, Volume 17, Issue 5, pp 485–489 | Cite as

Cadmium and health in the 21st Century – historical remarks and trends for the future

  • Gunnar F. Nordberg


The first health effect of cadmium (Cd) was lung damage, reported in workers already in the 1930's, while bone effects and proteinuria were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from cadmium pollution were issued in the 1970's. WHO, 1992, identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's population groups in China exposed to Cd via rice were studied and new information on skeletal, renal and reproductive toxicity of Cd was obtained in the ChinaCad project. There was a decrease in Bone Mineral Density (BMD), an increased prevalence of fractures and an increased urinary content of marker proteins of renal dysfunction among persons with long term exposure to Cd. The development of such biomarkers can be seen as a result of applied `proteomics' research. Variation in metallothionein gene expression was related to development of renal dysfunction, supporting the usefulness of this `genomic' approach. The ongoing rapid development of `genomics' and `proteomics' technologies will improve possibilities for molecular epidemiology studies in the future, providing an even better basis for preventive action. In many countries, Cd exposures are now under better control than in the past. The target for the 21st century is to achieve a totally acceptable exposure situation without adverse health effects from Cd.

cadmium health effects history humans 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aitio A., Tritscher A. 2004 Effects on Health of Cadmium-WHO approaches and conclusions. BioMetals 17, 491.Google Scholar
  2. Bernard A. 2004 Renal dysfunction induced by cadmium: biomark-ers of critical effects. BioMetals 17, 519–523.Google Scholar
  3. Bulmer FMR, Rothwell HE, Frankish ER. 1938 Industrial cadmium poisoning. Can Public Health J 29, 19-26.Google Scholar
  4. Chan H, Zhu L-F, Zhong R, Grant D, Goyer RA, Cherian GM. 1993 Nephrotoxicity in rats following liver transplantation from cadmium-exposed rats. Toxicol Appl Pharmacol 123, 89–96.Google Scholar
  5. Cai S, Yue L, Shang Q, Nordberg G. 1995 Cadmium exposure among residents in an area contaminated by irrigation water in China. Bull World Health Organ 73, 359–367.Google Scholar
  6. Faeder EJ, Chaney SO, King LC, Hinners TA, Bruce R, Fowler BA. 1977 Biochemical and ultrastructural changes in livers of cadmium treated rats. Toxicol Appl Pharmacol 39, 473–487.Google Scholar
  7. Ferm VH, Carpenter SJ. 1968 The relationship of cadmium and zinc in experimental mammalian teratogenesis. Lab invest 18, 429–432.Google Scholar
  8. Fowler BA, Nordberg GF. 1978 Renal toxicity of cadmium metal-lothionein: Morphomeric and microanalytical studies; Toxicol Appl Pharmacol 46, 609–623.Google Scholar
  9. Friberg L. 1948 Proteinuria and kidney injury among workmen exposed to cadmium and nickel dust. J Ind Hyg Toxicol 30, 32-36.Google Scholar
  10. Friberg L. 1950 Health Hazards in the manufacture of alkaline ac-cumulators with special reference to chronic cadmium poisoning. Acta Med Scand 138 (suppl 240), 1–124.Google Scholar
  11. Friberg L, Piscator M, Nordberg G. 1971 Cadmium in the Environ-ment. CRC press Cleveland, USA.Google Scholar
  12. Goyer RA, Liu J., Waalkes MP. 2004 Cadmium and Cancer of Prostate and Testis. BioMetals 17, 555–558.Google Scholar
  13. Gunnarsson D, Nordberg G, Lundgren P, Selstam G. 2003 Cadmium-induced decrement of the LH receptor expression and cAMP levles in the testis of rats. Toxicology 183, 57–63.Google Scholar
  14. Haddow A, Dukes CE, Mitchley BCV. 1961 Carcinogenicity of iron preparations and metal carbohydrate complexes. Rep Br Emp Cancer Campagn 39, 74–76.Google Scholar
  15. Hagino N. 1957 About investigations on Itai-itai disease. J. Toyama Med Ass.Dec 21, 7.Google Scholar
  16. IARC 1993 Beryllium, cadmium, mercury and exposure in the glass manufacturing industry. International Agency for Research on Cancer, Lyon IARC Monographs on the evaluation of carcino-genic risks to humans, Vol 58.Google Scholar
  17. Ishizaki A. 1969 On the so called Itai-itai disease. J Jpn Med Soc 62, 242–249. (in Japanese).Google Scholar
  18. Jarup L, Alfvén T. 2004 Low level cadmium exposure, renal and bone effects-The OSCAR study. BioMetals, 17, 505–509.Google Scholar
  19. Jin T, Wu X, Tang Y, Nordberg M, Bernard A, Ye T, Kong Q, Lund-strom NG, Nordberg GF 2004 Environmental epidemiological study and estimation of benchmark dose for renal dysfunction in a cadmium-polluted area in China. BioMetals, 17, 525–530.Google Scholar
  20. Jin T, Leffler P, Nordberg GF. 1987 Cadmium-metallothionein nephrotoxicity in the rat: Transient calcuria and proteinuria. Toxicology 45, 307–317.Google Scholar
