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{{short description|Chemicals that can interfere with endocrine or hormonal systems}} {{more medical citations needed|date=August 2019}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Use dmy dates|date=April 2024}} [[File:NonylphenolEstradiol.svg|250px|thumb|A comparison of the structures of the natural estrogen hormone [[estradiol]] (left) and one of the [[nonylphenol|nonyl-phenols]] (right), a xenoestrogen endocrine disruptor]] '''Endocrine disruptors''', sometimes also referred to as '''hormonally active agents''',<ref name="pmid11795392">{{cite journal | vauthors = Krimsky S | title = An epistemological inquiry into the endocrine disruptor thesis | journal = Annals of the New York Academy of Sciences | volume = 948 | issue = 1 | pages = 130–142 | date = December 2001 | pmid = 11795392 | doi = 10.1111/j.1749-6632.2001.tb03994.x | s2cid = 41532171 | bibcode = 2001NYASA.948..130K }}</ref> '''endocrine disrupting chemicals''',<ref name="pmid19502515">{{cite journal | vauthors = Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC | title = Endocrine-disrupting chemicals: an Endocrine Society scientific statement | journal = Endocrine Reviews | volume = 30 | issue = 4 | pages = 293–342 | date = June 2009 | pmid = 19502515 | pmc = 2726844 | doi = 10.1210/er.2009-0002 | url = http://www.endo-society.org/journals/scientificstatements/upload/edc_scientific_statement.pdf | access-date = 26 September 2009 | url-status = dead | archive-url = https://web.archive.org/web/20090929004630/http://www.endo-society.org/journals/ScientificStatements/upload/EDC_Scientific_Statement.pdf | archive-date = 29 September 2009 }}</ref> or '''endocrine disrupting compounds'''<ref name="urlEndocrine Disrupting Compounds">{{cite web | url = http://www.niehs.nih.gov/health/impacts/endocrine.cfm | title = Endocrine Disrupting Compounds | publisher = National Institutes of Health · U.S. Department of Health and Human Services | url-status = dead | archive-url = https://web.archive.org/web/20090924000314/http://www.niehs.nih.gov/health/impacts/endocrine.cfm | archive-date = 24 September 2009 }}</ref> are chemicals that can interfere with [[endocrine]] (or [[Hormone|hormonal]]) systems.<ref>{{cite journal | vauthors = Casals-Casas C, Desvergne B | title = Endocrine disruptors: from endocrine to metabolic disruption | journal = Annual Review of Physiology | volume = 73 | issue = 1 | pages = 135–162 | date = 17 March 2011 | pmid = 21054169 | doi = 10.1146/annurev-physiol-012110-142200 }}</ref> These disruptions can cause numerous adverse human health outcomes, including alterations in sperm quality and fertility; abnormalities in sex organs‚ [[endometriosis]]‚ [[Precocious puberty|early puberty]]‚ altered nervous system or immune function; certain cancers; respiratory problems; metabolic issues; diabetes, obesity, or cardiovascular problems; growth, neurological and learning disabilities, and more.<ref>{{Cite web |date=24 January 2022 |title=Endocrine-Disrupting Chemicals (EDCs) |url=https://www.endocrine.org/patient-engagement/endocrine-library/edcs |access-date=20 September 2023 |website=www.endocrine.org |language=en}}</ref><ref>{{cite web |author=Staff |publisher=NIEHS |date=5 June 2013 |url=http://www.niehs.nih.gov/health/topics/agents/endocrine/ |title=Endocrine Disruptors}}</ref> Found in many household and industrial products, endocrine disruptors "interfere with the synthesis, secretion, transport, binding, action, or elimination of natural [[hormone]]s in the body that are responsible for development, behavior, fertility, and maintenance of [[homeostasis]] (normal cell metabolism)."<ref>{{cite journal | vauthors = Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, Shioda T, Soto AM, vom Saal FS, Welshons WV, Zoeller RT, Myers JP | title = Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses | journal = Endocrine Reviews | volume = 33 | issue = 3 | pages = 378–455 | date = June 2012 | pmid = 22419778 | pmc = 3365860 | doi = 10.1210/er.2011-1050 }}</ref><ref name="pmid9539004">{{cite journal | vauthors = Crisp TM, Clegg ED, Cooper RL, Wood WP, Anderson DG, Baetcke KP, Hoffmann JL, Morrow MS, Rodier DJ, Schaeffer JE, Touart LW, Zeeman MG, Patel YM | title = Environmental endocrine disruption: an effects assessment and analysis | journal = Environmental Health Perspectives | volume = 106 | issue = Suppl 1 | pages = 11–56 | date = February 1998 | pmid = 9539004 | pmc = 1533291 | doi = 10.2307/3433911 | series = 106 | jstor = 3433911 }}</ref><ref>{{cite journal | vauthors = Huang AC, Nelson C, Elliott JE, Guertin DA, Ritland C, Drouillard K, Cheng KM, Schwantje HM | title = River otters (Lontra canadensis) "trapped" in a coastal environment contaminated with persistent organic pollutants: Demographic and physiological consequences | journal = Environmental Pollution | volume = 238 | pages = 306–316 | date = July 2018 | pmid = 29573713 | doi = 10.1016/j.envpol.2018.03.035 | doi-access = free | bibcode = 2018EPoll.238..306H }}</ref> Any system in the body controlled by [[hormone]]s can be derailed by hormone disruptors. Specifically, endocrine disruptors may be associated with the development of [[learning disabilities]], severe [[attention deficit disorder]], and [[cognitive]] and brain development problems.<ref>{{cite journal | vauthors = Eskenazi B, Chevrier J, Rauch SA, Kogut K, Harley KG, Johnson C, Trujillo C, Sjödin A, Bradman A | title = In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study | journal = Environmental Health Perspectives | volume = 121 | issue = 2 | pages = 257–62 | date = February 2013 | pmid = 23154064 | pmc = 3569691 | doi = 10.1289/ehp.1205597 | bibcode = 2013EnvHP.121..257E }}</ref><ref>{{cite journal | vauthors = Jurewicz J, Hanke W | title = Exposure to phthalates: reproductive outcome and children health. A review of epidemiological studies | journal = International Journal of Occupational Medicine and Environmental Health | volume = 24 | issue = 2 | pages = 115–41 | date = June 2011 | pmid = 21594692 | doi = 10.2478/s13382-011-0022-2 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bornehag CG, Engdahl E, Unenge Hallerbäck M, Wikström S, Lindh C, Rüegg J, Tanner E, Gennings C | title = Prenatal exposure to bisphenols and cognitive function in children at 7 years of age in the Swedish SELMA study | journal = Environment International | volume = 150 | pages = 106433 | date = May 2021 | pmid = 33637302 | doi = 10.1016/j.envint.2021.106433 | s2cid = 232064637 | doi-access = free | bibcode = 2021EnInt.15006433B }}</ref><ref>{{cite journal | vauthors = Repouskou A, Papadopoulou AK, Panagiotidou E, Trichas P, Lindh C, Bergman Å, Gennings C, Bornehag CG, Rüegg J, Kitraki E, Stamatakis A | title = Long term transcriptional and behavioral effects in mice developmentally exposed to a mixture of endocrine disruptors associated with delayed human neurodevelopment | journal = Scientific Reports | volume = 10 | issue = 1 | pages = 9367 | date = June 2020 | pmid = 32518293 | pmc = 7283331 | doi = 10.1038/s41598-020-66379-x | bibcode = 2020NatSR..10.9367R }}</ref> There has been controversy over endocrine disruptors, with some groups calling for swift action by regulators to remove them from the market, and regulators and other scientists calling for further study.<ref>{{cite journal | vauthors = Lupu D, Andersson P, Bornehag CG, Demeneix B, Fritsche E, Gennings C, Lichtensteiger W, Leist M, Leonards PE, Ponsonby AL, Scholze M, Testa G, Tresguerres JA, Westerink RH, Zalc B, Rüegg J | title = The ENDpoiNTs Project: Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity | journal = International Journal of Molecular Sciences | volume = 21 | issue = 11 | pages = 3978 | date = June 2020 | pmid = 32492937 | pmc = 7312023 | doi = 10.3390/ijms21113978 | doi-access = free }}</ref> Some endocrine disruptors have been identified and removed from the market (for example, a drug called [[diethylstilbestrol]]), but it is uncertain whether some endocrine disruptors on the market actually harm humans and wildlife at the doses to which wildlife and humans are exposed. The [[World Health Organization]] published a 2012 report stating that low-level exposures may cause adverse effects in humans.<ref>{{Cite web |title=State of the science of endocrine disrupting chemicals|date= 2012 |url=https://www.who.int/publications-detail-redirect/9789241505031 |access-date=20 October 2023 |publisher=World Health Organization |language=en}}</ref> ==History== The term ''endocrine disruptor'' was coined in 1991 at the Wingspread Conference Center in Wisconsin. One of the early papers on the phenomenon was by [[Theo Colborn]] in 1993.<ref name="pmid8080506">{{cite journal |vauthors=Colborn T, vom Saal FS, Soto AM | title = Developmental effects of endocrine-disrupting chemicals in wildlife and humans | journal = Environ. Health Perspect. | volume = 101 | issue = 5 | pages = 378–84 |date=October 1993 | pmid = 8080506 | pmc = 1519860 | doi = 10.2307/3431890 | jstor = 3431890 }}</ref> In this paper, she stated that environmental chemicals disrupt the development of the endocrine system, and that effects of exposure during development are often permanent. Although the endocrine disruption has been disputed by some,<ref name='Grady2010'>{{cite news |title=In Feast of Data on BPA Plastic, No Final Answer | vauthors = Grady D | url=https://www.nytimes.com/2010/09/07/science/07bpa.html | newspaper = [[The New York Times]] | date = 6 September 2010 | quote = A fierce debate has resulted, with some dismissing the whole idea of endocrine disruptors. }}</ref> work sessions from 1992 to 1999 have generated consensus statements from scientists regarding the hazard from endocrine disruptors, particularly in wildlife and also in humans.<ref name="isbn0-911131-35-3">{{cite book | vauthors = Bern HA, Blair P, Brasseur S, Colborn T, Cunha GR, Davis W, Kohler KD, Fox G, Fry M, Gray E, Green R, Hines M, Kubiak TJ, McLachlan J, Myers JP, Peterson RE, Reijnders PJ, Soto A, Van Der Kraal G, vom Saal F, Whitten P | veditors = Clement C, Colborn T | title = Chemically-induced alterations in sexual and functional development-- the wildlife/human connection | chapter = Statement from the Work Session on Chemically-Induced Alterations in Sexual Development: The Wildlife/Human Connection | publisher = Princeton Scientific Pub. Co | location = Princeton, N.J | year = 1992 | pages = 1–8 | isbn = 978-0-911131-35-2 | chapter-url = http://www.endocrinedisruption.org/files/wingspread_consensus_statement.pdf | access-date = 26 September 2010 | archive-url = https://web.archive.org/web/20110726031909/http://www.endocrinedisruption.org/files/wingspread_consensus_statement.pdf | archive-date = 26 July 2011 | url-status = dead }}</ref><ref name="pmid17539108">{{cite journal | vauthors = Bantle J, Bowerman WW IV, Carey C, Colborn T, Deguise S, Dodson S, Facemire CF, Fox G, Fry M, Gilbertson M, Grasman K, Gross T, Guillette L, Henny C, Henshel DS, Hose JE, Klein PA, Kubiak TJ, Lahvis G, Palmer B, Peterson C, Ramsay M, White D | title = Statement from the Work Session on Environmentally induced Alterations in Development: A Focus on Wildlife | journal = Environmental Health Perspectives | volume = 103 | issue = Suppl 4 | pages = 3–5 | date = May 1995 | pmid = 17539108 | pmc = 1519268 | doi = 10.2307/3432404 | jstor = 3432404 }}</ref><ref name="isbn1-880611-19-8">{{cite book | vauthors = Benson WH, Bern HA, Bue B, Colborn T, Cook P, Davis WP, Denslow N, Donaldson EM, Edsall CC, Fournier M, Gilbertson M, Johnson R, Kocan R, Monosson E, Norrgren L, Peterson RE, Rolland R, Smolen M, Spies R, Sullivan C, Thomas P, Van Der Kraak G | veditors = Rolland RM, Gilbertson M, Peterson RE | title = Chemically Induced Alterations in Functional Development and Reproduction of Fishes | publisher = Society of Environmental Toxicology & Chemist | year = 1997 | chapter = Statement from the work session on chemically induced alterations in functional development and reproduction of fishes | pages = [https://archive.org/details/chemicallyinduce1997unse/page/3 3–8] | isbn = 978-1-880611-19-7 | chapter-url = https://archive.org/details/chemicallyinduce1997unse/page/3 }}</ref><ref name="pmid9460166">{{cite journal | vauthors = Alleva E, Brock J, Brouwer A, Colborn T, Fossi MC, Gray E, Guillette L, Hauser P, Leatherland J, MacLusky N, Mutti A, Palanza P, Parmigiani S, Porterfield, Santi R, Stein SA, vom Saal F | title = Statement from the work session on environmental endocrine-disrupting chemicals: neural, endocrine, and behavioral effects | journal = Toxicology and Industrial Health | volume = 14 | issue = 1–2 | pages = 1–8 | year = 1998 | pmid = 9460166 | doi = 10.1177/074823379801400103 | bibcode = 1998ToxIH..14....1. | s2cid = 45902764 }}</ref><ref name="Brook_1999">{{cite journal |vauthors=Brock J, Colborn T, Cooper R, Craine DA, Dodson SF, Garry VF, Gilbertson M, Gray E, Hodgson E, Kelce W, Klotz D, Maciorowski AF, Olea N, Porter W, Rolland R, Scott GI, Smolen M, Snedaker SC, Sonnenschein C, Vyas NB, Welshons WV, Whitcomb CE | title = Statement from the Work Session on Health Effects of Contemporary-Use Pesticides: the Wildlife / Human Connection | journal = Toxicol Ind Health | volume = 15 | issue = 1–2 | pages = 1–5 | year = 1999 | doi = 10.1191/074823399678846547| bibcode = 1999ToxIH..15....1. }}</ref> [[The Endocrine Society]] released a scientific statement outlining mechanisms and effects of endocrine disruptors on "male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology," and showing how experimental and epidemiological studies converge with human clinical observations "to implicate endocrine disruptive chemicals (EDCs) as a significant concern to [[public health]]." The statement noted that it is difficult to show that endocrine disruptors cause human diseases, and it recommended that the [[precautionary principle]] should be followed.<ref name=autogenerated1>{{cite journal | vauthors = Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, [[Andrea Gore|Gore AC]] | title = Endocrine-disrupting chemicals: an Endocrine Society scientific statement | journal = Endocrine Reviews | volume = 30 | issue = 4 | pages = 293–342 | date = June 2009 | pmid = 19502515 | pmc = 2726844 | doi = 10.1210/er.2009-0002 }}</ref> A concurrent statement expresses policy concerns.<ref>{{cite journal | year = 2009 | title = Position statement: Endocrine-disrupting chemicals | journal = Endocrine News | volume = 34 | issue = 8 | pages = 24–27 | url = http://www.endo-society.org/advocacy/policy/upload/Endocrine-Disrupting-Chemicals-Position-Statement.pdf | url-status = dead | archive-url = https://web.archive.org/web/20101030032442/http://endo-society.org/advocacy/policy/upload/Endocrine-Disrupting-Chemicals-Position-Statement.pdf | archive-date = 30 October 2010 }}</ref> Endocrine disrupting compounds encompass a variety of chemical classes, including drugs, pesticides, compounds used in the [[plastics industry]] and in consumer products, industrial by-products and pollutants, [[heavy metals]] and even some naturally produced botanical chemicals. Industrial chemicals such as parabens, phenols and phthalates are also considered potent endocrine disruptors.<ref>{{cite journal | vauthors = Sangeetha S, Vimalkumar K, Loganathan BG |title=Environmental Contamination and Human Exposure to Select Endocrine-Disrupting Chemicals: A Review |journal=Sustainable Chemistry |date=June 2021 |volume=2 |issue=2 |pages=343–380 |doi=10.3390/suschem2020020 |doi-access=free |language=en |issn=2673-4079}}</ref> Some are pervasive and widely dispersed in the environment and may [[bioaccumulation|bioaccumulate]]. Some are [[persistent organic pollutants]] (POPs), and can be transported long distances across national boundaries and have been found in virtually all regions of the world, and may even concentrate near the North Pole, due to weather patterns and cold conditions.<ref name="Cold, Clear, and Deadly">{{cite web | url = https://msupress.org/9780870138027/cold-clear-and-deadly/ | title = Cold, Clear, and Deadly | vauthors = Visser MJ | access-date = 14 April 2012 }}</ref> Others are rapidly degraded in the environment or human body or may be present for only short periods of time.<ref name="urlREPIDISCA-Global assessment of the state-of-the-science of endocrine disruptors">{{cite web | url = http://bases.bireme.br/cgi-bin/wxislind.exe/iah/online/?IsisScript=iah/iah.xis&src=google&base=REPIDISCA&lang=p&nextAction=lnk&exprSearch=7600&indexSearch=ID | title = REPIDISCA-Global assessment of the state-of-the-science of endocrine disruptors |vauthors=Damstra T, Barlow S, Bergman A, Kavlock R, Van der Kraak G | year = 2002 | work = International programme on chemical safety, World Health Organization| access-date = 14 March 2009}}</ref> Health effects attributed to endocrine disrupting compounds include a range of reproductive problems (reduced fertility, male and female [[reproductive tract]] abnormalities, and skewed male/female [[sex ratio]]s, loss of fetus, menstrual problems<ref name="urlwww.cranfield.ac.uk">{{cite web | url = http://www.cranfield.ac.uk/health/researchareas/environmenthealth/ieh/ieh%20publications/a1.pdf | title = Environmental oestrogens: consequences to human health and wildlife | vauthors = Harrison PT, Humfrey CD, Litchfield M, Peakall D, Shuker LK | year = 1995 | work = IEH assessment | publisher = Medical Research Council, Institute for Environment and Health | access-date = 14 March 2009 | archive-url = https://web.archive.org/web/20110928081421/http://www.cranfield.ac.uk/health/researchareas/environmenthealth/ieh/ieh%20publications/a1.pdf | archive-date = 28 September 2011 | url-status = dead }}</ref>); changes in hormone levels; early puberty; brain and behavior problems; impaired immune functions; and various cancers.<ref name="urle.hormone | EDC Human Effects">{{cite web | url = http://e.hormone.tulane.edu/learning/human-effects.html | title = EDC Human Effects | work = e.hormone | publisher = Center for Bioenvironmental Research at Tulane and Xavier Universities | access-date = 14 March 2009}}</ref> One example of the consequences of the exposure of developing animals, including humans, to hormonally active agents is the case of the drug [[diethylstilbestrol]] (DES), a [[nonsteroidal]] [[estrogen]] and not an environmental pollutant. Prior to its ban in the early 1970s, doctors prescribed DES to as many as five million pregnant women to block spontaneous abortion, an [[off-label use]] of this medication prior to 1947. It was discovered after the children went through puberty that DES affected the development of the reproductive system and caused [[vaginal cancer]]. The relevance of the DES saga to the risks of exposure to endocrine disruptors is questionable, as the doses involved are much higher in these individuals than in those due to environmental exposures.