If you want to read the PDF, try requesting it from the authors.

Abstract and Figures

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.
Content may be subject to copyright.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Researchers have quantified BPA concentrations in thermal paper receipts in many countries, including the USA (Liao and Kannan, 2011a;Liao et al., 2012a;Mendum et al., 2011;Thayer et al., 2016), Belgium (Geens et al., 2012b), Denmark (Lassen et al., 2011), France (Ndaw et al., 2016), Germany (Eckardt and Simat, 2017), Switzerland (Biedermann et al., 2010;Goldinger et al., 2015), Brazil (Rocha et al., 2015), Japan, Vietnam, Korea (Liao and Kannan, 2011a;Liao et al., 2012a), and China (Fan et al., 2015;Lu et al., 2013). BPA concentrations were found to range from < 1 mg per g of paper to concentrations as high as 40 mg per g (< 0.1-4%), which is at least 250-to 1000-fold higher than findings in food-related matrices (Lopez-Espinosa et al., 2007;Lu et al., 2013). ...
... BPA was added to the restricted substances list by the European Commission (EC) in December 2016 (Regulation EC N°, 1907, leading to the prohibition of its presence in thermal paper at concentrations above 0.02% from January 2020 onward. Consequently, there has been an increase in the utilization of alternatives to BPÂ in thermal paper, most frequently bisphenol S (BPS) (Björnsdotter et al., 2017a(Björnsdotter et al., , 2017bLiao et al., 2012a), among others (Björnsdotter et al., 2017a(Björnsdotter et al., , 2017bEckardt and Simat, 2017;Goldinger et al., 2015). However, it is suspected that these alternatives may have similar toxicological properties to those of BPA (Eladak et al., 2015). ...
... Thus, in vitro studies have shown that BPS can bind to the ER (Björnsdotter et al., 2017b;Molina-Molina et al., 2013;Yamasaki et al., 2004), elicit estrogen-induced gene transcription (Hashimoto and Nakamura, 2000), induce cell proliferation in MCF7 cancer cells (Kuruto-Niwa et al., 2005), and inhibit free testosterone production (Goldinger et al., 2015). BPS has been detected and quantified in thermal paper receipts from different parts of the world (Eckardt and Simat, 2017;Goldinger et al., 2015;Liao et al., 2012a;Ndaw et al., 2018;Rocha et al., 2015). Likewise, widespread exposure to BPS has been reported in the general population of several countries (Liao et al., 2012b;Philips et al., 2018;Ye et al., 2015;Zhou et al., 2014), and increased BPS concentrations have been detected in the urine of workers handling thermal paper receipts (Hehn, 2016;Ndaw et al., 2018;Thayer et al., 2016). ...
Article
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.
... Several authors have developed studies about the diverse exposure sources for BPA: i) clothing items such as pantyhose [3] and socks [4]; ii) a wide variety of foods that are part of a normal diet [5]; iii) food packaging made of different materials [6,7]; iv) personal care products [8]; v) ambient sources such as dust in the home [9] or air in the workplace [10]; vi) other types of samples such as: toys [11], liquid medicines (syrups and injectables) [12], tickets (thermal paper) [13], printing inks [14], dental material [15] or medical devices [16]. In addition, the exposure of animals to BPA should also be taken into account, since bioaccumulation along the food chain can represent an additional source of BPA for humans [17]. ...
... In the bibliography consulted, it is noteworthy the wide variety of BPA substituents which were determined in different samples: foodstuffs [5], FCMs [24], thermal paper [13], source water and drinking water [25], human blood serum [26]. Nevertheless, a large number of investigations [27,28,29,30] showed that other bisphenols display similar effects as BPA, considering bisphenol AF (BPAF) more toxic and BPS less detrimental in comparison to BPA. ...
... Several analytical techniques have been used by other authors for the determination and quantification of BPA, such as molecular spectrofluorimetry from excitation-emission data matrices (EEMs) [33] or high performance liquid chromatography coupled to a fluorescence detector (HPLC-FLD) [11]. Simultaneous determination of BPA and other bisphenols has been carried out through gas chromatography-mass spectrometry (GC-MS) [34], ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) [25] or high performance liquid chromatography coupled to a diode array detector (HPLC-DAD) [13]. Regulation in force [35] suggests HPLC-DAD or HPLC-FLD in order to determine BPA, and that is why the previously optimized HPLC-DAD method [36] for the separation of the five selected bisphenols was chosen for the present work. ...
Article
Bisphenol A (BPA) is considered an endocrine disrupting chemical as it affects the human hormonal system and is widely used in polycarbonate (PC) manufacture. As the population is continually exposed to BPA, European regulations have limited its industrial use in cosmetics, thermal paper, toys and food contact materials. Because of these restrictions, other bisphenols are replacing BPA, but they show similar harmful effects as BPA. In this work, migration of five bisphenols (BPS, BPF, BPA, BPAF, BPZ) from BPA-free PC glasses into simulant B (3% acetic acid (w/v) in aqueous solution) has been determined by means of HPLC-DAD. For this task, twenty glasses were exposed to a migration test at 70°C for 24 hours, more severe conditions than the ones suggested in technical guides. Afterwards, PARAFAC (parallel factor analysis) decomposition, validation of PARAFAC models, and evaluation of CCα (decision limit) and CCβ (detection capability) were carried out. A study was performed by comparing the population results (concentration), obtained for analytical blanks (n=40) versus the ones obtained for the migration test from BPA-free polycarbonate glasses (n=40) by means of the corresponding probability density functions fitted for both populations. A statistically significant difference between both populations was only found for BPA. BPA migrated from PC glasses with concentration greater than 0.49 μg L⁻¹, for probabilities of false positive (α) and false negative (β) equal to 0.05 and 0.07, respectively. However, the maximum amount of BPA migrated from PC glasses was 5.60 μg L⁻¹, a value lower than the established limit for the specific migration of a non-authorised substance (10 μg kg⁻¹).
... The shapes of the cumulative distribution functions (CDFs) representing external exposures from TP differed for BPA and BPS exposure ( Figure S10) because of different BP amounts transferred per handling event: more BPS than BPA was transferred from TP to normal/dry skin, while more BPA was transferred to humid skin. 57 Therefore, assuming the same occurrence frequency for BPS and BPA, the exposures below the P90 (mostly estimates for normal/dry skin) were higher for BPS. Exposure estimates for BPA were significantly higher beyond the P90. ...
... Eckardt and Simat reported that the BPS amount transferred from TP to normal skin was considerably higher than the corresponding BPA amount, while for moist skin the transferred amount was higher for BPA. 57 Since generally the BP transfer to moist skin is higher than to normal skin, high cumulative exposures from TP were mostly driven by high BPA transfers from TP to moist skin, which was a skin type allocated to about 10% of the model population. The partial replacement of BPA with BPS in TP in the ARS reduced these high BPA exposure cases. ...
... Additionally, color developers other than BPA and BPS are increasingly used, such as Pergafast201 and D8, which can also lead to lower BPA occurrences. 57 Besides the occurrence, the daily handling frequency and the area of contact with TP are also variable and uncertain, 29 and the manner of handling is of importance, which we could not include in our assessment due to missing data. Since the BP transfer from TP to skin was found to be related to skin properties, 48,57,67 such properties need to be known for the population considered. ...
... None of the BPA alternatives was evaluated to be of no concern under all toxicological and ecological aspects, respectively. However, in recent studies, the actual use of several alternative color developers that were listed by the US EPA was reported [10][11][12][13][14][15][16][17]. In particular, the BPA analogue bisphenol S (BPS) was detected as one of the major substituents worldwide [12,[11][12][13][14][15][16][17]. ...
... In particular, the BPA analogue bisphenol S (BPS) was detected as one of the major substituents worldwide [12,[11][12][13][14][15][16][17]. On the European market, the non-phenolic substance Pergafast 201 (PF201) was also considered to be an important BPA alternative [10][11][12]15]. Besides, the use of a variety of structural BPS derivatives was observed [10,12,15,16]. ...
... On the European market, the non-phenolic substance Pergafast 201 (PF201) was also considered to be an important BPA alternative [10][11][12]15]. Besides, the use of a variety of structural BPS derivatives was observed [10,12,15,16]. In most studies, analysis of color developers from thermal papers was performed by HPLC coupled to an ultra violet (UV), a fluorescence (FL) [10,13] or a (high resolution) mass spectrometer (MS) [11,12,14,[11][12][13][14][15][16][17] subsequent to solvent extraction of the samples. ...
Article
Thermal papers (e.g. point of sale receipts, adhesive labels, tickets) significantly contribute to contamination of paper material cycles and the environment with substances of (eco-) toxicological concern. In particular, they contain color developers like endocrine disrupting bisphenols in typical concentrations of about 1–2 percent per weight (wt%). Bisphenol A (BPA) was used as the common color developer over the last decades, but it will be restricted for thermal paper application in the European Union to a limit of 0.02 wt% from 2020 onwards. Consequently, a variety of BPA substituents such as bisphenol S (BPS) and its derivatives gain importance in thermal paper application. In this study, a rapid, reliable and cost-effective method for identification and quantification of BPA, alternative color developers and related substances like sensitizers is presented based on HPLC separation coupled with diode array detection (DAD) and Corona charged aerosol detection (CAD). Quantification was performed with regard to the intended use of the substances in thermal papers. Besides traditional UV external calibration using reference standards, alternative quantification approaches, in particular UV chromophore concentration for BPS derivatives and CAD universal response technique for low-volatile color developers, were applied and compared in order to allow quantification without reference substances. A market analysis for intended used color developers and sensitizers was performed on thermal paper samples (n = 211) collected in Germany during 2018 and 2019. Pergafast 201 (in 41.7% of the samples) was the most common color developer with concentrations above 0.02 wt%, followed by BPA (36.0%), BPS (13.3%) and other BPS derivatives known as D8, D-90, BPS-MAE and TGSA, that are mainly present in adhesive labels. Sensitizers were determined in over 90% of the samples.
... BPA has the highest concentration in thermal paper [medians 15.0-15.9 mg g −1 (Eckardt and Simat, 2017), mean 13.5 mg g −1 (Goldinger et al., 2015), mean 3.61 mg g −1 (Yang et al., 2019)], followed by BPS, PF201, and D-8. In the study of Eckardt and Simat (2017), BPS, PF201, and D-8 concentrations ranged from 1.4 to 19.2 mg g −1 paper (median values between 2.5 and 14.7 mg g −1 ). ...
... mg g −1 (Eckardt and Simat, 2017), mean 13.5 mg g −1 (Goldinger et al., 2015), mean 3.61 mg g −1 (Yang et al., 2019)], followed by BPS, PF201, and D-8. In the study of Eckardt and Simat (2017), BPS, PF201, and D-8 concentrations ranged from 1.4 to 19.2 mg g −1 paper (median values between 2.5 and 14.7 mg g −1 ). Similar values were reported by Goldinger et al. (2015) (concentration range 3.3-13.2 ...
... normal condition) fingers was 1.1 µg finger −1 (Biedermann et al., 2010), 1.4 µg finger −1 (Lassen et al., 2011), and 1.1 µg finger −1 (Danish EPA, 2014). Eckardt and Simat (2017) observed no significant difference in the amount transferred when comparing samples with different colour developers (BPA, BPS, PF201, and D-8), and ranged from 0.05 to 6.0 µg finger −1 (mean 0.8 µg finger −1 , median 0.3 µg finger −1 ). By contrast, the Danish EPA reported mean values lower than BPA for both BPS (0.8 µg finger −1 ) and PF201 (0.4 µg finger −1 ). ...