  21. Kar AB, Das RP, Karkun JN. 1959 Ovarian Changes in prepubertal rats after treatment with cadmium chloride. Acta Biol Med Ger3, 372–379.Google Scholar
  22. Kazantzis G. (2004) Cadmium, osteoporosis and calcium metabol-ism. BioMetals, 17, 493–498.Google Scholar
  23. Kjellstrom T, Nordberg GF. 1978 A Kinetic model of cadmium metabolism in the human being. Environ Res 16, 248–269.Google Scholar
  24. Lemen RA, Lee JS, Wagoner JK and Blejer HP. 1976 Cancer mortal-ity among cadmium production workers. Ann NY Acad Sci 271, 273–279.Google Scholar
  25. Leffler P, Jin T, Nordberg GF. 2000 Differential calcium trans-port disturbances in renal membrane vesicles after cadmium-metallothionein injection in rats. Toxicology 143, 227–234.Google Scholar
  26. Lu J, Jin T, Nordberg G, Nordberg M. 2001 Metallothionein gene expression in peripheral lymphocytes from cadmium exposed workers. Cell Stress and Chaperones6, 97–104.Google Scholar
  27. Lu J, Jin T, Nordberg GF, Nordberg M. 2004 The application of metallothionein (MT) gene expression in peripheral blood lymphocytes (PBLs) as a biomarker of cadmium exposure. BioMetals, 27, 569–570.Google Scholar
  28. Murata I, Hirono T, Saeki Y and Nakagawa S. 1970 Cadmium en-teropathy, renal osteomalacia (Itai-itai disease in Japan). Bull Soc Int Chir1, 34–41.Google Scholar
  29. Nicaud P, Lafitte A, Gros A. 1942 Symptoms of chronic cadmium intoxication. Arch Mal Prof Med Trav Secur Soc4, 192–202.Google Scholar
  30. Nishijo M, Nakagawa H, Morikawa Y, Kuriwaki J-i, Miura K, Kido T, Nogawa K. 2004 Mortality in a cadmium polluted area in Japan. BioMetals, 17, 535–538.Google Scholar
  31. Nogawa K, Ishizaki A, Fukushima M, Shibata I, Hagino N. 1975 Studies on the women with acquired Fanconi syndrome observed in the Ichi river basin polluted by cadmium. Environ Res 10, 280–307.Google Scholar
  32. Nogawa K, Kobayashi E, Okubo Y, Suwazono Y. 2004 Envir-onmental cadmium exposure, adverse effects and preventive measures in Japan. BioMetals, 17, 581–587.Google Scholar
  33. Nordberg GF. 1972 Cadmium metabolism and toxicity. Environm Physiol Biochem, 2, 7–36.Google Scholar
  34. Nordberg GF. 1974 Health Hazards of Environmental Cadmium Pollution. Ambio3, 55–66.Google Scholar
  35. Nordberg, GF, Kjellström, T and Nordberg M. 1985: Kinetics and metabolism. In: L Friberg, C-G Elinder, T Kjellström, GF Nordberg Eds.: Cadmium and Health: A Toxicological and Epi-demiological Appraisal. Vol I, Exposure Dose and Metabolism. CRC Press, Boca Raton FL, pp. 103–178.Google Scholar
  36. Nordberg GF, Jin T and Nordberg M. 1994 Subcellular targets of cadmium nephrotoxicity: Cadmium binding to renal membrane proteins in animals with or without protective Metallothionein synthesis. Environ Health Perspect 102 (Supplement 3), 191–194.Google Scholar
  37. Nordberg G, Jin T, Bernard A, Fierens S, Buchet JP, Ye T, Kong Q, Wang H. 2002 Low Bone Density and Renal Dysfunction Following Environmental Cadmium Exposure in China. Ambio 31, 478–481.Google Scholar
  38. Nordberg M and Nordberg GF. 2000 Toxicological Aspects of Metallothionein. Cellular and Molecular Biology 46, 451–463.Google Scholar
  39. Oskarsson A, Lindén A, Olsson I-M, Petersson K. 2004 Cadmium in food chain and health effects in sensitive population groups. BioMetals, 17, 531–534.Google Scholar
  40. Parizek J and Zahor Z. 1956 Effect of cadmium salt on testicular tissue. Nature 177, 1036.Google Scholar
  41. Parizek J. 1965 The peculiar toxicity of cadmium during pregnancy-an experimental 'toxaemia of pregnancy' induced by cadmium salts J Reprod Fertil9, 111–112.Google Scholar
  42. U.S. Publ Health Serv. 1942 Public Health Report, Cadmium poisoning. Div Ind Hyg Natl Inst Health 57, 601–612.Google Scholar
  43. Zeng X, Jin T, Nordberg GF. 2003 Changes of serum sex hor-mone levels and MT mRNA expression in rats orally exposed to cadmium. Toxicology 186, 109–118.Google Scholar
  44. Zeng X, Jin T, Buchet JP, Jiang X, Kong Q, Ye T, Bernard A and Nordberg GF. Impact of cadmium exposure on male sex hormones: A population-based study in China. Environ Resin press.Google Scholar
  45. Zeng X, Jin T, Jiang X, Kong Q, Ye T, Nordberg GF. <nt>in press</nt> Effects on the Prostate of Environmental Cadmium Exposure-a Cross-Sectional Population Study in China 2004 BioMetals, 17, 559–566.Google Scholar
  46. Zhu G, Wang H, Shi Y, Weng S, Jin T, Kong Q, Nordberg GF. 2004 Environmental cadmium exposure and forearm bone density. BioMetals, 17, 499–503.Google Scholar
  47. WHO 1992 Cadmium. World Health Organisation, Geneva. Envir-onmental Health Criteria 134.Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Gunnar F. Nordberg
    • 1
  1. 1.Environmental Medicine, Department of Public Health and Clinical MedicineUmeå UniversityUmeåSweden E-mail

Personalised recommendations