CADMIBEL - PHEECAD

De risico’s van verhoogde blootstelling aan cadmium in de

bevolking

T. Nawrot, J.A. Staessen

K.U. Leuven

tim.nawrot@med.kuleuven.be

Contents

Study area and environmental data

Study designs

Exposure to Cd

Health effects of Cd

Cadmium pollution - soil

Bosmans H, Paenhuys J. Pedologie, 1980; 191-223

Past and current Cd exposure

Source: VMM.

0

10

20

30

40

50

60

70

Balen-Wezel

Beerse Hoboken Olen Overpelt Hechtel-Eksel

Non-ferro sites and reference area

Cd

in a

ir d

ust

(n

g/m

3)

'1980-'85

2000-'05

WHO limit value

II. Study design

Biomonitoring (1)

Biomonitoring (2)

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

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

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

III. Exposure to heavy metals

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

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.

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

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**

** p<0.01; *** p<0.001

Percentage of vegetables above the EU norm in the study area

0

10

20

30

40

50

60

70

80

90

100

Beans Carrots Leek Celery

Vegetables

Pe

rec

en

tag

e a

bo

ve

EU

no

rm*

Reference area

Polluted area

European legislation: maximal values are 2 mg/kg for leafy vegetables and 1 mg/kg for all others.

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)

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

Cd exposure at baseline vs follow-up

External and internal exposure

1030

60100

135

Number ofparticipants

0.18 - 0.25

0.25 - 0.40

0.40 - 0.60

0.60 - 0.73

Cd in dust(ng/cm²/92d)

7.1 - 8.0

8.0 - 10.0

10.0 - 12.0

12.0 - 13.3

Cd in blood(µmol/l)

7.9 - 10.0

10.0 - 15.0

15.0 - 20.0

20.0 - 23.0

Cd in urine(nmol/24-h)

S Zinc smelter

Municipality

Study area

0.93 - 1.50

1.50 - 5.00

5.00 - 10.0

10.0 - 10.6

Cd in soil(mg/kg)

0 1 2 3 km

BALEN

MOL

EKSEL

HECHTEL

LOMMEL

NEERPELT

OVERPELT

S

S

S

1030

60100

135

Number ofparticipants

0.18 - 0.25

0.25 - 0.40

0.40 - 0.60

0.60 - 0.73

Cd in dust(ng/cm²/92d)

7.1 - 8.0

8.0 - 10.0

10.0 - 12.0

12.0 - 13.3

Cd in blood(µmol/l)

7.9 - 10.0

10.0 - 15.0

15.0 - 20.0

20.0 - 23.0

Cd in urine(nmol/24-h)

S Zinc smelter

Municipality

Study area

0.93 - 1.50

1.50 - 5.00

5.00 - 10.0

10.0 - 10.6

Cd in soil(mg/kg)

0 1 2 3 km

BALEN

MOL

EKSEL

HECHTEL

LOMMEL

NEERPELT

OVERPELT

S

S

S

IV. Health effects

Cadmium and renal effectsCadmium and fracturesCadmium and mortality

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

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

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)

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**

* p<0.05, ** p<0.01, *** p<0.001

RR for a doubling of Cd conc.; analyses adjusted for significant covariates

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.

Rational to study hard endpoints

Source: MIRA, achtergronddocument: verspreiding van zware metalen, 2004

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

V. Summary

Cadmibel

Differences in exposure between polluted and control area.

Associations between external and internal exposure markers.

Renal effects of cadmium.

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