Bis(2-ethylhexyl) phthalate (di-2-ethylhexyl phthalate, diethylhexyl phthalate, diisooctyl phthalate, DEHP; incorrectly — dioctyl phthalate, DIOP) is an
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...
with the
formula
In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...
C
6H
4(CO
2C
8H
17)
2. DEHP is the most common member of the class of
phthalate
Phthalates (, ), 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 ...
s, which are used as
plasticizers
A plasticizer ( UK: plasticiser) is a substance that is added to a material to make it softer and more flexible, to increase its plasticity, to decrease its viscosity, and/or to decrease friction during its handling in manufacture.
Plasticiz ...
. It is the
diester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are ...
of
phthalic acid
Phthalic acid is an aromatic dicarboxylic acid, with formula C6H4(CO2H)2. Although phthalic acid is of modest commercial importance, the closely related derivative phthalic anhydride is a commodity chemical produced on a large scale. Phthalic aci ...
and the branched-chain
2-ethylhexanol
2-Ethylhexanol (abbreviated 2-EH) is an organic compound with formula CHO. It is a branched, eight-carbon chiral alcohol (chemistry), alcohol. It is a colorless liquid that is poorly soluble in water but soluble in most organic solvents. It is prod ...
. This colorless viscous liquid is soluble in oil, but not in water.
Production
Di(2-ethylhexyl) phthalate is produced commercially by the reaction of excess
2-ethylhexanol
2-Ethylhexanol (abbreviated 2-EH) is an organic compound with formula CHO. It is a branched, eight-carbon chiral alcohol (chemistry), alcohol. It is a colorless liquid that is poorly soluble in water but soluble in most organic solvents. It is prod ...
with
phthalic anhydride
Phthalic anhydride is the organic compound with the formula C6H4(CO)2O. It is the anhydride of phthalic acid. Phthalic anhydride is a principal commercial form of phthalic acid. It was the first anhydride of a dicarboxylic acid to be used commerc ...
in the presence of an acid catalyst such as
sulfuric acid
Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...
or
''para''-toluenesulfonic acid. It was first produced in commercial quantities in Japan around 1933 and in the United States in 1939.
:
As 2-ethylhexanol is produced as a
racemic
In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
mixture, DEHP consists of the (''R'',''R'')- and (''S'',''S'')-
diasteromer
In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have dif ...
s, and the ''
meso''-isomer.
:
Use
Due to its suitable properties and the low cost, DEHP is widely used as a
plasticizer
A plasticizer ( UK: plasticiser) is a substance that is added to a material to make it softer and more flexible, to increase its plasticity, to decrease its viscosity, and/or to decrease friction during its handling in manufacture.
Plasticiz ...
in manufacturing of articles made of
PVC.
[ Plastics may contain 1% to 40% of DEHP. It is also used as a ]hydraulic fluid
A hydraulic fluid or hydraulic liquid is the medium by which power is transferred in hydraulic machinery. Common hydraulic fluids are based on mineral oil or water. Examples of equipment that might use hydraulic fluids are excavators and backhoe ...
and as a dielectric
In electromagnetism, a dielectric (or dielectric medium) is an electrical insulator that can be polarised by an applied electric field. When a dielectric material is placed in an electric field, electric charges do not flow through the mate ...
fluid in capacitor
A capacitor is a device that stores electrical energy in an electric field by virtue of accumulating electric charges on two close surfaces insulated from each other. It is a passive electronic component with two terminals.
The effect of ...
s. DEHP also finds use as a solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
in glowstick
A glow stick, also known as a light stick, chem light, light wand, light rod, and rave light, is a self-contained, short-term light-source. It consists of a translucent plastic tube containing isolated substances that, when combined, make light ...
s.
Approximately three million tonnes are produced and used annually worldwide.
Manufacturers of flexible PVC articles can choose among several alternative plasticizers offering similar technical properties as DEHP. These alternatives include other phthalates such as diisononyl phthalate
Diisononyl phthalate (DINP) is a phthalate used as a plasticizer. DINP is typically a mixture of chemical compounds consisting of various isononyl esters of phthalic acid, and is commonly used in a large variety of plastic items.
Health Issues
...
