Brussels, October 2001 EU-Japan-Korea-USA Current State of Knowledge about Electromagnetic Fields, Mobile Telephony and Health [email protected].

Brussels, October 2001 EU-Japan-Korea-USA

Current State of Knowledge about

Electromagnetic Fields, Mobile Telephony and

Health

Current State of Knowledge about

Electromagnetic Fields, Mobile Telephony and

[email protected]@piom.u-bordeaux.fr


Frequency SpectrumFrequency SpectrumFrequency SpectrumFrequency Spectrum

1 GHz


Scientific approachesScientific approaches

Biological modelsDosimetry

Biological modelsDosimetry

animalsanimals

cellscells

FoundationsFoundations

epidemiologyepidemiology

humanshumans


Biophysicalintercation

Biochemical changes

Biological effect

Health effect


Definition of SARDefinition of SAR

• SAR: specific absorption rate

• SAR: rate of power absorption per unit of mass (watt / kilogramme; W/kg)

• SAR is proportional to the temperature increase in the tissue

• SAR: specific absorption rate

• SAR: rate of power absorption per unit of mass (watt / kilogramme; W/kg)

• SAR is proportional to the temperature increase in the tissue


Thermal versus nonthermalThermal versus nonthermal

• A ‘ thermal ’ biological effect is due to an increase in temperature at high SAR level

• A ‘ nonthermal ’ effect occurs at low SAR level with a negligible input of power and no temperature increase

• At medium SAR level the thermoregulation system prevents any temperature increase. ‘Athermal’ effects might occur due to stress.

• A ‘ thermal ’ biological effect is due to an increase in temperature at high SAR level

• A ‘ nonthermal ’ effect occurs at low SAR level with a negligible input of power and no temperature increase

• At medium SAR level the thermoregulation system prevents any temperature increase. ‘Athermal’ effects might occur due to stress.


Mobile telephones / base stationsMobile telephones / base stations• Handsets

- medium-level: up to 1/2 of guidelines- head-only exposure (so far)- SAR < 1.6-2 W/kg

• Base stations - low-level: often < guidelines / 10,000 - whole-body exposure- SAR < 0.08 W/kg

• Handsets - medium-level: up to 1/2 of guidelines- head-only exposure (so far)- SAR < 1.6-2 W/kg

• Base stations - low-level: often < guidelines / 10,000 - whole-body exposure- SAR < 0.08 W/kg


Sources of scientific informationSources of scientific information

• Peer-reviewed articles

• Review articles

• Reports (COST 244bis, Stewart ’s group,

Zmirou ’s group, FDA, etc.)

• Monographs (WHO, IARC, ICNIRP, etc.)

• Peer-reviewed articles

• Review articles

• Reports (COST 244bis, Stewart ’s group,

Zmirou ’s group, FDA, etc.)

• Monographs (WHO, IARC, ICNIRP, etc.)


WHO databaseWHO database

• Cancer relevant or related• completed ongoing total

epidemiology 8 18 26bioassays 6 8 14sensitized in vivo 11 7 18acute in vivo 22 5 27in vitro 50 26 76

Total 97 64 161

• Cancer relevant or related• completed ongoing total

epidemiology 8 18 26bioassays 6 8 14sensitized in vivo 11 7 18acute in vivo 22 5 27in vitro 50 26 76

Total 97 64 161


WHO databaseWHO database

• Non cancer• completed ongoing total

epidemiology 4 0 4human 45 21 66acute in vivo 32 10 42in vitro 15 10 25

Total 96 41 137

• Non cancer• completed ongoing total

epidemiology 4 0 4human 45 21 66acute in vivo 32 10 42in vitro 15 10 25

Total 96 41 137


Epidemiology 1/2Epidemiology 1/2• Study of the link between exposure and

disease– mobile telephony:

3 case-control (Hardell 1999, Muscat 2000, Inskip 2001) and 2 cohort studies (Morgan 2000, Johanson 2001)

– Main focus on brain cancer– Negative results

but link with laterality of use?

