biomonitoring results international symposium organised by the flemish center of expertise for...

Biomonitoring resultsBiomonitoring results

International Symposium organised by the Flemish Center of Expertise for Environment and HealthDecember 15,2006

Elly Den HondEnvironmental ToxicologyVITO

RecruitmentRecruitment

Newborns and mothers Period: Sept. 2002 – Dec. 2003Period: Sept. 2002 – Dec. 2003 Cord blood – questionnairesCord blood – questionnaires Medical files of maternityMedical files of maternity

Adolescents Period: Oct. 2003 – July 2004Period: Oct. 2003 – July 2004 Blood – urine – questionnairesBlood – urine – questionnaires Medical files of school doctorsMedical files of school doctors

Elderly Period: Sept. 2004 – June 2005Period: Sept. 2004 – June 2005 Blood – urine - questionnairesBlood – urine - questionnaires

Characteristics of populationCharacteristics of population

______________________________________________Newborns

& mothers Adolescents Elderly______________________________________________Age (years) - range 18-44 14-15 50-65

Age (years) - mean 29.6 14.9 57.6

% women 100% 47% 51%

% smokers 15% 14% 18%

Mean BMI (kg/m²) 23.3 20.5 26.9

Higher education 22% 49% 32%

Use of local food 42% 51% 49%______________________________________________

Biomarkers of exposure Biomarkers of exposure

Biomarkers of exposureBiomarkers of exposure

Persistent chlorinated compounds (serum)Dioxin-like compounds (pg Calux TEQ/g fat)

Marker PCB 138.153 & 180 (ng/g fat)

p,p’-DDE (ng/g fat)

Hexachlorobenzene (ng/g fat)

Heavy metals (blood & urine) Blood lead (µg/L)

Blood cadmium (µg/L)

Urinary cadmium (µg/g creatinine)

Metabolites of PAH and benzene (urine)1-hydroxy-pyrene (ng/g creatinine)

t,t’-muconic acid (µg/g creatinine)

newborn adolesc. elderly





newborn elderly

elderly

adolesc. elderly

adolesc. elderly

Reference values – Reference values – persistent chlorinated persistent chlorinated compounds compounds

Marker PCBs

333

6468

0

100

200

300

400

500

600

Newborns Adolesc. Elderlyn

g/g

fa

t

p,p'-DDE

423

110 940

400

800

1200

1600

Newborns Adolesc. Elderly

ng

/g f

at

Hexachlorobenzene

57

1921

0

20

40

60

80

100

120

Newborns Adolesc. Elderlyn

g/g

fa

t

Bar: geometric mean Line: 90e percentile

Adjusted for sex (except newborns), age, smoking and BMI

* Dioxins + furanes + dioxin-like PCBs** Dioxins + furanes

Dioxin-like compounds

1923

0

10

20

30

40

50

60

Newborns Elderly

pg

Ca

lux

TE

Q/g

fa

t

* **

Reference values – Reference values – heavy metals heavy metals

Blood lead

40

2215

0

20

40

60

80

100


µg

/L

Blood cadmium

0,420,360,21

0

0,3

0,6

0,9

1,2

1,5


µg

/L

Bar: geometric mean; line: 90e percentile

Adjusted for sex (except newborns), age and smoking

Urinary cadmium

0,62

0

0,3

0,6

0,9

1,2

1,5

Elderly

µg

/g c

rea

tin

ine

Reference values – Reference values – metabolites of PAH and metabolites of PAH and benzene benzene

Urinary 1-hydroxy-pyrene

14788

0

100

200

300

400

500

600

700

Adolesc. Elderly

ng

/g c

rea

tin

ine

Bar: geometric mean; line: 90e percentile

Adjusted for sex, age and smoking.