(DINP), di-2-propyl heptyl phthalate
Di(2-propylheptyl) phthalate (also known as bis(2-propylheptyl) benzene-1,2-dicarboxylate, di(propylheptyl) orthophthalate, or DPHP) is an organic compound with the formula C28H46O4. It is a phthalate and is the diester of phthalic acid and the 10 ...
(DPHP), diisodecyl phthalate
Diisodecyl phthalate (DIDP) is a commonly used plasticizer used in the production of plastic and plastic coating to increase flexibility. It is a mixture of compounds derived from the esterification of phthalic acid and isomeric decyl alcohols.
T ...
(DIDP), and non-phthalates such as 1,2-cyclohexane dicarboxylic acid diisononyl ester
1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH) is a mixture of organic compounds with the formula C6H10(CO2C9H19)2. DINCH is colorless oil. It is used as a plasticizer for the manufacture of flexible plastic articles in sensitive appl ...
(DINCH), dioctyl terephthalate
Dioctyl terephthalate commonly abbreviated DOTP or DEHT, is an organic compound with the chemical formula, formula C6H4(CO2C8H17)2. It is a non-phthalate plasticizer, being the ester, diester of terephthalic acid and the branched-chain 2-Ethylhexa ...
(DOTP), and citrate
Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in t ...
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
s.
Environmental exposure
DEHP is a component of many household items, including tablecloths, floor tiles, shower curtains, garden hoses, rainwear, dolls, toys, shoes, medical tubing, furniture upholstery, and swimming pool liners. DEHP is an indoor air pollutant in homes and schools. Common exposures come from the use of DEHP as a fragrance carrier in cosmetics
Cosmetics are constituted mixtures of chemical compounds derived from either natural sources, or synthetically created ones. Cosmetics have various purposes. Those designed for personal care and skin care can be used to cleanse or protect ...
, personal care
Personal care or toiletries are consumer products used in personal hygiene, personal grooming or for beautification.
Products
Personal care includes products as diverse as cleansing pads, colognes, cotton swabs, cotton pads, deodorant, eye lin ...
products, laundry detergent
A detergent is a surfactant or a mixture of surfactants with cleansing properties when in dilute solutions. There are a large variety of detergents, a common family being the alkylbenzene sulfonates, which are soap-like compounds that are more ...
s, colognes, scented candles, and air freshener
Air fresheners are consumer products that typically emit fragrance and are used in homes or commercial interiors such as restrooms, foyers, hallways, vestibules and other smaller indoor areas, as well as larger areas such as hotel lobbies, auto d ...
s.
The most common exposure to DEHP comes through food with an average consumption of 0.25 milligrams per day. It can also leach
Leach may refer to:
* Leach (surname)
* Leach, Oklahoma, an unincorporated community, United States
* Leach, Tennessee, an unincorporated community, United States
* Leach Highway, Western Australia
* Leach orchid
* Leach phenotype, a mutation in ...
into a liquid that comes in contact with the plastic; it extracts faster into nonpolar
In chemistry, polarity is a separation of electric charge leading to a molecule or its chemical groups having an electric dipole moment, with a negatively charged end and a positively charged end.
Polar molecules must contain one or more polar ...
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
s (e.g. oil
An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturated ...
s and fat
In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food.
The term often refers spec ...
s in foods packed in PVC). Fatty foods that are packaged in plastics that contain DEHP are more likely to have higher concentrations such as milk products, fish or seafood, and oils. The US FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...
therefore permits use of DEHP-containing packaging only for foods that primarily contain water.
DEHP can leach into drinking water
Drinking water is water that is used in drink or food preparation; potable water is water that is safe to be used as drinking water. The amount of drinking water required to maintain good health varies, and depends on physical activity level, a ...
from discharges from rubber and chemical factories; The US EPA
The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it be ...
limits for DEHP in drinking water is 6 ppb. It is also commonly found in bottled water, but unlike tap water, the EPA does not regulate levels in bottled water. DEHP levels in some European samples of milk, were found at 2000 times higher than the EPA Safe Drinking Water limits (12,000 ppb). Levels of DEHP in some European cheeses and creams were even higher, up to 200,000 ppb, in 1994. Additionally, workers in factories that utilize DEHP in production experience greater exposure. The U.S. agency OSHA
OSHA or Osha may refer to:
Work
* Occupational Safety and Health Administration, a federal agency of the United States that regulates workplace safety and health
* Occupational Safety and Health Act (United States) of 1970, a federal law in the Un ...
