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Unlabelled: Bisphenol A (BPA) belongs to chemicals that are produced in large quantities worldwide. It is commonly used as monomer in polycarbonate synthesis, plasticizer in the production of epoxy resins, as well as an additive for the elimination of surfeit of hydrochloric acid during the polyvinyl chloride (PVC) production. BPA is not only used in the production of plastics intended to a direct contact with food, including plastic packaging and kitchenware, but also in inner coatings of cans and jar caps. There are various routes of human exposure to this substance such as oral, by inhalation and transdermal. The main sources of exposure to BPA include food packaging and dust, dental materials, healthcare equipment, thermal paper, toys and articles for children and infants. BPA is metabolized in the liver to form bisphenol A glucuronide and mostly in this form is excreted with urine. Due to its phenolic structure BPA has been shown to interact with estrogen receptors and to act as agonist or antagonist via estrogen receptor (ER) dependent signalling pathways. Therefore, BPA has been shown to play a role in the pathogenesis of several endocrine disorders including female and male infertility, precocious puberty, hormone dependent tumours such as breast and prostate cancer and several metabolic disorders including polycystic ovary syndrome (PCOS). Because of the constant, daily exposure and its tendency to bio-accumulation, BPA seems to require special attention such as biomonitoring. This observation should include clinical tests of BPA concentration in the urine, which is not only one of the best methods of evaluation of the exposure to this compound, but also the dependence of the daily intake of BPA and the risk of some endocrine disorders. Key words: bisphenol A, BPA, estrogens, endocrine disrupting chemicals.
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Rocz Panstw Zakl Hig 2015;66(1):5-11
*Corresponding author: Aleksandra Rutkowska, Department of Clinical and Experimental Endocrinology, Medical University
of Gdańsk, Powstania Styczniowego 9B street, 81-519 Gdynia, Poland, e-mail: olarynio@gumed.edu.pl
© Copyright by the National Institute of Public Health - National Institute of Hygiene
HEALTH RISK OF EXPOSURE TO BISPHENOL A (BPA)
Aleksandra Konieczna, Aleksandra Rutkowska*, Dominik Rachoń
Department of Clinical and Experimental Endocrinology, Medical University of Gdańsk, Gdynia, Poland
ABSTRACT
Bisphenol A (BPA) belongs to chemicals that are produced in large quantities worldwide. It is commonly used as monomer
in polycarbonate synthesis, plasticizer in the production of epoxy resins, as well as an additive for the elimination of surfeit
of hydrochloric acid during the polyvinyl chloride (PVC) production. BPA is not only used in the production of plastics
intended to a direct contact with food, including plastic packaging and kitchenware, but also in inner coatings of cans and
jar caps. There are various routes of human exposure to this substance such as oral, by inhalation and transdermal. The
main sources of exposure to BPA include food packaging and dust, dental materials, healthcare equipment, thermal paper,
toys and articles for children and infants. BPA is metabolized in the liver to form bisphenol A glucuronide and mostly in
this form is excreted with urine. Due to its phenolic structure BPA has been shown to interact with estrogen receptors and
to act as agonist or antagonist via estrogen receptor (ER) dependent signalling pathways. Therefore, BPA has been shown
to play a role in the pathogenesis of several endocrine disorders including female and male infertility, precocious puberty,
hormone dependent tumours such as breast and prostate cancer and several metabolic disorders including polycystic ovary
syndrome (PCOS). Because of the constant, daily exposure and its tendency to bio-accumulation, BPA seems to require
special attention such as biomonitoring. This observation should include clinical tests of BPA concentration in the urine,
which is not only one of the best methods of evaluation of the exposure to this compound, but also the dependence of the
daily intake of BPA and the risk of some endocrine disorders.
Key words: bisphenol A, BPA, estrogens, endocrine disrupting chemicals
STRESZCZENIE
Bisfenol A (BPA) należy do substancji chemicznych produkowanych na świecie w znacznych ilościach. Używany jest jako
plastyfikator i półprodukt w syntezie żywic epoksydowych, tworzyw sztucznych poliwęglanowych oraz jako dodatek do
usuwania nadmiaru kwasu chlorowodorowego przy produkcji polichlorku winylu (PCW). BPA nie tylko jest używany do
syntezy tworzyw sztucznych służących do produkcji materiałów mających bezpośredni kontakt z żywnością, włączając
opakowania z tworzyw sztucznych oraz sprzęt kuchenny, ale także stanowi składnik lakierów do pokrywania wewnętrznych
powierzchni puszek metalowych przeznaczonych do żywności i napojów. BPA stosowany jest w produkcji poliwęglanów
(PC) i żywic epoksydowych, wykorzystywanych w produkcji wyrobów do kontaktu z żywnością. Może być także stosowany,
jako przeciwutleniacz i inhibitor w procesie polimeryzacji tworzyw sztucznych, m.in. polichlorku winylu (PCW). Narażenie
na BPA może zachodzić drogą pokarmową, wziewną oraz przez skórę, a głównymi źródłami ekspozycji są opakowania
żywności, kurz, materiały stomatologiczne, sprzęt medyczny, papier termiczny, a także zabawki i artykuły przeznaczone dla
niemowląt i dzieci. BPA jest metabolizowany w wątrobie do glukuronianu bisfenolu A i w tej postaci jest usuwany z moczem.
