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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 1
Proof of principle testsconfirm
genotoxic potential of RF-EMF
Franz Adlkofer
VERUM - Foundation for Behaviour and EnvironmentMunich, Germany
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 2
Scientific approach
Exposure Search for Effects Investigations
50 HzExtremely low
frequency (ELF) fields
900 MHz1800 MHz
Radiofrequency(RF) fields
UMTS
Epidemiological studies
Animal studies
Studies on cell and
tissue culture
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 3
Risk Evaluation of Potential Environmental Hazards From Low Energy Electromagnetic Field Exposure Using
Sensitive in vitro MethodsA project funded by the European Union under the programme "Quality of Life and Management of Living Resources",
Key Action 4 "Environment and Health": QLK4-CT-1999-01574
STUK, Helsinki
Free University of BerlinInstitute for Plant Genetics,Gatersleben
University of Hannover
RZPD, Heidelberg
Medical University of ViennaVERUM Foundation, München
University of Bordeaux
INSALUD, Madrid University of Bologna
University of Milan
ETH Zürich
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 4
State of the art in 1999
Even though the biological effects of EMF exposure have been studied for the past 80 years, no consensus has been reached with respect to either findings or their interpretation.
The reasons for this are numerous: difficulties in measuring EMF exposure at the putative sites of actionvast differences in exposure and experimental conditionsthe complete lack of agreement on biological endpoints appropriate forstudy
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 5
Assumption and aim of the study
REFLEX was based on the assumption that a health risk due to EMF below the current safety limits can only exist if scientific proof of biological effects, relevant for the development of diseases, is obtained.
The aim of REFLEX was to find out whether or not EMF below the currentsafety limits cause cellular, sub-cellular or molecular alterations in isolated mammalian cells that are relevant for the development of diseases.
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 6
Pathogenesis of chronic diseases
All chronic diseases such as cancer and neurodegenerative disorders are of extremely diverse and heterogeneous origin and this variability is generated by alterations of the structure and function of genes, leading to changes in gene and protein expression. This may result in a number of critical cellular events for example deregulated cell proliferation or cell differentiation and suppressed or exaggerated programmed cell death (apoptosis). Their convergence is required for the development of chronic diseases.
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 7
Working hypothesis
The hypothesis that was to be tested in the REFLEX project assumed that no biological effects of relevance for the pathogenesis of chronicdiseases will be detected and that the present safety limits reliablyprotect EMF-exposed people from any health risk.
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 8
Exposure chamber
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 9
© Clinical Chemistry, Free University of Berlin
sham exposition gamma-radiation; 0,5 Gy
RF-EMF: 1800 MHz continuously; SAR 1.3 W/kg; 24h
Comet assay
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 10
Micronucleus test
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 11
ELF-EMF _ Age-dependent increase of DNA strand breaksin human fibroblasts
50 Hz sinus; 1000 µT; 5 min on / 10 min off
0
2
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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24hours of exposure
com
et ta
ilfac
tor %
ES1, male, 6 years of age
AN2, female, 14 years of age
IH9, female, 28 years of age
KE1, male, 43 years of age
HN3, female, 56 years of age
WW3, male, 81 years of age
© Division of Occupational Health, Medical University of Vienna
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 12
ELF-EMF _ Flux density-dependent increase of DNA strand breaks in human fibroblasts
50 Hz sinus; 15 h; 5 min on / 10 min off
dose dependency (15 h, intermittent)
µT magnetic flux density
com
et ta
ilfac
tor
%
0
2
4
6
8
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16
18
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10 20 30 40 50 60 70 80 90 100
200
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AlkalineNeutral
35 µT
© Division of Occupational Health, Medical University of Vienna
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 13
0123456789
10
sham exp. sham exp. sham exp. sham exp.
continuous intermittent 5´/10´ Pulse-modulation
intermittent 5´/10´
Talk-modulationcontinuous, SAR
1.2
Com
et ta
ilfac
tor %
4 h
16 h
24 h
GSM _ Exposure- and signal pattern-dependent increase of DNA strand breaks in human fibroblasts
1800 MHz; SAR 2 W/kg
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 14
GSM-RF-EMF _ Dose-dependent increase of DNA strand breaks
GSM Basic; 1950 MHz; 24 h; 5 min on / 10 min off
8,07,98,07,9
5,9
4,7
4,1
4,04,04,14,04,14,04,1
0
1
2
3
4
5
6
7
8
9
0,1 W/kg 0,3 W/kg 0,6 W/kg 1,0 W/kg 1,3 W/kg 1,6 W/kg 2,0 W/kg
SAR in W/kg
Com
et-T
ailfa
ctor
%
exp.