<ref name="pmid9557209">{{cite journal |vauthors=Golden RJ, Noller KL, Titus-Ernstoff L, Kaufman RH, Mittendorf R, Stillman R, Reese EA | title = Environmental endocrine modulators and human health: an assessment of the biological evidence | journal = Crit. Rev. Toxicol. | volume = 28 | issue = 2 | pages = 109–227 |date=March 1998 | pmid = 9557209 | doi = 10.1080/10408449891344191 }}</ref> [[:wikt:aquatic|Aquatic]] life subjected to endocrine disruptors in an urban effluent have experienced decreased levels of [[serotonin]] and increased feminization.<ref>{{cite book | title = Progress in Environmental Research | vauthors = Willis IC | year = 2007 | publisher = Nova Publishers | location = New York | isbn = 978-1-60021-618-3 | page = 176 | url = https://books.google.com/books?id=So6jCeIDk74C }}</ref> In 2013 the [[WHO]] and the [[United Nations Environment Programme]] released a study, the most comprehensive report on EDCs to date, calling for more research to fully understand the associations between EDCs and the risks to health of human and animal life. The team pointed to wide gaps in knowledge and called for more research to obtain a fuller picture of the health and environmental impacts of endocrine disruptors. To improve global knowledge the team has recommended: * Testing: known EDCs are only the 'tip of the iceberg' and more comprehensive testing methods are required to identify other possible endocrine disruptors, their sources, and routes of exposure. * Research: more scientific evidence is needed to identify the effects of mixtures of EDCs on humans and wildlife (mainly from industrial by-products) to which humans and wildlife are increasingly exposed. * Reporting: many sources of EDCs are not known because of insufficient reporting and information on chemicals in products, materials and goods. * Collaboration: more data sharing between scientists and between countries can fill gaps in data, primarily in developing countries and emerging economies.<ref>{{cite web|url=https://www.who.int/ceh/publications/endocrine/en/index.html |archive-url=https://web.archive.org/web/20130223023915/http://www.who.int/ceh/publications/endocrine/en/index.html |url-status=dead |archive-date=23 February 2013 |title=State of the science of endocrine disrupting chemicals – 2012 |publisher=World Health Organization |date=2013 |access-date=6 April 2015}}</ref> == Endocrine system == {{Main|Endocrine system}} [[File:Endocrine English.svg|thumb|[[Endocrine system]] diagram within a human body.]] Endocrine systems are found in most varieties of [[animal]]s. The endocrine system consists of [[gland]]s that secrete [[hormone]]s, and [[receptor (biochemistry)|receptors]] that detect and react to the hormones.<ref>{{Cite web |date=19 November 2019 |title=Anatomy of the Endocrine System |url=https://www.hopkinsmedicine.org/health/wellness-and-prevention/anatomy-of-the-endocrine-system |access-date=11 April 2023 | work = Johns Hopkins Medicine |language=en}}</ref> Hormones travel throughout the body via the bloodstream and act as chemical messengers.<ref>{{Cite web |last=Services |first=Department of Health & Human |title=Hormonal (endocrine) system |url=https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/hormonal-endocrine-system#bhc-content |access-date=2025-02-09 |website=www.betterhealth.vic.gov.au |language=en}}</ref> Hormones interface with cells that contain matching receptors in or on their surfaces. The hormone binds with the receptor, much like a key would fit into a lock. The endocrine system regulates adjustments through slower internal processes, using hormones as messengers. The endocrine system secretes hormones in response to environmental stimuli and to orchestrate developmental and reproductive changes. The adjustments brought on by the endocrine system are biochemical, changing the cell's internal and external chemistry to bring about a long term change in the body.<ref>{{Cite web |title=Hormonal (endocrine) system |url=http://www.betterhealth.vic.gov.au/health/conditionsandtreatments/hormonal-endocrine-system |access-date=11 April 2023 | work = Better Health Channel | publisher = The Department of Health, Victorian Government |language=en}}</ref> These systems work together to maintain the proper functioning of the body through its entire life cycle. [[Sex steroids]] such as [[estrogens]] and [[androgens]], as well as [[thyroid]] hormones, are subject to [[feedback]] regulation, which tends to limit the sensitivity of these glands.<ref>{{cite journal | vauthors = Kim YJ, Tamadon A, Park HT, Kim H, Ku SY | title = The role of sex steroid hormones in the pathophysiology and treatment of sarcopenia | journal = Osteoporosis and Sarcopenia | volume = 2 | issue = 3 | pages = 140–155 | date = September 2016 | pmid = 30775480 | pmc = 6372754 | doi = 10.1016/j.afos.2016.06.002 }}</ref> Hormones work at very small doses (part per billion ranges).<ref>{{Cite journal |last1=Vandenberg |first1=Laura N. |last2=Colborn |first2=Theo |last3=Hayes |first3=Tyrone B. |last4=Heindel |first4=Jerrold J. |last5=Jacobs |first5=David R. |last6=Lee |first6=Duk-Hee |last7=Shioda |first7=Toshi |last8=Soto |first8=Ana M. |last9=vom Saal |first9=Frederick S. |last10=Welshons |first10=Wade V. |last11=Zoeller |first11=R. Thomas |last12=Myers |first12=John Peterson |date=2012-06-01 |title=Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses |journal=Endocrine Reviews |language=en |volume=33 |issue=3 |pages=378–455 |doi=10.1210/er.2011-1050 |issn=0163-769X |pmc=3365860 |pmid=22419778}}</ref> Endocrine disruption can thereby also occur from low-dose exposure to exogenous hormones or hormonally active chemicals such as [[BPA controversy|bisphenol A]]. These chemicals can bind to receptors for other hormonally mediated processes.<ref>{{cite web |title=Bisphenol A Overview |publisher=Environment California |url=http://www.environmentcalifornia.org/environmental-health/stop-toxic-toys/bisphenol-a-overview |archive-url=https://web.archive.org/web/20110422170104/http://www.environmentcalifornia.org/environmental-health/stop-toxic-toys/bisphenol-a-overview |archive-date=22 April 2011}}</ref> Furthermore, since [[endogenous]] hormones are already present in the body in biologically active concentrations, additional exposure to relatively small amounts of [[exogenous]] hormonally active substances can disrupt the proper functioning of the body's endocrine system. Thus, an endocrine disruptor can elicit adverse effects at much lower doses than a toxicity, acting through a different mechanism. The timing of exposure is also critical. Most critical stages of development occur in utero, where the fertilized egg divides, rapidly developing every structure of a fully formed baby, including much of the wiring in the brain. Interfering with the hormonal communication in utero can have profound effects both structurally and toward brain development. Depending on the stage of reproductive development, interference with hormonal signaling can result in irreversible effects not seen in adults exposed to the same dose for the same length of time.<ref name="Guo_1995">{{cite journal |vauthors=Guo YL, Lambert GH, Hsu CC | title = Growth abnormalities in the population exposed in utero and early postnatally to polychlorinated biphenyls and dibenzofurans | journal = Environ. Health Perspect. | issue = Suppl 6 | pages = 117–22 |date=September 1995 | volume = 103 | pmid = 8549457 | pmc = 1518940 | doi = 10.2307/3432359 | jstor = 3432359 }}</ref><ref name="Bigsby_1999">{{cite journal |vauthors=Bigsby R, Chapin RE, Daston GP, Davis BJ, Gorski J, Gray LE, Howdeshell KL, Zoeller RT, vom Saal FS | title = Evaluating the effects of endocrine disruptors on endocrine function during development | journal = Environ. Health Perspect. | pages = 613–8 |date=August 1999 | volume = 107 | issue = Suppl 4 | pmid = 10421771 | pmc = 1567510 | doi = 10.2307/3434553 | jstor = 3434553 }}</ref><ref name="pmid18848954">{{cite journal |vauthors=Castro DJ, Löhr CV, Fischer KA, Pereira CB, Williams DE | title = Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a, l]pyrene: the importance of in utero vs. lactational exposure | journal = Toxicol. Appl. Pharmacol. | volume = 233 | issue = 3 | pages = 454–8 |date=December 2008 | pmid = 18848954 | doi = 10.1016/j.taap.2008.09.009 | pmc = 2729560 | bibcode = 2008ToxAP.233..454C }}</ref> Experiments with animals have identified critical developmental time points in utero and days after birth when exposure to chemicals that interfere with or mimic hormones have adverse effects that persist into adulthood.<ref name="Bigsby_1999"/><ref name="Eriksson_1991">{{cite journal |vauthors=Eriksson P, Lundkvist U, Fredriksson A | title = Neonatal exposure to 3,3′,4,4′-tetrachlorobiphenyl: changes in spontaneous behaviour and cholinergic muscarinic receptors in the adult mouse | journal = Toxicology | volume = 69 | issue = 1 | pages = 27–34 | year = 1991 | pmid = 1926153 | doi = 10.1016/0300-483X(91)90150-Y }}</ref><ref name="Recabarren_2008">{{cite journal |vauthors=Recabarren SE, Rojas-García PP, Recabarren MP, Alfaro VH, Smith R, Padmanabhan V, -Petermann T | title = Prenatal testosterone excess reduces sperm count and motility | journal = Endocrinology | volume = 149 | issue = 12 | pages = 6444–8 |date=December 2008 | pmid = 18669598 | doi = 10.1210/en.2008-0785 | doi-access = free }}</ref><ref name="Szabo_2009">{{cite journal |vauthors=Szabo DT, Richardson VM, Ross DG, Diliberto JJ, Kodavanti PR, Birnbaum LS | title = Effects of perinatal PBDE exposure on hepatic phase I, phase II, phase III, and deiodinase 1 gene expression involved in thyroid hormone metabolism in male rat pups | journal = Toxicol. Sci. | volume = 107 | issue = 1 | pages = 27–39 |date=January 2009 | pmid = 18978342 | doi = 10.1093/toxsci/kfn230 | pmc = 2638650 }}</ref> Disruption of thyroid function early in development may be the cause of abnormal sexual development in both males<ref name="Lilienthal_2006">{{cite journal |vauthors=Lilienthal H, Hack A, Roth-Härer A, Grande SW, Talsness CE | title = Effects of developmental exposure to 2,2′,4,4′,5-pentabromodiphenyl ether (PBDE-99) on sex steroids, sexual development, and sexually dimorphic behavior in rats | journal = Environmental Health Perspectives| volume = 114 | issue = 2 | pages = 194–201 |date=February 2006 | pmid = 16451854 | pmc = 1367831 | doi = 10.1289/ehp.8391 | bibcode = 2006EnvHP.114..194L }}</ref> and females<ref name="Talsness_2005">{{cite journal |vauthors=Talsness CE, Shakibaei M, Kuriyama SN, Grande SW, Sterner-Kock A, Schnitker P, de Souza C, Grote K, Chahoud I | title = Ultrastructural changes observed in rat ovaries following in utero and lactational exposure to low doses of a polybrominated flame retardant | journal = Toxicol. Lett. | volume = 157 | issue = 3 | pages = 189–202 |date=July 2005 | pmid = 15917144 | doi = 10.1016/j.toxlet.2005.02.001 }}</ref> early motor development impairment,<ref name="Eriksson_2002">{{cite journal |vauthors=Eriksson P, Viberg H, Jakobsson E, Orn U, Fredriksson A | title = A brominated flame retardant, 2,2′,4,4′,5-pentabromodiphenyl ether: uptake, retention, and induction of neurobehavioral alterations in mice during a critical phase of neonatal brain development | journal = Toxicol. Sci. | volume = 67 | issue = 1 | pages = 98–103 |date=May 2002 | pmid = 11961221 | doi = 10.1093/toxsci/67.1.98 | doi-access = free }}</ref> and learning disabilities.<ref name="pmid16611620">{{cite journal |vauthors=Viberg H, Johansson N, Fredriksson A, Eriksson J, Marsh G, Eriksson P | title = Neonatal exposure to higher brominated diphenyl ethers, hepta-, octa-, or nonabromodiphenyl ether, impairs spontaneous behavior and learning and memory functions of adult mice | journal = Toxicol. Sci. | volume = 92 | issue = 1 | pages = 211–8 |date=July 2006 | pmid = 16611620 | doi = 10.1093/toxsci/kfj196 | doi-access = free }}</ref> There are studies of cell cultures, laboratory animals, wildlife, and accidentally exposed humans that show that environmental chemicals cause a wide range of reproductive, developmental, growth, and behavior effects, and so while "endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real."<ref name="pmid12837917">{{cite journal |vauthors=Rogan WJ, Ragan NB | title = Evidence of effects of environmental chemicals on the endocrine system in children | journal = Pediatrics | volume = 112 | issue = 1 Pt 2 | pages = 247–52 |date=July 2003 | pmid = 12837917 | url=http://pediatrics.aappublications.org/content/112/Supplement_1/247.full | doi=10.1542/peds.112.S1.247 | s2cid = 13058233 }}</ref> While compounds that produce estrogenic, androgenic, [[antiandrogen]]ic, and [[Antithyroid agent|antithyroid]] actions have been studied, less is known about interactions with other hormones. The interrelationships between exposures to chemicals and health effects are rather complex. It is hard to definitively link a particular chemical with a specific health effect, and exposed adults may not show any ill effects. But, fetuses and embryos, whose growth and development are highly controlled by the endocrine system, are more vulnerable to exposure and may develop overt or subtle lifelong health or reproductive abnormalities.<ref name="pmid1425407">{{cite journal | vauthors = Bern HA | title = The development of the role of hormones in development—a double remembrance | journal = Endocrinology | volume = 131 | issue = 5 | pages = 2037–8 |date=November 1992 | pmid = 1425407 | doi = 10.1210/endo.131.5.1425407 }}</ref> Prebirth exposure, in some cases, can lead to permanent alterations and adult diseases.<ref name = "Colborn_2007">{{cite journal |vauthors=Colborn T, Carroll LE | s2cid = 34600913 | year = 2007 | title = Pesticides, sexual development, reproduction, and fertility: current perspective and future | journal = Human and Ecological Risk Assessment | volume = 13 | issue = 5 | pages = 1078–1110 | doi = 10.1080/10807030701506405}}</ref> Some in the scientific community are concerned that exposure to endocrine disruptors in the womb or early in life may be associated with [[neurodevelopmental disorder]]s including reduced IQ, [[ADHD]], and [[autism]].<ref name="urlwww.iceh.org">{{cite web |author1=Collaborative on Health |author2=the Environment's Learning |author3=Developmental Disabilities Initiative |date=1 July 2008 |title=Scientific Consensus Statement on Environmental Agents Associated with Neurodevelopmental Disorders |url=https://www.healthandenvironment.org/uploads-old/LDDIStatement.pdf |access-date=14 March 2009 |publisher=Institute for Children's Environmental Health}}</ref> Certain cancers and uterine abnormalities in women are associated with exposure to [[diethylstilbestrol]] (DES) in the womb due to DES used as a medical treatment. In a 2005 publication, [[phthalate]]s in pregnant women's urine was linked to subtle, but specific, genital changes in their male infants—a shorter, more female-like [[anogenital distance]] and associated incomplete descent of testes and a smaller scrotum and penis.<ref name="Swan_2005">{{cite journal |vauthors=Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, Teague JL | title = Decrease in anogenital distance among male infants with prenatal phthalate exposure | journal = Environmental Health Perspectives| volume = 113 | issue = 8 | pages = 1056–61 |date=August 2005 | pmid = 16079079 | pmc = 1280349 | doi = 10.1289/ehp.8100 | bibcode = 2005EnvHP.113.1056S }}</ref> The science behind this study was questioned by phthalate industry consultants,<ref name="pmid16393642">{{cite journal | vauthors = McEwen GN, Renner G | title = Validity of anogenital distance as a marker of in utero phthalate exposure | journal = Environmental Health Perspectives| volume = 114 | issue = 1 | pages = A19–20; author reply A20–1 | date = January 2006 | pmid = 16393642 | pmc = 1332693 | doi = 10.1289/ehp.114-1332693 }}</ref> and back in 2008, there were only five studies of anogenital distance in humans,<ref name="pmid18519505">{{cite journal | vauthors = Postellon DC | title = Baby care products | journal = Pediatrics | volume = 121 | issue = 6 | pages = 1292; author reply 1292–3 |date=June 2008 | pmid = 18519505 | doi = 10.1542/peds.2008-0401 | s2cid = 27956545 }}</ref> with one researcher stating, "Whether AGD measures in humans relate to clinically important outcomes, however, remains to be determined, as does its utility as a measure of androgen action in epidemiological studies."<ref name="pmid17439530">{{cite journal |vauthors=Romano-Riquer SP, Hernández-Avila M, [[Beth Gladen|Gladen BC]], Cupul-Uicab LA, Longnecker MP | title = Reliability and determinants of anogenital distance and penis dimensions in male newborns from Chiapas, Mexico | journal = Paediatr Perinat Epidemiol | volume = 21 | issue = 3 | pages = 219–28 |date=May 2007 | pmid = 17439530 | doi = 10.1111/j.1365-3016.2007.00810.x | pmc = 3653615 }}</ref> Today, it is well-established that AGD is an indicator of fetal androgen exposure, and several studies have found a correlation between AGD and the incidence of prostate cancer.<ref>{{cite journal | vauthors = Maldonado-Cárceles AB, Sánchez-Rodríguez C, Vera-Porras EM, Árense-Gonzalo JJ, Oñate-Celdrán J, Samper-Mateo P, García-Escudero D, Torres-Roca M, Martínez-Díaz F, Mendiola J, Torres-Cantero AM | title = Anogenital Distance, a Biomarker of Prenatal Androgen Exposure Is Associated With Prostate Cancer Severity | journal = The Prostate | volume = 77 | issue = 4 | pages = 406–411 | date = March 2017 | pmid = 27862129 | doi = 10.1002/pros.23279 }}</ref><ref>{{cite journal | vauthors = Marín-Martínez FM, Arense-Gonzalo JJ, Artes MA, Bobadilla Romero ER, García Porcel VJ, Alcon Cerro P, Suárez-Pineda MC, Guzmán Martínez-Valls PL, Mendiola J | title = Anogenital distance, a biomarker of fetal androgen exposure and the risk of prostate cancer: A case-control study | journal = Urologia | volume = 90 | issue = 4 | pages = 715–719 | date = November 2023 | pmid = 37606191 | doi = 10.1177/03915603231192736 }}</ref> ==Effects on intrinsic hormones== [[Toxicology]] research shows that some endocrine disruptors target the specific hormone trait that allows one hormone to regulate the production or degradation of intrinsic hormones.<ref>{{cite book | vauthors = Harold Z | date = 2011 | title = Human Toxicology of Chemical Mixtures | edition = 2nd | publisher = Elsevier | isbn = 978-1-4377-3463-8 }}</ref><ref>{{cite book | vauthors = Yu MH, Tsunoda H, Tsunoda M | date = 2016 | title = Environmental Toxicology: Biological and Health Effects of Pollutants | edition = Third | publisher = CRC Press | isbn = 978-1-4398-4038-2 }}</ref> As endocrine disruptors have the potential to mimic or antagonize natural hormones, these chemicals can exert their effects by acting through interaction with [[nuclear receptor]]s, the [[aryl hydrocarbon receptor]] or membrane bound receptors.