive, high-throughput approach to their analysis by liquid chromatography coupled to electrospray ionization mass spectrometry.
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Bisphenol A (BPA) is an industrial chemical produced in large volumes. Its main use is associated with polycarbonate plastic, epoxy resins and thermal paper. In contrast to other applications, thermal paper contains BPA in its un-reacted form as an additive, which is subjected to migration. Receiving a significant amount of attention from the scientific community and beyond, due to its controversial endocrine-disrupting effects, the industry is attempting to substitute BPA in variety of applications. Alternative phenolic compounds have been proposed for use in thermal paper; however, information to what extent BPA alternatives have been used in paper is sparse. The aim of the present work was to quantify BPA and its alternatives (bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB), 4-cumylphenol (HPP) and bisphenol F (BPF)) in waste paper and board from Danish households, thermal paper receipts, non-carbon copy paper and conventional printer paper. BPA was found in all waste paper samples analysed, while BPS was identified in 73% of them. Only BPB was not identified in any of the samples. BPA and BPS were found in the majority of the receipts, which contained no measurable concentrations of the remaining alternatives. Although receipts showed the highest concentrations of BPA and BPS, office paper, flyers and corrugated boxes, together with receipts, represented the major flux of the two compounds in waste paper streams. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Plastics are highly versatile materials that have brought huge societal benefits. They can be manufactured at low cost and their lightweight and adaptable nature has a myriad of applications in all aspects of everyday life, including food packaging, consumer products, medical devices and construction. By 2050, however, it is anticipated that an extra 33 billion tonnes of plastic will be added to the planet. Given that most currently used plastic polymers are highly resistant to degradation, this influx of persistent, complex materials is a risk to human and environmental health. Continuous daily interaction with plastic items allows oral, dermal and inhalation exposure to chemical components, leading to the widespread presence in the human body of chemicals associated with plastics. Indiscriminate disposal places a huge burden on waste management systems, allowing plastic wastes to infiltrate ecosystems, with the potential to contaminate the food chain. Of particular concern has been the reported presence of microscopic plastic debris, or microplastics (debris ≤1 mm in size), in aquatic, terrestrial and marine habitats. Yet, the potential for microplastics and nanoplastics of environmental origin to cause harm to human health remains understudied. In this article, some of the most widely encountered plastics in everyday use are identified and their potential hazards listed. Different routes of exposure to human populations , both of plastic additives, microplastics and nanoplastics from food items and from discarded debris are discussed. Risks associated with plastics and additives considered to be of most concern for human health are identified. Finally, some recent developments in delivering a new generation of safer, more sustainable polymers are considered.
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Marine pollution gives rise to concern not only about the environment itself but also about the impact on food safety and consequently on public health. European authorities and consumers have therefore become increasingly worried about the transfer of contaminants from the marine environment to seafood. So-called “contaminants of emerging concern” are chemical substances for which no maximum levels have been laid down in EU legislation, or substances for which maximum levels have been provided but which require revision. Adequate information on their presence in seafood is often lacking and thus potential risks cannot be excluded. Assessment of food safety issues related to these contaminants has thus become urgent and imperative. A database (www.ecsafeseafooddbase.eu), containing available information on the levels of contaminants of emerging concern in seafood and providing the most recent data to scientists and regulatory authorities, was developed. The present paper reviews a selection of contaminants of emerging concern in seafood including toxic elements, endocrine disruptors, brominated flame retardants, pharmaceuticals and personal care products, polycyclic aromatic hydrocarbons and derivatives, microplastics and marine toxins. Current status on the knowledge of human exposure, toxicity and legislation are briefly presented and the outcome from scientific publications reporting on the levels of these compounds in seafood are presented and discussed.
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Due to the worldwide concern that bisphenol A might act as an endocrine disruptor, alternative materials for polycarbonate (PC) have been introduced on the European market. However, PC-replacement products might also release substances of which the toxicological profile - including their genotoxic effects - has not yet been characterized. Because a thorough characterization of the genotoxic profile of all these substances is impossible in the short term, a strategy was developed in order to prioritize those substances for which additional data are urgently needed. The strategy consisted of a decision tree using hazard information related to genotoxicity. The relevant information was obtained from the database of the European Chemicals Agency (ECHA), in silico prediction tools (ToxTree and Derek NexusTM) and the in vitro Vitotox® test for detecting DNA damage. By applying the decision tree, substances could be classified into different groups, each characterized by a different probability to induce genotoxic effects. Although none of the investigated substances could be unequivocally identified as genotoxic, the presence of genotoxic effects could neither be excluded for any of them. Consequently, all substances require more data to investigate the genotoxic potential. However, the type and the urge for these data differs among the substances.
