Phthalate

Phthalates, or phthalate esters, are esters of phthalic acid and are mainly used as plasticizers (substances added to plastics to increase their flexibility). They are chiefly used to soften polyvinyl chloride. Phthalates are being phased out of many products in the United States and European Union over health concerns.

Uses

Phthalates are used in a large variety of substances, from enteric coatings of pharmaceutical pills to viscosity control agents, gelling agent, film former, stabilizer, dispersant, lubricants, binder, emulsifying agents, and suspending agents. End applications include adhesives and glues, agriculture, building materials, personal care products, detergents and surfactants, plastic objects, paints, printing inks and coatings, pharmaceuticals, food products, polymerization and textiles.

As of 2004, manufacturers produce about 363 thousand metric tonnes (800 million pounds or 400 000 short tons) of phthalates each year. They were first produced during the 1920s, and have been produced in large quantities since the 1950s, when PVC was introduced. The most widely-used phthalates are di-2-ethyl hexyl phthalate (DEHP), diisodecyl phthalate (DIDP) and diisononyl phthalate (DINP). DEHP is the dominant plasticizer used in PVC, due to its low cost. Benzylbutylphthalate (BBzP) is used in the manufacture of foamed PVC, which is mostly used as a flooring material. Phthalates with small R and R' groups are used as solvents in perfumes and pesticides.

Phthalates are also frequently used in soft plastic fishing lures, nail polish, adhesives, caulk, paint pigments, and toys made of so-called "jelly rubber." Phthalates are used in a variety of household applications (shower curtains, adhesives, perfume), modern pop-culture electronics and medical applications such as catheters.

Properties

Phthalate esters are the dialkyl or alkyl aryl esters of phthalic acid (also called 1,2-benzenedicarboxylic acid, not be confused with the isomeric terephthalic or isophthalic acids ); the name phthalate derives from phthalic acid, which itself is derived from word "naphthalene". When added to plastics, phthalates allow the long polyvinyl molecules to slide against one another. The phthalates 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). They are colorless, odorless liquids produced by reacting phthalic anhydride with an appropriate alcohol (usually 6 to 13 carbon).

Table of more common phthalates

Name	Acronym	Structural formula	CAS No.
Dimethyl phthalate	DMP	C6H4(COOCH3)2	131-11-3
Diethyl phthalate	DEP	C6H4(COOC2H5)2	84-66-2
Diallyl phthalate	DAP	C6H4(COOCH2CH=CH2)2	131-17-9
Di-n-propyl phthalate	DPP	C6H4[COO(CH2)2CH3]2	131-16-8
Di-n-butyl phthalate	DBP	C6H4[COO(CH2)3CH3]2	84-74-2
Diisobutyl phthalate	DIBP	C6H4[COOCH2CH(CH3)2]2	84-69-5
Butyl cyclohexyl phthalate	BCP	CH3(CH2)3OOCC6H4COOC6H11	84-64-0
Di-n-pentyl phthalate	DNPP	C6H4[COO(CH2)4CH3]2	131-18-0
Dicyclohexyl phthalate	DCP	C6H4[COOC6H11]2	84-61-7
Butyl benzyl phthalate	BBP	CH3(CH2)3OOCC6H4COOCH2C6H5	85-68-7
Di-n-hexyl phthalate	DNHP	C6H4[COO(CH2)5CH3]2	84-75-3
Diisohexyl phthalate	DIHxP	C6H4[COO(CH2)3CH(CH3)2]2	146-50-9
Diisoheptyl phthalate	DIHpP	C6H4[COO(CH2)4CH(CH3)2]2	41451-28-9
Butyl decyl phthalate	BDP	CH3(CH2)3OOCC6H4COO(CH2)9CH3	89-19-0
Di(2-ethylhexyl) phthalate	DEHP, DOP	C6H4[COOCH2CH(C2H5)(CH2)3CH3]2	117-81-7
Di(n-octyl) phthalate	DNOP	C6H4[COO(CH2)7CH3]2	117-84-0
Diisooctyl phthalate	DIOP	C6H4[COO(CH2)5CH(CH3)2]2	27554-26-3
n-Octyl n-decyl phthalate	ODP	CH3(CH2)7OOCC6H4COO(CH2)9CH3	119-07-3
Diisononyl phthalate	DINP	C6H4[COO(CH2)6CH(CH3)2]2	28553-12-0
Diisodecyl phthalate	DIDP	C6H4[COO(CH2)7CH(CH3)2]2	26761-40-0
Diundecyl phthalate	DUP	C6H4[COO(CH2)10CH3]2	3648-20-2
Diisoundecyl phthalate	DIUP	C6H4[COO(CH2)8CH(CH3)2]2	85507-79-5
Ditridecyl phthalate	DTDP	C6H4[COO(CH2)12CH3]2	119-06-2
Diisotridecyl phthalate	DIUP	C6H4[COO(CH2)10CH(CH3)2]2	68515-47-9

Health effects

Exposure

People are commonly exposed to phthalates, and the majority of Americans tested by the Centers for Disease Control and Prevention have metabolites of multiple phthalates in their urine. Diet is believed to be the main source of DEHP and other phthalates in the general population, although inhalational exposure is also significant. Baby 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." Though 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.

