Bisphenol S: Difference between revisions

| Name = Bisphenol S

| ImageFile = Bisphenol S.svg

| ImageName = Bisphenol S

| ImageSize = 220px

| ImageFile2 = Bisphenol S 3D BS-fixed.png

| ImageName2 = Bisphenol S 3D BS

| ImageSize2 = 220px

| OtherNames = BPS, 4,4′-sulfonylbisphenol,<br /> Bis(4-hydroxyphenyl)sulfone

| PIN = 4,4′-Sulfonyldiphenol

| Section1 = {{Chembox Identifiers

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|ChemSpiderID = 6374

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = 3OX4RR782R

|PubChem = 6626

|KEGG_Ref = {{keggcite|correct|kegg}}

|KEGG = C14216

|EC_number = 201-250-5

|ChEBI = 34372

|InChI = 1/C12H10O4S/c13-9-1-5-11(6-2-9)17(15,16)12-7-3-10(14)4-8-12/h1-8,13-14H

|SMILES = O=S(=O)(c1ccc(O)cc1)c2ccc(O)cc2

|InChIKey = VPWNQTHUCYMVMZ-UHFFFAOYAO

|SMILES1 = c1cc(ccc1O)S(=O)(=O)c2ccc(cc2)O

|ChEMBL_Ref = {{ebicite|correct|EBI}}

|ChEMBL = 384441

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChI = 1S/C12H10O4S/c13-9-1-5-11(6-2-9)17(15,16)12-7-3-10(14)4-8-12/h1-8,13-14H

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = VPWNQTHUCYMVMZ-UHFFFAOYSA-N

|CASNo_Ref = {{cascite|correct|CAS}}

|CASNo = 80-09-1

| Section2 = {{Chembox Properties

|C=12 | H=10 | O=4 | S=1

|Appearance = White colorless solid; forms needle shaped crystals in water

|Density = 1.3663&nbsp;g/cm³

|Solubility = 1100 mg/L<ref>{{cite journal | vauthors = Pivnenko K, Pedersen GA, Eriksson E, Astrup TF | title = Bisphenol A and its structural analogues in household waste paper | journal = Waste Management | volume = 44 | pages = 39–47 | date = October 2015 | pmid = 26194879 | doi = 10.1016/j.wasman.2015.07.017 | bibcode = 2015WaMan..44...39P | s2cid = 217938141 | url = http://orbit.dtu.dk/ws/files/118749778/PostPrint_Davidsen_JoH_1_.pdf }}</ref>

|SolubleOther = Soluble in [[ethanol]]

|MeltingPtC = 245 to 250

|MeltingPt_ref = <ref>{{cite web|url=http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/103039|title=4,4′-Sulfonyldiphenol|access-date=4 February 2016}}</ref>

}}

| Section3 = {{Chembox Hazards

|GHSPictograms = {{GHS07}}{{GHS08}}

|GHSSignalWord = Warning

|HPhrases = {{H-phrases|319|361}}

|PPhrases = {{P-phrases|201|202|264|280|281|305+351+338|308+313|337+313|405|501}}

}}

| Watchedfields = changed

| verifiedrevid = 408399736

}}

'''Bisphenol S''' ('''BPS''') is an [[organic compound]] with the [[Chemical formula|formula]] {{chem2|(HOC6H4)2SO2}}. It has two [[phenol]] [[functional group]]s on either side of a [[sulfonyl]] group. It is commonly used in curing fast-drying [[epoxy]] resin adhesives. It is classified as a [[bisphenol]], and a close [[Structural analog|molecular analog]] of [[bisphenol A]] (BPA). BPS differentiates from BPA by possessing a [[sulfone]] group {{chem2|(SO2)}} as the central linker of the molecule instead of a dimethylmethylene group {{chem2|(C(CH3)2)}}, which is the case of bisphenol A.

