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Parabens in urine, serum and seminal plasma from healthy Danish men determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS)

Abstract

Parabens are used as anti-microbial preservatives in a range of consumer products, especially in cosmetics. In vitro and animal studies have shown weak estrogenic and other endocrine disrupting effects of parabens, including reduced testosterone levels in exposed male rats. The knowledge of paraben exposure, distribution and excretion in humans is limited. In this study we determined the concentration of five parabens; methyl-, ethyl-, n-propyl-, n-butyl- and benzylparaben in urine, serum and seminal plasma samples from 60 healthy Danish men. To conduct the study a sensitive and specific method using LC–MS/MS for simultaneous determination of the five parabens was developed for all three different matrices. Highest concentrations of the parabens were found in urine, wherein methyl-, ethyl-, n-propyl- and n-butyl parabens were measurable in 98%, 80%, 98% and 83% of the men, respectively. Benzyl paraben was only measurable in urine from 7% of the men. Methyl- and n-propyl parabens were also measurable in the majority of serum and seminal plasma samples, whereas the other parabens could only be detected in some of the samples. In all the three matrices significant correlations between the parabens were seen. Furthermore, urinary paraben concentrations correlate to the paraben concentrations in both serum and seminal plasma.

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References

  • Akomeah F., Nazir T., Martin G.P., and Brown M.B. Effect of heat on the percutaneous absorption and skin retention of three model penetrants. Eur J Pharm Sci 2004: 21: 337–345.

    Article  CAS  Google Scholar 

  • Blount B.C., Milgram K.E., Silva M.J., Malek N.A., Reidy J.A., Needham L.L., and Brock J.W. Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. Anal Chem 2000: 72: 4127–4134.

    Article  CAS  Google Scholar 

  • Byford J.R., Shaw L.E., Drew M.G., Pope G.S., Sauer M.J., and Darbre P.D. Oestrogenic activity of parabens in MCF7 human breast cancer cells. J Steroid Biochem Mol Biol 2002: 80: 49–60.

    Article  CAS  Google Scholar 

  • CIR Expert Panel. Final amended report on the safety assessment of methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben, and benzylparaben as used in cosmetic products. Int J Toxicol 2009: 27 (Suppl 4): 1–82.

    Google Scholar 

  • Darbre P.D., Aljarrah A., Miller W.R., Coldham N.G., Sauer M.J., and Pope G.S. Concentrations of parabens in human breast tumours. J Appl Toxicol 2004: 24: 5–13.

    Article  CAS  Google Scholar 

  • Darbre P.D., Byford J.R., Shaw L.E., Hall S., Coldham N.G., Pope G.S., and Sauer M.J. Oestrogenic activity of benzylparaben. J Appl Toxicol 2003: 23: 43–51.

    Article  CAS  Google Scholar 

  • Darbre P.D., Byford J.R., Shaw L.E., Horton R.A., Pope G.S., and Sauer M.J. Oestrogenic activity of isobutylparaben in vitro and in vivo. J Appl Toxicol 2002: 22: 219–226.

    Article  CAS  Google Scholar 

  • Frederiksen H., Taxvig C., Hass U., Vinggaard A.M., and Nellemann C. Higher levels of ethyl paraben and butyl paraben in rat amniotic fluid than in maternal plasma after subcutaneous administration. Toxicol Sci 2008: 106: 376–383.

    Article  CAS  Google Scholar 

  • Hoberman A.M., Schreur D.K., Leazer T., Daston G.P., Carthew P., Re T., Loretz L., and Mann P. Lack of effect of butylparaben and methylparaben on the reproductive system in male rats. Birth Defects Res B Dev Reprod Toxicol 2008: 83: 123–133.

    Article  CAS  Google Scholar 

  • Janjua N.R., Frederiksen H., Skakkebaek N.E., Wulf H.C., and Andersson A.M. Urinary excretion of phthalates and paraben after repeated whole-body topical application in humans. Int J Androl 2008: 31: 118–129.

    Article  CAS  Google Scholar 

  • Janjua N.R., Mortensen G.K., Andersson A.M., Kongshoj B., Skakkebaek N.E., and Wulf H.C. Systemic uptake of diethyl phthalate, dibutyl phthalate, and butyl paraben following whole-body topical application and reproductive and thyroid hormone levels in humans. Environ Sci Technol 2007: 41: 5564–5570.