Ze względu na swą fenolową strukturę BPA wykazuje zdolność jako agonista lub antagonista do interakcji z receptorami
estrogenowymi poprzez estrogenowe szlaki sygnalizacyjne. W wyniku takiego działania BPA odgrywa rolę w patogenezie
zaburzeń endokrynnych włączając zaburzenia płodności u kobiet i mężczyzn, przedwczesne dojrzewanie, nowotwory hor-
monozależne, jak rak piersi oraz rak prostaty oraz schorzeń metabolicznych włączając zespół wielotorbielowatych jajników
(PCOS). Biorąc pod uwagę stałe, codzienne narażenie na BPA z wielu źródeł oraz tendencje do bioakumulacji uzasadniony
jest monitoring biologiczny tego związku. Powinien on w szczególności uwzględniać monitoring BPA w moczu, jako sku-
teczną metodę szacowania narażenia na ten związek, umożliwiając jednocześnie badanie zależności pomiędzy narażeniem
na BPA a ryzykiem występowania niektórych chorób wynikających z zaburzenia czynności układu endokrynologicznego.
Słowa kluczowe: bisfenol A, BPA, estrogeny, związki endokrynnie czynne
A. Konieczna, A. Rutkowska, D. Rachoń
6No 1
INTRODUCTION
Bisphenol A (BPA) belongs to chemicals that are
produced in the large quantities. It is commonly used
as a plasticizer and an intermediate in the synthesis of
epoxy resins, polycarbonate plastics [29] as well as an
additive for the elimination of surfeit of hydrochloric
acid during the polyvinyl chloride (PVC) fabrication.
BPA is widely used in the production of healthcare
equipment [52], dental composites [13], contact lenses,
spectacle lenses, toys, storage media and window foils
[2]. BPA is one of the Food Contact Materials (FCMs),
which means that it is used in the preparation of plastics
for the manufacture of materials that have direct contact
with food [10], plastic packaging, kitchenware, jar cap
coatings, and the wall of cans that isolates the food from
metal, therefore preventing its corrosion [8].
It is estimated that in 2008 the total world produc-
tion of BPA was approximately 5.2 million tons [2]. The
world’s largest producers are the United States (22.9%
of global production), Taiwan and Japan (13.1% and
13%, respectively). Synthesis of BPA in Poland is about
12 000 tons per year (0.3% of the world production)
[42]. The highest percentage of BPA is used as a com-
ponent of the polycarbonate (74% of the total amount
of produced BPA) and the epoxy resins (nearly 20%).
As a result of the mass production, a large number of
derivatives of BPA are released into the environment,
which consequently leads to increasing pollution and
contamination of the soil and groundwater [22]. It is
estimated than China itself (where 3.6% of the global
amount of BPA is synthesized) produces annually ap-
proximately 5 000 tons of post-production waste [57].
HUMAN EXPOSURE TO BPA IN
EVERYDAY LIFE
BPA is a widely used compound in daily life.
Therefore, there are various routes of human exposure
to this substance such as oral, by inhalation and trans-
dermal. The main sources of exposure to BPA include
food packaging and dust, dental materials, healthcare
equipment, thermal paper, toys and articles for children
and infants. Food products are the major source of BPA
exposure, which is an order of magnitude higher than for
other routes [20]. The most important source of dietary
exposure to BPA is canned foods, but it may also be
present in fresh foods such as meat, milk or eggs, when
animals are bred in the polluted areas or watered with
the contaminated water [51]. In addition, the presence
of BPA was detected in the food products stored in the
cardboard boxes [41].
BPA is widely used in the manufacture of cans for
food preservation and for the inside coatings of jar caps
[23, 41]. It is used to prevent the direct contact of food
with the metal, to ensure the thermal stability and the
mechanical strength of the can [8]. Coatings that are
the most commonly used for this purpose are made of
epoxy resins. Approximately 9% of BPA produced an-
nually is used for the production of the lining material
in cans [23]. Heating cans during sterilization or food
preparation causes the BPA to leak into the can content
from the epoxy coating of the can wall and therefore,
increases the potential of BPA dietary exposure [9]. The
highest increase of BPA concentration was observed
after heating the product at 121°C for 90 minutes. The
temperature of heating food products turned out to be
more relevant for the migration level of BPA than the
time of the heating [30]. Sterilization of the canned food
causes migration of the 80-100% of the unconjugated
BPA to the content of the can and it seems to depend
on the conditions of the process and the ingredients of
the product [24]. The foods with lower pH and higher
fat content contain higher concentrations of BPA [38].
