Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter October 22, 2020

Reference values of trace elements in blood and/or plasma in adults living in Belgium

  • Perrine Hoet EMAIL logo , Chantal Jacquerye , Gladys Deumer , Dominique Lison and Vincent Haufroid



Trace elements (TEs) from natural and anthropogenic sources are ubiquitous. Essential or not, their relevance for human health and disease is constantly expanding. Biological monitoring is a widely integrated tool in risk assessment both in occupational and environmental settings. However, the determination of appropriate and accurate reference values in the (specific) population is a prerequisite for a correct interpretation of biomonitoring data. This study aimed at determining the reference distribution for TEs (Al, As, Sb, Be, Bi, Cd, Co, Cu, Mn, Hg, Mo, Ni, Pb, Se, Tl, Sn, V, Zn) in the blood and/or plasma of the adult population in Belgium.


Blood and plasma samples were analyzed for 178 males and 202 females, recruited according to an a priori selection procedure, by inductively coupled plasma mass spectrometry (ICP-MS).


Reference values were established with high confidence for AsT, Cd, Cu, HgT, Mn, Mo, Pb, Sn, Se, Tl and Zn. Compared to previously published data in the Belgian population, a decreasing time trend is observed for Zn, Cd and Pb. Globally, the results also indicate that the current exposure levels to TEs in the Belgian population are similar to those from other recent national surveys.


These reference values and limits obtained through validated analytical and statistical methods will be useful for future occupational and/or environmental surveys. They will contribute to decision-making concerning both public health policies but also exposure assessments on an individual scale.

Corresponding author: Perrine Hoet, Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université catholique de Louvain, Institute of Experimental and Clinical Research (IREC), Brussels, Belgium, E-mail:

Current affiliation: Fédération des Mutualités socialistes du Brabant, Brussels, Belgium

Funding source: CESI - Occupational Health Service


The authors wish to thank Francis Desmedt and Marleen Kestens (LTAP) for skillful (pre)analytical handling of the samples.

  1. Research funding: Part of this study was performed with the financial support of CESI (Occupational Health Service, Brussels, Belgium).

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

  3. Competing interests: Authors state no conflict of interest.

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

  5. Ethical approval: The Biomedical Ethical Commission of the Faculty of Health Sciences (Université catholique de Louvain, Brussels) approved the study protocol (CEHF 2015/544-B403).


1. Maret, W. The metals in the biological periodic system of the elements: concepts and conjectures. Int J Mol Sci 2016;17:66. in Google Scholar

2. Ganzleben, C, Antignac, JP, Barouki, R, Castaño, A, Fiddicke, U, Klánová, J, et al.. Human biomonitoring as a tool to support chemicals regulation in the European Union. Int J Hyg Environ Health 2017;220:94–7. in Google Scholar

3. National Research Council (NRC), Board on Environmental Studies and Toxicology. Using 21st Century Science to Improve Risk-Related Evaluations. Washington, DC: National Academies Press (US); 2017. Available from in Google Scholar

4. Solberg, HE, International Federation of Clinical Chemistry (IFCC), Scientific Committee, Clinical Section, Expert Panel on Theory of Reference Values, International Committee. Approved Recommendation (1986) on the theory of reference values. Part 1. The concept of reference values. J Clin Chem Clin Biochem 1987;25:337–42.10.1016/0009-8981(87)90224-5Search in Google Scholar

5. Gräsbeck, R. The evolution of the reference value concept. Clin Chem Lab Med 2004;42:692–7. in Google Scholar

6. Henny, J, Vassault, A, Boursier, G, Vukasovic, I, Mesko Brguljan, P, Lohmander, M, et al.. Recommendation for the review of biological reference intervals in medical laboratories. Clin Chem Lab Med 2016;54:1893–900. in Google Scholar

7. Clinical and Laboratory Standards Institute (CLSI). Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline, 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2008. CLSI Document C28-A3c.Search in Google Scholar

8. Cornelis, R, Sabbioni, E, Van der Venne, MT. Trace element reference values in tissues from inhabitants of the European Community. VII. Review of trace elements in blood, serum and urine of the Belgian population and critical evaluation of their possible use as reference values. Sci Total Environ 1994;158:191–226. in Google Scholar

