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| {{chembox | {{chembox | ||
| | Watchedfields = changed | |||
| | verifiedrevid = |
| verifiedrevid = 476999754 | ||
| | ImageFile = Diethylphthalat.png | |||
| | ImageFile = Diethyl phthalate 200.svg | |||
| ⚫ | | Reference = <ref name="ILS">{{cite web|url= |
||
| | ImageAlt = Skeletal formula of diethyl phthalate | |||
| ⚫ | | |
||
| | ImageFile1 = Diethyl phthalate 3D ball.png | |||
| | ImageSize1 = 175 | |||
| | ImageAlt1 = Ball-and-stick model of the diethyl phthalate molecule | |||
| ⚫ | | Reference = <ref name="ILS">{{cite web|url=https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/diethyl_phthalate_508.pdf |work=Integrated Laboratory Systems, Inc. |title=Chemical Information Profile for Diethyl Phthalate |access-date=3 March 2009 |archive-url=https://web.archive.org/web/20090201134838/http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/Diethyl_phthalate.pdf |archive-date=1 February 2009 }}</ref> | ||
| | PIN = Diethyl benzene-1,2-dicarboxylate | |||
| | OtherNames = Diethyl phthalate | |||
| ⚫ | |Section1={{Chembox Identifiers | ||
| | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ||
| | ChemSpiderID = 13837303 | | ChemSpiderID = 13837303 | ||
| Line 22: | Line 29: | ||
| | StdInChIKey = FLKPEMZONWLCSK-UHFFFAOYSA-N | | StdInChIKey = FLKPEMZONWLCSK-UHFFFAOYSA-N | ||
| | CASNo_Ref = {{cascite|correct|CAS}} | | CASNo_Ref = {{cascite|correct|CAS}} | ||
| | CASNo |
| CASNo = 84-66-2 | ||
| | PubChem |
| PubChem = 6781 | ||
| }} | }} | ||
| | |
|Section2={{Chembox Properties | ||
| | Formula |
| Formula = C<sub>12</sub>H<sub>14</sub>O<sub>4</sub> | ||
| | MolarMass |
| MolarMass = 222.24 g/mol | ||
| | Appearance |
| Appearance = Colourless, oily liquid | ||
| | LogP |
| LogP = 2.42 | ||
| | Density |
| Density = 1.12 g/cm<sup>3</sup> at 20 °C | ||
| | MeltingPtC |
| MeltingPtC = −4 | ||
| | BoilingPtC |
| BoilingPtC = 295 | ||
| | Solubility |
| Solubility = 1080 mg/L at 25 °C | ||
| | VaporPressure = 0.002 mmHg (25 °C)<ref name=PGCH/> | |||
| | MagSus = −127.5·10<sup>−6</sup> cm<sup>3</sup>/mol | |||
| }} | }} | ||
| | |
|Section3={{Chembox Hazards | ||
| | |
| NFPA-H = 1 | ||
| | |
| NFPA-F = 1 | ||
| | |
| NFPA-R = 0 | ||
| | MainHazards |
| MainHazards = | ||
| | |
| FlashPtC = 161.1 | ||
| | FlashPt_ref =<ref name=PGCH/> | |||
| | LD50 |
| LD50 = 8600 mg/kg (rat) | ||
| | Autoignition = }} | |||
| | AutoignitionPt = | |||
| | PEL = None<ref name=PGCH>{{PGCH|0213}}</ref> | |||
| | ExploLimits = 0.7%, lower<ref name=PGCH/> | |||
| | IDLH = N.D.<ref name=PGCH/> | |||
| | REL = TWA 5 mg/m<sup>3</sup><ref name=PGCH/> | |||
| }} | |||
| }} | }} | ||
| '''Diethyl phthalate''' ('''DEP''') is a ] ] |
'''Diethyl phthalate''' ('''DEP''') is a ] ]. It occurs as a colourless liquid without significant odour but has a bitter, disagreeable taste. It is more dense than water and insoluble in water; hence, it sinks in water. | ||
| ==Synthesis and applications== | |||
| Since the compound is a suitable solvent for many ], it is often used to bind cosmetics and fragrances.<ref name="Api 2001 97–108">{{cite journal|last=Api|first=A.M.|title=Toxicological profile of diethyl phthalate: a vehicle for fragrance and cosmetic ingredients|journal=Food and Chemical Toxicology|year=2001|volume=39|issue=2|pages=97–108|doi=10.1016/S0278-6915(00)00124-1}}</ref> Other industrial uses include plasticizers, detergent bases and aerosol sprays.<ref>{{cite journal|last=Ghorpade|first=N.|coauthors=Mehta, V., Khare, M.|title=Toxicity Study of Diethyl Phthalate on Freshwater Fish Cirrhina mrigala|journal=Ecotoxicology and Environmental Safety|year=2002|volume=53|issue=2|pages=255–258|doi=10.1006/eesa.2002.2212}}</ref> Because of the frequent dermal exposure of humans to the chemical, the question of toxicity is crucial. Several studies suggest that DEP can cause damage to the ] as well as to the ] in males and females.<ref>{{cite journal|last=Miodovnik|first=A.|title=Endocrine disruptors and childhood social impairment|journal=Neurotoxicology|year=2011|month=March|volume=32|issue=2|pages=261–267|doi=10.1016/j.neuro.2010.12.009|pmid=21182865}}</ref> | |||
