Phthalic acid ester

from Wikipedia, the free encyclopedia
o -phthalic acid alkyl ester
R 1 , R 2 = C n H 2n + 1 (n = 4–15)

Phthalic acid esters [ ˈftaːl… ] ( phthalates ) are esters of phthalic acid (= 1,2-benzene dicarboxylic acid) with various alcohols , mostly alkanols . The salts of phthalic acid are also called phthalates.

use

Most of the phthalates produced industrially in large quantities are used as plasticizers for plastics such as PVC , nitrocellulose or synthetic rubber . The most important representatives of the phthalates are diethylhexyl phthalate , ( DEHP , esterification product of o -phthalic acid with 2-ethylhexanol , is sometimes alternatively referred to as "dioctyl phthalate" DOP , but as an isomer can be chemically differentiated from it: di- n -octyl phthalate ) and diisononyl phthalate (DINP ). Dimethyl , diethyl or dibutyl phthalate are also used as a component of cosmetics or personal care products and pharmaceutical products. In 2010 the market was still dominated by phthalate-based plasticizers, but legal regulations and increasing environmental awareness are increasingly forcing the use of phthalate-free plasticizers.

Analytics

The reliable qualitative and quantitative determination of the phthalic acid esters succeeds after adequate sample preparation in various test materials by coupling gas chromatography with mass spectrometry .

toxicology

With BBP, DBP, DEHP, DIBP, BMEP, PIPP, DIPP, DPP and DnHP, nine phthalic acid esters are on the ECHA candidate list of substances of very high concern ( SVHC ). When evaluating phthalates, a distinction must be made between low molecular weight (DEHP, DBP, etc.) and higher molecular weight phthalates (DINP, DIDP, DPHP, etc.). DINP and DIDP were comprehensively examined as part of an EU risk assessment. Both products are now also registered under REACH . Since February 2015, BBP, DBP and DEHP only have approvals for medical packaging; Use is no longer permitted at DIBP.

Low-molecular phthalates are problematic compounds for health, as they are suspected of acting like hormones and, for example, causing infertility, obesity and diabetes in men. An EU study could not rule out that low molecular weight phthalates, parabens and PCBs disrupt the hormonal balance of male fetuses and children and thus lead to feminization. According to a study from the United States, phthalates could also be a risk factor for premature birth. A Canadian study published in April 2015 also reported no association between decreased fertility (longer time until pregnancy) and phthalate concentrations in the urine of women.

For a long time there was no evidence of harm in humans with the phthalates used in drugs, but the EMA nevertheless suggested that their use be restricted, as animal studies indicated that sufficient doses could cause harm.

In a Danish cohort study in 2019, an increase in the risk of estrogen receptor positive (ER +) breast cancer was observed, which was doubled at the highest exposure. A direct correlation was observed between the level of exposure and the increased risk. The exposure occurred through the ingestion of phthalate-containing drugs (mesalazine, budesonide, lithium and bisacodyl, phthalates: dibutyl phthalate, cellulose acetate phthalate, hypromellose phthalate and polyvinyl acetate phthalate). The exposure data came from the Danish drug registry, the disease data from the Danish cancer registry. The observation period was from 2005 to 2018. 1.12 million women were observed, 14% of the women were exposed to the pharmaceuticals, and 27111 cases of breast cancer occurred during the observation period.

Epidemiological Studies

In more recent epidemiological studies, the research results mentioned in the Toxicology section are partially confirmed and information about future research priorities is given.

distribution

An article in the WDR magazine Plusminus , which referred to phthalates in drugs, caused a stir . The consumer test magazine Öko-Test and Stiftung Warentest also repeatedly publish results on phthalates in various consumer products such as children's toys , sex toys , edible oils and rubber products. The Federation for the Environment and Nature Conservation Germany tested four fairy lights in a random sample in 2019 . The limit values ​​of the RoHS guidelines for the two phthalates DEHP and DBP measured were massively exceeded in three of the four products. In addition, the film Plastic Planet points out the global spread of plastic in general and the various health hazards of the plasticizers it contains in particular.