Contamination with BPA may also be caused by the
migration to food stored in polycarbonate plastics (reus-
able containers, polycarbonate water bottles and drink
dispensers) or prepared for consumption, such as bottles
for infants and children, especially during heating and
microwave cooking [53].
BPA can also migrate into dust from laminate
flooring, adhesives containing epoxy resins, paints and
household electronic equipment [27]. This compound
was detected in 95% of 56 dust samples, with the con-
centrations ranging between 0.8 mg to 10 mg per gram
of dust [18, 36]. Higher values were detected in dust
from offices and laboratories, mainly because they were
equipped with a vast quantity of furniture and electronic
devices. Home exposure among children and infants
may be higher due to the presence of commonplace
items containing BPA, which very often are being taking
by children in to the mouth, as well as by the inhalation
of the contaminated air [7]. The exposure through dust
was estimated to be less than 5% of the total exposure
to BPA [21]. Exposure resulting from polluted air is less
than 0.4 ng/kg body weight per day in adults, whereas
in infants is estimated to be 5.3 ng/kg of body weight
per day [35].
Dental materials consist of monomers that may
contain BPA, particularly in the form of bis-GMA
(bisphenol A-glycidyl methacrylate). This compound
is often released from the dental fillings, sealants or
materials used to rebuild the crown of the tooth [13].
It has been shown that the highest concentration of
BPA was in the saliva of the patient immediately after
acquiring the dental fillings and decreased afterwards.
However, chronic exposure to BPA released from
dental materials in small doses for a long time cannot
be excluded [17]. After applying the reconstruction of
Health risk of exposure to Bisphenol A 7No 1
a molar tooth crown, 13 mg to 30 mg BPA per day has
been shown to be released [51], which may suggest that
dental treatments can be a significant source of BPA
exposure, especially in the case of patients who have
many dental fillings [20].
Small amounts of BPA (0.3-0.35 mg) can be released
from several medical devices, which contain polycarbo-
nate or polysulfone plasticizers such as contact lenses,
probes, inhalers, intravenous cannulas, catheters, neo-
natal incubators or haemodialysis apparatus [6, 21, 26].
BPA is also used in the production of paper for
thermal printing in cash registers and payment card
terminals. Exposure to BPA from thermal paper occurs
through the contact of unwashed hands with food or
mouth directly, as well as transdermally [21].
It has been shown that thermal paper receipts are
the second, after dietary exposure, most common source
of BPA exposure in people over the age of three [16].
Several studies show that the cashiers having prolonged
contact with such receipts, presented higher concen-
tration of this compound in the urine compared to the
general population (2.4 mg/g and 1.2 mg/g, respectively)
[5]. The overall exposure to BPA migrating from thermal
paper also depends on the frequency and time of use
and cleanliness of hands. It has been estimated that oc-
cupational exposure after ten hours of work as a cashier
is 71 mg per day whereas in general population it ranges
from 7.1 mg to 42.6 mg per day [4].
Long-term exposure to BPA may be also due to the
contact with toys and products intended for infants and
young children, such as baby dummies and teethers
that may be put into the mouth, for several hours dur-
ing the day. Saliva BPA concentration was shown to be
0.14 – 2.1 mg/l saliva for rattles and 0.11 mg to14 mg/l
saliva for pacifiers, after 24h contact with such products
[31]. One minute exposure of saliva with pacifiers and
teethers caused the presence of BPA at the concentration
of 0.3 mg/l and 5.9 mg/l, respectively [53].
METABOLISM AND TOXICOKINETICS
OF BISPHENOL A
BPA is metabolized in the liver by the uridine
5’-diphospho-glucuronyl transferase (UGT), which
catalyzes the glucuronidation of BPA (Figure 1) [56].
BPA can also be metabolized into other substances
such as BPA-sulfate or bisphenol-3,4-quinone [55].
The half-life of BPA in the human body is estimated to
be 5.4 hours [48].
HEALTH RISKS RELATATED TO BPA
EXPOSURE
Due to its phenolic structure BPA has been shown
to interact with estrogen receptors and to act as agonist
or antagonist via endocrine receptor (ER) dependent
signalling pathways (Figure 2) [36]. Therefore, BPA
has been shown to play a role in the pathogenesis of
several endocrine disorders including female and male
infertility, precocious puberty, hormone dependent
tumours such as breast and prostate cancer and several
metabolic disorders including polycystic ovary syndro-
me (PCOS) [12].
