Phthalates

General chemical structure of orthophthalates. (R and R' are general placeholders.)

Phthalates (US: /ˈθæleɪts/ UK: /ˈθɑːleɪtsˌ ˈfθælɪts/^[1][2]), 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). While phthalates are commonly used as plasticizers, not all plasticizers are phthalates. The two terms are specific, unique, and not used interchangeably.

Lower-molecular-weight phthalates are typically replaced in many products in the United States, Canada, and European Union over health concerns.^[3][4] They are being replaced by higher molecular-weight phthalates as well as non-phthalic plasticizers.

Phthalates are commonly ingested in small quantities via the diet. There are numerous forms of phthalates not regulated by governments. One of the most commonly known phtalates is bis(2-ethylhexyl) phthalate (DEHP). In many countries, DEHP is regulated as a toxin, and is banned from use in broad categories of consumer goods, such as cosmetics, children's toys, medical devices, and food packaging.

Production

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:

C₆H₄(CO)₂O + ROH → C₆H₄(CO₂R)(CO₂H)

C₆H₄(CO₂R)(CO₂H) + ROH → C₆H₄(CO₂R)₂ + H₂O

The conversion is conducted at high temperatures to drive off the water. Typical catalysts are based on tin or titanium alkoxides or carboxylates.^[5]

The properties of the phthalate can be varied by changing the alcohol.^[6] 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,^[7] up from around 2.7 million tonnes in the 1980s.^[8] 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.^[9] 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.^[7]

Common phthalates
Ordered by molecular weight, 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)[10]
Dimethyl phthalate	DMP	1	194.18	131-11-3
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 PBT
Diisobutyl phthalate	DIBP	4	278.34	84-69-5	Toxic to reproduction, endocrine disrupting
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
Diisoheptyl phthalate	DIHpP	7	362.5	41451-28-9	Toxic to reproduction
Butyl decyl phthalate	BDP	4 – 10	362.5	89-19-0
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
Diisononyl phthalate	DINP	9	418.61	28553-12-0	Not classified but some uses restricted
Di(2-propylheptyl) phthalate	DPHP	10	446.66	53306-54-0	Under assessment as endocrine disrupting
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

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.^[11][12] They were the first commercially important compounds for this role,^[13] a historic advantage that has led to them becoming firmly embedded in flexible PVC technology.^[14] 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.^[14] Phthalates derived from alcohols with 7-13 carbon atoms occupy a privileged position as general purpose plasticizers, suitable for almost all flexible PVC applications.^[15][14] 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).^[14]

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.^[16][17] 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.^[17] DINP and DIDP are used as a substitutes for DEHP in many applications, as they are not classified as hazardous.^[18] Non-phthalate plasticizers are also being increasingly used.

Almost 90% of all plasticizers are used in PVC, giving this material improved flexibility and durability.^[19] The majority is used in films and cable sheathing.^[17] 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^[20]

	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
Rigid	0	1.4		900	41	<15	Unplasticized PVC (UPVC): window frames and sills, doors, 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 (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.^[19]

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.^[21] 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.^[22][23][5] Low-molecular-weight phthalates like dimethyl phthalate and diethyl phthalate are used as fixatives for perfumes.^[24][25] Dimethyl phthalate has been also used as an insect repellent and is especially useful against ixodid ticks responsible for Lyme disease.^[26] and species of mosquitoes such as Anopheles stephensi, Culex pipiens and Aedes aegypti,^[27][28][29]

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 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.

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.^[30] 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.^[31]

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

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 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.^[32] 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.^[32]

Many bio-based plasticizers based on vegetable oil have been developed.^[33]

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.^[34] Exposure to phthalates is more likely in women and people of color.^[35] Differences were found 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.^[35] Overall, the study concludes that phthalates may alter glucose homeostasis and insulin sensitivity. Higher levels of some phthalate metabolites were associated with elevated FBG, fasting insulin, and insulin resistance. Non-Hispanic black women and Hispanic women have higher levels of some phthalate metabolites.^[36]

Higher dust concentrations of DEHP were found in homes of children with asthma and allergies, compared with healthy children's homes.^[37] 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."^[37] 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.^[37]