== Use ==

[[File:BPA-Free Bottle.JPG|left|thumb|309x309px|BPA Free Plastic]]

BPS is used in curing fast-drying epoxy glues and as a [[corrosion inhibitor]]. It is also commonly used as a reactant in [[polymer]] reactions.

BPS has become increasingly common as a building block in [[polyethersulfone]] and some epoxies, following the public awareness that BPA has [[estrogen]]-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.<ref>{{cite journal | vauthors = Grignard E, Lapenna S, Bremer S | title = Weak estrogenic transcriptional activities of Bisphenol A and Bisphenol S | journal = Toxicology in Vitro | volume = 26 | issue = 5 | pages = 727–31 | date = August 2012 | pmid = 22507746 | doi = 10.1016/j.tiv.2012.03.013| bibcode = 2012ToxVi..26..727G }}</ref> BPS is now used to a variety of common consumer products.<ref name=":4">{{cite journal | vauthors = Liao C, Liu F, Kannan K | title = Bisphenol s, a new bisphenol analogue, in paper products and currency bills and its association with bisphenol a residues | journal = Environmental Science & Technology | volume = 46 | issue = 12 | pages = 6515–22 | date = June 2012 | pmid = 22591511 | doi = 10.1021/es300876n | bibcode = 2012EnST...46.6515L }}</ref><ref>{{cite journal | vauthors = Liao C, Liu F, Guo Y, Moon HB, Nakata H, Wu Q, Kannan K | title = Occurrence of eight bisphenol analogues in indoor dust from the United States and several Asian countries: implications for human exposure | journal = Environmental Science & Technology | volume = 46 | issue = 16 | pages = 9138–45 | date = August 2012 | pmid = 22784190 | doi = 10.1021/es302004w | bibcode = 2012EnST...46.9138L }}</ref> In some cases, BPS is used where the legal prohibition on BPA allows products (esp. [[plastic containers]]) containing BPS to be labelled "BPA free".<ref>{{cite journal|author=Jenna Bilbrey|date=Aug 11, 2014|title=BPA-Free Plastic Containers May Be Just as Hazardous|url=http://www.scientificamerican.com/article/bpa-free-plastic-containers-may-be-just-as-hazardous/|journal=[[Scientific American]]}}</ref> BPS also has the advantage of being more stable to heat and light than BPA.<ref name="ETP">{{cite journal | vauthors = Kuruto-Niwa R, Nozawa R, Miyakoshi T, Shiozawa T, Terao Y | title = Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives using a GFP expression system | journal = Environmental Toxicology and Pharmacology | volume = 19 | issue = 1 | pages = 121–30 | date = January 2005 | pmid = 21783468 | doi = 10.1016/j.etap.2004.05.009 | bibcode = 2005EnvTP..19..121K }}</ref>

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.<ref name="pmid11847978">{{cite journal | vauthors = Chen MY, Ike M, Fujita M | title = Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols | journal = Environmental Toxicology | volume = 17 | issue = 1 | pages = 80–6 | date = February 2002 | pmid = 11847978 | doi = 10.1002/tox.10035 | bibcode = 2002EnTox..17...80C | s2cid = 21979200}}</ref>

BPS is also used as an anticorrosive agent in [[epoxy]] 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]].<ref name="pmid20127078">{{cite journal | vauthors = Viñas P, Campillo N, Martínez-Castillo N, Hernández-Córdoba M | title = Comparison of two derivatization-based methods for solid-phase microextraction-gas chromatography-mass spectrometric determination of bisphenol A, bisphenol S and biphenol migrated from food cans | journal = Analytical and Bioanalytical Chemistry | volume = 397 | issue = 1 | pages = 115–125 | date = May 2010 | pmid = 20127078 | doi = 10.1007/s00216-010-3464-7 | s2cid = 11696149}}</ref>

