View source for Chemistry:Phthalate

{{short description|Any ester derived from phthalic acid}}
[[Image:Phthalates.svg|thumb|right|General chemical structure of orthophthalates. (R and R' are general placeholders.)]]
'''Phthalates''' ({{IPAc-en|US|ˈ|θ|æ|l|eɪ|t|s}},<ref>"{{YouTube|id=QH5PbE8wwMY|title=ACC Addresses Phthalates Safety"}}: video of Steve Risotto of the American Chemistry Council, uploaded by user AmericanChemistry on 23 October 2009, retrieved 23 December 2011.</ref> {{IPAc-en|UK|ˈ|θ|a:|l|eɪ|t|s|,|_|ˈ|f|θ|æ|l|ɪ|t|s}}<ref>{{Cite OED|phthalate}}</ref><ref>[https://www.collinsdictionary.com/dictionary/english/phthalate "phthalate"] in Collins English Dictionary</ref>), or '''phthalate esters''', are [[Chemistry:Ester|ester]]s of [[Chemistry:Phthalic acid|phthalic acid]]. They are mainly used as [[Chemistry:Plasticizer|plasticizer]]s, i.e., substances added to [[Chemistry:Plastic|plastic]]s to increase their flexibility, transparency, durability, and longevity. They are used primarily to soften [[Chemistry:Polyvinyl chloride|polyvinyl chloride]] (PVC).  Note that while phthalates are usually [[Chemistry:Plasticizer|plasticizer]]s, not all plasticizers are phthalates.  The two terms are specific and unique and cannot be used interchangeably.

Lower-molecular-weight phthalates, those derived from C3-C6 alcohols, are being gradually replaced in many products in the {{wipe|United States}}, {{wipe|Canada}}, and [[Social:European Union|European Union]] over health concerns.<ref name=":1">{{cite EU regulation|serial=143/2011|date=17 February 2011|description=amending Annex XIV to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals ('REACH')|eurlextag=OJ L 44, 18 February 2011}}</ref><ref>{{Cite web |url=https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/phthalates|title=Phthalates {{!}} Assessing and Managing Chemicals Under TSCA|date=2015-09-21|website=www.epa.gov|language=en|access-date=2017-04-07}}</ref> They are being replaced by high-molecular-weight phthalates (those with more than six carbons in their backbone, which gives them increased permanency and durability), as well as alternative plasticizers not based on phthalic anhydride. In 2010, the market was still dominated by high-phthalate plasticizers; however, due to legal provisions and growing environmental awareness and perceptions, producers are increasingly switching to non-phthalate plasticizers.<ref>{{cite web|url = http://www.ceresana.com/en/market-studies/additives/plasticizers/|title = Plasticizers – Study: Market, Analysis, Trends | work = Ceresana }}</ref> The legacy use of phthalate plasticizers has prevented manufacturers from using post-consumer recycled PVC since that recycled content would likely contain phthalates. Thus, many manufacturers have moved to use only virgin PVC in their products.<ref>{{cite web|url = https://www.floordaily.net/floorfocus/the-greening-of-lvt-mannington-armstrong-tarket|title = The Greening of LVT: Mannington, Armstrong, Tarkett and others| vauthors = Helm D |work =Floor Daily|date = 2014}}</ref><ref>{{Cite web|url=https://www.interface.com/US/en-US/campaign/LVT/LVT-Sustainability-en_US|title=Interface Resilient Vinyl Flooring and Sustainability|access-date=14 November 2019|archive-date=22 January 2020|archive-url=https://web.archive.org/web/20200122162313/https://www.interface.com/US/en-US/campaign/LVT/LVT-Sustainability-en_US|url-status=dead}}</ref><ref>{{Cite web|url=https://www.forbo.com/flooring/en-us/products/allura-lvt/c3ndzf#panel_102|title = Allura LVT}}</ref>  There are, however, efforts underway to collect post-consumer PVC for chemical recycling efforts that can remove legacy phthalates and create virgin-like PVC.  Those efforts are focused on areas like healthcare where PVC makes up a significant amount of medical devices.<ref>{{cite web|url = https://pvcmed.org/make-no-mistake-pvc-based-medical-devices-are-fit-for-recycling/|title = Make no mistake: PVC-based medical devices are fit for recycling| vauthors = Hansen OG |work = Plastics Today|date = March 2020}}</ref>

==Prevalence and human exposure==
Due to the ubiquity of plasticized plastics, the majority of people are exposed to some level of phthalates. For example, most Americans tested by the Centers for Disease Control and Prevention have [[Biology:Metabolite|metabolite]]s of multiple phthalates in their urine.<ref name=":3">{{cite report|url=https://www.cdc.gov/biomonitoring/pdf/Pthalates_FactSheet.pdf|title=Pthalates Fact Sheet|date=November 2009|publisher=Centers for Disease Control and Prevention|author=<!-- or |last= and -->}}</ref> In studies of rodents exposed to certain phthalates, high doses have been shown to change hormone levels and cause birth defects.<ref name=CDC/>

==Production==
Phthalates are produced industrially by the acid catalysed reaction of [[Chemistry:Phthalic anhydride|phthalic anhydride]] with excess [[Chemistry:Alcohol|alcohol]]. The synthesis of [[Chemistry:Diethyl phthalate|diethyl phthalate]] is illustrative of this:

[[File:Synthesis-DEP.png|300px|center|frameless]]

The properties of the phthalate can be varied by changing the alcohol,<ref>{{cite journal |last1=Krauskopf |first1=L. G. |title=Plasticizer structure/performance relationships |journal=Journal of Vinyl and Additive Technology |date=September 1993 |volume=15 |issue=3 |pages=140–147 |doi=10.1002/vnl.730150306}}</ref> allowing for an almost limitless range of products, although only around 30 are, or have been, commercially important. Phthalates' share of the global plasticisers market has been decreasing since around 2000. Despite this the global production of phthalates has continued to rise. In 2015 total production of was around 5.5 million tonnes,<ref name="OECD">{{cite journal |last1=Holland |first1=Mike |title=Socio-economic assessment of phthalates |journal=Organisation for Economic Co-operation and Development |series=OECD Environment Working Papers |date=6 June 2018 |page=15 |doi=10.1787/a38a0e34-en|s2cid=134543052 }}</ref> up from around 2.7 million tonnes in the 1980s.<ref>{{cite web |title=TR 019 – An Assessment of Occurrence and Effects of Dialkyl-o-Phthalates in the Environment |url=https://www.ecetoc.org/wp-content/uploads/2021/10/ECETOC-TR-019.pdf |publisher=ECETOC |date=1985-05-29}}</ref> The reason for this has been the increasing size of the plasticiser market (a smaller slice of a much bigger pie), driven by increases in PVC production, which doubled between 2000 and 2020. The People's Republic of China is the largest consumer, accounting for around 45% of all use. Europe and the United States together account for around 25% of use, with the remainder widely spread around the world.<ref name="OECD" />

{| class="wikitable" style="width:72em"
|+ Common Phthalates <BR><small>Commercially important compounds shown in bold</small>
|-
! Name
! Abbreviation
! style=max-width:4em | Alcohol carbon number
! style=max-width:5em |[[Physics:Molecular weight|Molecular weight]] (g/mol)
! style=min-width:5em |CAS No.
! Properties of concern for human health (ECHA classification 2022)<ref>{{cite web |title=Search for Chemicals - ECHA |url=https://echa.europa.eu/search-for-chemicals? |website=echa.europa.eu |publisher=European Chemicals Agency |access-date=9 June 2022 |quote=Enter CAS No's to validate manually}}</ref>
|-
| [[Chemistry:Dimethyl phthalate|Dimethyl phthalate]] || DMP || 1 || 194.18 || 131-11-3 ||
|-
| [[Chemistry:Diethyl phthalate|Diethyl phthalate]] || DEP || 2 || 222.24 || 84-66-2 || Under assessment as Endocrine Disrupting
|-
| Diallyl phthalate || DAP || 3 || 246.26 || 131-17-9 || Skin sensitising
|-
| Di-n-propyl phthalate || DPP || 3 || 250.29 || 131-16-8 ||
|-
| '''Di-n-butyl phthalate''' || '''DBP''' || 4 || 278.34 || 84-74-2 || Toxic to Reproduction, Endocrine Disrupting, Under assessment as [[Chemistry:Persistent, bioaccumulative and toxic substances|PBT]]
|-
| [[Chemistry:Diisobutyl phthalate|Diisobutyl phthalate]] || DIBP || 4 || 278.34 || 84-69-5 || Toxic to Reproduction, Endocrine Disrupting
|-
| [[Chemistry:Bis(2-methoxyethyl) phthalate|Di-2-methoxyethyl phthalate]] || DMEP || 3 || 282.29 ||  117-82-8 || Toxic to Reproduction
|-
| Butyl cyclohexyl phthalate || BCP || 4 – 6 || 304.38 || 84-64-0  ||
|-
| Di-n-pentyl phthalate || DNPP || 5 || 306.4 || 131-18-0 || Toxic to Reproduction
|-
| Dicyclohexyl phthalate || DCP || 6 || 330.42 || 84-61-7 || Toxic to Reproduction, Endocrine Disrupting, Skin sensitising
|-
| '''Butyl benzyl phthalate''' || '''BBP''' || 4 – 7 || 312.36 || 85-68-7 || Toxic to Reproduction, Endocrine Disrupting
|-
| Di-n-hexyl phthalate || DNHP || 6 || 334.45 || 84-75-3 || Toxic to Reproduction
|-
| Diisohexyl phthalate || DIHxP || 6 || 334.45 || 146-50-9, || Toxic to Reproduction
|-
| [[Chemistry:Diisoheptyl phthalate|Diisoheptyl phthalate]] || DIHpP || 7 || 362.5 || 41451-28-9 || Toxic to Reproduction
|-
| Butyl decyl phthalate || BDP || 4 – 10 || 362.5 || 89-19-0 ||
|-
| [[Chemistry:Dibutoxy ethyl phthalate|Dibutoxy ethyl phthalate]] || DBEP || 6 || 366.45 || 117-83-9 ||
|-
| '''Di(2-ethylhexyl) phthalate''' || '''DEHP, DOP''' || 8 || 390.56 || 117-81-7 || Toxic to Reproduction, Endocrine Disrupting
|-
| Di(n-octyl) phthalate || DNOP || 8 || 390.56 || 117-84-0 || Not classified but some uses restricted
|-
| Diisooctyl phthalate || DIOP || 8 || 390.56 || 27554-26-3 || Toxic to Reproduction
|-
| n-Octyl n-decyl phthalate || ODP || 8 – 10 || 418.61 || 119-07-3||
|-
| '''[[Chemistry:Diisononyl phthalate|Diisononyl phthalate]]''' || '''DINP''' || 9 || 418.61 || 28553-12-0 || Not classified but some uses restricted
|-
| '''[[Chemistry:DPHP|Di(2-propylheptyl) phthalate]]''' || '''DPHP''' || 10 || 446.66 || 53306-54-0 || Under assessment as Endocrine Disrupting 
|-
| '''[[Chemistry:Diisodecyl phthalate|Diisodecyl phthalate]]''' || '''DIDP''' || 10 || 446.66 || 26761-40-0 ||
|-
| Diundecyl phthalate || DUP || 11 || 474.72 || 3648-20-2 ||
|-
| Diisoundecyl phthalate || DIUP || 11 || 474.72 || 85507-79-5 ||
|-
| Ditridecyl phthalate || DTDP || 13 || 530.82 || 119-06-2 ||
|-
| Diisotridecyl phthalate || DITP || 13 || 530.82 || 68515-47-9 ||
|}

