Abstract
We focus on the recent evidence that elucidates our understanding about the effects of cadmium (Cd) on human health and their prevention. Recently, there has been substantial progress in the exploration of the shape of the Cd concentration-response function on osteoporosis and mortality. Environmental exposure to Cd increases total mortality in a continuous fashion without evidence of a threshold, independently of kidney function and other classical factors associated with mortality including age, gender, smoking and social economic status. Pooled hazard rates of two recent environmental population based cohort studies revealed that for each doubling of urinary Cd concentration, the relative risk for mortality increases with 17% (95% CI 4.2–33.1%; P < 0.0001). Tubular kidney damage starts at urinary Cd concentrations ranging between 0.5 and 2 μg urinary Cd/g creatinine, and recent studies focusing on bone effects show increased risk of osteoporosis even at urinary Cd below 1 μg Cd/g creatinine. The non-smoking adult population has urinary Cd concentrations close to or higher than 0.5 μg Cd/g creatinine. To diminish the transfer of Cd from soil to plants for human consumption, the bioavailability of soil Cd for the plants should be reduced (external bioavailability) by maintaining agricultural and garden soils pH close to neutral (pH-H2O of 7.5; pH-KCL of 6.5). Reducing the systemic bioavailability of intestinal Cd can be best achieved by preserving a balanced iron status. The latter might especially be relevant in groups with a lower intake of iron, such as vegetarians, and women in reproductive phase of life. In exposed populations, house dust loaded with Cd is an additional relevant exposure route. In view of the insidious etiology of health effects associated with low dose exposure to Cd and the current European Cd intake which is close to the tolerable weekly intake, one should not underestimate the importance of the recent epidemiological evidence on Cd toxicity as to its medical and public health implications.
This is a preview of subscription content, access via your institution.



References
Åkesson A, Berglund M, Schutz A, Bjellerup P, Bremme K, Vahter M (2002) Cadmium exposure in pregnancy and lactation in relation to iron status. Am J Public Health 92:284–287
Åkesson A, Lundh T, Vahter M, Bjellerup P, Lidfeldt J, Nerbrand C, Samsioe G, Stromberg U, Skerfving S (2005) Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure. Environ Health Perspect 113:1627–1631
Åkesson A, Bjellerup P, Lundh T, Lidfeldt J, Nerbrand C, Samsioe G, Skerfving S, Vahter M (2006) Cadmium-induced effects on bone in a population-based study of women. Environ Health Perspect 114:830–834
Åkesson A, Julin B, Wolk A (2008) Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence: a population-based prospective cohort study. Cancer Res 68:6435–6441
Alfaro-Moreno E, Nawrot TS, Nemmar A, Nemery B (2007) Particulate matter in the environment: pulmonary and cardiovascular effects. Curr Opin Pulm Med 13:98–106
Alfvén T, Elinder CG, Carlsson MD, Grubb A, Hellstrom L, Persson B, Pettersson C, Spang G, Schutz A, Järup L (2000) Low-level cadmium exposure and osteoporosis. J Bone Miner Res 15:1579–1586
Alfvén T, Elinder CG, Hellstrom L, Lagarde F, Järup L (2004) Cadmium exposure and distal forearm fractures. J Bone Miner Res 19:900–905
Arisawa K, Uemura H, Hiyoshi M, Dakeshita S, Kitayama A, Saito H, Soda M (2007) Cause-specific mortality and cancer incidence rates in relation to urinary beta2-microglobulin: 23-year follow-up study in a cadmium-polluted area. Toxicol Lett 173:168–174