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 μg/kg bodyweight/day in infants, 19 μg/kg bodyweight/day in toddlers, 14 μg/kg bodyweight/day in children, and 6 μg/kg bodyweight/day in adults.^[38] 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."^[39]

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)".^[40] 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".^[40]

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 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.^[41]

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.^[42] 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,^[43] 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%.^[44] A 2024 study by Consumer Reports found phthalates in all but one of the grocery store products and fast foods they tested.^[45]

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.^[46] Low-molecular-weight phthalates such as DEP, DBP, BBzP may be dermally absorbed. Inhalational exposure is also significant with the more volatile phthalates.^[38]

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."^[47]

Air

Outdoor air concentrations are higher in urban and suburban areas than in rural and remote areas.^[48] They also pose no acute toxicity.^[21]

Common plasticizers such as DEHP are only weakly volatile. 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.^[48] 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.^[49]

Natural occurrence

Various plants and microorganisms produce small amounts of phthalate esters, the so-called endogenous phthalates.^[50][51] Biosynthesis is believed to involve a modified Shikimate pathway^[52][53] The extent of this natural production is not fully known, but it may create a background of phthalate pollution.

Biodegradation

Phthalates do not persist due to rapid biodegradation, photodegradation, and anaerobic degradation.^[54]

Research

Toy dolls manufactured in China and seized by U.S. Customs and Border Protection in 2013 due to high phthalate levels

Further information: Endocrine disruptor § Phthalates

Phthalates are under research as a class of possible endocrine disruptors, substances that may interfere with normal hormonal responses in varied environmental conditions.^[55][56][57] The concern has sparked demands to ban or restrict the use of phthalates in baby toys.^[58]

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.^[55] Another review showed small reductions in lung function in adolescents and children who had been exposed to phthalates.^[59]

A 2017 review indicated ways to avoid exposure to phthalates:^[60] (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.^[60] Exposure to phthalates may increase the risk of asthma.^[61]

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.^[62]

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.^{[63][64][65][66]} The focus for regulation in these jurisdictions has been mainly on diethyl phthalate (DEHP), which is generally regarded as a carcinogenic toxin requiring regulation.^{[64][65][66][67]}

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.^[68] The EU also regulates some phthalates to protect the environment.^[68]

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.^[63] Australia has a permanent ban on certain children's products containing DEHP, which is considered poisonous if products containing it are placed in the mouths of children up to three years old.^[67]

Canada

In 1994, a 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, such as soft toys and child-care products.^[69] 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.^[64][70] It is on the List of Ingredients that are Prohibited for Use in Cosmetic Products.^[70]

Twenty of the 28 phthalate substances under national screening programs are considered possible risks to human health or the environment.^[64] As of 2021, regulations to protect the environment against DEHP and B79P have not been enacted.^[64]

European Union

Update on non-classified plasticisers and the European REACH Candidate Classification including pending authorisation

Some phthalates have been restricted in the European Union for use in children's toys since 1999.^[68][71] 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 2008–9, and added to the Authorisation list, Annex XIV, in 2012.^[3] 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, although they may still be imported in consumer products.^[68][72] 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.^[73]

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.^[68]

In November 2021, the European Commission added endocrine disrupting properties to DEHP and other phthalates, meaning that companies must apply for REACH authorization for some uses that were previously exempted, including in food packaging, medical devices, and drug packaging.^[68]

Legislation, additional

Date	Action	References
December 14, 2005	The European Union restricted phthalates from several children's toys.	^[citation needed]
June 8, 2011	Guarantees the sale of electronic products free of phthalates.	[74]
July 4, 2017	Included in the candidate list referred to as substances toxic for reproduction.	[75]
November 23, 2021	DIBP is declared as an endocrine disrupting chemical.	[76]
August 11, 2021	The European Parliament eliminates DIBP and other phthalates from sanitary products.	[77]

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.^[78] 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.^[79]

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.^[80] In December 2013, DINP was listed as a chemical "known to the State of California to cause cancer"^[81] 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.^[65]

The CDC provided a 2011 public health statement on diethyl phthalate describing regulations and guidelines concerning its possible harmful health effects.^[66] 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.^[66]

Identification in plastics

Some "Type 3" plastics contain Phthalates.^[82]