• Limited by exposure assessment, evolving technology, short latency, etc.

• Study of the link between exposure and disease– mobile telephony:

3 case-control (Hardell 1999, Muscat 2000, Inskip 2001) and 2 cohort studies (Morgan 2000, Johanson 2001)

– Main focus on brain cancer– Negative results

but link with laterality of use?

• Limited by exposure assessment, evolving technology, short latency, etc.


Epidemiology 2/2Epidemiology 2/2

• Ongoing large case-control questionnaire study led by IARC and funded in part by EU: Interphone

• Head and neck tumours: glioma, meningioma, acoustic neurinoma, and parotid gland malignant tumours

• 14 countries involved• Preliminary exposure assessment study in

progress• Results expected by 2004?

• Ongoing large case-control questionnaire study led by IARC and funded in part by EU: Interphone

• Head and neck tumours: glioma, meningioma, acoustic neurinoma, and parotid gland malignant tumours

• 14 countries involved• Preliminary exposure assessment study in

progress• Results expected by 2004?


Human laboratory studiesHuman laboratory studies

• Cognition

• Sleep

• EEG

• Blood pressure

• Subjective symptoms

• etc.

• Cognition

• Sleep

• EEG

• Blood pressure

• Subjective symptoms

• etc.


Cognition Cognition

• Thuroczy 1997: cerebral circulatory disturbances, alteration of electrical activity

• Freude 1998, 2000: Slow brain-wave potential influenced in visual monitoring tasks

• Preece 1999: decrease in choice reaction times

• Koivisto 2000: decreased response times

• Lee 2001: mobile telephone users performed better in 1 out of 3 attention tests

• Thuroczy 1997: cerebral circulatory disturbances, alteration of electrical activity

• Freude 1998, 2000: Slow brain-wave potential influenced in visual monitoring tasks

• Preece 1999: decrease in choice reaction times

• Koivisto 2000: decreased response times

• Lee 2001: mobile telephone users performed better in 1 out of 3 attention tests


SleepSleep

• Mann & Röschke 1996: alterations in sleep onset latency, REM sleep, EEG during REM sleep

• Wagner 1998: no alterations in sleep onset latency, REM sleep duration

• Borbély 1999: decreased waking duration, EEG increase in non-REM sleep

• Huber 2000: EEG increase in non-REM sleep

• Mann & Röschke 1996: alterations in sleep onset latency, REM sleep, EEG during REM sleep

• Wagner 1998: no alterations in sleep onset latency, REM sleep duration

• Borbély 1999: decreased waking duration, EEG increase in non-REM sleep

• Huber 2000: EEG increase in non-REM sleep


EEGEEG

• Reiser 1995: increase power 9.75-32 Hz

• Röschke & Mann 1997: No effects

• Hietanen 2000: statistically significant changes

• De Seze 2000: alterations of EEG patterns

• Krause 2000: Increase power in 8-10 Hz during memory task

• Reiser 1995: increase power 9.75-32 Hz

• Röschke & Mann 1997: No effects

• Hietanen 2000: statistically significant changes

• De Seze 2000: alterations of EEG patterns

• Krause 2000: Increase power in 8-10 Hz during memory task


Blood pressureBlood pressure

• Braune 1998: increased resting blood pressure

• Lindholm, ongoing: no effects so far

• Braune 1998: increased resting blood pressure

• Lindholm, ongoing: no effects so far


Subjective symptomsSubjective symptoms

• Oftedal, 2000; Sandström, 2001:

warmth on the ear, headaches, etc.

• Koivisto, 2001: no association between symptoms

and exposure (healthy subjects)

• Hietanen, 2001: no association between symptoms

and exposure (hypersensitive subjects)

• Oftedal, 2000; Sandström, 2001:

warmth on the ear, headaches, etc.

