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 application areas such as toys, medical devices, and food packaging. It is of interest as an alternative for phthalate plasticizers, which are implicated as endocrine disruptors.[2]
BASF sells DINCH under the tradename of Hexamoll DINCH.[5]
Useedit
In February 2009, Mattel and Learning Curve confirmed that they were substituting phthalates with Hexamoll DINCH and citrate-based plasticizers.[6]
Regulatory approvaledit
Food contactedit
In the European Union the European Food Safety Authority approved DINCH for a wide variety of food contact applications in October 2006.[7] In 2007 DINCH has been added to Annex III of the "Directive 2002/72/EC relating to plastic materials and articles intended to come into contact with food".[8] The EU Directive 2002/72 has meanwhile been superseded by Regulation (EU) No 10/2011.[9] Hexamoll DINCH is listed in Annex I of Regulation (EU) No 10/2011 by as Food Conctact Material (FCM) 775 by its chemical name, i.e. as 1,2-cyclohexanedicarboxylic acid, diisononylester.
Toysedit
In the European Union 1,2-cyclohexane dicarboxylic acid diisononyl ester was not listed in directive 2005/84/EC. These restrictions for certain phthalates are now transferred into Annex XVII, 51 and 52 of Regulation (EC) No 1907/2006 which ban the use of certain phthalates in toys and childcare articles and thus DINCH can be used safely in toys and childcare articles.[10]
Possible health effectsedit
A research group from Harvard and CDC found suggestive negative associations between urinary MHiNCH, the monoester of DINCH, a minor urinary metabolite. . Their research at a fertility clinic showed that women who had been exposed to DINCH had lower, but statistically not significant estradiol hormone levels and fewer, though not statistically significant number of oocytes in their ovaries. However, urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness.[11] The results are inconclusive and therefore, the authors suggest that more epidemiological studies would be needed for clarification.
The Swedish IVL Environmental Research Institute and researches from the Department of Environmental Science and Analytical Chemistry of Stockholm University recommend that "children's exposure to DINCH should be investigated in more detail and exposure to the general population should be closely monitored"[12] as DINCH is used as an alternative plasticizer in e.g. children's toys.
The Chronic Hazard Advisory Panel of the U.S. Consumer Product Safety Commission "strongly encourages the appropriate U.S. agencies to obtain the necessary toxicological and exposure data to assess any potential risk from DINX" because of "lack of publicly available information".[13][14]
A French group from the University of Clermont-Ferrand noted that clinical data and data regarding the migration from Medical Devices would be rare. The Project was funded by the French Agency for the Safety of Health Products (ANSM). It remains unclear why this Research Group was not able to identify the published human biomonitoring data which give a perfect overview on population exposure of alternative plasticizers (e.g. DINCH/DINX) and their metabolites.[15]
A report by the Danish Ministry of the Environment states that the available data for DINCH do not indicate a need for further investigations. Further, the conclusion is that 3 of the evaluated plasticizers, namely the substances COMGHA, DEHT and DINCH may be seen as the most promising alternatives, as these substances have an extended data set (complying to Annex X data requirements, i.e. a two-generation reproduction study) without indicating specific concern for reproductive toxicity or endocrine activity.[16]Toxicogenomic screening showed that 648 genes were significantly changed after 48 hours exposure to DINCH suggesting that "DINCH is biologically active".[17]
^Zamkowska D, Karwacka A, Jurewicz J, Radwan M (July 2018). "Environmental exposure to non-persistent endocrine disrupting chemicals and semen quality: An overview of the current epidemiological evidence". International Journal of Occupational Medicine and Environmental Health. 31 (4): 377–414. doi:10.13075/ijomeh.1896.01195. PMID 30160090.
^Innovative plasticizer alternative to phthalates for non-PVC applications
^Patent WO 99/32427, "Verfahren zur Hydrierung von Benzolpolycarbonsäuren oder Derivaten davon unter Verwendung eines Makroporen aufweisenden Katalysators", July 1, 1999, BASF AG
^Flexible vinyls get new non-phthalate plasticizer. (Keeping Up With Additives). (September 1, 2002). Plastics Technology. Allbusiness.com. Accessed 2009-02-12.
^Sarah Varney (February 12, 2009). New Safety Law Doesn't Mean All's Well In Toyland. NPR. Accessed 2009-02-12.
^EFSA: Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request related to a 12th list of substances 2018-06-03 at the Wayback Machine for food contact materials, EFSA-Journal, 2006, 395–401, 1–21.