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.<ref name="Pivnenko 39–47">{{cite journal | vauthors = Pivnenko K, Pedersen GA, Eriksson E, Astrup TF | title = Bisphenol A and its structural analogues in household waste paper | journal = Waste Management | volume = 44 | pages = 39–47 | date = October 2015 | pmid = 26194879 | doi = 10.1016/j.wasman.2015.07.017 | bibcode = 2015WaMan..44...39P | s2cid = 217938141 | url = https://backend.orbit.dtu.dk/ws/files/118749778/PostPrint_Davidsen_JoH_1_.pdf}}</ref> Finally, BPS can get into the human body through dermal absorption from handling [[banknotes]].<ref name=":4" />

== Health effects ==

{{main|Health effects of Bisphenol A}}

=== Cardiac effects ===

Although there is no direct link established between BPS and [[Cardiovascular disease|cardiac disease]], it is thought that BPS may operate by a similar mechanism to BPA and could cause cardiac toxicity.<ref name=":1" /> In animal studies, BPS has been shown to hinder [[Myocardial infarction|MI]] recovery, induce cardiac [[arrhythmia]]s and cause cardiac developmental deformities. Rats exposed to high doses of BPS were reported to have increased risk of [[atherosclerosis]] (a significant risk factor in cardiac disease) due to BPS inducing synthesis of [[cholesterol]] in peripheral tissues.<ref name=":1">{{cite journal | vauthors = Zhang YF, Shan C, Wang Y, Qian LL, Jia DD, Zhang YF, Hao XD, Xu HM | display-authors = 6 | title = Cardiovascular toxicity and mechanism of bisphenol A and emerging risk of bisphenol S | journal = The Science of the Total Environment | volume = 723 | pages = 137952 | date = June 2020 | pmid = 32213405 | doi = 10.1016/j.scitotenv.2020.137952 | bibcode = 2020ScTEn.72337952Z | s2cid = 214679291}}</ref>

=== Neurobehavioral 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 hormones|thyroid hormone]] 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]]s, BPS was shown to cause a reduction in length of [[neurite]]s in neuron-like cells. This disruption could lead to neurobehavioral problems such as [[Autism spectrum|ASD]].<ref name=":2">{{cite journal | vauthors = Naderi M, Kwong RW | title = A comprehensive review of the neurobehavioral effects of bisphenol S and the mechanisms of action: New insights from in vitro and in vivo models | journal = Environment International | volume = 145 | pages = 106078 | date = September 2020 | pmid = 32911243 | doi = 10.1016/j.envint.2020.106078 | doi-access = free| bibcode = 2020EnInt.14506078N }}</ref>

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 [[Neuron|neural cells]], [[synaptogenesis]] and [[myelin]]ation.<ref name=":2" />

=== Effects on obesity ===

It has been proposed that BPS has the potential to affect [[Human body weight|body weight]], and several studies have found a correlation between exposure to bisphenols and increased body weight.<ref name=":0">{{cite journal | vauthors = Thoene M, Dzika E, Gonkowski S, Wojtkiewicz J | title = Bisphenol S in Food Causes Hormonal and Obesogenic Effects Comparable to or Worse than Bisphenol A: A Literature Review | journal = Nutrients | volume = 12 | issue = 2 | pages = 532 | date = February 2020 | pmid = 32092919 | pmc = 7071457 | doi = 10.3390/nu12020532 | doi-access = free }}</ref> This is thought to be due to an accumulation of [[lipid]]s in [[adipocyte]]s i.e. a build-up of fat in fat cells.<ref name=":0"/> It has also been suggested that BPS leads to the formation of new adipocytes as exposure to it increases the expression of related markers.<ref name=":0" /> 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.<ref name=":0"/>

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.<ref name=":0" />

Only one study has demonstrated a decrease in body weight after BPS exposure, and the affected mice quickly regained the weight they had lost.<ref name=":0" />

=== 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.<ref name=":0" />

It has been suggested that there is a link between gestational diabetes mellitus and urinary BPS.<ref name=":0" /> Therefore, exposure to BPS may be a risk factor for developing the condition.<ref name=":0" />

