Skip to main content
SpringerLink
Log in

New analytical method for the determination of endocrine disruptors in human faeces using gas chromatography coupled to tandem mass spectrometry

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Endocrine-disrupting chemicals are environmental pollutants that can enter our bodies and cause diverse pathologies. Some bisphenols and parabens have been shown to be capable of modifying proper functioning of the endocrine system. Among other dysfunctions, endocrine-disrupting chemicals can cause changes in intestinal microbiota. Faeces are a convenient matrix that can be useful for identifying the quantity of endocrine disruptors that reach the intestine and the extent to which the organism is exposed to these pollutants. The present work developed a new analytical method to determine 17 compounds belonging to the paraben and bisphenol families found in human faeces. The extraction method was optimized using an ultrasound-assisted extraction technique followed by a clean-up step based on the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) technique. Optimization was performed using the design of experiments technique. In validation analysis, the method was proven to be linear over a wide range. R-squared outcomes were between 95 and 99%. Selectiveness and sensitivity outcomes were acceptable, with detection limits being between 1 and 10 ng g−1 in all cases, whilst quantification limits were between 3 and 25 ng g−1 in all instances, with the exception of bisphenol AF. The method was deemed accurate, with recovery values being close to 100% and relative standard deviations being lower than 15% in all cases. Applicability was examined by analysing 13 samples collected from volunteers (male and female). All samples were contaminated with at least one of the analytes studied. The most commonly found compounds were methylparaben and bisphenol A, which were detected in almost all samples and quantitatively determined in 11 and 12 samples, respectively. Of the 17 compounds analysed, 11 were found in at least one sample. Outcomes demonstrate that faeces can be a good matrix for the determination of exposure to contaminants of interest here.

Graphical abstract

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Nadal A, Quesada I, Tudurí E, Nogueiras R, Alonso-Magdalena P. Endocrine-disrupting chemicals and the regulation of energy balance. Nat Rev Endocrinol. 2017;13:536–46. https://doi.org/10.1038/nrendo.2017.51.

    Article  PubMed  CAS  Google Scholar 

  2. Yilmaz B, Terekeci H, Sandal S, Kelestimur F. Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention. Rev Endocr Metab Disord. 2020;21(1):127–47. https://doi.org/10.1007/s11154-019-09521-z.

    Article  PubMed  CAS  Google Scholar 

  3. Kahn LG, Philippat C, Nakayama SF, Slama R, Trasande L. Endocrine-disrupting chemicals: implications for human health. Lancet Diabetes Endocrinol. 2020;8:703–18. https://doi.org/10.1016/S2213-8587(20)30129-7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Gomes AC, Hoffmann C, Mota JF. The human gut microbiota: Metabolism and perspective in obesity. Gut Microbes. 2018;9:308–25. https://doi.org/10.1080/19490976.2018.1465157.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Velmurugan G, Ramprasath T, Gilles M, Swaminathan K, Ramasamy S. Gut microbiota, endocrine-disrupting chemicals, and the diabetes epidemic. Trends Endocrinol Metab. 2017;28(8):612–25. https://doi.org/10.1016/j.tem.2017.05.001.

    Article  PubMed  CAS  Google Scholar 

  6. Ghassabian A, Vandenberg L, Kannan K, Trasande L. Endocrine disrupting chemicals and child health. Ann Rev Pharmacol Toxicol. 2022;62:573–94. https://doi.org/10.1146/annurev-pharmtox-021921-093352.

    Article  CAS  Google Scholar 

  7. EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP). Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs. EFSA J. 2023;21:6857. https://doi.org/10.2903/j.efsa.2023.6857.

    Article  CAS  Google Scholar 

  8. Tonini C, Segatto M, Bertoli S, Leone A, Mazzoli A, Cigliano L, Barberio L, Mandalà M, Pallottini V. Prenatal exposure to BPA: the effects on hepatic lipid metabolism in male and female rat fetuses. Nutrients. 2021;13:1970. https://doi.org/10.3390/nu13061970.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Nguyen HT, Li L, Eguchi A, Kannan K, Kim EY, Iwata H. Effects on the liver lipidome of rat offspring prenatally exposed to bisphenol A. Sci Total Env. 2021;759:143466. https://doi.org/10.1016/j.scitotenv.2020.143466.