Banza CL, Nawrot TS, Haufroid V, Decree S, De PT, Smolders E, Kabyla BI, Luboya ON, Ilunga AN, Mutombo AM, Nemery B (2009) High human exposure to cobalt and other metals in Katanga, a mining area of the Democratic Republic of Congo. Environ Res 109:745–752
Benoff S, Hauser R, Marmar JL, Hurley IR, Napolitano B, Centola GM (2009) Cadmium concentrations in blood and seminal plasma: correlations with sperm number and motility in three male populations (infertility patients, artificial insemination donors, and unselected volunteers). Mol Med 15:248–262
Berglund M, Åkesson A, Nermell B, Vahter M (1994) Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. Environ Health Perspect 102:1058–1066
Bolte G, Heitmann D, Kiranoglu M, Schierl R, Diemer J, Koerner W, Fromme H (2008) Exposure to environmental tobacco smoke in German restaurants, pubs and discotheques. J Expo Sci Environ Epidemiol 18:262–271
Buchet JP, Lauwerys R, Roels H, Bernard A, Bruaux P, Claeys F, Ducoffre G, de PP, Staessen J, Amery A (1990) Renal effects of cadmium body burden of the general population. Lancet 336:699–702
Byrne C, Divekar SD, Storchan GB, Parodi DA, Martin MB (2009) Cadmium—a metallohormone? Toxicol Appl Pharmacol 238:266–271
Centers for Disease Control and Prevention (CDC) (2005) Third national report on human exposure to environmental chemicals. NCEH 05-0570, Atlanta, GA, 21 August 2008, pp 1–467. http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf. Accessed November 2010
CONTAM (2009) Scientific opinion of the panel on contaminants in the food chain on a request from the European commission on cadmium in food. EFSA J 980:1–139
Cuypers A, Plusquin M, Remans T, Jozefczak M, Keunen E, Gielen H, Opdenakker K, Nair AR, Munters E, Artois TJ, Nawrot T, Vangronsveld J, Smeets K (2010) Cadmium stress: an oxidative challenge. Biometals. doi:10.1007/s10534-010-9329-x
Engstrom A, Skerving S, Lidfeldt J, Burgaz A, Lundh T, Samsioe G, Vahter M, Åkesson A (2009) Cadmium-induced bone effect is not mediated via low serum 1, 25-dihydroxy vitamin D. Environ Res 109:188–192
European Community Report (EUR 23424 EN) http://ecb.jrc.ec.europa.eu/Documents/Existing-Chemicals/RISK_ASSESSMENT/SUMMARY/cdmetal_cdoxidesum303.pdf. Assessed February 2010
Ezaki T, Tsukahara T, Moriguchi J, Furuki K, Fukui Y, Ukai H, Okamoto S, Sakurai H, Honda S, Ikeda M (2003) Analysis for threshold levels of cadmium in urine that induce tubular dysfunction among women in non-polluted areas in Japan. Int Arch Occup Environ Health 76:197–204
Flanagan PR, McLellan JS, Haist J, Cherian G, Chamberlain MJ, Valberg LS (1978) Increased dietary cadmium absorption in mice and human subjects with iron deficiency. Gastroenterology 74:841–846
Gallagher CM, Kovach JS, Meliker JR (2008) Urinary cadmium and osteoporosis in U.S. Women ≥ 50 years of age: NHANES 1988–1994 and 1999–2004. Environ Health Perspect 116:1338–1343
Gennart JP, Buchet JP, Roels H, Ghyselen P, Ceulemans E, Lauwerys R (1992) Fertility of male workers exposed to cadmium, lead, or manganese. Am J Epidemiol 135:1208–1219
Grondin MA, Ruivard M, Perreve A, Derumeaux-Burel H, Perthus I, Roblin J, Thiollieres F, Gerbaud L (2008) Prevalence of iron deficiency and health-related quality of life among female students. J Am Coll Nutr 27:337–341
Hartwig A (2010) Mechanisms in cadmium-induced carcinogenicity: recent insights. Biometals. doi:10.1007/s10534-010-9330-4
Haswell-Elkins M, Satarug S, O’Rourke P, Moore M, Ng J, McGrath V, Walmby M (2008) Striking association between urinary cadmium level and albuminuria among Torres Strait Islander people with diabetes. Environ Res 106:379–383
Hill AB (1965) The environment and disease: association or causation? Proc R Soc Med 58:295–300