They are mainly used as plasticizers in products made from PVC and certain thermoplastic elastomers. In most standard plastics such as B. polyolefinic packaging materials are not included.

One study measured the migration or elution of phthalic acid esters from polyethylene terephthalate bottles for soft drinks . The highest values ​​contained drinks that were preserved with potassium sorbate or that had the lowest pH value . The measured values ​​did not pose a health risk , but small amounts could accumulate over time.

Protective measures

The work glove manufacturer Marigold gives a breakthrough time of> 480 minutes for dioctyl phthalate for its latex laboratory gloves, which indicates that latex seems to be a good barrier. It should be noted that laboratory gloves are made of thick latex and are seldom exposed to high mechanical stresses.

The plastics manufacturer Semadeni states in its 2007 product catalog that latex is “ not resistant ” when exposed to dioctyl phthalate .

According to information from the US media, a committee in the US Congress agreed on July 29, 2008 on a ban on phthalates, which are widely used as additives in plastics.

Pharmacies can use the ABDA database to determine which drugs contain phthalates .

Individual phthalates are already banned in cosmetics ; the details can be found in the German Cosmetics Ordinance ; the packaging label must inform about the others (for example DMP and DEP ).

In addition to plasticizers, there are also hardeners in plastics; see bisphenol A (BPA).

List of phthalates

Some phthalates are isomer mixtures of various branched and / or unbranched individual substances in various concentrations. Their properties are usually very similar. Even in the specialist literature, imprecise classifications can occasionally be found.

Surname Acronym Structural formula of phthalate CAS no. Stereoisomers [number] use
Dimethyl phthalate DMP Dimethylphthalate Structural Formula.svg 131-11-3 No
Diethyl phthalate DEP Diethylphthalate Structural Formula.svg 84-66-2 No Emulsion paints and plastic plasters , perfume fixation and denaturation of perfume alcohol
Diallyl phthalate DAP Diallylphthalate Structural Formula V1.svg 131-17-9 No Reactive thinner for radiation curing
Di- n -propyl phthalate DPRP Di-n-propylphthalate Structural Formula.svg 131-16-8 No
Di- n -butyl phthalate DBP Di-n-butylphthalate Structural Formula.svg 84-74-2 No universal plasticizer
Diisobutyl phthalate DIBP Diisobutylphthalate Structural Formula.svg 84-69-5 No universal plasticizer
Butyl cyclohexyl phthalate BCP Butylcyclohexylphthalate Structural Formula.svg 84-64-0 No
Di- n -pentyl phthalate DPP Di-n-pentylphthalate Structural Formula.svg 131-18-0 No
Dicyclohexyl phthalate DCHP Dicyclohexylphthalate Structural Formula.svg 84-61-7 No Plasticizers for film varnishes , in particular for cell glass
Benzyl n -butylphthalat BBP Benzyl-n-butylphthalate Structural Formula.svg 85-68-7 No Plasticizers in polystyrene , polyvinyl acetate , cellulose nitrate , ethyl cellulose , cellulose acetate butyrate , alkyd resins and acrylates
Di- n -hexyl phthalate DnHP Di-n-hexylphthalate Structural Formula.svg 84-75-3 No
Diisohexyl phthalate DIHxP Diisohexylphthalate.svg 68515-50-4 No
Diisoheptyl phthalate DIHpP Diisoheptylphthalate.svg 41451-28-9 No
Butyl decyl phthalate BDP Butyldecylphthalate.svg 89-19-0 No
Diethylhexyl phthalate DEHP, DOP Bis (2-ethylhexyl) phthalate.svg 117-81-7 Yes 3] Plasticizer for PVC and cellulose nitrate and for grinding color pigments
Di- n -octyl phthalate DNOP Dioctyl phthalate.svg 117-84-0 No
Diisooctyl phthalate DIOP Diisooctyl phthalate.svg 27554-26-3 No
n -Octyl- n -decyl phthalate ODP Octyl decyl phthalate.svg 119-07-3 No
Diisononyl phthalate DINP Diisononyl phthalate.svg 28553-12-0 / 68515-48-0 Yes 3] Soft PVC
Diisodecyl phthalate DIDP Diisodecyl phthalate.svg 26761-40-0 / 68515-49-1 No Soft PVC
Dipropyl heptyl phthalate DPHP DPHP.svg 53306-54-0 Yes 3]
Diundecyl phthalate DUP Diundecyl phthalate.svg 3648-20-2 No
Diisoundecyl phthalate DIUP Diisoundecylphthalate.svg 85507-79-5 No
Ditridecyl phthalate DTDP Ditridecyl phthalate.svg 119-06-2 No
Diisotridecyl phthalate DIUP Diisotridecylphthalate.svg 68515-47-9 / 27253-26-5 No
Bis (2-methoxyethyl) phthalate BMEP DMEP.svg 117-82-8
1,2-Benzene dicarboxylic acid, di-C7-11 branched and linear alkyl esters DHNUP 68515-42-4
1,2-Benzene dicarboxylic acid, di-C6-8 branched alkyl ester, C7-rich / diisoheptyl phthalate DIHP 71888-89-6
1,2-benzenedicarboxylic acid, dipentyl ester, branched and linear 84777-06-0
Diisopentyl phthalate DIPP Diisopentylphthalate.svg 605-50-5
n -pentyl isopentyl phthalate PIPP N-Pentyl-isopentylphthalat.svg 776297-69-9