    Article  CAS  Google Scholar 

  10. Dunder L, Halin Lejonklou M, Lind L, Risérus U, Lind PM. Low-dose developmental bisphenol A exposure alters fatty acid metabolism in Fischer 344 rat offspring. Env Res. 2018;166:117–29. https://doi.org/10.1016/j.envres.2018.05.023.

    Article  CAS  Google Scholar 

  11. Stoker C, Andreoli MF, Kass L, Bosquiazzo VL, Rossetti MF, Canesini G, Luque EH, Ramos JG. Perinatal exposure to bisphenol A (BPA) impairs neuroendocrine mechanisms regulating food intake and kisspetin system in adult male rats. Evidences of metabolic disruptor hypothesis. Mol Cell Endocrinol. 2020;499:110614. https://doi.org/10.1016/j.mce.2019.110614.

    Article  PubMed  CAS  Google Scholar 

  12. Lai KP, Chung YT, Li R, Wan HT, Wong CK. Bisphenol A alters gut microbiome: comparative metagenomics analysis. Env Poll. 2016;218:923–30. https://doi.org/10.1016/j.envpol.2016.08.039.

    Article  CAS  Google Scholar 

  13. Chen D, Kannan K, Tan H, Zheng Z, Feng YL, Wu Y, Widelka M. Bisphenol analogues other than BPA: environmental occurrence, human exposure and toxicity – A review. Environ Sci Technol. 2016;50:5438–53. https://doi.org/10.1021/acs.est.5b05387.

    Article  PubMed  CAS  Google Scholar 

  14. Li Y, Xiong Y, Lv L, Li X, Qin Z. Effects of low-dose bisphenol AF on mammal testis development via complex mechanisms: alterations are detectable in both infancy and adulthood. Arch Toxicol. 2022;96:3373–83. https://doi.org/10.1007/s00204-022-03377-0.

    Article  PubMed  CAS  Google Scholar 

  15. Lapp HE, Margolis AE, Champagne FA. Impact of a bisphenol A, F, and S mixture and maternal care on the brain transcriptome of rat dams and pups. Neurotoxicology. 2022;93:22–36. https://doi.org/10.1016/j.neuro.2022.08.014.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Wagner VA, Clark KC, Carrillo-Sáenz L, Holl KA, Velez-Bermudez M, Simonsen D, Grobe JL, Wang K, Thurman A, Solberg Woods LC, Lehmler HJ, Kwitek AE. Bisphenol F exposure in adolescent heterogeneous stock rats affects growth and adiposity. Toxicol Sci. 2021;181:246–61. https://doi.org/10.1093/toxsci/kfab035.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Commission Regulation (UE) No 1129/2011 of 11 November 2011 amending Annex II to Regulation (EC) No 1333/2008 of the European Parliament and of the Council establishing a Union list of food additives. Off. J. Eur. Union 2011; L295:1-177.

  18. Darbre PD. Endocrine disruptors and obesity. Curr Obes Rep. 2017;6:18–27. https://doi.org/10.1007/s13679-017-0240-4.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Elmore SE, Cano-Sancho G, La Merrill MA. Disruption of normal adipocyte development and function by methyl- and propyl- paraben exposure. Toxicol Lett. 2020;334:27–35. https://doi.org/10.1016/j.toxlet.2020.09.009.

    Article  PubMed  CAS  Google Scholar 

  20. Zhao H, Zheng Y, Zhu L, Xiang L, Zhou Y, Li J, Fang J, Xu S, Xia W, Cai Z. Paraben exposure related to purine metabolism and other pathways revealed by mass spectrometry-based metabolomics. Environ Sci Technol. 2020;54:3447–54. https://doi.org/10.1021/acs.est.9b07634.

    Article  PubMed  CAS  Google Scholar 

  21. Hu J, Raikhel V, Gopalakrishnan K, Fernandez-Hernandez H, Lambertini L, Manservisi F, Falcioni L, Bua L, Belpoggi F, Teitelbaum SL, Chen J. Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model. Microbiome. 2016;4:26. https://doi.org/10.1186/s40168-016-0173-2.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ilhan ZE, Brochard V, Lapaque N, Auvin S, Lepage P. Exposure to anti-seizure medications impact growth of gut bacterial species and subsequent host response. Neurobiol Dis. 2022;167:105664. https://doi.org/10.1016/j.nbd.2022.105664.