| Diethyl phthalate is produced by the reaction of ] with ], in the presence of a strong acid ]: | |||
| <ref name="Colon00">{{cite journal|journal=Environmental Health Perspectives|title=Identification of Phthalate Esters in the Serum of Young Puerto Rican Girls with Premature Breast Development|authors=Ivelisse Colón ''et al.''|year=2000|volume=108|pages=895–900|doi=10.1289/ehp.00108895}}</ref> | |||
| <ref name="Swan08">{{cite journal|journal=Environmental Research|volume=108|issue=2|year=2008|pages=177–184|doi=10.1016/j.envres.2008.08.007|title=Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans|author=Shanna H. Swan|pmc=2775531|pmid=18949837|bibcode=2008ER....108..177S}}</ref> | |||
| ⚫ | ] | ||
| ==Exposure== | |||
| Due to their use as ], diethyl phthalates are ubiquitous in the environment, especially near places of production and use. Biodegradation through microbially-mediated processes can result in products that can potentially harm ].<ref name=cartwright>{{cite journal|last=Cartwright|first=C.D.|title=Biodegradation of diethyl phthalate in soil by a novel pathway|journal=FEMS Microbiology Letters|year=2000|month=March|volume=186|issue=1|pages=27–34|doi=10.1016/S0378-1097(00)00111-7}}</ref> | |||
| There is also general evidence of widespread human ].<ref name="Calafat06">{{cite journal|journal=Environmental Health Perspectives|year=2006|volume=114|issue=11|pages=1783–1789|doi=10.1289/ehp.9059|title=Integrating Biomonitoring Exposure Data into the Risk Assessment Process: Phthalates as a Case Study|authors=Antonia M. Calafat and Richard H. McKee}}</ref><ref name=prenatalexposure>{{cite journal|last=Adibi|first=J.J.|title=Prenatal Exposures to Phthalates among Women in New York City and Krakow, Poland|journal=Environmental Health Perspectives|year=2003|volume=111|issue=14|pages=1719–1722|pmc=1241713|pmid=14594621}}</ref><ref>{{cite journal|last=Blount|first=B.C.|title=Quantitative Detection of Eight Phthalate Metabolites in Human Urine Using HPLC-APCI-MS/MS|journal=Anal. Chem.|month=July|year=2000|volume=72|issue=17|pages=4127–4134|doi=10.1021/ac000422r}}</ref><ref name=consumer>{{cite journal|last=Schettler|first=Ted|title=Human exposure to phthalates via consumer products|journal=International Journal of Andrology|year=2006|month=February|volume=29|issue=1|pages=134–139|doi=10.1111/j.1365-2605.2005.00567.x}}</ref> | |||
| Non-occupational exposure results from the diet, for example phthalate-coated medicines and ], and through consumer products.<ref name=consumer /> High ] was observed in workers directly manufacturing plasticizers.<ref name=Hines>{{cite journal|last=Hines|first=Cynthia J.|title=Urinary Phthalate Metabolite Concentrations among Workers in Selected Industries: A Pilot Biomonitoring Study|journal=The Annals of Occupational Hygiene|year=2008|volume=53|issue=1|pages=1–17|doi=10.1093/annhyg/men066}}</ref> | |||
| Studies suggest a high correlation between air and urine sample concentrations of short side-chain phthalates such as DEP, making inhalation an important route of exposure.<ref name=prenatalexposure /><ref name=Hines /> | |||
| It finds some use as a specialist ] in ], it has also been used as a blender and fixative in ].<ref>{{cite journal |last1=Api |first1=A.M. |title=Toxicological profile of diethyl phthalate: a vehicle for fragrance and cosmetic ingredients |journal=Food and Chemical Toxicology |date=February 2001 |volume=39 |issue=2 |pages=97–108 |doi=10.1016/s0278-6915(00)00124-1|pmid=11267702 }}</ref> | |||