=== Effects on skeletal development ===

The effect of long term exposure to BPS is an enrichment of [[osteoclast]] differentiation and enhanced development of the embryonic skeletal system.<ref>{{cite journal | vauthors = Chin KY, Pang KL, Mark-Lee WF | title = A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health | journal = International Journal of Medical Sciences | volume = 15 | issue = 10 | pages = 1043–1050 | date = 2018 | pmid = 30013446 | pmc = 6036156 | doi = 10.7150/ijms.25634}}</ref>

=== Effects on early development ===

BPS, like BPA, can cross the [[placenta]] in [[sheep]] and alter the [[Endocrine system|endocrine]] functionality of the [[placenta]]. It does this by reducing the maternal serum concentration of [[trophoblast]]ic proteins. BPS shows almost identical effects on the placenta as BPA, with both BPS and BPS altering almost identical sets of [[Gene|genes.]]<ref name=":02">{{cite journal | vauthors = Basak S, Das MK, Duttaroy AK | title = Plastics derived endocrine-disrupting compounds and their effects on early development | journal = Birth Defects Research | date = June 2020 | volume = 112 | issue = 17 | pages = 1308–1325 | pmid = 32476245 | doi = 10.1002/bdr2.1741 | doi-access = free| hdl = 10852/82658 | hdl-access = free }}</ref>

[[Fetus|Fetal]] exposure to BPS through the placenta, during a [[critical period]], can have negative effects on the developmental programming of the fetus. BPS exposure in the zebrafish model affected development of the [[hypothalamus]] and resulted in hyperactive behaviour.

Studies in the Mouse model have shown that exposure to BPS significantly reduced the secretion of [[testosterone]] within the mouse fetal [[Testicle|testes]], with exposure to BPS in female mice also causing a significant fall in [[egg]] number, whilst also negatively affecting the quality of [[oocyte]]s.<ref name=":02" />

Zebrafish and humans share 70% of the same genes that are expressed during development therefore, they are a useful [[model organism]] to understand the effects of BPS.<ref>{{Cite journal |last1=Catron |first1=Tara R. |last2=Keely |first2=Scott P. |last3=Brinkman |first3=Nichole E. |last4=Zurlinden |first4=Todd J. |last5=Wood |first5=Charles E. |last6=Wright |first6=Justin R. |last7=Phelps |first7=Drake |last8=Wheaton |first8=Emily |last9=Kvasnicka |first9=Allison |last10=Gaballah |first10=Shaza |last11=Lamendella |first11=Regina |last12=Tal |first12=Tamara |date=2019-02-01 |title=Host Developmental Toxicity of BPA and BPA Alternatives Is Inversely Related to Microbiota Disruption in Zebrafish |url=https://pubmed.ncbi.nlm.nih.gov/30321396/ |journal=Toxicological Sciences|volume=167 |issue=2 |pages=468–483 |doi=10.1093/toxsci/kfy261 |issn=1096-0929 |pmid=30321396}}</ref> Studies in the [[Zebrafish]] model have shown that parental exposure to BPS causes disrupted thyroid hormone levels in both the parental generation and [[F1 generation]]. [[Fetus|Fetal]] exposure to BPS through the placenta, during a [[critical period]], can have negative effects on the developmental programming of the fetus. Additionally, there is evidence to suggest that embryos with high levels of BPS exhibit teratogenic effects of vital organs such as the heart and liver. Additionally, BPS inhibits the expression of genes within the liver used for the metabolism thus leading to increased stress of the liver through the zebrafish life.<ref>{{Cite journal |last1=Moreman |first1=John |last2=Lee |first2=Okhyun |last3=Trznadel |first3=Maciej |last4=David |first4=Arthur |last5=Kudoh |first5=Tetsuhiro |last6=Tyler |first6=Charles R. |date=2017-11-07 |title=Acute Toxicity, Teratogenic, and Estrogenic Effects of Bisphenol A and Its Alternative Replacements Bisphenol S, Bisphenol F, and Bisphenol AF in Zebrafish Embryo-Larvae |url=https://pubs.acs.org/doi/10.1021/acs.est.7b03283 |journal=Environmental Science & Technology |language=en |volume=51 |issue=21 |pages=12796–12805 |doi=10.1021/acs.est.7b03283 |pmid=29016128 |bibcode=2017EnST...5112796M |hdl=10871/38729 |issn=0013-936X|hdl-access=free }}</ref> Adult zebrafish that are exposed to low levels of BPS during development display hyperactivity due to an exponential increase in neural activity within the hypothalamus.<ref>{{Cite journal |last1=Kinch |first1=Cassandra D. |last2=Ibhazehiebo |first2=Kingsley |last3=Jeong |first3=Joo-Hyun |last4=Habibi |first4=Hamid R. |last5=Kurrasch |first5=Deborah M. |date=2015-02-03 |title=Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=112 |issue=5 |pages=1475–1480 |doi=10.1073/pnas.1417731112 |issn=1091-6490 |pmc=4321238 |pmid=25583509 |bibcode=2015PNAS..112.1475K |doi-access=free }}</ref>

