Bisphenol S (BPS) is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

with the

formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...

(HOC₆H₄)₂SO₂. It has two

phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it req ...

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...

s on either side of a

sulfonyl In organosulfur chemistry, a sulfonyl group can refer either to a functional group found primarily in sulfones, or to a substituent obtained from a sulfonic acid by the removal of the hydroxyl group, similarly to acyl groups. Sulfonyl groups c ...

group. It is commonly used in curing fast-drying

epoxy Epoxy is the family of basic components or cured end products of epoxy resins. Epoxy resins, also known as polyepoxides, are a class of reactive prepolymers and polymers which contain epoxide groups. The epoxide functional group is also coll ...

resin adhesives. It is classified as a

bisphenol The bisphenols () are a group of chemical compounds related to diphenylmethane. Most are based on two hydroxyphenyl functional groups linked by a methylene bridge. Exceptions include bisphenol S, P, and M. "Bisphenol" is a common name; the lett ...

, and a close molecular analog of

Bisphenol A Bisphenol A (BPA) is a chemical compound primarily used in the manufacturing of various plastics. It is a colourless solid which is soluble in most common organic solvents, but has very poor solubility in water. BPA is produced on an industrial s ...

(BPA). BPS differentiates from BPA by possessing a

sulfone In organic chemistry, a sulfone is a organosulfur compound containing a sulfonyl () functional group attached to two carbon atoms. The central hexavalent sulfur atom is double-bonded to each of two oxygen atoms and has a single bond to each of ...

group (SO₂) as the central linker of the molecule instead of a dimethylmethylene group (C(CH₃)₂), which is the case of Bisphenol A.

Use

BPS is used in curing fast-drying epoxy glues and as a

corrosion inhibitor In chemistry, a corrosion inhibitor or anti-corrosive is a chemical compound that, when added to a liquid or gas, decreases the corrosion rate of a material, typically a metal or an alloy, that comes into contact with the fluid. The effectiveness ...

. It is also commonly used as a reactant in

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

reactions. BPS has become increasingly common as a building block in

polyethersulfone Polysulfones are a family of high performance thermoplastics. These polymers are known for their toughness and stability at high temperatures. Technically used polysulfones contain an aryl- SO2-aryl subunit. Due to the high cost of raw material ...

and some epoxies, following the public awareness that BPA has

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

-mimicking properties, and widespread-belief that enough of it remains in the products to be dangerous. However, BPS may have comparable estrogenic effects to BPA. BPS is now used to a variety of common consumer products. In some cases, BPS is used where the legal prohibition on BPA allows products (esp. plastic containers) containing BPS to be labelled "BPA free". BPS also has the advantage of being more stable to heat and light than BPA. To comply with restrictions and regulations on BPA due to its confirmed toxicity, manufacturers are gradually replacing BPA with other related compounds, mainly bisphenol S, as substitutes in industrial applications. BPS is also used as an anticorrosive agent in

glues. Chemically, BPS is being used as a reagent in polymer reactions. BPS has also been reported to occur in canned foodstuffs, such as

tin cans A steel can, tin can, tin (especially in British English, Australian English, Canadian English and South African English), steel packaging, or can is a container for the distribution or storage of goods, made of thin metal. Many cans ...

. In a 2015 study analyzing BPS in a variety of paper products worldwide, BPS was found in 100% of tickets, mailing envelopes, airplane boarding passes, and airplane luggage tags. In this study, very high concentrations of BPS were detected in thermal receipt samples collected from cities in the United States, Japan, Korea, and Vietnam. The BPS concentrations were large but varied greatly, from a few tens of nanograms per gram to several milligrams per gram. Nevertheless, concentrations of BPS used in thermal paper are usually lower compared to those of BPA. Finally, BPS can get into the human body through dermal absorption from handling

banknotes A banknote—also called a bill (North American English), paper money, or simply a note—is a type of negotiable instrument, negotiable promissory note, made by a bank or other licensed authority, payable to the bearer on demand. Banknotes w ...