's limit for occupational exposure is 5 mg/m3 of air.
Use in medical devices
DEHP is the most common phthalate plasticizer in medical device
A medical device is any device intended to be used for medical purposes. Significant potential for hazards are inherent when using a device for medical purposes and thus medical devices must be proved safe and effective with reasonable assura ...
s such as intravenous tubing and bags, IV catheter
In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cath ...
s, nasogastric tubes, dialysis Dialysis may refer to:
*Dialysis (chemistry), a process of separating molecules in solution
**Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
bags and tubing, blood bags and transfusion tubing, and air tubes. DEHP makes these plastics softer and more flexible and was first introduced in the 1940s in blood bags. For this reason, concern has been expressed about leachates of DEHP transported into the patient, especially for those requiring extensive infusions or those who are at the highest risk of developmental abnormalities, e.g. newborn
An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
s in intensive care nursery
A neonatal intensive care unit (NICU), also known as an intensive care nursery (ICN), is an intensive care unit (ICU) specializing in the care of ill or premature newborn infants. Neonatal refers to the first 28 days of life. Neonatal care, as kn ...
settings, hemophilia
Haemophilia, or hemophilia (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, ...
cs, kidney dialysis
Kidney dialysis (from Greek , , 'dissolution'; from , , 'through', and , , 'loosening or splitting') is the process of removing excess water, solutes, and toxins from the blood in people whose kidneys can no longer perform these functions natura ...
patients, neonates, premature babies, lactating, and pregnant women. According to the European Commission Scientific Committee on Health and Environmental Risks
The Scientific Committee on Health and Environmental Risks (SCHER) is one of the independent scientific committees managed by the Directorate-General for Health and Consumer Protection of the European Commission, which provide scientific advice to ...
(SCHER), exposure to DEHP may exceed the tolerable daily intake in some specific population groups, namely people exposed through medical procedures such as kidney dialysis. The American Academy of Pediatrics
The American Academy of Pediatrics (AAP) is an American professional association of pediatricians, headquartered in Itasca, Illinois. It maintains its Department of Federal Affairs office in Washington, D.C.
Background
The Academy was founded ...
has advocated not to use medical devices that can leach DEHP into patients and, instead, to resort to DEHP-free alternatives. In July 2002, the U.S. FDA issued a Public Health Notification on DEHP, stating in part, "We recommend considering such alternatives when these high-risk procedures are to be performed on male neonates, pregnant women who are carrying male fetuses, and peripubertal males" noting that the alternatives were to look for non-DEHP exposure solutions; they mention a database of alternatives. The CBC documentary ''The Disappearing Male'' raised concerns about sexual development
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. In ...
in male fetal development, miscarriage
Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
), and as a cause of dramatically lower sperm count
A semen analysis (plural: semen analyses), also called seminogram or spermiogram, evaluates certain characteristics of a male's semen and the sperm contained therein. It is done to help evaluate male fertility, whether for those seeking pregnancy ...
s in men. A review article in 2010 in the ''Journal of Transfusion Medicine'' showed a consensus that the benefits of a lifesaving treatments with these devices far outweigh the risks of DEHP leaching out of these devices. Although more research is needed to develop alternatives to DEHP that gives the same benefits of being soft and flexible, which are required for most medical procedures. If a procedure requires one of these devices and if patient is at high risk to suffer from DEHP then a DEHP alternative should be considered if medically safe.
Metabolism
DEHP hydrolyzes to mono-ethylhexyl phthalate (MEHP) and subsequently to phthalate
Phthalates (, ), 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 ...
salts. The released alcohol is susceptible to oxidation to the aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
and carboxylic acid.[
]
Effects on living organisms
Toxicity
The acute toxicity
Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effect ...
of DEHP is low in animal models: 30 g/kg in rats (oral) and 24 g/kg in rabbits (dermal).[ Concerns instead focus on its potential as an ]endocrine disruptor
Endocrine disruptors, sometimes also referred to as hormonally active agents, endocrine disrupting chemicals, or endocrine disrupting compounds are chemicals that can interfere with endocrine (or hormonal) systems. These disruptions can cause c ...
.