Not included in the above list are polymers , e.g. B. alkyd resins .

literature

  • PlasticsEurope: plastics and phthalates . (PDF; 222 kB). December 2006.
  • K. Becker, M. Seiwert, J. Angerer, W. Heger, HM Koch, R. Nagorka, E. Roßkamp, ​​C. Schlueter, B. Seifert, D. Ullrich: DEHP metabolites in urine of children and DEHP in house dust . In: Int. J. Hyg. Environ. Health. 207, 5, 2004, pp. 409-417. PMID 15575555
  • M. Wittassek, W. Heger, HM Koch, K. Becker, J. Angerer, M. Kolossa-Gehring: Daily intake of di (2-ethylhexyl) phthalate (DEHP) by German children - a comparison of two estimation models based on urinary DEHP metabolite levels. In: Int. J. Hyg. Environ. Health. 210, 1, 2007, pp. 35-42. PMID 17185035
  • P. Factor-Litvak, B. Insel, AM Calafat, X. Liu, F. Perera et al .: Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years. In: PLoS ONE . 9 (12), 2014. doi: 10.1371 / journal.pone.0114003
  • Sopheak Net, Richard Sempéré, Anne Delmont, Andrea Paluselli, Baghdad Ouddane: Occurrence, Fate, Behavior and Ecotoxicological State of Phthalates in Different Environmental Matrices. In: Environmental Science & Technology . 2015. doi: 10.1021 / es505233b