<ref>{{cite journal | vauthors = Toporova L, Balaguer P | title = Nuclear receptors are the major targets of endocrine disrupting chemicals | journal = Molecular and Cellular Endocrinology | volume = 502 | pages = 110665 | date = February 2020 | pmid = 31760044 | doi = 10.1016/j.mce.2019.110665 | s2cid = 209493576 | url = https://hal.archives-ouvertes.fr/hal-03488727/file/S0303720719303673.pdf }}</ref><ref>{{cite journal | vauthors = Balaguer P, Delfosse V, Grimaldi M, Bourguet W | title = Structural and functional evidences for the interactions between nuclear hormone receptors and endocrine disruptors at low doses | journal = Comptes Rendus Biologies | volume = 340 | issue = 9–10 | pages = 414–420 | date = 1 September 2017 | pmid = 29126514 | doi = 10.1016/j.crvi.2017.08.002 | series = Endocrine disruptors / Les perturbateurs endocriniens | doi-access = free }}</ref> ==U-shaped dose-response curve== {{See also|Hormesis}} Most toxicants, including endocrine disruptors, have been claimed to follow a U-shaped [[dose-response relationship|dose-response curve]].<ref>{{cite journal | vauthors = Calabrese EJ, Baldwin LA | title = Toxicology rethinks its central belief | journal = Nature | volume = 421 | issue = 6924 | pages = 691–2 | date = February 2003 | pmid = 12610596 | doi = 10.1038/421691a | bibcode = 2003Natur.421..691C | s2cid = 4419048 }}</ref> This means that very low and very high levels have more effects than mid-level exposure to a toxicant.<ref>{{cite report | vauthors = Steeger T, Tietge J | url = http://www.epa.gov/scipoly/sap/2003/june/finaljune2002telconfreport.pdf | archive-url = https://web.archive.org/web/20040711101409/http://www.epa.gov/scipoly/sap/2003/june/finaljune2002telconfreport.pdf | archive-date = 11 July 2004 | title = White Paper on Potential Developmental Effects of Atrazine on Amphibians | number = 54 | date = 29 May 2003 }}</ref> Endocrine-disrupting effects have been noted in animals exposed to environmentally relevant levels of some chemicals. For example, a common [[flame retardant]], [[PBDE|BDE]]-47, affects the reproductive system and thyroid gland of female rats in doses similar to which humans are exposed.<ref name="pmid18335096">{{cite journal |vauthors=Talsness CE, Kuriyama SN, Sterner-Kock A, Schnitker P, Grande SW, Shakibaei M, Andrade A, Grote K, Chahoud I | title = In utero and lactational exposures to low doses of polybrominated diphenyl ether-47 alter the reproductive system and thyroid gland of female rat offspring | journal = Environmental Health Perspectives| volume = 116 | issue = 3 | pages = 308–14 |date=March 2008 | pmid = 18335096 | pmc = 2265047 | doi = 10.1289/ehp.10536 | bibcode = 2008EnvHP.116..308T }}</ref> Low concentrations of endocrine disruptors can also have synergistic effects in amphibians, but it is not clear that this is an effect mediated through the endocrine system.<ref name="pmid16818245">{{cite journal |vauthors=Hayes TB, Case P, Chui S, Chung D, Haeffele C, Haston K, Lee M, Mai VP, Marjuoa Y, Parker J, Tsui M | title = Pesticide mixtures, endocrine disruption, and amphibian declines: are we underestimating the impact? | journal = Environmental Health Perspectives| issue = S–1| pages = 40–50 |date=April 2006 | volume = 114 | pmid = 16818245 | pmc = 1874187 | doi = 10.1289/ehp.8051 | bibcode = 2006EnvHP.114S..40H }}</ref> A consensus statement by the Learning and Developmental Disabilities Initiative argued that "The very low-dose effects of endocrine disruptors cannot be predicted from high-dose studies, which contradicts the standard 'dose makes the poison' rule of toxicology. Nontraditional dose-response curves are referred to as non-monotonic dose response curves."<ref name='urlwww.iceh.org'/> It has been claimed that [[tamoxifen]] and some [[phthalates]] have fundamentally different (and harmful) effects on the body at low doses than at high doses.<ref>{{cite web | vauthors = Curwood S, Young J | url = http://www.loe.org/shows/segments.htm?programID=09-P13-00036&segmentID=3 | title = Low Dose Makes the Poison | work = Living on Earth | date = 4 September 2009 }}</ref> ==Routes of exposure== [[File:Frozen pink salmon (2).jpg|thumb|Frozen salmon has been shown to have contained several man-made compounds and found to be contaminated with [[Polybrominated diphenyl ethers|PBDE]] along with several other products. ]] === Food === Food is a major mechanism by which people are exposed to pollutants. Diet is thought to account for up to 90% of a person's [[Polychlorinated biphenyl|PCB]] and [[DDT]] [[body burden]].<ref name="Fürst_2006">{{cite journal | vauthors = Fürst P | title = Dioxins, polychlorinated biphenyls and other organohalogen compounds in human milk. Levels, correlations, trends and exposure through breastfeeding | journal = Mol Nutr Food Res | volume = 50 | issue = 10 | pages = 922–33 |date=October 2006 | pmid = 17009213 | doi = 10.1002/mnfr.200600008 }}</ref> In a study of 32 different common food products from three grocery stores in Dallas, Texas, fish and other animal products were found to be contaminated with [[Polybrominated diphenyl ethers|PBDE]].<ref name="Schecter_2004">{{cite journal |vauthors=Schecter A, Päpke O, Tung KC, Staskal D, Birnbaum L | title = Polybrominated diphenyl ethers contamination of United States food | journal = Environ. Sci. Technol. | volume = 38 | issue = 20 | pages = 5306–11 |date=October 2004 | pmid = 15543730 | doi = 10.1021/es0490830 | bibcode = 2004EnST...38.5306S }}</ref> Since these compounds are fat-soluble, it is likely they are accumulating from the environment in the fatty tissue of animals eaten by humans. Some suspect fish consumption is a major source of many environmental contaminants. Indeed, both wild and farmed salmon from all over the world have been shown to contain a variety of man-made organic compounds.<ref name="pmid14716013">{{cite journal |vauthors=Hites RA, Foran JA, Carpenter DO, Hamilton MC, Knuth BA, Schwager SJ | title = Global assessment of organic contaminants in farmed salmon | journal = Science | volume = 303 | issue = 5655 | pages = 226–9 |date=January 2004 | pmid = 14716013 | doi = 10.1126/science.1091447 | bibcode = 2004Sci...303..226H | s2cid = 24058620 }}</ref> While pesticides are found in many food products, phthalates can also leech into crops, vegetables and fruits from contaminated soil and greenhouse plastic covers.<ref name=":2">{{cite journal | vauthors = Aldegunde-Louzao N, Lolo-Aira M, Herrero-Latorre C | title = Phthalate esters in clothing: A review | journal = Environmental Toxicology and Pharmacology | volume = 108 | pages = 104457 | date = June 2024 | pmid = 38677495 | doi = 10.1016/j.etap.2024.104457 | bibcode = 2024EnvTP.10804457A | doi-access = free }}</ref> [[File:Water Bottles Image.png|thumb|[[Phthalates]] are found in plastic water bottles.]] Endocrine disruptors can lead to hormonal changes in the body. Children and infants are more at risk of being affected by these chemicals. [[Phthalates|Phthalates (PAE]]) are used to make plastics last longer, and these plastics can be found in water bottles or in all dairy production stages.<ref name=":02">{{Cite journal |last=Ercan |first=Oya |last2=Tarcin |first2=Gurkan |date=2022-12-01 |title=Overview on Endocrine disruptors in food and their effects on infant's health |url=https://www.sciencedirect.com/science/article/pii/S2667009722000136 |journal=Global Pediatrics |volume=2 |pages=100019 |doi=10.1016/j.gpeds.2022.100019 |issn=2667-0097|doi-access=free }}</ref> Drinking water from plastic water bottles is a route of endocrine disruptor exposure. However, there is not a large concern of risk for humans. <ref>{{Cite journal |last=da Silva Costa |first=Rouse |last2=Sainara Maia Fernandes |first2=Tatiana |last3=de Sousa Almeida |first3=Edmilson |last4=Tomé Oliveira |first4=Juliene |last5=Carvalho Guedes |first5=Jhonyson Arruda |last6=Julião Zocolo |first6=Guilherme |last7=Wagner de Sousa |first7=Francisco |last8=do Nascimento |first8=Ronaldo Ferreira |date=2021-04-08 |title=Potential risk of BPA and phthalates in commercial water bottles: a minireview |url=https://iwaponline.com/jwh/article/19/3/411/81381/Potential-risk-of-BPA-and-phthalates-in-commercial |journal=Journal of Water and Health |volume=19 |issue=3 |pages=411–435 |doi=10.2166/wh.2021.202 |issn=1477-8920|doi-access=free }}</ref> [[Phytoestrogens]] are naturally occurring endocrine disrupters found in food. Soybeans contain a type of phytoestrogens called Geinstein.<ref name=":02" /> It has also been found that eggs contain PAEs. In a study done in Turkey, researchers examined three types of eggs: battery, free-range, and organic. They found that battery eggs contained PAEs and free-range eggs had [[DDT]] concentrations in them. DDTs are pesticides and were banned in Turkey in the late 1900s. <ref>{{Cite journal |last=Ercan |first=Oya |last2=Tarcin |first2=Gurkan |date=2022-12-01 |title=Overview on Endocrine disruptors in food and their effects on infant's health |url=https://www.sciencedirect.com/science/article/pii/S2667009722000136#sec0006 |journal=Global Pediatrics |volume=2 |pages=100019 |doi=10.1016/j.gpeds.2022.100019 |issn=2667-0097|doi-access=free }}</ref> === Indoor air and household dust === With the increase in household products containing pollutants and the decrease in the quality of building ventilation, indoor air has become a significant source of pollutant exposure.<ref name=Weschler2009>{{cite journal | vauthors = Weschler CJ | year = 2009 | title = Changes in indoor pollutants since the 1950s | journal = Atmospheric Environment | volume = 43 | issue = 1 | pages = 153–169 | doi = 10.1016/j.atmosenv.2008.09.044 | bibcode = 2009AtmEn..43..153W }}</ref> Residents living in houses with wood floors treated in the 1960s with PCB-based wood finish have a much higher body burden than the general population.<ref name="Rudel_2008">{{cite journal |vauthors=Rudel RA, Seryak LM, Brody JG | title = PCB-containing wood floor finish is a likely source of elevated PCBs in residents' blood, household air and dust: a case study of exposure | journal = Environ Health | volume = 7 | issue = 1| page = 2 | year = 2008 | pmid = 18201376 | pmc = 2267460 | doi = 10.1186/1476-069X-7-2 | doi-access = free | bibcode = 2008EnvHe...7....2R }}</ref> A study of indoor house dust and dryer lint of 16 homes found high levels of all 22 different PBDE [[Congener (chemistry)|congeners]] tested for in all samples.<ref name="pmid15773463">{{cite journal |vauthors=Stapleton HM, Dodder NG, Offenberg JH, Schantz MM, Wise SA | title = Polybrominated diphenyl ethers in house dust and clothes dryer lint | journal = Environ. Sci. Technol. | volume = 39 | issue = 4 | pages = 925–31 |date=February 2005 | pmid = 15773463 | doi = 10.1021/es0486824 | bibcode = 2005EnST...39..925S }}</ref> Recent studies suggest that contaminated house dust, not food, may be the major source of PBDE in the body.<ref name="Anderson_2008">{{cite journal |vauthors=Anderson HA, Imm P, Knobeloch L, Turyk M, Mathew J, Buelow C, Persky V | title = Polybrominated diphenyl ethers (PBDE) in serum: findings from a US cohort of consumers of sport-caught fish | journal = Chemosphere | volume = 73 | issue = 2 | pages = 187–94 |date=September 2008 | pmid = 18599108 | doi = 10.1016/j.chemosphere.2008.05.052 | bibcode = 2008Chmsp..73..187A }}</ref><ref name="Morland_2005">{{cite journal |vauthors=Morland KB, Landrigan PJ, Sjödin A, Gobeille AK, Jones RS, McGahee EE, Needham LL, Patterson DG | title = Body burdens of polybrominated diphenyl ethers among urban anglers | journal = Environmental Health Perspectives| volume = 113 | issue = 12 | pages = 1689–92 |date=December 2005 | pmid = 16330348 | pmc = 1314906 | doi = 10.1289/ehp.8138 | bibcode = 2005EnvHP.113.1689M }}</ref> One study estimated that ingestion of house dust accounts for up to 82% of humans' PBDE body burden.<ref name="Lorber_2008">{{cite journal | vauthors = Lorber M | title = Exposure of Americans to polybrominated diphenyl ethers | journal = J Expo Sci Environ Epidemiol | volume = 18 | issue = 1 | pages = 2–19 |date=January 2008 | pmid = 17426733 | doi = 10.1038/sj.jes.7500572 | doi-access = free | bibcode = 2008JESEE..18....2L }}</ref> It has been shown that contaminated house dust is a primary source of lead in young children's bodies.<ref name="pmid7354967">{{cite journal |vauthors=Charney E, Sayre J, Coulter M | title = Increased lead absorption in inner city children: where does the lead come from? | journal = Pediatrics | volume = 65 | issue = 2 | pages = 226–31 |date=February 1980 | pmid = 7354967 | doi = 10.1542/peds.65.2.226 }}</ref> It may be that babies and toddlers ingest more contaminated house dust than the adults they live with, and therefore have much higher levels of pollutants in their systems. [[File:Paraben-2D-skeletal.png|thumb|100px|The general chemical structure of a [[Paraben]]]] === Cosmetics and personal care products === Consumer goods are another potential source of exposure to endocrine disruptors. An analysis of the composition of 42 household cleaning and personal care products versus 43 "chemical-free" products has been performed. The products contained 55 different chemical compounds: 50 were found in the 42 conventional samples representing 170 product types, while 41 were detected in 43 "chemical-free" samples representing 39 product types. [[Parabens]], a class of chemicals that has been associated with reproductive-tract issues, were detected in seven of the "chemical-free" products, including three sunscreens that did not list parabens on the label. Vinyl products such as shower curtains were found to contain more than 10% by weight of the compound [[Bis(2-ethylhexyl) phthalate|DEHP]], which when present in dust has been associated with asthma and wheezing in children. The risk of exposure to EDCs increases as products, both conventional and "chemical-free", are used in combination. "If a consumer used the alternative surface cleaner, tub and tile cleaner, laundry detergent, bar soap, shampoo and conditioner, facial cleanser and lotion, and toothpaste [he or she] would potentially be exposed to at least 19 compounds: 2 parabens, 3 [[phthalate]]s, [[Monoethanolamine|MEA]], [[Diethanolamine|DEA]], 5 [[alkylphenol]]s, and 7 fragrances."<ref name="pmid22398195">{{cite journal |vauthors=Dodson RE, Nishioka M, Standley LJ, Perovich LJ, Brody JG, Rudel RA | title = Endocrine Disruptors and Asthma-Associated Chemicals in Consumer Products | journal = Environmental Health Perspectives| volume = 120| issue = 7| pages = 935–943|date=March 2012 | pmid = 22398195 | pmc = 3404651 | doi = 10.1289/ehp.1104052| bibcode = 2012EnvHP.120..935D }} * {{lay source |template = cite web|vauthors = Olver C|url = http://journalistsresource.org/studies/society/health/chemicals-consumer-products |title= Endocrine disruptors and asthma-associated chemicals in consumer products|date = 5 April 2012 |website = Journalist's Resource}}</ref> An analysis of the endocrine-disrupting chemicals in [[Old Order Mennonite]] women in mid-pregnancy determined that they have much lower levels in their systems than the general population. Mennonites eat mostly fresh, unprocessed foods, farm without pesticides, and use few or no cosmetics or personal care products. One woman who had reported using hairspray and perfume had high levels of monoethyl phthalate, while the other women all had levels below detection. Three women who reported being in a car or truck within 48 hours of providing a urine sample had higher levels of diethylhexyl phthalate, which is found in polyvinyl chloride and is used in car interiors.<ref name="pmid22739065">{{cite journal |vauthors=Martina CA, Weiss B, Swan SH | title = Lifestyle behaviors associated with exposures to endocrine disruptors | journal = Neurotoxicology | volume = 33| issue = 6| pages = 1427–1433|date=June 2012 | pmid = 22739065 | doi = 10.1016/j.neuro.2012.05.016 | pmc = 3641683| bibcode = 2012NeuTx..33.1427M }} * {{lay source |template = cite press release|url = https://www.sciencedaily.com/releases/2012/06/120626092546.htm |title= Simpler lifestyle found to reduce exposure to endocrine disrupting chemicals|date = 26 June 2012 |website = Science Daily}}</ref> === Clothing === A more recent discussion around exposure to EDCs has been around clothing. [[Greenpeace]] has reported on endocrine-disrupting chemicals in clothing since 2011. In 2013, Greenpeace found detectable levels of [[phthalates]] in 33 out of 35 printed articles of clothing from a global sample.<ref>{{Cite web | vauthors = Brigden K, Hetherington S, Wang M, Santillo D, Johnston P |date=June 2013 |title=Hazardous chemicals in branded textile products on sale in 25 countries/regions during 2013 |url=https://www.greenpeace.org/static/planet4-thailand-stateless/2019/09/192afd2f-a-little-story-about-the-monsters-in-your-closet-technical-report.pdf |publisher=Greenpeace Research Laboratories |publication-date=December 2013}}</ref> A particularly high level of [[Bis(2-ethylhexyl) phthalate|DEHP]] was found in a t-shirt from [[Primark]] Germany, and a high level of [[Diisononyl phthalate|DINP]] was found in a [[Infant|baby]] [[Infant bodysuit|one-piece]] from [[American Apparel]]. [[Perfluorinated compound|PFCs]] were commonly found in swimwear and waterproof clothing. [[Nonylphenol|NPEs]] were found in most clothing articles as well. A study by Greenpeace Germany published in 2014 again found high levels of phthalates in athletic gear.<ref>{{Cite web | vauthors = Cobbing M, Brodde K |date=May 2014 |title=A Red Card for sportswear brands |url=https://www.greenpeace.org/static/planet4-international-stateless/2014/05/ba7273a2-detox-football-report.pdf |publisher=Greenpeace e.V.}}</ref> The print of a t-shirt produced in Argentina contained phthalate levels as high as 15%, while a pair of gloves contained 6% phthalates. The study also found high levels of [[PFAS]], [[nonoxynols]] and [[dimethylformamide]] in shoes and boots. In research published in 2019, Li et al. stated that dermal absorption was the main route for [[Phthalates|phthalate]] exposure in infants,<ref>{{cite journal | vauthors = Li HL, Ma WL, Liu LY, Zhang Z, Sverko E, Zhang ZF, Song WW, Sun Y, Li YF | title = Phthalates in infant cotton clothing: Occurrence and implications for human exposure | journal = The Science of the Total Environment | volume = 683 | pages = 109–115 | date = September 2019 | pmid = 31129321 | doi = 10.1016/j.scitotenv.2019.05.132 | bibcode = 2019ScTEn.683..109L }}</ref> including through clothing. It was found that laundering could not remove phthalates completely. Out of the six different types of phthalates that were measured, DEHP and [[Dibutyl phthalate|DBP]] were found to be particularly present in infant clothing. Tang et al. published research in 2019 that found all 15 different phthalates that were measured in preschoolers' clothing.<ref name=":1">{{cite journal | vauthors = Tang Z, Chai M, Wang Y, Cheng J | title = Phthalates in preschool children's clothing manufactured in seven Asian countries: Occurrence, profiles and potential health risks | journal = Journal of Hazardous Materials | volume = 387 | pages = 121681 | date = April 2020 | pmid = 31757725 | doi = 10.1016/j.jhazmat.2019.121681 | bibcode = 2020JHzM..38721681T }}</ref> Levels were largely independent of country of manufacture though they differed by garment type, fabric composition, and garment color. It was found that "when children wore trousers, long-sleeved shirts, briefs and socks at the same time, the reproductive risks exceeded acceptable level".