Miljøudvalget 2014-15 (1. samling), Sundheds- og Forebyggelsesudvalget 2014-15 (1. samling)
MIU Alm.del Bilag 103, SUU Alm.del Bilag 170
Offentligt
1484105_0001.png
EDCs Why we should be concerned
Jorma Toppari
Departments of Physiology and Pediatrics
University of Turku
2014
 PDF to HTML - Convert PDF files to HTML files
1484105_0002.png
Authors:
Jorma Toppari, Finland
Malene Boas, Denmark
Helena E. Virtanen, Finland
Annika Adamsson, Finland
Katharina M. Main, Denmark
Anders Juul, Denmark
Niels E. Skakkebaek, Denmark
ISBN 978 92 4 150376 1 WHO
www.who.int/ceh
Funding: NIEHS with WHO
 PDF to HTML - Convert PDF files to HTML files
1484105_0003.png
Working group:
• Georg Becher, Norway
• Åke Bergman, Sweden (Leader)
• Poul Bjerregaard, Denmark
• Riana Bornman, South Africa
• Ingvar Brandt, Sweden
• Jerrold J. Heindel, USA
• Taisen Iguchi, Japan
• Susan Jobling, England
• Karen A. Kidd, Canada
• Andreas Kortenkamp, England
• Derek C.G. Muir, Canada
• Roseline Ochieng, Kenya
• Niels E. Skakkebaek, Denmark
• Jorma Toppari, Finland
• Tracey J. Woodruff, USA
• R. Thomas Zoeller, USA
 PDF to HTML - Convert PDF files to HTML files
1484105_0004.png
Trends of male reproductive
health related to development
•
•
•
•
Cryptorchidism
Hypospadias
Semen quality
Testicular cancer
 PDF to HTML - Convert PDF files to HTML files
1484105_0005.png
Carlsen et al. 1992
 PDF to HTML - Convert PDF files to HTML files
1484105_0006.png
+Suominen
& Vierula 1993
 PDF to HTML - Convert PDF files to HTML files
1484105_0007.png
Sperm concentration (million/ml)
120
100
80
60
40
20
0
DK
France
UK
FIN
Mean
Median
Jørgensen et al. Hum. Reprod. 2001
 PDF to HTML - Convert PDF files to HTML files
1484105_0008.png
Sperm concentration (million/ml)
60
50
40
30
20
10
0
DK
N
EST
FIN
Jørgensen et al., Hum. Reprod. 17:2199, 2002
 PDF to HTML - Convert PDF files to HTML files
1484105_0009.png
Sperm concentration (million/ml)
120
100
80
60
40
20
0
DK
N
EST
FIN
Fertile
Young
 PDF to HTML - Convert PDF files to HTML files
1484105_0010.png
+Jørgensen
et al.
2001,
2002
 PDF to HTML - Convert PDF files to HTML files
1484105_0011.png
Intrauterine exposure to smoking
• 2069 young men
around Baltic sea
• Data on maternal
smoking during
pregnancy
• Semen analysis
60
50
40
30
20
10
0
smoking
no
smoking
Sperm conc. mill/ml
Jensen et al., Am. J. Epid. 2004
 PDF to HTML - Convert PDF files to HTML files
1484105_0012.png
Young men from the Finnish general population
Total sperm counts according to year of birth
Total sperm counts
250
200
Millions
150
100
50
0
1979-81
1982-83
p=0.032
p=0.030
1987
Adjusted for duration of ejaculation abstinence
Jørgensen et al 2011, IJA
 PDF to HTML - Convert PDF files to HTML files
1484105_0013.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0014.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0015.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0016.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0017.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0018.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0019.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0020.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0021.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0022.png
 PDF to HTML - Convert PDF files to HTML files
1484105_0023.png
Inhibin B
Testis cancer incidence
Testosterone
0
2
4
AGE (years)
6
8
10
20
30
40
50
60
 PDF to HTML - Convert PDF files to HTML files
1484105_0024.png
1997-2001
4957 families
2562 boys
2006-2007
2008 -
Katharina Main
 PDF to HTML - Convert PDF files to HTML files
1484105_0025.png
Cryptorchidism
• The most common congenital malformation
of newborn boys
 PDF to HTML - Convert PDF files to HTML files
1484105_0026.png
Prevalence of cryptorchidism
10
9
8
7
6
5
4
3
2
1
0
At birth
Age
3 months
