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A comparative study of urinary mycotoxin biomarkers co-occurrence patterns and cumulative risk assessment in population from three typical areas in China

Abstract

Background

This biomonitoring study investigated levels of multi-mycotoxin biomarkers in the urine of subjects living in three different geographic locations and dietary patterns in China.

Objective

This study provides a comprehensive understanding of the inner-exposure characteristics to multiple mycotoxins within the Chinese population.

Methods

The study involved a total of 311 healthy volunteers, with 103 from Anhui Province, 102 from Henan Province, and 106 from Sichuan Province. UHPLC-MS/MS was employed to analyze seven mycotoxin biomarkers [total deoxynivalenol (DONt), β-zearalenol (β-ZEL), nivalenol (NIV), α-zearalenol (α-ZEL), diacetoxycyclohexenol (DAS), zearalenone (ZEN), aflatoxin M1 (AFM1)] in urine samples. Urinary biomarker concentrations were used to estimate probable daily intake (PDI), further calculate hazard quotient (HQ), and hazard index (HI).

Results

In the study population, DON was the most prevalent (100%) with a mean concentration of 90.77 ng/ml, followed by β-ZEL (27.97%), NIV (24.76%), α-ZEL (24.12%), DAS (12.86%), ZEN (6.11%) and AFM1 (10.96%) in urine samples. The mean PDI for DONt, ZENt and NIV in the total population were 3.02 µg/kg bw/d, 0.01 µg/kg bw/d and 0.79 µg/kg bw/d, respectively. There were 61.09% of the total population with an HQ > 1 for DONt, while 0.96% and 10.93% had an HQ > 1 for ZENt and NIV, respectively. Moreover, approximately 64.31% of urine samples exhibited the co-occurrence of two or more mycotoxins. The most common binary and ternary combinations were DONt-ZENt (46.34%) and DONt-ZENt-NIV (19.02%). The percentages of HI > 1 for DONt-ZENt and DONt-ZENt-NIV were 61.09% and 69.77% respectively.

Impact

In the present study, the co-occurrence pattern and cumulative risk of the metabolite biomarkers of multi-mycotoxins were firstly revealed in three typical areas with different climate types and dietary patterns. This study helps assess the health risks of mycotoxin exposure under different environmental and dietary conditions, reveals the relationship between diet and mycotoxin exposure, and provides scientific support for mitigating the harmful effects of mycotoxins on human health.

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Fig. 1: Co-occurrence patterns of urinary mycotoxin biomarkers among study participants.
Fig. 2: Probable daily intake (PDI) and hazard quotient (HQ) estimates for DONt, ZENt, and NIV based on urinary biomarkers.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Materials availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Goud KY, Kailasa SK, Kumar V, Tsang YF, Lee SE, Gobi KV, et al. Progress on nanostructured electrochemical sensors and their recognition elements for detection of mycotoxins: a review. Biosens Bioelectron. 2018;121:205–22.

    Article  CAS  PubMed  Google Scholar 

  2. Choi J, Aarøe Mørck T, Polcher A, Knudsen LE, Joas A. Review of the state of the art of human biomonitoring for chemical substances and its application to human exposure assessment for food safety. EFSA Supporting Publications. 2015;12:724E.

  3. Jager AV, Tonin FG, Baptista GZ, Souto PC, Oliveira CA. Assessment of aflatoxin exposure using serum and urinary biomarkers in São Paulo, Brazil: a pilot study. Int J Hyg Environ Health. 2016;219:294–300.

    Article  CAS  PubMed  Google Scholar 

  4. Heyndrickx E, Sioen I, Huybrechts B, Callebaut A, De Henauw S, De Saeger S. Human biomonitoring of multiple mycotoxins in the Belgian population: results of the BIOMYCO study. Environ Int. 2015;84:82–9.

    Article  CAS  PubMed  Google Scholar 

  5. Martins C, Vidal A, De Boevre M, De Saeger S, Nunes C, Torres D, et al. Exposure assessment of Portuguese population to multiple mycotoxins: the human biomonitoring approach. Int J Hyg Environ Health. 2019;222:913–25.

    Article  CAS  PubMed  Google Scholar 

  6. Meerpoel C, Vidal A, Andjelkovic M, De Boevre M, Tangni EK, Huybrechts B, et al. Dietary exposure assessment and risk characterization of citrinin and ochratoxin A in Belgium. Food Chem Toxicol. 2021;147:111914.

    Article  CAS  PubMed  Google Scholar 

  7. Gerding J, Cramer B, Humpf HU. Determination of mycotoxin exposure in Germany using an LC-MS/MS multibiomarker approach. Mol Nutr Food Res. 2014;58:2358–68.