<ref name=":1" /> In a review of 120 articles from 2014 to 2023 about phthalates in clothing, it was found that while [[screen printing]] ink,<ref>{{cite report | vauthors = Mohapatra P, Gaonkar O | location = New Delhi, India | work = Toxics Link | date = 2021 | page = 41 |title=An Overview of Chemicals in Textiles |url=https://www.researchgate.net/publication/358804949 }}</ref> vinyl patches and [[Artificial leather|synthetic leather]] may contain 30–60% phthalates, [[Waterproof fabric|waterproof]] items such as infant [[Mattress protector|mattress covers]] also contained very high levels of these chemicals.<ref name=":2" /> It was also noted that manufacturers work to replace more regulated substances, such as DEHP, with newer ones, that may not yet be as tightly regulated. === Environment === [[File:Landfill Hawaii.jpg|thumb|Plastics in landfills can be absorbed by the soil and can then get into groundwater.]] Additives added to [[plastics]] during manufacturing may leach into the environment after the plastic item is discarded; additives in [[microplastics]] in the ocean leach into ocean water and in plastics in [[landfills]] may escape and leach into the soil and then into [[groundwater]].<ref name="pmid19528054">{{cite journal | vauthors = Teuten EL, Saquing JM, Knappe DR, Barlaz MA, Jonsson S, Björn A, Rowland SJ, Thompson RC, Galloway TS, Yamashita R, Ochi D, Watanuki Y, Moore C, Viet PH, Tana TS, Prudente M, Boonyatumanond R, Zakaria MP, Akkhavong K, Ogata Y, Hirai H, Iwasa S, Mizukawa K, Hagino Y, Imamura A, Saha M, Takada H | title = Transport and release of chemicals from plastics to the environment and to wildlife | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 364 | issue = 1526 | pages = 2027–45 | year = 2009 | pmid = 19528054 | pmc = 2873017 | doi = 10.1098/rstb.2008.0284 }}</ref><ref name=":4">{{Cite web |title=Endocrine disrupting chemicals, wildlife and the environment |url=https://chemtrust.org/edcs-wildlife/ |access-date=2025-04-13 |website=CHEM Trust |language=en-US}}</ref> The chemicals occur in plastics, pesticides, food containers, children's toys, industrial waste, and some personal care products which can enter and accumulate in the environment by contaminating the soil, air, and water.<ref>{{Cite journal |last=Luo |first=Rui |last2=Zhang |first2=Tao |last3=Wang |first3=Li |last4=Feng |first4=Yong |date=2023-11-01 |title=Emissions and mitigation potential of endocrine disruptors during outdoor exercise: Fate, transport, and implications for human health |url=https://www.sciencedirect.com/science/article/abs/pii/S0013935123013798 |journal=Environmental Research |volume=236 |pages=116575 |doi=10.1016/j.envres.2023.116575 |issn=0013-9351}}</ref><ref>{{Cite web |title=Endocrine Disruptors |url=https://www.niehs.nih.gov/health/topics/agents/endocrine|access-date=2025-04-13 |website=National Institute of Environmental Health Sciences|date=22 July 2024 |language=en}}</ref> ==Types== All people are exposed to chemicals with estrogenic effects in their everyday life, because endocrine disrupting chemicals are found in low doses in thousands of products. Chemicals commonly detected in people include [[DDT]], [[polychlorinated biphenyl]]s (PCBs), [[bisphenol A]] (BPA), [[polybrominated diphenyl ethers]] (PBDEs), and a variety of [[phthalate]]s.<ref name="cdc:105345">{{cite report | title=Fourth national report on human exposure to environmental chemicals | publisher=National Center for Environmental Health | year=2021 | doi=10.15620/cdc:105345 | s2cid = 241050234}}</ref> In fact, almost all plastic products, including those advertised as BPA-free, have been found to leach endocrine-disrupting chemicals.<ref>{{cite journal | vauthors = Yang CZ, Yaniger SI, Jordan VC, Klein DJ, Bittner GD | title = Most plastic products release estrogenic chemicals: a potential health problem that can be solved | journal = Environmental Health Perspectives | volume = 119 | issue = 7 | pages = 989–96 | date = July 2011 | pmid = 21367689 | pmc = 3222987 | doi = 10.1289/ehp.1003220 | bibcode = 2011EnvHP.119..989Y }}</ref> In a 2011, study it was found that some BPA-free products released more endocrine-active chemicals than the BPA-containing products.<ref>{{cite news| url=http://content.usatoday.com/communities/greenhouse/post/2011/03/bpa-free-plastic-products-estrogen/1 | work=USA Today | date=7 March 2011 | title=Study: Most plastic products trigger estrogen effect}}</ref><ref>{{cite news| url=https://healthland.time.com/2011/03/08/study-even-bpa-free-plastics-leach-endrocrine-disrupting-chemicals/ | title = Study: Even "BPA-Free" Plastics Leach Endrocrine-Disrupting Chemicals | magazine=Time | date=8 March 2011}}</ref> Other forms of endocrine disruptors are [[phytoestrogens]], compounds with estrogen activity found in plants.<ref>{{cite web |url=http://www.niehs.nih.gov/health/materials/endocrine_disruptors_508.pdf |title=Endocrine Disruptors |publisher=National Institute of Environmental Health Sciences|date= May 2010|access-date=1 January 2014}}</ref> === Xenoestrogens === {{Main|Xenoestrogen}} Xenoestrogens are a type of [[xenohormone]] that imitates [[estrogen]].<ref>{{cite journal | vauthors = Watson CS, Bulayeva NN, Wozniak AL, Alyea RA | title = Xenoestrogens are potent activators of nongenomic estrogenic responses | journal = Steroids | volume = 72 | issue = 2 | pages = 124–134 | date = February 2007 | pmid = 17174995 | pmc = 1862644 | doi = 10.1016/j.steroids.2006.11.002 }}</ref> Synthetic xenoestrogens include widely used industrial compounds, such as [[Polychlorinated biphenyls|PCBs]], [[Bisphenol A|BPA]] and [[phthalates]], which have estrogenic effects on a living organism. ==== Alkylphenols ==== {{Main|Alkylphenols}} Alkylphenols are [[xenoestrogens]].<ref>{{cite journal | vauthors = Kochukov MY, Jeng YJ, Watson CS | title = Alkylphenol xenoestrogens with varying carbon chain lengths differentially and potently activate signaling and functional responses in GH3/B6/F10 somatomammotropes | journal = Environmental Health Perspectives| volume = 117 | issue = 5 | pages = 723–30 | date = May 2009 | pmid = 19479013 | pmc = 2685833 | doi = 10.1289/ehp.0800182 | bibcode = 2009EnvHP.117..723K }}</ref> The European Union has implemented sales and use restrictions on certain applications in which [[nonylphenol]]s are used because of their alleged "toxicity, persistence, and the liability to bioaccumulate" but the [[United States Environmental Protection Agency|United States Environmental Protections Agency]] (EPA) has taken a slower approach to make sure that action is based on "sound science".<ref name=ACSdebate>{{cite journal|doi=10.1021/es972366q | pmid=21650741 | volume=31 | issue=7 | title=European Bans on Surfactant Trigger Transatlantic Debate | year=1997 | journal=Environmental Science & Technology | pages=316A–320A | vauthors = Renner R | bibcode=1997EnST...31..316R }}</ref> The long-chain alkylphenols are used extensively as precursors to the [[detergent]]s, as additives for fuels and [[lubricant]]s, polymers, and as components in [[phenolic resin]]s. These compounds are also used as building block chemicals that are also used in making [[fragrances]], thermoplastic [[elastomers]], [[antioxidant]]s, oil field chemicals and [[fire retardant]] materials. Through the downstream use in making alkylphenolic resins, alkylphenols are also found in tires, adhesives, coatings, carbonless copy paper and high performance rubber products. They have been used in industry for over 40 years. Certain alkylphenols are degradation products from nonionic [[detergents]]. Nonylphenol is considered to be a low-level endocrine disruptor owing to its tendency to mimic estrogen.<ref name="pmid18282600">{{cite journal |vauthors=Soares A, Guieysse B, Jefferson B, Cartmell E, Lester JN | title = Nonylphenol in the environment: a critical review on occurrence, fate, toxicity and treatment in wastewaters | journal = Environ Int | volume = 34 | issue = 7 | pages = 1033–49 |date=October 2008 | pmid = 18282600 | doi = 10.1016/j.envint.2008.01.004 | bibcode = 2008EnInt..34.1033S }}</ref><ref name="urlwww.pca.state.mn.us">{{cite web | url = https://www.pca.state.mn.us/sites/default/files/tdr-g1-08.pdf | title = Statewide Endocrine Disrupting Compound Monitoring Study, 2007 – 2008 | publisher = Minnesota Pollution Control Agency }}</ref> ==== Bisphenol A (BPA) ==== {{more medical citations needed|section|date=March 2016}} {{Main|Bisphenol A}} [[File:BPAvEstdiol.svg|thumb|Overlay of estradiol and BPA.]] Bisphenol A is commonly found in plastic bottles, plastic food containers, dental materials, and the linings of metal [[Tin can|food and infant formula cans]]. Another exposure comes from receipt paper commonly used at grocery stores and restaurants, because today the paper is commonly coated with a BPA containing clay for printing purposes.<ref>{{cite journal |date=August 2010 | title = Receipts a large — and largely ignored — source of BPA | journal = Science News | volume = 178 | issue = 5 | page = 5 | url= http://www.sciencenews.org/view/generic/id/61764/title/Receipts_a_large_%E2%80%94_and_largely_ignored_%E2%80%94_source_of_BPA/ }}</ref> BPA is a known endocrine disruptor, and numerous studies have found that laboratory animals exposed to low levels of it have elevated rates of [[diabetes]], [[breast cancer|mammary]] and [[prostate cancer]]s, decreased sperm count, reproductive problems, early [[puberty]], [[obesity]], and neurological problems.<ref name="isbn1-58829-830-2">{{cite book | vauthors = [[Andrea Gore|Gore AC]] | title = Endocrine-Disrupting Chemicals: From Basic Research to Clinical Practice (Contemporary Endocrinology) | publisher = Humana Press | location = Totowa, NJ | year = 2007 | isbn = 978-1-58829-830-0 }}</ref><ref name = "O'Connor_Chapin_2003">{{cite journal | vauthors = O'Connor JC, Chapin RE | title = Critical evaluation of observed adverse effects of endocrine active substances on reproduction and development, the immune system, and the nervous system | journal=Pure Appl. Chem. | volume = 75 | issue = 11–12 | pages = 2099–2123 | year = 2003 | doi = 10.1351/pac200375112099| s2cid = 97899046 | doi-access = free }}</ref><ref name="pmid18197296">{{cite journal | vauthors = Okada H, Tokunaga T, Liu X, Takayanagi S, Matsushima A, Shimohigashi Y | title = Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor-gamma | journal = Environmental Health Perspectives | volume = 116 | issue = 1 | pages = 32–38 | date = January 2008 | pmid = 18197296 | pmc = 2199305 | doi = 10.1289/ehp.10587 | bibcode = 2008EnvHP.116...32O }}</ref><ref name="JAMAVS">{{cite journal | vauthors = vom Saal FS, Myers JP | title = Bisphenol A and risk of metabolic disorders | journal = JAMA | volume = 300 | issue = 11 | pages = 1353–1355 | date = September 2008 | pmid = 18799451 | doi = 10.1001/jama.300.11.1353 }}</ref> Studies in the US have shown that healthy women without any fertility problems found that urinary BPA was unrelated to time of pregnancy despite a shorter luteal phase (second part of the menstrual cycle) being reported.<ref>{{cite journal | vauthors = Buck Louis GM, Sundaram R, Sweeney AM, Schisterman EF, Maisog J, Kannan K | title = Urinary bisphenol A, phthalates, and couple fecundity: the Longitudinal Investigation of Fertility and the Environment (LIFE) Study | journal = Fertility and Sterility | volume = 101 | issue = 5 | pages = 1359–1366 | date = May 2014 | pmid = 24534276 | pmc = 4008721 | doi = 10.1016/j.fertnstert.2014.01.022 }}</ref><ref>{{cite journal | vauthors = Jukic AM, Calafat AM, McConnaughey DR, Longnecker MP, Hoppin JA, Weinberg CR, Wilcox AJ, Baird DD | title = Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss | journal = Environmental Health Perspectives | volume = 124 | issue = 3 | pages = 321–328 | date = March 2016 | pmid = 26161573 | pmc = 4786975 | doi = 10.1289/ehp.1408164 | bibcode = 2016EnvHP.124..321J }}</ref> Additional studies have been conducted in fertility centers say that BPA exposure is correlation with lower ovarian reserves.<ref>{{cite journal | vauthors = Souter I, Smith KW, Dimitriadis I, Ehrlich S, Williams PL, Calafat AM, Hauser R | title = The association of bisphenol-A urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments | journal = Reproductive Toxicology | volume = 42 | pages = 224–231 | date = December 2013 | pmid = 24100206 | pmc = 4383527 | doi = 10.1016/j.reprotox.2013.09.008 | bibcode = 2013RepTx..42..224S }}</ref> To combat this, most women will undergo IVF to help with the poor ovarian stimulation response; seemingly all of them have elevated levels of BPA in the urinary tract.<ref>{{cite journal | vauthors = Mok-Lin E, Ehrlich S, Williams PL, Petrozza J, Wright DL, Calafat AM, Ye X, Hauser R | title = Urinary bisphenol A concentrations and ovarian response among women undergoing IVF | journal = International Journal of Andrology | volume = 33 | issue = 2 | pages = 385–393 | date = April 2010 | pmid = 20002217 | pmc = 3089904 | doi = 10.1111/j.1365-2605.2009.01014.x }}</ref> Median conjugation of BPA concentrations were higher in those who did have a miscarriage compared to those who had a live birth.<ref>{{cite journal | vauthors = Lathi RB, Liebert CA, Brookfield KF, Taylor JA, vom Saal FS, Fujimoto VY, Baker VL | title = Conjugated bisphenol A in maternal serum in relation to miscarriage risk | journal = Fertility and Sterility | volume = 102 | issue = 1 | pages = 123–128 | date = July 2014 | pmid = 24746738 | pmc = 4711263 | doi = 10.1016/j.fertnstert.2014.03.024 }}</ref> All of these studies show that BPA can have an effect on ovarian functions and the pivotal early part of conception. One study did show racial or ethnic differences as Asian women were found to have an increased [[oocyte]] maturity rate, but all of the women had significantly lower concentration of BPA in the study.<ref>{{cite journal | vauthors = Fujimoto VY, Kim D, vom Saal FS, Lamb JD, Taylor JA, Bloom MS | title = Serum unconjugated bisphenol A concentrations in women may adversely influence oocyte quality during in vitro fertilization | journal = Fertility and Sterility | volume = 95 | issue = 5 | pages = 1816–1819 | date = April 2011 | pmid = 21122836 | doi = 10.1016/j.fertnstert.2010.11.008 | doi-access = free }}</ref> Early developmental stages appear to be the period of greatest sensitivity to its effects, and some studies have linked prenatal exposure to later physical and neurological difficulties.<ref name="HealthCanada"> {{cite web | url = http://www.ec.gc.ca/substances/ese/eng/challenge/batch2/batch2_80-05-7.cfm | title = Draft Screening Assessment for The Challenge Phenol, 4,4′-(1-methylethylidene)bis- (Bisphenol A) Chemical Abstracts Service Registry Number 80-05-7. | archive-url = https://web.archive.org/web/20120905045805/http://www.ec.gc.ca/substances/ese/eng/challenge/batch2/batch2_80-05-7.cfm | archive-date=5 September 2012 | work = [[Health Canada]] | date = 2008 }}</ref> Regulatory bodies have determined safety levels for humans, but those safety levels are currently being questioned or are under review as a result of new scientific studies.<ref name="EHP">{{cite journal | vauthors = Ginsberg G, Rice DC | title = Does Rapid Metabolism Ensure Negligible Risk from Bisphenol A?| journal = Environmental Health Perspectives| volume = 117 | issue = 11 | pages = 1639–1643 | year = 2009 | doi = 10.1289/ehp.0901010 | pmid = 20049111 | pmc = 2801165 | bibcode = 2009EnvHP.117.1639G}}</ref><ref name="pmid19931376">{{cite journal | vauthors = Beronius A, Rudén C, Håkansson H, Hanberg A | title = Risk to all or none? A comparative analysis of controversies in the health risk assessment of Bisphenol A | journal = Reproductive Toxicology | volume = 29 | issue = 2 | pages = 132–46 | date = April 2010 | pmid = 19931376 | doi = 10.1016/j.reprotox.2009.11.007 }}</ref> A 2011 [[cross-sectional study]] that investigated the number of chemicals pregnant women are exposed to in the U.S. found BPA in 96% of women.<ref>{{cite journal | vauthors = Woodruff TJ, Zota AR, Schwartz JM | title = Environmental chemicals in pregnant women in the United States: NHANES 2003–2004 | journal = Environmental Health Perspectives | volume = 119 | issue = 6 | pages = 878–85 | date = June 2011 | pmid = 21233055 | pmc = 3114826 | doi = 10.1289/ehp.1002727 | bibcode = 2011EnvHP.119..878W }}</ref> In 2010 the [[World Health Organization]] expert panel recommended no new regulations limiting or banning the use of bisphenol A, stating that "initiation of public health measures would be premature."<ref>{{cite web | vauthors = Brown E | url = https://www.latimes.com/health/la-xpm-2010-nov-11-la-heb-who-bpa-20101111-story.html | title = Jury still out on BPA, World Health Organization says | work = [[Los Angeles Times]] | date = 11 November 2010 | access-date = 7 February 2011 }}</ref> In August 2008, the U.S. FDA issued a draft reassessment, reconfirming their initial opinion that, based on scientific evidence, BPA is safe.<ref name="urlChemical Used in Plastic Bottles Is Safe, F.D.A. Says - NYTimes.com">{{cite news | url = https://www.nytimes.com/2008/08/16/business/16chemical.html | title = Chemical Used in Plastic Bottles Is Safe, F.D.A. Says | date = 16 August 2008 | work = The New York Times | access-date = 14 March 2009}}</ref> However, in October 2008, FDA's advisory Science Board concluded that the Agency's assessment was "flawed" and had not proven the chemical to be safe for formula-fed infants.<ref name="urlAdvisers: FDA decision on safety of BPA flawed - USATODAY.com">{{cite news | url = https://www.usatoday.com/news/health/2008-10-31-bpa-fda_N.htm | title = Advisers: FDA decision on safety of BPA 'flawed' | vauthors = Szabo L | date = 1 November 2008 | work = USA Today | access-date = 14 March 2009}}</ref> In January 2010, the FDA issued a report indicating that, due to findings of recent studies that used novel approaches in testing for subtle effects, both the National Toxicology Program at the National Institutes of Health as well as the FDA have some level of concern regarding the possible effects of BPA on the brain and behavior of fetuses, infants and younger children.<ref name="urlBisphenol A (BPA): Use in Food Contact Application">{{cite web | url = https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm064437.htm | archive-url = https://web.archive.org/web/20090605155623/http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm064437.htm | url-status = dead | archive-date = 5 June 2009 | title = Bisphenol A (BPA): Use in Food Contact Application | date = 30 March 2012 | work = News & Events | publisher = United States Food & Drug Administration | access-date = 14 April 2012 }}</ref> In 2012 the FDA did ban the use of BPA in baby bottles; however, the [[Environmental Working Group]] called the ban "purely cosmetic". In a statement they said, "If the agency truly wants to prevent people from being exposed to this toxic chemical associated with a variety of serious and chronic conditions it should ban its use in cans of infant formula, food and beverages." The [[Natural Resources Defense Council]] called the move inadequate saying, the FDA needs to ban BPA from all [[food packaging]].