Increased levels of urinary BPA concentration
were correlated with a reduced number of sperm in the
ejaculate, as well as its reduced motility and viability
[33, 46]. The pathomechanism of the fertility disrupting
potential of BPA in women as well as in men seems to
be due to its estrogenic activity in the hypothalamus
which in turn disrupts the proper function of the GnRH
Figure 1. Glucuronidation of BPA in human
A. Konieczna, A. Rutkowska, D. Rachoń
8No 1
pulse generator thus the adequate secretion of the FSH
and LH is impaired [14].
Data from animal experiments show that BPA
exposure can also be the cause of precocious puberty.
Prenatal rat exposure to BPA concentrations of 2 mg/kg
body weight per day accelerated puberty in compari-
son to the control group [28]. It seems that the main
mechanism of precocious puberty due to BPA exposure
is due to its weak estrogenic activity, which through the
positive feedback mechanism stimulate the activity of
the GnRH pulse generator, therefore giving the rise in
the pituitary LH and FSH secretion [43].
There are reports on a potential role of BPA in the
pathogenesis of breast cancer. Studies conducted in
vitro have shown that the exposure of the human breast
cancer cell line to BPA increased its proliferation and
caused increased oxidative stress [54]. Similar results
were obtained for the MCF-7 estrogen receptor posi-
tive cells (ER +), where low levels of BPA significantly
increased its proliferation and the expression of the
progesterone receptors [32]. High serum BPA concen-
trations in postmenopausal women also correlated with
the mammographic density of the breast tissue [47]. It
is also suggested that occupational exposure to BPA
increased incidence of breast cancer [11].
BPA may be one of the factors that contribute to
the development of prostate cancer. Studies conducted
in men with prostate cancer showed a much higher
concentration of BPA in the urine of those patients in
comparison with the control group [50]. In vitro studies
have shown that BPA induces the proliferation of the
androgen-sensitive human prostate cancer cells [54].
In rats treated with BPA an increase of prostate and
epididymis weight was also observed [25]. Moreover,
exposure to BPA in utero contributed to prostate enlarge-
ment in the male offspring [39].
Obesity is a metabolic disorder in which BPA has
also been shown to have an impact. Animal studies
have shown a correlation between prenatal exposure to
endocrine disrupting chemicals, including BPA, and the
prevalence of obesity, impaired glucose tolerance and
lipid metabolism in mice [40]. Mice exposed to 10 mg
BPA/kg body weight per day had higher concentrations
of plasma triglycerides, and increased body weight in
four months of age comparing to the control group.
An endocrine disorder, in the pathogenesis of which
BPA may also be involved, is the polycystic ovary
syndrome (PCOS) which is the most common endo-
crinopathy among women of child-bearing age [44]. In
patients with PCOS, especially obese ones, BPA serum
concentrations were significantly higher compared to
healthy controls [49]. The pathogenesis of PCOS is
very complex. One of the proposed mechanisms by
which BPA may be involved in the pathogenesis of this
syndrome is through the activation of the hypothalamic
GnRH pulse generator leading to a constant increase of
plasma LH concentrations which in turn stimulate the
ovarian androgen production and impair proper ovarian
follicle development [3, 34]. In addition, BPA has been
shown to directly increase ovarian androgen synthesis
[58] (Figure 3).
BPA AS AN ENDOCRINE DISRUPTING
CHEMICAL
According to the European Food Safety Authority
(EFSA), an endocrine disrupting chemical is every
synthetic or natural compound that meets the follow-
ing criteria: presents endocrine activity, causes adverse
Figure 2. Structural similarity of BPA to 17b-estradiol
Figure 3. Proposed mechanisms of the BPA action in the
pathogenesis of PCOS
Health risk of exposure to Bisphenol A 9No 1
health effects as well as link between its endocrine
activity and adverse affects is believable [15].
As aforementioned, BPA has been shown to present
a weak estrogenic activity and therefore may disrupt
the proper function of the endocrine system [10]. Thus
many international authorities express its concern
about the BPA exposure, especially among groups with
higher susceptibility to EDC [45]. EFSA applied a total
uncertainty factor of 150 (for inter- and intra-species
differences and uncertainty in mammary gland, re-
productive, neurobehavioural, immune and metabolic
system effects) to decrease recommended Tolerable
Daily Intake (TDI) from 50 μg/kg bw/day to 4 μg/kg
bw/day as a temporary TDI (t-TDI) [16].
As BPA meets all the above criteria it is indisputable
that BPA belongs to endocrine disrupting chemicals [1].
It is of human benefit to estimate the exposure to BPA
throughout biological monitoring ie. measuring BPA
concentration directly in human fluids like blood, urine
or breast milk [11]. Thus, biomonitoring seems to be the
best method of an assessment of BPA total intake from
diverse sources, because of many routes of exposure
to this compound.