===Natural occurrence===
Various plants and microorganisms have been reported to naturally produce phthalate esters (endogenous phthalates).<ref>{{cite journal |last1=Zhang |first1=Huawei |last2=Hua |first2=Yi |last3=Chen |first3=Jianwei |last4=Li |first4=Xiuting |last5=Bai |first5=Xuelian |last6=Wang |first6=Hong |title=Organism-derived phthalate derivatives as bioactive natural products |journal=Journal of Environmental Science and Health, Part C |date=3 July 2018 |volume=36 |issue=3 |pages=125–144 |doi=10.1080/10590501.2018.1490512|pmid=30444179 |s2cid=53565519 }}</ref><ref>{{cite journal |last1=Roy |first1=Raj Narayan |title=Bioactive natural derivatives of phthalate ester |journal=Critical Reviews in Biotechnology |date=2 October 2020 |volume=40 |issue=7 |pages=913–929 |doi=10.1080/07388551.2020.1789838|pmid=32683987 |s2cid=220654942 }}</ref> [[Biology:Biosynthesis|Biosynthesis]] is believed to involve a modified [[Biology:Shikimate pathway|Shikimate pathway]]<ref>{{cite journal |last1=Tian |first1=Congkui |last2=Ni |first2=Jinren |last3=Chang |first3=Fang |last4=Liu |first4=Sitong |last5=Xu |first5=Nan |last6=Sun |first6=Weiling |last7=Xie |first7=Yuan |last8=Guo |first8=Yongzhao |last9=Ma |first9=Yanrong |last10=Yang |first10=Zhenxing |last11=Dang |first11=Chenyuan |last12=Huang |first12=Yuefei |last13=Tian |first13=Zhexian |last14=Wang |first14=Yiping |title=Bio-Source of di-n-butyl phthalate production by filamentous fungi |journal=Scientific Reports |date=April 2016 |volume=6 |issue=1 |pages=19791 |doi=10.1038/srep19791|pmid=26857605 |pmc=4746570 |bibcode=2016NatSR...619791T }}</ref><ref>{{cite journal |last1=Enikeev |first1=A. G. |last2=Semenov |first2=A. A. |last3=Permyakov |first3=A. V. |last4=Sokolova |first4=N. A. |last5=Gamburg |first5=K. Z. |last6=Dudareva |first6=L. V. |title=Biosynthesis of Ortho-Phtalic Acid Esters in Plant and Cell Cultures |journal=Applied Biochemistry and Microbiology |date=May 2019 |volume=55 |issue=3 |pages=294–297 |doi=10.1134/S0003683819020066|s2cid=174809331 }}</ref> The extent of this natural production is not fully known, but it may create a background of phthalate pollution.

==Uses==
===PVC Plasticisers===
[[File:'Twin and Earth' electrical cable. BS 6004, 6mm².jpg|thumb|right|Plasticised PVC has excellent electrical insulation properties and is extensively used as sheathing for wires and cables.]]

Between 90 and 95% of all phthalates are used as plasticisers for the production of flexible PVC.<ref>{{cite journal |last1=Latini |first1=Giuseppe |last2=De Felice |first2=Claudio |last3=Verrotti |first3=Alberto |title=Plasticizers, infant nutrition and reproductive health |journal=Reproductive Toxicology |date=November 2004 |volume=19 |issue=1 |pages=27–33 |doi=10.1016/j.reprotox.2004.05.011|pmid=15336709 }}</ref><ref>{{cite journal |last1=Bi |first1=Mengyan |last2=Liu |first2=Wei |last3=Luan |first3=Xiaoyu |last4=Li |first4=Muyang |last5=Liu |first5=Min |last6=Liu |first6=Wenqiu |last7=Cui |first7=Zhaojie |title=Production, Use, and Fate of Phthalic Acid Esters for Polyvinyl Chloride Products in China |journal=Environmental Science & Technology |date=19 October 2021 |volume=55 |issue=20 |pages=13980–13989 |doi=10.1021/acs.est.1c02374|pmid=34617437 |bibcode=2021EnST...5513980B |s2cid=238422673 }}</ref> They were the first commercially important compounds for this role,<ref>{{cite journal |last1=Semon |first1=Waldo L. |last2=Stahl |first2=G. Allan |title=History of Vinyl Chloride Polymers |journal=Journal of Macromolecular Science: Part A - Chemistry |date=April 1981 |volume=15 |issue=6 |pages=1263–1278 |doi=10.1080/00222338108066464}}</ref> a historic advantage that has led to them becoming firmly embedded in flexible PVC technology.<ref name="additives handbook" /> Among the [[Chemistry:Commodity plastics|common plastics]], PVC is unique in its acceptance of large amounts of plasticizer with gradual changes in physical properties from a rigid solid to a soft gel.<ref name="additives handbook">{{cite book |last1=Krauskopf |first1=Leonard G. |title=Plastics additives handbook |date=2009 |publisher=Carl Hanser Verlag |location=Munich |isbn=978-3-446-40801-2 |pages=485–511 |edition=6. |chapter=3.13 Plasticizers}}</ref> Plasticizers, especially phthalates, derived from alcohols with 7-13 carbon atoms occupy a privileged position as general purpose plasticizers, suitable for almost all flexible PVC applications.<ref>{{cite web |last1=Godwin |first1=Allen |title=Uses of Phthalates and Other Plasticizers |url=https://www.cpsc.gov/s3fs-public/godwin.pdf |website=cpsc.gov |publisher=ExxonMobil Chemical Company |access-date=19 May 2022 |date=July 26, 2010}}</ref><ref name="additives handbook" /> Phthalates larger than this have limited compatibility in PVC, with di(isotridecyl) phthalate representing the practical upper limit. Conversely, plasticizers derived from alcohols with 4-6 carbon atoms are too volatile to be used on their own, but have been used alongside other compounds as secondary plasticizers, where they improve low-temperature flexibility. Compounds derived from alcohols with 1-3 carbon atoms are not used as plasticizers in PVC at all, due excessive fuming at processing temperatures (typically 180-210°C).<ref name="additives handbook" />

Historically DINP, DEHP, DIOP, DBP, and DIHP have been the most important phthalates, however many of these are now facing regulatory pressure and gradual phase-outs. Almost all phthalates derived from alcohols with 8 or fewer carbons are classed as toxic by ECHA. This includes [[Chemistry:Bis(2-ethylhexyl) phthalate|Bis(2-ethylhexyl) phthalate]] (DEHP or DOP), which has long been the most widely used phthalate, with commercial production dating back to the 1930s.<ref>{{cite book |title=IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans Volume 29: Some industrial chemicals and dyestuffs. |date=1982 |publisher=[[Organization:International Agency for Research on Cancer|International Agency for Research on Cancer]] |location=[Lyon] |isbn=978-92-832-1229-4 |page=271 |url=https://publications.iarc.fr/_publications/media/download/1577/2f8d8229f8923fd2509f7f95e848ba6bf7f88766.pdf}}</ref><ref name=ceresana /> In the EU, the use of DEHP is restricted under [[Chemistry:Registration, Evaluation, Authorisation and Restriction of Chemicals|REACH]] and it can only be used in specific cases if an authorisation has been granted; similar restrictions exist in many other jurisdictions. Despite this, the phase-out of DEHP is slow and it was still the most frequently used plasticizer in 2018, with an estimated global production of 3.24 million tonnes.<ref name=ceresana /> DINP and DIDP are used as a substitutes for DEHP in many applications, as they are not classified as hazardous.<ref>{{cite journal | vauthors = Ventrice P, Ventrice D, Russo E, De Sarro G | title = Phthalates: European regulation, chemistry, pharmacokinetic and related toxicity | journal = Environmental Toxicology and Pharmacology | volume = 36 | issue = 1 | pages = 88–96 | date = July 2013 | pmid = 23603460 | doi = 10.1016/j.etap.2013.03.014 }}</ref> Non-phthalate plasticizers are also being increasingly used.