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

=== Effects on reproductive health ===

The [[Endocrine disruptor|endocrine disrupting]] nature of BPS has encouraged investigations into its affinity to estrogenic receptors, showing BPS to be a weak [[agonist]]; similar in potency to BPA, which it has come to substitute. Select studies show BPS to be capable of mimicking [[estradiol]], and sometimes being more effective.<ref name=":3">{{Cite journal|title=Article|url=https://www.agriculturejournals.cz/web/cjas.htm?volume=61&firstPage=433&type=publishedArticle|journal=Czech Journal of Animal Science| date=31 October 2016 | volume=61 | issue=10 | pages=433–449 |language=en-US|doi=10.17221/81/2015-cjas|doi-access=free| last1=Žalmanová | first1=T. | last2=Hošková | first2=K. | last3=Nevoral | first3=J. | last4=Prokešová | first4=Š. | last5=Zámostná | first5=K. | last6=Kott | first6=T. | last7=Petr | first7=J. }}</ref> 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.<ref>{{cite journal | vauthors = Siracusa JS, Yin L, Measel E, Liang S, Yu X | title = Effects of bisphenol A and its analogs on reproductive health: A mini review | journal = Reproductive Toxicology | volume = 79 | pages = 96–123 | date = August 2018 | pmid = 29925041 | pmc = 6689411 | doi = 10.1016/j.reprotox.2018.06.005| bibcode = 2018RepTx..79...96S }}</ref> Studies on zebrafish have shown decreased egg quality, reduced [[sperm]] count, an increased frequency of [[embryo]] abnormalities, as well as changes in the mass of [[gonad]]s;<ref name=":3" /> suggesting that BPS is a [[Reproduction|reproductive]] toxin for both sexes.