9. Minoia, C, Pietra, R, Sabbioni, E, Ronchi, A, Gatti, A, Cavalleri, A, et al.. Trace element reference values in tissues from inhabitants of the European Community. III. The control of preanalytical factors in the biomonitoring of trace elements in biological fluids. Sci Total Environ 1992;120:63–79. in Google Scholar

10. Hoet, P, Jacquerye, C, Deumer, G, Lison, D, Haufroid, V. Reference values and upper reference limits for 26 trace elements in the urine of adults living in Belgium. Clin Chem Lab Med 2013;51:839–49. in Google Scholar PubMed

11. Nordberg, GF, Fowler, BA, Nordberg, M. Handbook on the toxicology of metals. 4th ed. Cambridge: Academic Press, Elsevier; 2015.10.1016/B978-0-444-59453-2.00001-9Search in Google Scholar

12. Patterson, N, Robust, A. Non-parametric method to identify outliers and improve final yield and quality. In: CS MANTECH Conference; 2012 April 23rd–26th, 2012. Boston, Massachusetts, USA.Search in Google Scholar

13. Fréry, N, Saoudi, A, Garnier, R, Zeghnoun, A, Falq, G. Exposition de la population française aux substances chimiques de l’environnement. Tome 1 – Présentation générale de l’étude – Métaux et métalloïdes. Saint-Maurice: Institut de Veille Sanitaire; 2011.Search in Google Scholar

14. Nisse, C, Tagne-Fotso, R, Howsam, M. Members of Health Examination Centres of the Nord – Pas-de-Calais region, Richeval, C, Labat, L, et al.. 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. in Google Scholar PubMed

15. Alimonti, A, Bocca, B, Mattei, D, Pino, A. Programme for biomonitoring the Italian population exposure (PROBE): internal dose of metals. Rapporti Istisan 11/9. Istituto Superiore di Sanità; 2011.Search in Google Scholar

16. Umweltbundesamt (UBA), German Environment Agency. German Environmental Surveys (GerES). Available from: in Google Scholar

17. Becker, K, Kaus, S, Krause, C, Lepom, P, Schulz, C, Seiwert, M, et al.. German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population. Int J Hyg Environ Health 2002;205:297–308. in Google Scholar PubMed

18. Centers for Disease Control and Prevention (CDC), National Report on Human Exposure to Environmental Chemicals. National Health and Nutrition Examination Survey (NHANES). Available from: in Google Scholar

19. Jain, RB, Choi, YS. Normal reference ranges for and variability in the levels of blood manganese and selenium by gender, age, and race/ethnicity for general U.S. population. J Trace Elem Med Biol 2015;30:142–52. in Google Scholar PubMed

20. Health Canada, Canadian Health Measures Survey (CHMS). Reports on Human Biomonitoring of Environmental Chemicals in Canada. [updated 2019-11-13]. Available from: in Google Scholar

21. LeBlanc, A, Lapointe, S, Beaudet, A, Côté, I, Dumas, P, Labrecque, F, et al.. Étude sur l’établissement de valeurs de référence d’éléments traces et de métaux dans le sang, le sérum et l’urine de la population de la grande région de Québec. Institut National de Santé Publique du Québec; 2003.Search in Google Scholar

22. Saravanabhavan, G, Werry, K, Walker, M, Haines, D, Malowany, M, Khoury, C. Human biomonitoring reference values for metals and trace elements in blood and urine derived from the Canadian Health Measures Survey 2007-2013. Int J Hyg Environ Health 2017;220:189–200. in Google Scholar PubMed

23. Batariova, A, Spevackova, V, Benes, B, Cejchanova, M, Smid, J, Cerna, M. Blood and urine levels of Pb, Cd and Hg in the general population of the Czech Republic and proposed reference values. Int J Hyg Environ Health 2006;209:359–66. in Google Scholar PubMed

24. Canas, AI, Cervantes-Amat, M, Esteban, M, Ruiz-Moraga, M, Perez-Gomez, B, Mayor, J, et al.. Blood lead levels in a representative sample of the Spanish adult population: the BIOAMBIENT.ES project. Int J Hyg Environ Health 2014;217:452–9. in Google Scholar PubMed

25. Castano, A, Pedraza-Diaz, S, Canas, AI, Perez-Gomez, B, Ramos, JJ, Bartolome, M, et al.. Mercury levels in blood, urine and hair in a nation-wide sample of Spanish adults. Sci Tot Environ 2019;670:262–70. in Google Scholar PubMed