Cohort 1997-99
(n=1492)
TUCH 1997-99
(n=5798)
Copenhagen
1997-2001
(n=1071)
Percentage
Boisen et al.,
Lancet 2004
 PDF to HTML - Convert PDF files to HTML files
1484105_0027.png
Incidence of cryptorchidism (%) and testicular
cancer (n/100 000) in Finland and Denmark
12
10
8
Rate
6
4
2
0
Crypt
Te Ca
Crypt
Te Ca
Finland
Denmark
Cryptorchidism data from Boisen et al., Lancet 2004;
Cancer data from WHO/IARC 1998
 PDF to HTML - Convert PDF files to HTML files
1484105_0028.png
<3 SG
A
7
w
ee
ks
Bl
Br
ee
ee
ch din
D
g
ie
Sp de
tt
liv
rin
re
er
at
g
ed
de y
liv
ge
er
st
y
at
io
na
ld
ia
be
te
s
>5
dr
in
G
Bi ks/w
re
ng
en
ee
e
ho
N
k
dr
us ico
in
t
ki
e
n
pe ine
Pa
pa g
st
ra
ic
id tch
ce
es
es
ta
m
Fu
o
ne
Pa l A
n
ra arh
ce
us
ta
*
Pa mo n=
4
r
l
Pa ace Cp 7.0
00
h
ta
ra
ce mo ** n
=
ta
m l Cp 49
1
ol
h
n=
Tu
83
rk
u
n= 4
14
63
Main
In
se
10
0
n
1
2
3
4
5
6
7
8
9
m
in
a
tio
BW
<2
50
0g
G
A
Adjusted OR's and confidence intervals
(* use > 4 weeks GA 8-14, ** use > 2 weeks in 2nd trimester)
 PDF to HTML - Convert PDF files to HTML files
1484105_0029.png
Hypospadias
 PDF to HTML - Convert PDF files to HTML files
1484105_0030.png
Prevalence of hypospadias in
Finland and Denmark
n/10 000 liveborn children
60
50
40
30
20
10
0
Finland
Denmark
Boisen et al., JCEM 2005
 PDF to HTML - Convert PDF files to HTML files
1484105_0031.png
Breast milk as a proxy for fetal
exposures
Breast milk (n=130)
non-persistant chemicals: 6
phthalate metabolites
Persistant chemicals:
polybrominated flame retardents
(PBDEs), polychlorinated
biphenyls (PCBs), dioxins and
some polychlorinated pesticides
 PDF to HTML - Convert PDF files to HTML files
1484105_0032.png
Six top significant chemicals of a
total of 111 chemicals
6,0
Relative differences
5,0
4,0
3,0
Finland
Denmark
2,0
1,0
0,0
be
nz
en
e
D
ie
ld
rin
20
9
D
D
15
6
B
C
B
,8
-H
C
C
P
P
lo
ro
ac
h
ex
Concentrations of 58 of 111 chemicals significantly higher in one country
54 of these 58 chemicals showed significantly higher levels in Denmark
Krysiak-Baltyn et al., Int J Androl. 2009 Sep 24.
H
1,
2,
3
,4
,7
P
C
B
15
7
 PDF to HTML - Convert PDF files to HTML files
1484105_0033.png
Country‐specific chemical signatures of
persistent environmental compounds in breast
milk
The top 10 most important chemicals in each of the two principal components are listed as follows:
PCI: 1,2,3,4,7,8-HCDD, PCB 209, PCB156, PCB 189, PCB 170, PCB 157, PCB 194,
PCB 180, o.p’-DDE, PCB 81.
PC2: 1,2,3,6,7,8-HCDD, 1,2,3,4,6,7,8-HepCDD, Mirex, 1,2,3,4,6,7,8-HepCDF, OCDD, PeBB, BDE-154,
1,2,3,4,7,8-HCDD, PCB 49, Octachlorostyrene.
International Journal of Andrology
Volume 33, Issue 2,
pages 270-278, 24 SEP 2009 DOI: 10.1111/j.1365-2605.2009.00996.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2605.2009.00996.x/full#f2
 PDF to HTML - Convert PDF files to HTML files
1484105_0034.png
Scatter plots from the PLS (Partial Least
Square): Danish and Finnish breast milk samples
Healthy boy
Cryptorchid boy
Krysiak-Baltyn et al, IJA, in press
 PDF to HTML - Convert PDF files to HTML files
1484105_0035.png
Summary: EDCs represent a Global
Problem
• There are increasing trends for more
diseases in more species in more
countries.
• There are more data on more
chemical exposures in humans and in
wildlife.
• There are stronger data linking
exposures to disease.
• Worldwide there has been a failure to
adequately address the underlying
environmental causes of trends in
endocrine diseases and disorders.
 PDF to HTML - Convert PDF files to HTML files
1484105_0036.png
Supporting Statements
•
•
•
•
Endocrine Society, 2009, 2012
CRO Forum on EDCs, 2012
SAICM, Narobi, 2012
Royal College of Obstetricians and
Gynaecologists, 2013
• SAICM, Mexico City, 2013
• American Society for Reproductive
Medicine/American Congress of Obstetricians
and Gynecologists, 2013