CONCLUSIONS
Taking into account numerous sources of BPA and
endocrine disrupting potential of this chemical it seems
to be advisable to introduce a nation-wide biomonitoring
in order to evaluate health risk for man with the special
attention paid to perinatal and child exposure. Such mo-
nitoring may also provide a valuable tool for searching
relations between exposure to BPA and prevalence of
hormone-related disorders.
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Received: 07.11.2014
Accepted: 22.01.2015
SCIENTIFIC CONFERENCE
UNDER THE HONORARY PATRONAGE
OF
Professor Mirosław J. Wysocki
NATIONAL CONSULTANT
ON PUBLIC HEALTH
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CONFERENCE TOPICS
1. Human nutrition
2. Physical activity
3. Health promotion
SCIENTIFIC COMMITTEE OF THE CONFERENCE
prof. Jadwiga Charzewska (Warszawa), prof. Adam Czaplicki (Biała Podlaska), Jolanta Czarnocimska
PhD (Poznań), Ewa Czeczelewska PhD (Siedlce), prof. Jan Czeczelewski (Biała Podlaska), prof. Jan
Gawęcki (Poznań), Paweł Goryński PhD (Siedlce), prof. Krystyna Górniak (Biała Podlaska), Jadwiga
Hamułka PhD (Warszawa), prof. Marzena Jeżewska-Zychowicz (Warszawa), prof. Jerzy Jurkiewicz
(Siedlce), prof. Jan K. Karczewski (Białystok), Henryk Komoń PhD (Siedlce), Dominik
Krzyżanowski PhD (Wrocław), prof. Longin Marianowski (Siedlce), Barbara Pietruszka PhD
(Warszawa), prof. Helena Popławska (Biała Podlaska), Jacek Putz PhD (Siedlce), prof. Barbara
Raczyńska (Biała Podlaska), prof. Jerzy Sadowski (Biała Podlaska), Małgorzata A. Słowińska PhD
(Olsztyn), prof. Mieczysław Szostek (Siedlce), prof. Andrzej Szpak (Białystok), prof. Lidia
Wądołowska (Olsztyn), prof. Andrzej Wojtczak (Siedlce), prof. Joanna Wyka (Wrocław)
ORGANISERS
Department of Biology and Anatomy
The Faculty of Physical Education and Sport
The Branch of Warsaw University of Physical
Education in Biała Podlaska
The Faculty of Health Sciences
Collegium MAZOVIA
Innovative Higher School in Siedlce
INFORMATION CONCERNING THE CONFERENCE IS AVAILABLE ON THE
FOLLOWING WEBSITES:
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http://www.mazovia.edu.pl - “Badania naukowe” → “Konferencje”
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Mazowiecki Regional Hospital in Siedlce
... This emphasizes the necessity for additional research into the mechanisms responsible for BPA-induced OS and the implementation of preventive strategies to mitigate exposure in at-risk populations. Concurrently, epidemiological studies have linked BPA exposure to various malignancies, including breast, prostate, and ovarian cancer, highlighting the multifaceted impact of this ubiquitous chemical on human health [15,16]. ...
Article
Full-text available
Bisphenol A (BPA) is a common environmental pollutant, and its specific mechanisms in cancer development and its impact on the tumor immune microenvironment are not yet fully understood. Transcriptome data from osteosarcoma (OS) patients were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. BPA-related genes were identified through the Comparative Toxicogenomics Database (CTD), yielding 177 genes. Differentially expressed genes were analyzed using the GSE162454 dataset from the Tumor Immune Single Cell Hub 2 (TISCH2). We constructed the prognostic model using univariate Cox regression and LASSO analysis. The model was validated using the GSE16091 dataset. GO, KEGG, and GSEA analyses were performed to investigate the mechanisms of BPA-related genes. A total of 15 BPA-related genes were identified as differentially expressed in OS. Univariate Cox regression and LASSO analysis identified four key prognostic genes (FOLR1, MYC, ESRRA, VEGFA). The prognostic model exhibited strong predictive performance with area under the curve (AUC) values of 0.89, 0.6, and 0.79 for predicting 1-, 2-, and 3-year survival, respectively. External validation using the GSE16091 dataset confirmed the model's high accuracy with AUC values exceeding 0.88. Our results indicated that the prognosis of the high-risk population is generally poorer, which may be associated with alterations in the tumor immune microenvironment. In the high-risk group, immune cells showed predominantly low expression levels, while immune checkpoint genes were significantly overexpressed, along with markedly elevated tumor purity. These findings revealed a correlation between upregulation of BPA-related genes and formation of an immunosuppressive microenvironment, leading to unfavorable patient outcomes. Our study highlighted the significant association of BPA with OS biology, particularly in its potential role in modulating the tumor immune microenvironment. We offered a fresh insight into the influence of BPA on cancer development, thus providing valuable insights for future clinical interventions and treatment strategies.