^Official Journal of the European Union: Corrigendum to Commission Directive 2007/19/EC of 30 March 2007 amending Directive 2002/72/EC relating to plastic materials and articles intended to come into contact with food and Council Directive 85/572/EEC laying down the list of simulants to be used for testing migration of constituents of plastic materials and articles intended to come into contact with foodstuffs, April 2, 2007.
^COMMISSION REGULATION (EU) No 10/2011 of 14 January 2011 on plastic materials and articles intended to come into contact with food Accessed 2013-08-05
^Official Journal of the European Union: Directive 2005/84/EC of the European Parliament and of the Council of 14 December 2005 amending for the 22nd time Council Directive 76/769/EEC on the approximation of the laws, regulations and administrative provisions of the Member States relating to restrictions on the marketing and use of certain dangerous substances and preparations (phthalates in toys and childcare articles)
^Mínguez-Alarcón, Lidia; Souter, Irene; Chiu, Yu-Han; Williams, Paige L.; Ford, Jennifer B.; Ye, Xiaoyun; Calafat, Antonia M.; Hauser, Russ (2016-11-01). "Urinary concentrations of cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester, a metabolite of the non-phthalate plasticizer di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), and markers of ovarian response among women attending a fertility center". Environmental Research. 151: 595–600. Bibcode:2016ER....151..595M. doi:10.1016/j.envres.2016.08.012. PMC5071161. PMID 27591839.
^Bui, Thuy T.; Giovanoulis, Georgios; Cousins, Anna Palm; Magnér, Jörgen; Cousins, Ian T.; de Wit, Cynthia A. (2016-01-15). "Human exposure, hazard and risk of alternative plasticizers to phthalate esters". Science of the Total Environment. 541: 451–467. Bibcode:2016ScTEn.541..451B. doi:10.1016/j.scitotenv.2015.09.036. PMID 26410720.
^Lioy, Paul J; Hauser, Russ; Gennings, Chris; Koch, Holger M; Mirkes, Philip E; Schwetz, Bernard A; Kortenkamp, Andreas (2015). "Assessment of phthalates/phthalate alternatives in children's toys and childcare articles: Review of the report including conclusions and recommendation of the Chronic Hazard Advisory Panel of the Consumer Product Safety Commission". Journal of Exposure Science and Environmental Epidemiology. 25 (4): 343–353. doi:10.1038/jes.2015.33. PMID 25944701.
^(PDF). United States Consumer Product Safety Commission. 2014. Archived from the original (PDF) on 2016-10-09.
^Bernard, L.; Décaudin, B.; Lecoeur, M.; Richard, D.; Bourdeaux, D.; Cueff, R.; Sautou, V. (2014-11-01). "Analytical methods for the determination of DEHP plasticizer alternatives present in medical devices: A review". Talanta. 129: 39–54. doi:10.1016/j.talanta.2014.04.069. PMID 25127563.
^B. S. Nielsen; D. Nørgaard Andersen; E. Giovalle; M. Bjergstrøm; P.B. Larsen (2014). "Alternatives to classified phthalates in medical devices, Danish Environmental Protection Agency, Environmental Project No. 1557, 2014, Copenhagen" (PDF).
^Nardelli, Thomas C.; Erythropel, Hanno C.; Robaire, Bernard (2015-10-07). "Toxicogenomic Screening of Replacements for Di(2-Ethylhexyl) Phthalate (DEHP) Using the Immortalized TM4 Sertoli Cell Line". PLOS ONE. 10 (10): e0138421. Bibcode:2015PLoSO..1038421N. doi:10.1371/journal.pone.0138421. ISSN 1932-6203. PMC4596883. PMID 26445464.