Almost 90% of all plasticizers are used in PVC, giving this material improved flexibility and durability.<ref>David F. Cadogan and Christopher J. Howick "Plasticizers" in Ullmann's Encyclopedia of Industrial Chemistry 2000, Wiley-VCH, Weinheim. {{doi|10.1002/14356007.a20_439}}</ref> The majority is used in films and cable sheathing.<ref name=ceresana>{{cite web |title=Market Report Plasticizers: Industry Analysis{{!}}Market Research |url=https://www.ceresana.com/en/market-studies/chemicals/plasticizers/ |website=www.ceresana.com |access-date=19 May 2022}}</ref> Flexible PVC can consist of over 85% plasticizer by mass, however unplasticized PVC (UPVC) should not contain any.

{| class="wikitable" style="width:71em"
|+ PVC properties as a function of phthalate plasticizer level<ref>{{cite book |last1=Krauskopf |first1=L. G. |title=Plastics additives handbook |date=2009 |publisher=Carl Hanser Verlag |location=Munich |isbn=978-3-446-40801-2 |page=495 |edition=6.}}</ref>
! !!  Plasticizer content  (% DINP by weight) !! [[Physics:Specific gravity|Specific gravity]] (20&nbsp;°C) !! Shore hardness <BR /><small>(type A, 15 s)</small> !! [[Physics:Flexural rigidity|Flexural stiffness]]  (Mpa) !! [[Physics:Ultimate tensile strength|Tensile strength]] (Mpa) !!  Elongation at break (%) !! Example applications 
|-
| Rigid || 0 || 1.4 ||  || 900 || 41 || <15 || Unplasticized PVC (UPVC): window frames and sills, doors, [[Engineering:Plastic pipework#uPVC (unplasticized Polyvinyl Chloride)|rigid pipe]]
|-
| Semi-rigid || 25 || 1.26 || 94 || 69 || 31 || 225 || Vinyl flooring, flexible pipe, thin films (stretch wrap), advertising banners 
|-
| Flexible || 33 || 1.22 || 84 || 12 || 21 || 295 ||  Wire and cable insulation, flexible pipe 
|-
| Very Flexible || 44 || 1.17 || 66 || 3.4 || 14 || 400 || Boots and clothing, inflatables, 
|-
| Extremely Flexible || 86 || 1.02 || < 10 ||  ||  ||  || Fishing lures ([[Engineering:Soft plastic bait|soft plastic bait]]), polymer clay, [[Chemistry:Plastisol|plastisol]] inks
|}

===Non-PVC Plasticisers===
Phthalates see use as plasticisers in various other polymers, with applications centred around coatings such as lacquers, varnishes, and paints. The addition of phthalates imparts some flexibility to these materials, reducing their tendency to chip. 
Phthalates derived from alcohols with between 1-4 carbon atoms are used as plasticisers for [[Chemistry:Cellulose|cellulose]]-type plastics, such as [[Chemistry:Cellulose acetate|cellulose acetate]], [[Chemistry:Nitrocellulose|nitrocellulose]] and [[Chemistry:Cellulose acetate butyrate|cellulose acetate butyrate]], with commonly encountered applications including nail polish. Most phthalates are also compatible with [[Chemistry:Alkyd|alkyd]]s and [[Chemistry:Acrylic resin|acrylic resin]]s, which are used in both oil and emulsion based paints.

Other plasticised polymer systems include [[Chemistry:Polyvinyl butyral|polyvinyl butyral]] (particularly the forms used to make [[Engineering:Laminated glass|laminated glass]]), [[Chemistry:Polyvinyl acetate|PVA]] and its co-polymers like [[Chemistry:Polyvinyl chloride acetate|PVCA]]. They are also compatible in [[Chemistry:Nylon|nylon]], [[Chemistry:Polystyrene|polystyrene]], [[Chemistry:Polyurethane|polyurethane]]s, and certain [[Chemistry:Rubber|rubber]]s; but their use in these is very limited.<ref>{{cite journal |last1=Cadogan |first1=David F. |last2=Howick |first2=Christopher J. |title=Plasticizers |journal=Ullmann's Encyclopedia of Industrial Chemistry |date=15 June 2000 |volume=27 |pages=613–614 |doi=10.1002/14356007.a20_439|isbn=3527306730 }}</ref> Phthalates have also been used for producing plastic explosives such as Semtex.

Phthalates can plasticise [[Chemistry:Ethyl cellulose|ethyl cellulose]], [[Chemistry:Polyvinyl acetate phthalate|polyvinyl acetate phthalate]] (PVAP) and [[Chemistry:Cellulose acetate phthalate|cellulose acetate phthalate]] (CAP), all of which are used to make [[Chemistry:Enteric coating|enteric coating]]s for [[Medicine:Tablet (pharmacy)|tablet]] and [[Medicine:Capsule (pharmacy)|capsule]] medications. These coatings protect drugs from the acidity of the stomach, but allow their release and absorption in the intestines.

===Solvent and phlegmatizer===
Phthalate esters are widely used as solvents for highly reactive [[Chemistry:Organic peroxide|organic peroxide]]s.  Thousands of tonnes are consumed annually for this purpose.  The great advantage offered by these esters is that they are [[Chemistry:Phlegmatizer|phlegmatizer]]s, i.e. they minimize the explosive tendencies of a family of chemical compounds that otherwise are potentially dangerous to handle.<ref name=Ullmann>{{Ullmann | vauthors = Herbert K, Götz PH, Siegmeier R, Mayr W | title = Peroxy Compounds, Organic | doi = 10.1002/14356007.a19_199}}</ref>

===Other uses===
Relatively minor amounts of some phthalates find use in personal-care items such as eye shadow, moisturizer, nail polish, liquid soap, and hair spray.<ref>{{cite journal |last1=Koo |first1=Hyun Jung |last2=Lee |first2=Byung Mu |title=Estimated Exposure to Phthalates in Cosmetics and Risk Assessment |journal=Journal of Toxicology and Environmental Health, Part A |date=December 2004 |volume=67 |issue=23–24 |pages=1901–1914 |doi=10.1080/15287390490513300|pmid=15513891 |s2cid=30617587 }}</ref><ref>{{cite journal |last1=Hubinger |first1=JC |last2=Havery |first2=DC |title=Analysis of consumer cosmetic products for phthalate esters. |journal=Journal of Cosmetic Science |date=March 2006 |volume=57 |issue=2 |pages=127–37 |pmid=16688376}}</ref><ref name=Ullmann2>Peter M. Lorz, Friedrich K. Towae, Walter Enke, Rudolf Jäckh, Naresh Bhargava, Wolfgang Hillesheim "Phthalic Acid and Derivatives" in Ullmann's Encyclopedia of Industrial Chemistry, 2007, Wiley-VCH, Weinheim. {{doi|10.1002/14356007.a20_181.pub2}}</ref> Low-molecular-weight phthalates like [[Chemistry:Dimethyl phthalate|dimethyl phthalate]] and [[Chemistry:Diethyl phthalate|diethyl phthalate]] are used as fixatives for perfumes.<ref>{{cite journal |last1=Al-Saleh |first1=Iman |last2=Elkhatib |first2=Rola |title=Screening of phthalate esters in 47 branded perfumes |journal=Environmental Science and Pollution Research |date=January 2016 |volume=23 |issue=1 |pages=455–468 |doi=10.1007/s11356-015-5267-z|pmid=26310707 |s2cid=22840018 }}</ref><ref>{{cite web |title=Phthalates in Cosmetics |url=https://www.fda.gov/cosmetics/cosmetic-ingredients/phthalates-cosmetics |website=U.S. Food and Drug Administration (FDA) |access-date=2 November 2022 |language=en |date=19 May 2022}}</ref> Dimethyl phthalate has been also used as an [[Chemistry:Insect repellent|insect repellent]] and is especially useful against [[Biology:Ixodidae|ixodid ticks]] responsible for [[Unsolved:Lyme disease|Lyme disease]].<ref>{{Cite journal |last1=Brown |first1=Margaret |last2=Hebert |first2=Adelaide A. |date=1997-02-01 |title=Insect repellents: An overview |url=https://www.sciencedirect.com/science/article/pii/S0190962297702895 |journal=Journal of the American Academy of Dermatology |language=en |volume=36 |issue=2 |pages=243–249 |doi=10.1016/S0190-9622(97)70289-5 |pmid=9039177 |issn=0190-9622}}</ref> and species of mosquitoes such as ''[[Biology:Anopheles stephensi|Anopheles stephensi]], [[Biology:Culex pipiens|Culex pipiens]] and [[Biology:Aedes aegypti|Aedes aegypti]]'',<ref name=":6">{{cite journal | vauthors = Karunamoorthi K, Sabesan S | title = Laboratory evaluation of dimethyl phthalate treated wristbands against three predominant mosquito (Diptera: Culicidae) vectors of disease | journal = European Review for Medical and Pharmacological Sciences | volume = 14 | issue = 5 | pages = 443–448 | date = May 2010 | pmid = 20556923 }}</ref><ref name=":7">{{Cite journal |last1=Nathan |first1=Sengottayan Senthil |last2=Kalaivani |first2=Kandaswamy |last3=Murugan |first3=Kadarkarai |date=October 2005 |title=Effects of neem limonoids on the malaria vector Anopheles stephensi Liston (Diptera: Culicidae) |url=http://dx.doi.org/10.1016/j.actatropica.2005.07.002 |journal=Acta Tropica |volume=96 |issue=1 |pages=47–55 |doi=10.1016/j.actatropica.2005.07.002 |pmid=16112073 |issn=0001-706X}}</ref><ref>{{Cite journal |last1=Kalyanasundaram |first1=Muthuswami |last2=Mathew |first2=Nisha |date=2006-05-01 |title=N,N-Diethyl Phenylacetamide (DEPA): A Safe and Effective Repellent for Personal Protection Against Hematophagous Arthropods |url=http://openurl.ingenta.com/content/xref?genre=article&issn=0022-2585&volume=43&issue=3&spage=518 |journal=Journal of Medical Entomology |language=en |volume=43 |issue=3 |pages=518–525 |doi=10.1603/0022-2585(2006)43[518:NPDASA]2.0.CO;2|pmid=16739410 |s2cid=22623121 }}</ref>

