Phthalates

Phthalate esters are produced industrially by the reaction of phthalic anhydride with excess alcohol. Often the phthalic anhydride is molten. The monoesterification occurs readily, but the second step is slow: : : The conversion is conducted at high temperatures to drive off the water. Typical catalysts are based on tin or titanium alkoxides or carboxylates. Around 30 are, or have been, commercially important. Phthalates' share of the global plasticisers market has been decreasing since around 2000 however total production has been increasing, with around 5.5 million tonnes made in 2015, up from around 2.7 million tonnes in the 1980s. The explanation for this is the increasing size of the plasticiser market, largely due driven by increases in PVC production, which nearly 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. ==Uses==

PVC plasticisers Between 90 and 95% of all phthalates are used as plasticisers for the production of flexible PVC. Flexible PVC can consist of over 85% plasticizer by mass, however unplasticized PVC (UPVC) should not contain any. Pthalates were the first commercially important compounds for this role, a historic advantage that has led to them becoming firmly embedded in flexible PVC technology. Phthalates derived from alcohols with 7–13 carbon atoms occupy a privileged position as general purpose plasticizers, suitable for almost all flexible PVC applications. Non-phthalate plasticizers are also being increasingly used. 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 good electrical insulation properties. These resins are used to manufacture of electronics components. ==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 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. ==Properties==

Phthalate esters usually refers to dialkyl 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 polyvinyl polymers 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 the reaction of phthalic anhydride with alcohols. The mechanism by which phthalates and related compounds plasticize 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 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. Because they are not chemically bonded to the host plastics, phthalates are released from the plastic article by relatively gentle means. For example, they can be extracted by extraction with organic solvents and, to some extent, by handling. Alternatives 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 plasticizers are dioctyl terephthalate (DEHT) (a terephthalate isomeric with DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) (a hydrogenated version of DINP). Both DEHT and DINCH have been used in high volumes for a variety of products used in contact with humans as alternative plasticizers for DEHP and DINP. Some of these products include medical devices, toys, and food packaging. DEHT and DINCH are more hydrophobic than other phthalate alternatives such as bis(2-ethylhexyl) adipate (DEHA) and diisodecyl adipate (DIDA). Since alternative plasticizers such as DEHT and DINCH are more likely to bind to organic matter and airborne particles indoors, exposure occurs primarily through food consumption and contact with dust. ==Occurrence and exposure==

Human exposure Due to the ubiquity of plasticized plastics, people are often exposed to phthalates. For example, most Americans tested by the Centers for Disease Control and Prevention have metabolites of multiple phthalates in their urine. Exposure to phthalates is more likely in women and people of color. Differences were found between Mexican-Americans, African-Americans, and Caucasian-Americans 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, African-Americans having a fasting blood glucose increase of 3.63 mg/dL, and Caucasian-Americans having a fasting blood glucose increase of 1.79 mg/dL, there was evidence of an increased risk for minorities. Higher dust concentrations of DEHP were found in homes of children with asthma and allergies, compared with healthy children's homes. 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." 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)". 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, "children undergoing certain medical procedures may represent a population at increased risk for the effects of DEHP". 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, qualifying them as too restrictive. It recommended instead that the effects of chemicals that cause similar adverse outcomes should be examined cumulatively. 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. Food Phthalates are found in food, especially 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%. A 2024 study by Consumer Reports found phthalates in all but one of the grocery store products and fast foods they tested. 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. Low-molecular-weight phthalates such as DEP, DBP, BBzP may be dermally absorbed. Inhalational exposure is also significant with the more volatile phthalates. PVC tubing, vinyl gloves used in food handling, and food packaging may serve as potential sources of phthalate contamination in fast food. One 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 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." Phthalates have a short half-life of less than five hours, so their widespread presence likely indicates continuous exposure rather than long-term accumulation in the body. Air Outdoor air concentrations are higher in urban and suburban areas than in rural and remote areas. They also pose no acute toxicity. Natural occurrence Various plants and microorganisms produce small amounts of phthalate esters, the so-called 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. Biodegradation Phthalates do not persist in the environment due to rapid biodegradation, as established by many studies. Aerobic and anaerobic bacteria promote oxidation of the ring to give phenolic derivatives which further degrade. Even in the absence of bacteria but especially in the presence of soil, phthalate esters undergo hydrolysis to phthalate as well as other processes that affect the ester bond. Photodegradation is another avenue for degradation. ==Research==

in 2013 due to high phthalate levels Phthalates are under research as a class of possible endocrine disruptors, substances that may interfere with normal hormonal responses in varied environmental conditions. The concern has sparked demands to ban or restrict the use of phthalates in baby toys. A 2024 review indicated that exposure of mothers to environmental phthalates may have adverse pregnancy outcomes, such as a higher miscarriage rate and lower birth weights. A 2017 review indicated ways to avoid exposure to phthalates: (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. A 2018 study indicated that exposure to phthalates during developmental stages in childhood may negatively affect adipose tissue function and metabolic homeostasis, possibly increasing the risk of obesity. ==Legal status==

The governments of Australia, New Zealand, Canada, the US, and California have determined that many phthalates are not harmful to human health or the environment in amounts typically found, and therefore are legally unregulated. The European Chemicals Agency (European Union, EU) regards ortho-phthalates, such as DEHP, dibutyl phthalate, diisobutyl phthalate, and benzyl butyl phthalate as potentially harmful to fertility, unborn babies, and the endocrine system. Australia and New Zealand A 2017 survey of foods and packaging in Australia and New Zealand led to recognition of DEHP and diisononyl phthalate as among possible contaminants posing a risk to human health, resulting in several regulations on these phthalates in both countries. In 1999, DEHP was put on the national List of Toxic Substances, under the Canadian Environmental Protection Act, 1999, and in 2021, it was deemed a risk to the environment. It is on the List of Ingredients that are Prohibited for Use in Cosmetic Products. European Union Some phthalates have been restricted in the European Union for use in children's toys since 1999. 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 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 2008–09, and added to the Authorisation list, Annex XIV, in 2012. 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. Since 2021, the European Waste Framework Directive requires manufacturers, importers and distributors of products containing phthalates on the REACH Candidate List to notify the European Chemicals Agency. 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, DBP, or 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, and 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. In 1986, California voters approved an initiative to address concerns about exposure to toxic chemicals. That initiative became the Safe Drinking Water and Toxic Enforcement Act of 1986, also called Proposition 65. In December 2013, DINP was listed as a chemical "known to the State of California to cause cancer" Beginning in December 2014, companies with ten or more employees manufacturing, distributing or selling the product(s) containing DINP were 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. The CDC provided a 2011 public health statement on diethyl phthalate describing regulations and guidelines concerning its possible harmful health effects. Under laws for Superfund sites, the Environmental Protection Agency named diethyl phthalate as a hazardous substance. The Occupational Safety and Health Administration stated that the maximum amount of diethyl phthalate allowed in workroom air during an 8-hour workday, 40-hour workweek, is 5 milligrams per cubic meter. ==Identification in plastics==

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 or liquid chromatography, can establish the presence of phthalates. 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. Despite this, however, many studies have found phthalates, such as DEHP in bottled water and soda. One hypothesis is that these may have been introduced during plastic recycling. == See also ==