26. Nunes, JA, Batista, BL, Rodrigues, JL, Caldas, NM, Neto, JA, Barbosa, FJr. A simple method based on ICP-MS for estimation of background levels of arsenic, cadmium, copper, manganese, nickel, lead, and selenium in blood of the Brazilian population. J Toxicol Environ Health A 2010;73:878–87. in Google Scholar PubMed

27. Freire, C, Koifman, RJ, Fujimoto, D, de Oliveira Souza, VC, Barbosa, FJr., Koifman, S. Reference values of cadmium, arsenic and manganese in blood and factors associated with exposure levels among adult population of Rio Branco, Acre, Brazil. Chemosphere 2015;128:70–8. in Google Scholar PubMed

28. Kuno, R, Roquetti, MH, Becker, K, Seiwert, M, Gouveia, N. Reference values for lead, cadmium and mercury in the blood of adults from the metropolitan area of Sao Paulo, Brazil. Int J Hyg Environ Health 2013;216:243–9. in Google Scholar PubMed

29. Son, JY, Lee, J, Paek, D, Lee, JT. Blood levels of lead, cadmium, and mercury in the Korean population: results from the second Korean National Human Exposure and Bio-monitoring Examination. Environ Res 2009;109:738–44. in Google Scholar

30. Choi, W, Kim, S, Baek, YW, Choi, K, Lee, K, Kim, S, et al.. Exposure to environmental chemicals among Korean adults-updates from the second Korean National Environmental Health Survey (2012-2014). Int J Hyg Environ Health 2017;220:29–35. in Google Scholar

31. Lee, JW, Lee, CK, Moon, CS, Choi, IJ, Lee, KJ, Yi, SM, et al.. Korea National Survey for environmental pollutants in the human body 2008: heavy metals in the blood or urine of the Korean population. Int J Hyg Environ Health 2012;215:449–57. in Google Scholar

32. Pan, X, Ding, C, Pan, Y, Zhang, A, Wu, B, Huang, H, et al.. [Distribution of copper and zinc in blood among general population from 8 provinces in China]. Zhonghua Yu Fang Yi Xue Za Zhi 2014;48:109–13.Search in Google Scholar

33. Pan, Y, Ding, C, Zhang, A, Wu, B, Huang, H, Zhu, C, et al.. [Distribution of manganese, cobalt and molybdenum in blood and urine among general population in 8 provinces of China]. Zhonghua Yu Fang Yi Xue Za Zhi 2014;48:784–90.Search in Google Scholar

34. Ding, CG, Pan, YJ, Zhang, AH, Wu, BH, Huang, HL, Zhu, C, et al.. [Distribution of chromium in whole blood and urine among general population in China between year 2009 and 2010]. Zhonghua Yu Fang Yi Xue Za Zhi 2012;46:679–82.Search in Google Scholar

35. Ding, C, Pan, Y, Zhang, A, Wu, B, Huang, H, Zhu, C, et al.. [Study of distribution and influencing factors of lead and cadmium in whole blood and urine among population in 8 provinces in China]. Zhonghua Yu Fang Yi Xue Za Zhi 2014;48:91–6.Search in Google Scholar

36. Ding, C, Pan, Y, Zhang, A, Wu, B, Huang, H, Zhu, C, et al.. [Study of distribution and influencing factors of arsenic in whole blood and urine among population in 8 provinces in China]. Zhonghua Yu Fang Yi Xue Za Zhi 2014;48:97–101.Search in Google Scholar

37. Zhang, LL, Lu, L, Pan, YJ, Ding, CG, Xu, DY, Huang, CF, et al.. Baseline blood levels of manganese, lead, cadmium, copper, and zinc in residents of Beijing suburb. Environ Res 2015;140:10–7. in Google Scholar

38. Hoet, P, Deumer, G, Bernard, A, Lison, D, Haufroid, V. Urinary trace element concentrations in environmental settings: is there a value for systematic creatinine adjustment or do we introduce a bias? J Expo Sci Environ Epidemiol 2016;26:296–302. in Google Scholar

39. Cornelis, R, Heinzow, B, Herber, R, Christensen, JM, Poulsen, O, Sabbioni, E, et al.. Sample collection guidelines for trace elements in blood and urine. J Trace Elem Med Biol 1995;10:103–27.10.1016/S0946-672X(96)80018-6Search in Google Scholar