The use of Bisphenol-A in manufacturing of household products has been reduced due to its effects as an endocrine disruptor, with research suggesting a disposition to greater deleterious effects to women as compared to men.<ref>{{Cite journal |last=Vogel |first=Sarah A. |date=November 2009 |title=The Politics of Plastics: The Making and Unmaking of Bisphenol A "Safety" |journal=American Journal of Public Health |language=en |volume=99 |issue=S3 |pages=S559–S566 |doi=10.2105/AJPH.2008.159228 |issn=0090-0036 |pmc=2774166 |pmid=19890158}}</ref> Research has suggested that BPA and its cousins (BPS,BPF, etc.) have sex dependent effects on development.<ref>{{Cite journal |last1=Lee |first1=Jiyun |last2=Moon |first2=Kyong Whan |last3=Ji |first3=Kyunghee |date=January 2021 |title=Systematic Review of Exposure to Bisphenol A Alternatives and Its Effects on Reproduction and Thyroid Endocrine System in Zebrafish |journal=Applied Sciences |language=en |volume=11 |issue=4 |pages=1837 |doi=10.3390/app11041837 |issn=2076-3417 |doi-access=free }}</ref> Male zebrafish exposed to BPS indicated a significant increase in estrogen levels and a decrease in testosterone levels. The decrease in testosterone when exposed to BPS was found to be 200 times more than the decrease in testosterone by BPA.<ref>{{Cite journal |last1=Schally |first1=A. V. |last2=Arimura |first2=A. |last3=Kastin |first3=A. J. |last4=Matsuo |first4=H. |last5=Baba |first5=Y. |last6=Redding |first6=T. W. |last7=Nair |first7=R. M. G. |last8=Debeljuk |first8=L. |last9=White |first9=W. F. |date=1971-09-10 |title=Gonadotropin-Releasing Hormone: One Polypeptide Regulates Secretion of Luteinizing and Follicle-Stimulating Hormones |url=https://www.science.org/doi/10.1126/science.173.4001.1036 |journal=Science |language=en |volume=173 |issue=4001 |pages=1036–1038 |doi=10.1126/science.173.4001.1036 |pmid=4938639 |bibcode=1971Sci...173.1036S |s2cid=10052615 |issn=0036-8075}}</ref> There are increased levels of mRNA transcription of the aromatase gene and increased levels of mRNA transcription of GnRH genes with decreased levels of follicle stimulating hormone and luteinizing hormone.<ref>{{Cite journal |last1=Kallivretaki |first1=Evangelia |last2=Eggen |first2=Rik |last3=Neuhauss |first3=Stephan |last4=Alberti |first4=Martin |last5=Kausch |first5=Ulf |last6=Segner |first6=Helmut |date=2006-01-01 |title=Aromatase in zebrafish: A potential target for endocrine disrupting chemicals |journal=Marine Environmental Research |series=Pollutant Responses in Marine Organisms (PRIMO 13) |language=en |volume=62 |pages=S187–S190 |doi=10.1016/j.marenvres.2006.04.003 |pmid=16698076 |bibcode=2006MarER..62S.187K |issn=0141-1136|doi-access=free }}</ref><ref>{{Cite journal |last1=Qiu |first1=Wenhui |last2=Fang |first2=Meijuan |last3=Liu |first3=Jingyu |last4=Fu |first4=Caixia |last5=Zheng |first5=Chunmiao |last6=Chen |first6=Bei |last7=Wang |first7=Ke-Jian |date=2019-05-15 |title=In vivo actions of Bisphenol F on the reproductive neuroendocrine system after long-term exposure in zebrafish |url=https://www.sciencedirect.com/science/article/pii/S0048969719306424 |journal=Science of the Total Environment |language=en |volume=665 |pages=995–1002 |doi=10.1016/j.scitotenv.2019.02.154 |pmid=30893755 |bibcode=2019ScTEn.665..995Q |s2cid=84844426 |issn=0048-9697}}</ref>