• Koivisto, 2001: no association between symptoms

and exposure (healthy subjects)

• Hietanen, 2001: no association between symptoms

and exposure (hypersensitive subjects)


Animal models: in vivoAnimal models: in vivo


3 types of exposure systems3 types of exposure systems


Head-only exposureHead-only exposure

Loop antenna


Whole-body exposure systemWhole-body exposure system

ITIS


Head-mainly exposureHead-mainly exposure


Cancer in vivo studiesCancer in vivo studies

• Bioassays

• Grafted tumours

• Sensitized models (carcinogens, ionizing

radiation, genetic factors, etc.)

• Genotoxicity

• Bioassays

• Grafted tumours

• Sensitized models (carcinogens, ionizing

radiation, genetic factors, etc.)

• Genotoxicity


2-year bioassays2-year bioassays

• Adey

1999: 836.55 MHz, TDMA

2000: 836.55 MHz, FM

Fisher 344 rats: No Effects

• Zook

2000: 850 MHz, MiRS - TDMA

850 MHz, FM

Sprague Dawley rats: No Effects

• Adey

1999: 836.55 MHz, TDMA

2000: 836.55 MHz, FM

Fisher 344 rats: No Effects

• Zook

2000: 850 MHz, MiRS - TDMA

850 MHz, FM

Sprague Dawley rats: No Effects


2-year bioassays: ongoing2-year bioassays: ongoing

• Roti Roti – 847.74 MHz, CDMA, 835.62 MHz, FM – Fisher 344 rats

• Anderson– 1616 MHz, IRIDIUM, Fisher 344 rats

• Dasenbrock– GSM-900, and 1800, B6C3F1 mice

• Dotti– GSM-900, and 1800; Wistar rats

• NIEHS, planned

• Roti Roti – 847.74 MHz, CDMA, 835.62 MHz, FM – Fisher 344 rats

• Anderson– 1616 MHz, IRIDIUM, Fisher 344 rats

• Dasenbrock– GSM-900, and 1800, B6C3F1 mice

• Dotti– GSM-900, and 1800; Wistar rats

• NIEHS, planned


Grafted tumoursGrafted tumours

• Salford, 1993: 915-MHz, CW and AM,

up to 8.3 W/kg, Fisher rats,

glioma injection in brain:

No effect on tumour growth

• Roti Roti, 1999: 835.62-MHz FM or 847.74-MHz

CDMA, 0.75 W/kg, glioma injection in brain:


• Salford, 1993: 915-MHz, CW and AM,

up to 8.3 W/kg, Fisher rats,

glioma injection in brain:


• Roti Roti, 1999: 835.62-MHz FM or 847.74-MHz

CDMA, 0.75 W/kg, glioma injection in brain:



Chemically-induced tumoursChemically-induced tumours• Chagnaud, 1999: GSM-900, whole-body,

BP- induced tumors: No effects on tumour latency or survival nor on lymphocyte subpopulations,

• Shirai, 1999: local 923-MHz exposure, rat liver carcinogenesis chemically-induced : No effects.

• Adey, 1999, 2000: ENU-initiated brain tumors in Fisher 344 rats; 836.55 MHz, TDMA or FM: No effects on tumour growth.

• Shirai: ENU-initiated brain tumors, 1.5 GHz ongoing

• Chagnaud, 1999: GSM-900, whole-body, BP- induced tumors: No effects on tumour latency or survival nor on lymphocyte subpopulations,

• Shirai, 1999: local 923-MHz exposure, rat liver carcinogenesis chemically-induced : No effects.

• Adey, 1999, 2000: ENU-initiated brain tumors in Fisher 344 rats; 836.55 MHz, TDMA or FM: No effects on tumour growth.