External linksedit
Hexamoll
October 27, 2023
cyclohexane, dicarboxylic, acid, diisononyl, ester, dinch, mixture, organic, compounds, with, formula, c6h10, co2c9h19, dinch, colorless, used, plasticizer, manufacture, flexible, plastic, articles, sensitive, application, areas, such, toys, medical, devices, . 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 application areas such as toys medical devices and food packaging It is of interest as an alternative for phthalate plasticizers which are implicated as endocrine disruptors 2 1 2 Cyclohexane dicarboxylic acid diisononyl ester NamesPreferred IUPAC name Bis 7 methyloctyl cyclohexane 1 2 dicarboxylateOther names Cyclohexane 1 2 dicarboxylic acid diisononyl ester Hexamoll DINCH tradename IdentifiersCAS Number 166412 78 8 Y3D model JSmol Interactive imageChEMBL ChEMBL3182578ChemSpider 9699466 YECHA InfoCard 100 121 507EC Number 605 439 7PubChem CID 11524680UNII H26MNT7GT7 YCompTox Dashboard EPA DTXSID20274044InChI InChI 1S C26H48O4 c1 21 2 15 9 5 7 13 19 29 25 27 23 17 11 12 18 24 23 26 28 30 20 14 8 6 10 16 22 3 4 h21 24H 5 20H2 1 4H3 YKey HORIEOQXBKUKGQ UHFFFAOYSA N YSMILES O C OCCCCCCC C C C1C C O OCCCCCCC C C CCCC1PropertiesChemical formula C 26H 48O 4Molar mass 424 666 g mol 1Appearance colorless liquid 1 Odor almost odorless 1 Density 0 944 0 954 g cm 3 1 Melting point Pour point 54 C 65 F 219 K 1 HazardsSafety data sheet SDS BASF Safety Data SheetExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references Contents 1 Production 2 Use 3 Regulatory approval 3 1 Food contact 3 2 Toys 4 Possible health effects 5 References 6 External linksProduction editDINCH can be produced by the catalytic hydrogenation of diisononyl phthalate 3 4 Alternatively it can be prepared by Diels Alder reaction of a diisononyl maleate with 1 3 butadiene followed by hydrogenation In the case of the catalytic hydrogenation the aromatic planar part of the diisononyl phthalate is transformed to a cyclohexane ring Commercial DINCH consists of 90 of the cis and 10 of the trans chiral isomers BASF sells DINCH under the tradename of Hexamoll DINCH 5 Use editIn February 2009 Mattel and Learning Curve confirmed that they were substituting phthalates with Hexamoll DINCH and citrate based plasticizers 6 Regulatory approval editFood contact edit In the European Union the European Food Safety Authority approved DINCH for a wide variety of food contact applications in October 2006 7 In 2007 DINCH has been added to Annex III of the Directive 2002 72 EC relating to plastic materials and articles intended to come into contact with food 8 The EU Directive 2002 72 has meanwhile been superseded by Regulation EU No 10 2011 9 Hexamoll DINCH is listed in Annex I of Regulation EU No 10 2011 by as Food Conctact Material FCM 775 by its chemical name i e as 1 2 cyclohexanedicarboxylic acid diisononylester Toys edit In the European Union 1 2 cyclohexane dicarboxylic acid diisononyl ester was not listed in directive 2005 84 EC These restrictions for certain phthalates are now transferred into Annex XVII 51 and 52 of Regulation EC No 1907 2006 which ban the use of certain phthalates in toys and childcare articles and thus DINCH can be used safely in toys and childcare articles 10 Possible health effects editA research group from Harvard and CDC found suggestive negative associations between urinary MHiNCH the monoester of DINCH a minor urinary metabolite Their research at a fertility clinic showed that women who had been exposed to DINCH had lower but statistically not significant estradiol hormone levels and fewer though not statistically significant number of oocytes in their ovaries However urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness 11 The results are inconclusive and therefore the authors suggest that more epidemiological studies would be needed for clarification The Swedish IVL Environmental Research Institute and researches from the Department of Environmental Science and Analytical Chemistry of Stockholm University recommend that children s exposure to DINCH should be investigated in more detail and exposure to the general population should be closely monitored 12 as DINCH is used as an alternative plasticizer in e g children s toys The Chronic Hazard Advisory Panel of the U S Consumer Product Safety Commission strongly encourages the appropriate U S agencies to obtain the necessary toxicological and exposure data to assess any potential risk from DINX because of lack of publicly available information 13 14 A French group from the University of Clermont Ferrand noted that clinical data and data regarding the migration from Medical Devices would be rare The Project was funded by the French Agency for the Safety of Health Products ANSM It remains unclear why this Research Group was not able to identify the published human biomonitoring data which give a perfect overview on population exposure of alternative plasticizers e g DINCH DINX and their metabolites 15 A report by the Danish Ministry of the Environment states that the available data for DINCH do not indicate a need for further investigations Further the