40. EFSA (European Food Safety Authority). Dietary Reference Values for nutrients. Summary report. EFSA Supporting publication 2017:e15121.Search in Google Scholar

41. de Benoist, B, Darnton-Hill, I, Davidsson, L, Fontaine, O, Hotz, C. Conclusions of the Joint WHO/UNICEF/IAEA/IZiNCG interagency Meeting on zinc status indicators. Food Nutr Bull 2007;28:S480–4. in Google Scholar

42. Thijs, L, Staessen, J, Amery, A, Bruaux, P, Buchet, JP, Claeys, F, et al.. Determinants of serum zinc in a random population sample of four Belgian towns with different degrees of environmental exposure to cadmium. Environ Health Perspect 1992;98:251–8. in Google Scholar PubMed PubMed Central

43. Rifai, N, Horvath, AR, Wittwer, C. Tietz textbook of clinical chemistry and molecular diagnostics. St Louis, Missouri: Elsevier; 2018.Search in Google Scholar

44. Van Cauwenbergh, R, Robberecht, H, Van Vlaslaer, V, De Smet, A, Emonds, MP, Hermans, N. Plasma selenium levels in healthy blood bank donors in the central-eastern part of Belgium. J Trace Elem Med Biol 2007;21:225–33. in Google Scholar PubMed

45. Stoffaneller, R, Morse, NL. A review of dietary selenium intake and selenium status in Europe and the Middle East. Nutrients 2015;7:1494–537. in Google Scholar PubMed PubMed Central

46. Lauwerys, R, Hoet, P. Industrial chemical exposure. Guidelines for biological monitoring, 3rd ed. Boca Raton, Florida: Lewis Publisher. CRC Press, Inc.; 2001.10.1201/9781482293838Search in Google Scholar

47. Neve, J. New approaches to assess selenium status and requirement. Nutr Rev 2000;58:363–9.10.1111/j.1753-4887.2000.tb01837.xSearch in Google Scholar PubMed

48. Combs, GFJr. Biomarkers of selenium status. Nutrients 2015;7:2209–36. in Google Scholar PubMed PubMed Central

49. Institute of Medicine (US) PoDAaRC. Dietary reference intakes: vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academies Press (US); 2000.Search in Google Scholar

50. Thomson, CD. Assessment of requirements for selenium and adequacy of selenium status: a review. Eur J Clin Nutr 2004;58:391–402. in Google Scholar PubMed

51. Hoet, P, Roels, H. Significance and usefulness of biomarkers of exposure to Manganese. In: Costa, LG, Aschner, M, editors. Manganese in health and disease. Issues in toxicology 22. Cambridge, UK: Royal Society of Chemistry; 2015.10.1039/9781782622383-00355Search in Google Scholar

52. Rentschler, G, Rodushkin, I, Cerna, M, Chen, C, Harari, F, Harari, R, et al.. Platinum, palladium, rhodium, molybdenum and strontium in blood of urban women in nine countries. Int J Hyg Environ Health 2018;221:223–30. in Google Scholar PubMed

53. Hall, M, Chen, Y, Ahsan, H, Slavkovich, V, van Geen, A, Parvez, F, et al.. Blood arsenic as a biomarker of arsenic exposure: results from a prospective study. Toxicology 2006;225:225–33. in Google Scholar PubMed

54. Lauwerys, R, Bernard, A, Buchet, JP, Roels, H, Bruaux, P, Claeys, F, et al.. Does environmental exposure to cadmium represent a health risk? Conclusions from the Cadmibel study. Acta Clin Belg 1991;46:219–25. in Google Scholar PubMed

55. Schoeters, G, Den Hond, E, Colles, A, Loots, I, Morrens, B, Keune, H, et al.. Concept of the Flemish human biomonitoring programme. Int J Hyg Environ Health 2012;215:102–8. in Google Scholar PubMed

56. Watanabe, T, Nakatsuka, H, Shimbo, S, Iwami, O, Imai, Y, Moon, CS, et al.. Reduced cadmium and lead burden in Japan in the past 10 years. Int Arch Occup Environ Health 1996;68:305–14. in Google Scholar