• Shirai: ENU-initiated brain tumors, 1.5 GHz ongoing


DMBA -induced tumorsDMBA -induced tumors

• Rat model of mammary tumors:- Anane 1999, 2000: GSM-900 and -1800, whole-body, several SAR levels- Bartsch 2001: GSM-900, whole-body, low SAR level: 0.1 W/kg3 one-year studies: No delay in onset of malignant tumors

• Perform A: Hruby, GSM-900, several SAR levels: ongoing

• China; Chiang, ongoing

• Rat model of mammary tumors:- Anane 1999, 2000: GSM-900 and -1800, whole-body, several SAR levels- Bartsch 2001: GSM-900, whole-body, low SAR level: 0.1 W/kg3 one-year studies: No delay in onset of malignant tumors

• Perform A: Hruby, GSM-900, several SAR levels: ongoing

• China; Chiang, ongoing


Appearance of first malignant tumourAppearance of first malignant tumour

0

.2

.4

.6

.8

1

0 20 40 60 80 100

Time (days)

1.4 W/kg

Sham

P = 0.22

DMBA

GSM-1800

60 rats/group


DNA fragmentationDNA fragmentation

• Increased DNA fragmentation reported by Lai and Singh 1995, 1996, (comet assay) in rats exposed to 2.45-GHz pulsed fields

• Failure of a replication study by Roti Roti 1999

• Negative results in an analog mobile-phone study by Tice & Hook, 1999

• Negative results in a GSM-900 study by Lagroye and Anane, 2000

• Increased DNA fragmentation reported by Lai and Singh 1995, 1996, (comet assay) in rats exposed to 2.45-GHz pulsed fields

• Failure of a replication study by Roti Roti 1999

• Negative results in an analog mobile-phone study by Tice & Hook, 1999

• Negative results in a GSM-900 study by Lagroye and Anane, 2000


B

T

60

40

20

00 5 10 15 20

% lymphoma in transgenic mice

time (months)

Transgenic miceTransgenic mice

• Repacholi 1997• Large effect but:

– Exposure system?– Transgenic model?– Interpretation?

• Replication– Australia– Italy

• Repacholi 1997• Large effect but:

– Exposure system?– Transgenic model?– Interpretation?

• Replication– Australia– Italy

Sham

Exposed


Non-cancer in vivo studiesNon-cancer in vivo studies

• Behaviour (only at high SAR levels)

• Hearing

• Memory and learning

• Blood Brain Barrier

• Heat Shock Proteins

• etc.

• Behaviour (only at high SAR levels)

• Hearing

• Memory and learning

• Blood Brain Barrier

• Heat Shock Proteins

• etc.


HearingHearing

• Work of the Marino and Aran groups have yielded

negative results on alterations of the functions of

the inner ear

• More research in progress within the European

GUARD programme

• Work of the Marino and Aran groups have yielded

negative results on alterations of the functions of

the inner ear

• More research in progress within the European

GUARD programme


Memory and learningMemory and learning

• Lai 1994: decreased learning in 12-arm maze, whole-body exposure to pulsed fields

• Sienkiewicz 2000, GSM 900, whole-body, low SAR: negative

• Dubreuil 2001: GSM 900, head only: negative

• Replication by Cobb, ongoing: negative so far

• Thuroczy, Sienkiewicz & Cassel : ongoing

• Long-term memory, Nagawa: negative

• Lai 1994: decreased learning in 12-arm maze, whole-body exposure to pulsed fields

• Sienkiewicz 2000, GSM 900, whole-body, low SAR: negative

• Dubreuil 2001: GSM 900, head only: negative

• Replication by Cobb, ongoing: negative so far

• Thuroczy, Sienkiewicz & Cassel : ongoing

• Long-term memory, Nagawa: negative


Blood-brain-barrier BBBBlood-brain-barrier BBB

• Persson & Salford 1997: increased BBB permeability at low SAR levels

• Fritze 1997: reversible effect seen only at high SAR

• Tsurita 2000: no effect even at high SAR

• Aubineau 2001: effect at 2 W/kg and inflammation of the dura mater. Ongoing search for threshold