    Article  PubMed  CAS  Google Scholar 

  23. Abbas S, Greige-Gerges H, Karam N, Piet MH, Netter P, Magdalou J. Metabolism of parabens (4-hydroxybenzoic acid esters) by hepatic esterases and UDP-glucuronosyltransferases in man. Drug Metab Pharmacokinet. 2010;25:568–77. https://doi.org/10.2133/dmpk.dmpk-10-rg-013.

    Article  PubMed  CAS  Google Scholar 

  24. Iwano H, Inoue H, Nishikawa M, Yokota JFA. Biotransformation of bisphenol A and its adverse effects on the next generation. In Endocrine Disruptors. 2018. Edited by Ahmed RG Beni-Suef University, Egypt. https://doi.org/10.5772/intechopen.78275

  25. Nachman RM, Hartle JC, Lees PS, Groopman JD. Early life metabolism of bisphenol A: a systematic review of the literature. Curr Environ Health Rep. 2014;1:90–100. https://doi.org/10.1007/s40572-013-0003-7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Thayer K, Doerge D, Hunt D, Schurman S, Twaddle N, Churchwell M, Garantziotis S, Kissling G, Easterling M, Bucher J, Birnbaum L. Pharmacokinetics of bisphenol A in humans following a single oral administration. Environ Int. 2015;83:107–15. https://doi.org/10.1016/j.envint.2015.06.008.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Moos R, Angerer J, Dierkes G, Brüning T, Koch H. Metabolism and elimination of methyl, iso- and n-butyl paraben in human urine after single oral dosage. Arch Toxicol. 2016;90:2699–709. https://doi.org/10.1007/s00204-015-1636-0.

    Article  PubMed  CAS  Google Scholar 

  28. Czarczynska-Goslinska B, Grzeskowiak T, Frankowski R, Lulek J, Pieczak J, Zgola-Grzeskowiak A. Determination of bisphenols and parabens in breast milk and dietary risk assessment for Polish breastfed infants. J Food Compos Anal. 2021;98:103839. https://doi.org/10.1016/j.jfca.2021.103839.

    Article  CAS  Google Scholar 

  29. Fu X, He J, Zheng D, Yang X, Wang P, Tuo F, Wang L, Li S, Xu J, Yu J. Association of endocrine disrupting chemicals levels in serum, environmental risk factors, and hepatic function among 5- to 14- years old children. Toxicology. 2022;465:153011. https://doi.org/10.1016/j.tox.2021.153011.

    Article  PubMed  CAS  Google Scholar 

  30. Li C, Cui X, Chen Y, Liao C. Paraben concentrations in human fingernail and its association with personal care product use. Ecotox Environ Safe. 2020;202:110933. https://doi.org/10.1016/j.ecoenv.2020.110933.

    Article  CAS  Google Scholar 

  31. Claessens J, Pirard C, Charlier C. Determination of contamination levels for multiple endocrine disruptors in hair from a non-occupationally exposed population living in Liege (Belgium). Sci Total Env. 2022;815:152734. https://doi.org/10.1016/j.scitotenv.2021.152734.

    Article  CAS  Google Scholar 

  32. Fernández MF, Mustieles V, Suárez B, Reina-Pérez I, Olivas-Martínez A, Vela-Soria F. Determination of bisphenols, parabens, and benzophenones in placenta by dispersive liquid-liquid microextraction and gas chromatography-tandem mass spectrometry. Chemosphere. 2021;274:129707. https://doi.org/10.1016/j.chemosphere.2021.129707.

    Article  PubMed  CAS  Google Scholar 

  33. Moscoso-Ruiz I, Gálvez-Ontiveros Y, Cantarero-Malagón S, Rivas A, Zafra-Gómez A. Optimization of an ultrasound-assisted extraction method for the determination of parabens and bisphenol homologues in human saliva by liquid chromatography-tandem mass spectrometry. Michrochem J. 2022;175:107122. https://doi.org/10.1016/j.microc.2021.107122.

