Food Analytical Methods

, Volume 10, Issue 7, pp 2619–2628 | Cite as

Development of an Extraction Method Using Mixture Design for the Evaluation of Migration of Non-target Compounds and Dibutyl Phthalate from Baby Bottles

  • Wellington da Silva Oliveira
  • Thais Cristina Lima de Souza
  • Marisa Padula
  • Helena Teixeira Godoy


This work introduces a simple and rapid method for the extraction of baby bottle migrants from milk simulants employing a mixture of ethyl acetate:dichloromethane:hexane (27.5:22.5:50), using a simplex centroid design for optimization. Initially, the baby bottle materials were identified by FT-IR followed by migration test using 50% EtOH in water at 70 °C/2 h. Next, extraction and identification of migrants were performed by GC-MS. Furthermore, the additives in the baby bottle materials were quantified by HPLC-DAD. On the account of the toxicological potential of dibutyl phthalate, the optimized mixture was used for in-house validation by GC-MS of the proposed method. Dibutyl phthalate (DBP) migration was detected in three baby bottles with a concentration range of 175 to 235 μg kg−1, which is lower than the specific migration limit determined by the Brazilian Health Regulatory Agency. However, exposure to DBP from baby bottles was estimated, and this was higher than the tolerable daily intake recommended by the European Food Safety Authority, indicating a potential public health concern.


Baby bottle Polypropylene Phthalate Food contact materials Migrants 



This study was carried out with the support of São Paulo Research Foundation (FAPESP), process no. 2014/14248-7 and National Council for Scientific and Technological Development (CNPq) process no. 444909/2014-1.

Compliance with Ethical Standards

Conflict of Interest

Wellington da Silva Oliveira declares no conflict of interest. Thais Cristina Lima de Souza declares no conflict of interest. Marisa Padula declares no conflict of interest. Helena Teixeira Godoy declares no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

Not applicable.


