CADMIBEL - PHEECAD De risico

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CADMIBEL - PHEECADDe risicos van verhoogde
blootstelling aan cadmium in de bevolking

• T. Nawrot, J.A. Staessen
• K.U. Leuven
• tim.nawrot_at_med.kuleuven.be

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Contents

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

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Cadmium pollution - soil
Bosmans H, Paenhuys J. Pedologie, 1980 191-223
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Past and current Cd exposure
WHO limit value
Source VMM.
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II. Study design
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Biomonitoring (1)
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Biomonitoring (2)
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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

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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

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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

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III. Exposure to heavy metals
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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 plt0.001

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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.

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Urinary cadmium vs. cadmium in soil and
vegetables

• Staessen et al. Lancet 19943431523-7.
• Soil samples from kitchen gardens
• Vegetable samples from participants with garden

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Cadmium in soil and vegetables geometric means

• Characteristics control 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
• plt0.01 plt0.001

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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.
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Cadmium in urine, soil and vegetables
correlations

• Correlation between Cd in soil and
• Cd in celery r 0.77 (p0.02)
• Cd in leek r 0.63 (p0.05)
• Cd in carrots r 0.52 (p0.15)
• Cd in beans r 0.67 (p0.05)
• Correlation between urinary Cd and
• Cd in soil r 0.76 (p0.01)
• Cd in celery r 0.63 (p0.07)
• Cd in leek r 0.70 (p0.03)
• Cd in carrots r 0.57 (p0.11)
• Cd in beans r 0.92 (p0.001)

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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

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Cd exposure at baseline vs follow-up
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External and internal exposure
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IV. Health effects
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Cadmium and renal effectsCadmium and
fracturesCadmium and mortality
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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

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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

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Cadmium and bone prospective analysis

• Staessen et al. Lancet 1999 3531140-4.
• n 506
• baseline exposure to cadmium
• after a median follow-up of 6.6 years
• incidence of fractures (questionnaire
  confirmation by family physician)

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• Relative risk of fracture and 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
• plt0.05, plt0.01, plt0.001
• RR for a doubling of Cd conc. analyses adjusted
  for significant covariates

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• 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.

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Rational to study hard endpoints
Source MIRA, achtergronddocument verspreiding
van zware metalen, 2004
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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
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V. Summary
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Cadmibel

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

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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