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.^[83] Despite this, however, many studies have found phthalates, such as DEHP in bottled water and soda.^[84] One hypothesis is that these may have been introduced during plastic recycling.^[84]

See also

• Xenoestrogen
• Non-phthalate plasticizers such as
  • 1,2-Cyclohexane dicarboxylic acid diisononyl ester,
  • Dioctyl terephthalate, and
  • Citrates
• Antiandrogens in the environment

References

1. "phthalate". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
2. "phthalate" in Collins English Dictionary
3. Commission Regulation (EU) No 143/2011 of 17 February 2011 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’)
4. "Phthalates | Assessing and Managing Chemicals Under TSCA". www.epa.gov. 21 September 2015. Retrieved 7 April 2017.
5. 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
6. Krauskopf LG (September 1993). "Plasticizer structure/performance relationships". Journal of Vinyl and Additive Technology. 15 (3): 140–147. doi:10.1002/vnl.730150306.
7. Holland M (6 June 2018). "Socio-economic assessment of phthalates". Organisation for Economic Co-operation and Development. OECD Environment Working Papers: 15. doi:10.1787/a38a0e34-en. S2CID 134543052.
8. "TR 019 – An Assessment of Occurrence and Effects of Dialkyl-o-Phthalates in the Environment" (PDF). ECETOC. 29 May 1985.
9. Geyer, Roland; Jambeck, Jenna R.; Law, Kara Lavender (July 2017). "Production, use, and fate of all plastics ever made". Science Advances. 3 (7): e1700782. Bibcode:2017SciA....3E0782G. doi:10.1126/sciadv.1700782. PMC 5517107. PMID 28776036.
10. "Search for Chemicals - ECHA". echa.europa.eu. European Chemicals Agency. Retrieved 9 June 2022. Enter CAS No's to validate manually
11. Latini G, De Felice C, Verrotti A (November 2004). "Plasticizers, infant nutrition and reproductive health". Reproductive Toxicology. 19 (1): 27–33. Bibcode:2004RepTx..19...27L. doi:10.1016/j.reprotox.2004.05.011. PMID 15336709.
12. Bi M, Liu W, Luan X, Li M, Liu M, Liu W, Cui Z (October 2021). "Production, Use, and Fate of Phthalic Acid Esters for Polyvinyl Chloride Products in China". Environmental Science & Technology. 55 (20): 13980–13989. Bibcode:2021EnST...5513980B. doi:10.1021/acs.est.1c02374. PMID 34617437. S2CID 238422673.
13. Semon WL, Stahl GA (April 1981). "History of Vinyl Chloride Polymers". Journal of Macromolecular Science: Part A - Chemistry. 15 (6): 1263–1278. doi:10.1080/00222338108066464.
14. Krauskopf LG (2009). "3.13 Plasticizers". Plastics additives handbook (6. ed.). Munich: Carl Hanser Verlag. pp. 485–511. ISBN 978-3-446-40801-2.
15. Godwin A (26 July 2010). "Uses of Phthalates and Other Plasticizers" (PDF). cpsc.gov. ExxonMobil Chemical Company. Retrieved 19 May 2022.
16. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans Volume 29: Some industrial chemicals and dyestuffs (PDF). [Lyon]: International Agency for Research on Cancer. 1982. p. 271. ISBN 978-92-832-1229-4.
17. "Market Report Plasticizers: Industry Analysis|Market Research". www.ceresana.com. Retrieved 19 May 2022.
18. Ventrice P, Ventrice D, Russo E, De Sarro G (July 2013). "Phthalates: European regulation, chemistry, pharmacokinetic and related toxicity". Environmental Toxicology and Pharmacology. 36 (1): 88–96. Bibcode:2013EnvTP..36...88V. doi:10.1016/j.etap.2013.03.014. PMID 23603460.
19. Cadogan DF, Howick CJ (15 June 2000). "Plasticizers". Ullmann's Encyclopedia of Industrial Chemistry. 27: 613–614. doi:10.1002/14356007.a20_439. ISBN 3527306730.
20. Krauskopf LG (2009). Plastics additives handbook (6. ed.). Munich: Carl Hanser Verlag. p. 495. ISBN 978-3-446-40801-2.
