Health C o u n c i l o f t h e Netherlands

Mobile phones and cancer

Part 2. Animal studies on carcinogenesis

Health Council of the Netherlands

Mobile phones and cancer

Part 2. Animal studies on carcinogenesis

JH

Gezondheidsraad
H e a l t h C o u n c i l of t h e N e t h e r l a n d s

Aan de staatssecretaris van Infrastructuur & Milieu

Onderwerp

: Aanbieding advies Mobile phones and cancer. Part 2. Animal studies
on carcinogenesis
Uw kenmerk : Ons kenmerk : U-8204/EvR/ts/673-N2
Bijlagen
: 1
Datum
: 5 september 2014

Geachte staatssecretaris.
Hierbij bied ik u het advies Hdobile phones and cancer. Part 2. Animal studies on
carcinogenesis aan. Het advies is opgesteld door de Commissie Elektromagnetische velden
en getoetst door de Beraadsgroep Gezondheid en omgeving van de Gezondheidsraad.
Het gebruik van het radiofrequente deel van het eleku-omagnetisch spectrum voor mobiele
telecommunicatie toepassingen biedt vele voordelen voor het dagelijks leven. De daannee
gepaard gaande blootstelling aan elektromagnetische velden leidt echter ook tot zorgen,
bijvoorbeeld dat er een verhoogde kans is op het krijgen van kanker.
De Commissie Elektromagnetische velden heeft systematische literatuurstudies uitgevoerd
van de epidemiologische en dierexperimentele gegevens over de relatie tussen blootstelling
aan radiofrequente elektromagnetische velden en kanker In ons advies dat injuni 2013 is
uitgebracht zijn de epidemiologische gegevens besproken. Het huidige advies bevat de
analyse van de dierexperimentele studies. De commissie concludeert op grond van deze
gegevens dat het uiterst onwaarschijnlijk is dat blootstelling aan radiofrequente elektromagnetische velden bij proefdieren kanker kan veroorzaken of de ontwikkeling van kanker kan
stimuleren.

Bezoekadres

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E-mail:

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16052

Gezondheidsraad
H e a l t h C o u n c i l of t h e N e t h e r l a n d s

Onderwerp

: Aanbieding advies Mobile phones and cancer Part 2.
Animal studies on carcinogenesis
Ons kenmerk : U-8204/EvR/ts/673-N2
Pagina
:2
Datum
: 5 september 2014

In een derde advies zal de commissie de bevindingen uit de eerste twee adviezen integreren
en bespreken in het licht van de classificatie van radiofrequente elektromagnetische velden
door het Intemational Agency for Research on Cancer (lARC) van de Wereldgezondheidsorganisade als "mogelijk kankerverwekkend bij mensen". Dat advies wordt begin volgend
jaar verwacht.

prof. dr. J.L. Severens,
vicevoorzitter

Bezoekadres

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Gezondheidsraad
H e a l t h C o u n c i l of t h e N e t h e r l a n d s

To the State Secretary for Infrastructure and the Environment

Subject

: Advisory report Mobile phones and cancer.
Part 2. Animal studies on carcinogenesis

Your reference
Our reference U-8204/EvR/ts/673-N2
1
Enclosure(s)
September 5, 2014
Date

Dear State Secretary,
I have the pleasure of presenting you the advisory report Mobile phones and cancer Part 2.
Animal studies on carcinogenesis. It has been drafted by the Electromagnetie Fields
Committee ofthe Health Council and reviewed by its Standing Committee on Health and
the Environment.
The use ofthe radiofrequency part of the electromagnetie specUum for mobile telecommunication purposes offers many benefits for daily life. The associated exposure to
electromagnetie fields, however, also leads to concems, for instanee on an increased risk of
cancer.
The Electromagnetie Fields Committee has performed systematic reviews of the
epidemiological data and the data from animal experiments on the relation between
exposure to radiofrequency electromagnetie fields and cancer. A report that was published
in June 2013 diseussed the epidemiological data. The current report contains the anaiysis of
the studies on animal experiments. The Committee concludes from this evidence that it is
highly uniikely that exposure to radiofrequency electromagnetie fields can cause or
stimulate the development of cancer in animals.