| ==Structure and reactivity== | |||
| Diethyl phthalate, or o-Benzenedicarboxylic acid diethyl ester consists of a ] with two carboxylic acid ethyl ] attached to it in the ] (1,2) pattern.<ref name="ILS" /> It is a highly ], as the pi-cloud on the benzene ring, the ] on the carbonyl atoms and the lone pairs on the oxygens are all conjugated. The substituents are ],<ref>{{cite book|last=Jones|first=Jr., Maitland|title=Organic Chemistry|year=2005|publisher=W.W Norton & Company|location=New York|pages=715}}</ref> and they are ortho to each other, so all positions in the ring are more or less equally activated. Diethyl phthalate is likely to undergo ] in the environment.<ref>U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry June 1995</ref> Abiotic degradation processes such as ], ], and ] are unlikely to play significant roles in the environmental fate of diethyl phthalate. | |||
| == |
==Biodegradation== | ||
| Diethyl phthalate is produced by the reaction of ] with ] in the presence of a catalytic amount of concentrated ].<ref name="ILS" /> Phthalic anhydride is produced by either the ] or the Ald-Ox process from ethanol and the oxidation of ] or o-xylene.<ref name="Peakall D.B. 1975 1–41">{{cite journal|journal=Residue Rev|year=1975|volume=54|pages=1–41|title=Phthalate esters: Occurrence and biological effects.|author=Peakall D.B.}}</ref> The purity of manufactured phthalate esters is reportedly between 99.70% and 99.97% with the main impurities being ], ], and ].<ref name="Peakall D.B. 1975 1–41"/> | |||
| ⚫ | ] | ||
| ==Metabolism== | |||
| Diethyl phthalate is hydrolyzed to ], ] and ethanol after oral administration in the ] of the ] or in the ]. Hydrolysis of DEP also takes place at the ] and ] after ]. After tissue distribution throughout the body, DEP accumulates in the liver and kidney. The metabolites are excreted in the urine.<ref name="Api 2001 97–108" /> DEP is metabolized by ], which is synthesized in the human liver. In vitro studies show that DEP reduces the ] activity. It was also observed that the activity of ] ] is increased in cultures of rat liver cells.<ref name="Api 2001 97–108" /> Furthermore DEP induces the enzyme activity of ], which leads to ] peroxisome proliferation and possibly causes ].<ref>{{cite book|last=Timbrell|first=J.|title=Principles of Biochemical Toxicology|year=2009|publisher=Informa Healthcare|location=London|pages=179, 200–201}}</ref> | |||
| ==Biodegradation== | |||
| ===Biodegradation by microorganisms=== | ===Biodegradation by microorganisms=== | ||
| ] of DEP in soil occurs by sequential ] of the two diethyl chains of the phthalate to produce monoethyl phthalate, followed by phthalic acid. This reaction occurs very slowly in an abiotic environment. Thus there exists an alternative pathway of biodegradation which includes transesterification or demethylation by microorganisms, if the soil is also contaminated with ], that would produce another three intermediate compounds, ethyl methyl phthalate, dimethyl phthalate and monomethyl phthalate. This biodegradation has been observed in several soil ].<ref name=cartwright /> Some bacteria with these abilities have specific enzymes involved in the degradation of phthalic acid esters such as phthalate oxygenase, phthalate dioxygenase, phthalate dehydrogenase and phthalate decarboxylase.<ref name=saito>{{cite journal|last=Saito|first=T.| |
