Skip to main content
Log in

Persistent plasticizers and bisphenol in the cheese of Tunisian markets induced biochemical and histopathological alterations in male BALB/c mice

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Clinical evidences, experimental models, and epidemiology of many studies suggest that phthalate-based plasticizers, aliphatic ester, and bisphenol A (BPA) have major risks for humans by targeting different organs and body systems. The current study has been designed firstly to analyze three categories of cheese with and without their exposure to the sun and packed in packages with an inner surface plastic-covered film in order to identify the dibutyl phthalate (DBP); benzyl butyl phthalate (BBP); bis(2-ethylhexyl) phthalate (DEHP); diisodecyl phthalate (DiDP); diisononyl phthalate (DiNP); and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) by GC-MS/MS, except for the bisphenol A, which is by UPLC-MS/MS, and secondly to assess the toxicity of the identified chemical molecules and cheese samples on the liver and kidney of mice. Our results showed that the cheese contains high quantities of DBP and DEHP with the concentrations up to 0.46 and 2.339 mg/kg, respectively. Other types of cheese, such as rolled and triangular cheeses, contain little quantities of the all substances at concentrations below the standard limits. In vivo, the obtained data clearly demonstrated that the acute administration of DBP, DEHP, and the tested cheese significantly induced liver and kidney injuries in mice manifested by a rise in plasma alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, lactate dehydrogenase, urea, creatinine, and uric acid when compared with control animals. In addition, the histopathological study confirmed the perturbation of biochemical parameters and showed that the hepatic and renal structures were altered. Indeed, the hepatotoxic and nephrotoxic effects are more pronounced when cheese was exposed to the sun.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Bornehag CG, Sundell J, Weschler CJ, Sigsgaard T, Lundgren B, Hasselgren M, Hagerhed-Engman L (2004) The association between asthma and allergic symptoms in children and phthalates in house dust: a nested case-control study. Environ Health Perspect 112(14):1393–1397. https://doi.org/10.1289/ehp.7187

    Article  CAS  Google Scholar 

  • Cao XL, Zhao W, Churchill R, Hilts C (2014) Occurrence of di-(2-ethylhexyl) adipate and phthalate plasticizers in samples of meat, fish, and cheese and their packaging films. J Food Prot 77(4):610–620. https://doi.org/10.4315/0362-028X.JFP-13-380

    Article  CAS  Google Scholar 

  • Chevalier N, Féniche IP (2015) Endocrine disruptors: new players in the pathophysiology of type 2 diabetes? Diabetes Metab 42:107–115

    Article  Google Scholar 

  • Desdoits-Lethimonier C, Albert O, Le BB, Perdu E, Zalko D, Courant F, Lesne L, Guille F, Dejucq-Rainsford N, Jegou B (2012) Human testis steroidogenesis is inhibited by phthalates. Hum Reprod 27(5):1451–1459. https://doi.org/10.1093/humrep/des069

    Article  CAS  Google Scholar 

  • Di Bella G, Potortì AG, Lo Turco V, Saitta M, Dugo G (2014) Plasticizer residues by HRGC-MS in espresso coffees from capsules, pods and moka pots. Food Control 41:185–192. https://doi.org/10.1016/j.foodcont.2014.01.026

    Article  Google Scholar 

  • Dugo G, Fotia V, Lo Turco V, Maisano R, Potortì AG, Salvo A, Bella D (2011) Phthalate, adipate and sebacate residues by HRGC-MS in olive oils from Sicily and Molise (Italy). Food Control 22(6):982–988. https://doi.org/10.1016/j.foodcont.2010.12.006

    Article  CAS  Google Scholar 

  • EFSA (2005a) 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: question no. EFSA-Q-2003-192. EFSA J 242:3–17

    Google Scholar 

  • EFSA (2005b) Opinion of the scientific panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the commission related to bis(2-ethylhexyl) phthalate (DEHP) for use in food contact materials: question no. EFSA-Q-2003-191. EFSA J 243:1–2

    Google Scholar 

  • Engel SM, Miodovnik A, Canfield RL, Zhu C, Silva MJ, Calafat AM, Wolff MS (2010) Prenatal phthalate exposure is associated with childhood behavior and executive functioning. Environ Health Perspect 118(4):565–571. https://doi.org/10.1289/ehp.0901470

    Article  CAS  Google Scholar 

  • Food and Agriculture (1989) (FAO Agriculture Series, no. 22). ISBN 92-5-102838-9. ISSN 0081-453"9