  1. ANVISA (2008) Resolution RDC n 17, from 17 March 2008. States on technical regulation on positive list of additives for plastics materials intended to produce packages and equipments for contact with foodstuffs. Diário Oficial [da] República Federativa do Brasil, Seção 1, Brasilia, DFGoogle Scholar
  2. ANVISA (2010) Resolution RDC n 51 from 26 November 2010. States on migration from plastics materials, packages and equipments intended to come into contact with foodstuffs. Diário Oficial [da] República Federativa do Brasil, Seção 1, Brasília, DFGoogle Scholar
  3. ANVISA (2012) Resolution RDC n 56 from 16 November 2012. State on positive list of monomers, other starting substances and authorized polymers to development of packaging and plastic equipment in contact with foodstuffs. Diário Oficial [da] República Federativa do Brasil, Seção 1, Brasília, DFGoogle Scholar
  4. ASTM (2009) D6953-03: standard test method for determination of antioxidants and erucamide slip additives in polyethylene using liquid chromatography (LC). ASTM International, PhiladelphiaGoogle Scholar
  5. Brasil (2010) II Pesquisa de prevalência de aleitamento materno em municípios brasileiros. Editora do Ministério da Saúde, BrasíliaGoogle Scholar
  6. Bratinova S, Raffael B, Simoneau C (2009) Guidelines for performance criteria and validation procedures of analytical methods used in controls of food contact materials. 1st edition. Joint Research Centre LuxembourgGoogle Scholar
  7. Castle L, Mayo A, Gilbert J (1989) Migration of plasticizers from printing inks into foods. Food Addit Contam 6:437–443CrossRefGoogle Scholar
  8. Cherif Lahimer M, Ayed N, Horriche J, Belgaied S (2013) Characterization of plastic packaging additives: food contact, stability and toxicity. Arabian J ChemGoogle Scholar
  9. Cirillo T et al (2015) Exposure to di-2-ethylhexyl phthalate, di-n-butyl phthalate and bisphenol a through infant formulas. J Agr Food Chem 63:3303–3310CrossRefGoogle Scholar
  10. Contat-Rodrigo L, Haider N, Ribes-Greus A, Karlsson S (2001) Ultrasonication and microwave assisted extraction of degradation products from degradable polyolefin blends aged in soil. J Appl Polym Sci 79:1101–1112CrossRefGoogle Scholar
  11. Derringer GC, Suich R (1980) Simultaneous optimization of several response variables. J Qual Technol 12:214–219Google Scholar
  12. Dopico-García MS, López-Vilariñó JM, González-Rodríguez MV (2007) Antioxidant content of and migration from commercial polyethylene, polypropylene, and polyvinyl chloride packages. J Agr Food Chem 55:3225–3231CrossRefGoogle Scholar
  13. EFSA (2005) Opinion of the scientific panel on food additives, flavourings, processing aids and material in contact with food (AFC) on a request from the commission related to di-butylphthalate (DBP) for use in food contact materials. EFSA J 242:1–17Google Scholar
  14. Espert A, De Las Heras LA, Karlsson S (2005) Emission of possible odourous low molecular weight compounds in recycled biofibre/polypropylene composites monitored by head-space SPME-GC-MS. Polym Degrad Stab 90:555–562CrossRefGoogle Scholar
  15. European-Commission (2011) Commission Regulation (EU) no 10/2011 of 14 January 2011 on plastic materials and article intended to come into contact with food. Official Journal of the European Union, BrusselsGoogle Scholar
  16. Factor-Litvak P, Insel B, Calafat AM, Liu X, Perera F, Rauh VA, Whyatt RM (2014) Persistent associations between maternal prenatal exposure to phthalates on child IQ at age 7 years. PLoS ONE 9 doi: 10.1371/journal.pone.0114003
  17. Fankhauser-Noti A, Grob K (2007) Blank problems in trace analysis of diethylhexyl and dibutyl phthalate: investigation of the sources, tips and tricks. Anal Chim Acta 582:353–360CrossRefGoogle Scholar
  18. Farajzadeh MA, Khoshmaram L (2015) Development of dispersive liquid-liquid microextraction technique using ternary solvents mixture followed by heating for the rapid and sensitive analysis of phthalate esters and di(2-ethylhexyl) adipate. J Chromatogr A 1379:24–33CrossRefGoogle Scholar
  19. Farzanehfar V, Naderi N, Kobarfard F, Faizi M (2016) Determination of dibutyl phthalate neurobehavioral toxicity in mice. Food Chem Toxicol 94:221–226. doi: 10.1016/j.fct.2016.05.006 CrossRefGoogle Scholar
  20. Fierens T, Servaes K, Van Holderbeke M, Geerts L, De Henauw S, Sioen I, Vanermen G (2012) Analysis of phthalates in food products and packaging materials sold on the Belgian market. Food Chem Toxicol 50:2575–2583CrossRefGoogle Scholar
  21. Gärtner S, Balski M, Koch M, Nehls I (2009) Analysis and migration of phthalates in infant food packed in recycled paperboard. J Agr Food Chem 57:10675–10681CrossRefGoogle Scholar