Urinary t,t'-muconic acid

8572

0

50

100

150

200

250

300

350

Adolesc. Elderlyµ

g/g

cre

ati

nin

e

Regional comparisonRegional comparison

Dioxin-like compounds ! !PCBs ! ! ! !p,p'-DDE ! !HCB ! !Lead

B-Cadmium ! !U-Cadmium

1-OH-pyrene

t,t'-muconic acid


PCBs !p,p'-DDE ! ! ! ! ! !HCB

Lead

B-Cadmium !U-Cadmium !1-OH-pyrene

t,t'-muconic acid

Harbour Non ferro industry (Olen)

Chemical industry (Albert canal)

Waste incinerators

City of Antwerp City of Ghent Fruit region Rural area

Significantly higher than reference valueSignificantly lower than reference value

! Significantly more than 10% of values above P90

Regional comparison –Regional comparison –fruit and rural areafruit and rural area

Dioxin-like compounds ! !PCBs ! ! !p,p'-DDE ! !HCB ! !Lead

B-Cadmium !U-Cadmium

1-OH-pyrene

t,t'-muconic acid

Fruit region Rural area



Regional comparison –Regional comparison –non-ferro and chemical non-ferro and chemical industryindustry


PCBs

p,p'-DDE ! ! ! ! !HCB

Lead

B-Cadmium !U-Cadmium !1-OH-pyrene

t,t'-muconic acid

Non ferro industry (Olen)

Chemical industry (Albert canal)



DDT: a problem of the past?DDT: a problem of the past?

DDT is metabolised to DDE Ratio DDT / DDE is measure for more or less recent

exposure

0 1 2 3 4 5

City of Antwerp

City of Ghent

Fruit region

Rural area

Harbours

Non-ferro industry

Chemical industry

Waste incinerators

(DDT/p,p'-DDE)*100

n=58

n=49

n=16

n=38

n=26

n=56

n=53

n=25

ANOVA: p=0,04

Regional comparison –Regional comparison –urban areasurban areas




PCBs !p,p'-DDE

HCB

Lead

B-Cadmium !U-Cadmium

1-OH-pyrene

t,t'-muconic acid

City of Antwerp City of Ghent

Regional comparison –Regional comparison –waste incineratorswaste incinerators


PCBs

p,p'-DDE

HCB

Lead

B-Cadmium

U-Cadmium

1-OH-pyrene

t,t'-muconic acid

Waste incinerators




PCBs

p,p'-DDE

HCB

Lead

B-Cadmium

U-Cadmium

1-OH-pyrene

t,t'-muconic acid

Menen Harelbeke Roeselare Wilrijk

Regional comparison –Regional comparison –harboursharbours

combination of 2 harbours: - port of Antwerp

- port of Ghent exposure differs between 2 ports exposure resembles the exposure of the neighboring city

Antw 'n H aven Antw 'n Gent H aven Gent0

50

100

150

200

250

300

350

so

m m

erke

r PC

Bs (n

g/g

ve

t)

b

73

78

76

60

63

62

0 20 40 60 80 100

verbrandingsovenGent

Gentse kanaalzone

Gentse agglomeratie

verbrandingsovenWilrijk

Antwerpshavengebied

Antwerpseagglomeratie

Merker PCB's (ng/g vet)

adolescentsnewborns

Comparison with reference Comparison with reference valuesvalues

Blood lead > 100 µg/L 0.2% 1.6%

Blood cadmium > 5 µg/L 0% n=1

Urinary cadmium > 2 µg/g crt - 2.3%

Urinary 1-OH-pyrene > 2 µg/g crt 0.2% 1.1%

Urinary t,t’-MA > 0.5 µg/g crt 3.5% 4.7%

adolescents elderly

Determinants of exposureDeterminants of exposure(stepwise multiple (stepwise multiple modelbuilding)modelbuilding)

Marker PCBtotally explained: 46,6%

0,1

0,2

0,4

0,4

0,4

0,4

0,6

2,7

2,9

6,2

13,3

19,1

0 5 10 15 20 25

dairy consumption

smoking

eel consumption

school type

milk consumption

mothers' smoking pregnancy

mothers' age at delivery

local meat consumption

area

breast feeding at birth

sex

BMI

% explainedadolescents

Determinants of exposureDeterminants of exposure

Sex higher in males for adolescentshigher in males for adolescents higher in females for elderlyhigher in females for elderly

Age Body-mass index, weight change

for persistent lipophylic compoundsfor persistent lipophylic compounds Smoking

for cadmium, lead, PAH and benzenefor cadmium, lead, PAH and benzene Nutrition

fat products for persistent lipophylic compoundsfat products for persistent lipophylic compounds vegetables for cadmium and lead (in elderly)vegetables for cadmium and lead (in elderly) local productslocal products breast feeding in adolescentsbreast feeding in adolescents

Area remains significant

Exposure: conclusionsExposure: conclusions

Area of residence determines exposure

No alarming trends were detected

People living in rural areas have high exposure to persistent chlorinated compounds