Diallyl phthalate is used to prepare [[Chemistry:Vinyl ester resin|vinyl ester resin]]s with excellent electrical insulation properties, these are used to manufacture of electronics components. [[Chemistry:Alkyd|Alkyd]]s are sometimes classes as phthalates, as they meet the technical definition, however, being polymeric esters of [[Chemistry:Phthalic acid|phthalic acid]] their properties and applications are very different.

==History==
The development of cellulose nitrate plastic in 1846 led to the patent of [[Chemistry:Castor oil|castor oil]] in 1856 for use as the first plasticizer. In 1870, [[Chemistry:Camphor|camphor]] became the more favored plasticizer for cellulose nitrate. Phthalates were first introduced in the 1920s and quickly replaced the volatile and odorous camphor. In 1931, the commercial availability of [[Chemistry:Polyvinyl chloride|polyvinyl chloride]] (PVC) and the development of [[Chemistry:Bis(2-ethylhexyl) phthalate|di(2-ethylhexyl) phthalate]] (DEHP) began the boom of the plasticizer PVC industry.

In February 2009, the Joint Research Centre (JRC) of the European Commission published a review of methods to measure phthalates in food.<ref>[http://irmm.jrc.ec.europa.eu/publications/technical_reports/food,_biotechnology_and_health/Documents/eur_23682_en-phthalates.pdf Methods for the determination of phthalates in food], (PDF) European Commission, Joint Research Centre {{webarchive|url=https://web.archive.org/web/20110720161821/http://irmm.jrc.ec.europa.eu/publications/technical_reports/food,_biotechnology_and_health/Documents/eur_23682_en-phthalates.pdf|date=20 July 2011}}</ref>

In 2021, a study looked for phthalates in 64 fast food items. Phthalate DnBP was detected in 81 percent of the samples, while DEHP was found in 70 percent. Diethylhexyl terephthalate (DEHT), the main alternative to DEHP, was detected in 86%.<ref>{{cite journal | vauthors = Edwards L, McCray NL, VanNoy BN, Yau A, Geller RJ, Adamkiewicz G, Zota AR | title = Phthalate and novel plasticizer concentrations in food items from U.S. fast food chains: a preliminary analysis | language = en-US | journal = Journal of Exposure Science & Environmental Epidemiology | date = October 2021 | volume = 32 | issue = 3 | pages = 366–373 | pmid = 34702987 | doi = 10.1038/s41370-021-00392-8 | pmc = 9119856 | doi-access = free }}</ref>

==Properties==
Phthalate [[Chemistry:Ester|ester]]s are the di[[Chemistry:Alkyl|alkyl]] or alkyl [[Chemistry:Aryl|aryl]] esters of [[Chemistry:Phthalic acid|phthalic acid]] (also called 1,2-benzenedicarboxylic acid, not be confused with the [[Chemistry:Structural isomer#Position isomerism|structurally]] [[Chemistry:Phthalic acid#Isomers|isomeric]] [[Chemistry:Terephthalic acid|terephthalic]] or [[Chemistry:Isophthalic acid|isophthalic]] acids); the name "phthalate" derives from [[Chemistry:Phthalic acid|phthalic acid]], which itself is derived from the word "[[Chemistry:Naphthalene|naphthalene]]". When added to plastics, phthalates allow the long polyvinyl molecules to slide against one another. The phthalates have a clear syrupy liquid consistency and show low water solubility, high oil solubility, and low volatility. The polar carboxyl group contributes little to the physical properties of the phthalates, except when R and R' are very small (such as ethyl or methyl groups). Phthalates are colorless, odorless liquids produced by reacting [[Chemistry:Phthalic anhydride|phthalic anhydride]] with an appropriate [[Chemistry:Alcohol|alcohol]] (usually 6- to 13-carbon).

The mechanism by which phthalates and related compounds effect plasticization to polar polymers has been a subject of intense study since the 1960s.<ref>{{cite journal |last1=Daniels |first1=Paul H. |title=A brief overview of theories of PVC plasticization and methods used to evaluate PVC-plasticizer interaction |journal=Journal of Vinyl and Additive Technology |date=December 2009 |volume=15 |issue=4 |pages=219–223 |doi=10.1002/vnl.20211|s2cid=137535663 }}</ref> The mechanism is one of polar interactions between the polar centres of the phthalate molecule (the C=O functionality) and the positively charged areas of the vinyl chain, typically residing on the carbon atom of the carbon-chlorine bond. For this to be established, the polymer must be heated in the presence of the plasticizer, first above the Tg of the polymer and then into a melt state. This enables an intimate mix of polymer and plasticizer to be formed, and for these interactions to occur. When cooled, these interactions remain and the network of PVC chains cannot reform (as is present in unplasticized PVC, or PVC-U). The alkyl chains of the phthalate then screen the PVC chains from each other as well. They are blended within the plastic article as a result of the manufacturing process.<ref>{{Cite book |title=PVC handbook | vauthors = Wilkes CE, Summers JW, Daniels CA, Berard M |date=2005-01-01 |publisher=Hanser |isbn=978-3446227149 |oclc=488962111}}</ref>

Because they are not [[Chemistry:Chemical bond|chemically bonded]] to the host [[Chemistry:Plastic|plastic]]s, phthalates are released from the plastic article by relatively gentle means. For example, they can be removed by heating or by extraction with organic solvents.

===Alternatives===
[[File:European Plasticiser Market Trends 2005 - 2014.jpg|thumb|Market trend in decreasing use of low orthophthalates including DEHP]]
Being inexpensive, nontoxic (in an acute sense), colorless, noncorrosive, biodegradable, and with easily tuned physical properties, phthalate esters are nearly ideal plasticizers. Among the numerous alternative [[Chemistry:Plasticizer|plasticizer]]s are [[Chemistry:Dioctyl terephthalate|Dioctyl terephthalate]] (DEHT) (a terephthalate isomeric with DEHP) and [[Chemistry:1,2-Cyclohexane dicarboxylic acid diisononyl ester|1,2-Cyclohexane dicarboxylic acid diisononyl ester]] (a hydrogenated version of DINP).

Many bio-based plasticizers based on vegetable oil have been developed. They can be substituted for dioctyl phthalate.<ref>{{cite web|title=Bio-based plasticizer|url=http://www.license.umn.edu/Products/Bio-Based--Phthalate-Free-Polyvinyl-Chloride-Plasticizer__20100213.aspx|publisher=University of Minnesota|access-date=7 October 2011|archive-url=https://web.archive.org/web/20120406140605/http://www.license.umn.edu/Products/Bio-Based--Phthalate-Free-Polyvinyl-Chloride-Plasticizer__20100213.aspx|archive-date=6 April 2012|url-status=dead}}</ref>

==Environmental impact==
Phthalates are easily released into the environment. In general, they do not persist due to rapid biodegradation, [[Biology:Photodegradation|photodegradation]], and [[Physics:Anaerobic digestion|anaerobic degradation]]. Outdoor air concentrations are higher in urban and [[Engineering:Suburb|suburb]]an areas than in [[Earth:Rural area|rural]] and remote areas.<ref name="endo">{{cite journal | vauthors = Rudel RA, Perovich LJ | title = Endocrine disrupting chemicals in indoor and outdoor air | journal = Atmospheric Environment | volume = 43 | issue = 1 | pages = 170–181 | date = January 2009 | pmid = 20047015 | pmc = 2677823 | doi = 10.1016/j.atmosenv.2008.09.025 | bibcode = 2009AtmEn..43..170R }}</ref>  They also pose no acute toxicity.<ref name=Ullmann/>

Because of their [[Chemistry:Volatility|volatility]], [[Chemistry:Diethyl phthalate|DEP]] and [[Chemistry:Dimethyl phthalate|DMP]] are present in higher concentrations in air in comparison with the heavier and less volatile [[Chemistry:Bis(2-ethylhexyl) phthalate|DEHP]]. Higher air temperatures result in higher concentrations of phthalates in the air. PVC flooring leads to higher concentrations of BBP and DEHP, which are more prevalent in dust.<ref name=endo/> A 2012 Swedish study of children found that phthalates from PVC flooring were taken up into their bodies, showing that children can ingest phthalates not only from food but also by breathing and through the skin.<ref>{{cite journal | vauthors = Carlstedt F, Jönsson BA, Bornehag CG | title = PVC flooring is related to human uptake of phthalates in infants | journal = Indoor Air | volume = 23 | issue = 1 | pages = 32–39 | date = February 2013 | pmid = 22563949 | doi = 10.1111/j.1600-0668.2012.00788.x | doi-access = free }}</ref>