  22. Guo Y, Kannan K (2012) Challenges encountered in the analysis of phthalate esters in foodstuffs and other biological matrices. Anal Bioanal Chem 404:2539–2554CrossRefGoogle Scholar
  23. Howdeshell KL, Rider CV, Wilson VS, Furr JR, Lambright CR, Gray JLE (2015) Dose addition models based on biologically relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats. Toxicol Sci 148:488–502. doi: 10.1093/toxsci/kfv196 CrossRefGoogle Scholar
  24. Jeon DH, Park GY, Kwak IS, Lee KH, Park HJ (2007) Antioxidants and their migration into food simulants on irradiated LLDPE film. LWT-Food Sci Technol 40:151–156CrossRefGoogle Scholar
  25. Jurewicz J, Hanke W (2011) Exposure to phthalates: reproductive outcome and children health. a review of epidemiological studies. Int J Occup Med Environ Health 24:115–141CrossRefGoogle Scholar
  26. Lin QB, Li B, Song H, Li XM (2011) Determination of 7 antioxidants, 8 ultraviolet absorbents, and 2 fire retardants in plastic food package by ultrasonic extraction and ultraperformance liquid chromatography. J Liq Chromatogr Relat Technol 34:730–743CrossRefGoogle Scholar
  27. Makwana U, Naik DG, Singh G, Patel V, Patil HR, Gupta VK (2009) Nature of phthalates as internal donors in high performance MgCl2 supported titanium catalysts. Catal Lett 131:624–631CrossRefGoogle Scholar
  28. Nerin C, Alfaro P, Aznar M, Domeño C (2013) The challenge of identifying non-intentionally added substances from food packaging materials: a review. Anal Chim Acta 775:14–24CrossRefGoogle Scholar
  29. Nerin C, Bentayeb K, Rodriguez-Lafuente A (2012) 4.15—sampling techniques for the determination of migrants from packaging materials in food. In: Pawliszyn J (ed) Comprehensive sampling and sample preparation. Academic Press, Oxford, pp 357–379CrossRefGoogle Scholar
  30. Onghena M, Negreira N, Van Hoeck E, Quirynen L, Van Loco J, Covaci A (2016) Quantitative determination of migrating compounds from plastic baby bottles by validated GC-QqQ-MS and LC-QqQ-MS methods. Food Anal Methods 9:2600–2612. doi: 10.1007/s12161-016-0451-4 CrossRefGoogle Scholar
  31. Onghena M, van Hoeck E, Vervliet P, Scippo ML, Simon C, van Loco J, Covaci A (2014) Development and application of a non-targeted extraction method for the analysis of migrating compounds from plastic baby bottles by GC-MS. Food Addit Contam A 31:2090–2102CrossRefGoogle Scholar
  32. Onghena M et al (2015) Identification of substances migrating from plastic baby bottles using a combination of low-resolution and high-resolution mass spectrometric analysers coupled to gas and liquid chromatography. J Mass Spectrom 50:1234–1244. doi: 10.1002/jms.3644 CrossRefGoogle Scholar
  33. Osimitz TG, Eldridge ML, Sloter E, Welsh W, Ai N, Sayler GS, Menn F, Toole C (2012) Lack of androgenicity and estrogenicity of the three monomers used in Eastman's Tritan™ copolyesters. Food Chem Toxicol 50:2196–2205Google Scholar
  34. Sathyanarayana S (2008) Phthalates and children’s health. Curr Probl Pediatr Adolesc Health Care 38:34–49CrossRefGoogle Scholar
  35. Silveira TFF, Meinhart AD, Souza TCL, Teixeira Filho J, Godoy HT (2016) Phenolic compounds from yerba mate based beverages—a multivariate optimisation. Food Chem 190:1159–1167. doi: 10.1016/j.foodchem.2015.06.031 CrossRefGoogle Scholar
  36. Simoneau C, van den Eede L, Valzacchi S (2012) Identification and quantification of the migration of chemicals from plastic baby bottles used as substitutes for polycarbonate. Food Addit Contam A 29:469–480Google Scholar
  37. Tadokoro H, Kobayashi M, Ukita M, Yasufuku K, Mtirahashi S, Torii T (1965) Normal vibrations of the polymer molecules of helical conformation. V. Isotactic polypropylene and its deuteroderivatives. J Chem Phys 42:1432–1449CrossRefGoogle Scholar
  38. Thompson M, Ellison SLR, Wood R (2002) Harmonized guidelines for single-laboratory validation of methods of analysis (IUPAC technical report). Pure Appl Chem 74:835–855CrossRefGoogle Scholar
  39. Wenzl T (2009) Methods for the determination of phthalates in food. Joint Research Centre, LuxembourgGoogle Scholar
  40. WHO child growth standards: Methods and development (2006) from Accessed 02/05/16

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Wellington da Silva Oliveira
    • 1
  • Thais Cristina Lima de Souza
    • 1
  • Marisa Padula
    • 2
  • Helena Teixeira Godoy
    • 1
  1. 1.Department of Food Science, Faculty of Food EngineeringUniversity of Campinas (UNICAMP)CampinasBrazil
  2. 2.Packaging Technology CenterInstitute of Food Technology (ITAL)CampinasBrazil

Personalised recommendations