CADMIBEL - PHEECAD De risico’s van verhoogde blootstelling aan cadmium in de bevolking

1. CADMIBEL - PHEECADDe risico’s van verhoogde blootstelling aan cadmium in de bevolking T. Nawrot, J.A. Staessen K.U. Leuven tim.nawrot@med.kuleuven.be

2. Contents • Study area and environmental data • Study designs • Exposure to Cd • Health effects of Cd

4. Cadmium pollution - soil Bosmans H, Paenhuys J. Pedologie, 1980; 191-223

5. Past and current Cd exposure WHO limit value Source: VMM.

6. II. Study design

7. Biomonitoring (1)

8. Biomonitoring (2)

9. Cadmibel : design • CADMIum in BELgium Study • Cross-sectional study • 1985 - 1989 • Aim: to study the health effects of environmental exposure to cadmium • Research partners: K.U.L. - U.C.L. - Université de Liège - Institute of Hygiene and Epidemiology, Brussels, Universiteit Hasselt

10. Cadmibel : design • Fieldwork • home visits: anthropometry, blood pressure, questionnaire on medical history, life style, etc. • 24 h urine sample: Cd, As, Ca, creatinine, retinol-binding protein, ß2-microglobulin, N-acetyl-ß-glucosaminidase, albumin, amino acids • whole blood: Cd, Pb, Se, ZPP • serum: Zn, creatinine, ß2-microglobulin

11. PheeCad : design • Public Health and Environmental Exposure to CADmium Study • Prospective follow-up study of Cadmibel: 1991-’94 • Aim: How does exposure change over time ? • Additional measurements on bone metabolism and calcium homeostasis • Hard endpoints

12. III. Exposure to heavy metals

13. Cadmibel : exposure to cadmium Polluted Reference MEN Blood Cd, nmol/L 11.0 8.5*** Urinary Cd, nmol/24h 10.2 7.9*** WOMEN Blood Cd, nmol/L 11.0 8.3*** Urinary Cd, nmol/24h 7.6 6.6*** data are geometric means; *** p<0.001

14. Determinants of urinary cadmium Percentage of explained variance for U-Cd MEN WOMEN age (linear and squared) 26.8 29.0 place of residence 7.4 9.4 smoking 6.3 3.3 past smoking 2.7 n.s.

15. Urinary cadmium vs.cadmium in soil and vegetables Staessen et al. Lancet 1994;343:1523-7. • Soil samples from kitchen gardens • Vegetable samples from participants with garden

16. Cadmium in soil and vegetables : geometric means Characteristicscontrol polluted Cd in soil, ppm 0.81 4.86*** Cd in celery, ppm 0.68 2.43*** Cd in leek, ppm 0.67 1.58*** Cd in carrots, ppm 0.45 0.98*** Cd in beans, ppm 0.15 0.42*** Urinary Cd, nmol/24h 8.4 9.8** ** p<0.01; *** p<0.001

17. Percentage of vegetables above the EU norm in the study area European legislation: maximal values are 2 mg/kg for leafy vegetables and 1 mg/kg for all others.

18. Cadmium in urine, soil and vegetables : correlations • Correlation between Cd in soil and • Cd in celery: r = 0.77 (p=0.02) • Cd in leek: r = 0.63 (p=0.05) • Cd in carrots: r = 0.52 (p=0.15) • Cd in beans: r = 0.67 (p=0.05) • Correlation between urinary Cd and • Cd in soil: r = 0.76 (p=0.01) • Cd in celery: r = 0.63 (p=0.07) • Cd in leek: r = 0.70 (p=0.03) • Cd in carrots: r = 0.57 (p=0.11) • Cd in beans: r = 0.92 (p=0.001)

19. PheeCad : Cd-exposure over time • Since mid ‘60 : reductions in emission • change from thermic to electrolytic procedure • transport of zinc ore concentrates was covered (hangars) • Since 1985 : information on risk reduction • using tap water in stead of well water • liming soil of kitchen gardens • not grow leafy vegetables

23. Cd exposure at baseline vs follow-up

24. External and internal exposure

25. IV. Health effects

26. Cadmium and renal effectsCadmium and fracturesCadmium and mortality

27. Cadmium and renal effects • Cadmium accumulates in the kidney • Half-life = 10 to 20 years • Urinary Cd represents life-long exposure • Markers of kidney function: • tubular function: urinary excretion of NAG, RBP, ß2-microglobulin, AA, Ca

29. Cadmium and fractures • Chronic exposure to cadmium may promote urinary calcium loss • Cadmium may interfere with the metabolism of calcium, vit. D, collagen • Severe cadmium poisoning is associated with ostemalacia or osteoporosis

30. Cadmium and bone : prospective analysis • Staessen et al. Lancet 1999; 353:1140-4. • n = 506 • baseline exposure to cadmium • after a median follow-up of 6.6 years: • incidence of fractures (questionnaire + confirmation by family physician)

31. Relative risk of fractureand height loss in Cox regression fractures men women N° endpoints 20 24 Cd excretion 1.20 1.73** Polluted area 2.76* 4.30** Cd in soil 1.39* 1.54*** Cd in leek 1.93* 2.27** Cd in celery 1.69* 2.07** * p<0.05, ** p<0.01, *** p<0.001 RR for a doubling of Cd conc.; analyses adjusted for significant covariates

32. In postmenopausal women, urinary cadmium correlated negatively with bone density. • The population-based risk for fractures in districts near the smelters was 35%. Conclusion: cadmium may promote skeletal demineralisation, which may lead to increased bone fragility and raised risk of fractures.

33. Rational to study hard endpoints Source: MIRA, achtergronddocument: verspreiding van zware metalen, 2004

34. Hard-end points: study in progress • 17 year of follow-up • Causes of mortality (national institute of statistics) • Incidence of diseases (general practioner) • Endpoints of interest: total mortality, total cancer and lung cancer mortality.* *based on evidence from IARC

35. V. Summary

36. Cadmibel • Differences in exposure between polluted and control area. • Associations between external and internal exposure markers. • Renal effects of cadmium.

37. PheeCad • Prevention measures result in a reduction of internal exposure markers for cadmium. • Exposure to cadmium is associated with decreased bone density and an increased risk for fractures