Endocrine disruption
DEHP, along with other phthalates
Phthalates (, ), 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 ...
, is believed to cause endocrine disruption in males, through its action as an androgen antagonist
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...
, and may have lasting effects on reproductive function, for both childhood and adult exposures. Prenatal phthalate exposure has been shown to be associated with lower levels of reproductive function in adolescent males. In another study, airborne concentrations of DEHP at a PVC pellet plant were significantly associated with a reduction in sperm motility and chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
DNA integrity. Additionally, the authors noted the daily intake estimates for DEHP were comparable to the general population, indicating a "high percentage of men are exposed to levels of DEHP that may affect sperm motility and chromatin DNA integrity". The claims have received support by a study using dogs as a "sentinel species to approximate human exposure to a selection of chemical mixtures present in the environment". The authors analyzed the concentration of DEHP and other common chemicals such as PCBs
Polychlorinated biphenyls (PCBs) are highly carcinogenic chemical compounds, formerly used in industrial and consumer products, whose production was banned in the United States by the Toxic Substances Control Act in 1979 and internationally by t ...
in testes
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
from dogs from five different world regions. The results showed that regional differences in concentration of the chemicals are reflected in dog testes and that pathologies such as tubule atrophy and germ cell
Germ or germs may refer to:
Science
* Germ (microorganism), an informal word for a pathogen
* Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually
* Germ layer, a primary layer of cells that forms during embry ...
s were more prevalent in testes of dogs proveining from regions with higher concentrations.
Development
Numerous studies of DEHP have shown changes in sexual function and development in mice and rats. DEHP exposure during pregnancy has been shown to disrupt placental growth and development in mice, resulting in higher rates of low birthweight, premature birth, and fetal loss. In a separate study, exposure of neonatal mice to DEHP through lactation caused hypertrophy of the adrenal glands and higher levels of anxiety during puberty. In another study, pubertal administration of higher-dose DEHP delayed puberty in rats, reduced testosterone production, and inhibited androgen-dependent development; low doses showed no effect.
Obesity
When DEHP is ingested intestinal lipase
Lipase ( ) is a family of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; however, these are usually tr ...
s convert it to MEHP, which then is absorbed. MEHP is suspected to have an obesogenic effect. Rodent studies and human studies have shown DEHP to be a possible disruptor of thyroid function, which plays a key role in energy balance and metabolism. Exposure to DEHP has been associated with lower plasma thyroxine
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
levels and decreased uptake of iodine in thyroid follicular cells. Previous studies have shown that slight changes in thyroxine levels can have dramatic effects on resting energy expenditure, similar to that of patients with hypothyroidism
Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
, which has been shown to cause increased weight gain in those study populations.
Cardiotoxicity
Even at relatively low doses of DEHP, cardiovascular reactivity was significantly affected in mice. A clinically relevant dose and duration of exposure to DEHP has been shown to have a significant impact on the behavior of cardiac
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
cells in culture. This includes an uncoupling effect that leads to irregular rhythms in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
. Untreated cells had fast conduction velocity, along with homogenous activation wave fronts and synchronized beating. Cells treated with DEHP exhibited fractured wave fronts with slow propagation speeds. This is observed in conjunction with a significant decrease in the amount of expression and instability of gap junction
Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulate ...
al connexin
Connexins (Cx)TC# 1.A.24, or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. An entirely different family of proteins, the innexins, form gap junctions in invertebrates. Each ...
proteins, specifically connexin-43
Gap junction alpha-1 protein (GJA1), also known as connexin 43 (Cx43), is a protein that in humans is encoded by the ''GJA1'' gene on chromosome 6. As a connexin, GJA1 is a component of gap junctions, which allow for gap junction intercellular ...
, in cardiomyocytes
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...
treated with DEHP.
The decrease in expression and instability of connexin-43
Gap junction alpha-1 protein (GJA1), also known as connexin 43 (Cx43), is a protein that in humans is encoded by the ''GJA1'' gene on chromosome 6. As a connexin, GJA1 is a component of gap junctions, which allow for gap junction intercellular ...
may be due to the down regulation of tubulin
Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...
and kinesin
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells.
Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzy ...
genes, and the alteration of microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
structure, caused by DEHP; all of which are responsible for the transport of protein products. Also, DEHP caused down regulation of several growth factors, such as angiotensinogen
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adren ...