    Article  CAS  PubMed  Google Scholar 

  8. Turner PC, Flannery B, Isitt C, Ali M, Pestka J. The role of biomarkers in evaluating human health concerns from fungal contaminants in food. Nutr Res Rev. 2012;25:162–79.

    Article  CAS  PubMed  Google Scholar 

  9. Warth B, Sulyok M, Fruhmann P, Berthiller F, Schuhmacher R, Hametner C, et al. Assessment of human deoxynivalenol exposure using an LC-MS/MS-based biomarker method. Toxicol Lett. 2012;211:85–90.

    Article  CAS  PubMed  Google Scholar 

  10. Santonen T, Mahiout S, Alvito P, Apel P, Bessems J, Bil W, et al. How to use human biomonitoring in chemical risk assessment: methodological aspects, recommendations, and lessons learned from HBM4EU. Int J Hyg Environ Health. 2023;249:114139.

    Article  CAS  PubMed  Google Scholar 

  11. Solfrizzo M, Gambacorta L, Visconti A. Assessment of multi-mycotoxin exposure in southern Italy by urinary multi-biomarker determination. Toxins. 2014;6:523–38.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Huang Q, Jiang K, Tang Z, Fan K, Meng J, Nie D, et al. Exposure assessment of multiple mycotoxins and cumulative health risk assessment: a biomonitoring-based Study in the Yangtze River Delta, China. Toxins. 2021;13:103.

  13. Fan K, Xu J, Jiang K, Liu X, Meng J, Di Mavungu JD, et al. Determination of multiple mycotoxins in paired plasma and urine samples to assess human exposure in Nanjing, China. Environ Pollut. 2019;248:865–73.

    Article  CAS  PubMed  Google Scholar 

  14. Turner PC, Ji BT, Shu XO, Zheng W, Chow WH, Gao YT, et al. A biomarker survey of urinary deoxynivalenol in China: the Shanghai Women’s Health Study. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2011;28:1220–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Janaviciene S, Suproniene S, Kadziene G, Pavlenko R, Berzina Z, Bartkevics V. Toxigenicity of F. graminearum residing on host plants alternative to wheat as influenced by environmental conditions. Toxins. 2022;14:541.

  16. Wallin S, Gambacorta L, Kotova N, Lemming EW, Nälsén C, Solfrizzo M, et al. Biomonitoring of concurrent mycotoxin exposure among adults in Sweden through urinary multi-biomarker analysis. Food Chem Toxicol. 2015;83:133–9.

    Article  CAS  PubMed  Google Scholar 

  17. Minglu, L. Risk Assessment of Internal and External Exposure to Mycotoxins in the Chinese Population (in Chinese) (Master’s thesis). Huazhong University of Science and Technology, Wuhan, China; 2022.

  18. Zhao J, Han X, Xu W, Li F. Investigation of 12 mycotoxins in wheat grains from four provinces of China in 2019. Chin Chin J Food Hyg. 2021;33:765–70.

    Google Scholar 

  19. Mei M, Jiang Y, Wang Z, Liu L, Ye D, Wang Y, et al. Climatic characteristics and major meteorological events over China in 2016. Chin Meteorol Mon. 2017;45:468–76.

    Google Scholar 

  20. Deng C, Li C, Zhou S, Wang X, Xu H, Wang D, et al. Risk assessment of deoxynivalenol in high-risk areas of China by human biomonitoring using an improved high-throughput UPLC-MS/MS method. Sci Rep. 2018;8:3901.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Li C, Deng C, Zhou S, Zhao Y, Wang D, Wang X, et al. High-throughput and sensitive determination of urinary zearalenone and metabolites by UPLC-MS/MS and its application to a human exposure study. Anal Bioanal Chem. 2018;410:5301–12.

    Article  CAS  PubMed  Google Scholar 

  22. Arce-López B, Lizarraga E, Flores-Flores M, Irigoyen Á, González-Peñas E. Development and validation of a methodology based on captiva EMR-lipid clean-up and LC-MS/MS analysis for the simultaneous determination of mycotoxins in human plasma. Talanta. 2020;206:120193.

    Article  PubMed  Google Scholar 

  23. Ayelign A, Woldegiorgis AZ, Adish A, De Boevre M, Heyndrickx E, De Saeger S. Assessment of aflatoxin exposure among young children in Ethiopia using urinary biomarkers. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2017;34:1606–16.

    Article  CAS  PubMed  Google Scholar 

  24. Warth B, Sulyok M, Fruhmann P, Mikula H, Berthiller F, Schuhmacher R, et al. Development and validation of a rapid multi-biomarker liquid chromatography/tandem mass spectrometry method to assess human exposure to mycotoxins. Rapid Commun Mass Spectrom. 2012;26:1533–40.

    Article  CAS  PubMed  Google Scholar 

  25. EMA (European Medicines Agency). ICH M10 on bioanalytical method validation—Scientific guideline. 2011. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf. Accessed 17 Jan 2024.

