phthalate phthalate phthalates (us: /ˈθæleɪts/, uk: /ˈθɑːleɪtsˌ ˈfθælɪts/), or phthalate esters, are esters of phthalic acid. they are mainly used as plasticizers, i.e., substances added to plastics to increase their flexibility, transparency, durability, and longevity. they are used primarily to soften polyvinyl chloride (pvc). note that while phthalates are usually plasticizers, not all plasticizers are phthalates. the two terms are specific and unique and cannot be used interchangeably. general chemical structure of orthophthalates. (r and r' are general placeholders.) lower-molecular-weight phthalates, those derived from c3-c6 alcohols, are being gradually replaced in many products in the united states, canada, and european union over health concerns. 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. 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. 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. 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 metabolites of multiple phthalates in their urine. in studies of rodents exposed to certain phthalates, high doses have been shown to change hormone levels and cause birth defects. disparities among minority populations the question of how these plastics are affecting the population has arisen as plasticizer use in everyday items has increased. additionally, if there are any disparities in how these plasticizers may affect minority populations and if they are more susceptible to complications. it has been found that exposure to phthalates is more likely in women and people of color. in one study, researchers looked into potential differences between gender and race as well as potential consequences of this higher phthalate exposure. the study paid particular attention to the relationship between urinary phthalate metabolites and risk factors for diabetes in individuals with no previous diabetes diagnosis. it was found that while there were no statistically significant differences between men and women overall, there were differences between mexican-americans, blacks, and whites in terms of the overall risk of disturbance of glucose homeostasis. with mexican-americans having a fasting blood glucose (fbg) increase of 5.82 mg/dl, blacks having a fasting blood glucose increase of 3.63 mg/dl, and whites having a fasting blood glucose increase of 1.79 mg/dl, there was evidence of an increased risk for minorities. overall, the study concludes that phthalates may alter glucose homeostasis and insulin sensitivity, and that different populations may be more severely impacted. higher levels of some phthalate metabolites were associated with elevated fbg, fasting insulin, and insulin resistance. in a different study looking at the presence of phthalate metabolites in pregnant women, it was found that non-hispanic black women and hispanic women had higher levels of some phthalate metabolites, indicating potential racial disparities in pregnancy outcomes. production phthalates are produced industrially by the acid catalysed reaction of phthalic anhydride with excess alcohol. the synthesis of diethyl phthalate is illustrative of this: the properties of the phthalate can be varied by changing the alcohol, 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, up from around 2.7 million tonnes in the 1980s. 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. common phthalates commercially important compounds shown in bold name abbreviation alcohol carbon number molecular weight (g/mol) cas no. properties of concern for human health (echa classification 2022) dimethyl phthalatedmp1194.18131-11-3 diethyl phthalatedep2222.2484-66-2under assessment as endocrine disrupting diallyl phthalatedap3246.26131-17-9skin sensitising di-n-propyl phthalatedpp3250.29131-16-8 di-n-butyl phthalatedbp4278.3484-74-2toxic to reproduction, endocrine disrupting, under assessment as pbt diisobutyl phthalatedibp4278.3484-69-5toxic to reproduction, endocrine disrupting di-2-methoxyethyl phthalatedmep3282.29117-82-8toxic to reproduction butyl cyclohexyl phthalatebcp4 – 6304.3884-64-0 di-n-pentyl phthalatednpp5306.4131-18-0toxic to reproduction dicyclohexyl phthalatedcp6330.4284-61-7toxic to reproduction, endocrine disrupting, skin sensitising butyl benzyl phthalatebbp4 – 7312.3685-68-7toxic to reproduction, endocrine disrupting di-n-hexyl phthalatednhp6334.4584-75-3toxic to reproduction diisohexyl phthalatedihxp6334.45146-50-9,toxic to reproduction diisoheptyl phthalatedihpp7362.541451-28-9toxic to reproduction butyl decyl phthalatebdp4 – 10362.589-19-0 dibutoxy ethyl phthalatedbep6366.45117-83-9 di(2-ethylhexyl) phthalatedehp, dop8390.56117-81-7toxic to reproduction, endocrine disrupting di(n-octyl) phthalatednop8390.56117-84-0not classified but some uses restricted diisooctyl phthalatediop8390.5627554-26-3toxic to reproduction n-octyl n-decyl phthalateodp8 – 10418.61119-07-3 diisononyl phthalatedinp9418.6128553-12-0not classified but some uses restricted di(2-propylheptyl) phthalatedphp10446.6653306-54-0under assessment as endocrine disrupting diisodecyl phthalatedidp10446.6626761-40-0 diundecyl phthalatedup11474.723648-20-2 diisoundecyl phthalatediup11474.7285507-79-5 ditridecyl phthalatedtdp13530.82119-06-2 diisotridecyl phthalateditp13530.8268515-47-9 natural occurrence various plants and microorganisms have been reported to naturally produce phthalate esters (endogenous phthalates). biosynthesis is believed to involve a modified shikimate pathway the extent of this natural production is not fully known, but it may create a background of phthalate pollution. uses pvc plasticisers 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. they were the first commercially important compounds for this role, a historic advantage that has led to them becoming firmly embedded in flexible pvc technology. among the 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. 