Hogervorst J, Plusquin M, Vangronsveld J, Nawrot T, Cuypers A, Van HE, Roels HA, Carleer R, Staessen JA (2007) House dust as possible route of environmental exposure to cadmium and lead in the adult general population. Environ Res 103:30–37
Honda R, Tsuritani I, Noborisaka Y, Suzuki H, Ishizaki M, Yamada Y (2003) Urinary cadmium excretion is correlated with calcaneal bone mass in Japanese women living in an urban area. Environ Res 91:63–70
Järup L, Alfvén T (2004) Low level cadmium exposure, renal and bone effects—the OSCAR study. Biometals 17:505–509
Järup L, Alfvén T, Persson B, Toss G, Elinder CG (1998a) Cadmium may be a risk factor for osteoporosis. Occup Environ Med 55:435–439
Järup L, Bellander T, Hogstedt C, Spang G (1998b) Mortality and cancer incidence in Swedish battery workers exposed to cadmium and nickel. Occup Environ Med 55:755–759
Järup L, Berglund M, Elinder CG, Nordberg G, Vahter M (1998c) Health effects of cadmium exposure—a review of the literature and a risk estimate. Scand J Work Environ Health 24(Suppl 1):1–51
Jaworowski Z, Barbalat F, Blain C, Peyre E (1985) Heavy metals in human and animal bones from ancient and contemporary France. Sci Total Environ 43:103–126
Jin YH, Clark AB, Slebos RJ, Al-Refai H, Taylor JA, Kunkel TA, Resnick MA, Gordenin DA (2003) Cadmium is a mutagen that acts by inhibiting mismatch repair. Nat Genet 34:326–329
Jin T, Nordberg G, Ye T, Bo M, Wang H, Zhu G, Kong Q, Bernard A (2004) Osteoporosis and renal dysfunction in a general population exposed to cadmium in China. Environ Res 96:353–359
Kazantzis G, Blanks RG, Sullivan KR (1992) Is cadmium a human carcinogen? IARC Sci Publ 118:435–446
Kellen E, Zeegers MP, Hond ED, Buntinx F (2007) Blood cadmium may be associated with bladder carcinogenesis: the Belgian case–control study on bladder cancer. Cancer Detect Prev 31:77–82
Kippler M, Goessler W, Nermell B, Ekstrom EC, Lonnerdal B, El AS, Vahter M (2009) Factors influencing intestinal cadmium uptake in pregnant Bangladeshi women—a prospective cohort study. Environ Res 109:914–921
Kobayashi E, Suwazono Y, Honda R, Dochi M, Nishijo M, Kido T, Nakagawa H (2008) Changes in renal tubular and glomerular functions and biological acid-base balance after soil replacement in Cd-polluted rice paddies calculated with a general linear mixed model. Biol Trace Elem Res 124:164–172
Kriegel AM, Soliman AS, Zhang Q, El-Ghawalby N, Ezzat F, Soultan A, bdel-Wahab M, Fathy O, Ebidi G, Bassiouni N, Hamilton SR, Abbruzzese JL, Lacey MR, Blake DA (2006) Serum cadmium levels in pancreatic cancer patients from the East Nile Delta region of Egypt. Environ Health Perspect 114:113–119
Kurihara I, Kobayashi E, Suwazono Y, Uetani M, Inaba T, Oishiz M, Kido T, Nakagawa H, Nogawa K (2004) Association between exposure to cadmium and blood pressure in Japanese peoples. Arch Environ Health 59:711–716
McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA (2006) Cadmium exposure and breast cancer risk. J Natl Cancer Inst 98:869–873
Menke A, Muntner P, Silbergeld EK, Platz EA, Guallar E (2009) Cadmium levels in urine and mortality among U.S. adults. Environ Health Perspect 117:190–196
Messner B, Bernhard D (2010) Cadmium and cardiovascular diseases: cell biology, pathophysiology, and epidemiological relevance. Biometals. doi:10.1007/s10534-010-9314-4
Messner B, Knoflach M, Seubert A, Ritsch A, Pfaller K, Henderson B, Shen YH, Zeller I, Willeit J, Laufer G, Wick G, Kiechl S, Bernhard D (2009) Cadmium is a novel and independent risk factor for early atherosclerosis mechanisms and in vivo relevance. Arterioscler Thromb Vasc Biol 29:1392–1398
Nakagawa H, Nishijo M (1996) Environmental cadmium exposure, hypertension and cardiovascular risk. J Cardiovasc Risk 3:11–17