] of DEP in soil occurs by sequential ] of the two diethyl chains of the phthalate to produce monoethyl phthalate, followed by phthalic acid. This reaction occurs very slowly in an abiotic environment. Thus there exists an alternative pathway of biodegradation which includes transesterification or demethylation by microorganisms, if the soil is also contaminated with ], that would produce another three intermediate compounds, ethyl methyl phthalate, dimethyl phthalate and monomethyl phthalate. This biodegradation has been observed in several soil ].<ref name="cartwright">{{cite journal|last=Cartwright|first=C.D.|date=March 2000|title=Biodegradation of diethyl phthalate in soil by a novel pathway|journal=FEMS Microbiology Letters|volume=186|issue=1|pages=27–34|doi=10.1016/S0378-1097(00)00111-7|pmid=10779708|doi-access=free}}</ref> Some bacteria with these abilities have specific enzymes involved in the degradation of phthalic acid esters such as phthalate oxygenase, phthalate dioxygenase, phthalate dehydrogenase and phthalate decarboxylase.<ref name=saito>{{cite journal|last=Saito|first=T.|author2=Peng, H.|author3=Tanabe, R.|author4=Nagai, K.|author5=Kato, K.|title=Enzymatic hydrolysis of structurally diverse phthalic acid esters by porcine and bovine pancreatic cholesterol esterases.|journal=Chemosphere|date=December 2010|volume=81|issue=1|doi=10.1016/j.chemosphere.2010.08.020|pages=1544–1548|pmid=20822795|bibcode=2010Chmsp..81.1544S|s2cid=6958344 }}</ref> | ||
| The developed intermediates of the transesterification or demethylation, ethyl methyl phthalate and dimethyl phthalate, enhance the toxic effect and are able to disrupt the membrane of microorganisms. |
The developed intermediates of the transesterification or demethylation, ethyl methyl phthalate and dimethyl phthalate, enhance the toxic effect and are able to disrupt the membrane of microorganisms. | ||
| ===Biodegradation by mammals=== | ===Biodegradation by mammals=== | ||
| Recent studies show that DEP, a phthalic acid ester (PAE), is enzymatically hydrolyzed to its monoesters by pancreatic cholesterol esterase (CEase) in pigs and cows. These ] ] CEases have been found to be nonspecific for degradation in relation to the diversity of the alkyl side chains of PAEs |
Recent studies show that DEP, a phthalic acid ester (PAE), is enzymatically hydrolyzed to its monoesters by pancreatic cholesterol esterase (CEase) in pigs and cows. These ] ] CEases have been found to be nonspecific for degradation in relation to the diversity of the alkyl side chains of PAEs.<ref name=saito /> | ||
| ==Toxicity== | ==Toxicity== | ||
| Little is known about the ] of diethyl phthalate, but existing information suggests only a low toxic potential.<ref>{{cite journal|journal=Environmental Health Perspectives|year=1973|volume=4|pages= |
Little is known about the ] of diethyl phthalate, but existing information suggests only a low toxic potential.<ref>{{cite journal|journal=Environmental Health Perspectives|year=1973|volume=4|pages=3–25|title=Toxicity and health threats of phthalate esters: review of the literature|author=J. Autian|pmc=1474854|pmid=4578674|doi=10.2307/3428178|jstor=3428178}}</ref> Studies suggest that some phthalates affect male reproductive development via inhibition of ] biosynthesis. In rats, for instance, repeated administration of DEP results in loss of ] populations in the ]. However, diethyl phthalate does not alter ] in male rats.