57. Nakayama, SF, Iwai-Shimada, M, Oguri, T, Isobe, T, Takeuchi, A, Kobayashi, Y, et al.. Blood mercury, lead, cadmium, manganese and selenium levels in pregnant women and their determinants: the Japan Environment and Children’s Study (JECS). J Expo Sci Environ Epidemiol 2019;29:633–47. in Google Scholar

58. Hartwig, A, Bolt, HM, Levy, L, Manno, M, Papameletiou, D, Klein, CL. SCOEL/OPIN/336 – cadmium and its inorganic compounds. Opinion from the Scientific Committee on Occupational Exposure Limits; 2017. Available from in Google Scholar

59. Nordberg, GF, Bernard, A, Diamond, GL, Duffus, JH, Illing, P, Nordberg, M, et al.. Risk assessment of effects of cadmium on human health (IUPAC Technical Report). Pure Appl Chem 2018;90:755–808. in Google Scholar

60. Agence Nationale Sécurité Sanitaire de l’alimentation, de l’environnement et du Travail (ANSES). Valeurs limites d’exposition en milieu professionnel. Evaluation des indicateurs biologiques d’exposition et recommandation de valeurs limites biologiques et de valeurs biologiques de référence pour le cadmium et ses composés. Rapport d’expertise collective; 2018. Available from in Google Scholar

61. Barbosa, FJr., Tanus-Santos, JE, Gerlach, RF, Parsons, PJ. A critical review of biomarkers used for monitoring human exposure to lead: advantages, limitations, and future needs. Environ Health Persp 2005;113:1669–74. in Google Scholar

62. Ducoffre, G, Claeys, F, Bruaux, P. Lowering time trend of blood lead levels in Belgium since 1978. Environ Res 1990;51:25–34. in Google Scholar

63. European Food Safety Authority (EFSA), Panel on Contaminants in the Food Chain (CONTAM), Scientific opinion on lead in food [151 pp.]. revised in 2013. EFSA J 2010;8:1570. Available from in Google Scholar

64. National Toxicology Program (NTP). NTP Monograph. Health effects of low-level lead. U.S. Department of Health and Human Services; 2012. Available from in Google Scholar

65. Centers for Disease Control and Prevention (CDC), The National Institute for Occupational Safety and Health (NIOSH). Adult blood lead epidemiology & surveillance (ABLES). Atlanta, GA: US Department of Health and Human Services. [last reviewed May 2018]. Available from in Google Scholar

66. Boerleider, RZ, Roeleveld, N, Scheepers, PTJ. Human biological monitoring of mercury for exposure assessment. AIMS Environ Sci 2017;4:251–76.10.3934/environsci.2017.2.251Search in Google Scholar

67. Basu, N, Horvat, M, Evers, DC, Zastenskaya, I, Weihe, P, Tempowski, J. A state-of-the-science review of mercury biomarkers in human populations worldwide between 2000 and 2018. Environ Health Persp 2018;126:106001. in Google Scholar

68. Sheehan, MC, Burke, TA, Navas-Acien, A, Breysse, PN, McGready, J, Fox, MA. Global methylmercury exposure from seafood consumption and risk of developmental neurotoxicity: a systematic review. Bull World Health Organ 2014;92:254–69F. in Google Scholar PubMed PubMed Central

69. Sharma, BM, Sanka, O, Kalina, J, Scheringer, M. An overview of worldwide and regional time trends in total mercury levels in human blood and breast milk from 1966 to 2015 and their associations with health effects. Environ Int 2019;125:300–19. in Google Scholar PubMed

70. Umweltbundesamt (UBA). German Environment Agency. Human Biomonitoring Commission. Available from: in Google Scholar

71. Snoj Tratnik, J, Falnoga, I, Mazej, D, Kocman, D, Fajon, V, Jagodic, M, et al.. Results of the first national human biomonitoring in Slovenia: trace elements in men and lactating women, predictors of exposure and reference values. Int J Hyg Environ Health 2019;222:563–82. in Google Scholar PubMed

72. Grandjean, P, Nielsen, GD, Jørgensen, PJ, Hørder, M. Reference intervals for trace elements in blood: significance of risk factors. Scand J Clin Lab Invest 1992;52:321–37. in Google Scholar PubMed

Received: 2020-05-20
Accepted: 2020-10-09
Published Online: 2020-10-22
Published in Print: 2021-03-26

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 4.3.2024 from
Scroll to top button