Transcript Pb: blootstelling

CADMIBEL - PHEECAD
De risico’s van verhoogde
blootstelling aan cadmium in de
bevolking
T. Nawrot, J.A. Staessen
K.U. Leuven
[email protected]
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
70
'1980-'85
Cd in air dust (ng/m3)
60
2000-'05
50
40
30
20
10
WHO limit
value
0
BalenWezel
Source: VMM.
Beerse
Hoboken
Olen
Overpelt HechtelEksel
Non-ferro sites and reference area
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, retinolbinding protein, ß2-microglobulin, N-acetyl-ßglucosaminidase, 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
MEN
Blood Cd, nmol/L
Urinary Cd, nmol/24h
WOMEN
Blood Cd, nmol/L
Urinary Cd, nmol/24h
data are geometric means; *** p<0.001
Polluted
Reference
11.0
10.2
8.5***
7.9***
11.0
7.6
8.3***
6.6***
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
Cd in celery, ppm
Cd in leek, ppm
Cd in carrots, ppm
Cd in beans, ppm
0.81
0.68
0.67
0.45
0.15
4.86***
2.43***
1.58***
0.98***
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
100
Perecentage above EU norm*
90
Reference area
Polluted area
80
70
60
50
40
30
20
10
0
Beans
Carrots
Leek
Vegetables
Celery
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
IV. Health effects
Cadmium and renal effects
Cadmium and fractures
Cadmium 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, ß2microglobulin, 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
N° endpoints
Cd excretion
Polluted area
Cd in soil
Cd in leek
Cd in celery
fractures
men
women
20
24
1.20
1.73**
2.76*
4.30**
1.39*
1.54***
1.93*
2.27**
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