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Chemicals are used in materials as additives in order to improve the performance of the material or the production process itself. The presence of these chemicals in recyclable waste materials may potentially affect the recyclability of the materials. The addition of chemicals may vary depending on the production technology or the potential end-use of the material. Paper has been previously shown to potentially contain a large variety of chemicals. Quantitative data on the presence of chemicals in paper are necessary for appropriate waste paper management, including the recycling and re-processing of paper. However, a lack of quantitative data on the presence of chemicals in paper is evident in the literature. The aim of the present work is to quantify the presence of selected chemicals in waste paper derived from households. Samples of paper and board were collected from Danish households, including both residual and source-segregated materials, which were disposed of (e.g., through incineration) and recycled, respectively. The concentration of selected chemicals was quantified for all of the samples. The quantified chemicals included mineral oil hydrocarbons, phthalates, phenols, polychlorinated biphenyls, and selected toxic metals (Cd, Co, Cr, Cu, Ni, and Pb). The results suggest large variations in the concentration of chemicals depending on the waste paper fraction analysed. Research on the fate of chemicals in waste recycling and potential problem mitigation measures should be focused on in further studies.
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The gavage route is often used for the toxicological evaluation of food contaminants. This route does not take into account absorption of the toxicants through the buccal mucosa, as evidenced in dogs for bisphenol A (BPA). Our goal was to determine the functional significance of buccal BPA absorption during dietary exposure. Four ewes received BPA by nasogastric gavage (100 mg/kg) and through food pellets (10 mg/kg), 13 days apart. The time course of serum concentrations of BPA and its main metabolite BPA-G was submitted to non-compartmental analysis. The dietary route led to 3-fold higher bioavailability as compared to gavage. The ratio of BPA-G to BPA concentrations varied greatly over time after the food administration, but not after gavage, suggesting a delayed metabolism of BPA after dietary exposure. The maximum entrance rate of BPA in the systemic circulation, determined by deconvolution analysis, was much higher after dietary administration than after gavage and a biphasic pattern of BPA entry was observed in 3 of the 4 ewes. Our results evidenced a dual mechanism of BPA absorption (buccal and digestive) after dietary exposure and highlight the necessity to take buccal absorption into account when evaluating food contaminants.
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Rehabilitation of aged drinking water pipes is an extensive renovation and increasingly topical in many European cities. Spray-on-lining of drinking water pipes is an alternative cost-effective rehabilitation technology in which the insides of pipes are relined with organic polymer. A commonly used polymer is epoxy resin consisting of monomer bisphenol A (BPA). Leaching of BPA from epoxy lining to drinking water has been a concern among public and authorities. Currently epoxy lining is not recommended in some countries. BPA leaching has been demonstrated in laboratory studies but the behavior and ageing process of epoxy lining in situ is not well known. In this study 6 locations with different age epoxy linings of drinking water pipes done using two distinct technologies were studied. While bisphenol F, 4-n-nonylphenol, and 4-t-octylphenol were rarely found and in trace concentrations, BPA was detected in majority of samples. Pipes lined with the older technology (LSE) leached more BPA than those with more recent technology (DonPro): maxima in cold water were 0.25 μg/L and 10 ng/L, respectively. Incubation of water in pipes 8–10 h prior to sampling increased BPA concentration in cold water 1.1–43-fold. Hot water temperature caused even more BPA leaching - at maximum 23.5 μg/L. The influence of ageing of epoxy lining on BPA leaching on could be shown in case of LSE technology: locations with 8–9 years old lining leached 4–20-fold more BPA compared to a location with 2-year-old lining. Analysis of metals showed that epoxy lining can reduce especially iron concentration in water. No significant burden to water could be shown by the analyzed 72 volatile organic compounds, including epichlorhydrin, precursor used in epoxy resin. Estrogenicity was detected in water samples with the highest BPA loads. Comparable responses of two yeast bioreporters (estrogen receptor α and BPA-targeted) indicated that bisphenol-like compounds were the main cause of estrogenicity. Compared to the estimated average daily BPA exposure, additional BPA load via cold drinking water in the studied locations was low, maximum 8.7%. However, hot water should also be considered as exposure source due to higher BPA concentrations. Epoxy lined locations should be monitored in future in order to evaluate ageing process and control increasing leaching of potentially harmful chemicals.
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Early in 2013, the World Health Organization (WHO) released a 2012 update to the 2002 State of the Science of Endocrine Disrupting Chemicals. Several significant concerns have been identified that raise questions about conclusions reached in this report regarding endocrine disruption. First, the report is not a state-of-the-science review and does not follow the 2002 WHO recommended weight-of-evidence approach. Second, endocrine disruption is often presumed to occur based on exposure or a potential mechanism despite a lack of evidence to show that chemicals are causally established as endocrine disruptors. Additionally, causation is often inferred by the presentation of a series of unrelated facts, which collectively do not demonstrate causation. Third, trends in disease incidence or prevalence are discussed without regard to known causes or risk factors; endocrine disruption is implicated as the reason for such trends in the absence of evidence. Fourth, dose and potency are ignored for most chemicals discussed. Finally, controversial topics (i.e., low dose effects, non-monotonic dose response) are presented in a one-sided manner and these topics are important to understanding endocrine disruption. Overall, the 2012 report does not provide a balanced perspective, nor does it accurately reflect the state of the science on endocrine disruption.
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