== Bisphenol-S concentrations within populations ==

A relationship to higher BPS concentrations is linked to individuals within certain socio-economic classes hence placing those individuals at greater risk of possible deleterious effects. Individuals with an annual income of less than $20,000 were found to have the highest concentrations of bisphenol and individuals with an annual income of $75,000 or more to have the lowest concentrations, suggesting a linear relationship between bodily concentrations of BPS and income.<ref>{{Cite journal |last1=Nelson |first1=Jessica W. |last2=Scammell |first2=Madeleine Kangsen |last3=Hatch |first3=Elizabeth E. |last4=Webster |first4=Thomas F. |date=2012-03-06 |title=Social disparities in exposures to bisphenol A and polyfluoroalkyl chemicals: a cross-sectional study within NHANES 2003-2006 |journal=Environmental Health |volume=11 |issue=1 |pages=10 |doi=10.1186/1476-069X-11-10 |pmid=22394520 |pmc=3312862 |bibcode=2012EnvHe..11...10N |s2cid=9872387 |issn=1476-069X |doi-access=free }}</ref> Black women had the highest concentrations of BPS with levels 93% higher than those of white women.<ref>{{Cite journal |last1=Nguyen |first1=Vy Kim |last2=Kahana |first2=Adam |last3=Heidt |first3=Julien |last4=Polemi |first4=Katelyn |last5=Kvasnicka |first5=Jacob |last6=Jolliet |first6=Olivier |last7=Colacino |first7=Justin A. |date=April 2020 |title=A comprehensive analysis of racial disparities in chemical biomarker concentrations in United States women, 1999–2014 |journal=Environment International |language=en |volume=137 |pages=105496 |doi=10.1016/j.envint.2020.105496 |pmc=7137529 |pmid=32113086|bibcode=2020EnInt.13705496N }}</ref>

== Environmental considerations ==

Recent work suggests that, like BPA, BPS also has endocrine disrupting properties.<ref name="Manjumol2014">{{cite journal | vauthors = Mathew M, Sreedhanya S, Manoj P, Aravindakumar CT, Aravind UK | title = Exploring the interaction of bisphenol-S with serum albumins: a better or worse alternative for bisphenol a? | journal = The Journal of Physical Chemistry B | volume = 118 | issue = 14 | pages = 3832–43 | date = April 2014 | pmid = 24635450 | doi = 10.1021/jp500404u }}</ref><ref>{{cite journal | vauthors = Horan TS, Pulcastro H, Lawson C, Gerona R, Martin S, Gieske MC, Sartain CV, Hunt PA | display-authors = 6 | title = Replacement Bisphenols Adversely Affect Mouse Gametogenesis with Consequences for Subsequent Generations | journal = Current Biology | volume = 28 | issue = 18 | pages = 2948–2954.e3 | date = September 2018 | pmid = 30220498 | pmc = 6156992 | doi = 10.1016/j.cub.2018.06.070 | bibcode = 2018CBio...28E2948H }}</ref> 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.<ref>{{cite journal | vauthors = Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL | title = Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population | journal = Environmental Health Perspectives | volume = 113 | issue = 4 | pages = 391–5 | date = April 2005 | pmid = 15811827 | pmc = 1278476 | doi = 10.1289/ehp.7534 | bibcode = 2005EnvHP.113..391C }}</ref> Another study done on thermal receipt paper shows that 88% of human exposure to BPS is through receipts.<ref>{{cite journal|title=EHP – Thermal Reaction: The Spread of Bisphenol S via Paper Products|year=2013|doi=10.1289/ehp.121-a76|url=http://ehp.niehs.nih.gov/121-a76/|access-date=4 February 2016|last1=Konkel|first1=Lindsey|journal=Environmental Health Perspectives|volume=121|issue=3|pages=A76|pmid=23454568|pmc=3621184}}</ref>

The recycling of [[thermal paper]] can introduce BPS into the cycle of paper production and cause BPS contamination of other types of paper products.<ref>European Commission-Joint Research Centre. European Union Risk Assessment Report, 4,4′-Isopropylidenediphenol (Bisphenol-A). 2008, available from http://ecb.jrc.ec.europa.eu/documents/ExistingChemicals/RISK_ASSESSMENT/ADDENDUM/bisphenola_add_{{dead link|date=November 2016 |bot=InternetArchiveBot |fix-attempted=yes}} 325.pdf</ref> 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.<ref name="Pivnenko 39–47" />

BPS is more resistant to environmental degradation than BPA, and although not persistent cannot be characterised as readily biodegradable.<ref name="Pivnenko 39–47"/><ref>{{cite journal | vauthors = Ike M, Chen MY, Danzl E, Sei K, Fujita M | title = Biodegradation of a variety of bisphenols under aerobic and anaerobic conditions | journal = Water Science and Technology | volume = 53 | issue = 6 | pages = 153–9 | year = 2006 | pmid = 16749452 | doi = 10.2166/wst.2006.189 | doi-access = | bibcode = 2006WSTec..53..153I }}</ref>