Article
Objectives Bisphenol A (BPA) is the most used colour developer in thermal paper for cashiers receipts, labels, and tickets. BPA can migrate onto the skin and be absorbed when handling these papers. BPA is a known endocrine disruptor and is therefore being replaced in thermal paper by some alternatives such as Bisphenol S (BPS), D-8, and Pergafast 201® (PF201). To our knowledge, no studies have characterized skin permeation of these BPA alternatives. Methods We measured/characterized skin absorption for BPA, BPS, D-8, and PF201 through ex vivo human skin using flow-through diffusion cells according to OECD guideline 428. Skin samples were 7–12 per test substance from three different skin donors. Skin metabolism was studied for BPA. Dermal absorption was expressed as the amount of the BPA alternatives in the receptor fluid over applied dose in percent (%). Results The absorbed dose after 24 h of exposure was 25% for BPA, 17% for D-8, 0.4% for BPS, and <LLOQ for PF201. The amount of BPA-glucuronide in the receptor fluid after 24 h was under the limit of quantification (LLOQ = 0.2 µg l−1). Despite the 10-fold lower concentration of the aq solution applied on the skin, D-8’s permeation rate JMAX was 5-fold higher than the one for BPS (0.032 versus 0.006 µg cm−2 h−1). Neither D-8 nor BPS permeated readily through the skin (tlag = 3.9 h for D-8, 6.4 h for BPS). None of PF201’s skin permeation kinetic parameters could be determined because this BPA analogue was not quantifiable in the receptor fluid in our test conditions. Conclusions Skin absorption was in decreasing order: BPA > D-8 >> BPS > PF201. These results are in agreement with their log Kow and molecular weights. We provided here the necessary data to estimate the extent of skin absorption of BPA analogues, which is a necessary step in risk assessment, and ultimately evaluate public health risks posed by D-8, BPS, and PF201.
... The active components are dissolved in the solvent and upon heating of certain areas of the coating with a hot printing stylus, a change of colour is induced, producing an image. The colour is generated by the reversible interaction of the developer with the thermochromic dye, promoting the ring-opening action of the dye by donating protons (Björnsdotter et al., 2017a;Eckardt and Simat, 2017;Gontani et al., 2017Liao, 2011Mendum et al., 2011; U.S. Environmental Protection Agency (U.S. EPA), 2015). ...
... This list includes bisphenol S (4,4′-sulfo- nyldiphenol, BPS) and Pergafast 201 (N-(4-Methylphenylsulfonyl)-N'- [3-(4-methylphenyl-sulfonyloxy)phenyl]urea), together with other previously reported compounds. Yet information on the safety of most of these substitutes is limited (Eckardt and Simat, 2017). Their struc- tural similarity suggests the potential to be released from the thermal paper upon dermal contact as well and moreover, to exert toxicological effects similar to BPA. ...
... In 2017, Björnsdotter et al have reported the non-phenolic compound with molecular formula C 42 H 36 N 6 O 8 S ( Björnsdotter et al., 2017a). In the same year, Eckardt and Simat in- vestigated thermal paper from Germany and reported the presence of UU with a molecular formula C 40 H 32 N 6 O 8 S, a difference of two methyl functional groups located on the benzene rings (Eckardt and Simat, 2017). In our study, we have only identified a molecule with molecular formula C 42 H 36 N 6 O 8 S. Using the acquired MS/MS spectra, we can re- port this compound with a confirmation of Level 3. ...
Article
Thermal printing is a fast, widespread and inexpensive technology that uses a developer to produce a print on the paper, among many applications. A common developer is bisphenol A (BPA), used for this purpose in its free form. Consequently, the handling of thermal paper, as evaluated by the European Food Safety Authority, was reported to be the second largest source of external human exposure to this endocrine disrupting chemical. Recently, reports have been made on the substitution of BPA by alternative developers, which are yet less studied. In this study, 311 receipts and other thermal paper products were collected from 14 countries in Europe, Asia, North America and Oceania and analysed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. BPA was the most frequently used main developer and was detected in 194 thermal paper samples, which represents a detection frequency of 63 %. A statistically significant difference in the detection of BPA was shown between continents. BPA was followed by bisphenol S (BPS) which was detected in 64 samples as the main developer. Pergafast 201 was the third most abundant main developer and detected in 37 samples as the main developer. Less frequently used main developers included BPS-MAE, TGSA, D-8, and D-90, many of them being BPS derivatives. Two oligomers of D-90 (n = 1 and n = 2) were also identified. The sensitizer diphenyl sulphone (DPS) was identified using high-resolution mass spectrometry for the first time and detected in combination with other developers than BPS for the first time. Despite the lack of structural, nation-wide legislation prohibiting the use of BPA in thermal paper, it is clear that alternative developers are currently globally in use for the manufacturing of thermal paper.
... The shapes of the cumulative distribution functions (CDFs) representing external exposures from TP differed for BPA and BPS exposure ( Figure S10) because of different BP amounts transferred per handling event: more BPS than BPA was transferred from TP to normal/dry skin, while more BPA was transferred to humid skin. 57 Therefore, assuming the same occurrence frequency for BPS and BPA, the exposures below the P90 (mostly estimates for normal/dry skin) were higher for BPS. Exposure estimates for BPA were significantly higher beyond the P90. ...
... Eckardt and Simat reported that the BPS amount transferred from TP to normal skin was considerably higher than the corresponding BPA amount, while for moist skin the transferred amount was higher for BPA. 57 Since generally the BP transfer to moist skin is higher than to normal skin, high cumulative exposures from TP were mostly driven by high BPA transfers from TP to moist skin, which was a skin type allocated to about 10% of the model population. The partial replacement of BPA with BPS in TP in the ARS reduced these high BPA exposure cases. ...
... Additionally, color developers other than BPA and BPS are increasingly used, such as Pergafast201 and D8, which can also lead to lower BPA occurrences. 57 Besides the occurrence, the daily handling frequency and the area of contact with TP are also variable and uncertain, 29 and the manner of handling is of importance, which we could not include in our assessment due to missing data. Since the BP transfer from TP to skin was found to be related to skin properties, 48,57,67 such properties need to be known for the population considered. ...
Article
The bisphenols S, F, and AF (BPS, BPF, BPAF) are used to replace the endocrine disrupting chemical bisphenol A (BPA), while exerting estrogenic effects of comparable potency. We assessed the cumulative risk for the aforementioned BPs in Europe, and compared the risk before and after the year 2011, which was when the first BPA restrictions became effective. For this, we probabilistically modeled external exposures from food, personal care products (PCPs), thermal paper, and dust (using the tools MCRA and PACEM for exposures from food and PCPs, respectively). We calculated internal concentrations of unconjugated BPs with substance-specific PBPK models and cumulated these concentrations normalized by estrogenic potency. The resulting mean internal cumulative exposures to unconjugated BPs were 3.8 and 2.1 ng/kg bw/day before and after restrictions, respectively. This decline was mainly caused by the replacement of BPA by BPS in thermal paper, and the lower dermal uptake of BPS compared to BPA. However, the decline was not significant: the selected uncertainty intervals overlapped (P2.5-P97.5 uncertainty intervals of 2.7-4.9 and 1.3-6.3 ng/kg bw/day before and after restrictions, respectively). The upper uncertainty bounds for cumulative exposure were higher after restrictions, which reflects the larger uncertainty around exposures to substitutes compared to BPA.
... 24 Kruse et al. (2006). 25 Eckardt and Simat (2017). 26 Bjornsdotter et al. (2017). ...
... Despite the growing number of publications on BPA analogues, there was still very little to no toxicity data available for several of the BPA analogues. D-8, D-90, TGSA, BPS-MAE, 2,4-BPS, Pergafast 201, BDP, BPPH, and 2,2-BPF, remain under studied, despite the fact that D-8, D90, TGSA, BPS-MAE, 2,4-BPA, and Pergafast 201 are currently used or detected in thermal receipt papers (Bjornsdotter et al., 2017;Eckardt and Simat, 2017). There were no studies recovered from the literature search for five of the 24 BPA analogues (BPS-MPE, BTUM, DD-70, MBHA, UU). ...
Article
Recent studies report widespread usage or exposure to a variety of chemicals with structural or functional similarity to bisphenol A (BPA), referred to as BPA analogues or derivatives. These have been detected in foodstuffs, house dust, environmental samples, human urine or blood, and consumer products. Compared to BPA, relatively little is known about potential toxicity of these compounds. This scoping review aimed to summarize the human, animal, and mechanistic toxicity data for 24 BPA analogues of emerging interest to research and regulatory communities. PubMed was searched from March 1, 2015 to January 5, 2019 and combined with the results obtained from literature searches conducted through March 23, 2015, in The National Toxicology Program’s Research Report 4 (NTP RR-04), “Biological Activity of Bisphenol A (BPA) Structural Analogues and Functional Alternatives”. Study details are presented in interactive displays using Tableau Public. In total, 5748 records were screened for inclusion. One hundred sixty seven studies were included from NTP RR-04 and 175 studies were included from the updated literature search through January 2019. In total, there are 22, 117, and 221 human epidemiological, experimental animal, or in vitro studies included. The most frequently studied BPA analogues are bisphenol S (BPS), bisphenol F (4,4-BPF), and bisphenol AF (BPAF). Notable changes in the literature since 2015 include the growing body of human epidemiological studies and in vivo studies conducted in zebrafish. Numerous new endpoints were also evaluated across all three evidence streams including diabetes, obesity, and oxidative stress. However, few studies have addressed endpoints such as neurodevelopmental outcomes or impacts on the developing mammary or prostate glands, which are known to be susceptible to disruption by BPA. Further, there remains a critical need for better exposure information in order to prioritize experimental studies. Moving forward, researchers should also ensure that full dose responses are performed for all main effects in order to support hazard and risk characterization efforts. The evidence gathered here suggests that hazard and risk characterizations should expand beyond BPA in order to consider BPA structural and functional analogues.
... An elevated urinary BPA (2.8 μg/g) has also been reported in cashiers, who handle many thermal papers for extended periods compared to those in other occupations (Braun et al., 2011). Eckardt and Simat (2017) found the per-figure transfer of 0.8 mg of BPA by holding printed thermal paper for 5 s. Although no differences were observed between the samples with differently colored developers, exposure could be amplified over 40-folds (35 mg/figure) if the skin was wet or greasy (Eckardt and Simat, 2017). ...
... Eckardt and Simat (2017) found the per-figure transfer of 0.8 mg of BPA by holding printed thermal paper for 5 s. Although no differences were observed between the samples with differently colored developers, exposure could be amplified over 40-folds (35 mg/figure) if the skin was wet or greasy (Eckardt and Simat, 2017). It is unclear still whether dermally transferred BPA can affect human metabolism; skin penetration by BPA deep enough that is difficult to wash off (Biedermann et al., 2010). ...
Article
Bisphenol A (BPA) is a ubiquitous environmental toxin worldwide. Despite the many studies documenting the toxicity of this substance, it remains a popular choice for consumer products. The internet, magazine articles, and newspaper reports are replete with tips on how to avoid BPA exposure, which mostly spread contradictory and often unscientific information. Therefore, based on a comprehensive search of the available biomedical literature, we summarized several confounding factors that may be directly or indirectly related to human BPA exposure. We found that the unique properties of BPA materials (i.e. low cost, light-weight, resistance to corrosion, and water/air-tightness), lack of personal health and hygiene education, fear of BPA-substitutes (with yet unknown risks), inappropriate production, processing, and marketing of materials containing BPA, as well as the state of regulatory guidance are influencing the increased exposure to BPA. Besides, we detailed the disparities between scientifically derived safe dosages of BPA and those designated as “safe” by government regulatory agencies. Therefore, in addition to providing a current assessment of the states of academic research, government policies, and consumer behaviors, we make several reasonable and actionable recommendations for limiting human exposure to BPA through improved labeling, science-based dosage limits, and public awareness campaigns.