Health effects

Cardiac effects

Although there is no direct link established between BPS and

cardiac disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

, it is thought that BPS may operate by a similar mechanism to BPA and could cause cardiac toxicity. In animal studies, BPS has been shown to hinder MI recovery, induce cardiac

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

s and cause cardiac developmental deformities. Rats exposed to high doses of BPS were reported to have increased risk of

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...

(a significant risk factor in cardiac disease) due to BPS inducing synthesis of

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

in peripheral tissues.

Neurobehavioural effects

BPS has the potential to have an effect on a wide range of neurological functions. A recent study showed that exposure to BPS during pregnancy may disrupt

thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...

levels. These are important in foetal neurodevelopment and prenatal exposure to BPS has been linked to impaired psychomotor development in children. In a study using human

embryonic stem cell Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consi ...

s, BPS was shown to cause a reduction in length of

neurite A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture ...

s in neuron-like cells. This disruption could lead to neurobehavioral problems such as ASD. The mechanism of the neurological impact of BPS is thought to be related to its oestrogenic effect which can interfere in the levels and action of thyroid hormone, which is essential for normal development of the nervous system; it regulates migration and differentiation of

neural cells In Biology, biology, the nervous system is the Complex system, highly complex part of an animal that coordinates its Behavior, actions and Sense, sensory information by transmitting action potential, signals to and from different parts of its ...

synaptogenesis Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenes ...

and

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...

ation.

Effects on obesity

It has been proposed that BPS has the potential to affect

body weight Human body weight is a person's mass or weight. Strictly speaking, body weight is the measurement of weight without items located on the person. Practically though, body weight may be measured with clothes on, but without shoes or heavy accessor ...

, and several studies have found a correlation between exposure to bisphenols and increased body weight. This is thought to be due to an accumulation of

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

s in

adipocyte Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...

s i.e. a build-up of fat in fat cells. It has also been suggested that BPS leads to the formation of new adipocytes as exposure to it increases the expression of related markers. A correlation between exposure to BPS before birth and being overweight has been found in mice, although this was only found when they were also fed a high fat diet. The pathway through which BPS acts on cells to increase body weight is suggested to be different to the pathway through which BPA acts, even though they have very similar chemical structures. Only one study has demonstrated a decrease in body weight after BPS exposure, and the affected mice quickly regained the weight they had lost.

Other metabolic effects

BPS levels in the human body can be measured in the urine. In one study of children, there was a significant correlation between urinary levels of BPS and insulin resistance, abnormal kidney function and abnormal vascular function. It has been suggested that there is a link between gestational diabetes mellitus and urinary BPS. Therefore, exposure to BPS may be a risk factor for developing the condition.

Effects on skeletal development

The effect of long term exposure to BPS is an enrichment of

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...

differentiation and enhanced development of the embryonic skeletal system.

Effects on early development

BPS, like BPA, can cross the

placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...

sheep Sheep or domestic sheep (''Ovis aries'') are domesticated, ruminant mammals typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus ''Ovis'', in everyday usage it almost always refers to domesticated s ...

and alter the

endocrine The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...

functionality of the

. It does this by reducing the maternal serum concentration of

trophoblast The trophoblast (from Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the pl ...

ic proteins. BPS shows almost identical effects on the placenta as BPA, with both BPS and BPS altering almost identical sets of genes.

Fetal A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal develo ...

exposure to BPS through the placenta, during a

critical period In developmental psychology and developmental biology, a critical period is a maturational stage in the lifespan of an organism during which the nervous system is especially sensitive to certain environmental stimuli. If, for some reason, the org ...

, can have negative effects on the developmental programming of the fetus. BPS exposure in the zebrafish model affected development of the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

and resulted in hyperactive behaviour. Studies in the Mouse model have shown that exposure to BPS significantly reduced the secretion of

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...

within the mouse fetal

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...

, with exposure to BPS in female mice also causing a significant fall in

egg An egg is an organic vessel grown by an animal to carry a possibly fertilized egg cell (a zygote) and to incubate from it an embryo within the egg until the embryo has become an animal fetus that can survive on its own, at which point the a ...

number, whilst also negatively affecting the quality of

oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...

s. Studies in the

Zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...

model have shown that parental exposure to BPS causes disrupted thyroid hormone levels in both the parental generation and

F1 generation An F1 hybrid (also known as filial 1 hybrid) is the first filial generation of offspring of distinctly different parental types. F1 hybrids are used in genetics, and in selective breeding, where the term F1 crossbreed may be used. The term is somet ...