Diet is believed to be the main source of DEHP and other phthalates in the general population. Fatty foods such as milk, butter, and meats are a major source. Studies show that exposure to phthalates is greater from ingestion of certain foods, rather than exposure via water bottles as is most often first thought of with plastic chemicals.<ref>{{cite journal | vauthors = Erythropel HC, Maric M, Nicell JA, Leask RL, Yargeau V | title = Leaching of the plasticizer di(2-ethylhexyl)phthalate (DEHP) from plastic containers and the question of human exposure | journal = Applied Microbiology and Biotechnology | volume = 98 | issue = 24 | pages = 9967–9981 | date = December 2014 | pmid = 25376446 | doi = 10.1007/s00253-014-6183-8 | s2cid = 11715151 }}</ref> Low-molecular-weight phthalates such as DEP, DBP, BBzP may be dermally absorbed. Inhalational exposure is also significant with the more volatile phthalates.<ref name="phthalates">{{cite journal | vauthors = Heudorf U, Mersch-Sundermann V, Angerer J | title = Phthalates: toxicology and exposure | journal = International Journal of Hygiene and Environmental Health | volume = 210 | issue = 5 | pages = 623–634 | date = October 2007 | pmid = 17889607 | doi = 10.1016/j.ijheh.2007.07.011 }}</ref>

Another study, conducted between 2003 and 2010 analysing data from 9,000 individuals, found that those who reported that they had eaten at a fast food restaurant had much higher levels of two separate phthalates—DEHP and DiNP—in their urine samples. Even small consumption of [[Finance:Fast food|fast food]] caused higher presence of phthalates. "People who reported eating only a little fast food had DEHP levels that were 15.5 percent higher and DiNP levels that were 25 percent higher than those who said they had eaten none. For people who reported eating a sizable amount, the increase was 24 percent and 39 percent, respectively."<ref>{{cite journal | vauthors = Zota AR, Phillips CA, Mitro SD | title = Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003-2010 | journal = Environmental Health Perspectives | volume = 124 | issue = 10 | pages = 1521–1528 | date = October 2016 | pmid = 27072648 | pmc = 5047792 | doi = 10.1289/ehp.1510803 }}</ref>

In a 2008 Bulgarian study, higher dust concentrations of DEHP were found in homes of children with asthma and allergies, compared with healthy children's homes.<ref name="dust">{{cite journal | vauthors = Kolarik B, Bornehag CG, Naydenov K, Sundell J, Stavova P, Nielsen OF |title=The concentrations of phthalates in settled dust in Bulgarian homes in relation to building characteristic and cleaning habits in the family |journal=Atmospheric Environment |date=December 2008 |volume=42 |issue=37 |pages=8553–8559 |doi=10.1016/j.atmosenv.2008.08.028 |bibcode=2008AtmEn..42.8553K |s2cid=96190203 }}</ref> The author of the study stated, "The concentration of DEHP was found to be significantly associated with wheezing in the last 12 months as reported by the parents."<ref name=dust /> Phthalates were found in almost every sampled home in Bulgaria. The same study found that DEHP, BBzP, and DnOP were in significantly higher concentrations in dust samples collected in homes where polishing agents were used. Data on flooring materials was collected, but there was not a significant difference in concentrations between homes where no polish was used that have balatum (PVC or linoleum) flooring and homes with wood. High frequency of dusting did decrease the concentration.<ref name=dust />

In general, children's exposure to phthalates is greater than that of adults. In a 1990s Canadian study that modeled ambient exposures, it was estimated that daily exposure to DEHP was 9&nbsp;μg/kg bodyweight/day in infants, 19&nbsp;μg/kg bodyweight/day in toddlers, 14&nbsp;μg/kg bodyweight/day in children, and 6&nbsp;μg/kg bodyweight/day in adults.<ref name=phthalates/> Infants and toddlers are at the greatest risk of exposure, because of their mouthing behavior. Body-care products containing phthalates are a source of exposure for infants. The authors of a 2008 study "observed that reported use of infant lotion, infant powder, and infant shampoo were associated with increased infant urine concentrations of [phthalate metabolites], and this association is strongest in younger infants. These findings suggest that dermal exposures may contribute significantly to phthalate body burden in this population." Although they did not examine health outcomes, they noted that "Young infants are more vulnerable to the potential adverse effects of phthalates given their increased dosage per unit body surface area, metabolic capabilities, and developing endocrine and reproductive systems."<ref>{{cite journal | vauthors = Sathyanarayana S, Karr CJ, Lozano P, Brown E, Calafat AM, Liu F, Swan SH | title = Baby care products: possible sources of infant phthalate exposure | journal = Pediatrics | volume = 121 | issue = 2 | pages = e260–e268 | date = February 2008 | pmid = 18245401 | doi = 10.1542/peds.2006-3766 | s2cid = 22218732 }}</ref>

Infants and hospitalized children are particularly susceptible to phthalate exposure. Medical devices and tubing may contain 20–40% Di(2-ethylhexyl) phthalate (DEHP) by weight, which "easily leach out of tubing when heated (as with warm saline / blood)".<ref name="Sathyanarayana">{{cite journal | vauthors = Sathyanarayana S | title = Phthalates and children's health | journal = Current Problems in Pediatric and Adolescent Health Care | volume = 38 | issue = 2 | pages = 34–49 | date = February 2008 | pmid = 18237855 | doi = 10.1016/j.cppeds.2007.11.001 }}</ref> Several medical devices contain phthalates including, but not limited to, IV tubing, gloves, nasogastric tubes, and respiratory tubing. The Food and Drug Administration did an extensive risk assessment of phthalates in the medical setting and found that neonates may be exposed to five times greater than the allowed daily tolerable intake. This finding led to the conclusion by the FDA that, "[c]hildren undergoing certain medical procedures may represent a population at increased risk for the effects of DEHP".<ref name="Sathyanarayana" />

In 2008, the Danish Environmental Protection Agency (EPA) found a variety of phthalates in erasers and warned of health risks when children regularly suck and chew on them. The European Commission [[Organization:Scientific Committee on Health and Environmental Risks|Scientific Committee on Health and Environmental Risks]] (SCHER), however, considers that, even in the case when children bite off pieces from erasers and swallow them, it is unlikely that this exposure leads to health consequences.<ref>{{cite report|url=http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_106.pdf|title=Opinion on phthalates in school supplies|date=17 October 2008|publisher=Scientific Committee on Health and Environmental Risks, European Commission}}</ref>

Phthalates are also found in medications, where they are used as inactive ingredients in producing [[Chemistry:Enteric coating|enteric coating]]s. It is not known how many medications are made using phthalates, but some include [[Chemistry:Omeprazole|omeprazole]], [[Chemistry:Didanosine|didanosine]], mesalamine, and [[Biology:Theophylline|theophylline]]. A recent study found that urinary concentrations of [[Chemistry:Monobutyl phthalate|monobutyl phthalate]], the DBP metabolite, of Asacol (a particular formulation of mesalamine) users was 50 times higher than the mean of nonusers.<ref name=meds/> The study showed that exposures from phthalate-containing medications can far exceed population levels from other sources.<ref name="meds">{{cite journal | vauthors = Hernández-Díaz S, Mitchell AA, Kelley KE, Calafat AM, Hauser R | title = Medications as a potential source of exposure to phthalates in the U.S. population | journal = Environmental Health Perspectives | volume = 117 | issue = 2 | pages = 185–189 | date = February 2009 | pmid = 19270786 | pmc = 2649218 | doi = 10.1289/ehp.11766 }}</ref> DBP in medications raises concern about health risks due to the high level of exposures associated with taking these medications, especially in vulnerable segments of the population, including pregnant women and children.<ref name=meds/>

In 2008, the United States National Research Council recommended that the cumulative effects of phthalates and other antiandrogens be investigated. It criticized U.S. EPA guidances, which stipulate that, when examining cumulative effects, the chemicals examined should have similar mechanisms of action or similar structures, as too restrictive. It recommended instead that the effects of chemicals that cause similar adverse outcomes should be examined cumulatively.<ref>{{Cite book|title=Phthalates and Cumulative Risk Assessment: The Tasks Ahead|publisher=National Research Council|date=2008-12-18|isbn=9780309128414|language=en|doi=10.17226/12528|pmid=25009926|doi-access=free|author1=National Research Council (US) Committee on the Health Risks of Phthalates}}</ref> Thus, the effect of phthalates should be examined together with other antiandrogens, which otherwise may have been excluded because their mechanisms or structure are different.