... In turn, new products containing BPA-like chemicals (BPs) that are structurally or functionally similar to BPA have entered the marketplace. For example, some BPs have been detected in foodstuff (bisphenol AF: BPAF; bisphenol AP: BPAP; bisphenol B: BPB; 4,4-bisphenol F: 4,4-BPF; bisphenol P: BPP; bisphenol S: BPS; bisphenol Z: BPZ (Cacho et al., 2012;Liao et al., 2013)), household dust (BPAF, BPAP, BPB, 4,4-BPF, BPP, BPS (Liao et al., 2012b)), personal care products (BPAF, BPAP, BPB, 4,4-BPF, BPP, BPS, BPZ (Liao et al., 2014)), or in thermal paper (BPS,Pergafast 201,D90,TGSA,2,urea urethane compound (Becerra et al., 2013;Bjornsdotter et al., 2017;Eckardt et al., 2017;Liao et al., 2012c)). BPs have also been detected in urine, blood, breast milk, or adipose tissue in human biomonitoring studies (e.g. ...
... This is particularly important given that some of the data poor BPs are already known to be used in consumer products (e.g. BDP, Pergafast 201, TGSA (Bjornsdotter, et al., 2017;Eckardt, et al., 2017)). In particular, the data set presented here should be useful in supporting future read across efforts. ...
Article
Full-text available
Bisphenol A (BPA) is a high production volume chemical widely used in plastics, food packaging, and many other products. It is well known that endocrine-disrupting chemicals (EDC) might be harmful to human health due to interference with normal hormone actions. Recent studies report widespread usage and exposure to many BPA-like chemicals (BPs) that are structurally or functionally similar to BPA. However, the biological actions and toxicity of those BPs are still relatively unknown. To address this data gap, we used in vitro cell models to evaluate the ability of twenty-two BPs to induce or inhibit estrogenic and androgenic activity. BPA, Bisphenol AF (BPAF), bisphenol Z (BPZ), bisphenol C (BPC), tetramethyl bisphenol A (TMBPA), bisphenol S (BPS), bisphenol E (BPE), 4,4-bisphenol F (4,4-BPF), bisphenol AP (BPAP), bisphenol B (BPB), tetrachlorobisphenol A (TCBPA), and benzylparaben (PHBB) induced estrogen receptor (ER)α and/or ERβ-mediated activity. With the exception of BPS, TCBPA, and PHBB, these same BPs were also androgen receptor (AR) antagonists. Only three BPs were found to be ER antagonists. Bisphenol P (BPP) selectively inhibited ERβ-mediated activity and 4-(4-phenylmethoxyphenyl)sulfonylphenol (BPS-MPE) and 2,4-bisphenol S (2,4-BPS) selectively inhibited ERα-mediated activity. None of the BPs induced AR mediated activity. In addition, we identify that the BPs can bind to ER or AR with varying degrees by a molecular modeling analysis. Taken together, these findings help us to understand the molecular mechanism of BPs and further consideration of their usage in consumer products.
... Moreover, the BPA detection was higher compared to the respective BPS among all of the samples, which is similar to previous findings of a detection frequency of 78% for BPA and 49% for BPS in thermal paper cash receipts from different sources in the Netherlands, Sweden, Norway, Spain, and Austria [13,30]. Additionally, a study of thermal paper receipts collected in Germany also revealed the abundance of BPA, where BPS was found less frequently in the receipts [31]. Regarding the detection of other bisphenols such as BPB, BPF, and BPAF, these substances were not detected in our present study. ...
... BPS, which is widely used as a BPA substitute in plastic, food can lining, and thermal paper (Björnsdotter et al. 2017;Eckardt and Simat 2017;Liao and Kannan 2014;Pivnenko et al. 2015), has been detected in surface water samples from Japan, Korea, China, and India, with a concentration up to 7.2 μg/L in the Adyar river in India (Yamazaki et al. 2015). BPS was also found in 81% of 315 urine samples from the USA and seven in the Asian countries at the average concentration of 0.654 ng/mL (Liao et al. 2012;Wang et al. 2018b). ...
Article
Full-text available
While road network expansion is crucial for economic development, it can cause a notable disturbance of fauna, especially in protected area in terms of habitat fragmentation, risk of collision, and also indirect threat such as pollution. In this study, we monitored the 4.6-km long tarmac road crossing the Kibale National Park in Uganda, home to a rich variety of wild species including the endangered chimpanzees. We evaluated the effects of collisions and pollution, as well as the impact of the renovation process in terms of disturbance and the mitigation measures deployed. This survey reports the death of 24 wild animals killed by cars, including two chimpanzees. The atmospheric concentrations of O3, NO2, SO2, and BTEX did not exceed recommended limits. More than 5000 plastic bottles were collected along the road within 4 months, and for the first time, the presence of BPA and BPS was detected in the hairs of wild chimpanzees. The road bisecting the Kibale National Park poses a high danger in terms of traffic and an underestimated risk related to plastic pollution. Measures (signpost, speed bumps) should be urgently deployed to decrease the risk posed by the renovated road for emblematic species such as chimpanzees, which are crucial for tourism and economy in Uganda.
... 1-(benzyloxy)naphthalene and methyl dehydroabietate were found in sample CM1. The first is an UV-active sensitizer, a substance that acts as a kind of solvent for the reactants of the coloring process [50], while methyl dehydroabietate is a component of varnishes and printing inks used as a tackifier for the enhancement of adhesive performance [44,46]. Octocrylene, detected in sample CM3, is used as UV light absorber to prevent degradation of polymers. ...
Article
Full-text available
Polymeric coating formulations may contain different components such as cross-linking agents, resins, lubricants, and solvents, among others. If the reaction process or curing conditions are not applied in a proper way, these components may remain unreacted in the polymeric network and could be released and migrate into foods. In this study, several polyester coatings intended for food contact were investigated. Firstly, Fourier-transform infrared spectroscopy with an attenuated total reflectance (ATR-FTIR) spectrometer and confocal Raman microscopy were used to identify the type of coating. Then, different techniques, including gas chromatography coupled to mass spectrometry (GC-MS) and analysis by matrix-assisted laser desorption coupled to time-of-flight mass spectrometry (MALDI-TOF-MS), among others, were used to investigate the potential volatile and non-volatile migrants. Moreover, migration assays were carried out to evaluate the presence of monomers and to tentatively identify possible oligomers below 1000 Da. The analyses were performed by liquid chromatography coupled to ion trap mass spectrometry (LC-MSn). Using the information collected from each analytical technique, it was possible to elucidate some of the starting substances used in the formulation of the polyester coatings analyzed in this study. In migration tests, several polyester oligomers were tentatively identified for which there is not toxicological data available and, therefore, no migration limits established to date.
... Bisphenols are man-made chemicals, widely used in the production of polycarbonate plastics, epoxy resins, and thermal receipt paper [52,53]. With the exception of bisphenol A (BPA), the effect of bisphenol exposure on the development of the placenta is not well established. ...
Article
Endocrine disrupting chemicals (EDCs) are chemicals that can interfere with normal endocrine signals. Human exposure to EDCs is particularly concerning during vulnerable periods of life, such as pregnancy. However, often overlooked is the effect that EDCs may pose to the placenta. The abundance of hormone receptors makes the placenta highly sensitive to EDCs. We have reviewed the most recent advances in our understanding of EDC exposures on the development and function of the placenta such as steroidogenesis, spiral artery remodeling, drug-transporter expression, implantation and cellular invasion, fusion, and proliferation. EDCs reviewed include those ubiquitous in the environment with available human biomonitoring data. This review also identifies critical gaps in knowledge to drive future research in the field.
... 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. ...
Article
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.
... Consequently, it is ubiquitously present in the environment, which causes huge concern as many studies reported that BPA induces adverse environmental and human health effects. It is considered that food is the major contributor to the total exposure to BPA for most population groups (EFSA, 2015), however, recently thermal paper has been identified as important source of exposure through dermal transfer (Björnsdotter et al., 2017;Eckardt and Simat, 2017). In 2017 The European Chemical Agency (ECHA) added BPA to the Candidate List of substances of very high concern. ...
Article
The use of bisphenol A (BPA) in manufacturing of plastics is being gradually replaced by presumably safer analogues such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). Despite their widespread occurrence in the environment, there is a knowledge gap in their toxicological profiles. We investigated cytotoxic/genotoxic effects as well as changes in the expression of selected genes involved in the xenobiotic metabolism, response to oxidative stress and DNA damage upon exposure to BPs and their mixtures in human hepatocellular carcinoma HepG2 cells. BPS and BPF slightly decreased the viability of HepG2 cells, while BPAF was the most cytotoxic compound tested. BPA, BPF and BPAF induced the formation of DNA double strand breaks determined with γH2AX assay, while BPS was inactive (5–20 μg/mL). All four BPs up-regulated the expression of CYP1A1 and UGT1A1, while BPS up-regulated and BPAF down-regulated also the expression of GST1A. Only BPA up-regulated oxidative stress responsive gene GCLC, while BPAF up-regulated the expression of CDKN1A and GADD45a. At concentrations relevant for human exposure (ng/mL range) BPA and its analogues as individual compounds and in mixtures did not exert genotoxic activity, whereas BPA and BPAF as well as the mixtures up-regulated the expressions of CYP1A1 and UGT1A1.
... They are strongly dependent on the assumptions (e.g., dermal absorption with or without skin deposition) and parameters (e.g., percentage absorption, maximum flux using the permeability coefficient) considered in the estimate. Other important factors in these estimates include paper handling time and frequency, concentration of BPA in thermal paper (typical concentration for functional use: 1-2% by weight (Eckardt and Simat, 2017)), skin area in contact with paper, length of time between contacts, and hand washing. Assuming a rather low concentration of BPA in thermal paper of 0.03%, Liao and Kannan (2011) estimated intakes of 0.00022 µg/kg/d for the general population and 0.0162 µg/ kg/d for occupationally exposed individuals. ...
Article
Full-text available
Background Human exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA following dermal exposure. Objective To examine the absorption, distribution, metabolism and excretion of BPA in humans following dermal administration. Methods We dermally administered deuterated BPA (d6-BPA) to 10 subjects (6 men and 4 women) at a dose of 100 µg/kg over a 12-hour period and conducted blood and urine analysis from the beginning of dosing through a three- or six-day period. We present time-course serum and urine concentrations of total and unconjugated (“free”) d6-BPA and used this information to calculate terminal half-life and area under the curve. Results and Conclusions Detectable serum levels of total d6-BPA were observed at 1.4 h after the start of dosing, and a maximum serum concentration (Cmax) of 3.26 nM was observed. Free d6-BPA was detectable in serum 2.8 h after start of dermal administration, with Cmax of 0.272 nM. Beginning at approximately seven hours and continuing to 12 h (which corresponds to cessation of exposure), the concentration of free and total serum d6-BPA plateaued. The terminal half-lives of total d6-BPA and free d6-BPA in the body were 21.4 ± 9.81 h and 17.6 ± 7.69 h, respectively. Elimination from the body was rate-limited by kinetics in the dermal compartment. Free d6-BPA was a greater percentage of the area under the curve of total serum BPA (8.81%) compared to the 0.56% observed in our previously published oral study. Recovery of total d6-BPA in urine was <2% of the applied dose after six days. Analysis of the area under the curve for dermal and oral administration revealed that 2.2% of the dermal dose became systemically available. These data are in line with prior studies indicating how pharmacokinetics of BPA differ following oral and dermal exposures. Dermal exposure resulted in a longer apparent half-life and higher free:total d6-BPA ratio compared to oral.
... Given that most people come into contact with thermal receipt papers and paper products daily, exposure to BPS through dermal contact with paper products is a significant source of human exposure to BPS (Becerra and Odermatt, 2012). Table 2 shows the levels of BPS measured in paper from different countries (Eckardt and Simat, 2017;Pivnenko et al., 2015;Rocha et al., 2015;Russo et al., 2017). BPS was found in 100% of tested thermal receipt paper, and the concentrations of BPS in thermal receipt papers from Missouri, USA ranged from 15.2 to 30.1 mg/g, which were far higher than the concentrations found in other types of paper. ...