<ref name="Calafat06">{{cite journal|author1=Antonia M. Calafat |author2=Richard H. McKee |year=2006|title=Integrating Biomonitoring Exposure Data into the Risk Assessment Process: Phthalates as a Case Study|journal=Environmental Health Perspectives|volume=114|issue=11|pages=1783–1789|doi=10.1289/ehp.9059|pmc=1665433|pmid=17107868}}</ref><ref>{{cite journal|journal=]|volume=54|issue=3|year=1980|pages=392–398|doi=10.1016/0041-008X(80)90165-9|title=Study of the testicular effects and changes in zinc excretion produced by some ''n''-alkyl phthalates in the rat|author=Paul M. D. Foster|pmid=7394794|display-authors=etal}}</ref><ref>{{cite journal|journal=Chemico-Biological Interactions|volume=34|issue=2|year=1981|pages=233–238|doi=10.1016/0009-2797(81)90134-4|title=Studies on the testicular effects and zinc excretion produced by various isomers of monobutyl-''o''-phthalate in the rat|author=P. M. D. Foster |display-authors=etal |pmid=7460085}}</ref><ref>{{cite journal|journal=]|volume=58|issue=2|pages=350–365|title=Perinatal Exposure to the Phthalates DEHP, BBP, and DINP, but Not DEP, DMP, or DOTP, Alters Sexual Differentiation of the Male Rat|author=L. Earl Gray Jr |year=2000|doi=10.1093/toxsci/58.2.350|pmid=11099647|display-authors=etal|doi-access=}}</ref> Dose response experiments in fiddler crabs have shown that seven-day exposure to diethyl phthalate at 50 mg/L significantly inhibited the activity of ] in the epidermis and ].<ref>{{cite journal|journal=Comparative Biochemistry and Physiology C|volume=122|issue=1|year=1999|pages=115–120|doi=10.1016/S0742-8413(98)10093-2|title=Effects of exposure to diethyl phthalate, 4-(''tert'')-octylphenol, and 2,4,5-trichlorobiphenyl on activity of chitobiase in the epidermis and hepatopancreas of the fiddler crab, ''Uca pugilator''|last1=Zou|first1=Enmin|last2=Fingerman|first2=Milton|pmid=10190035}}</ref> Chitobiase plays an important role in degradation of the old ] ] during the pre-] phase.<ref>{{citation|url=http://www.nioz.nl/public/annual_report/2006/baars.pdf |contribution=Free chitobiase, a marker enzyme for the growth of crustaceans |author=M. A. Baars & S.S. Oosterhuis |title=NIOZ Annual Report 2006 |publisher=], Texel |pages=62–64 |archive-url=https://web.archive.org/web/20110720210742/http://www.nioz.nl/public/annual_report/2006/baars.pdf |archive-date=2011-07-20 }}</ref> | ||
| ===Teratogenicity=== | ===Teratogenicity=== | ||
| When pregnant rats |
When pregnant rats were treated with diethyl phthalate, it became evident that certain doses caused skeletal malformations, whereas the untreated control group showed no ]. The amount of skeletal malformations was highest at highest dose.<ref>{{cite journal|title=Teratogenicity of Phthalate Esters in Rats |author=A. R. Singh |author2=W. H. Lawrence |author3=J. Autian|journal=Journal of Pharmaceutical Sciences|volume=61|issue=1|pages=51–55|year=1972|doi=10.1002/jps.2600610107|pmid=5058645}}</ref> In a following study it was found that both phthalate diesters and their metabolic products were present in each of these compartments, suggesting that the toxicity in embryos and fetuses could be the result of a direct effect.<ref>{{cite journal|title=Maternal-Fetal transfer of <sup>14</sup>C-Di-2-ethylhexyl phthalate and <sup>14</sup>C-diethyl phthalate in rats |author=A. R. Singh |author2=W. H. Lawrence |author3=J. Autian|journal=Journal of Pharmaceutical Sciences|volume=64|issue=8|pages=1347–1350|year=1975|doi=10.1002/jps.2600640819|pmid=1151708}}</ref> | ||
| ===Long-term effects on children=== | |||
| There is a study that suggests a possible association between plasticizers (such as diethyl phthalate) with known ] and ]ic activity and the cause of premature ] in girls.<ref name="Colon00" /> Other studies show that phthalates in ] flooring can influence the behaviour of children. Phthalate dusts have been linked to higher rates of ] and ] symptoms.<ref>{{cite journal|journal=Biological Psychiatry|volume=66|issue=10|pages=958–963|year=2009|title=Phthalates Exposure and Attention-Deficit/Hyperactivity Disorder in School-Age Children|authors=Bung-Nyun Kim ''et al.''|doi=10.1016/j.biopsych.2009.07.034|url=http://www.biologicalpsychiatryjournal.com/article/S0006-3223%2809%2900952-4/abstract|pmid=19748073}}</ref> Prenatal exposure to phthalates is associated with childhood social impairment, which can have important adverse effects over a child's lifetime.<ref name="Swan08" /> | |||