21. Herbert K, Götz PH, Siegmeier R, Mayr W. "Peroxy Compounds, Organic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a19_199. ISBN 978-3527306732.
22. Koo HJ, Lee BM (December 2004). "Estimated exposure to phthalates in cosmetics and risk assessment". Journal of Toxicology and Environmental Health. Part A. 67 (23–24): 1901–1914. Bibcode:2004JTEHA..67.1901K. doi:10.1080/15287390490513300. PMID 15513891. S2CID 30617587.
23. Hubinger JC, Havery DC (March 2006). "Analysis of consumer cosmetic products for phthalate esters". Journal of Cosmetic Science. 57 (2): 127–137. PMID 16688376.
24. Al-Saleh I, Elkhatib R (January 2016). "Screening of phthalate esters in 47 branded perfumes". Environmental Science and Pollution Research International. 23 (1): 455–468. Bibcode:2016ESPR...23..455A. doi:10.1007/s11356-015-5267-z. PMID 26310707. S2CID 22840018.
25. "Phthalates in Cosmetics". U.S. Food and Drug Administration (FDA). 19 May 2022. Retrieved 2 November 2022.
26. Brown M, Hebert AA (February 1997). "Insect repellents: an overview". Journal of the American Academy of Dermatology. 36 (2 Pt 1): 243–249. doi:10.1016/S0190-9622(97)70289-5. PMID 9039177.
27. Karunamoorthi K, Sabesan S (May 2010). "Laboratory evaluation of dimethyl phthalate treated wristbands against three predominant mosquito (Diptera: Culicidae) vectors of disease". European Review for Medical and Pharmacological Sciences. 14 (5): 443–448. PMID 20556923.
28. Nathan SS, Kalaivani K, Murugan K (October 2005). "Effects of neem limonoids on the malaria vector Anopheles stephensi Liston (Diptera: Culicidae)". Acta Tropica. 96 (1): 47–55. doi:10.1016/j.actatropica.2005.07.002. PMID 16112073.
29. Kalyanasundaram M, Mathew N (May 2006). "N,N-diethyl phenylacetamide (DEPA): A safe and effective repellent for personal protection against hematophagous arthropods". Journal of Medical Entomology. 43 (3): 518–525. doi:10.1603/0022-2585(2006)43[518:NPDASA]2.0.CO;2. PMID 16739410. S2CID 22623121.
30. Daniels PH (December 2009). "A brief overview of theories of PVC plasticization and methods used to evaluate PVC-plasticizer interaction". Journal of Vinyl and Additive Technology. 15 (4): 219–223. doi:10.1002/vnl.20211. S2CID 137535663.
31. Wilkes CE, Summers JW, Daniels CA, Berard M (1 January 2005). PVC handbook. Hanser. ISBN 978-3446227149. OCLC 488962111.
32. Bui TT, Giovanoulis G, Cousins AP, Magnér J, Cousins IT, de Wit CA (January 2016). "Human exposure, hazard and risk of alternative plasticizers to phthalate esters". The Science of the Total Environment. 541: 451–467. Bibcode:2016ScTEn.541..451B. doi:10.1016/j.scitotenv.2015.09.036. PMID 26410720.
33. "Bio-based plasticizer". University of Minnesota. Archived from the original on 6 April 2012. Retrieved 7 October 2011.
34. Pthalates Fact Sheet (PDF) (Report). Centers for Disease Control and Prevention. November 2009.
35. Huang T, Saxena AR, Isganaitis E, James-Todd T (February 2014). "Gender and racial/ethnic differences in the associations of urinary phthalate metabolites with markers of diabetes risk: National Health and Nutrition Examination Survey 2001-2008". Environmental Health. 13 (1): 6. Bibcode:2014EnvHe..13....6H. doi:10.1186/1476-069X-13-6. PMC 3922428. PMID 24499162.
36. James-Todd TM, Meeker JD, Huang T, Hauser R, Seely EW, Ferguson KK, et al. (March 2017). "Racial and ethnic variations in phthalate metabolite concentration changes across full-term pregnancies". Journal of Exposure Science & Environmental Epidemiology. 27 (2): 160–166. Bibcode:2017JESEE..27..160J. doi:10.1038/jes.2016.2. PMC 4980273. PMID 26860587.