... Due to its negative impact on organisms as well as the prohibition of BPA to be used in thermal paper from 2020 in the European Union, there is an urgent need for safe replacements (Björnsdotter et al., 2017;Eckardt and Simat, 2017). Several BPA congeners with a similar chemical structure as well as chemically different substitution candidates have been developed in recent years. ...
Article
Full-text available
Bisphenol A (BPA) is a high production volume chemical with a broad application spectrum. As an endocrine disrupting chemical, mainly by modulation of nuclear receptors (NRs), BPA has an adverse impact on organisms and is identified as a substance of very high concern under the European REACH regulation. Various BPA substitution candidates have been developed in recent years, however, information concerning the endocrine disrupting potential of these substances is still incomplete or missing. In this study, we intended to investigate the endocrine potential of BPA substitution candidates used in environmentally relevant applications such as thermal paper or epoxy resins. Based on an extensive literature and patent search, 33 environmentally relevant BPA substitution candidates were identified. In order to evaluate the endocrine potential of the BPA replacements, a screening cascade consisting of biochemical and cell-based assays was employed to investigate substance binding to the NRs estrogen receptor α and β, as well as androgen receptor, co-activator recruitment and NR-mediated reporter gene activation. In addition, a computational docking approach for retrospective prediction of receptor binding was carried out. Our results show that some BPA substitution candidates, for which so far no or only very few data were available, possess a substantial endocrine disrupting potential (TDP, BPZ), while several substances (BPS, D-8, DD70, DMP-OH, TBSA, D4, CBDO, ISO, VITC, DPA, and DOPO) did not reveal any NR binding.
... Replacements have also been introduced into the market for this aim, namely BPS and other less known compounds such as 4hydroxyphenyl 4-isopropoxyphenyl Sulfone (D-8), 4,4 0 -sulfonylbis (2-allylphenol) (TGSA), 4-((4-(allyloxy)phenyl)sulfonyl)phenol (BPS-MAE), Pergafast 201 and D-90 (US EPA, 2015). Although there are some recent studies about the presence of these compounds in thermal paper products and their potential toxic effects (Goldinger et al., 2015;Bj€ ornsdotter et al., 2017b;Eckardt and Simat, 2017) their migration and presence in the environment have not been assessed so far. Indoor dust is a potential source of human exposure to BPA and its analogs due to their migration from many materials and slow degradation (Rudel et al., 2003;V€ olkel et al., 2008;Geens et al., 2011Geens et al., , 2012. ...
Article
Bisphenol A (BPA) is present in a wide variety of materials and it is a well-known endocrine disruptor that is widespread in indoor and outdoor environments. For this reason, industry has introduced a variety of replacements, such as Bisphenol S (BPS) or Bisphenol F (BPF), and other less known structural analogs, such as BPS-MAE, D-8 or TGSA. These emerging potential contaminants have been identified in thermal paper products, according to recent studies, but their potential toxic effects and their migration into the environment remain unclear. In this study, we report for the first time the presence of emerging BPA replacements in indoor dust from public environments (shops, restaurants, etc.). For this purpose, we optimized a novel supramolecular solvent (SUPRAS)-based microextraction method. SUPRAS are multi-target solvents made up of self-assembled amphiphiles. They offer multiple extraction interactions (dispersion, polar, hydrophobic, etc.) and they constitute excellent candidates to develop generic and fast sample treatment procedures at low cost. By this method, emerging BPA replacements (BPS-MAE, D-8 and TGSA) were detected in dust at median concentrations in the range 6–22 ng g⁻¹ (around ten times lower than BPS) with detection frequencies in the range 50–90%. These results constitute a first insight into the migration of emerging BPA replacements into the environment via indoor dust, which is a common route of human exposure to contaminants.
... Similar findings were reported in a study by Björnsdotter et al. (2017) where 100 thermal paper cash receipts from different sources in the Netherlands, Sweden, Norway and Spain were analyzed, showing a detection frequency of 78 % for BPA and of 49 % for BPS in the samples, but the bisphenols were either used as main developer or found as traces probably introduced from recycled papers. In a study published by Eckardt and Simat (2017) investigating 311 thermal paper receipts collected in Germany in the years, 2015 (55), 2016 (45) and 2017 (51), BPA was found most and BPS was found less frequently in the samples. The median concentrations detected comprised 15,900 μg/g (2015), 17,700 μg/g (2016) and 15,000 μg/g (2017) for BPA and 13,100 μg/g (2015), 14,700 μg/g (2016) and 13, 700 μg/g (2017) for BPS. ...
Article
Full-text available
Bisphenol A (BPA) a synthetic, high production volume chemical identified as endocrine disruptor and toxic to reproduction is mainly used in the production of polycarbonate plastics, in epoxy resins, polyvinylchloride, thermal papers as color developer, and is present in a wide range of consumer goods such as food packaging materials, storage containers, and cash receipts. Due to its effects on health and legal restrictions, BPA is increasingly replaced by other bisphenols. In this study, BPA and 13 alternatives including BPS, Bisphenol F (BPF), Bisphenol B (BPB), Bisphenol C (BPC), Bisphenol Z (BPZ), Bisphenol M (BPM), Bisphenol P (BPP), Bisphenol AF (BPAF), Bisphenol FL (BPFL), Bisphenol C12 (BPC12), Tetramethylbisphenol A (tmBPA), 4,4-bisphenol (BP-4,4), and p,p-oxybisphenol were analyzed in thermal paper cash receipts (content) and migration studies were carried out in BPA-free labelled reusable plastic drinking bottles using a sensitive UHPLC-MS/MS method. The receipts contained almost only BPA and BPS, whereas BPS was found in all samples ranging at levels up to 38 μg/g. BPA was detected at low concentrations, only in one sample 11,000 μg/g were found, exceeding the EU limit of BPA in thermal paper of 0.02% per weight. In leaching solutions from the drinking bottles BPA, BPS and BPF were found at concentrations up to 0.047 μg/L BPA, 0.043 μg/L BPS, and <0.01 μg/L BPF. No other analogs were detected. However, these levels identified are far below the legal limits. In addition, a theoretical exposure assessment was conducted indicating that exposures were within the current regulatory guidelines.
... Given that most people come into contact with thermal receipt papers and paper products daily, exposure to BPS through dermal contact with paper products is a significant source of human exposure to BPS (Becerra and Odermatt, 2012). Table 2 shows the levels of BPS measured in paper from different countries (Eckardt and Simat, 2017;Pivnenko et al., 2015;Rocha et al., 2015;Russo et al., 2017). BPS was found in 100% of tested thermal receipt paper, and the concentrations of BPS in thermal receipt papers from Missouri, USA ranged from 15.2 to 30.1 mg/g, which were far higher than the concentrations found in other types of paper. ...
Article
The occurrence and distribution of antibiotics were investigated in surface water and sediment collected from the main rivers of Shenzhen, China. Total concentrations of 20 selected antibiotics ranged from 36.510 to 1075.687 ng L⁻¹ (mean 244.992 ng L⁻¹) in 31 water samples and from 28.124 to 2728.810 ng g⁻¹ (mean 680.169 ng g⁻¹) in 31 sediment samples. Notably, STZ and SDZ were the dominant antibiotics in both water and sediment as their higher concentrations compared with the other compounds. Furthermore, comprehensive profiling of antibiotic resistance genes (ARGs) and microbial community was performed to gain an understanding of the evolution and dissemination of ARGs in microbial communities caused by the occurrence of antibiotics in sediment samples from Maozhou River. As a result, the sul1 gene was found to be the most abundant ARG and Proteobacteria was the most abundant microorganism in all the samples (37.4–51.7%), followed by Bacteroidetes (15.3–18.4%). Statistical analysis figured out the relations among antibiotics, ARGs and microbial community. A specific conclusion could be drawn from the positive correlations among the bla_d gene, Fusobacteria, and sulfamethoxazole. It suggests that antibiotics may be positively linked to the expression of ARGs in certain bacteria, and thus high reproduction would occur within the bacterial community. Overall, the widespread distribution of ARGs underscores the need for further research on the mechanism of antibiotics influence as emerging contaminants in the environment and the associated risks to microbial community.
... "sippy") cups, 13 and cash register receipts. 14 As a result of these deleterious health effects, many regulatory agencies have banned the use of BPA in commercial products. 15 Manufacturers have replaced BPA with a variety of alternatives; 16 however, the use of BPA-like derivatives are particularly concerning due to the limited amount of toxicity data associated with these compounds, 17 and the fact that available data suggests that BPA derivatives can be even more toxic than BPA itself. ...
Article
Full-text available
Reported herein is the sensitive and selective detection of bisphenol A (BPA) and six BPA derivatives in buffer and urine environments. This detection system relies on the ability of γ-cyclodextrin to act as a supramolecular scaffold to promote highly analyte-specific, proximity-induced fluorescence modulation of high quantum yield fluorophores, which led to unique modulation responses for each cyclodextrin-analyte-fluorophore combination investigated in both buffer and urine environments, and high selectivity between structurally similar analytes using linear discriminant analysis of the resulting response signals. This method was sensitive (low micromolar detection limits), selective (able to differentiate between structurally similar analytes), and broadly applicable (with successful detection in both buffer and urine environments), and has significant potential in the detection of BPA and its derivatives in a wide variety of complex environments.
... Bisphenol A (BPA; 4,40-dihydroxy-2,2-diphenylpropane) is a synthetic chemical widely used in the industry for the manufacturing of polymers. Consequently, BPA is found in such objects used in our everyday life as plastic food and beverage containers, the lining of metal food and drink cans, computers, thermal paper, medical devices, dental materials, and many others (Lathi et al;Geens et al., 2011;Acconcia et al., 2015;Eckardt and Simat, 2017). BPA can leach from these products and enter human body, it can be found in skin, saliva or blood (Acconcia et al., 2015). ...
... However, Pergafast 201 have been found at higher DF in other European countries, e.g. a value of 14% was reported in the Netherlands (Björnsdotter et al., 2017). Similarly, Eckardt et al., 2017 reported DFs for Pergafast 201 of 36% in 2017, 34% in 2018 and 49.5% in 2019 in thermal papers from Germany. ...
Article
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.
... normal, dry or moist) were available on an individual basis from the questionnaires from the BM study. We used Danish occurrence frequencies of BPA and BPS in TP (Eckardt and Simat, 2018;Pivnenko et al., 2015), and referred to studies by Biedermann et al. (2010) and Lassen et al. (2011) for the number of fingers used for handling TP and to a study by Eckardt and Simat (2017) for the amount of BPA and BPS transferred per finger (see SI paragraph 3 for further information on exposure modeling from TP: handling frequency and skin type, occurrence frequency, number of fingers used for handling and BP amount transferred per finger, exposure model and settings). Dust exposure was modeled with BP concentrations in indoor dust from France (ANSES, 2013; EHESP, CSTB, 2011), Belgium (Geens et al., 2009), Greece, and Romania (Wang et al., 2015). ...
