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Health-related reference intervals for heavy metals in non-exposed young adults

  • Chiara Di Resta , Francesco Paleari , Assunta Naclerio , Floriana Iannace , Roberto Leone , Ivan Shashkin , Marco Fumagalli , Chiara Sacco , Lucia Bellocchi , Massimo Locatelli , Giuseppe Banfi EMAIL logo , Paola M.V. Rancoita und Rossella Tomaiuolo ORCID logo
Veröffentlicht/Copyright: 16. Juni 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 63 Heft 10

Abstract

Objectives

Heavy metals (HMs) concentrations vary with living environments, diet, and personal habits. This study aims to establish health-related reference intervals (RIs) for selected HMs in healthy, non-occupationally exposed young adults living in an urban environment.

Methods

The Uni4Me study enrolled 154 healthy university volunteers (median age: 23 years) to assess the concentrations of seven HMs (lead, nickel, cadmium, zinc, chromium, cobalt, and mercury) using inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectroscopy (ICP-EOS). CLSI guidelines were followed to estimate the 2.5th and 97.5th percentiles as RIs.

Results

Most metals were detected at low concentrations. Zinc showed consistent physiological levels in all participants. Mercury and chromium were the most frequently detected, indicating potential environmental or dietary exposure.

Conclusions

This study defines baseline values for HMs in an urban, healthy, young adult population. These results may support future biomonitoring efforts and public health initiatives targeting subclinical exposure in non-occupationally exposed populations.

Keywords: biomonitoring; reference values; heavy metals
Corresponding author: Professor Giuseppe Banfi, Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132, Milan, Italy; and IRCCS Galeazzi-Sant’Ambrogio, 20157, Milan, Italy, E-mail:

Funding source: Regione Lombardia _ Italy

Award Identifier / Grant number: Progetto Neon

Acknowledgments

We would like to express our sincere gratitude to the International Medical Doctor Program (IMDP) students at UniSR for their enthusiasm and participation as volunteers in this study. Their active collaboration was instrumental in achieving the research objectives. Special thanks to the Dean of the Faculty of Medicine, Prof. Flavia Valtorta, and the Dean of the IMDP, Prof. Andrea Salonia, of Vita-Salute San Raffaele University, for their steadfast support and encouragement throughout the project.

  1. Research ethics: The Ethical Committee approved the study protocol (Uni4Me, V1.1, 2022/01/26).

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: The financial support was provided by “Project Neon”-Regione Lombardia.

  7. Data availability: The raw data are available in the Institutional Repository.

References

1. Briffa, J, Sinagra, E, Blundell, R. Heavy metal pollution in the environment and their toxicological effects on humans. Heliyon 2020;6. https://doi.org/10.1016/j.heliyon.2020.e04691.Suche in Google Scholar PubMed PubMed Central

2. Filipoiu, DC, Bungau, SG, Endres, L, Negru, PA, Bungau, AF, Pasca, B, et al.. Characterization of the toxicological impact of heavy metals on human health in conjunction with modern analytical methods. Toxics 2022;10. https://doi.org/10.3390/toxics10120716.Suche in Google Scholar PubMed PubMed Central

3. Tchounwou, PB, Yedjou, CG, Patlolla, AK, Sutton, DJ. Heavy metal toxicity and the environment. Exper Suppl (Basel) 2012)2012;101:133–64. https://doi.org/10.1007/978-3-7643-8340-4_6.Suche in Google Scholar PubMed PubMed Central

4. Fuller, R, Landrigan, PJ, Balakrishnan, K, Bathan, G, Bose-O’Reilly, S, Brauer, M, et al.. Pollution and health: a progress update. Lancet Planet Health 2022;6:e535–47. https://doi.org/10.1016/s2542-5196(22)00090-0.Suche in Google Scholar PubMed PubMed Central