, transforming growth factor-beta, vascular endothelial growth factor C
Vascular endothelial growth factor C (VEGF-C) is a protein that is a member of the platelet-derived growth factor / vascular endothelial growth factor (PDGF/VEGF) family. It is encoded in humans by the ''VEGFC'' gene, which is located on chromosom ...
and A, and endothelial-1. The DEHP-induced down regulation of these growth factors may also contribute to the reduced expression and instability of connexin-43.
DEHP has also been shown, ''in vitro'' using cardiac muscle cells, to cause activation of PPAR-alpha gene, which is a key regulator in lipid metabolism and peroxisome
A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pero ...
proliferation; both of which can be involved in atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
and hyperlipidemia
Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbre ...
, which are precursors of cardiovascular disease.
Once metabolized into MEHP, the molecule has been shown to lengthen action potential duration and slow epicardial conduction velocity in Langendorff perfused rodent hearts.
Other health effects
Studies in mice have shown other adverse health effects due to DEHP exposure. Ingestion of 0.01% DEHP caused damage to the blood-testis barrier as well as induction of experimental autoimmune orchitis. There is also a correlation between DEHP plasma levels in women and endometriosis.
DEHP is also a possible cancer causing agent in humans, although human studies remain inconclusive, due to the exposure of multiple elements and limited research. In vitro and rodent studies indicate that DEHP is involved in many molecular events, including increased cell proliferation, decreased apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
, oxidative damage
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...
, and selective clonal expansion of the initiated cells; all of which take place in multiple sites of the human body.
Government and industry response
Taiwan
In October 2009, Consumers' Foundation, Taiwan (CFCT) published test results that found 5 out of the sampled 12 shoes contained over 0.1% of phthalate plasticizer content, including DEHP, which exceeds the government's Toy Safety Standard (CNS 4797). CFCT recommend that users should first wear socks to avoid direct skin contact.
In May 2011, the illegal use of the plasticizer DEHP in clouding agent
Clouding agents or cloudifiers are a type of food additive used to make beverages such as fruit juices to look more cloudy, and thus more natural-looking and visually appealing, typically by creating an emulsion of oil droplets.
Natural fruit ju ...
s for use in food and beverages has been reported in Taiwan
Taiwan, officially the Republic of China (ROC), is a country in East Asia, at the junction of the East and South China Seas in the northwestern Pacific Ocean, with the People's Republic of China (PRC) to the northwest, Japan to the nort ...
. An inspection of products initially discovered the presence of plasticizers. As more products were tested, inspectors found more manufacturers using DEHP and DINP. The Department of Health
A health department or health ministry is a part of government which focuses on issues related to the general health of the citizenry. Subnational entities, such as states, counties and cities, often also operate a health department of their ow ...
confirmed that contaminated food and beverages had been exported to other countries and regions, which reveals the widespread prevalence of toxic plasticizers.
European Union
Concerns about chemicals ingested by children when chewing plastic toys prompted the European Commission
The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...
to order a temporary ban on phthalates in 1999, the decision of which is based on an opinion by the Commission's Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE). A proposal to make the ban permanent was tabled. Until 2004, EU banned the use of DEHP along with several other phthalates ( DBP, BBP, DINP
Diisononyl phthalate (DINP) is a phthalate used as a plasticizer. DINP is typically a mixture of chemical compounds consisting of various isononyl esters of phthalic acid, and is commonly used in a large variety of plastic items.
Health Issues
...
, DIDP
Diisodecyl phthalate (DIDP) is a commonly used plasticizer used in the production of plastic and plastic coating to increase flexibility. It is a mixture of compounds derived from the esterification of phthalic acid and isomeric decyl alcohols.
T ...
and DNOP) in toys for young children. In 2005, the Council and the Parliament compromised to propose a ban on three types of phthalates (DINP
Diisononyl phthalate (DINP) is a phthalate used as a plasticizer. DINP is typically a mixture of chemical compounds consisting of various isononyl esters of phthalic acid, and is commonly used in a large variety of plastic items.
Health Issues
...
, DIDP
Diisodecyl phthalate (DIDP) is a commonly used plasticizer used in the production of plastic and plastic coating to increase flexibility. It is a mixture of compounds derived from the esterification of phthalic acid and isomeric decyl alcohols.