• Mason: replication of Persson & Salford ’s data: ongoing

• Persson & Salford 1997: increased BBB permeability at low SAR levels

• Fritze 1997: reversible effect seen only at high SAR

• Tsurita 2000: no effect even at high SAR

• Aubineau 2001: effect at 2 W/kg and inflammation of the dura mater. Ongoing search for threshold

• Mason: replication of Persson & Salford ’s data: ongoing


Heat Shock Proteins HSPHeat Shock Proteins HSP

• de Pomerai 2000

• Transgenicnematodes- 700 MHz CW- Low SAR

• Increase in HSPexpression

• de Pomerai 2000

• Transgenicnematodes- 700 MHz CW- Low SAR

• Increase in HSPexpression


Cellular models: in vitroCellular models: in vitro


In vitro: exposure systemsIn vitro: exposure systems

Petri dishes


In-vitro studies (1/3)In-vitro studies (1/3)

• Completed Ongoing TotalCancer 38 23 61Non-Cancer 36 19 55

• Genotoxicity and DNA breaksMicronuclei, SCE, chromosome aberrationsObe, Maes & Verschaeve, Eberle, Tice, Roti Roti, Meltz, Scarfi, etc.

• Proliferation and transformationFitzner, Kwee, Wobus, Lagroye, Bersani, etc.

• Completed Ongoing TotalCancer 38 23 61Non-Cancer 36 19 55

• Genotoxicity and DNA breaksMicronuclei, SCE, chromosome aberrationsObe, Maes & Verschaeve, Eberle, Tice, Roti Roti, Meltz, Scarfi, etc.

• Proliferation and transformationFitzner, Kwee, Wobus, Lagroye, Bersani, etc.


In vitro studies (2/3)In vitro studies (2/3)

• Gene expression- Leszczynski, ongoing: increased expression of hsp27 at 2 W/kg

• Enzyme activity: ODC- Byus, 1998, Litovitz,1997- replication by Billaudel & Naraala

• Signal transduction- Byus, 1984

• Gene expression- Leszczynski, ongoing: increased expression of hsp27 at 2 W/kg

• Enzyme activity: ODC- Byus, 1998, Litovitz,1997- replication by Billaudel & Naraala

• Signal transduction- Byus, 1984


In vitro studies (3/3)In vitro studies (3/3)

• Role of free radicals- Juutilainen

• Calcium- Bawin, Blackman, Meyer

• Role of co-factors (UV, etc.)??

• Role of free radicals- Juutilainen

• Calcium- Bawin, Blackman, Meyer

• Role of co-factors (UV, etc.)??


MechanismsMechanisms

• Only well-established mechanisms is heating

• Others are being explored and tested in the

laboratory:

– Spatial and temporal temperature gradients

– Membrane rectification

– Absorption by magnetite

– Radical pair mechanisms

– etc.

• Only well-established mechanisms is heating

• Others are being explored and tested in the

laboratory:

– Spatial and temporal temperature gradients

– Membrane rectification

– Absorption by magnetite

– Radical pair mechanisms

– etc.


ConclusionsConclusions

• 200 studies related to mobile telephony have been completed / 100 more are ongoing.

• No constant reported positive finding at nonthermal levels

• Some key large-scale studies are in progress and their results should provide a solid database for risk assessment

• Known thermal effects are portable to 3G

• Assessment will have to be provided for both mobile telephones and base stations

• 200 studies related to mobile telephony have been completed / 100 more are ongoing.

• No constant reported positive finding at nonthermal levels

• Some key large-scale studies are in progress and their results should provide a solid database for risk assessment

• Known thermal effects are portable to 3G

• Assessment will have to be provided for both mobile telephones and base stations

Brussels, October 2001 EU-Japan-Korea-USA Current State of Knowledge about Electromagnetic Fields, Mobile Telephony and Health [email protected].

Documents

medium sar level

low sar level

high sar level

tissue sar

wkg slide

temperature increase

koreausa thermal

wholebody exposure sar