5. Yu, G, Lu, R, Yang, J, Rahman, ML, Li, LJ, Wang, DD, et al.. Healthy dietary patterns are associated with exposure to environmental chemicals in a pregnancy cohort. Nat Food 2024;5:563–8. https://doi.org/10.1038/s43016-024-01013-x.Suche in Google Scholar PubMed PubMed Central

6. WHO. Trace elements in human nutrition and health. Geneva, Vienna, Rome: World Health Organization, International Atomic Energy Agency & Food and Agriculture Organization of the United Nation; 1996:343 p.Suche in Google Scholar

7. Dignam, T, Kaufmann, RB, Lestourgeon, L, Brown, MJ. Control of lead sources in the United States, 1970-2017: public health progress and current challenges to eliminating lead exposure. J Publ Health Manag Pract: JPHMP 2019;25:S13–22. https://doi.org/10.1097/phh.0000000000000889.Suche in Google Scholar PubMed PubMed Central

8. Zhu, R, Zeng, YY, Liu, LM, Yin, L, Xu, KP, Chen, WF, et al.. Pollution status and assessment of seven heavy metals in the seawater and sediments of Hangzhou Bay, China. Mar Pollut Bull 2024;209. https://doi.org/10.1016/j.marpolbul.2024.117261.Suche in Google Scholar PubMed

9. Kristensen, AKB, Thomsen, JF, Mikkelsen, S. A review of mercury exposure among artisanal small-scale gold miners in developing countries. Int Arch Occup Environ Health 2014;87:579–90. https://doi.org/10.1007/s00420-013-0902-9.Suche in Google Scholar PubMed

10. Skerfving, S, Schütz, A, Ranstam, J. Decreasing lead exposure in Swedish children, 1978–84. Sci Total Environ 1986;58:225–9. https://doi.org/10.1016/0048-9697(86)90201-9.Suche in Google Scholar PubMed

11. Renu, K, Chakraborty, R, Myakala, H, Koti, R, Famurewa, AC, Madhyastha, H, et al.. Molecular mechanism of heavy metals (lead, chromium, arsenic, mercury, nickel and cadmium) – induced hepatotoxicity – a review. Chemosphere 2021;271. https://doi.org/10.1016/j.chemosphere.2021.129735.Suche in Google Scholar PubMed

12. Chowdhury, R, Ramond, A, O’Keeffe, LM, Shahzad, S, Kunutsor, SK, Muka, T, et al.. Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis. BMJ (Clin Res Ed) 2018:362.10.1136/bmj.k3310Suche in Google Scholar PubMed PubMed Central

13. Chen, YW, Yang, CY, Huang, CF, Hung, DZ, Leung, YM, Liu, SH. Heavy metals, islet function and diabetes development. Islets 2009;1:169–76. https://doi.org/10.4161/isl.1.3.9262.Suche in Google Scholar PubMed

14. Zimta, AA, Schitcu, V, Gurzau, E, Stavaru, C, Manda, G, Szedlacsek, S, et al.. Biological and molecular modifications induced by cadmium and arsenic during breast and prostate cancer development. Environ Res 2019;178. https://doi.org/10.1016/j.envres.2019.108700.Suche in Google Scholar PubMed

15. Goutam Mukherjee, A, Ramesh Wanjari, U, Renu, K, Vellingiri, B, Valsala Gopalakrishnan, A. Heavy metal and metalloid – induced reproductive toxicity. Environ Toxicol Pharmacol 2022;92. https://doi.org/10.1016/j.etap.2022.103859.Suche in Google Scholar PubMed

16. Larsen, B, Sánchez-Triana, E. Global health burden and cost of lead exposure in children and adults: a health impact and economic modelling analysis. Lancet Planet Health 2023;7:e831–40. https://doi.org/10.1016/s2542-5196(23)00166-3.Suche in Google Scholar PubMed

17. Roohani, N, Hurrell, R, Kelishadi, R, Schulin, R. Zinc and its importance for human health: an integrative review. J Res Med Sci 2013;18:144–57.Suche in Google Scholar