Article
Full-text available
Background: Bisphenol A (BPA) and, with increasing occurrence, its analogs bisphenol S (BPS) and bisphenol F (BPF) are applied in many consumer products, leading to humans being exposed from a vast number of sources and via several routes. Estrogenic and anti-androgenic effects are exerted by the chemical BPA, and also by its analogs. Therefore, realistic exposure assessments are needed for assessing risks related to cumulative exposure. Objectives: Biomonitoring for BPA, BPS, and BPF was conducted in a human study embedded in the EU project EuroMix and the measured urinary concentrations were compared to source-to-dose calculations for source allocation and plausibility test of the model. Methods: For two 24-hour study periods separated by 2-3 weeks, 144 adult volunteers in Norway kept detailed diaries on food consumption, personal care product (PCP) use, and thermal paper (TP) handling. Concurrently, 24 h urine was collected and urinary levels of BPA, BPS, and BPF were analyzed using ultra-high performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS). In line with the information obtained from the first study day, bisphenol exposure from food, PCPs, TP, and dust was modeled primarily individual-based with probabilistic models. Estimates for BP excretion over 24 h were obtained with the models and compared to measured amounts. Results: Modeled aggregate internal exposures covered the full range of measured urinary amounts for all BP analogs. In general, individual-based medians of modeled BPA exposures were in good agreement with the measurements, but individual-specific correlation was lacking. Modeled exposures mostly underestimated BPS and BPF levels in participants with positive measurements (53% and 8%), except for the P95 values of modeled BPS exposure that were higher than measured amounts if TP was handled. Most likely, diet and TP were the sources contributing the most to BP exposure in this study. Urinary measurements did not reveal a significant correlation between the amounts of canned food consumed, the number of PCPs used, or the number of TP handling events and levels of BPA, BPS, or BPF. Conclusions: The good agreement between the ranges of modeled BPA exposure and measured BPA amounts indicates that available concentrations, especially from the main exposure source food, mirror the exposure situation realistically, and suggests that the exposure model considers the relevant exposure sources. The lack of individual-specific correlations means that the individual measured amounts and modeled exposures did not vary in parallel, e.g. due to mismatch of BP concentrations in food, TP, and other sources, or delayed internal exposure. The underestimation of modeled BPS and BPF exposure suggests that not all relevant sources were included in the respective exposure models. This could be due to a lack of input data, e.g. for food items, or due to an increased replacement of BPA with structural analogs compared to the used concentration and occurrence data.
Article
Contact with thermal printing paper is a relevant source of dermal exposure to unbonded bisphenol A (BPA). In order to limit this exposure route, the European Union has introduced a drastic reduction in the maximum allowed concentration of BPA in thermal paper produced after beginning of year 2020. This study investigates the suitability of direct analysis in real time (DART), combined with accurate mass spectrometry, as a faster alternative to chromatography-based methods for the quantitative determination of BPA, and three analogues species, in receipts and tickets usually printed on thermal paper. The ionization efficiency of these compounds is evaluated under different conditions, and the effect of instrumental parameters of the DART source in the observed responses is discussed. The yield of the DART desorption-ionization process was greatly improved when compounds are previously converted into their acetyl derivatives; thereafter, the temperature of electronically excited helium atoms was the most relevant of the evaluated instrumental parameters. Under optimized conditions, the reported method provided recoveries in the range from 90 to 110%, a limit of quantification of 0.004% (w:w), well below the maximum concentration established after 2020 for BPA (0.02%, w:w), and permitted to perform duplicate determinations of each sample extract with a response time around 1 min. The accuracy of BPA levels found in non-spiked samples was confirmed using GC-EI-MS as reference technique. BPA was systematically noticed in the processed samples with concentrations ranging from 0.005% to more than 6%.
Article
In this study a sensitive analytical method based on liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) was developed for the simultaneous analysis of bisphenol A (BPA), bisphenol AF (BPAF), bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF) and bisphenol S in different paper and board products, including virgin fibre samples and recycled samples. Analytes were extracted from the paper matrix using a simple solvent extraction and chromatographic separation was performed on a C18 core-shell (100 mm x 2.1 mm i.d.; 1.7 µm particle size) column. The developed method showed good linearity (R² > 0.9921) for all analytes. Absolute recoveries ranged from 71 to 115% and precision in terms of reproducibility and repeatability (intra- and inter-day) yielded in relative standard deviations (RSDs) of less than 15.0% and 17.4%, respectively. The limit of detection (LOD) and limit of quantification (LOQ) for the different analytes ranged from 0.29 to 0.40 µg kg⁻¹ paper and from 1.09 to 1.32 µg kg⁻¹ paper, being in the same range for all analytes. Quantitation of the analytes was performed using the internal standard procedure, with concentrations of < LOQ to 9599 µg kg⁻¹ for the different analytes. Furthermore, a calculation of the maximum migration, assuming the ‘worst case’ scenario of 100% migration was performed.
Article
Bisphenol S (BPS) has been increasingly used as a substitute for bisphenol A (BPA), a known endocrine disruptor. Early-life exposure to BPA affects fetal development and the risk of obesity in adolescence and adulthood. However, the effects of fetal exposure BPS in later life are unknown. This study aimed to investigate the effects of prenatal BPS exposure on adiposity in adult F1 mice. Pregnant C57BL/6 N mice were exposed to BPS (0, 0.05, 0.5, 5, and 50 mg/kg/d) via drinking water from gestation day 9 until delivery. Thereafter, two groups of offspring (6 weeks old) were either administered a standard diet (STD) or a high-fat diet (HFD) for 4 weeks until euthanasia. The body weight and gonadal white adipose tissue (gWAT) mass were determined, and the energy expenditure for the adiposity phenotype was computed especially for male mice, followed by histological analysis of the gWAT. Thereafter, the expression levels of adipogenic marker genes (Pparg, Cebpa, Fabp4, Lpl, and Adipoq) were analyzed in the gWAT via reverse-transcription PCR analysis. BPS-exposed male mice displayed apparent gWAT hypertrophy, consistent with the significant increase in adipocyte size in the gWAT and upregulation of Pparg and its direct target genes among HFD mice in comparison with the control mice. These results suggest that prenatal BPS exposure potentially increases the susceptibility to HFD-induced adipogenesis in male adult mice.
Article
The use of bisphenol A (BPA) is restricted due to its reproductive toxicity and endocrine disrupting (ED) properties. The public concern and regulatory restrictions on BPA stimulated the development of alternative substances to replace BPA. The aim of this study is to review the available data on carcinogenic, mutagenic, reproductive toxicity, and ED properties of BPA alternatives used in consumer products. The focus is on the potential hazard for (young) children and/or pregnant women. An inventory of known potential alternative substances (n = 99) was made, of which 20 were prioritized based on reported use by the general population. For all the selected alternatives, data on ED potential, carcinogenicity and reproductive toxicity was very limited or even absent (i.e. Tefacid Stearic 95, Bisphenol C, AP, and P). For the alternative substances bisphenol S (BPS), bisphenol AF (BPAF), p-tert-butylphenol and to a lesser extent bisphenol F (BPF), fluorine-9-bisphenol (BHPF), bisphenol E, M, and Z (BPE, BPM, BPZ), Irganox 1076, and butylated hydroxytoluene (BHT), the data indicates a reproductive toxicity hazard with a possible ED mode of action. 3,3′,5,5′-Tetrabromobisphenol A (TBBPA) tested positive for carcinogenicity. Data gaps are present for most of these substances. In this study, data on reproductive toxicity and/or ED potential were only negative, although not complete, for benzoic acid and Irganox 1010, tetra methyl bis phenol F (TMBPF) and bisphenol-A bis(diphenyl phosphate) (BDP). A full evaluation of all data, including in vitro data, is recommended to guide targeted testing prioritization.
Article
In this study, a set of 15 bisphenols and one emerging derivative (4-hydroxyphenyl 4-isoprooxyphenylsulfone, BPSIP) were analyzed in 60 pairs of maternal plasma, cord plasma, and placenta samples from pregnant women in South China. Four of the 15 target BPs, i.e., BPA, bisphenol S (BPS), bisphenol AF (BPAF), and bisphenol E (BPE), were frequently detected in the three human biological matrices. The derivative BPSIP was identified in all maternal plasma samples at unexpectedly high levels, second only to BPA. The concentrations of bisphenols in maternal plasma were slightly higher than in cord plasma for BPA, BPS, and BPE but much higher for BPSIP and much lower for BPAF, indicating that the five frequently bisphenols have different placental transfer behaviors. The placental transfer efficiencies (PTEs) of BPA, BPS and BPE was similar, which were significantly higher than the PTE of BPSIP. The PTE of BPAF was much higher than other BPs, indicating its strong maternal transfer and high fetal accumulation. The PTEs of bisphenols were structure-dependent, and passive diffusion was suggested as the potential mechanism of placental transfer. Significant concentration correlations of the five major bisphenols between maternal plasma and cord plasma were observed (p < 0.05). Meanwhile, significant associations of BPAF concentrations in maternal/cord plasma with some maternal characteristics and adverse birth outcomes were also identified (p < 0.05).
Article
Xenoestrogens exert antiandrogenic effects on the human androgen receptor. In the analytical field, such antagonists block the detection of testosterone and falsify results obtained by sum parameter assays. Currently, such agonistic versus antagonistic effects are not differentiated in complex mixtures. Oppositely acting hormonal effects present in products of everyday use can only be differentiated after tedious fractionation and isolation of the individual compounds along with subjection of each fraction/compound to the status quo bioassay testing. However, such long-lasting procedures are not suited for routine. Hence, we developed a fast bioanalytical tool that figures out agonists versus antagonists directly in complex mixtures. Exemplarily, 8 cosmetics and 15 thermal papers were analyzed. The determined antagonistic potentials of active compounds found were comparable to the ones of known antagonists (in reference shown for bisphenol A, 4-n-nonylphenol and four parabens). Relevant biological/chromatographic parameters such as cell viability, culture conditions, dose response curves, limits of biological detection/quantification and working range (shown for testosterone, dihydrotestosterone, nandrolone and trenbolone) were investigated to obtain the best sensitivity of the biological detection. The developed and validated method was newly termed reversed phase high-performance thin-layer chromatography planar yeast ant-/agonistic androgen screen (RP-HPTLC-pYAAS bioassay). Results were also compared with the RP-HPTLC-Aliivibrio fischeri bioassay (applied on RP plates for the first time). As proof-of-concept, the transfer to another bioassay (RP-HPTLC-pYES) was successfully demonstrated, analogously termed RP-HPTLC-pYAES bioassay detecting anti-/estrogens (exemplarily shown for evaluation of 4 pharmaceuticals used in breast cancer treatment). The new imaging concept provides (1) detection and differentiation of individual agonistic versus antagonistic effects in the bioprofiles, (2) bioanalytical quantification of their activity potential by scanning densitometry and (3) characterization of unknown bioactive compound zones by hyphenation to high-resolution mass spectrometry. Depending on the hormonal bioassay, 15 samples were analyzed in parallel within 5 h or 6 h (calculated as 20 or 24 min per sample). For the first time, piezoelectric spraying of the cells was successfully demonstrated for the planar yeast–based bioassays.
Article
Full-text available
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.
Article
Introduction: Bisphenol A (BPA) is the most used colour developer in thermal paper products such as cashiers' receipts, followed by Bisphenol S (BPS), Wincon 8 (D-8), and Pergafast 201® (PF201). These chemicals can migrate from the paper onto the skin and possibly be absorbed and metabolised. Until now, D-8 and PF201 have not been analysed in biological matrices, nor has a method been developed to simultaneously quantify these even though they are often found as mixtures. Our aim was to develop and validate a method to quantify BPA, its glucuronide metabolite (BPA-G), BPS, D-8 and PF201 in in vitro skin absorption samples. Method: After solid-phase extraction (SPE) and reversed-phase chromatography, we quantified the substances in saline that had been in contact with human dermis for 24 hours using a triple quadrupole mass detector equipped with an electrospray ionisation source. We assessed the method in three in vitro skin absorption assays using ex-vivo human skin from one skin donor per test substance. Results: The quantification range of our method was 0.2 - 200 µg/L for BPA and 0.2 - 20 µg/L for BPA-G, BPS, D-8, and PF201. Accuracies were within ±8% of nominal concentrations. Intra-day and total precisions (%RSD) were <10% for all analytes, except for BPA in low-concentration quality control solutions (low QCs) (12.2% and 15.5%, respectively). Overall, process efficiency was 100-113% for all analytes, except BPS low and high QCs (80% and 71%, respectively) and BPA low QCs (134%). The absorbed dose ranged 0.02% - 49% depending on the test substance, and was not determinable for PF201. Conclusions: This is the first analytical method to quantify simultaneously BPA, BPA-G and BPA alternatives in saline from in vitro skin absorption samples.