37. Kolarik B, Bornehag CG, Naydenov K, Sundell J, Stavova P, Nielsen OF (December 2008). "The concentrations of phthalates in settled dust in Bulgarian homes in relation to building characteristic and cleaning habits in the family". Atmospheric Environment. 42 (37): 8553–8559. Bibcode:2008AtmEn..42.8553K. doi:10.1016/j.atmosenv.2008.08.028. S2CID 96190203.
38. Heudorf U, Mersch-Sundermann V, Angerer J (October 2007). "Phthalates: toxicology and exposure". International Journal of Hygiene and Environmental Health. 210 (5): 623–634. Bibcode:2007IJHEH.210..623H. doi:10.1016/j.ijheh.2007.07.011. PMID 17889607.
39. Sathyanarayana S, Karr CJ, Lozano P, Brown E, Calafat AM, Liu F, Swan SH (February 2008). "Baby care products: possible sources of infant phthalate exposure". Pediatrics. 121 (2): e260–e268. doi:10.1542/peds.2006-3766. PMID 18245401. S2CID 22218732.
40. Sathyanarayana S (February 2008). "Phthalates and children's health". Current Problems in Pediatric and Adolescent Health Care. 38 (2): 34–49. doi:10.1016/j.cppeds.2007.11.001. PMID 18237855.
41. Opinion on phthalates in school supplies (PDF) (Report). Scientific Committee on Health and Environmental Risks, European Commission. 17 October 2008.
42. National Research Council (US) Committee on the Health Risks of Phthalates (18 December 2008). Phthalates and Cumulative Risk Assessment: The Tasks Ahead. National Research Council. doi:10.17226/12528. ISBN 9780309128414. PMID 25009926.
43. "Methods for the determination of phthalates in food" (PDF). European Commission, Joint Research Centre. Archived from the original (PDF) on 20 July 2011.
44. Edwards L, McCray NL, VanNoy BN, Yau A, Geller RJ, Adamkiewicz G, Zota AR (October 2021). "Phthalate and novel plasticizer concentrations in food items from U.S. fast food chains: a preliminary analysis". Journal of Exposure Science & Environmental Epidemiology. 32 (3): 366–373. doi:10.1038/s41370-021-00392-8. PMC 9119856. PMID 34702987.
45. "The Plastic Chemicals Hiding in Your Food". Consumer Reports. 4 January 2024. Retrieved 17 January 2024.
46. Erythropel HC, Maric M, Nicell JA, Leask RL, Yargeau V (December 2014). "Leaching of the plasticizer di(2-ethylhexyl)phthalate (DEHP) from plastic containers and the question of human exposure". Applied Microbiology and Biotechnology. 98 (24): 9967–9981. doi:10.1007/s00253-014-6183-8. PMID 25376446. S2CID 11715151.
47. Zota AR, Phillips CA, Mitro SD (October 2016). "Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003-2010". Environmental Health Perspectives. 124 (10): 1521–1528. doi:10.1289/ehp.1510803. PMC 5047792. PMID 27072648.
48. Rudel RA, Perovich LJ (January 2009). "Endocrine disrupting chemicals in indoor and outdoor air". Atmospheric Environment. 43 (1): 170–181. Bibcode:2009AtmEn..43..170R. doi:10.1016/j.atmosenv.2008.09.025. PMC 2677823. PMID 20047015.
49. Carlstedt F, Jönsson BA, Bornehag CG (February 2013). "PVC flooring is related to human uptake of phthalates in infants". Indoor Air. 23 (1): 32–39. Bibcode:2013InAir..23...32C. doi:10.1111/j.1600-0668.2012.00788.x. PMID 22563949.
50. Zhang H, Hua Y, Chen J, Li X, Bai X, Wang H (3 July 2018). "Organism-derived phthalate derivatives as bioactive natural products". Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews. 36 (3): 125–144. Bibcode:2018JESHC..36..125Z. doi:10.1080/10590501.2018.1490512. PMID 30444179. S2CID 53565519.
51. Roy RN (November 2020). "Bioactive natural derivatives of phthalate ester". Critical Reviews in Biotechnology. 40 (7): 913–929. doi:10.1080/07388551.2020.1789838. PMID 32683987. S2CID 220654942.