. It is not clear the mechanism of BPS’s effect on thyroid hormone levels after human exposure.

Effects on reproductive health

The endocrine disrupting nature of BPS has encouraged investigations into its affinity to estrogenic receptors, showing BPS to be a weak

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

; similar in potency to BPA, which it has come to substitute. Select studies show BPS to be capable of mimicking

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...

, and sometimes being more effective. The estrogenic activity of BPS has been demonstrated through in vivo rodent studies, inducing growth of the womb, with a range of dosages. These are pathways necessary for cell function, cell cycle regulation, and neuroendocrine induced behaviours which are important for reproduction. BPS has shown to both disrupt signalling and damage DNA. Androgenic and antiandrogenic activity have also been confirmed by BPS disrupting function of the androgen receptors. Studies on zebrafish have shown decreased egg quality, reduced

sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...

count, an increased frequency of

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

abnormalities, as well as changes in the mass of

gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...

s; suggesting that BPS is a

reproductive The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pheromones are als ...

toxin for both sexes.

Environmental considerations

Recent work suggests that, like BPA, BPS also has endocrine disrupting properties. What makes BPS, and BPA, endocrine disruptors is the presence of the hydroxy group on the benzene ring. This phenol moiety allows BPA and BPS to mimic estradiol. In a study of human urine, BPS was found in 81% of the samples tested. This percentage is comparable to BPA which was found in 95% of urine samples. Another study done on thermal receipt paper shows that 88% of human exposure to BPS is through receipts. The recycling of

thermal paper A thermal column (or thermal) is a rising mass of buoyant air, a convective current in the atmosphere, that transfers heat energy vertically. Thermals are created by the uneven heating of Earth's surface from solar radiation, and are an example ...

can introduce BPS into the cycle of paper production and cause BPS contamination of other types of paper products. A recent study showed presence of BPS in more than 70% of the household waste paper samples, potentially indicating spreading of BPS contamination through paper recycling. BPS is more resistant to environmental degradation than BPA, and although not persistent cannot be characterised as readily biodegradable.

History

BPS was first made in 1869 as a dye and is currently common in everyday consumer products. BPS is an analog of BPA that has replaced BPA in a variety of ways, being present in thermal receipt paper, plastics, and indoor dust. After health concerns associated with bisphenol A grew in 2012, BPS began to be used as a replacement.

Regulation

It is difficult for consumers to determine if a product contains BPS due to limited labeling regulations.

Synthesis

Bisphenol S is prepared by the

reaction Reaction may refer to a process or to a response to an action, event, or exposure: Physics and chemistry *Chemical reaction *Nuclear reaction *Reaction (physics), as defined by Newton's third law *Chain reaction (disambiguation). Biology and me ...

of two equivalents of

with one equivalent of

sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...

oleum Oleum (Latin ''oleum'', meaning oil), or fuming sulfuric acid, is a term referring to solutions of various compositions of sulfur trioxide in sulfuric acid, or sometimes more specifically to disulfuric acid (also known as pyrosulfuric acid). Ole ...

.METHOD OF PREPARATION OF 4,4′-DIHYDROXYDIPHENYLSULPHONE (Freepatentsonline)
:2 C₆H₅OH + H₂SO₄ → (C₆H₄OH)₂SO₂ + 2 H₂O :2 C₆H₅OH + SO₃ → (C₆H₄OH)₂SO₂ + H₂O This reaction can also produce 2,4'-sulfonyldiphenol, a common

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

ic complication in

electrophilic aromatic substitution Electrophilic aromatic substitution is an organic reaction in which an atom that is attached to an aromatic system (usually hydrogen) is replaced by an electrophile. Some of the most important electrophilic aromatic substitutions are aromatic ni ...

reactions. : bisphenol synthesis

References

{{Estrogen receptor modulators Bisphenols Endocrine disruptors Estrogens Nonsteroidal antiandrogens Benzosulfones

Use