... A well-recognized EDC is Bisphenol A (BPA) that is used in plastic manufacturing within a broad range of products, namely, packaging, bags, and puericulture items (Konieczna et al. 2015;WHO and FAO 2009). Due to its adverse effects on reproduction, metabolism, development, neurobehavior, and others (Gioiosa et al. 2015;Ma et al. 2019;Mileva et al. 2014;Rochester 2013), BPA has been categorically banned in the food industry since 2015. ...
Article
Full-text available
Thyroid hormones play a crucial role in numerous physiological processes, including reproduction. Bisphenol S (BPS) is a structural analog of Bisphenol A known for its toxic effects. Interference of this substitute with normal thyroid function has been described. To investigate the effect of thyroid disruption on ovarian development following maternal exposure to BPS, female rats were exposed, daily, to either AT 1–850 (a thyroid hormone receptor antagonist) (10 nmol/rat) or BPS (0.2 mg/kg) during gestation and lactation. The effects on reproductive outcome, offspring development, histological structures, hormone levels, oxidative status, cytoskeleton proteins expression, and oocyte development gene expression were examined. Our results are in favor of offspring ovarian development disruption due to thyroid disturbance in adult pregnant females. During both fetal and postnatal stages, BPS considerably altered the histological structure of the thyroid tissue as well as oocyte and follicular development, which led to premature ovarian failure and stimulation of oocyte atresia, being accompanied with oxidative stress, hypothalamic-pituitary-ovarian axis disorders, and cytoskeletal dynamic disturbance. Crucially, our study underscores that BPS may induce reproductive toxicity by blocking nuclear thyroid hormone receptors, evidenced by the parallelism and the perfect meshing between the data obtained following exposure to AT 1–850 and those after the treatment by this substitute.
Article
In this study, significant improvements in mechanical properties have been seen through the efficient inclusion of Oil Palm Cellulose Nanofibrils (CNF) as nano-fillers into green polymer matrices produced from biomass with a 28 % carbon content. The goal of the research was to make green epoxy nanocomposites utilizing solution blending process with acetone as the solvent with the different CNF loadings (0.1, 0.25, and 0.5 wt%). An ultrasonic bath was used in conjunction with mechanical stirring to guarantee that CNF was effectively dispersed throughout the green epoxy. The resultant nanocomposites underwent thorough evaluation, comparing them to unfilled green epoxy and evaluating their morphological, mechanical, and thermal behavior using a variety of instruments. Field-emission scanning electron microscopy (FE-SEM) was used to validate findings, which showed that the CNF were dispersed optimally inside the nanocomposites. The thermal degradation temperature (Td) of the nanocomposites showed a marginal decrement of 0.8 % in temperatures (from 348 °C to 345 °C), between unfilled green epoxy (neat) and 0.1 wt% of CNF loading. The mechanical test results, which showed a 13.3 % improvement in hardness and a 6.45 % rise in tensile strength when compared to unfilled green epoxy, were in line with previously published research. Overall, the outcomes showed that green nanocomposites have significantly improved in performance.
Article
Full-text available
Iatrogenic gestational exposure to diethylstilbestrol (DES) induced alterations of the genital tract and predisposed individuals to develop clear cell carcinoma of the vagina as well as breast cancer later in life. Gestational exposure of rodents to a related compound, the xenoestrogen bisphenol-A (BPA) increases the propensity to develop mammary cancer during adulthood, long after cessation of exposure. Exposure to BPA during gestation induces morphological alterations in both the stroma and the epithelium of the fetal mammary gland at 18 days of age. We postulate that the primary target of BPA is the fetal stroma, the only mammary tissue expressing estrogen receptors during fetal life. BPA would then alter the reciprocal stroma-epithelial interactions that mediate mammogenesis. In addition to this direct effect on the mammary gland, BPA is postulated to affect the hypothalamus and thus in turn affect the regulation of mammotropic hormones at puberty and beyond.
Article
Full-text available
Food Contact Materials (FCMs) are a major source of endocrine disrupting chemical substances (EDCs), thus forming an important part of human exposure to these compounds, to which this article is addressed. The potential impact of such exposures on endocrine function, and thereby health outcomes, requires scientifically valid evidence so that appropriate risk management decisions can be taken to diminish human exposure, particularly in vulnerable population groups like infants and small children. Relevant aspects of exposure assessment are discussed based on testing migration of EDCs from FCMs, together with the different approaches so used. The specific migration testing determines whether limits for defined substances are met. However not all EDCs present in the leachate may be found by these means. In fact, the chances of detecting EDCs in the food simulant (leachate) are improved when it is subjected the relevant biological testing, thus helping to provide improved protection against these chemical substances. Nevertheless, official controls and risk management decisions do not necessarily take such testing into account, as the relevant legislation is based on specific migration limits that may be easily quantified and addressed in the risk management process. Elucidating the link between observed endocrine activity and any toxic effects so arising, is complicated by the complexity of endocrine interrelationships coupled with relatively limited sensitivity of toxicological tests. Any risk assessment implies a rather high uncertainty and should include also any cumulative effects. This review discusses the effects of the EDCs like bisphenol A, phthalates and benzophenone found in FCMs. In addition, the approaches from the USA and EU for systematically evaluating man-made EDCs in the environment are also considered, including appropriate prioritisation criteria.