52. Tian C, Ni J, Chang F, Liu S, Xu N, Sun W, et al. (February 2016). "Bio-Source of di-n-butyl phthalate production by filamentous fungi". Scientific Reports. 6 (1): 19791. Bibcode:2016NatSR...619791T. doi:10.1038/srep19791. PMC 4746570. PMID 26857605.
53. Enikeev AG, Semenov AA, Permyakov AV, Sokolova NA, Gamburg KZ, Dudareva LV (May 2019). "Biosynthesis of ortho-Phtalic Acid Esters in Plant and Cell Cultures". Applied Biochemistry and Microbiology. 55 (3): 294–297. doi:10.1134/S0003683819020066. S2CID 174809331.
54. Boll, Matthias; Geiger, Robin; Junghare, Madan; Schink, Bernhard (2020). "Microbial degradation of phthalates: Biochemistry and environmental implications". Environmental Microbiology Reports. 12 (1): 3–15. doi:10.1111/1758-2229.12787. PMID 31364812.
55. Liu B, Lu X, Jiang A, Lv Y, Zhang H, Xu B (January 2024). "Influence of maternal endocrine disrupting chemicals exposure on adverse pregnancy outcomes: A systematic review and meta-analysis". Ecotoxicology and Environmental Safety. 270: 115851. doi:10.1016/j.ecoenv.2023.115851. PMID 38157800.
56. Zamkowska D, Karwacka A, Jurewicz J, Radwan M (July 2018). "Environmental exposure to non-persistent endocrine disrupting chemicals and semen quality: An overview of the current epidemiological evidence". International Journal of Occupational Medicine and Environmental Health. 31 (4): 377–414. doi:10.13075/ijomeh.1896.01195. PMID 30160090.
57. Bansal A, Henao-Mejia J, Simmons RA (January 2018). "Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health". Endocrinology. 159 (1): 32–45. doi:10.1210/en.2017-00882. PMC 5761609. PMID 29145569.
58. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, et al. (June 2009). "Endocrine-disrupting chemicals: an Endocrine Society scientific statement". Endocrine Reviews. 30 (4): 293–342. doi:10.1210/er.2009-0002. PMC 2726844. PMID 19502515.
59. Boissiere-O'Neill T, Lee WR, Blake TL, Sly PD, Vilcins D (February 2024). "Exposure to endocrine-disrupting plasticisers and lung function in children and adolescents: A systematic review and meta-analysis". Environmental Research. 243: 117751. doi:10.1016/j.envres.2023.117751. PMID 38061586.
60. Braun JM (March 2017). "Early-life exposure to EDCs: role in childhood obesity and neurodevelopment". Nature Reviews. Endocrinology. 13 (3): 161–173. doi:10.1038/nrendo.2016.186. PMC 5322271. PMID 27857130.
61. Dodson RE, Nishioka M, Standley LJ, Perovich LJ, Brody JG, Rudel RA (July 2012). "Endocrine disruptors and asthma-associated chemicals in consumer products". Environmental Health Perspectives. 120 (7): 935–943. doi:10.1289/ehp.1104052. PMC 3404651. PMID 22398195.
62. Xia B, Zhu Q, Zhao Y, Ge W, Zhao Y, Song Q, et al. (December 2018). "Phthalate exposure and childhood overweight and obesity: Urinary metabolomic evidence". Environment International. 121 (Pt 1): 159–168. Bibcode:2018EnInt.121..159X. doi:10.1016/j.envint.2018.09.001. PMID 30208345.
63. "Chemicals in food packaging (updated 6 December 2023)". Food Standards - Australia/New Zealand. August 2018. Retrieved 26 November 2024.
64. "Phthalate Substance Grouping – information sheet". canada.ca. Government of Canada. 18 June 2021. Retrieved 25 November 2024.
65. "Current Proposition 65 No Significant Risk Levels (NSRLs) Maximum Allowable Dose Levels (MADLs)". California Office of Environmental Health Hazard Assessment. 1 October 2021. Retrieved 23 March 2022.
66. "Public health statement for diethyl phthalate". Agency for Toxic Substances and Disease Registry, US Centers for Disease Control and Prevention. 21 October 2011. Retrieved 24 November 2024.
67. "DEHP in children's plastic items ban". Australian Competition and Consumer Commission, Product Safety. 2024. Retrieved 26 November 2024.