  • Fasano E, Bono-Blay F, Cirillo T, Montuori P, Lacorte S (2012) Migration of phthalates, alkylphenols, bisphenol A and di(2-ethylhexyl) adipate from food packaging. Food Control 27(1):132–138. https://doi.org/10.1016/j.foodcont.2012.03.005

    Article  CAS  Google Scholar 

  • Ge J, Han B, Hu H, Liu J, Liu Y (2015) Epigallocatechin-3-O-gallate protects against hepatic damage and testicular toxicity in male mice exposed to di-(2-ethylhexyl) phthalate. J Med Food 7:753–761

    Article  Google Scholar 

  • Huang T, Saxena AR, Isganaitis E, Todd TJ (2014) Gender and racial/ethnic differences in the associations of urinary phthalate metabolites with markers of diabetes risk: national health and nutrition examination survey 2001–2008. Environ Health 13(1):6. https://doi.org/10.1186/1476-069X-13-6

    Article  Google Scholar 

  • Inoue M, Nobukuni Y, Ando Y, Hirota M, Hirata E, Morino Y (1986) Interorgan metabolism of glutathione as the defense mechanism against oxidative stress. Dev Toxicol Environ Sci 14:51–60

    CAS  Google Scholar 

  • Jaakkola JJK, Verkasalo PK, Jaakkola N (2000) Plastic wall materials in the home and respiratory health in young children. Am J Public Health 90(5):797–799

    Article  CAS  Google Scholar 

  • Kasahara E, Sato EF, Miyoshi M, Konaka R, Hiramoto K, Sasaki J (2002) Role of oxidative stress in germ cell apoptosis induced by di (2-ethylhexyl) phthalate. Biochem J 365(3):849–856. https://doi.org/10.1042/bj20020254

    Article  CAS  Google Scholar 

  • Latini G, De Felice C, Presta G, Del Vecchio A, Paris I, Ruggieri F, Mzzeo P (2003) In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy. Environ Health Perspect 111(14):1783–1785. https://doi.org/10.1289/ehp.6202

    Article  CAS  Google Scholar 

  • Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, Chellakooty M, Schmidt IM, Suomi AM, Virtanen HE, Petersen DV, Andersson AM, Toppari J, Skakkebaek NE (2006) Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect 114(2):270–276. https://doi.org/10.1289/ehp.8075

    Article  CAS  Google Scholar 

  • Marmugi A, Ducheix S, Lasserre F, Polizzi A, Paris A, Priymenko N, Bertrand-Michel J, Pineau T, Guillou H, Martin PG, Mselli-Lakhal L (2012) Perturbations métaboliques hépatiques: implication des xénosenseurs CAR (Constitutive Androstane Receptor) et PXR (Pregnane X Receptor) et d'un perturbateur endocrinien, le Bisphénol A. Hepatology 55(2):395–407

  • Miodovnik A, Engel SM, Zhu C, Ye X, Soorya LV, Silva MJ, Calafat AM, Wolff MS (2011) Endocrine disruptors and childhood social impairment. Neurotoxicology 32(2):261–267. https://doi.org/10.1016/j.neuro.2010.12.009

    Article  CAS  Google Scholar 

  • Miura Y, Naito M, Ablake M, Terayama H, Yi SQ, Qu N, Cheng LX, Suna S, Jitsunari F, Itoh M (2007) Short-term effects of di-(2-ethylhexyl) phthalate on testes, liver, kidneys and pancreas in mice. Asian J Androl 2:199–205

    Article  Google Scholar 

  • Pérez-Albaladejo E, Fernandes D, Lacorte S, Porte C (2017) Comparative toxicity, oxidative stress and endocrine disruption potential of plasticizers in JEG-3 human placental cells. Toxicol in Vitro 38:41–48. https://doi.org/10.1016/j.tiv.2016.11.003

    Article  Google Scholar 

  • Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28(1):56–63. https://doi.org/10.1093/ajcp/28.1.56

    Article  CAS  Google Scholar 

  • Rozati R, Reddy PP, Reddanna P, Mujtaba R (2002) Role of environmental estrogens in the deterioration of male factor fertility. Fertil Steril 78(6):1187–1194. https://doi.org/10.1016/S0015-0282(02)04389-3