conclusion is that 3 of the evaluated plasticizers namely the substances COMGHA DEHT and DINCH may be seen as the most promising alternatives as these substances have an extended data set complying to Annex X data requirements i e a two generation reproduction study without indicating specific concern for reproductive toxicity or endocrine activity 16 Toxicogenomic screening showed that 648 genes were significantly changed after 48 hours exposure to DINCH suggesting that DINCH is biologically active 17 References edit a b c d BASF Technical Leaflet Hexamoll DINCH Zamkowska D Karwacka A Jurewicz J Radwan M July 2018 Environmental exposure to non persistent endocrine disrupting chemicals and semen quality An overview of the current epidemiological evidence International Journal of Occupational Medicine and Environmental Health 31 4 377 414 doi 10 13075 ijomeh 1896 01195 PMID 30160090 Innovative plasticizer alternative to phthalates for non PVC applications Patent WO 99 32427 Verfahren zur Hydrierung von Benzolpolycarbonsauren oder Derivaten davon unter Verwendung eines Makroporen aufweisenden Katalysators July 1 1999 BASF AG Flexible vinyls get new non phthalate plasticizer Keeping Up With Additives September 1 2002 Plastics Technology Allbusiness com Accessed 2009 02 12 Sarah Varney February 12 2009 New Safety Law Doesn t Mean All s Well In Toyland NPR Accessed 2009 02 12 EFSA Opinion of the Scientific Panel on food additives flavourings processing aids and materials in contact with food AFC on a request related to a 12th list of substances Archived 2018 06 03 at the Wayback Machine for food contact materials EFSA Journal 2006 395 401 1 21 Official Journal of the European Union Corrigendum to Commission Directive 2007 19 EC of 30 March 2007 amending Directive 2002 72 EC relating to plastic materials and articles intended to come into contact with food and Council Directive 85 572 EEC laying down the list of simulants to be used for testing migration of constituents of plastic materials and articles intended to come into contact with foodstuffs April 2 2007 COMMISSION REGULATION EU No 10 2011 of 14 January 2011 on plastic materials and articles intended to come into contact with food Accessed 2013 08 05 Official Journal of the European Union Directive 2005 84 EC of the European Parliament and of the Council of 14 December 2005 amending for the 22nd time Council Directive 76 769 EEC on the approximation of the laws regulations and administrative provisions of the Member States relating to restrictions on the marketing and use of certain dangerous substances and preparations phthalates in toys and childcare articles Minguez Alarcon Lidia Souter Irene Chiu Yu Han Williams Paige L Ford Jennifer B Ye Xiaoyun Calafat Antonia M Hauser Russ 2016 11 01 Urinary concentrations of cyclohexane 1 2 dicarboxylic acid monohydroxy isononyl ester a metabolite of the non phthalate plasticizer di isononyl cyclohexane 1 2 dicarboxylate DINCH and markers of ovarian response among women attending a fertility center Environmental Research 151 595 600 Bibcode 2016ER 151 595M doi 10 1016 j envres 2016 08 012 PMC 5071161 PMID 27591839 Bui Thuy T Giovanoulis Georgios Cousins Anna Palm Magner Jorgen Cousins Ian T de Wit Cynthia A 2016 01 15 Human exposure hazard and risk of alternative plasticizers to phthalate esters Science of the Total Environment 541 451 467 Bibcode 2016ScTEn 541 451B doi 10 1016 j scitotenv 2015 09 036 PMID 26410720 Lioy Paul J Hauser Russ Gennings Chris Koch Holger M Mirkes Philip E Schwetz Bernard A Kortenkamp Andreas 2015 Assessment of phthalates phthalate alternatives in children s toys and childcare articles Review of the report including conclusions and recommendation of the Chronic Hazard Advisory Panel of the Consumer Product Safety Commission Journal of Exposure Science and Environmental Epidemiology 25 4 343 353 doi 10 1038 jes 2015 33 PMID 25944701 Report to the U S Consumer Product Safety Commission by the CHRONIC HAZARD ADVISORY PANEL ON PHTHALATES AND PHTHALATE ALTERNATIVES PDF United States Consumer Product Safety Commission 2014 Archived from the original PDF on 2016 10 09 Bernard L Decaudin B Lecoeur M Richard D Bourdeaux D Cueff R Sautou V 2014 11 01 Analytical methods for the determination of DEHP plasticizer alternatives present in medical devices A review Talanta 129 39 54 doi 10 1016 j talanta 2014 04 069 PMID 25127563 B S Nielsen D Norgaard Andersen E Giovalle M Bjergstrom P B Larsen 2014 Alternatives to classified phthalates in medical devices Danish Environmental Protection Agency Environmental Project No 1557 2014 Copenhagen PDF Nardelli Thomas C Erythropel Hanno C Robaire Bernard 2015 10 07 Toxicogenomic Screening of Replacements for Di 2 Ethylhexyl Phthalate DEHP Using the Immortalized TM4 Sertoli Cell Line PLOS ONE 10 10 e0138421 Bibcode 2015PLoSO 1038421N doi 10 1371 journal pone 0138421 ISSN 1932 6203 PMC 4596883 PMID 26445464 External links editHexamoll Retrieved from https en wikipedia org w index php title 1 2 Cyclohexane dicarboxylic acid diisononyl ester amp oldid 1092076886, wikipedia, wiki, book, books, library,