Article
Bisphenol A (BPA) is a synthetic ubiquitous environmental toxicant present in many industrial and consumer products. BPA is recognized as an endocrine-disrupting chemical (EDC), and its mechanisms of perturbation of the physiological process include interference with hormone pathways and epigenetic modifications. An increase in industrial productions and food packaging across Africa has resulted in increased utilization of BPA-containing products with a concomitant increase in environmental bioaccumulation and human exposure. In order to assess the extent of this bioaccumulation, we identified, collated, and summarized the levels of BPA that have been reported across Africa. To achieve this aim, we performed a systematic search of four indexing databases to identify articles and extracted the necessary data from the selected articles. Of the 42 publications we retrieved, 42% were on water samples, 22% on food, 20% on human biological fluids, 10% on sediments, soils, and sludge and 6% on consumer and personal care products (PCPs). The highest level of BPA reported in literature across Africa was 251 ng/mL, 384.8 ng/mL, 937.49 ng/g, 208.55 ng/mL, 3,590 μg/g, and 154,820 μg/g for water, wastewater, food, biological fluids, consumer and PCPs, and semisolids, respectively. This review presented a comparative perspective of these levels relative to regulatory limits and levels reported from other continents. Finally, this review highlighted critical needs for the regulation of BPA across Africa in order to stem its environmental and toxicological impact. We hope that this review will stimulate further research in understanding the impact of BPA on health outcomes and wellbeing across Africa.
Article
Bisphenols (BPs), which act as endocrine disruptors, are extensively used in epoxy resin and polycarbonate plastic production and are found in various environmental media. This study investigated the occurrence and distribution of seven BPs in water and sediment samples from the Lanzhou section of the Yellow River, China. Previous studies have focused on the southern and more developed regions in China. Paired water and sediments were collected in the Yellow River from August 2016 to March 2017. Bisphenol A (BPA), bisphenol AF (BPAF) and bisphenol S (BPS) were measured in the study samples. Mean concentrations of BPs were 88 and 61.2 ng/L in the rainy and dry seasons, respectively, in water samples. The concentrations were 40.4 and 29.9 ng/g in the rainy and dry seasons, respectively, in sediment samples. BPA accounted for the largest proportion in ∑BPs, followed by BPAF and BPS, which indicates that BPA and BPAF have been widely used and discharged in this region. 17β-estradiol equivalents for BP analogues were 21.57–203.83 pg/L and 13.06–185.30 pg/L in the dry and rainy seasons, respectively, in water samples. BPAF had the highest mean estrogenic activity (> 80%) amongst the study samples. The concentration of ∑BPs was lower than those in previous studies; however, the concentration of BPAF was high. The present study also surveyed the estrogenicity of BPs from the samples, and BPAF contributed the highest mean estrogenic activity. The results of this study demonstrate that BP pollution exists to some degree, and the use and discharge of BPAF should be monitored.
Article
Bisphenol S (BPS) derivatives have recently been reported as new bisphenol A (BPA) or BPS substitutes that occur in thermal paper worldwide. However, little is known about human exposure to these emerging chemicals. In this study, the occurrence of BPA, five commonly used BPA analogues, and a broad suite of 10 BPS derivatives was investigated in human breast milk samples from Chinese lactating women. In addition to BPA and five BPA analogues, seven of the ten target BPS derivatives were identified in the breast milk samples. Total concentrations of seven detectable BPS derivatives were in the range of 8.45-943 pg/mL, just slightly lower than those of five commonly used BPA analogues (34.5-1420 pg/mL). 2,4′-Bis(hydroxyphenyl)sulfone (2,4-BPS) and 4-hydroxyphenyl 4-isoprooxyphenylsulfone were the most frequently detected BPS derivatives, followed by 4-{[4-(allyloxy)phenyl]sulfonyl}phenol, 4-hydroxy-4′-benzyloxydiphenylsulfone, and bis(3-allyl-4-hydroxyphenyl)sulfone. Concentrations of 2,4-BPS were found to be similar to that of BPS in human breast milk. If BPS derivatives were included in a comprehensive exposure assessment, the estimated total daily intakes of BPA alternatives via breast-feeding would increase significantly for breast-fed infants but still correspond to low health risks. This is the first study to report multiple BPS derivatives in human breast milk.
Article
The paper shows a procedure for selecting the control method parameters (factors) to obtain a preset ‘analytical target profile’ when a liquid chromatographic technique is going to be carried out for the simultaneous determination of five bisphenols (bisphenol-A, bisphenol-S, bisphenol-F, bisphenol-Z and bisphenol-AF), some of them regulated by the European Union. The procedure has three steps. The first consists of building a D-optimal combined design (mixture-process design) for the control method parameters, which are the composition of the ternary mobile phase and its flow rate. The second step is to fit a PLS2 model to predict six analytical responses (namely, the resolution between each pair of consecutive peaks, and the initial and final chromatographic time) as a function of the control method parameters. The third final step is the inversion of the PLS2 model to obtain the conditions needed for attaining a preset analytical target profile. The computational inversion of the PLS2 prediction model looking for the Pareto front of these six responses provides a set of experimental conditions to conduct the chromatographic determination, specifically 22% of water, mixed with 58% methanol and 20% of acetonitrile, keeping the flow rate at 0.66 mL min⁻¹. These conditions give a chromatogram with retention times of 2.180, 2.452, 2.764, 3.249 and 3.775 minutes for BPS, BPF, BPA, BPAF and BPZ, respectively, and excellent resolution among all the chromatographic peaks. Finally, the analytical method is validated under the selected experimental conditions, in terms of trueness and precision. In addition, the detection capability for the five bisphenols were: 596, 334, 424, 458 and 1156 μg L⁻¹, with probabilities of false positive and of false negative equal to 0.05.
Article
As more and more countries have prohibited the manufacture and sale of plastic products with bisphenol A (BPA), a number of bisphenol analogues (BPs), including BPS, BPF and BPAF, have gradually been used as its primary substitutes. Ideally, substitutes used to replace chemicals with environmental risks should be inert, so it makes sense that the risk of the similar chemical substitutes (BPS, BPF, and BPAF) should be assessed before they used. Therefore, in the present study, the neurotoxicity of four BPs at environmentally relevant concentration (200 μg/L) were systematically compared using zebrafish as a model. Our results showed that the four BPs (BPA, BPS, BPF and BPAF) exhibited no obvious effect on the hatchability, survival rate and body length of zebrafish larvae, noteworthily a significant inhibitory effect on spontaneous movement at 24 hpf was observed in the BPA, BPF and BPAF treatment groups. Behavioral tests showed that BPAF, BPF and BPA exposure significantly reduced the locomotor activity of the larvae. Additionally, BPAF treatment adversely affected motor neuron axon length in transgenic lines hb9-GFP zebrafish and decreased central nervous system (CNS) neurogenesis in transgenic lines HuC-GFP zebrafish. Intriguingly, BPAF displayed the strongest effects on the levels and metabolism of neurotransmitters, followed by BPF and BPA, while BPS showed the weakest effects on neurotransmitters. In conclusion, our study deciphered that environmentally relevant concentrations of BPs exposure exhibited differential degrees of neurotoxicity, which ranked as below: BPAF > BPF ≈ BPA > BPS. The possible mechanisms can be partially ascribed to the dramatical changes of multiple neurotransmitters and the inhibitory effects on neuronal development. These results suggest that BPAF and BPF should be carefully considered as alternatives to BPA.
Article
Recycled paperboard contains hundreds of non-evaluated or even unidentified substances that could endanger human health if they turn out to be highly toxic. It seems as unrealistic to evaluate each of them as it is to phase out the use of the problematic ones or sort out the papers and boards introducing them into the recyclate. Therefore, measures should be taken that generally reduce migration into food, such as functional barriers or functional sorbents. A general approach is used for the recycling of plastics, particularly poly(ethylene terephthalate), PET: as not every potential contaminant can be regulated, a pragmatic approach is applied, for PET mainly on the required decontamination efficiency. Criteria are required on the required efficacy of the measures to be taken. Recycled paperboard is used for various types of food contact: mostly contact is through the gas phase (evaporation and recondensation), often indirect through other layers (e.g. internal bags or for transport boxes), seldom in wetting contact. Numerous factors have to be considered. For typical folding boxes and at least strongly dominating gas phase contact, it was proposed that no more than 1% of each contaminant in the recycled paperboard should enter the food. The efficiency of the measures required to comply with this criterion depends on the application. The three main measures are reviewed with regard to this criterion: (i) internal bags with an incorporated functional barrier (successfully used for some time), (ii) a barrier layer on the internal wall of the box (for which the design of the closures might be most critical) and (iii) functional sorbents added to the paperboard (for which the sorbent capacity is critical). For transport boxes, commonly of corrugated board (quantitatively the most important use of recycled paperboard in food contact), an adjusted or different criterion is needed.
Article
Bisphenol A (BPA) is a synthetic organic compound that is mainly used in the production of polymer materials polycarbonate and epoxy resin. Widespread use and irregular processing methods have led to BPA being detected globally, raising concerns about its environmental and health effects. This review outlines an overview of the presence and removal of BPA in the environment and consumer products. We also summarized the endocrine-disrupting toxicity of BPA, and the relatively less summarized neurotoxicity, cytotoxicity, reproductive toxicity, genotoxicity, and carcinogenicity. Human exposure data show that humans have been exposed to low concentrations of BPA for a long time, future research should focus on the long-term exposure and the migration of BPA from consumer products to humans and the possible health risks associated with human exposure to BPA. Exploring economical and effective methods to reduce and remove BPA from the environment is imperative. The development of safe, functional and reproducible BPA analogs and the study of its degradation products can be the focus of subsequent research.
Article
It has been suggested that dramatic increase in obesity may be caused by growing exposure to environmental chemicals. In vitro data has suggested bisphenol S (BPS), a compound widely used in polycarbonate plastic production, can induce lipid accumulation in preadipocytes. However, the mechanisms responsible for BPS-induced obesity in vivo remain unclear. In this study, we used translucent zebrafish (Danio rerio) larvae as a model to investigate the effect of environmentally relevant BPS exposure (1, 10, and 100 μg/L from 2 h to 15 d post fertilization) on lipid accumulation, triacylglycerol (TAG) and lipoproteins content, and mRNA expression of genes involved in the regulation of lipid synthesis, transport, degradation, and storage. We also analyzed activities of two enzymes critical to TAG metabolism: lipoprotein lipase and diglyceride acyltransferase. Overfed, obese larvae were used as positive control. The results indicated that BPS-treated and overfed larvae had much higher TAG levels and visceral fat accumulation compared with control. BPS exhibited obesogenic effects by interfering with lipid metabolism as evidenced by (a) upregulation of the mRNA expression of fasn, acc1, and agpat4 genes encoding enzymes involved in the de novo synthesis of TAG in the liver, (b) downregulation of apolipoprotein expression, which should reduce TAG transport from the liver, and (c) increase in rxrα expression, which should promote visceral fat accumulation. Our study is the first to demonstrate that the obesogenic effects of BPS in zebrafish are related to the disruption of TAG metabolism.
Article
Full-text available
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.
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.