P.O.Box 1 6052

Visiting

Address

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Netherlands

Hague

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The

E-mail:

www.healthcouncil.nl

E.van.Rongen@gr.nl

Netherlands

Gezondheidsraad
H e a l t h C o u n c i l of t h e N e t h e r l a n d s

Subject

: Advisory report Mobile phones and cancer Part 2.
Animal studies on carcinogenesis
Our reference U-8204/EvR/ts/673-N2
2
Page
September 5, 2014
Date

In a third report the Committee will integrate thefindingsfrom the two previous reports and
discuss them in the light of the classification of radiofrequency electromagnetie fields by
the Intemadonal Agency for Research on Cancer (lARC) of the World Health Organization
as "possibly carcinogenic to humans". That report is expected early next year.
Kind regards,
(signed)
Prof. dr. J.L. Severens
Vice President

P.O.Box 1 6052

Visiting

Address

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The

E-mail:

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E.van.Rongen@gr.nl

Netherlands

Mobile phones and cancer
Part 2. Animal studies on carcinogenesis

to:
the State Secretary for Infrastructure and the Environment
the Minister of Economie Affairs
the Minister of Health, Welfare and Sport
No. 2014/22, The Hague, September 2014

The Health Council of the Netherlands, established in 1902, is an independent
scientific advisory body. Its remit is "to advise the government and Parliament on
the current level of knowledge with respect to public heaith issues and heaith
(services) research..." (Section 22, Health Act).
The Health Council receives most requests for advice from the Ministers of
Health, Welfare & Sport, Infrastructure & the Environment, Social Affairs &
Employment, Economie Affairs, and Educafion, Culture & Science. The Council
can publish advisory reports on its own inifiative. It usually does this in order to
ask attenfion for developments or trends that are thought to be relevant to
government policy.
Most Health Council reports are prepared by multidisciplinary committees of
Dutch or, sometimes, foreign experts, appointed in a personal capacity. The
reports are available to the public.
The Health Council of the Netherlands is a member of the European
Science Advisory Network for Health (EuSANH), a network of science
advisory biodies in Europe.

This report can be downloaded from www.healthcouncil.nl.
Preferred citation:
Health Council of the Netherlands. Mobile phones and cancer: Part 2. Animal
studies on carcinogenesis. The Hague: Health Council of the Netherlands, 2014;
publicadon no. 2014/22.
all rights reserved
ISBN: 978-94-6281-012-9

Contents

Samenvatfing /5
Summary 19
Introduction 23
Literature search 25
Data anaiysis 27
4
4.1
4.2
4.3

Results 31
RF alone 31
RF -1- carcinogenic agent 55
Implanted tumours 40
Quality assessment 43
Conclusions 47
References 53

Contents

13

A
B
C
D

Annexes 59
The Committee 61
Items used in the validity assessment 65
Experimental details 71
Abbreviafions 81

14

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Samenvatting

Waarom dit rapport?
De blootstelling aan radiofrequente elektromagnetische velden (RF EMV) is de
afgelopentientallenjaren aanzienlijk veranderd als gevolg van de snelle groei
van mobiele telecommunicatie, draadloos intemet en andere bronnen. Parallel
hieraan is de ongerustheid over mogelijk nadelige effecten op de gezondheid van
die blootstelling toegenomen. De classificatie door het International Agency for
Research on Cancer (lARC, een agentschap van de Wereldgezondheidsorganisatie) van RF EMV als 'mogelijk kankerverwekkend bij mensen' heeft die ongerustheid verder doen toenemen. Deze classificatie was vooral gebaseerd op de
resultaten van epidemiologische onderzoeken, aangevuld met die van onderzoeken aan proefdieren.
De commissie Elektromagnetische velden van de Gezondheidsraad heeft
besloten om een onafhankelijke systematische analyse uit te voeren van zowel de
epidemiologische als de experimentele gegevens. Hierbij wordt rekening gehouden met de wetenschappelijk kwaliteit van de onderzoeken. De analyse van de
epidemiologische gegevens is gepubliceerd in een rapport dat in 2013 is uitgebracht. Het huidige rapport bevat de analyse van de gegevens over carcinogenese
in proefdieren.