Some vendors of jelly rubber sex toys advise covering them in condoms when used internally, due to the possible leaching of phthalates. Other vendors do not carry jelly rubber sex toys, in favor of phthalate-free varieties.

Endocrine disruption

In studies of rodents exposed to certain phthalates, high doses have been shown to change hormone levels and cause birth defects. A recent British study showed that the phthalate di(n-butyl) phthalate (DBP) or its metabolite monobutyl phthalate (MBP) suppresses steroidogenesis by fetal-type Leydig cells in primates as in rodents.

A seminal study by Swan et al. published in 2005 reported that human phthalate exposure during pregnancy resulted in decreased anogenital distance among baby boys later born, a change that in rodents exposed to phthalates is associated with genital abnormalities. In this study phthalate metabolites were measured in urine samples collected from pregnant women. Upon birth, the genital features and anogenital distance of these women's babies were measured and correlated with the residue levels in the mother's urine. Boys born to mothers with the highest levels of phthalates were 7 times more likely to have a shortened anogenital distance. While anogenital distance is routinely used as a measure of fetal exposure to endocrine disruptors in animals, the Swan study is one of only 5 in which the parameter has been assessed in humans. Another of these studies states that "Whether anogenital distance measurements in humans relate to clinically important outcomes … remains to be determined, and a National Toxicology Program expert panel concluded that anogenital distance is a "'novel index' whose relevance in humans 'has not been established,'" and that there is "insufficient evidence in humans" that DEHP causes harm. Still, the Swan study has been widely cited, and "suggest[s] that male reproductive development in humans could be affected by prenatal exposure to environmentally relevant levels of phthalates." Authors of a more recent study of boys with undescended testis suggested that exposure to a combination of phthalates and anti-androgenic pesticides may have contributed to that condition.

In contrast to the Swan study, and earlier study found that "adolescents exposed to significant quantities of DEHP as neonates showed no significant adverse effects on their physical growth and pubertal maturity. This study, however, examined children exposed intravenously to phthalate diesters, and intravenous exposure results in relatively little metabolic conversion of the relatively nontoxic phthalate diester to its toxic monoester metabolite.

Other effects

Large amounts of specific phthalates fed to rodents have been show to damage to their liver and testes, and initial rodent studies also indicated hepatocarcinogenity. Following this result, diethyl hexyl phthalate was listed as a possible carcinogen by IARC, EC and WHO. Later studies on primates showed that the mechanism was specific to rodents - humans are resistant to the effect. The carcinogen classification was subsequently withdrawn.

In 2004, a joint Swedish-Danish research team found a very strong link between allergies in children and the phthalates DEHP and BBzP. The first systematic review of the evidence relating phthalates to asthma found evidence of association between phthalates in the home and asthma especially in children, but this evidence was limited by imprecise data on exact levels of exposure. Phthalates migrate from PVC plastics and into the dust, where they may be inhaled.

In 2007, a cross-sectional study of U.S. males concluded that urine concentrations of four phthalate metabolites correlate with waist size and three phthalate metabolites correlate with the cellular resistance to insulin, a precursor to Type II diabetes. The authors note the need for follow-up longitudinal studies, as waist size is known to correlate with insulin resistance.

Legal status

European Union

The use of some phthalates has 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 phthalates may not be greater than 0.1% mass percent of the plasticized part of the toy. These phthalates are allowed at any concentration in other products and other phthalates are not restricted.

There are no other specific restrictions in the European Union although draft proposals have been tabled for the inclusion of BBP, DEHP and DBP on the Candidate list of Substances for Authorisation under REACH. Fourteen other countries, including Japan, Argentina, and Mexico, have also banned phthalates from children's toys. The Dutch office of Greenpeace UK sought to encourage the European Union to ban sex toys that contained phthalates.

United States

Some phthalates will be restricted in the U.S. state of California (for children's toys) starting in 2009. In Connecticut, state legislators are considering a bill that would ban phthalates in children's products. Following California, the US Congress passed a bill banning 6 phthalates from toys nationally, effective beginning sometime in 2009. President Bush signed the bill into law in August 2008.

Identification in plastics

Phthalates are used in some but not all PVC formulations, and there are no labeling requirements for phthalates specifically. PVC plastics are typically used for various containers and hard packaging, medical tubing and bags, and are labelled "Type 3" for recycling reasons. However, the presence of phthalates rather than other plasticizers is not marked on PVC items, and thus it is not possible to identify phthalate-containing items by markings alone.

Chemical analysis, for example by gas chromatography, can establish the presence of phtalates.