| ===Future investigation=== | ===Future investigation=== | ||
| Some data suggest that exposure to multiple phthalates at low doses significantly increases the risk in a dose additive manner.<ref>{{cite journal|journal=International Journal of Andrology|title=Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals| |
Some data suggest that exposure to multiple phthalates at low doses significantly increases the risk in a dose additive manner.<ref>{{cite journal|journal=International Journal of Andrology|title=Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals|author1=L. Earl Gray Jr |volume=29|issue=1|pages=96–104|year=2006|doi=10.1111/j.1365-2605.2005.00636.x|pmid=16466529|display-authors=etal|doi-access=}}</ref><ref>{{cite journal|journal=Toxicological Sciences|volume=105|issue=1|pages=153–165|title=A Mixture of Five Phthalate Esters Inhibits Fetal Testicular Testosterone Production in the Sprague-Dawley Rat in a Cumulative, Dose-Additive Manner|author=Kembra L. Howdeshell|year=2008|doi=10.1093/toxsci/kfn077|pmid=18411233|display-authors=etal|doi-access=free}}</ref><ref>{{cite journal|journal=Environmental Research|volume=108|issue=2|year=2008|pages=168–176|doi=10.1016/j.envres.2008.08.009|title=Mechanisms of action of phthalate esters, individually and in combination, to induce abnormal reproductive development in male laboratory rats|author=Kembra L. Howdeshell|pmid=18949836|bibcode = 2008ER....108..168H |url=https://zenodo.org/record/1258923|display-authors=etal|doi-access=free}}</ref> Therefore, the risk from a mixture of phthalates or phthalates and other anti-androgens, may not be accurately assessed studying one chemical at a time. The same may be said about risks from several exposure routes together. Humans are exposed to phthalates by multiple exposure routes (predominantly dermal), while toxicological testing is done via oral exposure.<ref name="Swan08">{{cite journal|author=Shanna H. Swan|author-link=Shanna Swan|year=2008|title=Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans|journal=Environmental Research|volume=108|issue=2|pages=177–184|bibcode=2008ER....108..177S|doi=10.1016/j.envres.2008.08.007|pmc=2775531|pmid=18949837}}</ref> | ||
| == References == | == References == | ||
| {{ |
{{Reflist}} | ||
| {{Authority control}} | |||
| {{DEFAULTSORT:Diethyl Phthalate}} | {{DEFAULTSORT:Diethyl Phthalate}} | ||
| ] | ] | ||
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Latest revision as of 17:32, 29 November 2023
| |
| |
| Names | |
|---|---|
| Preferred IUPAC name Diethyl benzene-1,2-dicarboxylate | |
| Other names Diethyl phthalate | |
| Identifiers | |
| CAS Number | |
| 3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.001.409 
|
| KEGG | |
| PubChem CID | |
| UNII | |
| CompTox Dashboard (EPA) | |
InChI
| |
SMILES
| |
| Properties | |
| Chemical formula | C12H14O4 |
| Molar mass | 222.24 g/mol |
| Appearance | Colourless, oily liquid |
| Density | 1.12 g/cm at 20 °C |
| Melting point | −4 °C (25 °F; 269 K) |
| Boiling point | 295 °C (563 °F; 568 K) |
| Solubility in water | 1080 mg/L at 25 °C |
| log P | 2.42 |
| Vapor pressure | 0.002 mmHg (25 °C) |
| Magnetic susceptibility (χ) | −127.5·10 cm/mol |
| Hazards | |
| NFPA 704 (fire diamond) |
 |
| Flash point | 161.1 °C (322.0 °F; 434.2 K) |
| Explosive limits | 0.7%, lower |
| Lethal dose or concentration (LD, LC): | |
| LD50 (median dose) | 8600 mg/kg (rat) |
| NIOSH (US health exposure limits): | |
| PEL (Permissible) | None |
| REL (Recommended) | TWA 5 mg/m |
| IDLH (Immediate danger) | N.D. |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa).