Article
Full-text available
Human exposure to bisphenol A (BPA) is ubiquitous. Animal studies found that BPA contributes to development of prostate cancer, but human data are scarce. Our study examined the association between urinary BPA levels and Prostate cancer and assessed the effects of BPA on induction of centrosome abnormalities as an underlying mechanism promoting prostate carcinogenesis. The study, involving 60 urology patients, found higher levels of urinary BPA (creatinine-adjusted) in Prostate cancer patients (5.74 µg/g [95% CI; 2.63, 12.51]) than in non-Prostate cancer patients (1.43 µg/g [95% CI; 0.70, 2.88]) (p = 0.012). The difference was even more significant in patients <65 years old. A trend toward a negative association between urinary BPA and serum PSA was observed in Prostate cancer patients but not in non-Prostate cancer patients. In vitro studies examined centrosomal abnormalities, microtubule nucleation, and anchorage-independent growth in four Prostate cancer cell lines (LNCaP, C4-2, 22Rv1, PC-3) and two immortalized normal prostate epithelial cell lines (NPrEC and RWPE-1). Exposure to low doses (0.01-100 nM) of BPA increased the percentage of cells with centrosome amplification two- to eight-fold. Dose responses either peaked or reached the plateaus with 0.1 nM BPA exposure. This low dose also promoted microtubule nucleation and regrowth at centrosomes in RWPE-1 and enhanced anchorage-independent growth in C4-2. These findings suggest that urinary BPA level is an independent prognostic marker in Prostate cancer and that BPA exposure may lower serum PSA levels in Prostate cancer patients. Moreover, disruption of the centrosome duplication cycle by low-dose BPA may contribute to neoplastic transformation of the prostate.
Article
Full-text available
Abstract The FACET tool is a probabilistic model to estimate exposure to chemicals in foodstuffs, originating from flavours, additives and food contact materials. This paper demonstrates the use of the FACET tool to estimate exposure to BPA (bisphenol A) from light metal packaging. For exposure to migrants from food packaging, FACET uses industry supplied data on the occurrence of substances in the packaging, their concentrations and construction of the packaging, which were combined with data from a market research organisation and food consumption data supplied by national database managers. To illustrate the principles, UK packaging data were used together with consumption data from the UK NDNS (National Diet and Nutrition Survey) dietary survey for 19-64 year olds for a refined deterministic verification. The UK data were chosen mainly because the consumption surveys are detailed, data for UK packaging at a detailed level were available and, arguably, the UK population are high consumers of packaged foodstuffs. Exposures were run for each food category that could give rise to BPA from light metal packaging. Consumer loyalty to a particular type of packaging, commonly referred to as packaging loyalty, was set. The BPA extraction levels used for the 13 types of coating chemistries that could release BPA, were in the range of 0.00005 to 0.012 mg/dm(2). The estimates of exposure to BPA using FACET for the total diet were 0.0098 (mean) and 0.0466 (97.5th%ile) mg/person/day, corresponding to 0.00013 (mean) and 0.00059 (97.5th%ile) mg/kg body weight/day, for consumers of foods packed in light metal packaging. This is well below the current EFSA (and other recognised bodies) TDI of 0.05 mg/kg body weight/day. These probabilistic estimates were compared with estimates using a refined deterministic approach drawing on the same input data. The results from FACET for the mean, 95th and 97.5th percentile exposures to BPA lay between the lowest and the highest estimates from the refined deterministic calculations. Since this should be the case, for a fully probabilistic compared to a deterministic approach, it is concluded that the FACET tool has been verified in this example. A recent EFSA draft opinion on exposure to BPA from different sources showed that canned foods were a major contributor and compared results from various models, including those from FACET. The results from FACET were overall conservative.