  26. FDA (U.S. Food and Drug Administration). Bioanalytical Method Validation Guidance for Industry. 2018. https://www.fda.gov/media/70858/download. Accessed 17 Jan 2024.

  27. Gong YY, Shirima CP, Srey C, Martin K, Michael R. Deoxynivalenol and fumonisin exposure in children and adults in a family study in rural Tanzania. World Mycotoxin J. 2015;8:1–8.

    Article  Google Scholar 

  28. Haga M, Sakata T. Daily salt intake of healthy Japanese infants of 3-5 years based on sodium excretion in 24-hour urine. J Nutr Sci Vitaminol. 2010;56:305–10.

    Article  CAS  PubMed  Google Scholar 

  29. Gambacorta S, Solfrizzo H, Visconti A, Powers S, Oswald IP. Validation study on urinary biomarkers of exposure for aflatoxin B1, ochratoxin A, fumonisin B1, deoxynivalenol and zearalenone in piglets. World Mycotoxin J. 2013;6:299–308.

    Article  CAS  Google Scholar 

  30. Schwartz-Zimmermann HE, Binder SB, Hametner C, Miró-Abella E, Schwarz C, et al. Metabolism of nivalenol and nivalenol-3-glucoside in rats. Toxicol Lett. 2019;306:43–52.

    Article  CAS  PubMed  Google Scholar 

  31. Lee SY, Cho S, Woo SY, Hwang M, Chun HS. Risk assessment considering the bioavailability of 3-β-d-glucosides of deoxynivalenol and nivalenol through food intake in Korea. Toxins. 2023;15:460.

  32. McKeon HP, Schepens MAA, van den Brand AD, de Jong MH, van Gelder MMHJ, Hesselink ML, et al., Assessment of mycotoxin exposure and associated risk in pregnant Dutch women: the human biomonitoring approach. Toxins. 2024;16:278.

  33. Zhang S, Zhou S, Gong YY, Zhao Y, Wu Y. Human dietary and internal exposure to zearalenone based on a 24-hour duplicate diet and following morning urine study. Environ Int. 2020;142:105852.

    Article  CAS  PubMed  Google Scholar 

  34. Turner PC, White KL, Burley VJ, Hopton RP, Rajendram A, Fisher J, et al. A comparison of deoxynivalenol intake and urinary deoxynivalenol in UK adults. Biomarkers. 2010;15:553–62.

    Article  CAS  PubMed  Google Scholar 

  35. EPA (U.S. Environmental Protection Agency). Framework for Cumulative Risk Assessment. 2003. http://www.epa.gov/sites/default/files/2014-11/documents/frmwrk_cum_risk_assmnt.pdf. Accessed 17 Jan 2024.

  36. Evans RM, Scholze M, Kortenkamp A. Examining the feasibility of mixture risk assessment: a case study using a tiered approach with data of 67 pesticides from the joint FAO/WHO meeting on pesticide residues (JMPR). Food Chem Toxicol. 2015;84:260–9.

  37. Wu L, Li P, Ding X, Yue X, Bai Y. Advances in research on co-occurrence and cumulative risk assessment of mycotoxins in agricultural products. Chin J Food Saf Qual. 2018;9:3553–60.

    Google Scholar 

  38. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain). Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed. EFSA J. 2017;15:e04718.

    Google Scholar 

  39. Knutsen HK, Alexander J, Barregård L, Bignami M, Brüschweiler B, et al. Risks for animal health related to the presence of zearalenone and its modified forms in feed. EFSA J. 2017;15:e04851.

    PubMed  PubMed Central  Google Scholar 

  40. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain)Scientific Opinion on risks for animal and public health related to the presence of nivalenol in food and feed. EFSA J. 2013;11:3262.

    Article  Google Scholar 

  41. Altman DG. Practical Statistics for Medical Research. Chapman and Hall/CRC; 1990. p. 624.

  42. R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing. 2022. https://www.R-project.org/.

  43. Shephard GS, Burger HM, Gambacorta L, Gong YY, Krska R, et al. Multiple mycotoxin exposure determined by urinary biomarkers in rural subsistence farmers in the former Transkei, South Africa. Food Chem Toxicol. 2013;62:217–25.

    Article  CAS  PubMed  Google Scholar 

  44. Govarts E, Gilles L, Rodriguez Martin L, Santonen T, Apel P, Alvito P, et al. Harmonized human biomonitoring in European children, teenagers and adults: EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014-21). Int J Hyg Environ Health. 2023;249:114119.

    Article  CAS  PubMed  Google Scholar 

  45. Wang L, Yan Z, Zhao QY, Liu N, Yu DZ, Jia BX, et al. A prospective study of total urinary deoxynivalenol in adolescents in Shanghai, China. Chemosphere. 2022;307:135727.