18. Angerer, J, Ewers, U, Wilhelm, M. Human biomonitoring: state of the art. Int J Hyg Environ Health 2007;210:201–28. https://doi.org/10.1016/j.ijheh.2007.01.024.Suche in Google Scholar PubMed

19. Alimonti, A, Bocca, B, Mannella, E, Petrucci, F, Zennaro, F, Cotichini, R, et al.. Assessment of reference values for selected elements in a healthy urban population. Ann Ist Super Sanita 2005;41:181–7.Suche in Google Scholar

20. Goullé, JP, Mahieu, L, Castermant, J, Neveu, N, Bonneau, L, Lainé, G, et al.. Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma, urine and hair. Reference values. Forensic Sci Int 2005;153:39–44. https://doi.org/10.1016/j.forsciint.2005.04.020.Suche in Google Scholar PubMed

21. Jannetto, PJ, Cowl, CT. Elementary overview of heavy metals. Clin Chem 2023;69:336–49. https://doi.org/10.1093/clinchem/hvad022.Suche in Google Scholar PubMed

22. Ge, M, Wang, X, Yang, G, Wang, Z, Li, Z, Zhang, X, et al.. Persistent organic pollutants (POPs) in deep-sea sediments of the tropical western Pacific Ocean. Chemosphere 2021;277. https://doi.org/10.1016/j.chemosphere.2021.130267.Suche in Google Scholar PubMed

23. Schoeters, G, Den Hond, E, Zuurbier, M, Naginiene, R, Van Den Hazel, P, Stilianakis, N, et al.. Cadmium and children: exposure and health effects. Acta Paediatr Suppl 2006;95:50–4. https://doi.org/10.1080/08035320600886232.Suche in Google Scholar PubMed

24. Ettinger, AS, Arbuckle, TE, Fisher, M, Liang, CL, Davis, K, Cirtiu, CM, et al.. Arsenic levels among pregnant women and newborns in Canada: results from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. Environ Res 2017;153:8–16. https://doi.org/10.1016/j.envres.2016.11.008.Suche in Google Scholar PubMed

25. Simons, TJB. Lead-calcium interactions in cellular lead toxicity. NeuroToxicology 1993;14:77–86.Suche in Google Scholar

26. Solberg, HE. International federation of clinical chemistry. Scientific committee, clinical section. Expert panel on theory of reference values and international committee for standardization in haematology standing committee on reference values. Approved recommendation (1986) on the theory of reference values. Part 1. The concept of reference values. Clin Chim Acta; Int J Clin Chem 1987;165:111–8. https://doi.org/10.1016/0009-8981(87)90224-5.Suche in Google Scholar PubMed

27. Caroli, S, Alimonti, A, Coni, E, Petrucci, F, Senofonte, OVN, Violante, N. The assessment of reference values for elements in human biological tissues and fluids: a systematic review. Crit Rev Anal Chem 1994;24:363–98. https://doi.org/10.1080/10408349408048824.Suche in Google Scholar

28. CLSI. EP28 A3C: define and verify reference intervals in lab. CLSI Document EP28-A3c 2008. https://clsi.org/standards/products/method-evaluation/documents/ep28/ [Accessed 19 January 2025].Suche in Google Scholar

29. Plebani, M. Harmonization in laboratory medicine: requests, samples, measurements and reports. Crit Rev Clin Lab Sci 2016;53:184–96. https://doi.org/10.3109/10408363.2015.1116851.Suche in Google Scholar PubMed

30. Plebani, M, Astion, ML, Barth, JH, Chen, W, De Oliveira Galoro, CA, Escuer, MI, et al.. Harmonization of quality indicators in laboratory medicine. A preliminary consensus. Clin Chem Lab Med 2014;52:951–8. https://doi.org/10.1515/cclm-2014-0142.Suche in Google Scholar PubMed

31. Wahlen, R, Evans, LTJAHR. The use of collision reaction cell ICP-MS for the simultaneous determination of 18 elements in blood and serum sample. Spectroscopy 2005;20:84.Suche in Google Scholar