==Health effects==
[[File:CBP Seizes Hazardous Toy Dolls (10928300625).jpg|thumb|Toy dolls manufactured in China and seized by U.S. Customs and Border Protection in 2013 due to high phthalate levels]]A study in the peer-reviewed journal ''Environmental Pollution'' published October 12, 2021 found that high phthalate levels are weakly correlated with a greater risk of dying from any cause and with a stronger correlation to dying from heart problems, but the calculated hazard ratios were below 2 in both cases. The study estimated that phthalates may contribute to 91,000–107,000 premature deaths each year among people aged 55–64 in the United States.<ref>{{Cite web| vauthors = LaMotte S |date=12 October 2021|title=Synthetic chemical in consumer products linked to early death, study finds|url=https://www.cnn.com/2021/10/12/health/plastic-chemical-early-death-wellness/index.html|url-status=live|access-date=2021-10-12|website=CNN}}</ref>

===Endocrine disruption===

Phthalates enter the bloodstream and disrupt sex hormone production, interfering with sexual development in infants and sexual behaviour in adults. Levels of phthalates have been dose-dependently linked to reduced [[Biology:Anogenital distance|anogenital distance]]<ref>{{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 | display-authors = 6 | title = Decrease in anogenital distance among male infants with prenatal phthalate exposure | journal = Environmental Health Perspectives | volume = 113 | issue = 8 | pages = 1056–1061 | date = August 2005 | pmid = 16079079 | pmc = 1280349 | doi = 10.1289/ehp.8100 | collaboration = Study for Future Families Research Team | doi-access = free }}</ref> decreased sexual desire and satisfaction in women,<ref>{{cite journal | vauthors = Barrett ES, Parlett LE, Wang C, Drobnis EZ, Redmon JB, Swan SH | title = Environmental exposure to di-2-ethylhexyl phthalate is associated with low interest in sexual activity in premenopausal women | journal = Hormones and Behavior | volume = 66 | issue = 5 | pages = 787–792 | date = November 2014 | pmid = 25448532 | pmc = 5035677 | doi = 10.1016/j.yhbeh.2014.10.003 }}</ref> and malformed genital development in rats.

Phthalates act by mimicking the female hormone estrogen, which in turn inhibits production of the male hormone testosterone. As such, phthalates are considered to be [[Chemistry:Endocrine disruptor|endocrine disruptor]]s<ref name=DiamantiKandarakis2009 /><ref name=Zamkowska2018>{{cite journal | vauthors = Zamkowska D, Karwacka A, Jurewicz J, Radwan M | title = Environmental exposure to non-persistent endocrine disrupting chemicals and semen quality: An overview of the current epidemiological evidence | journal = International Journal of Occupational Medicine and Environmental Health | volume = 31 | issue = 4 | pages = 377–414 | date = July 2018 | pmid = 30160090 | doi = 10.13075/ijomeh.1896.01195 | doi-access = free }}</ref><ref name=Bansal2018>{{cite journal | vauthors = Bansal A, Henao-Mejia J, Simmons RA | title = Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health | journal = Endocrinology | volume = 159 | issue = 1 | pages = 32–45 | date = January 2018 | pmid = 29145569 | pmc = 5761609 | doi = 10.1210/en.2017-00882 }}</ref>—a substance that interferes with the normal hormonal mechanisms that allow a biological organism to interact with its environment, and has sparked demands to ban or restrict its use in baby toys.<ref name=DiamantiKandarakis2009>{{cite journal | vauthors = Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC | display-authors = 6 | 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>

Endocrine disruptors exhibit numerous behaviors that can make studying them a challenge. There can be a lag between when someone is exposed to an endocrine disruptor and any symptoms manifesting themselves–in particular fetal and early childhood exposure may have consequences later in adulthood.<ref name=DiamantiKandarakis2009 /><ref name=Braun2017>{{cite journal | vauthors = Braun JM | title = Early-life exposure to EDCs: role in childhood obesity and neurodevelopment | journal = Nature Reviews. Endocrinology | volume = 13 | issue = 3 | pages = 161–173 | date = March 2017 | pmid = 27857130 | pmc = 5322271 | doi = 10.1038/nrendo.2016.186 }}</ref> Many studies refer to this period of fetal and postnatal development as particularly important to development, but studying this is difficult; it is obviously a huge challenge to measure endocrine disruptor exposure during fetal development and then decades later diagnosing any health problems. Additionally, endocrine disruptor exposure can transmit epigenetically to one's offspring without them being directly exposed to the endocrine disruptors.<ref>{{cite journal | vauthors = Anway MD, Cupp AS, Uzumcu M, Skinner MK | title = Epigenetic transgenerational actions of endocrine disruptors and male fertility | journal = Science | volume = 308 | issue = 5727 | pages = 1466–1469 | date = June 2005 | pmid = 15933200 | doi = 10.1126/science.1108190 | s2cid = 236588 | bibcode = 2005Sci...308.1466A | url = https://digitalcommons.unl.edu/animalscifacpub/169 }}</ref> Finally, particularly low levels of exposure may still have significant effects, and exposure to multiple endocrine disruptors across a variety of compounds (not just phthalates) may synergistically combine to cause a greater effect.<ref name=DiamantiKandarakis2009 /><ref name=Braun2017 /> Evaluating the actual effects of a specific compound such as a particular phthalate requires examining cumulative exposure across multiple compounds, rather than evaluating one compound in isolation.<ref name=Braun2017 />

A widespread concern about phthalate exposure is the possibility (though not conclusive) that it is the cause of a worldwide drop in male fertility.<ref>{{Cite web| vauthors = Halpern DN | title = What Happens If We Hit Sperm Count Zero?| work = GQ| access-date = 15 November 2018| date = 2018-09-04| url = https://www.gq.com/story/sperm-count-zero}}</ref><ref>{{Cite web|  vauthors = Belluz J | title = Sperm counts are falling. This isn't the reproductive apocalypse — yet.| work = Vox| access-date = 15 November 2018| date = 2018-09-17| url = https://www.vox.com/science-and-health/2018/9/17/17841518/low-sperm-count-semen-male-fertility}}</ref><ref>{{Cite news| issn = 0362-4331| vauthors = Salam M | title = Sperm Count in Western Men Has Dropped Over 50 Percent Since 1973, Paper Finds| work = The New York Times| access-date = 15 November 2018| date = 2018-01-20| url = https://www.nytimes.com/2017/08/16/health/male-sperm-count-problem.html}}</ref> Studies have shown that phthalates cause abnormalities in the reproductive systems of animals,<ref>{{cite journal | vauthors = Hauser R, Calafat AM | title = Phthalates and human health | journal = Occupational and Environmental Medicine | volume = 62 | issue = 11 | pages = 806–818 | date = November 2005 | pmid = 16234408 | pmc = 1740925 | doi = 10.1136/oem.2004.017590 }}</ref> with the greatest effects when the animal is exposed during gestation and immediately thereafter.<ref name=Lyche2009>{{cite journal | vauthors = Lyche JL, Gutleb AC, Bergman A, Eriksen GS, Murk AJ, Ropstad E, Saunders M, Skaare JU | display-authors = 6 | title = Reproductive and developmental toxicity of phthalates | journal = Journal of Toxicology and Environmental Health Part B: Critical Reviews | volume = 12 | issue = 4 | pages = 225–249 | date = April 2009 | pmid = 20183522 | doi = 10.1080/10937400903094091 | s2cid = 28086323 }}</ref> Numerous studies on adult male humans show the similar result that phthalate exposure correlates with worsening metrics of male fertility, such as semen quality, the quantity of damaged DNA in sperm, decreased sperm motility, decreased semen volume, and other metrics.<ref name=Zamkowska2018 /><ref name=Lyche2009 /><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 = 115–141 | date = June 2011 | pmid = 21594692 | doi = 10.2478/s13382-011-0022-2 | doi-access = free }}</ref> Phthalates causing harm to the male reproductive system is plausible,<ref>{{cite journal | vauthors = Albert O, Jégou B | title = A critical assessment of the endocrine susceptibility of the human testis to phthalates from fetal life to adulthood | journal = Human Reproduction Update | volume = 20 | issue = 2 | pages = 231–249 | date = March 2014 | pmid = 24077978 | doi = 10.1093/humupd/dmt050 | doi-access = free }}</ref> and continues to be researched.

The effect of phthalates on the female reproductive system is also not fully understood yet. Current studies indicate phthalates have negative effects on folliculogenesis and steroidogenesis.<ref>{{cite journal | vauthors = Hannon PR, Flaws JA | title = The effects of phthalates on the ovary | journal = Frontiers in Endocrinology | volume = 6 | pages = 8 | date = 2015-02-02 | pmid = 25699018 | pmc = 4313599 | doi = 10.3389/fendo.2015.00008 | doi-access = free }}</ref>

Early research also shows phthalate exposure may be associated with diabetes and insulin resistance, breast cancer, obesity,<ref>{{cite journal | vauthors = Giulivo M, Lopez de Alda M, Capri E, Barceló D | title = Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review | journal = Environmental Research | volume = 151 | pages = 251–264 | date = November 2016 | pmid = 27504873 | doi = 10.1016/j.envres.2016.07.011 | bibcode = 2016ER....151..251G }}</ref> metabolic disorders, and immune function.<ref name=Bansal2018 />