Cadmium is problematic in some regions

Although DDT is forbidden, metabolites are still detected in the human body in considerable amounts

Factors such as age, sex, smoking and nutritional intake are important determinants of exposure

Biomarkers of effectBiomarkers of effect

Asthma and allergy Asthma and allergy Endocrine effect markersEndocrine effect markersGenotoxic effect markersGenotoxic effect markers

Asthma & allergy – Asthma & allergy – reference meansreference means

______________________________________________14-15 y. 18-44 y. 50-65

y.______________________________________________Asthma - doctor 8.8% 4.3% 5.5%

Asthma - ever 25.3% 16.2% 15.3%

Hay fever - doctor 22.8% 34.2% 21.4%

Food allergy 25.5% 7.0% 22.7%

Contact allergy 21.5% 11.3% 24.9%

Allergy for animals 10.8% 12.0% 1.1%_______________________________________________________

mothers of newbornsadolesc. elderly

Asthma & allergy – Asthma & allergy – regional comparisonregional comparison

Asthma: more frequent in the cities Significant in mothersSignificant in mothers Trends in adolescents and Trends in adolescents and

elderlyelderly

Allergy for animals: less frequent in rural areas Significant in mothersSignificant in mothers Trends in adolescents and Trends in adolescents and

elderlyelderly

0

5

10

15

20

25

30

Antwerp Ghent Fruit Rural Harbour Non-fer. Chem. Incin.

Per

cen

t m

oth

ers

(%)

ASTHMA

0

5

10

15

20

25

30

35

Antwerp Ghent Fruit Rural Harbour Non-fer. Chem. Incin.

Per

cen

t m

oth

ers

(%)

ALLERGY FOR ANIMALS

Asthma & allergy – Asthma & allergy – dose-responsedose-response

Exposure Effect Odds for doubling pof exposure

Cadmium Asthma 1.15 (1.02-1.30) 0.02PCBs Hay fever 0.82 (0.72-0.94) 0.004

Lead Asthma 1.20 (1.04-1.39) 0.001Lead Hay fever 2.45 (1.06-5.66) 0.04Cadmium Asthma 3.10 (1.07-8.95) 0.04

PCBs Asthma 0.57 (0.41-0.78) <0.001p,p’-DDE Asthma 0.86 (0.76-0.97) 0.02HCB Asthma 0.79 (0.63-0.99) 0.04

Adolescents

Mothers of newborns

Elderly

asthma: adjusted for smoking and familial history; hay fever adjusted for smoking

Endocrine effectsEndocrine effects

Thyroid hormones (♀ & ♂) and sex hormones (♂) normal ranges, no regional differencesnormal ranges, no regional differences

Age at menarche (♀) and pubertal stages of Marshall and Tanner (♀ & ♂) validation against questionnaires and blood hormonesvalidation against questionnaires and blood hormones regional differences: significantly lower pubertal stage in regional differences: significantly lower pubertal stage in

Antwerp and harbourAntwerp and harbour

65

156

327

442449

0

100

200

300

400

500

G1 G2 G3 G4 G5

Genital stage in boys

Tes

tost

eron

(ng

/dL)

n=8 n=61 n=214 n=282 n=202

25

38

83

93

98

0

20

40

60

80

100

B1 B2 B3 B4 B5

Breast development in girls

% g

irls

at m

enar

che

n=4 n=8 n=41 n=264 n=307

Adolescents


pubertal stages of Marshall and Tanner In boys:In boys:

genital development (G) – stages 1,2 vs. 3,4,5 pubic hair development (P) – stages 1,2 vs. 3,4,5

In girls:In girls: breast development (B) – stages 1,2,3 vs. 4,5 pubic hair development (P) – stages 1,2,3 vs. 4,5

0

20

40

60

80

100

Antwerp Ghent Fruit Rural Harbour Non-ferro Chemical Inciner.