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. 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). historically dinp, dehp, bbp, 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 between 3 and 8 carbons are classed as toxic by echa. this includes bis(2-ethylhexyl) phthalate (dehp or dop), which has long been the most widely used phthalate, with commercial production dating back to the 1930s. in the eu, the use of dehp is restricted under 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. dinp and didp are used as a substitutes for dehp in many applications, as they are not classified as hazardous. non-phthalate plasticizers are also being increasingly used. almost 90% of all plasticizers are used in pvc, giving this material improved flexibility and durability. the majority is used in films and cable sheathing. flexible pvc can consist of over 85% plasticizer by mass, however unplasticized pvc (upvc) should not contain any. pvc properties as a function of phthalate plasticizer level plasticizer content (% dinp by weight)specific gravity (20 °c)shore hardness (type a, 15 s)flexural stiffness (mpa)tensile strength (mpa)elongation at break (%)example applications rigid01.490041<15unplasticized pvc (upvc): window frames and sills, doors, rigid pipe semi-rigid251.26946931225vinyl flooring, flexible pipe, thin films (stretch wrap), advertising banners flexible331.22841221295wire and cable insulation, flexible pipe very flexible441.17663.414400boots and clothing, inflatables, extremely flexible861.02< 10fishing lures (soft plastic bait), polymer clay, 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 cellulose-type plastics, such as cellulose acetate, nitrocellulose and cellulose acetate butyrate, with commonly encountered applications including nail polish. most phthalates are also compatible with alkyds and acrylic resins, which are used in both oil and emulsion based paints. other plasticised polymer systems include polyvinyl butyral (particularly the forms used to make laminated glass), pva and its co-polymers like pvca. they are also compatible in nylon, polystyrene, polyurethanes, and certain rubbers; but their use in these is very limited. phthalates can plasticise ethyl cellulose, polyvinyl acetate phthalate (pvap) and cellulose acetate phthalate (cap), all of which are used to make enteric coatings for tablet and 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 organic peroxides. thousands of tonnes are consumed annually for this purpose. the great advantage offered by these esters is that they are phlegmatizers, i.e. they minimize the explosive tendencies of a family of chemical compounds that otherwise are potentially dangerous to handle. phthalates have also been used for producing plastic explosives such as semtex. 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. low-molecular-weight phthalates like dimethyl phthalate and diethyl phthalate are used as fixatives for perfumes. dimethyl phthalate has been also used as an insect repellent and is especially useful against ixodid ticks responsible for lyme disease. and species of mosquitoes such as anopheles stephensi, culex pipiens and aedes aegypti, diallyl phthalate is used to prepare vinyl ester resins with excellent electrical insulation properties, these are used to manufacture of electronics components. alkyds are sometimes classes as phthalates, as they meet the technical definition, however, being polymeric esters of phthalic acid their properties and applications are very different. history the development of cellulose nitrate plastic in 1846 led to the patent of castor oil in 1856 for use as the first plasticizer. in 1870, 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 polyvinyl chloride (pvc) and the development of 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. 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%. properties phthalate esters are the dialkyl or alkyl aryl esters of phthalic acid (also called 1,2-benzenedicarboxylic acid, not be confused with the structurally isomeric terephthalic or isophthalic acids); the name "phthalate" derives from phthalic acid, which itself is derived from the word "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 phthalic anhydride with an appropriate 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. 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