There are possible (though not conclusive) associations between phthalate exposure and adverse child neurodevelopment,<ref>{{cite journal | vauthors = Factor-Litvak P, Insel B, Calafat AM, Liu X, Perera F, Rauh VA, Whyatt RM | title = Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years | journal = PLOS ONE | volume = 9 | issue = 12 | pages = e114003 | date = 10 December 2014 | pmid = 25493564 | pmc = 4262205 | doi = 10.1371/journal.pone.0114003 | doi-access = free | bibcode = 2014PLoSO...9k4003F }}</ref><ref>{{cite journal | vauthors = Balalian AA, Whyatt RM, Liu X, Insel BJ, Rauh VA, Herbstman J, Factor-Litvak P | title = Prenatal and childhood exposure to phthalates and motor skills at age 11 years | journal = Environmental Research | volume = 171 | pages = 416–427 | date = April 2019 | pmid = 30731329 | pmc = 6814270 | doi = 10.1016/j.envres.2019.01.046 | bibcode = 2019ER....171..416B }}</ref> including the development of ADHD and autistic behaviors and lower cognitive and motor development.<ref name="Engel_2021">{{cite journal | vauthors = Engel SM, Patisaul HB, Brody C, Hauser R, Zota AR, Bennet DH, Swanson M, Whyatt RM | display-authors = 6 | title = Neurotoxicity of Ortho-Phthalates: Recommendations for Critical Policy Reforms to Protect Brain Development in Children | journal = American Journal of Public Health | volume = 111 | issue = 4 | pages = 687–695 | date = April 2021 | pmid = 33600256 | pmc = 7958063 | doi = 10.2105/AJPH.2020.306014 }}</ref> Most common associations found in medical reports link the phthalates exposure to hyperactivity, aggression, and other adverse behaviors.<ref name="Engel_2021"/> Some studies have found the childhood exposure to be as early as in utero.<ref>{{cite journal | vauthors = Factor-Litvak P, Insel B, Calafat AM, Liu X, Perera F, Rauh VA, Whyatt RM | title = Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years | journal = PLOS ONE | volume = 9 | issue = 12 | pages = e114003 | date = 2014-12-10 | pmid = 25493564 | pmc = 4262205 | doi = 10.1371/journal.pone.0114003 | doi-access = free | bibcode = 2014PLoSO...9k4003F }}</ref>

In many cases, there are studies that show connections between phthalates and these negative outcomes, as well as studies that show no connection; this is likely due to the research challenges outlined above, and when resolved, could show that phthalate exposure does not cause health effects, or even that they have a much greater effect than currently predicted.<ref name=Braun2017 /> In all cases, larger studies are needed to demonstrate incontrovertibly what effect phthalate exposure has on human health.

A Nature Reviews Endocrinology review paper from 2017<ref name=Braun2017 /> gives some advice for avoiding exposure to phthalates for concerned people; while they make pains to state that there is no evidence that shows this advice will positively affect one's health, they suggest (1) eating a balanced diet to avoid ingesting too many endocrine disruptors from a single source, (2) eliminating canned or packaged food in order to limit ingestion of DEHP phthalates leached from plastics, and (3) eliminating use of any personal product such as moisturizer, perfume, or cosmetics that contain phthalates.<ref name=Braun2017 /> Eliminating personal products containing phthalates can be particularly difficult or impossible due to some countries such as the United States not requiring them to be disclosed in a list of ingredients.<ref>{{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 = July 2012 | pmid = 22398195 | pmc = 3404651 | doi = 10.1289/ehp.1104052 }}</ref>

=== Endocannabinoid system disruption ===
Phthalates block [[Biology:Cannabinoid receptor type 1|CB<sub>1</sub>]] as [[Biology:Allosteric regulation|allosteric]] [[Biology:Agonist|antagonists]].<ref>{{cite journal | vauthors = McPartland JM, Guy GW, Di Marzo V | title = Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system | journal = PLOS ONE | volume = 9 | issue = 3 | pages = e89566 | date = 12 March 2014 | pmid = 24622769 | pmc = 3951193 | doi = 10.1371/journal.pone.0089566 | doi-access = free | bibcode = 2014PLoSO...989566M }}</ref>

===Other effects===

There may be a link between the obesity epidemic and endocrine disruption and metabolic interference. Studies conducted on mice exposed to phthalates in utero did not result in metabolic disorder in adults.<ref name="obesity">{{cite journal | vauthors = Desvergne B, Feige JN, Casals-Casas C | title = PPAR-mediated activity of phthalates: A link to the obesity epidemic? | journal = Molecular and Cellular Endocrinology | volume = 304 | issue = 1–2 | pages = 43–48 | date = May 2009 | pmid = 19433246 | doi = 10.1016/j.mce.2009.02.017 | s2cid = 12880759 }}</ref> However, "in a national cross-section of U.S. men, concentrations of several prevalent phthalate metabolites showed statistically significant correlations with abnormal obesity and insulin resistance."<ref name="obesity"/>  Mono-ethylhexyl-phthalate (MEHP), a metabolite of [[Chemistry:Bis(2-ethylhexyl) phthalate|DEHP]], has been found to interact with all three peroxisome proliferator-activated receptors (PPARs).<ref name="obesity"/> PPARs are members of the nuclear receptor superfamily. The author of the study stated "The roles of PPARs in lipid and carbohydrate metabolism raise the question of their activation by a sub-class of pollutants, tentatively named metabolic disrupters."<ref name="obesity"/> Phthalates belong to this class of metabolic disruptors. It is a possibility that, over many years of exposure to these metabolic disruptors, they are able to deregulate complex metabolic pathways in a subtle manner.<ref name=obesity />

Large amounts of specific phthalates fed to rodents have been shown to damage their [[Biology:Liver|liver]] and testes,<ref name="CDC">[https://www.cdc.gov/exposurereport/pdf/thirdreport.pdf Third National Report on Human Exposure to Environmental Chemicals], (PDF) U.S. CDC, July 2005. {{webarchive |url=https://web.archive.org/web/20070401141153/http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf |date=1 April 2007 }}</ref> and initial rodent studies also indicated [[Medicine:Liver cancer|hepatocarcinogenicity]]. Following this result, [[Chemistry:Bis(2-ethylhexyl) phthalate|di(2-ethylhexyl) phthalate]] was listed as a possible [[Biology:Carcinogen|carcinogen]] by [[Organization:International Agency for Research on Cancer|IARC]], EC, and WHO. Later studies on primates showed that the mechanism is specific to rodents; humans are resistant to the effect.<ref>{{cite web |title=Chronic Hazard Advisory on Diisononyl Phthalate |url=http://www.cpsc.gov/library/foia/foia01/os/dinp.pdf |page=87 |year=2001 |quote=Human risk is therefore seen as negligible |access-date=2009-01-31 |url-status=dead |archive-url=https://web.archive.org/web/20081005052725/https://www.cpsc.gov/library/foia/foia01/os/dinp.pdf |archive-date=2008-10-05 }}</ref> The carcinogen classification was subsequently withdrawn.

==Legal status==
===Canada===
In 1994, a [[Organization:Health Canada|Health Canada]] assessment found that DEHP and another phthalate product, B79P, were harmful to human health. The Canadian federal government responded by banning their use in cosmetics and restricting their use in other applications.<ref name="GovCan">{{cite web |url=https://www.canada.ca/en/health-canada/services/chemicals-product-safety/phthalates.html |title=Phthalates |date=6 October 2017 |publisher=Government of Canada |access-date=11 July 2019 |language=en}}</ref>

A more recent assessment in 2017 found that B79P and DEHP may cause environmental damage. As of 2019, regulations to protect the environment against DEHP and B79P have not yet been put into place.<ref name="GovCan2">{{cite web | url=https://www.canada.ca/en/health-canada/services/chemical-substances/fact-sheets/chemicals-glance/phthalates.html |title=Phthalate Substance Grouping – information sheet |website=canada.ca |date=12 March 2017 |publisher=Government of Canada |access-date=11 July 2019 |language=en}}</ref>

===European Union===
[[File:European Plasticisers - Classified and Non Classified.jpg|thumb|Update on non-classified plasticisers and the European REACH Candidate Classification including pending authorisation]]
The use of some phthalates has been restricted in the European Union for use in children's toys since 1999.<ref>{{cite EU law|title=Commission Decision of 7 December 1999 adopting measures prohibiting the placing on the market of toys and childcare articles intended to be placed in the mouth by children under three years of age made of soft PVC containing one or more of the substances di-iso-nonyl phthalate (DINP), di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), di-iso-decyl phthalate (DIDP), di-n-octyl phthalate (DNOP), and butylbenzyl phthalate (BBP)|eurlextag=CELEX:31999D0815|eurlexscheme=|url=http://eur-lex.europa.eu/legal-content/EN/TXT/?qid=1491589449914&uri=CELEX:31999D0815}}</ref> DEHP, BBP, and DBP are restricted for all toys; DINP, DIDP, and DNOP are restricted only in toys that can be taken into the mouth. The restriction states that the amount of these phthalates may not be greater than 0.1% mass percent of the plasticized part of the toy.

Generally, the high molecular weight phthalates DINP, DIDP, and DPHP have been registered under [[Chemistry:Registration, Evaluation, Authorisation and Restriction of Chemicals|REACH]] and have demonstrated their safety for use in current applications. They are not classified for any health or environmental effects.

