Därför måste företag substituera
Carl-Gustaf Bornehag
Professor in Public Health Sciences
Karlstad University, Sweden
Our natural hormones are of the greatest
importance for a healthy development
during the entire life span from the
moment of conception
until death
Endocrine Disrupting Chemicals
(EDCs)
-Natural estrogen
hormone
Binding
Adverse health effect
Pharmaceutical
drugs
Metals
Natural
occuring
hormones
Building
materials
Endocrine
Disrupting
Chemicals
Pesticides
Herbicides
Fungicides
Personal
care
products
Consumer
products
Food
Water
Early life is important
David Barker (1938-2013)
The fetal period is important for
chronic diseases later on in life,
e.g., hypertonia, diabetes,
cardiovascular diseases...
Birth weight
Low birth weight
Body weight
Macrosomia
IUGR***
Median
IUGR
Birth Wean
Adult
Low birth weight & Centile crossing
Body weight
Macrosomia
IUGR***
Median
IUGR
Birth Wean
Adult
Stress
Infections
Malnutrition
Pharmaceuticals
Environmental chemicals
Environmental influences
during development
A 70 year old man with cardiovascular disease
A 60 year old man with Parkinson's disease
A 50 year old women with breast cancer
A 40 year old man with type 2 diabetes
A 30 year man with infertility problem
A 20 year old man with overweight
A 10 year old boy with asthma
A 6 year old boy with ADHD
A newborn boy with
malformed genitals
The dirty dozen
The 12 worst endocrine disrupters (EWG)
Bisphenol-A
(BPA)
Dioxin
Atrazine
Phthalates
Perchlorate
Fire
retardants
Lead
Mercury
Arsenic
Perfluorinated
chemicals
(PFCs)
Organophosphates
Glycol
ethers
The dirty dozen
The 12 worst endocrine disrupters (EWG)
Bisphenol-A
(BPA)
Dioxin
Atrazine
Phthalates
Perchlorate
Fire
retardants
Lead
Mercury
Arsenic
Perfluorinated
chemicals
(PFCs)
Organophosphates
Glycol
ethers
Fyra exempel på svårigheter vid
riskvärdering av hormonstörande
ämnen
Kontroversen kring lågdosexponering!
EFSAs riskvärdering av Bisfenol a!
Substituering av ftalater som mjukgörare i PVC!
Perfluorerade ämnen och hälsorisker
The low dose controversy
exemplified by bisphenol A
The low dose controversy
exemplified by bisphenol A
Myer et al., 2008
Response
The dose-response paradigm
Phillippus
Aureolus
Theophrastus
Bombastus
von Hohenheim
Paracelsus
1493-1541
Dose
Response
Non-monotonic dose responses
Toxicity
Programming
Dose
Regulatory science
Response
MTD
1493-1541
LOAEL
NOAEL
Safe
dose
Safety
factors
Dose
EDCs are not poisons!
Available information
Standardized studies
Academic research
Good Laboratory Practice
(GLP)
Industry
Animals
“dose response paradigm”
Epidemiology
Animals
In-vitro Cells
Around 450
studies!
2 studies
Tyl et al., 2002
Tyl et al., 2008
Efsas risk assessment of BPA
Standardized studies
Academic research
Good Laboratory Practice
(GLP)
Industry
“dose response paradigm”
Epidemiology
91 studies/60 with positive findings!
Animals
Tyl et al., 2002
Tyl et al., 2008
Focus on EDC problems
Cells
Low dose exposure
• Det finns en utbredd oro över BPA bland forskare
världen över!
• Vi känner väl till källorna och vi mäter rutinmässigt
BPA i urin hos barn och vuxna!
• Oenighet om gränsvärden för olika myndigheter
och organisationer (Anses, WHO, etc.)!
• Oenighet om hur man ska se på standardstudier
och forskningsstudier!
• Oenighet hur man ska värdera epidemiologiska
studier!
• Svårt att mäta BPA i blod (risk för kontaminering)!
• Stort behov av bättre riskvärdering där all
tillgänglig information vägs samman!!!!!!!!