Sta

ge

4-5

(%

gir

ls)

B P B P B P B P B P B P B P B P0

20

40

60

80

100


Sta

ge

3-4

-5 (

% b

oys

)

G P G P G P G P G P G P G P G P


Reference mean: Time to pregnacy: 9.7 monthsTime to pregnacy: 9.7 months Fertility treatment: 7.6%Fertility treatment: 7.6% Miscarriages: 15.9%Miscarriages: 15.9%

No significant differences between 8 regions

Reference mean: Miscarriages: 17.7%Miscarriages: 17.7% Diabetes: 4.0%Diabetes: 4.0%

No significant differences between 8 regions

Mothers of newborns

Elderly

Endocrine effects – Endocrine effects – dose-responsedose-response


Lead pubic hair, girls 0.65 (0.45-0.93) 0.02

PCBs pubic hair, boys 2.58 (1.71-3.91) <0.001HCB pubic hair, boys 3.81 (2.18-6.66) <0.001p,p’-DDE pubic hair, boys 1.39 (1.13-1.72) 0.002

PCBs genital stage, boys 3.03 (1.87-4.89) <0.001HCB genital stage, boys 3.12 (1.69-5.75) <0.001 p,p’-DDE genital stage, boys 1.51 (1.18-1.93) 0.001

PCBs testosterone + 12% * <0.001

Adolescents

all relations: adjusted for age and BMI (+ oral contraceptive use in girls)* for doubling from 50 to 100 ng PCB/g fat



Calux fertility treatment 1.40 (1.09-1.80) 0.008

PCBs fertility treatment 1.29 (1.04-1.59) 0.002

HCB fertility treatment 1.21 (1.01-1.45) 0.04

Calux miscarriages 0.81 (0.65-0.99) 0.04

PCBs Diabetes 2.14 (1.32-3.50) 0.002

HCB Diabetes 1.99 (1.38-2.87) <0,001

Mothers of newborns

Elderly

fertility treatment and miscarriages: adjusted for age and smoking;diabetes: adjusted for age, smoking, sex and BMI

Genotoxic effects – Genotoxic effects – reference meansreference means

Comet assay: 1.03% DNA

Comet assay: 1.92% DNA Micronucleus: 6.6 mironucleï / 1000 binuclear cells 8-hydroxy-deoxguanosine: 14.9 µg/g creatinine Prostate specific antigen (PSA) – average: 1.03 µg/L

– PSA > 4 µg/L: 3.7% of men Carcino Embryonal Antigen (CEA): 1.82 ng/mL p53 – number above LOD: 35.6%

– average: 86.3 ng/mL (in subjects >LOD)

Cancer (self-report): 4.7%

Elderly

Adolescents

Genotoxic effects – Genotoxic effects – regional comparisonregional comparison

0,0

0,5

1,0

1,5

2,0

2,5

3,0


Co

met

ass

ay (

%D

NA

)

COMET ASSAYelderly

0

2

4

6

8

10


µn

uc

leï /

100

0 b

inu

clea

r ce

lls MICRONUCLEUSelderly

0

4

8

12

16

20

24


8-H

DG

(µ

g/g

cre

atin

ine)

8-HYDROXY-DEOXYGUANOSINEelderly

0,0

0,5

1,0

1,5

2,0

2,5

3,0


Co

met

ass

ay (

%D

NA

)

COMET ASSAYadolesc.

adjusted for age (in elderly only), sex and smoking



Lead comet assay +7% (2-12) 0.004

1-hydroxy-pyrene 8-DHG +3% (1-6) 0.01

Lead CEA +9% (3-15) 0.004

Urinary cadmium CEA +7% (2-13) 0.01

1-hydroxy-pyrene CEA +4% (1-7) 0.01

Elderly

comet assay adjusted for sex and smoking; 8-DHG adjusted for age, sex and smoking; CEA adjusted for age and smoking.

Adolescents

Health effects: conclusionsHealth effects: conclusions

Asthma and allergy occur frequently in Flanders; regional differences are present between cities and rural areas

Some endocrine and genotoxic markers differ between regions, but the clinical relevance is probably low

Several dose-response relationships were detected:

asthma and allergy asthma and allergy vs.vs. heavy metals and chlorinated persistent heavy metals and chlorinated persistent pollutantspollutants

endocrine effects endocrine effects vs. vs. lead and chlorinated persistent pollutantslead and chlorinated persistent pollutants

genotoxic markers genotoxic markers vs.vs. heavy metals and PAHs heavy metals and PAHs

biomonitoring results international symposium organised by the flemish center of expertise for...

Documents

p90 slide

smoking slide

elderly slide

reference values blood

recent exposure slide

biomarkers of exposure

dioxins furanes slide

blood urine questionnaires