Individual evidence

  1. Mark study plasticizers , Ceresana May 2011th
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  3. MV Russo, P. Avino, I. Notardonato: Fast analysis of phthalates in freeze-dried baby foods by ultrasound-vortex-assisted liquid-liquid microextraction coupled with gas chromatography-ion trap / mass spectrometry. In: J Chromatogr A. 1474, Nov 25, 2016, pp. 1-7. PMID 28314431
  4. MS Oh, SH Lee, MH Moon, DS Lee, HM Park: Simultaneous analysis of phthalates, adipate and polycyclic aromatic hydrocarbons in edible oils using isotope dilution-gas chromatography-mass spectrometry. In: Food Addit Contam Part B Surveill. 7 (3), 2014, pp. 168-175. PMID 25029399
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  7. IDW-Online May 29, 2012
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  9. Two-year-olds at risk from 'gender-bending' chemicals, report says. In: The Guardian. November 6, 2009. (English)
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  12. Phthalates increase the risk of premature birth
  13. Maria P. Vélez, Tye E. Arbuckle, William D. Fraser: Female exposure to phenols and phthalates and time to pregnancy: the Maternal-Infant Research on Environmental Chemicals (MIREC) Study . In: Fertility and Sterility . tape 103 , no. 4 , p. 1011-1020.e2 , doi : 10.1016 / j.fertnstert.2015.01.005 , PMID 25681860 .
  14. EMA: Guideline on the use of phthalates as excipients in human medicinal products (PDF; 169 kB).
  15. Thomas P. Ahern, Anne Broe, Timothy L. Lash, Deirdre P. Cronin-Fenton, Sinna Pilgaard Ulrichsen: Phthalate Exposure and Breast Cancer Incidence: A Danish Nationwide Cohort Study. In: Journal of Clinical Oncology. April 17, 2019, ISSN 0732-183X, S. JCO.18.02202, doi : 10.1200 / JCO.18.02202 (ascopubs.org [accessed April 27, 2019]).
  16. O. Solomon, P. Yousefi, K. Huen, RB Gunier, M. Escudero-Fung, LF Barcellos, B. Eskenazi, N. Holland: Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood. In: Environ Mol Mutagen. May 28, 2017. PMID 28556291
  17. N. Holland, K. Huen, V. Tran, K. Street, B. Nguyen, A. Bradman, B. Eskenazi: Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy . In: Toxics. 4 (1). March 4, 2016, p. 7. PMID 28008399
  18. ^ J. Botton, C. Philippat, AM Calafat, S. Carles, MA Charles, R. Slama, The Eden Mother-Child Cohort Study Group: Phthalate pregnancy exposure and male offspring growth from th1e intra-uterine period to five years of age . In: Environ Res. 151, Nov 2016, pp. 601-609. PMID 27596487
  19. M. Morgan, A. Deoraj, Q. Felty, D. Roy: Environmental estrogen-like endocrine disrupting chemicals and breast cancer. In: Mol Cell Endocrinol. 457, Oct 4, 2016, pp. 89-102. PMID 27717745
  20. T. Zhang, W. Shen, M. De Felici, XF Zhang: Di (2-ethylhexyl) phthalate: Adverse effects on folliculogenesis that cannot be neglected. In: Environ Mol Mutagen. 57 (8), Oct 2016, pp. 579-588. PMID 27530864
  21. HJ Wen, L. Sie, PH Su, CJ Chuang, HY Chen, CW Sun, LH Huang, CA Hsiung, SL Julie Wang: Prenatal and childhood exposure to phthalate diesters and sex steroid hormones in 2-, 5-, 8- , and 11-year-old children: A pilot study of the Taiwan Maternal and Infant Cohort Study. In: J Epidemiol. May 30, 2017. PMID 28576446
  22. Phthalates in pharmaceuticals: BfArM warns of uncertainty. ( Memento from July 16, 2013 in the archive.today web archive ) Status: March 7, 2006. (on: archive.is )
  23. Stiftung Warentest: FAQ Phthalates: What you should know about plasticizers . In: test.de from August 22, 2018.
  24. Christmas lights: BUND detects high levels of illegal pollutants in fairy lights. BUND, November 19, 2019, accessed December 11, 2019 .
  25. Jasna Bošnir, Dinko Puntarić, Antonija Galić, Ivo Škes, Tomislav Dijanić, Maja Klarić, Matijana Grgić, Mario Čurković, Zdenko Šmit: Migration of Phthalates from Plastic Containers into Soft Drinks and Mineral Water ; Food Technology and Biotechnology, vol. 45 no. 1, 2007 (abstract); ( PDF file, full article )
  26. Marigold Industrial: Hand protection (PDF; 1.3 MB).
  27. ^ Semadeni AG: Homepage .
  28. Cosmetics Ordinance. ( Memento of January 13, 2012 in the Internet Archive ) (PDF file; 485 kB) in the version of July 6, 2012, see No. 675, 677, 678, 1151 and 1152 of Annex 1 (to Section 1).
  29. a b c d e Entry on phthalic acid ester. In: Römpp Online . Georg Thieme Verlag, accessed on July 17, 2014.
  30. Denaturants in cosmetics - health is of secondary importance
  31. Entry on dipropyl phthalate at ChemicalBook , accessed on December 11, 2017.
  32. Entry on di-n-pentyl phthalate at ChemicalBook , accessed on December 11, 2017.
  33. Entry on di-n-hexyl phthalate at ChemicalBook , accessed December 11, 2017.

Web links

Wiktionary: Phthalate  - explanations of meanings, word origins, synonyms, translations