Group
Phthalates
(urine)
Phenols
(urine)
Per- and
polyfluorinated
alkyl substances
(serum)
Parent
compound
Metabolite
n>LOD
GM (95% CI)
(ng/mL)
95%
(ng/mL)
DEP
MEP
2,356
67.97 (60.30 - 76.60)
511.49
DBP
MBP
2,356
63.99 (57.72 - 70.94)
236.03
BBzP
MBzP
2,356
16.11 (14.17 - 18.32)
101.59
2,356
2,356
2,356
2,356
3.28 (2.98 - 3.61)
DEHP
MEHP
MEHHP
MEOHP
MECCP
17.30
67.57
46.33
65.30
DiNP
7OH-MMeOP
7OXO-MMeOP
7CX-MMeOP
2,356
2,356
2,356
3.06 (2.81 - 3.34)
10.84 (10.00 - 11.75)
60.18
20.92
78.31
BPA
2,356
1.54 (1.48 - 1.91)
6.37
Triclosan
2,356
0.75 (0.61 - 1.18)
315.41
PFNA
PFDA
PFUnDA
PFDoDA
PFHxS
PFHpA
PFOA
PFOS
2,393
2,393
2,381
1,083
2,393
1,748
2,393
2,393
0.54 (0.53-0.55)
0.26 (0.25-0.27)
0.21 (0.20-0.22)
0.05 (0.04-0.06)
1.31 (1.30-1.32)
0.03 (0.01-0.04)
1.61 (1.60-1.62)
5.24 (5.23-5.25)
1.33
0.60
0.53
0.08
3.66
0.10
3.96
12.00
Phenols
PFASs
14.49 (13.23 - 15.87)
9.73 (8.86 - 10.68)
14.25 (13.03 - 15.58)
6.82 (6.14 - 7.58)
Natural
hormones
Estrogen
Testosterone
Thyroids. etc.
EDCs
“Xenoestrogens”
Anti-androgens
Phthalates
1st trimester DiNP exposure increase the risk
for shorter AGDas in 196 SELMA boys (21m)
OR
(95% CI)
10
1
Bornehag et al., 2015
0,1
1st ref 2nd
3rd
MEP
MEP
4th 1st ref 2nd
3rd
MBP
MBP
4th 1st ref 2nd
3rd
MBzP
MBzP
4th 1st ref 2nd
3rd
4th 1st ref 2nd
3rd
4th
DEHPsum
DiNPsum
DEHPsum
DiNPsum
Phthalate metabolites in quartiles
Replacement of phthalates in PVC
?
DINCH
Non-phthalate
DiNP
DEHP
1990
2000
2010
2015
Replacement of phthalates in PVC
?
DINCH
Non-phthalate
Greenscreen 2012
Campioli et al., 2015
DiNP
Lee et al., 2001
Lee et al., 2006
Borch et al., 2004
DEHP
Clevell et al., 2013
Boberg et al., 2011
Hannas et al., 2011
Bornehag et al., 2015
Axelsson et al., 2015
Foster et al., 2005
# studies
Swan et al., 2005
Gray et al., 2000
1990
2000
Swan et al., 2015
Bustamente al., 2013
Suzuki et al., 2012
2010
2015
DINCH/MINCH vs. PPAR expression
Campioli et al., 2015
1st trimester urinary levels in
2,355 SELMA mothers
DEHP
DiNP
BBzP
Need for better
procedures for how
chemicals are replaced
and how new molecules
are introduced on the
market
Natural
hormones
Estrogen
Testosterone
Thyroids. etc.
EDCs
PFASs
Livsmedelsverkets inventering visar
att upp till 66 vattentäkter i landet
kan vara kontaminerade med
PFAS från brandskum
Landets länsstyrelser har identifierat
över 500 platser där yt- och grundvatten kan ha förorenats av
kemikalier från bland
annat brandskum
Sveriges Radio 16 maj 2015
Low birth weight & Centile crossing
Body weight
Macrosomia
IUGR***
Median
IUGR
Birth Wean
Adult
Reglering av PFAS
Sedan juni 2008 är det förbjudet, med vissa
undantag, att använda PFOS och ämnen som
kan brytas ned till PFOS i kemiska produkter
och varor inom EU. Sedan 2009 är PFOS
inkluderad i Stockholmskonventionen för
persistenta organiska miljögifter samt FNs
LRTAP-konvention.
För PFOA och övriga PFAS-ämnen finns det
idag inga restriktioner.
Thank you!
Vandenberg et al., 2013, Reproductive Toxicology
Regulatory decision and research on EDCs
have to be based on principles of
endocrinology!