== History ==

BPS was first made in 1869 as a dye<ref>{{cite journal | vauthors = Glausiusz J | title = Toxicology: The plastics puzzle | journal = Nature | volume = 508 | issue = 7496 | pages = 306–8 | date = April 2014 | pmid = 24740050 | doi = 10.1038/508306a | publisher = Nature Publishing Group | bibcode = 2014Natur.508..306G | doi-access = free }}</ref> 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.<ref name="Manjumol2014" /> After health concerns associated with bisphenol A grew in 2012, BPS began to be used as a replacement.<ref>{{cite journal | vauthors = Liao C, Liu F, Alomirah H, Loi VD, Mohd MA, Moon HB, Nakata H, Kannan K | display-authors = 6 | title = Bisphenol S in urine from the United States and seven Asian countries: occurrence and human exposures | journal = Environmental Science & Technology | volume = 46 | issue = 12 | pages = 6860–6 | date = June 2012 | pmid = 22620267 | doi = 10.1021/es301334j | bibcode = 2012EnST...46.6860L}}</ref>

== Regulation ==

In the US it is difficult for consumers to determine if a product contains BPS due to limited labelling regulations.<ref>{{cite web|last1=Howard|first1=Brian | name-list-style = vanc |title=Chemical in BPA-Free Products Linked to Irregular Heartbeats|url=http://news.nationalgeographic.com/2015/02/150226-bisphenol-s-bpa-plastics-health-science/|archive-url=https://web.archive.org/web/20150303204248/http://news.nationalgeographic.com/2015/02/150226-bisphenol-s-bpa-plastics-health-science/|url-status=dead|archive-date=March 3, 2015|access-date=29 March 2015|website=National Geographic}}</ref> In January 2023 the [[European Chemicals Agency]] added bisphenol S to the candidate list for [[substance of very high concern]] designation, while it is investigated for reproductive toxicity and [[Endocrine disruptor|endocrine disruption]].<ref>{{cite web |title=Substance Information -4,4'-sulphonyldiphenol - ECHA |url=https://echa.europa.eu/substance-information/-/substanceinfo/100.001.137 |website=echa.europa.eu |publisher=[[European Chemicals Agency]] |access-date=16 February 2023}}</ref>

== Synthesis ==

Bisphenol S is prepared by the [[chemical reaction|reaction]] of two [[Equivalent (chemistry)|equivalents]] of [[phenol]] with one equivalent of [[sulfuric acid]] or [[oleum]].<ref>[http://www.freepatentsonline.com/EP0489788.html METHOD OF PREPARATION OF 4,4′-DIHYDROXYDIPHENYLSULPHONE (Freepatentsonline)].</ref>

:{{chem2|2 C6H5OH + H2SO4 → (C6H4OH)2SO2 + 2 H2O}}

:{{chem2|2 C6H5OH + SO3 → (C6H4OH)2SO2 + H2O}}

This reaction can also produce 2,4'-sulfonyldiphenol, a common [[isomer]]ic complication in [[electrophilic aromatic substitution]] reactions.

:[[File:bisphenol synthesis.svg|left|600px|Chemical reaction to bisphenol S]]

{{clear|left}}

== See also ==

* [[Bisphenol A]]

* [[Tetramethyl bisphenol F|Tetramethyl Bisphenol F]]

== References ==

{{Reflist|30em}}

{{Xenoestrogens}}{{Androgen receptor modulators}}{{Estrogen receptor modulators}}

[[Category:Bisphenols]]

[[Category:Endocrine disruptors]]

[[Category:Estrogens]]

[[Category:Nonsteroidal antiandrogens]]

[[Category:Benzosulfones]]