<ref name="commondreams">{{cite web|url=http://www.commondreams.org/headline/2012/07/17-4 |title=FDA to Ban BPA from Baby Bottles; Plan Falls Short of Needed Protections: Scientists |publisher=Common Dreams |date=17 July 2012 |access-date=6 April 2015}}</ref> In a statement a FDA spokesman said the agency's action was not based on safety concerns and that "the agency continues to support the safety of BPA for use in products that hold food."<ref name="huffpo">{{cite news| url=http://www.huffingtonpost.com/2012/07/17/fda-bans-bpa-baby-bottles_n_1679795.html | work=The Huffington Post | title=BPA Banned From Baby Bottles | date=17 July 2012}}</ref> A program initiated by [[NIEHS]], [[National Toxicology Program|NTP]], and the U.S. [[Food and Drug Administration]] (named CLARITY-BPA) found no effect of chronic exposure to BPA on rats<ref>{{cite web | url = https://ntp.niehs.nih.gov/results/areas/bpa/index.html | title = CLARITY-BPA Program | work = [[NIH National Toxicology Program]] | date = 23 February 2018 | access-date = 5 August 2019 }}</ref> and the FDA considers currently authorized uses of BPA to be safe for consumers.<ref>{{cite web | vauthors = Ostroff S | url = https://www.fda.gov/news-events/press-announcements/statement-stephen-ostroff-md-deputy-commissioner-foods-and-veterinary-medicine-national-toxicology | archive-url = https://web.archive.org/web/20191210045925/https://www.fda.gov/news-events/press-announcements/statement-stephen-ostroff-md-deputy-commissioner-foods-and-veterinary-medicine-national-toxicology | url-status = dead | archive-date = 10 December 2019 | title = Statement from Stephen Ostroff M.D., Deputy Commissioner for Foods and Veterinary Medicine, on National Toxicology Program draft report on Bisphenol A | work = U.S. Food and Drug Administration | date = 23 February 2018 | access-date = 5 August 2019 }}</ref> The [[United States Environmental Protection Agency|Environmental Protection Agency]] set{{when|date=October 2023}} a reference dose for BPA at 50 μg/kg/day for mammals, although exposure to doses lower than the reference dose has been shown to affect both male and female reproductive systems.<ref>{{Cite journal | vauthors = Vandenberg LN, Ehrlich S, Belcher SM, Ben-Jonathan N, Dolinoy DC, Hugo ER, Hunt PA, Newbold RR, Rubin BS, Saili KS, Soto AM | title = Low dose effects of bisphenol A: An integrated review of in vitro, laboratory animal, and epidemiology studies. | journal = Endocrine Disruptors | date = October 2013 | volume = 1 | issue = 1 | pages = e26490 | doi = 10.4161/endo.26490 | s2cid = 82372971 | doi-access = free }}</ref> ===Bisphenol S (BPS) and bisphenol F (BPF)=== [[Bisphenol S]] and Bisphenol F are analogs of bisphenol A. They are commonly found in thermal receipts, plastics, and household dust. Traces of BPS have also been found in personal care products.<ref>{{cite journal | vauthors = Rochester JR, Bolden AL | title = Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes | journal = Environmental Health Perspectives| volume = 123 | issue = 7 | pages = 643–50 | date = July 2015 | pmid = 25775505 | doi = 10.1289/ehp.1408989 | pmc=4492270| bibcode = 2015EnvHP.123..643R }}</ref> It is more presently being used because of the ban of BPA. BPS is used in place of BPA in BPA-free items. However, BPS and BPF have been shown to be endocrine disruptors as much as BPA.<ref>{{cite journal | vauthors = Eladak S, Grisin T, Moison D, Guerquin MJ, N'Tumba-Byn T, Pozzi-Gaudin S, Benachi A, Livera G, Rouiller-Fabre V, Habert R | title = A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound | journal = Fertility and Sterility | volume = 103 | issue = 1 | pages = 11–21 | date = January 2015 | pmid = 25475787 | doi = 10.1016/j.fertnstert.2014.11.005 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tanner EM, Hallerbäck MU, Wikström S, Lindh C, Kiviranta H, Gennings C, Bornehag CG | title = Early prenatal exposure to suspected endocrine disruptor mixtures is associated with lower IQ at age seven | journal = Environment International | volume = 134 | pages = 105185 | date = January 2020 | pmid = 31668669 | doi = 10.1016/j.envint.2019.105185 | doi-access = free | bibcode = 2020EnInt.13405185T }}</ref> === DDT === {{Main|DDT}} [[File:DDT.svg|thumb|right|DDT Chemical structure]] Dichlorodiphenyltrichloroethane (DDT) was first used as a pesticide against [[Colorado potato beetle]]s on crops beginning in 1936.<ref name="Davis_1971">{{cite journal | vauthors = Davis KS | title = The deadly dust: the unhappy history of DDT | journal = American Heritage Magazine | volume = 22 | issue = 2 | year = 1971 | url = http://www.americanheritage.com/articles/magazine/ah/1971/2/1971_2_44.shtml | access-date = 15 February 2009 | archive-url = https://web.archive.org/web/20080912003246/http://www.americanheritage.com/articles/magazine/ah/1971/2/1971_2_44.shtml | archive-date = 12 September 2008 | url-status = dead }}</ref> An increase in the incidence of [[malaria]], epidemic [[typhus]], [[dysentery]], and [[typhoid fever]] led to its use against the mosquitoes, lice, and houseflies that carried these diseases. Before World War II, [[pyrethrum]], an extract of a flower from Japan, had been used to control these insects and the diseases they can spread. During World War II, Japan stopped exporting pyrethrum, forcing the search for an alternative. Fearing an epidemic outbreak of typhus, every British and American soldier was issued DDT, who used it to routinely dust beds, tents, and barracks all over the world. DDT was approved for general, non-military use after the war ended.<ref name="Davis_1971"/> It became used worldwide to increase [[monoculture]] crop yields that were threatened by pest infestation, and to reduce the spread of malaria which had a high mortality rate in many parts of the world. Its use for agricultural purposes has since been prohibited by national legislation of most countries, while its use as a control against malaria vectors is permitted, as specifically stated by the [[Stockholm Convention on Persistent Organic Pollutants]].<ref>{{cite web|url=http://chm.pops.int/Convention/tabid/54/language/en-US/Default.aspx#convtext/|title=Stockholm Convention on Persistent Organic Pollutants}}</ref> As early as 1946, the harmful effects of DDT on birds, beneficial insects, fish, and marine invertebrates were seen in the environment. The most infamous example of these effects were seen in the eggshells of large predatory birds, which did not develop to be thick enough to support the adult bird sitting on them.<ref name="Lundholm_1997">{{cite journal | vauthors = Lundholm CD | title = DDE-induced eggshell thinning in birds: effects of p, p′-DDE on the calcium and prostaglandin metabolism of the eggshell gland | journal = Comp. Biochem. Physiol. C | volume = 118 | issue = 2 | pages = 113–28 |date=October 1997 | pmid = 9490182 | doi = 10.1016/S0742-8413(97)00105-9 }}</ref> Further studies found DDT in high concentrations in carnivores all over the world, the result of [[biomagnification]] through the [[food chain]].<ref name="Szlinder-Richert_2008">{{cite journal |vauthors=Szlinder-Richert J, Barska I, Mazerski J, Usydus Z | title = Organochlorine pesticides in fish from the southern Baltic Sea: levels, bioaccumulation features and temporal trends during the 1995–2006 period | journal = Mar. Pollut. Bull. | volume = 56 | issue = 5 | pages = 927–40 |date=May 2008 | pmid = 18407298 | doi = 10.1016/j.marpolbul.2008.01.029 | bibcode = 2008MarPB..56..927S }}</ref> Twenty years after its widespread use, DDT was found trapped in ice samples taken from Antarctic snow, suggesting wind and water are another means of environmental transport.<ref name="Peterle_1969">{{cite journal | vauthors = Peterle TJ | title = DDT in Antarctic snow | journal = Nature | volume = 224 | issue = 5219 | page = 620 |date=November 1969 | pmid = 5346606 | doi = 10.1038/224620a0 | bibcode = 1969Natur.224..620P | s2cid = 4188794 | doi-access = free }}</ref> Recent studies show the historical record of DDT deposition on remote glaciers in the Himalayas.<ref name="Daly_2005">{{cite journal |vauthors=Daly GL, Wania F | s2cid = 19072832 | title = Organic contaminants in mountains | journal = Environ. Sci. Technol. | volume = 39 | issue = 2 | pages = 385–98 |date=January 2005 | pmid = 15707037 | doi = 10.1021/es048859u | bibcode = 2005EnST...39..385D }}</ref> More than sixty years ago when biologists began to study the effects of DDT on laboratory animals, it was discovered that DDT interfered with reproductive development.<ref name="pmid14808278">{{cite journal | vauthors = Tauber OE, Hughes AB | title = Effect of DDT ingestion on total cholesterol content of ovaries of white rat | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 75 | issue = 2 | pages = 420–422 | date = November 1950 | pmid = 14808278 | doi = 10.3181/00379727-75-18217 | s2cid = 252206 }}</ref><ref name="Stoner_1953">{{cite journal | vauthors = Stoner HB | title = Effect of 2,2-bis (parachlorophenyl)-1,1-dichloroethane (DDD) on the adrenal cortex of the rat | journal = Nature | volume = 172 | issue = 4388 | pages = 1044–1045 | date = December 1953 | pmid = 13111250 | doi = 10.1038/1721044a0 | s2cid = 4200580 | bibcode = 1953Natur.172.1044S }}</ref> Recent studies suggest DDT may inhibit the proper development of female reproductive organs that adversely affects reproduction into maturity.<ref name="Tiemann_2008">{{cite journal | vauthors = Tiemann U | title = In vivo and in vitro effects of the organochlorine pesticides DDT, TCPM, methoxychlor, and lindane on the female reproductive tract of mammals: a review | journal = Reproductive Toxicology | volume = 25 | issue = 3 | pages = 316–326 | date = April 2008 | pmid = 18434086 | doi = 10.1016/j.reprotox.2008.03.002 | bibcode = 2008RepTx..25..316T }}</ref> Additional studies suggest that a marked decrease in fertility in adult males may be due to DDT exposure.<ref name="Hallegue_2003">{{cite journal |vauthors=Hallegue D, Rhouma KB, Tébourbi O, Sakly M | title = Impairment of Testicular Endocrine and Exocrine Functions after Dieldrin Exposure in Adult Rats | journal = Polish Journal of Environmental Studies | volume = 12 | issue = 5 | pages = 557–562 |date=April 2003| url = http://6csnfn.pjoes.com/pdf/12.5/557-561.pdf }}</ref> Most recently, it has been suggested that exposure to DDT in utero can increase a child's risk of [[childhood obesity]].<ref name="Verhulst_2009">{{cite journal | vauthors = Verhulst SL, Nelen V, Hond ED, Koppen G, Beunckens C, Vael C, Schoeters G, Desager K | title = Intrauterine exposure to environmental pollutants and body mass index during the first 3 years of life | journal = Environmental Health Perspectives | volume = 117 | issue = 1 | pages = 122–126 | date = January 2009 | pmid = 19165398 | pmc = 2627855 | doi = 10.1289/ehp.0800003 | bibcode = 2009EnvHP.117..122V }}</ref> DDT is still used as anti-malarial insecticide in Africa and parts of Southeast Asia in limited quantities. === Polychlorinated biphenyls === {{Main|Polychlorinated biphenyls}} Polychlorinated biphenyls (PCBs) are a class of chlorinated compounds used as industrial coolants and lubricants. PCBs are created by heating benzene, a byproduct of gasoline refining, with chlorine.<ref name="urlMarch/April 2001 Sierra Magazine - Sierra Club">{{cite web | url = http://www.sierraclub.org/sierra/200103/conspiracy.asp | title = March/April 2001 Sierra Magazine – Sierra Club | vauthors = Francis E | date = 1 September 1994 | work = Sierra Magazine | access-date = 14 March 2009 | archive-url = https://web.archive.org/web/20090620074809/http://www.sierraclub.org/sierra/200103/conspiracy.asp | archive-date = 20 June 2009 | url-status = dead }}</ref> They were first manufactured commercially by the Swann Chemical Company in 1927.<ref name="urlFox River History of PCBs">{{cite web | url = http://www.foxriverwatch.com/fox_river_history_pcbs.html | archive-url = https://web.archive.org/web/20020221182634/http://www.foxriverwatch.com/fox_river_history_pcbs.html | url-status = dead | archive-date = 21 February 2002 | title = Fox River History of PCBs | work = Fox River Watch | publisher = Clean Water Action Council | access-date = 14 March 2009 }}</ref> In 1933, the health effects of direct PCB exposure was seen in those who worked with the chemicals at the manufacturing facility in Alabama. In 1935, [[Monsanto]] acquired the company, taking over US production and licensing PCB manufacturing technology internationally. General Electric was one of the largest US companies to incorporate PCBs into manufactured equipment.<ref name="urlFox River History of PCBs"/> Between 1952 and 1977, the New York GE plant had dumped more than 500,000 pounds of PCB waste into the Hudson River. PCBs were first discovered in the environment far from its industrial use by scientists in Sweden studying DDT.<ref name="pmid5388040">{{cite journal |vauthors=Jensen S, Johnels AG, Olsson M, Otterlind G | title = DDT and PCB in marine animals from Swedish waters | journal = Nature | volume = 224 | issue = 5216 | pages = 247–50 |date=October 1969 | pmid = 5388040 | doi = 10.1038/224247a0 | bibcode = 1969Natur.224..247J | s2cid = 4182319 }}</ref> The effects of acute exposure to PCBs were well known within the companies who used Monsanto's PCB formulation who saw the effects on their workers who came into contact with it regularly. Direct skin contact results in a severe acne-like condition called [[chloracne]].<ref name="pmid18329192">{{cite journal |vauthors=Tang NJ, Liu J, Coenraads PJ, Dong L, Zhao LJ, Ma SW, Chen X, Zhang CM, Ma XM, Wei WG, Zhang P, Bai ZP | title = Expression of AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in skin lesions from dioxin-exposed humans with chloracne | journal = Toxicol. Lett. | volume = 177 | issue = 3 | pages = 182–7 |date=April 2008 | pmid = 18329192 | doi = 10.1016/j.toxlet.2008.01.011 | url = https://pure.rug.nl/ws/files/6717241/Tang_2008_Toxicol_Lett.pdf | hdl = 11370/f27e334f-9133-421b-9d78-ff322686e1ae | s2cid = 9665736 }}</ref> Exposure increases the risk of skin cancer,<ref name="Loomis_1997">{{cite journal |vauthors=Loomis D, Browning SR, Schenck AP, Gregory E, Savitz DA | title = Cancer mortality among electric utility workers exposed to polychlorinated biphenyls | journal = Occup Environ Med | volume = 54 | issue = 10 | pages = 720–8 |date=October 1997 | pmid = 9404319 | pmc = 1128926 | doi = 10.1136/oem.54.10.720 }}</ref> liver cancer,<ref name="Brown_1987">{{cite journal | vauthors = Brown DP | title = Mortality of workers exposed to polychlorinated biphenyls--an update | journal = Archives of Environmental Health | volume = 42 | issue = 6 | pages = 333–339 | year = 1987 | pmid = 3125795 | doi = 10.1080/00039896.1987.9934355 | s2cid = 4615591 }}</ref> and brain cancer.<ref name="Loomis_1997"/><ref name="Sinks_1992">{{cite journal |vauthors=Sinks T, Steele G, Smith AB, Watkins K, Shults RA | title = Mortality among workers exposed to polychlorinated biphenyls | journal = Am. J. Epidemiol. | volume = 136 | issue = 4 | pages = 389–98 |date=August 1992 | pmid = 1415158 | doi = 10.1093/oxfordjournals.aje.a116511 }}</ref> Monsanto tried for years to downplay the health problems related to PCB exposure in order to continue sales.<ref name="urlMonsanto Hid Decades Of Pollution (washingtonpost.com)">{{cite news | url = https://www.washingtonpost.com/ac2/wp-dyn?pagename=article&contentId=A46648-2001Dec31 | archive-url = https://web.archive.org/web/20100821062037/http://www.washingtonpost.com/ac2/wp-dyn?pagename=article&contentId=A46648-2001Dec31 | url-status = dead | archive-date = 21 August 2010 | title = Monsanto Hid Decades Of Pollution | vauthors = Grunwald M | date = 1 January 2002 | newspaper = The Washington Post | access-date = 14 March 2009 }}</ref> The detrimental health effects of PCB exposure to humans became undeniable when two separate incidents of contaminated cooking oil [[Yushō disease|poisoned thousands of residents]] in Japan (Yushō disease, 1968) and Taiwan (Yu-cheng disease, 1979),<ref name="EHC002">{{EHC-ref | id = 002 | name = Polychlorinated biphenyls and terphenyls| date = 1976 | isbn = 92-4-154062-1 }}</ref> leading to a worldwide ban on PCB use in 1977. Recent studies show the endocrine interference of certain PCB congeners is toxic to the liver and thyroid,<ref name="Kodavanti_2006">{{cite journal | vauthors = Kodavanti PR | title = Neurotoxicity of persistent organic pollutants: possible mode(s) of action and further considerations | journal = Dose-Response | volume = 3 | issue = 3 | pages = 273–305 | date = May 2006 | pmid = 18648619 | pmc = 2475949 | doi = 10.2203/dose-response.003.03.002 }}</ref> increases childhood obesity in children exposed prenatally,<ref name="Verhulst_2009"/> and may increase the risk of developing diabetes.<ref name="Uemura_2008">{{cite journal | vauthors = Uemura H, Arisawa K, Hiyoshi M, Satoh H, Sumiyoshi Y, Morinaga K, Kodama K, Suzuki T, Nagai M, Suzuki T | title = Associations of environmental exposure to dioxins with prevalent diabetes among general inhabitants in Japan | journal = Environmental Research | volume = 108 | issue = 1 | pages = 63–68 | date = September 2008 | pmid = 18649880 | doi = 10.1016/j.envres.2008.06.002 | bibcode = 2008ER....108...63U }}</ref><ref name="Mullerova_2008">{{cite journal | vauthors = Mullerova D, Kopecky J, Matejkova D, Muller L, Rosmus J, Racek J, Sefrna F, Opatrna S, Kuda O, Matejovic M | title = Negative association between plasma levels of adiponectin and polychlorinated biphenyl 153 in obese women under non-energy-restrictive regime | journal = International Journal of Obesity | volume = 32 | issue = 12 | pages = 1875–1878 | date = December 2008 | pmid = 18825156 | doi = 10.1038/ijo.2008.169 | doi-access = free }}</ref> PCBs in the environment may also be related to reproductive and infertility problems in wildlife. In Alaska, it is thought that they may contribute to reproductive defects, infertility and antler malformation in some deer populations. Declines in the populations of otters and sea lions may also be partially due to their exposure to PCBs, the insecticide DDT, other persistent organic pollutants. Bans and restrictions on the use of EDCs have been associated with a reduction in health problems and the recovery of some wildlife populations.