sham
© Division of Occupational Health, Medical University of Vienna
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 15
UMTS 1950 MHznormal human fibroblasts (cell line ES-1)exposure duration: 24 hoursexposure pattern: continuousSAR values: 0.05 W/kg, 0.1 W/kg, 0.5 W/kg, 1.0 W/kg and 2.0 W/kgendpoints: comet assay, micronucleus test
positive controls in the comet assay: UV light, 254 nm, 3 min, 800 µW/cm²
positive control in the micronucleus test: 25 nM Vincristin
UMTS _ Dose-dependency
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 16
Dose-dependent increase in DNA strand breaks after UMTS exposure
4,8 4,9 4,7 4,5 4,4
7,9
13,5
10,08,3 8,5
4,8 4,9 4,8 4,9 4,8
32,032,032,131,632,2
0,0
5,0
10,0
15,0
20,0
25,0
30,0
35,0
0,05 W/kg 0,1 W/kg 0,5 W/kg 1,0 W/kg 2,0 W/kg
Com
etAs
say
Tailf
acto
rin
%
scheinexponiert
positive Kontrolle
sham exposedexposednegative controlpositive control
© Division of Occupational Health, Medical University of Vienna
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 17
Dose-dependent increase of micronuclei after UMTS exposure
5,4 5,7 5,4 5,7 5,4
7,7
10,9 10,7 11,1 11,0
5,35,1
5,55,1
5,3
17,4 17,518,0
17,518,0
0,0
2,0
4,0
6,0
8,0
10,0
12,0
14,0
16,0
18,0
20,0
0,05 W/kg 0,1 W/kg 0,5 W/kg 1,0 W/kg 2,0 W/kg
Mic
ronu
cleu
s/50
0 B
NC
´sschein-exponiertexponiert
positive Kontrolle
sham exposedexposednegative controlpositive control
© Division of Occupational Health, Medical University of Vienna
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 18
UMTS 1950 MHznormal human fibroblasts (cell line ES-1)SAR value: 0.1 W/kgexposure pattern: continuousexposure duration: 4, 8, 12, 16, 20, 24 and 48 hoursendpoints: comet assay, micronucleus test
positive controls in the comet assay: UV light, 254 nm, 3 min, 800 µW/cm²
positive control in the micronucleus test: 25 nM Vincristin
UMTS _ Time-dependency
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 19
Time-dependent increase of DNA strand breaks after UMTS exposure
4,8 4,7 4,7 4,7 4,9 4,9 4,94,9
6,88,3
10,6
14,2 13,6 13,5
4,8 4,8 4,8 4,8 4,7 4,8 4,9
32,1 32,032,132,231,932,031,7
0,0
5,0
10,0
15,0
20,0
25,0
30,0
35,0
4 h 8 h 12 h 16 h 20 h 24 h 48 h
Com
etAs
say
Tailf
acto
rin
%scheinexponiertnegative Kontrollepositive Kontrolle
sham exposedexposednegative controlpositive control
© Division of Occupational Health, Medical University of Vienna
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 20
Time-dependent increase of micronuclei after UMTS exposure
5,3 5,1 5,3 5,2 5,25,7 5,35,3 5,1
7,9
11,0 10,9 10,9 11,1
5,2 5,1 5,2 5,0 5,35,1 5,3
17,017,6
17,2 17,1 17,4 17,5 17,2
0,0
2,0
4,0
6,0
8,0
10,0
12,0
14,0
16,0
18,0
20,0
4 h 8 h 12 h 16 h 20 h 24 h 48 h
MN
/500
BN
C´s
scheinexponiertnegative Kontrollepositive Kontrolle
sham exposedexposednegative controlpositive control
© Division of Occupational Health, Medical University of Vienna
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 21
UMTS 1950 MHzSAR value: 0.1 W/kgexposure duration: 16 hoursexposure pattern: 5 mon on / 10 min offcells: 3 different cell lines from human fibroblasts
UMTS _ Repetition with 3 different cell lines
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 22
Increase of DNA strand breaks in fibroblasts from threedifferent persons after UMTS exposure
4,6 4,9 5,2
13,1 13,8 14,1
4,6 4,9 5,3
35,2 35,938,0
0,0
5,0
10,0
15,0
20,0
25,0
30,0
35,0
40,0
45,0
ES-1 IH-9 HW-2
Com
etAs
say
Tailf
acto
rin
%
scheinexponiertnegative Kontrollepositive Kontrolle
sham exposedexposednegative controlpositive control
© Division of Occupational Health, Medical University of Vienna
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 23
Increase of micronuclei in fibroblasts from threedifferent persons after UMTS exposure
5,45,7
4,4
12,4
10,910,4
6,1
4,94,6
18,017,517,6
0,0
2,0
4,0
6,0
8,0
10,0
12,0
14,0
16,0
18,0
20,0
ES-1 IH-9 HW-2
Mic
ronu
cleu
s/50
0 B
NC
´sscheinexponiert
positive Kontrolle
sham exposedexposednegative controlpositive control
© Division of Occupational Health, Medical University of Vienna
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 24
RF-EMF _ Effects on gene and protein expressionGSM; 900 MHz; SAR 2 W/kg; 1h
from: Dariusz Leszczynski, Radiation and Nuclear Safety Authority (STUK), Finland
RF-EMF activatesgene expression (MAPK p38, PKC)protein expression (HSP27)metabolism (phosphorylation of HSP27)
Cells react to exposure with RF-EMF with stress the physiologicalrelevance of which has not been sufficiently investigated yet.