See also

• Xenoestrogen

References

Further reading

• Hauser R, Meeker JD, Singh NP, et al (2007). "DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites". Hum. Reprod. 22 (3): 688–95.
• Susan M. Duty, Narendra P. Singh, Manori J. Silva, Dana B. Barr, John W. Brock, Louise Ryan, Robert F. Herrick, David C. Christiani, and Russ Hauser (2003). "The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay". Environmental Health Perspectives 111 (July): 1164–1169 Abstract.
• Shanna H. Swan, Katharina M. Main, Fan Liu, Sara L. Stewart, Robin L. Kruse, Antonia M. Calafat, Catherine S. Mao, J. Bruce Redmon, Christine L. Ternand, Shannon Sullivan, J. Lynn Teague, and the Study for Future Families Research Team (2005). "Decrease in anogenital distance among male infants with prenatal phthalate exposure". Environmental Health Perspectives In press Abstract.
• Swan, S.H. 2004. Phthalates in pregnant women and children. e.hormone 2004 conference. October 27-30. New Orleans.
• Swan, S.H. et al. 2005. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environmental Health Perspectives 113:1056--1061.
• Barbara J. Davis, Tara Lovekamp-Swant (2003). "Mechanisms of Phthalate Ester Toxicity in the Female Reproductive System". Environmental Health Perspectives 111
• {{cite journal

| author = L. Earl Gray, Jr.*,1, Joseph Ostby*, Johnathan Furr*, Matthew Price*, D. N. Rao Veeramachaneni{dagger} and Louise Parks | title = Perinatal Exposure to the Phthalates DEHP, BBP, and DINP, but Not DEP, DMP, or DOTP, Alters Sexual Differentiation of the Male Rat | journal = Toxicological Sciences | year = 2000 | volume = 58 | issue = | pages = 350-365 | url = http://171.66.120.171/cgi/reprint/58/2/350 }}

• Joel A. Tickner, ScD 1 *, Ted Schettler, MD, MPH 2, Tee Guidotti, MD, MPH 3, Michael McCally, MD, MPH 4, Mark Rossi, MA 5 (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.
• Shanna H. Swan,1 Katharina M. Main,2 Fan Liu,3 Sara L. Stewart,3 Robin L. Kruse,3 Antonia M. Calafat,4 Catherine S. Mao,5 J. Bruce Redmon,6 Christine L. Ternand,7 Shannon Sullivan,8 and J. Lynn Teague9 (2005). "Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure". Environmental Health Perspectives 113 (8): 1056–1061.
• Michael C. Kohn; Frederick Parham; Scott A. Masten; Christopher J. Portier; Michael D. Shelby; John W. Brock; Larry L. Needham (2000). "Human Exposure Estimates for Phthalates". Environmental Health Perspectives 108 (10): A440–A442.
• Carl-Gustaf Bornehag,1,2,3 Jan Sundell,2 Charles J. Weschler,2,4 Torben Sigsgaard,5 Björn Lundgren,1 Mikael Hasselgren,3 and Linda Hägerhed-Engman1 (2004). "The Association between Asthma and Allergic Symptoms in Children and Phthalates in House Dust: A Nested Case–Control Study". Environmental Health Perspectives 112 (14): 1393–1397.
• Richard W Stahlhut, Edwin van Wijngaarden, Timothy D Dye, Stephen Cook and Shanna H Swan (2007). "Concentrations of Urinary Phthalate Metabolites are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males". Environmental Health Perspectives

External links

Media

• NOW on PBS: Phthalates and Toxic Toys? Why does the United States allow children to play with toys some scientists say may cause infertility in boys?
• Interview with Mark Schapiro from Fresh Air (NPR) ; November 26, 2007
• Phthalates Now Linked to Fat, Related Health Risks, University of Rochester Medical Center, March 14 2007.
• New Scientist and Scientific American articles on Environmental Health Perspectives report; see Research.
• Unsafe Sex Toys with Violet Blue
• Naughty by Nature: Ever thought about the toxins in your sex toys? by Emily Gertz, "Grist magazine", 6 December 2005
• Panel Ranks Risks of Common Phthalate: Additional research underscores concerns about DEHP that were first expressed in 2000 report, Bette Hileman, Chemical and Engineering News, NOVEMBER 14, 2005, 83(46):32–36.
• Congress Bans Toxic Phthalates from Toys, Everett Sizemore, US Recall News, August 13, 2008.

Research

• The Association between Asthma and Allergic Symptoms in Children and Phthalates in House Dust: A Nested Case-Control Study
• DIDP, DINP, and DBP - Risk Assessment Reports by the European Chemicals Bureau (ECB).

Sources suggesting low/no health risks

• Phthalates Information Centre; an initiative of the European Council for Plasticisers and Intermediates (ECPI)
• Phthalates Information Center; from the American Chemistry Council, Inc.
• Phthalates and Human Health, by Kenneth Green, D.Env.; Director of the Environmental Program at Reason Public Policy Institute, Reason Foundation, 2000