Navas-Acien A, Selvin E, Sharrett AR, Calderon-Aranda E, Silbergeld E, Guallar E (2004) Lead, cadmium, smoking, and increased risk of peripheral arterial disease. Circulation 109:3196–3201
Navas-Acien A, Silbergeld EK, Sharrett R, Calderon-Aranda E, Selvin E, Guallar E (2005) Metals in urine and peripheral arterial disease. Environ Health Perspect 113:164–169
Navas-Acien A, Tellez-Plaza M, Guallar E, Muntner P, Silbergeld E, Jaar B, Weaver V (2009) Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis. Am J Epidemiol 170:1156–1164
Nawrot T, Den HE, Thijs L, Staessen JA (2003) Isolated systolic hypertension and the risk of vascular disease. Curr Hypertens Rep 5:372–379
Nawrot T, Plusquin M, Hogervorst J, Roels HA, Celis H, Thijs L, Vangronsveld J, Van HE, Staessen JA (2006) Environmental exposure to cadmium and risk of cancer: a prospective population-based study. Lancet Oncol 7:119–126
Nawrot TS, Van HE, Thijs L, Richart T, Kuznetsova T, Jin Y, Vangronsveld J, Roels HA, Staessen JA (2008) Cadmium-related mortality and long-term secular trends in the cadmium body burden of an environmentally exposed population. Environ Health Perspect 116:1620–1628
Nawrot TS, Kuenzli N, Sunyer J, Shi TM, Moreno T, Viana M, Heinrich J, Forsberg B, Kelly FJ, Sughis M, Nemery B, Borm P (2009) Oxidative properties of ambient PM2.5 and elemental composition: heterogeneous associations in 19 European cities. Atmos Environ 43:4595–4602
Nawrot T, Geusens P, Nulens T, Nemery B (2010). Occupational cadmium exposure, calcium excretion, bone density and risk for osteoporosis. J Bone Miner Res 25(6):1441–1445
Nishijo M, Tawara K, Honda R, Kuriwaki J, Nakagawa H, Tanebe K, Saito S (2004) Cadmium and nutritional intake in pregnant Japanese women. Toxicol Lett 148:171–176
Nishijo M, Morikawa Y, Nakagawa H, Tawara K, Miura K, Kido T, Ikawa A, Kobayashi E, Nogawa K (2006) Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment. Occup Environ Med 63:545–550
Nordberg GF, Nogawa K, Nordberg M et al (2007) Cadmium. In: Nordberg GF, Fowler BF, Nordberg M et al (eds) Handbook on the toxicology of metals. Elsevier, Amsterdam, pp 445–486
Olsson IM, Bensryd I, Lundh T, Ottosson H, Skerfving S, Oskarsson A (2002) Cadmium in blood and urine—impact of sex, age, dietary intake, iron status, and former smoking—association of renal effects. Environ Health Perspect 110:1185–1190
Plusquin M, Nawrot TS, Staessen JA (2005) Peripheral arterial disease and metals in urine and blood. Environ Health Perspect 113:A510–A511
Resnick HE, Lindsay RS, McDermott MM, Devereux RB, Jones KL, Fabsitz RR, Howard BV (2004) Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong Heart Study. Circulation 109:733–739
Roels HA, Roels HA, Hoet P, Lison D (1999) Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity. Ren Fail 21:251–262
Satarug S, Nishijo M, Ujjin P, Vanavanitkun Y, Moore MR (2005) Cadmium-induced nephropathy in the development of high blood pressure. Toxicol Lett 157:57–68
Schutte R, Nawrot T, Richart T, Thijs L, Roels HA, Van Bortel LM, Struijker-Boudier H, Staessen JA (2008a) Arterial structure and function and environmental exposure to cadmium. Occup Environ Med 65:412–419
Schutte R, Nawrot TS, Richart T, Thijs L, Vanderschueren D, Kuznetsova T, Van HE, Roels HA, Staessen JA (2008b) Bone resorption and environmental exposure to cadmium in women: a population study. Environ Health Perspect 116:777–783
Schwartz GG, Il’yasova D, Ivanova A (2003) Urinary cadmium, impaired fasting glucose, and diabetes in the NHANES III. Diabetes Care 26:468–470
Sorahan T, Lancashire RJ (1997) Lung cancer mortality in a cohort of workers employed at a cadmium recovery plant in the United States: an analysis with detailed job histories. Occup Environ Med 54:194–201