Article
In utero exposure to bisphenol-A (BPA) at doses relevant to human consumption has been reported to accelerate weight gain and puberty in female mice, but the effect of low dose BPA on female reproduction has not been described. In this study, we investigated low dose effects of BPA on sexual maturation and reproduction in female ICR/Jcl mice. Pregnant ICR mice (F0) were injected (s.c.) with BPA (2 and 20 g/kg), diethylstilbestrol (DES; 0.02, 0.2, and 2 g/kg) or oil vehicle once per day from gestational days 11–17. For both female and male offspring (F1), body weights were measured on postnatal day (PND) 0 (the day of birth), 11, 22, and 60, and anogenital distance (AGD) was measured on PNDs 22 and 60. Pups were weaned at PND 22 and males were caged separately from females. Vaginal smears were taken daily beginning the day of vaginal opening for 30 days. The age at vaginal opening was significantly earlier in all exposed females except for 2 g/kg BPA females compared to oil controls. Body weight at vaginal opening was lower than controls in all exposed females. The first vaginal estrus was earlier in all exposed females except for the 2 g/kg BPA group females compared to controls. From PND 90 to 120, gestationally exposed F1 female mice were mated with unexposed males. Total numbers of pups and sex ratio in F1 mice exposed to BPA or DES, and those of their offspring (F2) were not different from controls in any treatment group. The present results indicate that prenatal exposure to low doses of BPA and DES induces early vaginal opening, but does not affect reproductive functioning at the first breeding.
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
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans. The CERHR Expert Panel on Bisphenol A completed its evaluation in August 2007. CERHR selected bisphenol A for evaluation because of the: widespread human exposure; public concern for possible health effects from human exposures; high production volume; evidence of reproductive and developmental toxicity in laboratory animal studies Bisphenol A (CAS RN: 80-05-7) is a high production volume chemical used primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics are used in some food and drink containers; the resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. To a lesser extent bisphenol A is used in the production of polyester resins, polysulfone resins, polyacrylate resins, and flame retardants. In addition, bisphenol A is used in the processing of polyvinyl chloride plastic and in the recycling of thermal paper. Some polymers used in dental sealants and tooth coatings contain bisphenol A. The primary source of exposure to bisphenol A for most people is assumed to occur through the diet. While air, dust, and water (including skin contact during bathing and swimming) are other possible sources of exposure, bisphenol A in food and beverages accounts for the majority of daily human exposure. The highest estimated daily intakes of bisphenol A in the general population occur in infants and children. The results of this bisphenol A evaluation are published in an NTP-CERHR Monograph that includes the (1) NTP Brief and (2) Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A. Additional information related to the evaluation process, including the peer review report for the NTP Brief and public comments received on the draft NTP Brief and the final expert panel report, are available on the CERHR website (http://cerhr.niehs.nih.gov/). See bisphenol A under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs. nih.gov/chemicals/bisphenol/bisphenol.html). The NTP reached the following conclusions on the possible effects of exposure to bisphenol A on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. The NTP has some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has minimal concern for effects on the mammary gland and an earlier age for puberty for females in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects, or reduced birth weight and growth in their offspring. The NTP has negligible concern that exposure to bisphenol A will cause reproductive effects in non-occupationally exposed adults and minimal concern for workers exposed to higher levels in occupational settings. NTP will transmit the NTP-CERHR Monograph on Bisphenol A to federal and state agencies, interested parties, and the public and make it available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD from CERHR.
Article
A visible-light driven photoelectrochemical (PEC) sensor based on aptamer immobilized TiO2-Fe2O3 nanotubes was proposed for the first time and highly sensitive and selective bisphenol A determination was realized. Taking advantage of the alloy oxide nanotube structure, high surface area, good biocompatibility, superior photoelectrocatalytic performance, a limit of detection toward BPA as low as 1.8×10−11 M with linearity in the range from 1.8×10−11 to 3.2×10−9 M could be achieved. Specificity was greatly exhibited for this aptasensor under 100-fold excess concentration of estriol, resorcinol, nonylphenol, 2,4-D, acetamiprid, chlorpyrifos and omethoate. Simultaneously, satisfactory results were obtained in real water sample investigation from industrial plastics and drinking water. A novel visible-light driven PEC method for highly sensitive and selective detection of BPA was thus established.
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Abstract Polycystic ovary syndrome (PCOS) is the most common and the most heterogeneous endocrine disorder in premenopausal women. Apart from signs of hyperandrogenism such as acne, hirsutism and hair loss, women with PCOS usually present with menstrual irregularities and fertility problems.Additionally, they are often characterized by impaired glucose tolerance, which usually leads to the development of type 2 diabetes mellitus (T2DM). This review article describes current and novel approach to the pathomechanisms of PCOS and the potential role of an endocrine disrupting chemical ("endocrine disruptor" - ED) - bisphenol A (BPA), which is commonly used as a plasticizer and due to its molecular structure can interact with estrogen receptors (ERs). Recent observations point to the higher levels of BPA in biological fluids of women with PCOS and its role in the pathogenesis of hyperandrogenism and hyperinsulinemia. It seems that mother's exposure to BPA during pregnancy may also lead to the development of PCOS in the female offspring.