68. "Phthalates". European Chemicals Agency. November 2021. Retrieved 25 November 2024.
69. "Phthalates". Government of Canada. 6 October 2017. Retrieved 11 July 2019.
70. "Di(2-ethylhexyl) phthalate (DEHP) in Canadians". Government of Canada. 23 August 2023. Retrieved 25 November 2024.
71. 1999/815/EC: 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)
72. "Echa and Denmark to prepare phthalates restriction".
73. "Registry of Intentions - ECHA".
74. "Directive 2011/65/EU of the European Parliament and of the Council of 8 June 2011 on the restriction of the use of certain hazardous substances in electrical and electronic equipment (recast) Text with EEA relevance". EUR-Lex - 32011L0065 - EN - EUR-Lex.
75. "Commission Implementing Decision (EU) 2017/1210 of 4 July 2017 on the identification of bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP) and diisobutyl phthalate (DIBP) as substances of very high concern according to Article 57(f) of Regulation (EC) No 1907/2006 of the European Parliament and of the Council (notified under document C(2017) 4462)". EUR-Lex - 32017D1210 - EN - EUR-Lex. (n.d.-b).
76. "Commission Regulation (EU) 2021/2045 of 23 November 2021 amending Annex XIV to Regulation (EC) No 1907/2006 of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)". EUR-Lex - 32021R2045 - EN - EUR-Lex.
77. "Commission Delegated Directive (EU) 2021/1978 of 11 August 2021 amending, for the purposes of adapting to scientific and technical progress, Annex IV to Directive 2011/65/EU of the European Parliament and of the Council as regards an exemption for the use of bis(2-ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBP), dibutyl phthalate (DBP) and diisobutyl phthalate (DIBP) in spare parts recovered from and used for the repair or refurbishment of medical devices". EUR-Lex - 32021L1978 - EN - EUR-Lex.
78. GovTrack.us. "H.R. 4040--110th Congress (2007): Consumer Product Safety Improvement Act of 2008, GovTrack.us (database of federal legislation). Retrieved 14 August 2009.
79. Hamilton, Jon (1 April 2009). "Public Concern, Not Science, Prompts Plastics Ban". NPR.
80. "OEHHA Proposition 65: Proposition 65 in Plain Language!". ca.gov.
81. "OEHHA Proposition 65 (2013) Diisononyl Phthalate (DINP) listed". ca.gov.
82. "Types of Plastic - I-Cycle". www2.illinois.gov. Retrieved 23 March 2022.
83. "Learn the Facts About Food Packaging and Phthalates". Plasticsmythbuster.org. Archived from the original on 6 July 2009. Retrieved 23 September 2013.
84. Sax L (April 2010). "Polyethylene terephthalate may yield endocrine disruptors". Environmental Health Perspectives. 118 (4): 445–448. doi:10.1289/ehp.0901253. PMC 2854718. PMID 20368129.

Further reading

• Tickner JA, Schettler T, Guidotti T, McCally M, Rossi M (January 2001). "Health risks posed by use of Di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review". American Journal of Industrial Medicine. 39 (1): 100–111. doi:10.1002/1097-0274(200101)39:1<100::AID-AJIM10>3.0.CO;2-Q. PMID 11148020. S2CID 23676863.
• Kohn MC, Parham F, Masten SA, Portier CJ, Shelby MD, Brock JW, Needham LL (October 2000). "Human exposure estimates for phthalates". Environmental Health Perspectives. 108 (10): A440–A442. doi:10.2307/3435033. JSTOR 3435033. PMC 1240144. PMID 11097556.
• Centers for Disease Control. "National Report on Human Exposure to Environmental Chemicals. Updated Tables, February 2011". Archived from the original on 4 January 2010.

External links

• ACC Addresses Phthalates Safety on YouTube: video of Steve Risotto of the American Chemistry Council, 23 October 2009