Sorahan T, Waterhouse JA (1983) Mortality study of nickel-cadmium battery workers by the method of regression models in life tables. Br J Ind Med 40:293–300
Sorahan T, Lister A, Gilthorpe MS, Harrington JM (1995) Mortality of copper cadmium alloy workers with special reference to lung cancer and non-malignant diseases of the respiratory system, 1946–92. Occup Environ Med 52:804–812
Staessen JA, Lauwerys RR, Ide G, Roels HA, Vyncke G, Amery A (1994) Renal function and historical environmental cadmium pollution from zinc smelters. Lancet 343:1523–1527
Staessen JA, Roels HA, Emelianov D, Kuznetsova T, Thijs L, Vangronsveld J, Fagard R (1999) Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group. Lancet 353:1140–1144
Staessen JA, Kuznetsova T, Roels HA, Emelianov D, Fagard R (2000) Exposure to cadmium and conventional and ambulatory blood pressures in a prospective population study. Public Health and Environmental Exposure to Cadmium Study Group. Am J Hypertens 13:146–156
Staessen JA, Nawrot T, Hond ED, Thijs L, Fagard R, Hoppenbrouwers K, Koppen G, Nelen V, Schoeters G, Vanderschueren D, Van HE, Verschaeve L, Vlietinck R, Roels HA (2001) Renal function, cytogenetic measurements, and sexual development in adolescents in relation to environmental pollutants: a feasibility study of biomarkers. Lancet 357:1660–1669
Tellez-Plaza M, Navas-Acien A, Crainiceanu CM, Guallar E (2008) Cadmium exposure and hypertension in the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Environ Health Perspect 116:51–56
Vahter M, Åkesson A, Liden C, Ceccatelli S, Berglund M (2007) Gender differences in the disposition and toxicity of metals. Environ Res 104:85–95
Van Der Klift M, Pols HA, Geleijnse JM, Van Der Kuip DA, Hofman A, De Laet CE (2002) Bone mineral density and mortality in elderly men and women: the Rotterdam Study. Bone 30:643–648
van Wijngaarden, Singer EA, Palapattu GS (2008) Prostate-specific antigen levels in relation to cadmium exposure and zinc intake: results from the 2001–2002 National Health and Nutrition Examination Survey. Prostate 68:122–128
Verougstraete V, Lison D, Hotz P (2003) Cadmium, lung and prostate cancer: a systematic review of recent epidemiological data. J Toxicol Environ Health B Crit Rev 6:227–255
Vinceti M, Venturelli M, Sighinolfi C, Trerotoli P, Bonvicini F, Ferrari A, Bianchi G, Serio G, Bergomi M, Vivoli G (2007) Case-control study of toenail cadmium and prostate cancer risk in Italy. Sci Total Environ 373:77–81
Wang H, Zhu G, Shi Y, Weng S, Jin T, Kong Q, Nordberg GF (2003) Influence of environmental cadmium exposure on forearm bone density. J Bone Miner Res 18:553–560
Watkin RD, Nawrot T, Potts RJ, Hart BA (2003) Mechanisms regulating the cadmium-mediated suppression of Sp1 transcription factor activity in alveolar epithelial cells. Toxicology 184:157–178
Yiin LM, Rhoads GG, Rich DQ, Zhang J, Bai Z, Adgate JL, Ashley PJ, Lioy PJ (2002) Comparison of techniques to reduce residential lead dust on carpet and upholstery: the New Jersey assessment of cleaning techniques trial. Environ Health Perspect 110:1233–1237
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
Acknowledgement
The Environmental Health research at Hasselt University is supported by grants from the Flemish Fund for Scientific Research (FWO, krediet aan navorsers to T.N.) and internal Hasselt University grants (Bijzonder Onderzoekdsfonds, BOF).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nawrot, T.S., Staessen, J.A., Roels, H.A. et al. Cadmium exposure in the population: from health risks to strategies of prevention. Biometals 23, 769–782 (2010). https://doi.org/10.1007/s10534-010-9343-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10534-010-9343-z