Article
Full-text available
Background: Bisphenol A (BPA) is a chemical with widespread human exposure suspected of causing low-dose effects. Thus, a need for developing alternatives to BPA exists. Structural analogues of BPA have already been detected in foods and humans. Due to the structural analogy of the alternatives, there is a risk of effects similar to BPA. Objectives: The aim was to elucidate and compare the hazards of bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF), bisphenol S (BPS) and 4-cumylphenol (HPP) to BPA. Methods: In vitro studies on steroidogenesis, receptor activity, and biomarkers of effect, as well as Quantitative Structure-Activity Relationship (QSAR) modeling. Results: All test compounds caused the same qualitative effects on estrogen receptor and androgen receptor activities, and most of the alternatives exhibited potencies within the same range as BPA. Hormone profiles for the compounds indicated a specific mechanism of action on steroidogenesis which generally lead to decreased androgen, and increased estrogen and progestagen levels. Differential effects on corticosteroid synthesis were observed suggesting a compound-specific mechanism. Overall, BPS was less estrogenic and antiandrogenic than BPA, but BPS showed the largest efficacy on 17α-hydroxyprogesterone (17α-OH progesterone). Finally, there were indications of DNA damage, carcinogenicity, oxidative stress, effects on metabolism, and skin sensitization of one or more of the test compounds. Conclusions: Interference with the endocrine system was the predominant effect of the test compounds. A substitution of BPA with these structural analogues should be carried out with caution.
Article
Full-text available
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.
Article
Full-text available
Composites formulated from pH-sensitive colour formers mixed with fatty acid co-solvents and acidic developers have been prepared and their thermochromic properties investigated. Possible explanations for the thermochromic effect have been considered and evidence is presented in support of a mechanism based on phase changes occurring within the compositions during heating and cooling. © British Crown Copyright 1998/MOD. Published with the permission of the Controller of Her Britannic Majesty's Stationery Office.
Article
Full-text available
Of 13 thermal printing papers analyzed, 11 contained 8-17 g/kg bisphenol A (BPA). When taking hold of a receipt consisting of thermal printing paper for 5 s, roughly 1 microg BPA (0.2-6 microg) was transferred to the forefinger and the middle finger if the skin was rather dry and about ten times more if these fingers were wet or very greasy. This amount transferred to dry skin was neither significantly increased when taking hold of the paper at up to 10 sites, nor reduced when BPA-free paper was contacted afterwards. After 60-90 min, BPA applied to the skin as a solution in ethanol was only partially or no longer at all extractable with ethanol, whereas BPA transferred to the skin by holding thermal printer paper remained largely extractable after 2 h. This suggests that penetration of the skin depends on the conditions. Extractability experiments did not enable us to conclude whether BPA passes through the skin, but indicated that it can enter the skin to such a depth that it can no longer be washed off. If this BPA ends up in the human metabolism, exposure of a person repeatedly touching thermal printer paper for 10 h/day, such as at a cash register, could reach 71 microg/day, which is 42 times less than the present tolerable daily intake (TDI). However, if more than just the finger pads contact the BPA-containing paper or a hand cream enhances permeability of the skin, this margin might be smaller.
Article
Bisphenol A (BPA), a synthetic xenoestrogen widely used in various industrial fields, can be present, in its un-reacted form, as an additive in thermal paper. BPA is virtually ubiquitous in industrialized societies and humans are exposed to this chemical via dietary and non-dietary sources. Since in 2015 European Food Safety Authority (EFSA) indicated that thermal paper, is the second source of BPA exposure after the food chain, some suppliers replaced BPA with its analogue Bisphenol S (BPS), speculatively supposed to be safer. In this work BPA and BPS concentration levels were determined in 50 thermal paper receipts collected in Italy by liquid chromatography coupled to tandem fluorescence and ultraviolet detection. BPA was found in 44 samples at mean concentration of 107.47 µg/100 mg of paper (from below Limits of Quantification (LOQ) to 1533.733 µg/100 mg of paper). BPS was found in 31 samples at mean concentration of 41.97 µg/100 mg of paper (from below the LOQ to 357.989 µg/100 mg of paper). 26 samples were positive to both BPA and BPS. The estimate daily intake (EDI) values of BPA and BPS occurring through dermal absorption were calculated for 70 kg body weight individuals. For general population, they were 0.0625 µg/day for BPA and 0.0244 µg/day for BPS, based on the mean content of bisphenols found. For occupationally exposed individuals, they were 66.8 µg/day for BPA and 15.6 µg/day for BPS, based on the worst scenario. Such levels would produce a dermal intake below the Tolerable Day Intake established by EFSA (4 µg/kg bw/day); nevertheless, the occurrence of co-exposure to dietary and non-dietary sources should be considered in the health risk assessment, mainly for people frequently exposed to thermal paper contact, as for occupational reason.
Article
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.
Article
Endocrine disruption is a named field of research which has been very active for over 10 years, although the effects of endocrine disruptors in wildlife have been studied mainly in vast since the 1940s. A large number of chemicals have been identified as endocrine disruptors and humans can be exposed to them either due to their occupations or through dietary and environmental exposure (water, soil and air). Endocrine disrupting chemicals are compounds that alter the normal functioning of the endocrine system of both humans and wildlife. In order to understand the vulnerability and risk factors of people due to endocrine disruptors as well as the remedies for these, methods need to be developed in order to predict effects on populations and communities from the knowledge of effects on individuals. For several years there have been a growing interest on the mechanism and effect of endocrine disruptors and their relation with environment and human health effect. This paper, based on extensive literature survey, briefly studies the progress mainly in human to provide information concerning causative substances, mechanism of action, ubiquity of effects and important issues related to endocrine disruptors. It also reviews the current knowledge of the potential impacts of endocrine disruptors on human health so that the effects can be known and remedies applied for the problem as soon as possible. Copyright © 2015 Elsevier B.V. All rights reserved.
Article
Bisphenol A (BPA) is a chemical widely used both in plastics production as a food and beverage container and in thermal papers as a color developer. Dietary consumption is the main route of human exposure to BPA, but dermal absorption through handling different papers might be underestimated or ignored. In this study, BPA in different paper products, including different types of papers, receipts and Chinese currencies, were investigated. BPA was detected in receipts (n = 87) and Chinese currencies (n = 46) with concentrations of 0.17-2.675 × 10(4) μg per g paper and 0.09-288.55 μg per g paper, respectively. Except for parchment papers (n = 3), copy papers (n = 3) and food contact papers (n = 3), BPA was measured in all of the other paper products, with levels of 0.01-6.67 μg per g paper. BPA transferred from thermal papers to common papers increased with the increasing contact pressure. Compared with that in water, the migration speed of BPA was doubled in the synthetic sweat. Washing hands could reduce BPA dermal exposure, and washing hands with lotion was the most efficient way. However, about 19-47% of BPA was still found on hands after different washing methods. Dermal absorption via handling of receipts and papers was estimated to be 36.45 ng per day for the general population and 1.54 × 10(-3) to 248.73 μg per day for a cashier. These values are below the maximum doses recommended by the U.S. Environmental Protection Agency and the European Food Safety Authority. However, due to its uncertain adverse effects on human beings, long-term BPA exposure through dermal absorption should be paid more attention, particularly for some occupational populations.
Article
Individual pancreatic β-cells are functionally heterogeneous. Their sensitivity to glucose is variable, so that the proportion of active cells increases with the glucose concentration (recruitment). We have investigated whether sulphonylureas also recruit β-cells, by measuring cytoplasmic Ca2+ ([Ca2+]i) – the triggering signal of insulin secretion – in single cells and clusters of cells prepared from mouse islets. In 4 mM glucose, the threshold concentration of tolbutamide inducing a [Ca2+]i rise was variable (5 – 50 μM). The proportion of responsive cells and clusters therefore increased with the tolbutamide concentration, to reach a maximum of 90% of the cells and 100% of the clusters. This recruitment occurred faster when the glucose concentration was increased from 4 to 5 mM (EC50 of ∼14 and ∼4 μM tolbutamide respectively). Within responsive clusters little recruitment was observed; when a cluster was active, all or nearly all cells were active probably because of cell coupling. Thus, tolbutamide-induced [Ca2+]i oscillations were synchronous in all cells of each cluster, whereas there was no synchrony between clusters or individual cells. Independently of cell recruitment, tolbutamide gradually augmented the magnitude of the [Ca2+]i rise in single cells and clusters. This increase occurred over a broader range of concentrations than did recruitment (EC50 of ∼50 and 25 μM tolbutamide at 4 and 5 mM glucose respectively). Tolbutamide (10 μM) accelerated the recruitment of single cells and clusters brought about by increasing glucose concentrations (range of 3 – 7 mM instead of 4 – 10 mM glucose), and potentiated the amplification of the individual responses that glucose also produced. In conclusion, both metabolic (glucose) and pharmacologic (sulphonylurea) inhibition of K+-ATP channels recruits β-cells to generate a [Ca2+]i response. However, the response is not of an all-or-none type; it increases in amplitude with the concentration of either glucose or tolbutamide. British Journal of Pharmacology (2001) 133, 575–585; doi:10.1038/sj.bjp.0704108
Article
Bisphenol A (BPA) is widely used as a color developer in thermal paper. Thermal paper is ubiquitous in daily life due to its use in cash register receipts, so opportunities for human contact abound. For this study, 10 blank cash register receipts were obtained from businesses in suburban Boston. BPA was extracted and analysis of concentration was performed using gas chromatograph/flame ionization detector. In some receipts, BPA was not detected but in others it was as high as 19 mg for a 12-inch long receipt, which is in line with concentrations indicated in patents. This study is intended to highlight the potential for human exposure to BPA as well as the ease with which exposure may be reduced through the use of BPA-free thermal paper.
Article
Bisphenol-A (BPA) is a commonly used color developer in thermal paper. In this application, BPA is present in its free, unbound form and can be readily released, making thermal paper a potential source for human exposure. In this study, BPA was determined in 44 thermal paper samples collected in Belgium. BPA was detected in all the samples; 73% of the samples had concentrations between 0.9% and 2.1% (between 9 and 21mg BPA/g paper), while the remaining 27% of the samples had concentrations below 0.01% (0.1mg BPA/g paper). The BPA concentrations measured in thermal paper were comparable with those reported in other international studies. Since thermal paper is a feedstock for paper recycling processes, contamination of other "BPA-free" papers can occur. An estimation of human exposure through thermal paper results in a median intake of 445ng BPA/day for the general population, which corresponds to an exposure of 6.4ng/kg bw/day for a person of 70kg. The exposure of those people who come occupationally in contact with thermal paper can be much higher.
Article
As the evidence of the toxic effects of bisphenol A (BPA) grows, its application in commercial products is gradually being replaced with other related compounds, such as bisphenol S (BPS). Nevertheless, very little is known about the occurrence of BPS in the environment. In this study, BPS was analyzed in 16 types of paper and paper products (n = 268), including thermal receipts, paper currencies, flyers, magazines, newspapers, food contact papers, airplane luggage tags, printing paper, kitchen rolls (i.e., paper towels), and toilet paper. All thermal receipt paper samples (n = 111) contained BPS at concentrations ranging from 0.0000138 to 22.0 mg/g (geometric mean: 0.181 mg/g). The overall mean concentrations of BPS in thermal receipt papers were similar to the concentrations reported earlier for BPA in the same set of samples. A significant negative correlation existed between BPS and BPA concentrations in thermal receipt paper samples (r = -0.55, p < 0.0001). BPS was detected in 87% of currency bill samples (n = 52) from 21 countries, at concentrations ranging from below the limit of quantification (LOQ) to 6.26 μg/g (geometric mean: 0.029 μg/g). BPS also was found in 14 other paper product types (n = 105), at concentrations ranging from <LOQ to 8.38 μg/g (geometric mean: 0.0036 μg/g; detection rate: 52%). The estimated daily intake (EDI) of BPS, through dermal absorption via handling of papers and currency bills, was estimated on the basis of concentrations and frequencies of the handling of papers by humans. The median and 95th percentile EDI values, respectively, were 4.18 and 11.0 ng/kg body weight (bw)/day for the general population and 312 and 821 ng/kg bw/day for occupationally exposed individuals. Among the paper types analyzed, thermal receipt papers were found to be the major sources of human exposure to BPS (>88%). To our knowledge, this is the first report on the occurrence of BPS in paper products and currency bills.