    Article  CAS  Google Scholar 

  34. Moscoso-Ruiz I, Navalón A, Rivas A, Zafra-Gómez A. Presence of parabens in children’s faeces. Optimization and validation of a new analytical method based on the use of ultrasound-assisted extraction and liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2022;225:115212. https://doi.org/10.1016/j.jpba.2022.115212.

    Article  PubMed  CAS  Google Scholar 

  35. Yang Y, Yin J, Yang Y, Zhou N, Zhang J, Shao B, Wu Y. Determination of bisphenol AF in tissues, serum, urine and feces of orally dosed rats by ultra-high-pressure liquid chromatography-electrospray tandem mass spectrometry. J Chromatogr B. 2012;901:93–7. https://doi.org/10.1016/j.jchromb.2012.06.005.

    Article  CAS  Google Scholar 

  36. Twaddle NCI, Churchwell M, Vanlandingham M, Doerge DR. Quantification of deuterated bisphenol A in serum, tissues and excreta from adult Sprague-Dawley rats using liquid chromatography with tandem mass spectrometry. Rapid Commun Mass Spectrom. 2010;24:3011–20. https://doi.org/10.1002/rcm.4733.

    Article  PubMed  CAS  Google Scholar 

  37. Tao H, Zhang J, Shi J, Guo W, Liu X, Zhang M, Ge H, Li X. Occurrence and emission of phthalates, bisphenol A, and oestrogenic compounds in concentrated animal feeding operations in Southern China. Ecotoxicol Environ Saf. 2021;207:111521. https://doi.org/10.1016/j.ecoenv.2020.111521.

    Article  PubMed  CAS  Google Scholar 

  38. Tekin Z, Karlidag NE, Özdogan N, Koçoglu ES, Bakirdere S. Dispersive solid phase extraction based on reduced graphene oxide modified Fe3O4 nanocomposite for trace determination of parabens in rock, soil, moss, seaweed, feces, and water samples from Horseshoe and Faure Islands. J Hazard Mater. 2022;426:127819. https://doi.org/10.1016/j.jhazmat.2021.127819.

    Article  PubMed  CAS  Google Scholar 

  39. Zhang J, Wang L, Kannan K. Polyethylene terephthalate and polycarbonate microplastics in pet food and faeces from the United States. Environ Sci Technol. 2019;53:12035–42. https://doi.org/10.1021/acs.est.9b03912.

    Article  PubMed  CAS  Google Scholar 

  40. Sturm S, Skibin A, Pogacnik M, Cerkvenik-Flajs V. Determination of free and total bisphenol A in urine and feces of orally and subcutaneously dosed sheep by high-performance liquid chromatography with fluorescence detection. J Environ Sci Health B. 2020;55:655–68. https://doi.org/10.1080/03601234.2020.1759329.

    Article  PubMed  CAS  Google Scholar 

  41. EMEA (European Medicines Agency). ICH guideline Q2(R2) on validation of analytical procedures-Step 2b. 2022. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-q2r2-validation-analytical-procedures-step-2b_en.pdf. Accessed 15 Dec 2023

  42. Peillex C, Kerever A, Lachhab A, Pelletier M, Bisphenol A. bisphenol S and their glucuronidated metabolites modulate glycolysis and functional responses of human neutrophils. Env Res. 2021;196:110336. https://doi.org/10.1016/j.envres.2020.110336.

    Article  CAS  Google Scholar 

  43. Rancière F, Botton J, Slama R, Lacroix MZ, Debrauwer L, Charles MA, Roussel R, Balkau B, Magliano DJ. Exposure to bisphenol A and bisphenol S and incident Type 2 Diabetes: a case-cohort study in the French cohort D.E.S.I.R. Environ Health Perspect. 2019;127:107013. https://doi.org/10.1289/EHP5159.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Zhang H, Shi J, Liu X, Zhan X, Dang J, Bo T. Occurrence of free estrogens, conjugated estrogens, and bisphenol A in fresh livestock excreta and their removal by composting in North China. Environ Sci Pollut Res. 2014;21:9939–47. https://doi.org/10.1007/s11356-014-3002-9.

    Article  CAS  Google Scholar 

  45. Mao W, Mao L, Zhao N, Zhang Y, Zhao M, Jin H. Disposition of Bisphenol S metabolites in Sprague-Dawley rats. Sci Total Env. 2022;811:152288. https://doi.org/10.1016/j.scitotenv.2021.152288.