32. Nyblom, J. Note on interpolated order statistics. Stat Probab Lett 1992;14:129–31. https://doi.org/10.1016/0167-7152(92)90076-h.Suche in Google Scholar

33. Satarug, S, Baker, JR, Urbenjapol, S, Haswell-Elkins, M, Reilly, PEB, Williams, DJ, et al.. A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett 2003;137:65–83. https://doi.org/10.1016/s0378-4274(02)00381-8.Suche in Google Scholar PubMed

34. Osman, D, Cooke, A, Young, TR, Deery, E, Robinson, NJ, Warren, MJ. The requirement for cobalt in vitamin B12: a paradigm for protein metalation. Biochim Biophys Acta Mol Cell Res 2021;1868. https://doi.org/10.1016/j.bbamcr.2020.118896.Suche in Google Scholar PubMed PubMed Central

35. Hong, YS, Kim, YM, Lee, KE. Methylmercury exposure and health effects. J Preven Med Public Health = Yebang Uihakhoe Chi 2012;45:353–63. https://doi.org/10.3961/jpmph.2012.45.6.353.Suche in Google Scholar PubMed PubMed Central

36. Grandjean, P, Landrigan, PJ. Neurobehavioural effects of developmental toxicity. Lancet Neurol 2014;13:330–8. https://doi.org/10.1016/s1474-4422(13)70278-3.Suche in Google Scholar

37. Bridges, CC, Zalups, RK. The aging kidney and the nephrotoxic effects of mercury. J Toxicol Environ Health B Crit Rev 2017;20:55–80. https://doi.org/10.1080/10937404.2016.1243501.Suche in Google Scholar PubMed PubMed Central

38. National Institute of Environmental Health Sciences: hexavalent chromium n.d. https://www.niehs.nih.gov/health/topics/agents/hex-chromium [Accessed 19 January 2025].Suche in Google Scholar

39. Genchi, G, Carocci, A, Lauria, G, Sinicropi, MS, Catalano, A. Nickel: human health and environmental toxicology. Int J Environ Res Publ Health 2020;17. https://doi.org/10.3390/ijerph17030679.Suche in Google Scholar PubMed PubMed Central

40. Inoue, H, Sanefuji, M, Sonoda, Y, Ogawa, M, Hamada, N, Shimono, M, et al.. No association between prenatal lead exposure and neurodevelopment during early childhood in the Japan Environment and Children’s Study. Sci Rep 2022;12. https://doi.org/10.1038/s41598-022-19509-6.Suche in Google Scholar PubMed PubMed Central

41. Samule, K, Aditya, S, Garnick, MS. Zinc and wound healing: a review of zinc physiology and clinical applications – PubMed. Wounds 2017;1:02–106.Suche in Google Scholar

42. Evans, JR, Lawrenson, JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev 2017;2017. https://doi.org/10.1002/14651858.cd000254.pub4.Suche in Google Scholar

43. Stiles, LI, Ferrao, K, Mehta, KJ. Role of zinc in health and disease. Clin Exp Med 2024;24. https://doi.org/10.1007/s10238-024-01302-6.Suche in Google Scholar PubMed PubMed Central

44. Nisse, C, Tagne-Fotso, R, Howsam, M, Richeval, C, Labat, L, Leroyer, A. Blood and urinary levels of metals and metalloids in the general adult population of Northern France: the IMEPOGE study, 2008–2010. Int J Hyg Environ Health 2017;220:341–63. https://doi.org/10.1016/j.ijheh.2016.09.020.Suche in Google Scholar PubMed

45. Hoet, P, Jacquerye, C, Deumer, G, Lison, D, Haufroid, V. Reference values of trace elements in blood and/or plasma in adults living in Belgium. Clin Chem Lab Med 2020;59:729–42. https://doi.org/10.1515/cclm-2020-1019.Suche in Google Scholar PubMed

46. Alimonti, A, Bocca, B, D, M, A, P. Biomonitoraggio Delaa Popolazione Italiana per l’esposizione ai metalli: Valori di Riferimento 1990–2009 (Biomonitoring of the Italian Population to Metals: Reference Values 1990–2009. Health & Environmental Research Online (HERO). Rome: Istituto Superiore di Sanità; 2009. GRA and I.Suche in Google Scholar

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0076).