The low molecular weight products BBP, DEHP, DIBP, and DBP were added to the Candidate list of Substances for Authorisation under REACH in 2008–9, and added to the Authorisation list, Annex XIV, in 2012.<ref name=":1" /> This means that from February 2015 they are not allowed to be produced in the EU unless authorisation has been granted for a specific use, however they may still be imported in consumer products.<ref>{{Cite web | url=https://chemicalwatch.com/23104/echa-and-denmark-to-prepare-phthalates-restriction | title=Echa and Denmark to prepare phthalates restriction}}</ref> The creation of an Annex XV dossier, which could ban the import of products containing these chemicals, was being prepared jointly by the ECHA and Danish authorities, and expected to be submitted by April 2016.<ref>{{Cite web | url=http://echa.europa.eu/registry-of-current-restriction-proposal-intentions/-/substance-rev/6301/term | title=Registry of Intentions - ECHA}}</ref>

In 2006 the Dutch office of Greenpeace UK sought to encourage the [[Social:European Union|European Union]] to ban sex toys that contained phthalates.<ref>[http://www.mskft.com/sex-toys-contain-toxins/ Ms. KFT] Retrieved 22 December 2014  {{webarchive|url=https://archive.today/20140915175616/http://www.mskft.com/sex-toys-contain-toxins/ |date=15 September 2014 }}</ref>

===United States===
During August 2008, the United States Congress passed and President George W. Bush signed the Consumer Product Safety Improvement Act (CPSIA), which became public law 110–314.<ref>GovTrack.us. "[http://www.govtrack.us/congress/bill.xpd?bill=h110-4040 H.R. 4040--110th Congress (2007): Consumer Product Safety Improvement Act of 2008], GovTrack.us (database of federal legislation). Retrieved 14 August 2009.</ref> Section 108 of that law specified that as of February 10, 2009, "it shall be unlawful for any person to manufacture for sale, offer for sale, distribute in commerce, or import into the United States any children's toy or child care article that contains concentrations of more than 0.1 percent of" DEHP, [[Chemistry:Dibutyl phthalate|DBP]], or [[Chemistry:Benzyl butyl phthalate|BBP]] and "it shall be unlawful for any person to manufacture for sale, offer for sale, distribute in commerce, or import into the United States any children's toy that can be placed in a child's mouth or child care article that contains concentrations of more than 0.1 percent of" DINP, DIDP, DnOP. Furthermore, the law requires the establishment of a permanent review board to determine the safety of other phthalates. Prior to this legislation, the Consumer Product Safety Commission had determined that voluntary withdrawals of DEHP and diisononyl phthalate (DINP) from teethers, pacifiers, and rattles had eliminated the risk to children, and advised against enacting a phthalate ban.<ref>[https://www.npr.org/templates/story/story.php?storyId=102567295 Public Concern, Not Science, Prompts Plastics Ban] by Jon Hamilton, NPR.</ref>

In another development in 1986, California voters approved an initiative to address their growing concerns about exposure to toxic chemicals. That initiative became the Safe Drinking Water and Toxic Enforcement Act of 1986, better known by its original name of Proposition 65.<ref>{{cite web|url=http://oehha.ca.gov/prop65/background/p65plain.html|title=OEHHA Proposition 65: Proposition 65 in Plain Language!|work=ca.gov}}</ref> In December 2013 DINP was listed as a chemical "known to the State of California to cause cancer"<ref>{{cite web|url=http://oehha.ca.gov/prop65/CRNR_notices/list_changes/122013P65list.html|title=OEHHA Proposition 65 (2013) Diisononyl Phthalate (DINP) listed|work=ca.gov}}</ref> This means that, starting December 2014, companies with ten or more employees manufacturing, distributing or selling the product(s) containing DINP are required to provide a clear and reasonable warning for that product. The California Office of Environmental Health Hazard Assessment, charged with maintaining the Proposition 65 list and enforcing its provisions, has implemented a "No Significant Risk Level" of 146 μg/day for DINP.<ref>{{Cite web |date=October 1, 2021 |title=Current Proposition 65 No Significant Risk Levels (NSRLs) Maximum Allowable Dose Levels (MADLs) |url=https://oehha.ca.gov/proposition-65/general-info/current-proposition-65-no-significant-risk-levels-nsrls-maximum |url-status=live |access-date=March 23, 2022 |website=California Office of Environmental Health Hazard Assessment}}</ref>

==Identification in plastics==
[[File:Plastic-recyc-03.svg|thumb|100px|Some "Type 3" plastics contain Phthalates.<ref>{{Cite web |title=Types of Plastic - I-Cycle |url=https://www2.illinois.gov/cms/agency/recycling/i-cycle/Pages/plastics.aspx |access-date=2022-03-23 |website=www2.illinois.gov}}</ref>]]
Phthalates are used in some, but not all, PVC formulations, and there are no specific labeling requirements for phthalates. PVC plastics are typically used for various containers and hard packaging, medical tubing and bags, and are labeled "Type 3". However, the presence of phthalates rather than other plasticizers is not marked on PVC items. Only unplasticized PVC (uPVC), which is mainly used as a hard construction material, has no plasticizers. If a more accurate test is needed, chemical analysis, for example by [[Gas chromatography|gas chromatography]] or liquid chromatography, can establish the presence of phthalates.

[[Chemistry:Polyethylene terephthalate|Polyethylene terephthalate]] (PET, PETE, Terylene, Dacron) is the main substance used to package bottled water and many sodas. Products containing PETE are labeled "Type 1" (with a "1" in the recycle triangle). Although the word "phthalate" appears in the name, PETE does not use phthalates as plasticizers. The terephthalate polymer PETE and the phthalate ester plasticizers are chemically different substances.<ref>{{cite web |url=http://www.plasticsmythbuster.org/s_mythbuster/sec.asp?CID=1985&DID=8371 |title=Learn the Facts About Food Packaging and Phthalates |publisher=Plasticsmythbuster.org |access-date=2013-09-23 |archive-url=https://web.archive.org/web/20090706092722/http://www.plasticsmythbuster.org/s_mythbuster/sec.asp?CID=1985&DID=8371 |archive-date=6 July 2009 |url-status=dead }}</ref> Despite this, however, a number of studies have found phthalates such as DEHP in bottled water and soda.<ref name=":0">{{cite journal | vauthors = Sax L | title = Polyethylene terephthalate may yield endocrine disruptors | journal = Environmental Health Perspectives | volume = 118 | issue = 4 | pages = 445–448 | date = April 2010 | pmid = 20368129 | pmc = 2854718 | doi = 10.1289/ehp.0901253 }}</ref> One hypothesis is that these may have been introduced during [[Physics:Plastic recycling|plastic recycling]].<ref name=":0" />

== See also ==
* [[Earth:Xenoestrogen|Xenoestrogen]]
* Non-phthalate plasticizers such as
**[[Chemistry:1,2-Cyclohexane dicarboxylic acid diisononyl ester|1,2-Cyclohexane dicarboxylic acid diisononyl ester]],
**[[Chemistry:Dioctyl terephthalate|Dioctyl terephthalate]], and
**[[Chemistry:Citrate|Citrate]]s
*[[Chemistry:Antiandrogens in the environment|Antiandrogens in the environment]]

== References ==
{{Reflist|colwidth=35em}}

=== Further reading ===
{{Refbegin}}
* {{cite journal | vauthors = Lovekamp-Swan T, Davis BJ | title = Mechanisms of phthalate ester toxicity in the female reproductive system | journal = Environmental Health Perspectives | volume = 111 | issue = 2 | pages = 139–145 | date = February 2003 | pmid = 12573895 | pmc = 1241340 | doi = 10.1289/ehp.5658 }}
* {{cite journal | vauthors = Tickner JA, Schettler T, Guidotti T, McCally M, Rossi M | title = Health risks posed by use of Di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review | journal = American Journal of Industrial Medicine | volume = 39 | issue = 1 | pages = 100–111 | date = January 2001 | pmid = 11148020 | doi = 10.1002/1097-0274(200101)39:1<100::AID-AJIM10>3.0.CO;2-Q | s2cid = 23676863 }}
* {{cite journal | vauthors = Kohn MC, Parham F, Masten SA, Portier CJ, Shelby MD, Brock JW, Needham LL | title = Human exposure estimates for phthalates | journal = Environmental Health Perspectives | volume = 108 | issue = 10 | pages = A440–A442 | date = October 2000 | pmid = 11097556 | pmc = 1240144 | doi = 10.2307/3435033 | jstor = 3435033 }}
* {{cite web|url=https://www.cdc.gov/exposurereport/data_tables/chemical_group_12.html|title=National Report on Human Exposure to Environmental Chemicals. Updated Tables, February 2011|author=Centers for Disease Control|url-status=dead|archive-url=https://web.archive.org/web/20101129054623/http://www.cdc.gov/exposurereport/data_tables/chemical_group_12.html|archive-date=29 November 2010}}
* {{cite web|url=https://www.cdc.gov/exposurereport/Phthalates_FactSheet.html|title=Phthalate Fact Sheet|author=Centers for Disease Control|url-status=dead|archive-url=https://web.archive.org/web/20101229125242/http://www.cdc.gov/exposurereport/Phthalates_FactSheet.html|archive-date=29 December 2010}}
* {{cite web|url=http://www.atsdr.cdc.gov/PHS/PHS.aspid=376&tid=65|title=Agency for Toxic Substances and Disease Registry-Public Health Statement for Di(2-ethylhexyl) phthalate DEHP|author=Centers for Disease Control|archive-url=https://web.archive.org/web/20191102151411/https://www.atsdr.cdc.gov/PHS/PHS.aspid%3D376%26tid%3D65|archive-date=2 November 2019|url-status=dead|access-date=28 December 2021}}
* {{cite journal | vauthors = Latini G, Del Vecchio A, Massaro M, Verrotti A, De Felice C | title = Phthalate exposure and male infertility | journal = Toxicology | volume = 226 | issue = 2–3 | pages = 90–98 | date = September 2006 | pmid = 16905236 | doi = 10.1016/j.tox.2006.07.011 }}
* {{cite journal | vauthors = Amaral Mendes JJ | title = The endocrine disrupters: a major medical challenge | journal = Food and Chemical Toxicology | volume = 40 | issue = 6 | pages = 781–788 | date = June 2002 | pmid = 11983272 | doi = 10.1016/S0278-6915(02)00018-2 }}

== External links ==

{{HealthIssuesOfPlastics}}

[[Category:Plasticizers]]
[[Category:Suspected teratogens]]
[[Category:Endocrine disruptors]]

{{Sourceattribution|Phthalate|1}}