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 25
RF-EMF _ Contribution to pathogenesis 875 MHz; SAR < 2 W/kg; minutes
Friedman et al. (2007) Mechanisms of short-term ERK activation by electromagnetic fields at mobile phone frequencies. Biochem J 405: 559-568 (The Weizman Institute of Science, Israel)
RF-EMF activates
NADH oxidase ROS gene damages?
matrix metalloproteinase Hb-EGF
ERK cascades signal transductioncell differentiationcell proliferationcoping with stressmetabolism
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 26
Summary of the REFLEX results
The results of the REFLEX study did not confirm our hypothesis which assumed that no biological effects of relevance for the pathogenesis of chronic diseases will be found below the existing safety limits. However, ELF-EMF below 100 µT and RF-EMF below 2 W/kg alter the structure and function of genes in different animal and human cells. We saw an
A significant increase of DNA strand breaks was observed in human fibro-blasts after GSM exposure at a SAR of 0.3 W/kg and after UMTS exposure at a SAR of 0.05 W/kg.
increase of single and double DNA strand breaks in human fibroblasts, HL60 cells and granulosa cells of rats, but not in human lymphocytes an increase of micronuclei and chromosome aberrations in human fibroblasts alterations in gene and protein expression of several cell types, especially in human fibroblasts, human endothelial cells and embryonic stem cells from mice
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 27
on the "reduction of electrosmog in wireless local networks":
"Thus it has been possible to show that mobile radio radiation can cause damage to genetic material, in particular in human white blood cells, whereby both the DNA itself is damaged and the number of chromosomes changed. This mutation can consequently lead to increased cancer risk. In particular, it could also be shown that this destruction is not dependent upon temperature increases, i.e. is non-thermal. ..."
Swisscom patent
International Publication Number: WO 2004/075583 A1
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 28
None of the single approaches in basic research, animal experiments and epidemiological studies is at present in the position to provide proof of a health risk caused by EMF with sufficient certainty. However, as the results from the three approaches complement each other, they strongly speak in favour of the assumption that a health risk could arise from ELF-EMF as well as from RF-EMF.
A risk to our health?
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V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 29
Genotoxic effects caused by mobile phone radiation in living cells in vitro speak in favour of a causality between the long-term use of mobile phones and the increase of a brain tumour risk.This in mind, we have to consider:
The Interphone study, although not published yet in a final report, found asignificantly increased risk for brain tumours in long-term users of mobilephones.
Causal or not? We do not know yet
Lennard Hardell recently reported in young people below 20 years of age amore than 5-fold increase in the risk for brain tumours at the side of thehead at which they used the mobile phone.
Causal or not? We do not know yet
Worst case scenario
V E R U MSTIFTUNG FÜR VERHALTEN UND UMWELT Genotoxic potential of RF-EMF - NIR and Health Workshop, Porto Alegre - May 18-19, 2009 - page 30
Available scientific data clearly demonstrate that biological effects of electromagnetic fields below the current safety limits are athermal by nature. Since current safety limits are based upon the assumption that athermal biological effects do not exist at all, the only possible conclusion is that they are invalid and do not protect people. Lowering the safety limits by a factor between 10-1 and 10-5 may be a first and easily to accomplish step to adjust the radiation intensity to the conditions of living organisms. In the long range, the development of adequate safety limits away from physical EMF effects towards biological EMF effects by independent researchers is a top priority.All-clear signals by the industry and their scientific advisers that deny possible health risks of people exposed to RF-EMF below the current safety limits do not have a sound basis. Therefore, national governments which are responsible for the health protection of their citizens are badly advised, if they back the safety limits and the all-clear signals.
Conclusions