 Y verify (what is ?)
Infobox references
| |
Diethyl phthalate (DEP) is a phthalate ester. It occurs as a colourless liquid without significant odour but has a bitter, disagreeable taste. It is more dense than water and insoluble in water; hence, it sinks in water.
Synthesis and applications
Diethyl phthalate is produced by the reaction of ethanol with phthalic anhydride, in the presence of a strong acid catalyst:
It finds some use as a specialist plasticiser in PVC, it has also been used as a blender and fixative in perfume.
Biodegradation
Biodegradation by microorganisms
Biodegradation of DEP in soil occurs by sequential hydrolysis of the two diethyl chains of the phthalate to produce monoethyl phthalate, followed by phthalic acid. This reaction occurs very slowly in an abiotic environment. Thus there exists an alternative pathway of biodegradation which includes transesterification or demethylation by microorganisms, if the soil is also contaminated with methanol, that would produce another three intermediate compounds, ethyl methyl phthalate, dimethyl phthalate and monomethyl phthalate. This biodegradation has been observed in several soil bacteria. Some bacteria with these abilities have specific enzymes involved in the degradation of phthalic acid esters such as phthalate oxygenase, phthalate dioxygenase, phthalate dehydrogenase and phthalate decarboxylase. The developed intermediates of the transesterification or demethylation, ethyl methyl phthalate and dimethyl phthalate, enhance the toxic effect and are able to disrupt the membrane of microorganisms.
Biodegradation by mammals
Recent studies show that DEP, a phthalic acid ester (PAE), is enzymatically hydrolyzed to its monoesters by pancreatic cholesterol esterase (CEase) in pigs and cows. These mammalian pancreatic CEases have been found to be nonspecific for degradation in relation to the diversity of the alkyl side chains of PAEs.
Toxicity
Little is known about the chronic toxicity of diethyl phthalate, but existing information suggests only a low toxic potential. Studies suggest that some phthalates affect male reproductive development via inhibition of androgen biosynthesis. In rats, for instance, repeated administration of DEP results in loss of germ cell populations in the testis. However, diethyl phthalate does not alter sexual differentiation in male rats. Dose response experiments in fiddler crabs have shown that seven-day exposure to diethyl phthalate at 50 mg/L significantly inhibited the activity of chitobiase in the epidermis and hepatopancreas. Chitobiase plays an important role in degradation of the old chitin exoskeleton during the pre-moult phase.
Teratogenicity
When pregnant rats were treated with diethyl phthalate, it became evident that certain doses caused skeletal malformations, whereas the untreated control group showed no resorptions. The amount of skeletal malformations was highest at highest dose. In a following study it was found that both phthalate diesters and their metabolic products were present in each of these compartments, suggesting that the toxicity in embryos and fetuses could be the result of a direct effect.
Future investigation
Some data suggest that exposure to multiple phthalates at low doses significantly increases the risk in a dose additive manner. Therefore, the risk from a mixture of phthalates or phthalates and other anti-androgens, may not be accurately assessed studying one chemical at a time. The same may be said about risks from several exposure routes together. Humans are exposed to phthalates by multiple exposure routes (predominantly dermal), while toxicological testing is done via oral exposure.
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