    Article  Google Scholar 

  • Sakhi AK, Lillegaard ITL, Voorspoels S, Carlsen MH, Elin B, Løken EB, Brantsæter AL, Haugen M, Meltzer HM, Thomsen C (2014) Concentrations of phthalates and bisphenol A in Norwegian foods and beverages and estimated dietary exposure in adults. Environ Int 73:259–269. https://doi.org/10.1016/j.envint.2014.08.005

    Article  CAS  Google Scholar 

  • Silva MJ, Reidy JA, Samandar E, Herbert AR, Needham LL, Calafat AM (2005) Detection of phthalate metabolites in human saliva. Arch Toxicol 79(11):647–652. https://doi.org/10.1007/s00204-005-0674-4

    Article  CAS  Google Scholar 

  • Silva MJ, Reidy JA, Herbert AR, Preau JL Jr, Needham LL, Calafat AM (2004a) Detection of phthalate metabolites in human amniotic fluid. Bull Environ Contam Toxicol 72:1226–1231

    Article  CAS  Google Scholar 

  • Silva MJ, Slakman AR, Reidy JA, Preau JL Jr, Herbert AR, Samandar E, Needham LL, Calafat AM (2004b) Analysis of human urine for fifteen phthalate metabolites using automated solid-phase extraction. J Chromatogr B Anal Technol Biomed Life Sci 805(1):161–167. https://doi.org/10.1016/j.jchromb.2004.02.038

    Article  CAS  Google Scholar 

  • Stojanoska MM, Milosevic N, Milic N, Abenavoli L (2016) The influence of phthalates and bisphenol A on the obesity development and glucose metabolism disorders. Endocrine 55(3):666–681. https://doi.org/10.1007/s12020-016-1158-4

    Article  Google Scholar 

  • Tranfo G, Caporossi L, Paci E, Aragona C, Romanzi D, De CC, De RM, Capanna S, Papaleo B, Pera A (2012) Urinary phthalate monoesters concentration in couples with infertility problems. Toxicol Lett 213(1):15–20. https://doi.org/10.1016/j.toxlet.2011.11.033

    Article  CAS  Google Scholar 

  • Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR Jr, Lee DH, Shioda T, Soto AM, vom Saal FS, Welshons WV, Zoeller RT, Myers JP (2012) Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev 33(3):378–455. https://doi.org/10.1210/er.2011-1050

    Article  CAS  Google Scholar 

  • Venturelli AC, Fischer SV, de Morais RN, Grassiolli S, Martino Andrade AJ (2015) Effects of exposure to di-(2-ethylhexyl) phthalate (DEHP) during lactation and puberty on sexual maturation and glycemic homeostasis in males rats. Clin Nutr ESPEN 10:5–12

    Article  Google Scholar 

  • Whyatt RM, Adibi JJ, Calafat AM, Camann DE, Rauh V, Bhat HK, Perera FP, Andrews H, Just AC, Hoepner L, Tang D, Hauser R (2009) Prenatal di(2-ethylhexyl)phthalate exposure and length of gestation among an inner-city cohort. Pediatrics 124:1213–1220

    Article  Google Scholar 

  • Wolff MS, Teitelbaum SL, Pinney SM, Windham G, Liao L, Biro F, Kushi LH, Erdmann C, Hiatt RA, Rybak ME, Calafat AM (2010) Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls. Environ Health Perspect 118(7):1039–1046. https://doi.org/10.1289/ehp.0901690

    Article  CAS  Google Scholar 

  • Wormuth M, Scheringer M, Vollenweider M, Hungerbuhler K (2006) What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Anal 26(3):803–824. https://doi.org/10.1111/j.1539-6924.2006.00770.x

    Article  Google Scholar 

  • Wroblewski F, La Due JS (1955) Colorimetric method for LDH. In: Wootton IDP (ed) Microanalysis in medical biochemistry, vol. 104, 4th edn. JA Churchill Ltd, Gloucester, pp 115–118

    Google Scholar 

  • Zhou W, Chen MH, Weibin S (2015) Influence of phthalates on glucose homeostasis and atherosclerosis in hyperlipidemic mice. BMC Endocr Disord 15(1):13. https://doi.org/10.1186/s12902-015-0015-4

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hedi Ben Mansour.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Responsible editor: Philippe Garrigues

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Beltifa, A., Feriani, A., Macherki, M. et al. Persistent plasticizers and bisphenol in the cheese of Tunisian markets induced biochemical and histopathological alterations in male BALB/c mice. Environ Sci Pollut Res 25, 6545–6557 (2018). https://doi.org/10.1007/s11356-017-0857-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-017-0857-6

Keywords

Navigation