<ref>{{cite web|url=https://www.sciencedaily.com/releases/2013/02/130219115501.htm |title=Effects of human exposure to hormone-disrupting chemicals examined in landmark United Nations report |work=Science Daily |date=19 February 2013 |access-date=6 April 2015}}</ref> === Polybrominated diphenyl ethers === {{Main|Polybrominated diphenyl ethers}} Polybrominated diphenyl ethers (PBDEs) are a class of compounds found in [[flame retardant]]s used in plastic cases of televisions and computers, electronics, carpets, lighting, bedding, clothing, car components, foam cushions and other [[textiles]]. Potential health concern: PBDEs are structurally very similar to [[polychlorinated biphenyls]] (PCBs), and have similar [[neurotoxic]] effects.<ref name="Eriksson_2006">{{cite journal |vauthors=Eriksson P, Fischer C, Fredriksson A | title = Polybrominated diphenyl ethers, a group of brominated flame retardants, can interact with polychlorinated biphenyls in enhancing developmental neurobehavioral defects | journal = Toxicol. Sci. | volume = 94 | issue = 2 | pages = 302–9 |date=December 2006 | pmid = 16980691 | doi = 10.1093/toxsci/kfl109 | doi-access = free }}</ref> <!--this needs to be rewritten, but I moved it since it was repeated(seemed unnecessary to have it repeated, but I have class and can't rewrite it now)-->Research has correlated [[halogenated hydrocarbons]], such as PCBs, with [[neurotoxicity]].<ref name="Kodavanti_2006"/> PBDEs are similar in chemical structure to PCBs, and it has been suggested that PBDEs act by the same mechanism as PCBs.<ref name="Kodavanti_2006"/> In the 1930s and 1940s, the plastics industry developed technologies to create a variety of plastics with broad applications.<ref name="urlPlastics Division : the history of plastic">{{cite web | url = http://www.americanchemistry.com/s_plastics/doc.asp?CID=1102&DID=4665 | title = The history of plastic | work = Plastics Division | publisher = American Chemistry Council | access-date = 14 March 2009 | url-status = dead | archive-url = https://web.archive.org/web/20081231093541/http://www.americanchemistry.com/s_plastics/doc.asp?CID=1102&DID=4665 | archive-date = 31 December 2008 }}</ref> Once [[World War II]] began, the US military used these new plastic materials to improve weapons, protect equipment, and to replace heavy components in aircraft and vehicles.<ref name="urlPlastics Division : the history of plastic"/> After WWII, manufacturers saw the potential plastics could have in many industries, and plastics were incorporated into new consumer product designs. Plastics began to replace wood and metal in existing products as well, and today plastics are the most widely used manufacturing materials.<ref name="urlPlastics Division : the history of plastic"/> By the 1960s, all homes were wired with electricity and had numerous electrical appliances. Cotton had been the dominant textile used to produce home furnishings,<ref>{{cite web | title = Cotton Products Research: Durable Press and Flame Retardant Cotton | work = National Historic Chemical Landmarks | publisher = American Chemical Society | url = http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/cottonproducts.html | access-date = 21 February 2014 }}</ref> but now home furnishings were composed of mostly synthetic materials. More than 500 billion cigarettes were consumed each year in the 1960s, as compared to less than 3 billion per year in the beginning of the twentieth century.<ref name="urlwww.lungusa.org">{{cite web | url = http://www.lung.org/finding-cures/our-research/trend-reports/Tobacco-Trend-Report.pdf | title = Trends in Tobacco Use | author = Epidemiology and Statistics Unit | date = July 2011 | publisher = American Lung Association | access-date = 2 April 2015}}</ref> When combined with high-density living, the potential for home fires was higher in the 1960s than it had ever been in the US. By the late 1970s, approximately 6000 people in the US died each year in home fires.<ref name="urlwww.nfpa.org">{{cite web|url=http://www.nfpa.org/assets/files/PDF/OS.fireloss.pdf |title=Fire Loss In The United States 2007 | vauthors = Karter MJ |date=1 August 2008 |publisher=National Fire Protection Association |access-date=14 March 2009 |url-status=dead |archive-url=https://web.archive.org/web/20081207044028/http://www.nfpa.org/assets/files/PDF/OS.fireloss.pdf |archive-date=7 December 2008 }}</ref> In 1972, in response to this situation, the National Commission on Fire Prevention and Control was created to study the fire problem in the US. In 1973 they published their findings in "America Burning", a 192-page report that made recommendations to increase fire prevention.<ref name="urlwww.usfa.dhs.gov">{{cite report |url=http://www.usfa.dhs.gov/downloads/pdf/publications/fa-264.pdf |title=America Burning |date=4 May 1973 |publisher=[[U.S. Fire Administration]] |access-date=14 March 2009}}</ref> Most of the recommendations dealt with fire prevention education and improved building engineering, such as the installation of fire sprinklers and smoke detectors. The Commission expected that with the recommendations, a 5% reduction in fire losses could be expected each year, halving the annual losses within 14 years. Historically, treatments with alum and borax were used to reduce the [[Fire-retardant fabric|flammability of fabric]] and wood, as far back as Roman times.<ref name="EHC192">{{EHC-ref | id = 192| name = Flame retardants: a general introduction | date = 1997 | isbn = 92-4-157192-6 }}</ref> Since it is a non-absorbent material once created, flame retardant chemicals are added to plastic during the polymerization reaction when it is formed. Organic compounds based on halogens like bromine and chlorine are used as the flame retardant additive in plastics, and in fabric based textiles as well.<ref name="EHC192"/> The widespread use of brominated [[flame retardant]]s may be due to the push from Great Lakes Chemical Corporation (GLCC) to profit from its huge investment in bromine.<ref name="urlGreat Lakes Chemical Corporation -- Company History">{{cite web | url = http://www.fundinguniverse.com/company-histories/Great-Lakes-Chemical-Corporation-Company-History.html | title = Great Lakes Chemical Corporation – Company History | access-date = 14 March 2009}}</ref> In 1992, the world market consumed approximately 150,000 tonnes of bromine-based flame retardants, and GLCC produced 30% of the world supply.<ref name="EHC192"/> PBDEs have the potential to disrupt thyroid hormone balance and contribute to a variety of neurological and developmental deficits, including [[low intelligence]] and [[learning disabilities]].<ref name="urlwww.epa.gov">{{cite web | url = http://www.epa.gov/iris/toxreviews/0035tr.pdf | title = Toxicological review of decabromodiphenyl ether (BDE-209) | date = June 2008 | publisher = U.S. Environmental Protection Agency | access-date = 14 March 2009}}</ref><ref name=autogenerated2>{{cite web | url = http://www.epa.gov/iris/toxreviews/1010tr.pdf | title = toxicological review of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) | date = 1 June 2008 | publisher = U.S. Environmental Protection Agency | access-date = 14 March 2009}}</ref> Many of the most common PBDE's were banned in the [[European Union]] in 2006.<ref name="pmid18470294">{{cite journal | vauthors = Betts KS | title = New thinking on flame retardants | journal = Environmental Health Perspectives | volume = 116 | issue = 5 | pages = A210–A213 | date = May 2008 | pmid = 18470294 | pmc = 2367656 | doi = 10.1289/ehp.116-a210 }}</ref> Studies with rodents have suggested that even brief exposure to PBDEs can cause developmental and behavior problems in juvenile rodents<ref name="Eriksson_2002"/><ref name="Costa_2007">{{cite journal |vauthors=Costa LG, Giordano G | title = Developmental neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants | journal = Neurotoxicology | volume = 28 | issue = 6 | pages = 1047–67 |date=November 2007 | pmid = 17904639 | pmc = 2118052 | doi = 10.1016/j.neuro.2007.08.007 | bibcode = 2007NeuTx..28.1047C }}</ref> and exposure interferes with proper thyroid hormone regulation.<ref name="Lema_2008">{{cite journal |vauthors=Lema SC, Dickey JT, Schultz IR, Swanson P | title = Dietary exposure to 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) alters thyroid status and thyroid hormone-regulated gene transcription in the pituitary and brain | journal = Environmental Health Perspectives| volume = 116 | issue = 12 | pages = 1694–9 |date=December 2008 | pmid = 19079722 | pmc = 2599765 | doi = 10.1289/ehp.11570 | bibcode = 2008EnvHP.116.1694L }}</ref> [[File:Phthalates.svg|thumb|General chemical structure of [[Phthalates]]]] === Phthalates === {{Main|Phthalates}} Phthalates are found in some soft toys, flooring, medical equipment, cosmetics and air fresheners. They are of potential health concern because they are known to disrupt the endocrine system of animals, and some research has implicated them in the rise of birth defects of the male reproductive system.<ref name="Swan_2005"/><ref name="Fisher">{{cite journal | vauthors = Fisher JS | title = Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome | journal = Reproduction | volume = 127 | issue = 3 | pages = 305–315 | date = March 2004 | pmid = 15016950 | doi = 10.1530/rep.1.00025 | doi-access = free }}</ref><ref name=Barrett2005>{{Cite journal | doi = 10.1289/ehp.113-a542a | pmc = 1280383 | vauthors = Barrett JR | year = 2005 | title = Phthalates and Baby Boys: Potential Disruption of Human Genital Development | journal = Environmental Health Perspectives| pages = A542 | volume = 113 | issue = 8 | jstor = 3436340}}</ref> Although an expert panel has concluded that there is "insufficient evidence" that they can harm the reproductive system of infants,<ref name="pmid16239449">{{cite journal | vauthors = Kaiser J | title = Toxicology. Panel finds no proof that phthalates harm infant reproductive systems | journal = Science | volume = 310 | issue = 5747 | pages = 422 | date = October 2005 | pmid = 16239449 | doi = 10.1126/science.310.5747.422a | s2cid = 39080713 }}</ref> California,<ref name="Copbocp">{{cite news | url = https://www.reuters.com/article/healthNews/idUSN1443724320071015 | title = California OKs phthalates ban on children's products | date = 15 October 2007 | work = Reuters | access-date = 14 March 2009}}</ref><ref name="urlChemical & Engineering News: Latest News - California Bans Phthalates In Toys For Children">{{cite web | url = http://pubs.acs.org/cen/news/85/i43/8543news4.html | title = California Bans Phthalates In Toys For Children | author = Hileman B | date = 17 October 2007 | publisher = Chemical & Engineering News | access-date = 14 March 2009}}</ref> Washington state,<ref>{{cite web |url=http://www.ecy.wa.gov/programs/hwtr/RTT/cspa/pdf/LeadCadmiumPhthalatesenforcement.pdf |title=Children's Safe Product Act – RCW 70.240.020 Lead, Cadmium, and Phthalates | date = 12 February 2016 | work = Washington State Department of Ecology |access-date=27 April 2022 |archive-url=https://web.archive.org/web/20170210190407/http://www.ecy.wa.gov/programs/hwtr/RTT/cspa/pdf/LeadCadmiumPhthalatesenforcement.pdf |archive-date=10 February 2017 |url-status=dead}}</ref> and Europe have banned them from toys. One phthalate, [[bis(2-ethylhexyl) phthalate]] (DEHP), used in medical tubing, catheters and blood bags, may harm sexual development in male infants.<ref name="Fisher"/> In 2002, the [[Food and Drug Administration]] released a public report which cautioned against exposing male babies to DEHP. Although there are no direct human studies the FDA report states: "Exposure to DEHP has produced a range of adverse effects in laboratory animals, but of greatest concern are effects on the development of the male reproductive system and production of normal sperm in young animals. In view of the available animal data, precautions should be taken to limit the exposure of the developing male to DEHP".<ref name="urlUS FDA/CDRH: FDA Public Health Notification: PVC Devices Containing the Plasticizer DEHP">{{cite web | url = https://www.fda.gov/cdrh/safety/dehp.html | archive-url = https://web.archive.org/web/20020802013815/http://www.fda.gov/cdrh/safety/dehp.html | url-status = dead | archive-date = 2 August 2002 | title = PVC Devices Containing the Plasticizer DEHP | vauthors = Feigal DW | date = 12 July 2002 | work = US FDA/CDRH: FDA Public Health Notification | publisher = Food and Drug Administration | access-date = 14 March 2009}}</ref> Similarly, phthalates may play a causal role in disrupting masculine neurological development when exposed prenatally.<ref name="pmid19919614">{{cite journal | vauthors = Swan SH, Liu F, Hines M, Kruse RL, Wang C, Redmon JB, Sparks A, Weiss B | title = Prenatal phthalate exposure and reduced masculine play in boys | journal = International Journal of Andrology | volume = 33 | issue = 2 | pages = 259–269 | date = April 2010 | pmid = 19919614 | pmc = 2874619 | doi = 10.1111/j.1365-2605.2009.01019.x }}</ref> [[Dibutyl phthalate]] (DBP) has also disrupted [[insulin]] and [[glucagon]] signaling in animal models.<ref name="Williams2016">{{cite journal | vauthors = Williams MJ, Wiemerslage L, Gohel P, Kheder S, Kothegala LV, Schiöth HB | title = Dibutyl Phthalate Exposure Disrupts Evolutionarily Conserved Insulin and Glucagon-Like Signaling in Drosophila Males. | journal = Endocrinology | year = 2016 | pmid = 27100621 | doi = 10.1210/en.2015-2006 | volume=157 | issue = 6 | pages=2309–21| doi-access = free }}</ref> === Perfluorooctanoic acid === {{main|Perfluorooctanoic acid}} PFOA is a stable chemical that has been used for its grease-, fire-, and water-resistant properties in products such as [[Non-stick surface|non-stick]] pan coatings, furniture, firefighter equipment, industrial, and other common household items.<ref>{{cite journal | vauthors = Steenland K, Fletcher T, Savitz DA | title = Epidemiologic evidence on the health effects of perfluorooctanoic acid (PFOA) | journal = Environmental Health Perspectives | volume = 118 | issue = 8 | pages = 1100–1108 | date = August 2010 | pmid = 20423814 | pmc = 2920088 | doi = 10.1289/ehp.0901827 | bibcode = 2010EnvHP.118.1100S }}</ref><ref name="Chaparro-Ortega_2018">{{cite journal | vauthors = Chaparro-Ortega A, Betancourt M, Rosas P, Vázquez-Cuevas FG, Chavira R, Bonilla E, Casas E, Ducolomb Y | title = Endocrine disruptor effect of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on porcine ovarian cell steroidogenesis | journal = Toxicology in Vitro | volume = 46 | pages = 86–93 | date = February 2018 | pmid = 28982594 | doi = 10.1016/j.tiv.2017.09.030 | bibcode = 2018ToxVi..46...86C }}</ref> There is evidence to suggest that PFOA is an endocrine disruptor affecting male and female reproductive systems.<ref name="Chaparro-Ortega_2018"/> PFOA delivered to pregnant rats produced male offspring with decreased levels of 3-β and 17-β-hydroxysteroid dehydrogenase,<ref name="Chaparro-Ortega_2018" /> a gene that transcribes for proteins involved in the production of sperm.<ref>{{cite journal | vauthors = Ben Rhouma B, Kallabi F, Mahfoudh N, Ben Mahmoud A, Engeli RT, Kamoun H, Keskes L, Odermatt A, Belguith N | title = Novel cases of Tunisian patients with mutations in the gene encoding 17β-hydroxysteroid dehydrogenase type 3 and a founder effect | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 165 | issue = Pt A | pages = 86–94 | date = January 2017 | pmid = 26956191 | doi = 10.1016/j.jsbmb.2016.03.007 | s2cid = 25889473 }}</ref> Adult women have exhibited low progesterone and androstenedione production when exposed to PFOA, leading to menstrual and reproductive health issues.<ref name="Chaparro-Ortega_2018"/> [[PFOA]] exerts hormonal effects including alteration of thyroid hormone levels. Blood serum levels of PFOA were associated with an increased time to pregnancy—or "infertility"—in a 2009 study. PFOA exposure is associated with decreased semen quality. PFOA appeared to act as an endocrine disruptor by a potential mechanism on breast maturation in young girls. A C8 Science Panel status report noted an association between exposure in girls and a later onset of puberty. === Other suspected endocrine disruptors === Some other examples of putative EDCs are [[Dioxins and dioxin-like compounds|polychlorinated dibenzo-dioxins]] (PCDDs) and [[Polychlorinated dibenzofurans|-furan]]s (PCDFs), [[polycyclic aromatic hydrocarbon]]s (PAHs), [[phenols|phenol derivatives]] and a number of [[pesticides]] (most prominent being [[organochlorine]] insecticides like [[endosulfan]], [[kepone]] (chlordecone) and [[DDT]] and its derivatives, the herbicide [[atrazine]], and the fungicide [[vinclozolin]]), the contraceptive 17-alpha [[ethinylestradiol]], as well as naturally occurring [[phytoestrogens]] such as [[genistein]] and [[mycoestrogens]] such as [[zearalenone]]. The molting in crustaceans is an endocrine-controlled process. In the marine penaeid shrimp ''[[whiteleg shrimp|Litopenaeus vannamei]]'', exposure to [[endosulfan]] resulted increased susceptibility to acute toxicity and increased mortalities in the postmolt stage of the shrimp.<ref name="pmid22119282">{{cite journal |vauthors=Tumburu L, Shepard EF, Strand AE, Browdy CL | title = Effects of endosulfan exposure and Taura Syndrome Virus infection on the survival and molting of the marine penaeid shrimp, Litopenaeus vannamei | journal = Chemosphere | volume = 86| issue = 9| pages = 912–8|date=November 2011 | pmid = 22119282 | doi = 10.1016/j.chemosphere.2011.10.057 }}</ref> Many sunscreens contain [[oxybenzone]], a chemical blocker that provides broad-spectrum UV coverage, yet is subject to a lot of controversy due its potential estrogenic effect in humans.<ref>{{cite journal | vauthors = Burnett ME, Wang SQ | s2cid = 29173997 | title = Current sunscreen controversies: a critical review | journal = Photodermatology, Photoimmunology & Photomedicine | volume = 27 | issue = 2 | pages = 58–67 | date = April 2011 | pmid = 21392107 | doi = 10.1111/j.1600-0781.2011.00557.x | doi-access = free }}</ref> [[Tributyltin]] (TBT) are organotin compounds. For 40 years TBT was used as a [[biocide]] in [[anti-fouling paint]], commonly known as bottom paint. TBT has been shown to impact invertebrate and vertebrate development, disrupting the endocrine system, resulting in masculinization, lower survival rates, as well as many health problems in mammals. ==Temporal trends of body burden== Since being banned, the average human [[body burden]]s of DDT and PCB have been declining.<ref name="Fürst_2006"/><ref name="Knobeloch_2009">{{cite journal |vauthors=Knobeloch L, Turyk M, Imm P, Schrank C, Anderson H | title = Temporal changes in PCB and DDE levels among a cohort of frequent and infrequent consumers of Great Lakes sportfish | journal = Environ. Res. | volume = 109 | issue = 1 | pages = 66–72 |date=January 2009 | pmid = 18950754 | doi = 10.1016/j.envres.2008.08.010 | bibcode = 2009ER....109...66K }}</ref><ref name="Norén_2000">{{cite journal |vauthors=Norén K, Meironyté D | title = Certain organochlorine and organobromine contaminants in Swedish human milk in perspective of past 20-30 years | journal = Chemosphere | volume = 40 | issue = 9–11 | pages = 1111–23 | year = 2000 | pmid = 10739053 | doi = 10.1016/S0045-6535(99)00360-4 | bibcode = 2000Chmsp..40.1111N }}</ref> Since their ban in 1972, the PCB body burden in 2009 is one-hundredth of what it was in the early 1980s. On the other hand, monitoring programs of European breast milk samples have shown that PBDE levels are increasing.