Article
Cyclic oligomers are the major substances migrating from polyamide (PA) food contact materials. However, no commercial standards are available for the quantification of these substances. For the first time the quantification of cyclic oligomers was carried out by HPLC coupled with a chemiluminescence nitrogen detector (CLND) and single-substance calibration. Cyclic monomer (MW = 226 Da) and dimer (MW = 452 Da) of PA66 were synthesised and equimolar N detection of CLND to synthesised oligomers, caprolactam, 6-aminohexanoic acid (monomers of PA6) and caffeine (a typical nitrogen calibrant) was proven. Relative response factors (UVD at 210 nm) referring to caprolactam were determined for cyclic PA6 oligomers from dimer to nonamer, using HPLC-CLND in combination with a UVD. A method for quantification of cyclic oligomer content in PA materials was introduced using HPLC-CLND analysis and caffeine as a single nitrogen calibrant. The method was applied to the quantification of cyclic PA oligomers in several PA granulates. For two PA6 granulates from different manufacturers markedly different oligomer contents were analysed (19.5 versus 13.4 g kg⁻¹). The elution pattern of cyclic oligomers offers the possibility of identifying the PA type and differentiating between PA copolymers and blends.
Article
Bisphenol A (BPA) is used in a variety of consumer products, including some paper products, particularly thermal receipt papers, for which it is used as a color developer. Nevertheless, little is known about the magnitude of BPA contamination or human exposure to BPA as a result of contact with paper and paper products. In this study, concentrations of BPA were determined in 15 types of paper products (n = 202), including thermal receipts, flyers, magazines, tickets, mailing envelopes, newspapers, food contact papers, food cartons, airplane boarding passes, luggage tags, printing papers, business cards, napkins, paper towels, and toilet paper, collected from several cities in the USA. Thermal receipt papers also were collected from Japan, Korea, and Vietnam. BPA was found in 94% of thermal receipt papers (n = 103) at concentrations ranging from below the limit of quantitation (LOQ, 1 ng/g) to 13.9 mg/g (geometric mean: 0.211 mg/g). The majority (81%) of other paper products (n = 99) contained BPA at concentrations ranging from below the LOQ to 14.4 μg/g (geometric mean: 0.016 μg/g). Whereas thermal receipt papers contained the highest concentrations of BPA (milligram-per-gram), some paper products, including napkins and toilet paper, made from recycled papers contained microgram-per-gram concentrations of BPA. Contamination during the paper recycling process is a source of BPA in paper products. Daily intake (DI) of BPA through dermal absorption was estimated based on the measured BPA concentrations and handling frequency of paper products. The daily intake of BPA (calculated from median concentrations) through dermal absorption from handling of papers was 17.5 and 1300 ng/day for the general population and occupationally exposed individuals, respectively; these values are minor compared with exposure through diet. Among paper products, thermal receipt papers contributed to the majority (>98%) of the exposures.
Article
Skin contact has been hypothesized to contribute to human exposure to bisphenol A (BPA). We examined the diffusion and metabolism of BPA using viable skin models: human skin explants and short-term cultures of pig ear skin, an alternative model for the study of the fate of xenobiotics following contact exposure. 14C-BPA [50-800 nmol] was applied on the surface of skin models. Radioactivity distribution was measured in all skin compartments and in the diffusion cells of static cells diffusion systems. BPA and metabolites were further quantified by radio-HPLC. BPA was efficiently absorbed in short-term cultures, with no major difference between the models used in the study [viable pig ear skin: 65%; viable human explants: 46%; non-viable (previously frozen) pig skin: 58%]. BPA was extensively metabolized in viable systems only. Major BPA metabolites produced by the skin were BPA mono-glucuronide and BPA mono-sulfate, accounting together for 73% and 27% of the dose, in pig and human, respectively. In conclusion, experiments with viable skin models unequivocally demonstrate that BPA is readily absorbed and metabolized by the skin. The trans-dermal route is expected to contribute substantially to BPA exposure in human, when direct contact with BPA (free monomer) occurs.
Article
Eight phenolics were detected in samples collected from areas where paper-recycling process water is discharged. The detected concentration levels were up to 270 microg/L and 230 microg/g in water samples and sediment samples, respectively, obtained from both the outfall of the paper-recycling process water and its downstream areas. In particular, totarol (compound 4), 2,4-bis(1-phenylethyl)phenol (compound 6), 4,4'-butylidenebis(6-t-butyl-m-cresol) (compound 7), 2,4-bis(1-phenylethyl)-6-chlorophenol (compound 8), and 4-hydroxy-4'-isopropoxydiphenyl sulfone (compound 9) were identified for the first time as environmental pollutants. The estrogenicities of the identified compounds were assessed by yeast two-hybrid assays incorporating either the human or medaka fish (Oryzias latipes) estrogen receptor alpha (hERalpha and medERalpha, respectively) and an estrogen receptor competitive enzyme-linked immunosorbent assay (ER-ELISA) both with and without metabolic activation by a rat liver S9 mix. Bisphenol A (compound 3) and 2-naphthol (compound 1) exhibited activity in the assays of both hERalpha and medERalpha without the S9 mix. The relative activity (%) to 17beta-estradiol was 0.0015% for compound 3 and 0.0009% for compound 1 in the hERalpha assay and 0.027% for compound 3 and 0.0093% for compound 1 in the medERalpha assay. These compounds were attenuated by the S9 mix. The binding affinity was evaluated using an ER-ELISA. Compounds 3, 4, 6, and 7 exhibited affinity without the S9 mix. After exposure to the S9 mix, however, the binding affinity of compound 7 was eliminated by the S9 mix; those of compounds 3, 4, and 6 were attenuated; and that of compound 8 exhibited affinity. A comprehensive assessment of the estrogenicities of the phenolics originating from thermal paper and their implications for an aquatic environment may require an examination of the components of the phenolics, as in the present study.
BASF the Chemical Company Material Safety Data Sheet
BASF, 2015. BASF the Chemical Company Material Safety Data Sheet. Pergafast® 201. Not available.
Danish Environmental Protection Agency Alternative Technologies and Substances to Bisphenol a (BPA) in Thermal Paper Receipts Environmental Project No. 1553
  • Epa Danish
Danish EPA, 2014. Danish Environmental Protection Agency Alternative Technologies and Substances to Bisphenol a (BPA) in Thermal Paper Receipts Environmental Project No. 1553. Online available: http://www2.mst.dk/Udgiv/ publications/2014/03/978-87-93178-20-5.pdf.
Paper and board intended to come into contact with foodstuffs e determination of colour fastness of dyed paper and board
DIN EN 646, 2006. Paper and board intended to come into contact with foodstuffs e determination of colour fastness of dyed paper and board. Ger. version En. 646, 2006.
Proposal for Restriction, Substance Name: 4.4'-isopropylidenediphenol (Bisphenol a; BPA) European Chemicals Agency. Online available: https://echa.europa
ECHA, 2014. Annex XV Restriction Report, Proposal for Restriction, Substance Name: 4.4'-isopropylidenediphenol (Bisphenol a; BPA). European Chemicals Agency. Online available: https://echa.europa.eu/documents/10162/c6a8003c81f3-4df6-b7e8-15a3a36baf76.
EFSA panel on food contact materials, enzymes, flavourings and processing aids scientific opinion on the risks to public health related to the presence of bisphenol A (bpa) in foodstuffs: executive summary
EFSA, 2015. EFSA panel on food contact materials, enzymes, flavourings and processing aids scientific opinion on the risks to public health related to the presence of bisphenol A (bpa) in foodstuffs: executive summary. EFSA J. 13 (1), 3978. http://dx.doi.org/10.2903/j.efsa.2015.3978.
Thermally-responsive record material Patent
  • M R Fisher
  • F S Chakar
  • Y Defrenne
M.R. Fisher, F.S. Chakar, Y. Defrenne. 2014. Thermally-responsive record material Patent. US 8,916,497 B2.
Migration of Bisphenol a from Cash Register Receipts and Baby Dummies, Survey of Chemical Substances in Consumer Products
  • C Lassen
  • S H Mikkelsen
  • U K Brandt
Lassen, C., Mikkelsen, S.H., Brandt, U.K., 2011. Migration of Bisphenol a from Cash Register Receipts and Baby Dummies, Survey of Chemical Substances in Consumer Products, No. 110. Danish Ministry of the Environment, Copenhagen, Denmark.
BPA Coats Cash Register Receipts. Environmental Working Group
  • S Lunder
  • D Andrews
  • J Houlihan
S. Lunder, D. Andrews, J. Houlihan. BPA Coats Cash Register Receipts. Environmental Working Group. Online available: http://www.ewg.org/bpa-in-store-receipts.
National Industrial Chemicals Notification and Assessment Scheme. Full public report. Pergafast 201 National Industrial Chemicals Notification and Assessment Scheme. National Occupational Health and Safety Commission
NICNAS, 2004. National Industrial Chemicals Notification and Assessment Scheme. Full public report. Pergafast 201 National Industrial Chemicals Notification and Assessment Scheme. National Occupational Health and Safety Commission, Australia.
Registration, Evaluation, Authorisation and Restriction of Chemicals 4,4'-Diaminodiphenylsulfon (Dapsone) CAS-nr
REACH, 2017. Registration, Evaluation, Authorisation and Restriction of Chemicals 4,4'-Diaminodiphenylsulfon (Dapsone) CAS-nr. 80-08-0 Umwelt Bundesamt. Online available: http://www.reach-info.de/dapsone.htm. (Accessed 24 March 2017).
French Agency for Food, Environmental and Occupational Health and Safety Opinion of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) on the Restriction Proposal under the REACh Regulation: Bisphenol a in Thermal Paper ANSES Opinion No 2013-RE-004
ANSES, 2014. French Agency for Food, Environmental and Occupational Health and Safety Opinion of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) on the Restriction Proposal under the REACh Regulation: Bisphenol a in Thermal Paper ANSES Opinion No 2013-RE-004. Online available: https://www.anses.fr/en/system/files/REACH2013re0004EN.pdf.
Annex XV Restriction Report, Proposal for Restriction, Substance Name: 4.4'-isopropylidenediphenol (Bisphenol a; BPA)
ECHA, 2014. Annex XV Restriction Report, Proposal for Restriction, Substance Name: 4.4'-isopropylidenediphenol (Bisphenol a; BPA). European Chemicals Agency. Online available: https://echa.europa.eu/documents/10162/c6a8003c-81f3-4df6-b7e8-15a3a36baf76.
Pergafast 201 National Industrial Chemicals Notification and Assessment Scheme. National Occupational Health and Safety Commission
  • Australia
  • T Ostberg
  • E Noaksson
NICNAS, 2004. National Industrial Chemicals Notification and Assessment Scheme. Full public report. Pergafast 201 National Industrial Chemicals Notification and Assessment Scheme. National Occupational Health and Safety Commission, Australia. € Ostberg, T., Noaksson, E., 2010. Bisfenol a I Svenska Kvitton, Analysresultat J€ amtlands L€ ans Landsting. Institutet f€ or Till€ ampad Gr€ on Kemi, Sweden. REACH, 2017. Registration, Evaluation, Authorisation and Restriction of Chemicals 4,4'-Diaminodiphenylsulfon (Dapsone) CAS-nr. 80-08-0 Umwelt Bundesamt. Online available: http://www.reach-info.de/dapsone.htm. (Accessed 24 March 2017).
  • U S Epa
U.S. EPA, 2015. U.S. Environmental Protection Agency. Bisphenol a Alternatives in Thermal Paper. final report. Online available: https://www.epa.gov/sites/ production/files/2015-08/documents/bpa_final.pdf.