T ...
, and DNOP) "in toys and childcare articles which can be placed in the mouth by children". Therefore, more products than initially planned will thus be affected by the directive. In 2008, six substances were considered to be of very high concern (SVHC
A substance of very high concern (SVHC) is a chemical substance (or part of a group of chemical substances) concerning which it has been proposed that use within the European Union be subject to authorisation under the REACH Regulation. Indeed, li ...
s) and added to the Candidate List including musk xylene
Musk xylene is a synthetic musk fragrance which mimics natural musk. It has been used as a perfume fixative in a wide variety of consumer products, and is still used in some cosmetics and fragrances.
Musk xylene was once the most widely used of ...
, MDA, HBCDD
Hexabromocyclododecane (HBCD or HBCDD) is a brominated flame retardant. It consists of twelve carbon, eighteen hydrogen, and six bromine atoms tied to the ring. Its primary application is in extruded (XPS) and expanded (EPS) polystyrene foam that ...
, DEHP, BBP, and DBP. In 2011, those six substances have been listed for Authorization in Annex XIV of REACH
Reach or REACH may refer to:
Companies and organizations
* Reach plc, formerly Trinity Mirror, large British newspaper, magazine, and digital publisher
* Reach Canada, an NGO in Canada
* Reach Limited, an Asia Pacific cable network company
* ...
by Regulation (EU) No 143/2011. According to the regulation, phthalates including DEHP, BBP and DBP will be banned from February 2015.
In 2012, Danish Environment Minister Ida Auken
Ida Margrete Meier Auken (born 22 April 1978, in Frederiksberg) is a Danish politician and member of the Folketing for the Social Democrats political party. She has been a member of parliament since 2007. She was Minister for the Environment of ...
announced the ban of DEHP, DBP, DIBP and BBP, pushing Denmark
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, song_type = National and royal anthem
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, subdivision_type = Sovereign state
, subdivision_name = Danish Realm, Kingdom of Denmark
...
ahead of the European Union which has already started a process of phasing out phthalates. However, it was postponed by two years and would take effect in 2015 and not in December 2013, which was the initial plan. The reason is that the four phthalates are far more common than expected and that producers cannot phase out phthalates as fast as the Ministry of Environment requested.
In 2012, France
France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...
became the first country in the EU to ban the use of DEHP in pediatrics, neonatal, and maternity wards in hospitals.
DEHP has now been classified as a Category 1B reprotoxin, and is now on the Annex XIV of the European Union's REACH
Reach or REACH may refer to:
Companies and organizations
* Reach plc, formerly Trinity Mirror, large British newspaper, magazine, and digital publisher
* Reach Canada, an NGO in Canada
* Reach Limited, an Asia Pacific cable network company
* ...
legislation. DEHP has been phased out in Europe under REACH and can only be used in specific cases if an authorization has been granted. Authorizations are granted by the European Commission, after obtaining the opinion of the Committee for Risk Assessment (RAC) and the Committee for Socio-economic Analysis (SEAC) of the European Chemicals Agency (ECHA).
California
DEHP is classified as a "chemical known to the State of California to cause cancer and birth defects or other reproductive harm" (in this case, ''both'') under the terms of Proposition 65
Proposition 65 (formally titled The Safe Drinking Water and Toxic Enforcement Act of 1986, and also referred to as Prop 65) is a California law passed by direct voter initiative in 1986 by a 63%–37% vote. Its goals are to protect drinking water s ...
.
References
Further reading
*
External links
FDA Public Health Notification: PVC devices containing the plasticizer DEHP (archived page)
ATSDR ToxFAQs
Healthcare without Harm - PVC and DEHP
accessed 25 March 2014
Healthcare without Harm: "Weight of the Evidence on DEHP: Exposures are a Cause for Concern, Especially During Medical Care"; 6p-fact sheet, 16 March 2009
accessed 25 March 2014
Safety Assessment of Di(2-ethylhexyl)phthalate (DEHP) Released from PVC Medical Devices - Center for Devices and Radiological Health U.S. Food and Drug Administration (archived page)
{{HealthIssuesOfPlastics
Ester solvents
IARC Group 2B carcinogens
Phthalate esters
Endocrine disruptors
Plasticizers