    Article  CAS  PubMed  Google Scholar 

  46. Ali N, Degen GH. Urinary biomarkers of exposure to the mycoestrogen zearalenone and its modified forms in German adults. Arch Toxicol. 2018;92:2691–700.

    Article  CAS  PubMed  Google Scholar 

  47. Carballo D, Pallarés N, Ferrer E, Barba FJ, Berrada H. Assessment of human exposure to deoxynivalenol, ochratoxin A, zearalenone and their metabolites biomarker in urine samples using LC-ESI-qTOF. Toxins. 2021;13:530.

  48. De Santis B, Debegnach F, Toscano P, Crisci A, Battilani P, Brera C. Overall exposure of the European adult population to mycotoxins by statistically modelled biomonitoring data. Toxins. 2021;13:695.

  49. Marchese S, Polo A, Ariano A, Velotto S, Costantini S, Severino L. Aflatoxin B1 and M1: biological properties and their involvement in cancer development. Toxins. 2018;10:214.

    Article  PubMed  PubMed Central  Google Scholar 

  50. EFSA Panel on Contaminants in the Food Chain (CONTAM), et al. Risk to human and animal health related to the presence of 4,15-diacetoxyscirpenol in food and feed. EFSA J. 2018;16:e05367.

    Google Scholar 

  51. Abia WA, Warth B, Sulyok M, Krska R, Tchana A, Njobeh PB, et al. Bio-monitoring of mycotoxin exposure in Cameroon using a urinary multi-biomarker approach. Food Chem Toxicol. 2013;62:927–34.

    Article  CAS  PubMed  Google Scholar 

  52. Chinese Center for Disease Control and Prevention, Report on Chinese Residents’ Chronic Diseases and Nutrition 2020. National Institute for Nutrition and Health, China CDC, 2020.

  53. Wild, CP, Miller, JD, Groopman, JD (Eds.). Mycotoxin Control in Low- and Middle-Income Countries. International Agency for Research on Cancer (IARC), World Health Organization, 2015. Available at: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Scientific-Publications/Mycotoxin-Control-In-Low-And-Middle-Income-Countries-2015.

  54. Han X, Li F, Xu W, Zhang H, Zhang J, Zhao X, et al. Natural occurrence of important mycotoxins produced by Fusarium in wheat flour from five provinces in China. China Swine Ind. 2017;12:45 33-39.

    Google Scholar 

  55. Fan K, Ji F, Xu J, Qian M, Duan J, Nie D, et al. Natural occurrence and characteristic analysis of 40 mycotoxins in agro-products from the Yangtze Delta region. Sci Agric Sin. 2021;54:2870–84.

    Google Scholar 

  56. Yue W, Chen X, Wu Q, Chen J, Cai Y, Wang X, et al. Effect of climate change on meteorological yield of summer maize in Huaibei area of Anhui province. Resour Environ Yangtze Basin. 2021;30:407–18.

    Google Scholar 

  57. Dong F, Qiu J, Xu J, Yu M, Wang S, Sun Y, et al. Effect of environmental factors on Fusarium population and associated trichothecenes in wheat grain grown in Jiangsu province, China. Int J Food Microbiol. 2016;230:58–63.

    Article  CAS  PubMed  Google Scholar 

  58. China Department of Science & Technology and Climate Change, China Climate Bulletin 2016. China Department of Science & Technology and Climate Change, 2017.

  59. Vidal A, Claeys L, Mengelers M, Vanhoorne V, Vervaet C, Huybrechts B, et al. Humans significantly metabolize and excrete the mycotoxin deoxynivalenol and its modified form deoxynivalenol-3-glucoside within 24 h. Sci Rep. 2018;8:5255.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank the staff of the Centers for Disease Control and Prevention in Anhui, Henan, and Sichuan Provinces for their support of the field work in this study population.

Funding

This work was supported by the China Food Safety Talent Competency Development Initiative (CFSA 523 Program).

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The following authors have contributed substantially to the work reported. Conceptualization, JL; Methodology, ML and YZ; Software, ML; Validation, YZ; Formal Analysis, ML; Investigation, XW and JL; Resources, JL; Data Curation, XW; Writing-Original Draft Preparation, ML and YZ; Writing-Review & Editing, JL and YZ; Visualization, ML; Supervision, JL and XW; Funding Acquisition, JL and HX. All authors have approved the submitted version. All authors have agreed to be personally accountable for the author’s contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

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Correspondence to Jiang Liang.

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Zhou, YY., Li, ML., Wang, XD. et al. A comparative study of urinary mycotoxin biomarkers co-occurrence patterns and cumulative risk assessment in population from three typical areas in China. J Expo Sci Environ Epidemiol (2025). https://doi.org/10.1038/s41370-025-00830-x

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