<ref name="Fürst_2006"/><ref name="Norén_2000"/> An analysis of PBDE content in breast milk samples from Europe, Canada, and the US shows that levels are 40 times higher for North American women than for Swedish women, and that levels in North America are doubling every two to six years.<ref name="Hites_2004">{{cite journal | vauthors = Hites RA | title = Polybrominated diphenyl ethers in the environment and in people: a meta-analysis of concentrations | journal = Environmental Science & Technology | volume = 38 | issue = 4 | pages = 945–956 | date = February 2004 | pmid = 14998004 | doi = 10.1021/es035082g | s2cid = 32909270 | bibcode = 2004EnST...38..945H }}</ref><ref name="Betts_2002">{{cite journal | vauthors = Betts KS | title = Rapidly rising PBDE levels in North America | journal = Environmental Science & Technology | volume = 36 | issue = 3 | pages = 50A–52A | date = February 2002 | pmid = 11871568 | doi = 10.1021/es022197w | doi-access = free | bibcode = 2002EnST...36...50B }}</ref> It has been discussed that the long-term slow decline in average body temperature observed since the beginning of the industrial revolution<ref>{{cite journal | vauthors = Protsiv M, Ley C, Lankester J, Hastie T, [[Julie Parsonnet|Parsonnet J]] | title = Decreasing human body temperature in the United States since the industrial revolution | journal = eLife | volume = 9 | date = January 2020 | pmid = 31908267 | pmc = 6946399 | doi = 10.7554/eLife.49555 | doi-access = free }}</ref> may result from disrupted thyroid hormone signalling.<ref>{{cite journal | vauthors = Vancamp P, Demeneix BA | title = Is the Observed Decrease in Body Temperature During Industrialization Due to Thyroid Hormone-Dependent Thermoregulation Disruption? | journal = Frontiers in Endocrinology | volume = 11 | pages = 470 | date = 22 July 2020 | pmid = 32793119 | pmc = 7387406 | doi = 10.3389/fendo.2020.00470 | doi-access = free }}</ref> == Animal models == As endocrine disruptors affect complex metabolic, reproductive, and neuroendocrine systems, animal models may be used to assess the risk of endocrine disrupting chemicals.<ref name="pmid29779582">{{cite journal | vauthors = Patisaul HB, Fenton SE, Aylor D | title = Animal models of endocrine disruption | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 32 | issue = 3 | pages = 283–297 | date = June 2018 | pmid = 29779582 | pmc = 6029710 | doi = 10.1016/j.beem.2018.03.011 }}</ref> Some common animal models used for assessing these risks are mice, fish egg yolks, and frogs.<ref>{{Cite web |title=Endocrine disruptor assessment {{!}} NC3Rs |url=https://nc3rs.org.uk/3rs-resource-library/endocrine-disruptor-assessment#:~:text=Many%20animals,%20typically%20fish,%20frogs,in%20humans%20and%20wildlife%20populations. |access-date=2025-02-10 |website=nc3rs.org.uk |language=en}}</ref> ===Mice=== [[File:Lab mouse mg 3216.jpg|thumb|A mouse in a laboratory setting]] Genetically-engineered mice can be used as population-based genetic foundations. For instance, one population is named ''multi-parent'' and can be a ''collaborative cross'' (CC) or ''diversity outbred'' (DO) strain.<ref name="pmid21406540">{{cite journal | vauthors = Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, Baric RS, Ferris MT, Frelinger JA, Heise M, Frieman MB, Gralinski LE, Bell TA, Didion JD, Hua K, Nehrenberg DL, Powell CL, Steigerwalt J, Xie Y, Kelada SN, Collins FS, Yang IV, Schwartz DA, Branstetter LA, Chesler EJ, Miller DR, Spence J, Liu EY, McMillan L, Sarkar A, Wang J, Wang W, Zhang Q, Broman KW, Korstanje R, Durrant C, Mott R, Iraqi FA, Pomp D, Threadgill D, de Villena FP, Churchill GA|display-authors=3 | title = Genetic analysis of complex traits in the emerging Collaborative Cross | journal = Genome Research | volume = 21 | issue = 8 | pages = 1213–22 | date = August 2011 | pmid = 21406540 | pmc = 3149489 | doi = 10.1101/gr.111310.110 }}</ref><ref name="pmid22345604">{{cite journal | vauthors = Threadgill DW, Churchill GA | title = Ten years of the Collaborative Cross | journal = Genetics | volume = 190 | issue = 2 | pages = 291–4 | date = February 2012 | pmid = 22345604 | pmc = 3276648 | doi = 10.1534/genetics.111.138032 }}</ref><ref name="pmid11956758">{{cite journal | vauthors = Threadgill DW, Hunter KW, Williams RW | title = Genetic dissection of complex and quantitative traits: from fantasy to reality via a community effort | journal = Mammalian Genome | volume = 13 | issue = 4 | pages = 175–8 | date = April 2002 | pmid = 11956758 | doi = 10.1007/s00335-001-4001-Y | s2cid = 17568717 }}</ref> The eight founder strains combine strains that are wild-derived (with high genetic diversity) and research bred strains. Each genetically differential line is used to assess EDCs responses.<ref name="pmid19750107">{{cite journal | vauthors = La Merrill M, Kuruvilla BS, Pomp D, Birnbaum LS, Threadgill DW | title = Dietary fat alters body composition, mammary development, and cytochrome p450 induction after maternal TCDD exposure in DBA/2J mice with low-responsive aryl hydrocarbon receptors | journal = Environmental Health Perspectives | volume = 117 | issue = 9 | pages = 1414–9 | date = September 2009 | pmid = 19750107 | pmc = 2737019 | doi = 10.1289/ehp.0800530 | bibcode = 2009EnvHP.117.1414L }}</ref> The CC population consists of 83 inbred mouse strains that over many generations in labs came from the eight founder strains. While DO mice have the identical alleles to the CC mice population, there are two major differences: every individual is unique, allowing for hundreds of individuals to be applied in one mapping study, making DO mice useful for determining genetic relationships; however, DO individuals cannot be reproduced.{{cn|date=April 2025}} ===Transgenic=== These rodents, mainly mice, have been bred by inserting other genes from another organism to make transgenic lines (thousands of lines) of rodents, in a technique such as [[CRISPR]].<ref name="pmid26397828">{{cite journal | vauthors = Rocha-Martins M, Cavalheiro GR, Matos-Rodrigues GE, Martins RA | title = From Gene Targeting to Genome Editing: Transgenic animals applications and beyond | journal = Anais da Academia Brasileira de Ciências | volume = 87 | issue = 2 Suppl | pages = 1323–48 | date = August 2015 | pmid = 26397828 | doi = 10.1590/0001-3765201520140710 | doi-access = free }}</ref> Genes may be manipulated in a particular cell populations if done under the correct conditions.<ref name="pmid25545386">{{cite journal | vauthors = Dubois SL, Acosta-Martínez M, DeJoseph MR, Wolfe A, Radovick S, Boehm U, Urban JH, Levine JE | title = Positive, but not negative feedback actions of estradiol in adult female mice require estrogen receptor α in kisspeptin neurons | journal = Endocrinology | volume = 156 | issue = 3 | pages = 1111–20 | date = March 2015 | pmid = 25545386 | pmc = 4330313 | doi = 10.1210/en.2014-1851 }}</ref> For endocrine-disrupting chemical research, these rodents are used to produce [[humanized mouse]] models.<ref name="Stefkovich_2018">{{cite journal | vauthors = Stefkovich ML, Arao Y, Hamilton KJ, Korach KS | title = Experimental models for evaluating non-genomic estrogen signaling | journal = Steroids | volume = 133 | pages = 34–37 | date = May 2018 | pmid = 29122548 | pmc = 5864539 | doi = 10.1016/j.steroids.2017.11.001 }}</ref> Additionally, scientists use [[gene knockout]] lines of mice in order to study how certain mechanisms work when impacted by EDCs.<ref name="Stefkovich_2018" /><ref name="pmid20577047">{{cite journal | vauthors = Chambliss KL, Wu Q, Oltmann S, Konaniah ES, Umetani M, Korach KS, Thomas GD, Mineo C, Yuhanna IS, Kim SH, Madak-Erdogan Z, Maggi A, Dineen SP, Roland CL, Hui DY, Brekken RA, Katzenellenbogen JA, Katzenellenbogen BS, Shaul PW|display-authors=3 | title = Non-nuclear estrogen receptor alpha signaling promotes cardiovascular protection but not uterine or breast cancer growth in mice | journal = The Journal of Clinical Investigation | volume = 120 | issue = 7 | pages = 2319–30 | date = July 2010 | pmid = 20577047 | pmc = 2898582 | doi = 10.1172/JCI38291 }}</ref> Transgenic rodents are used to study mechanisms impacted by EDC, but take a long time to produce and are expensive.{{cn|date=April 2025}} ===Social models=== Experiments (gene by environment) with rodent models may be able to discover if there are mechanisms that EDCs could impact in behavioral disorders.<ref name="McGraw_2010">{{cite journal | vauthors = McGraw LA, Young LJ | title = The prairie vole: an emerging model organism for understanding the social brain | journal = Trends in Neurosciences | volume = 33 | issue = 2 | pages = 103–9 | date = February 2010 | pmid = 20005580 | pmc = 2822034 | doi = 10.1016/j.tins.2009.11.006 }}</ref> This is because [[Prairie vole|prairie]] and [[Woodland vole|pine voles]] are socially monogamous, making them a better model for human social behaviors and development in relation to EDCs.<ref name="Adkins-Regan_2009">{{cite journal | vauthors = Adkins-Regan E | title = Neuroendocrinology of social behavior | journal = ILAR Journal | volume = 50 | issue = 1 | pages = 5–14 | date = 2009 | pmid = 19106448 | doi = 10.1093/ilar.50.1.5 | doi-access = free }}</ref><ref name="Albers_2015">{{cite journal | vauthors = Albers HE | title = Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network | journal = Frontiers in Neuroendocrinology | volume = 36 | pages = 49–71 | date = January 2015 | pmid = 25102443 | doi = 10.1016/j.yfrne.2014.07.001 | pmc = 4317378 }}</ref><ref name="pmid27102938">{{cite journal | vauthors = Rebuli ME, Gibson P, Rhodes CL, Cushing BS, Patisaul HB | title = Sex differences in microglial colonization and vulnerabilities to endocrine disruption in the social brain | journal = General and Comparative Endocrinology | volume = 238 | pages = 39–46 | date = November 2016 | pmid = 27102938 | pmc = 5067172 | doi = 10.1016/j.ygcen.2016.04.018 }}</ref> ===Zebrafish=== [[File:Weizmann's labs (10).jpg|thumb|Zebrafish being studied in a laboratory]] The endocrine systems between mammals and fish are similar; because of this, [[zebrafish]] (''Danio rerio'') may be used.<ref name="Segner_2009">{{cite journal | vauthors = Segner H | title = Zebrafish (Danio rerio) as a model organism for investigating endocrine disruption | journal = Comparative Biochemistry and Physiology. Toxicology & Pharmacology | volume = 149 | issue = 2 | pages = 187–95 | date = March 2009 | pmid = 18955160 | doi = 10.1016/j.cbpc.2008.10.099 }}</ref>{{better source|date=April 2025}} The zebrafish embryos are transparent, relatively small fish (larvae are less than a few millimeters in size),<ref name="Reif_2016">{{cite journal | vauthors = Reif DM, Truong L, Mandrell D, Marvel S, Zhang G, Tanguay RL | title = High-throughput characterization of chemical-associated embryonic behavioral changes predicts teratogenic outcomes | journal = Archives of Toxicology | volume = 90 | issue = 6 | pages = 1459–1470 | date = June 2016 | pmid = 26126630 | pmc = 4701642 | doi = 10.1007/s00204-015-1554-1 | bibcode = 2016ArTox..90.1459R }}</ref> and have simple modes of endocrine disruption,<ref>{{cite journal | vauthors = Blanc M, Antczak P, Cousin X, Grunau C, Scherbak N, Rüegg J, Keiter SH | title = The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio) | journal = The Science of the Total Environment | volume = 779 | pages = 146404 | date = July 2021 | pmid = 33752003 | doi = 10.1016/j.scitotenv.2021.146404 | s2cid = 232323014 | doi-access = free | bibcode = 2021ScTEn.77946404B }}</ref> along with homologous physiological, sensory, anatomical and signal-transduction mechanisms similar to mammals. Another helpful tool available to scientists is their recorded genome along with multiple [[Transgene|transgenic]] lines accessible for breeding. Zebrafish and mammalian genomes when compared have prominent similarities with about 80% of human genes expressed in the fish.<ref name="pmid24136191">{{cite journal | vauthors = Truong L, Reif DM, St Mary L, Geier MC, Truong HD, Tanguay RL | title = Multidimensional in vivo hazard assessment using zebrafish | journal = Toxicological Sciences | volume = 137 | issue = 1 | pages = 212–233 | date = January 2014 | pmid = 24136191 | pmc = 3871932 | doi = 10.1093/toxsci/kft235 }}</ref><ref name="pmid23594743">{{cite journal | vauthors = Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, etal | title = The zebrafish reference genome sequence and its relationship to the human genome | journal = Nature | volume = 496 | issue = 7446 | pages = 498–503 | date = April 2013 | pmid = 23594743 | pmc = 3703927 | doi = 10.1038/nature12111 | bibcode = 2013Natur.496..498H }}</ref><ref name="Reif_2016" /> ==Directions of research== Research on endocrine disruptors is challenged by five complexities requiring special trial designs and sophisticated study protocols:<ref name="Dietrich_2019">{{cite book | vauthors = Dietrich JW |title=Intelligenzabnahme in der Bevölkerung entwickelter Länder: Der negative "Flynn-Effekt" – die unbekannte Seite endokriner Disruptoren. In: Schatz H, Weber M: Endokrinologie – Diabetologie – Stoffwechsel: Neues über Hormone und Metabolismus im Jahre 2019 |year=2020 |publisher=Wecom |location=Hildesheim |isbn=978-3-00-065109-0 |pages=35–39}}</ref> # The ''dissociation of space'' means that, although disruptors may act by a common pathway via [[hormone receptor]]s, their impact may also be mediated by effects at the levels of [[transport protein]]s, [[deiodinase]]s, degradation of hormones or modified [[Set point (endocrinology)|setpoint]]s of [[feedback loop]]s (i.e. [[allostatic load]]).<ref name="Demeneix_Europarl_2019">{{cite web | vauthors = Demeneix B, Slama R |title=Endocrine Disruptors: from Scientific Evidence to Human Health Protection |url=http://www.europarl.europa.eu/RegData/etudes/STUD/2019/608866/IPOL_STU(2019)608866_EN.pdf |publisher=European Parliament |access-date=6 May 2020}}</ref> # The ''dissociation of time'' may ensue from the fact that unwanted effects may be triggered in a small time window in the [[Embryonic development|embryonal]] or [[Fetal programming|fetal]] period, but consequences may ensue decades later or even in the generation of grandchildren.<ref name = "Stacy2017">{{cite journal | vauthors = Stacy SL, Papandonatos GD, Calafat AM, Chen A, Yolton K, Lanphear BP, Braun JM | title = Early life bisphenol A exposure and neurobehavior at 8years of age: Identifying windows of heightened vulnerability | journal = Environment International | volume = 107 | pages = 258–265 | date = October 2017 | pmid = 28764921 | pmc = 5567845 | doi = 10.1016/j.envint.2017.07.021 | bibcode = 2017EnInt.107..258S }}</ref> # The ''dissociation of substance'' results from additive, multiplicative or more complex interactions of disruptors in combination that yield fundamentally different effects from that of the respective substances alone.<ref name="Dietrich_2019"/> # The ''dissociation of dose'' implies that dose-effect relationships use to be nonlinear and sometimes even [[#U-shaped dose-response curve|U-shaped]], so that low or medium doses may have stronger effects than high doses.<ref name="Demeneix_Europarl_2019"/> # The ''dissociation of sex'' reflects the fact that effects may be different depending on whether embryos or fetuses are female or male.<ref name = "Stacy2017"/><ref>{{cite journal | vauthors = Nakiwala D, Peyre H, Heude B, Bernard JY, Béranger R, Slama R, Philippat C | title = In-utero exposure to phenols and phthalates and the intelligence quotient of boys at 5 years | journal = Environmental Health | volume = 17 | issue = 1 | pages = 17 | date = February 2018 | pmid = 29458359 | pmc = 5819230 | doi = 10.1186/s12940-018-0359-0 | doi-access = free | bibcode = 2018EnvHe..17...17N }}</ref> ==Legal approach== ===United States=== The multitude of possible endocrine disruptors are technically regulated in the United States by many laws, including the [[Toxic Substances Control Act]], the [[Food Quality Protection Act]],<ref name=":0">{{cite web | vauthors = Wayland S, Fenner-Crisp P | url = http://www.epaalumni.org/hcp/pesticides.pdf | title = Reducing Pesticide Risks: A Half Century of Progress. | work = EPA Alumni Association | date = March 2016 }}</ref> the [[Food, Drug and Cosmetic Act]], the [[Clean Water Act]], the [[Safe Drinking Water Act]], and the [[Clean Air Act (United States)|Clean Air Act]]. The [[Congress of the United States]] has improved the evaluation and regulation process of drugs and other chemicals. The Food Quality Protection Act of 1996 and the Safe Drinking Water Act of 1996 simultaneously provided the first legislative direction requiring the [[EPA]] to address endocrine disruption through establishment of a program for screening and testing of chemical substances. In 1998, the EPA announced the Endocrine Disruptor Screening Program by establishment of a framework for priority setting, screening and testing more than 85,000 chemicals in commerce. While the Food Quality Protection Act only required the EPA to screen pesticides for potential to produce effects similar to estrogens in humans, it also gave the EPA the authority to screen other types of chemicals and endocrine effects.<ref name=":0" /> Based on recommendations from an advisory panel, the agency expanded the screening program to include male hormones, the thyroid system, and effects on fish and other wildlife.<ref name=":0" /> The basic concept behind the program is that prioritization will be based on existing information about chemical uses, production volume, structure-activity and toxicity. Screening is done by use of ''in vitro'' test systems (by examining, for instance, if an agent interacts with the [[estrogen receptor]] or the [[androgen receptor]]) and via the use of in animal models, such as development of tadpoles and uterine growth in prepubertal rodents. Full-scale testing will examine effects not only in mammals (rats) but also in a number of other species (frogs, fish, birds and invertebrates). Since the theory involves the effects of these substances on a functioning system, animal testing is essential for scientific validity, but has been opposed by [[animal rights]] groups. Similarly, proof that these effects occur in humans would require human testing, and such testing also has opposition. After failing to meet several deadlines to begin testing, the EPA finally announced that they were ready to begin the process of testing dozens of chemical entities that are suspected endocrine disruptors early in 2007, eleven years after the program was announced. When the final structure of the tests was announced there was objection to their design. Critics have charged that the entire process has been compromised by chemical company interference.