    Article  CAS  Google Scholar 

  • Jorgensen N., Carlsen E., Nermoen I., Punab M., Suominen J., Andersen A-G., Andersson A-M., Haugen T.B., Horte A., Jensen T.K., Magnus Ø., Petersen J.H., Vierula M., Toppari J., and Skakkebæk N.E. East-West gradient in semen quality in the Nordic-Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland. Hum Reprod 2002: 17: 2199–2208.

    Article  Google Scholar 

  • Kang K.S., Che J.H., Ryu D.Y., Kim T.W., Li G.X., and Lee Y.S. Decreased sperm number and motile activity on the F1 offspring maternally exposed to butyl p-hydroxybenzoic acid (butyl paraben). J Vet Med Sci 2002: 64: 227–235.

    Article  CAS  Google Scholar 

  • Lemini C., Jaimez R., Avila M.E., Franco Y., Larrea F., and Lemus A.E. In vivo and in vitro estrogen bioactivities of alkyl parabens. Toxicol Ind Health 2003: 19: 69–79.

    Article  CAS  Google Scholar 

  • Lobemeier C., Tschoetschel C., Westie S., and Heymann E. Hydrolysis of parabenes by extracts from differing layers of human skin. Biol Chem 1996: 377: 647–651.

    CAS  PubMed  Google Scholar 

  • Oishi S. Effects of butylparaben on the male reproductive system in rats. Toxicol Ind Health 2001: 17: 31–39.

    Article  CAS  Google Scholar 

  • Oishi S. Effects of propyl paraben on the male reproductive system. Food Chem Toxicol 2002: 40: 1807–1813.

    Article  CAS  Google Scholar 

  • Oishi S. Lack of spermatotoxic effects of methyl and ethyl esters of p-hydroxybenzoic acid in rats. Food Chem Toxicol 2004: 42: 1845–1849.

    Article  CAS  Google Scholar 

  • Okubo T., Yokoyama Y., Kano K., and Kano I. ER-dependent estrogenic activity of parabens assessed by proliferation of human breast cancer MCF-7 cells and expression of ERalpha and PR. Food Chem Toxicol 2001: 39: 1225–1232.

    Article  CAS  Google Scholar 

  • Pugazhendhi D., Pope G.S., and Darbre P.D. Oestrogenic activity of p-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines. J Appl Toxicol 2005: 25: 301–309.

    Article  CAS  Google Scholar 

  • Soni M.G., Carabin I.G., and Burdock G.A. Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food Chem Toxicol 2005: 43: 985–1015.

    Article  CAS  Google Scholar 

  • Tavares R.S., Martins F.C., Oliveira P.J., Ramalho-Santos J., and Peixoto F.P. Parabens in male infertility-is there a mitochondrial connection? Reprod Toxicol 2009: 27: 1–7.

    Article  CAS  Google Scholar 

  • Taxvig C., Vinggaard A.M., Hass U., Axelstad M., Boberg J., Hansen P.R., Frederiksen H., and Nellemann C. Do parabens have the ability to interfere with steroidogenesis? Toxicol Sci 2008: 106: 206–213.

    Article  CAS  Google Scholar 

  • Ye X., Bishop A.M., Reidy J.A., Needham L.L., and Calafat A.M. Parabens as urinary biomarkers of exposure in humans. Environ Health Perspect 2006a: 114: 1843–1846.

    Article  CAS  Google Scholar 

  • Ye X., Kuklenyik Z., Bishop A.M., Needham L.L., and Calafat A.M. Quantification of the urinary concentrations of parabens in humans by on-line solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2006b: 844: 53–59.

    Article  CAS  Google Scholar 

  • Ye X., Tao L.J., Needham L.L., and Calafat A.M. Automated on-line column-switching HPLC-MS/MS method for measuring environmental phenols and parabens in serum. Talanta 2008: 76: 865–871.

    Article  CAS  Google Scholar 

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Acknowledgements

For skilled technical assistance, the authors thank Ole Nielsen, Department of Growth and Reproduction, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. The instrumental equipment was financially supported by Velux Fonden and this work was supported by the Danish Research Agency (Grant no. 2107-05-0006) and the Lundbeck Foundation (j.nr. 124/05).

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Correspondence to Hanne Frederiksen.

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Frederiksen, H., Jørgensen, N. & Andersson, AM. Parabens in urine, serum and seminal plasma from healthy Danish men determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS). J Expo Sci Environ Epidemiol 21, 262–271 (2011). https://doi.org/10.1038/jes.2010.6

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