    Article  CAS  Google Scholar 

  46. Aznar R, Albero B, Pérez RA, Sánchez-Brunete C, Miguel E, Tadeo JL. Analysis of emerging organic contaminants in poultry manure by gas chromatography-tandem mass spectrometry. J Sep Sci. 2017;41:940–7. https://doi.org/10.1002/jssc.201700883(AccessedonJuly2023).

    Article  PubMed  Google Scholar 

  47. Senta I, Rodríguez-Mozaz S, Corominas L, Petrovic M. Wastewater-based epidemiology to assess human exposure to personal care and household products – a review of biomarkers, analytical methods, and applications. Trends Environ Anal Chem. 2020;28:e00103. https://doi.org/10.1016/j.teac.2020.e00103.

    Article  CAS  Google Scholar 

  48. Ricciuto A, Griffiths AM. Clinical value of fecal calprotectin. Crit Rev Clin Lab Sci. 2019;56(5):307–20. https://doi.org/10.1080/10408363.2019.1619159.

    Article  PubMed  CAS  Google Scholar 

  49. Bull ID, Lockheart MJ, Elhmmali MM, Roberts DJ, Evershed RP. The origin of faeces by means of biomarker detection. Env Int. 2002;27:647–54. https://doi.org/10.1016/S0160-4120(01)00124-6.

    Article  CAS  Google Scholar 

  50. Kang JH, Katayama Y, Kondo F. Biodegradation or metabolism of Bisphenol A: from microorganisms to mammals. Toxicology. 2006;217:81–90. https://doi.org/10.1016/j.tox.2005.10.001.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This research was carried out within the GP/EFSA/ENCO/380 2018/03/G04 framework. It was also funded by the Spanish Government, with joint funding from FEDER-ISCIII PI20/01278 and the Andalusian Government-FEDER, projects PE-0250-2019 and P18-RT-4247. The results presented in this work are part of a doctoral thesis conducted by IMR within the Analytical Chemistry Doctorate Program at the University of Granada. The authors would like to thank Fundación para la Investigación Biosanitaria de Andalucía Oriental—Alejandro Otero (FIBAO) for giving IMR the opportunity to participate in this work.

Author information

Authors and Affiliations

  1. Department of Analytical Chemistry, University of Granada, 18071, Granada, Spain

    Inmaculada Moscoso-Ruiz & Alberto Zafra-Gómez

  2. Instituto de Investigación Biosanitaria Ibs.Granada, 18016, Granada, Spain

    Inmaculada Moscoso-Ruiz, Ana Rivas & Alberto Zafra-Gómez

  3. Center of Scientific Instrumentation, University of Granada, 18071, Granada, Spain

    Samuel Cantarero-Malagón

  4. Department of Nutrition and Food Science, University of Granada, 18071, Granada, Spain

    Ana Rivas

  5. Institute of Nutrition and Food Technology (INYTA)“José Mataix Verdú”, Biomedical Research Centre (CIBM), University of Granada, 18100, Granada, Spain

    Ana Rivas & Alberto Zafra-Gómez

Authors
  1. Inmaculada Moscoso-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samuel Cantarero-Malagón
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Rivas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alberto Zafra-Gómez
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

IMR, investigation, methodology and writing of the original draft. SCM, investigation and methodology. AR, writing, review and editing, supervision, and funding acquisition. AZG, writing, review and editing, supervision, and funding acquisition.

Corresponding author

Correspondence to Alberto Zafra-Gómez.

Ethics declarations

The present study was approved by the ethics committees of the University of Granada and of the Provincial Biomedical Research of Granada (CEI), Spain (reference 1939-M1-22, Andalusian Biomedical Research Ethics Portal). The study was conducted in accordance with relevant ethical standards. All subjects provided written informed consent to participate.

Competing interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 686 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moscoso-Ruiz, I., Cantarero-Malagón, S., Rivas, A. et al. New analytical method for the determination of endocrine disruptors in human faeces using gas chromatography coupled to tandem mass spectrometry. Anal Bioanal Chem 416, 1085–1099 (2024). https://doi.org/10.1007/s00216-023-05087-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-023-05087-7

Keywords

Search

Navigation