<ref name="urlScientists criticize EPA chemical screening program | News for Dallas, Texas | Dallas Morning News | Science and Medicine | Health">{{cite web | url = http://www.dallasnews.com/sharedcontent/dws/news/healthscience/stories/052707dnentendocrine.3a08215.html | title = Scientists criticize EPA chemical screening program | vauthors = Ambrose SG | date = 27 May 2007 | publisher = Dallas Morning News | access-date = 14 March 2009}}</ref> In 2005, the EPA appointed a panel of experts to conduct an open peer-review of the program and its orientation. Their results found that "the long-term goals and science questions in the EDC program are appropriate",<ref name="pmid16882539">{{cite journal |vauthors=Harding AK, Daston GP, Boyd GR, Lucier GW, Safe SH, Stewart J, Tillitt DE, Van Der Kraak G | title = Endocrine disrupting chemicals research program of the U.S. Environmental Protection Agency: summary of a peer-review report | journal = Environmental Health Perspectives| volume = 114 | issue = 8 | pages = 1276–82 |date=August 2006 | pmid = 16882539 | pmc = 1552001 | doi = 10.1289/ehp.8875 | bibcode = 2006EnvHP.114.1276H }}</ref> however this study was conducted over a year before the EPA announced the final structure of the screening program. The EPA is still finding it difficult to execute a credible and efficient endocrine testing program.<ref name=":0" /> As of 2016, the EPA had estrogen screening results for 1,800 chemicals.<ref name=":0" /> ===Europe=== In 2013, a number of pesticides containing endocrine disrupting chemicals were in draft EU criteria to be banned. On 2 May, US [[Transatlantic Trade and Investment Partnership]] (TTIP) negotiators insisted the EU drop the criteria. They stated that a risk-based approach should be taken on regulation. Later the same day [[Catherine Day (civil servant)|Catherine Day]] wrote to Karl Falkenberg asking for the criteria to be removed.{{r|guardian22may15}} The [[European Commission]] had been to set criteria by December 2013 identifying endocrine-disrupting chemicals (EDCs) in thousands of products—including disinfectants, pesticides and toiletries—that have been linked to cancers, birth defects and development disorders in children. However, the body delayed the process, prompting Sweden to state that it would sue the commission in May 2014—blaming chemical industry lobbying for the disruption.<ref name="capitalfm.co.ke">{{cite news|url=http://www.capitalfm.co.ke/business/2014/05/sweden-to-sue-eu-for-delay-on-hormone-disrupting-chemicals/|title=Sweden to sue EU for delay on hormone disrupting chemicals|date=22 May 2014|access-date=10 October 2015}}</ref> "This delay is due to the European chemical lobby, which put pressure again on different commissioners. Hormone disrupters are becoming a huge problem. In some places in [[Sweden]] we see double-sexed fish. We have scientific reports on how this affects fertility of young boys and girls, and other serious effects," Swedish Environment Minister [[Lena Ek]] told the [[Agence France-Presse|AFP]], noting that [[Denmark]] had also demanded action.<ref name="capitalfm.co.ke"/> In November 2014, the [[Copenhagen]]-based [[Nordic Council of Ministers]] released its own independent report that estimated the impact of environmental EDCs on male reproductive health, and the resulting cost to [[public health]] systems. It concluded that EDCs likely cost [[health system]]s across the EU anywhere from 59 million to 1.18 billion Euros a year, noting that even this represented only "a fraction of the endocrine related diseases".<ref>{{cite web|url=http://norden.diva-portal.org/smash/record.jsf?pid=diva2%3A763442&dswid=6377|title=The Cost of Inaction: A Socioeconomic analysis of costs linked to effects of endocrine disrupting substances on male reproductive health| vauthors = Olsson IM |date=24 November 2014|access-date=10 October 2015}}</ref> In 2020, the EU published their [[Chemicals Strategy for Sustainability]] which is concerned with a [[green transition]] of the chemical industry away from xenohormones and other [[hazardous chemical]]s. == Environmental and human body cleanup == There is evidence that once a pollutant is no longer in use, or once its use is heavily restricted, the human [[body burden]] of that pollutant declines. Through the efforts of several large-scale monitoring programs,<ref name="cdc:105345"/><ref name="urlCalifornia Biomonitoring Program,">{{cite web | url = http://www.cdph.ca.gov/programs/Biomonitoring/Pages/default.aspx | title = California Biomonitoring Program | publisher = State of California | access-date = 14 March 2009 | archive-url = https://web.archive.org/web/20090316072400/http://www.cdph.ca.gov/programs/Biomonitoring/Pages/default.aspx | archive-date = 16 March 2009 | url-status = dead }}</ref> the most prevalent pollutants in the human population are fairly well known. The first step in reducing the body burden of these pollutants is eliminating or phasing out their production. The second step toward lowering human body burden is awareness of and potentially labeling foods that are likely to contain high amounts of pollutants. This strategy has worked in the past—pregnant and nursing women are [[Mercury in fish|cautioned against eating seafood]] that is known to accumulate high levels of mercury.<ref>{{Cite web | work = U.S. Environmental Protection Agency |date=10 November 2014 |title=Fish and Shellfish Advisories and Safe Eating Guidelines |url=https://www.epa.gov/choose-fish-and-shellfish-wisely/fish-and-shellfish-advisories-and-safe-eating-guidelines |access-date=4 March 2023 |language=en}}</ref> The most challenging aspect of this problem is discovering how to eliminate these compounds from the environment and where to focus remediation efforts. Even pollutants no longer in production persist in the environment and bio-accumulate in the food chain. An understanding of how these chemicals, once in the environment, move through ecosystems, is essential to designing ways to isolate and remove them. Global efforts have been made to label the most common POPs routinely found in the environment through usage of chemicals like insecticides. The twelve main POPs have been evaluated and placed in a demographic so as to streamline the information around the general population. Such facilitation has allowed nations around the world to effectively work on the testing and reduction of the usage of these chemicals. With an effort to reduce the presence of such chemicals in the environment, they can reduce the leaching of POPs into food sources which contaminate the animals commercially fed to the U.S. population.<ref>{{cite journal | vauthors = Guo W, Pan B, Sakkiah S, Yavas G, Ge W, Zou W, Tong W, Hong H | title = Persistent Organic Pollutants in Food: Contamination Sources, Health Effects and Detection Methods | journal = International Journal of Environmental Research and Public Health | volume = 16 | issue = 22 | pages = 4361 | date = November 2019 | pmid = 31717330 | pmc = 6888492 | doi = 10.3390/ijerph16224361 | doi-access = free }}</ref> Many persistent organic compounds, PCB, DDT and PBDE included, accumulate in river and marine sediments. Several processes are currently being used by the EPA to clean up heavily polluted areas, as outlined in their [[Green Remediation]] program.<ref name="urlCLU-IN.ORG | Green Remediation | Overview">{{cite web | url = http://www.clu-in.org/greenremediation | title = Green Remediation | publisher = United States Environmental Protection Agency | access-date = 14 March 2009 | archive-date = 15 March 2009 | archive-url = https://web.archive.org/web/20090315092458/http://www.clu-in.org/greenremediation/ | url-status = dead }}</ref> Naturally occurring microbes that degrade PCB congeners to remediate contaminated areas are utilized.<ref name="Field_2008">{{cite journal |vauthors=Field JA, Sierra-Alvarez R | title = Microbial transformation and degradation of polychlorinated biphenyls | journal = Environ. Pollut. | volume = 155 | issue = 1 | pages = 1–12 |date=September 2008 | pmid = 18035460 | doi = 10.1016/j.envpol.2007.10.016 | bibcode = 2008EPoll.155....1F }}</ref> There are many success stories of cleanup efforts of large heavily contaminated [[Superfund]] sites. A {{convert|10|acre|m2|adj=on}} landfill in Austin, Texas, contaminated with illegally dumped [[Volatile organic compound|VOCs]] was restored in a year to a wetland and educational park.<ref name="urlCLU-IN.ORG | Green Remediation | Profiles of Green Strategies | Rhizome Collective Inc. Brownfield Site, Austin, TX">{{cite web | url = http://www.clu-in.org/greenremediation/subtab_d11.cfm | title = Profiles of Green Strategies: Rhizome Collective Inc. Brownfield Site, Austin, TX | work = Green Remediation | publisher = United States Environmental Protection Agency | access-date = 14 March 2009 | archive-date = 17 March 2009 | archive-url = https://web.archive.org/web/20090317084121/http://www.clu-in.org/greenremediation/subtab_d11.cfm | url-status = dead }}</ref> A US uranium enrichment site that was contaminated with uranium and PCBs was cleaned up with high tech equipment used to find the pollutants within the soil.<ref name="urlCLU-IN.ORG | Green Remediation | Profiles & Case Studies of Green Remediation | Paducah Gaseous Diffusion Plant, Paducah, KY">{{cite web | url = http://www.clu-in.org/greenremediation/subtab_d28.cfm | title = Profiles & Case Studies of Green Remediation: Paducah Gaseous Diffusion Plant, Paducah, KY | work = Green Remediation | publisher = United States Environmental Protection Agency | access-date = 14 March 2009 | archive-date = 17 March 2009 | archive-url = https://web.archive.org/web/20090317004948/http://www.clu-in.org/greenremediation/subtab_d28.cfm | url-status = dead }}</ref> The soil and water at a polluted wetlands site were cleaned of VOCs, PCBs and lead, native plants were installed as [[Biofilter|biological filters]], and a community program was implemented to ensure ongoing monitoring of pollutant concentrations in the area.<ref name="urlCLU-IN.ORG | Green Remediation | Profiles & Case Studies of Green Remediation: Re-Solve, Inc., North Dartmouth, MA">{{cite web | url = http://www.clu-in.org/greenremediation/subtab_d29.cfm | title = Case Studies of Green Remediation: Re-Solve, Inc., North Dartmouth, MA | work = Green Remediation | publisher = United States Environmental Protection Agency | access-date = 14 March 2009 | archive-date = 15 March 2009 | archive-url = https://web.archive.org/web/20090315194428/http://www.clu-in.org/greenremediation/subtab_d29.cfm | url-status = dead }}</ref> These case studies are encouraging due to the short amount of time needed to remediate the site and the high level of success achieved. Studies suggest that bisphenol A,<ref name="pmid22253637">{{cite journal |vauthors=Genuis SJ, Beesoon S, Birkholz D, Lobo RA |title=Human excretion of bisphenol A: blood, urine, and sweat (BUS) study |journal=J Environ Public Health |volume=2012 |pages=1–10 |year=2012 |pmid=22253637 |pmc=3255175 |doi=10.1155/2012/185731 |doi-access=free }}</ref> certain PCBs,<ref name="pmid24083032">{{cite journal |vauthors=Genuis SJ, Beesoon S, Birkholz D |title=Biomonitoring and Elimination of Perfluorinated Compounds and Polychlorinated Biphenyls through Perspiration: Blood, Urine, and Sweat Study |journal=ISRN Toxicol |volume=2013 |pages=1–7 |year=2013 |pmid=24083032 |pmc=3776372 |doi=10.1155/2013/483832 |doi-access=free }}</ref> and phthalate compounds<ref name="pmid23213291">{{cite journal |vauthors=Genuis SJ, Beesoon S, Lobo RA, Birkholz D |title=Human elimination of phthalate compounds: blood, urine, and sweat (BUS) study |journal=ScientificWorldJournal |volume=2012 |pages=1–10 |year=2012 |pmid=23213291 |pmc=3504417 |doi=10.1100/2012/615068 |doi-access=free }}</ref> are preferentially eliminated from the human body through sweat. Although some pollutants like bisphenol A (BPA) are preferentially eliminated from the human body through sweat, recent scientific advances have been made to increase the rate of elimination of pollutants from the human body. For example, BPA removal techniques have been proposed that use enzymes such as [[laccase]] and [[peroxidase]] to degrade BPA into less harmful compounds. Another technique for BPA removal is the use of highly reactive radicals for degradation.<ref>{{Cite journal | vauthors = Ohore OE, Zhang S |date= 1 September 2019 |title=Endocrine disrupting effects of bisphenol A exposure and recent advances on its removal by water treatment systems. A review |journal=Scientific African |language=en |volume=5 |pages=e00135 |doi=10.1016/j.sciaf.2019.e00135 |bibcode= 2019SciAf...500135O |s2cid= 202079156 |issn=2468-2276|doi-access=free }}</ref> == Economic effects == Human exposure may cause some health effects, such as lower [[Intelligence quotient|IQ]], adult [[obesity]], female [[Reproductive system disease|reproductive disorders]], and male reproductive disorders.<ref name=":3">{{Cite journal |last=Kassotis |first=Christopher D. |last2=Vandenberg |first2=Laura N. |last3=Demeneix |first3=Barbara A. |last4=Porta |first4=Miquel |last5=Slama |first5=Remy |last6=Trasande |first6=Leonardo |date=August 2020 |title=Endocrine-disrupting chemicals: economic, regulatory, and policy implications |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC7437819/ |journal=The Lancet. Diabetes & Endocrinology |volume=8 |issue=8 |pages=719–730 |doi=10.1016/S2213-8587(20)30128-5 |issn=2213-8595 |pmc=7437819 |pmid=32707119}}</ref> These effects may lead to lost productivity, disability, or premature death in some people. One source estimated that, within the [[European Union]], this economic effect might have about twice the [[Economic impact analysis|economic impact]] as the effects caused by mercury and [[Lead poisoning|lead contamination]].<ref name="pmid25742516">{{cite journal |author5-link=Philippe Grandjean (professor) |vauthors=Trasande L, Zoeller RT, Hass U, Kortenkamp A, Grandjean P, Myers JP, DiGangi J, Bellanger M, Hauser R, Legler J, Skakkebaek NE, Heindel JJ |date=2015 |title=Estimating burden and disease costs of exposure to endocrine-disrupting chemicals in the European union |journal=The Journal of Clinical Endocrinology and Metabolism |volume=100 |issue=4 |pages=1245–55 |doi=10.1210/jc.2014-4324 |pmc=4399291 |pmid=25742516}}</ref> Within the last 5 years, the socio-economic burden of EDC-associated health effects was recorded at an estimated annual cost of €163 in the EU and $340 billion in the USA, which can even be viewed as an underestimate due to how many health outcomes take place due to EDC exposure<ref name=":3" /> == See also == * [[Antiandrogens in the environment]] * [[Theo Colborn]] * [[Endocrine system]] * [[Environmental hormones]] * [[Hormone]] * [[Obesogen]] * [[Pollutant-induced abnormal behaviour]] * [[Precautionary principle]] * ''[[Stink!]]'' * [[John Sumpter]] * [[Xenoestrogen]] == References == {{Reflist|refs= <ref name=guardian22may15>{{cite news|title=EU dropped pesticide laws due to US pressure over TTIP, documents reveal|url=https://www.theguardian.com/environment/2015/may/22/eu-dropped-pesticide-laws-due-to-us-pressure-over-ttip-documents-reveal#comments|newspaper=Guardian|access-date=22 May 2015|date=22 May 2015| vauthors = Brussels AN }}</ref> <!-- <ref>{{Cite journal |last=Cabry |first=Rosalie |last2=Merviel |first2=Philippe |last3=Madkour |first3=Aicha |last4=Lefranc |first4=Elodie |last5=Scheffler |first5=Florence |last6=Desailloud |first6=Rachel |last7=Bach |first7=Véronique |last8=Benkhalifa |first8=Moncef |date=June 2020 |title=The impact of endocrine disruptor chemicals on oocyte/embryo and clinical outcomes in IVF |url=https://ec.bioscientifica.com/view/journals/ec/9/6/EC-20-0135.xml |journal=Endocrine Connections |volume=9 |issue=6 |pages=R134–R142 |doi=10.1530/EC-20-0135 |issn=2049-3614}}</ref> --> }} ==Further reading== {{refbegin|30em}} * {{cite book | vauthors = Krimsky S | title = Hormonal chaos: the scientific and social origins of the environmental endocrine hypothesis | publisher = Johns Hopkins University Press | location = Baltimore | year = 2000 | isbn = 978-0-8018-6279-3 | url = https://archive.org/details/hormonalchaossci00krim_0 }} * {{cite book | veditors = Bergman Å, Heindel JJ, Jobling S, Kidd KA, Zoeller RT | title = State of the Science of Endocrine Disrupting Chemicals - 2012 | url = http://unep.org/pdf/9789241505031_eng.pdf | year = 2013 | publisher = United Nations Environment Programme and the World Health Organization | isbn = 978-92-807-3274-0 | access-date = 24 February 2013 | archive-url = https://web.archive.org/web/20130522073844/http://unep.org/pdf/9789241505031_eng.pdf | archive-date = 22 May 2013 | url-status = dead }} and {{ISBN|978-92-4-150503-1}} * {{Cite book | publisher = Dutton | isbn = 978-0-525-93982-5 | vauthors = Colborn T, Dumanoski D, Meyers P | title = Our stolen future: are we threatening our fertility, intelligence, and survival?: a scientific detective story | location = New York | year = 1996 | url = https://archive.org/details/ourstolenfuturea00colb_0 }} * {{cite journal | collaboration = European Chemical Agency (ECHA) and European Food Safety Authority (EFSA) with the technical support of the Joint Research Centre (JRC) | vauthors = Andersson N, Arena M, Auteri D, Barmaz S, Grignard E, Kienzler A, Lepper P, Lostia AM, Munn S, Parra Morte JM | title = Guidance for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009. | journal = EFSA Journal | date = June 2018 | volume = 16 | issue = 6 | pages = e05311 | doi = 10.2903/j.efsa.2018.5311 | pmid = 32625944 | pmc = 7009395 }} * {{cite journal | title = Revised Guidance Document 150 on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption | journal = [[OECD]] | series = OECD Series on Testing and Assessment | date = 2018 | doi = 10.1787/9789264304741-en | isbn = 978-92-64-30474-1 | s2cid = 240274054 }} * {{Cite book |title=Endocrine Disrupting Chemicals in Freshwater: Monitoring and Regulating Water Quality |date=12 October 2023 |publisher=OECD |isbn=978-92-64-53751-4 |series=OECD Studies on Water |language=en |doi=10.1787/5696d960-en |s2cid=264081548 |id=[https://www.oecd.org/environment/resources/policy-highlights-endocrine-disrupting-chemicals%20in-freshwater.pdf Policy Highlights]}} {{refend}} ==External links== * [http://ec.europa.eu/environment/chemicals/endocrine/documents/studies_en.htm Endocrine Disruptors], [[European Commission]], 2023 * [https://www.epa.gov/endocrine-disruption Endocrine Disruption Screening Program], US [[United States Environmental Protection Agency|Environmental Protection Agency]], April 2023 * [https://edlists.org/the-ed-lists Endocrine Disruptor Lists], provided by European authorities, 2023 {{Commons category|Endocrine disruptors}} {{Androgenics}} {{Estrogenics}} {{HealthIssuesOfPlastics}} {{Authority control}} {{DEFAULTSORT:Endocrine Disruptor}} [[Category:Endocrine disruptors| ]] [[Category:Endocrinology]]
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