Received: 2025-01-21
Accepted: 2025-05-27
Published Online: 2025-06-16
Published in Print: 2025-09-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2025-0076
Schlagwörter für diesen Artikel
biomonitoring; reference values; heavy metals

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Quality indicators: an evolving target for laboratory medicine
  4. Reviews
  5. Regulating the future of laboratory medicine: European regulatory landscape of AI-driven medical device software in laboratory medicine
  6. The spectrum of nuclear patterns with stained metaphase chromosome plate: morphology nuances, immunological associations, and clinical relevance
  7. Opinion Papers
  8. Comprehensive assessment of medical laboratory performance: a 4D model of quality, economics, velocity, and productivity indicators
  9. Detecting cardiac injury: the next generation of high-sensitivity cardiac troponins improving diagnostic outcomes
  10. Perspectives
  11. Can Theranos resurrect from its ashes?
  12. Guidelines and Recommendations
  13. Australasian guideline for the performance of sweat chloride testing 3rd edition: to support cystic fibrosis screening, diagnosis and monitoring
  14. General Clinical Chemistry and Laboratory Medicine
  15. Recommendations for the integration of standardized quality indicators for glucose point-of-care testing
  16. A cost-effective assessment for the combination of indirect immunofluorescence and solid-phase assay in ANA-screening
  17. Assessment of measurement uncertainty of immunoassays and LC-MS/MS methods for serum 25-hydroxyvitamin D
  18. A novel immunoprecipitation-based targeted liquid chromatography-tandem mass spectrometry analysis for accurate determination for copeptin in human serum
  19. Histamine metabolite to basal serum tryptase ratios in systemic mastocytosis and hereditary alpha tryptasemia using a validated LC-MS/MS approach
  20. Machine learning algorithms with body fluid parameters: an interpretable framework for malignant cell screening in cerebrospinal fluid
  21. Impact of analytical bias on machine learning models for sepsis prediction using laboratory data
  22. Immunochemical measurement of urinary free light chains and Bence Jones proteinuria
  23. Serum biomarkers as early indicators of outcomes in spontaneous subarachnoid hemorrhage
  24. High myoglobin plasma samples risk being reported as falsely low due to antigen excess – follow up after a 2-year period of using a mitigating procedure
  25. Candidate Reference Measurement Procedures and Materials
  26. Commutability evaluation of glycated albumin candidate EQA materials
  27. Reference Values and Biological Variations
  28. Health-related reference intervals for heavy metals in non-exposed young adults
  29. Hematology and Coagulation
  30. Practical handling of hemolytic, icteric and lipemic samples for coagulation testing in European laboratories. A collaborative survey from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM)
  31. Cancer Diagnostics
  32. Assessment of atypical cells in detecting bladder cancer in female patients
  33. Cardiovascular Diseases
  34. False-positive cardiac troponin I values due to macrotroponin in healthy athletes after COVID-19
  35. Diabetes
  36. A comparison of current methods to measure antibodies in type 1 diabetes
  37. Letters to the Editor
  38. The neglected issue of pyridoxal- 5′ phosphate
  39. Error in prostate-specific antigen levels after prostate cancer treatment with radical prostatectomy
  40. Arivale is dead ‒ Hooke is alive
  41. A single dose of 20-mg of ostarine is detectable in hair
  42. Growing importance of vocabularies in medical laboratories
  43. Congress Abstracts
  44. 62nd National Congress of the Hungarian Society of Laboratory Medicine Szeged, Hungary, August 28–30, 2025
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