Samenvatting

15

Systematisch onderzoek
De systematische zoektocht die de commissie heeft uitgevoerd leverde 54 proefdier onderzoeken naar carcinogenese door blootstelling aan RF velden op. In 23
onderzoeken is gekeken naar het effect van blootstelling aan alleen RF velden.
Daarbij is een verscheidenheid aan diermodellen en tumortypen gebruikt, evenals een aantal verschillende typen RF velden, hoewel de nadruk wel lag op het
type signalen zoals dat wordt gebruikt in de huidige mobiele telecommunicatie.
In de onderzoeken is gekeken naar blootstelling variërend van enkele weken tot
twee jaar, en de gezondheidstoestand van de dieren is doorgaans levenslang
gevolgd. Daarnaast zijn er 24 onderzoeken waarin een mogelijke beïnvloeding
van blootstelling aan RF velden is onderzocht op de carcinogenese door verschillende bekende kankerverwekkende stoffen. En verder zijn er nog zeven onderzoeken waarin het effect van blootstelling aan RF velden op de groei van
geïmplanteerde tumoren is onderzocht. Deze gegevens hebben bij elkaar betrekking op een breed scala van experimentele omstandigheden en kunnen dus een
redelijk goed inzicht geven in de mogelijke effecten van blootstelling aan RF
EMV op carcinogenese in knaagdieren.
Geen effecten in de meeste onderzoeken
De kwaliteit van de onderzoeken is geanalyseerd door na te gaan of de inteme of
externe validiteit van de onderzoeken beïnvloed zou kunnen zijn. Uit deze analyse bleek dat de meeste onderzoeken goed opgezet zijn. Bij zeven onderzoeken
leidden verschillende oorzaken tot een negatieve waardering en die onderzoeken
zijn derhalve verder niet meegenomen in de analyse. In vijf van de resterende 47
onderzoeken werd een toename gevonden van verschillende typen tumoren. Vier
van deze onderzoeken waren nauw verwant en uitgevoerd door dezelfde onderzoeksgroep. Deze gebruikte tamelijk hoge blootstellingsniveaus en de auteurs
konden niet uitsluiten dat er een invloed was van warmteontwikkeling. In het
vijfde onderzoek werd een toename gevonden van chemisch opgewekte longtumoren, maar in het onderzoek ontbrak de juiste controlegroep. De auteurs
beschouwen het als een voorlopig onderzoek dat herhaald moet worden. De commissie heeft het in de analyse een laag gewicht gegegeven. In drie andere onderzoeken is een lager aantal tumoren gevonden in dieren die aan RF EMV waren
blootgesteld in vergelijking met de controle groep. Hiervoor is geen logische verklaring te geven, en deze gegevens worden daarom als toevalstreffers
beschouwd. Dat kan ook de verklaring zijn voor de positieve bevindingen in de

16

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

eerder beschreven onderzoeken. In het merendeel van de onderzoeken, 39 in
totaal en met een scala aan tumortypen en verschillende soorten proefdieren, is
echter geen effect van blootstelling aan RF EMV gevonden op carcinogenese.

Conclusies
Op grond van de resultaten van de proefdieronderzoeken die in deze systematische analyse zijn opgenomen concludeert de Commissie dat het hoogst onwaarschijnlijk is dat langdurige continue of herhaalde blootstelling aan RF EMV de
ontwikkeling van van kanker kan veroorzaken of bevorderen.
De Commissie vindt het op dit moment niet nuttig om voorstellen te doen voor
nader proefdieronderzoek naar carcinogenese door radiofrequente elektromagnetische velden. Er is momenteel een groot, goed opgezet onderzoek hiemaar
gaande in de Verenigde Staten. Voordat er mogelijk nieuwe voorstellen voor
onderzoek worden gedaan moeten de resultaten van dit onderzoek, die naar verwachting in 2016 worden gepubliceerd, worden afgewacht.

Samenvatting

17

18

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Summary

Why this report?
Exposure to radiofrequency electromagnetie fields (RF EMF) has considerably
changed in the past decades, as a result of the fast growth of mobile
telecommunication, wireless internet access and other sources. This has
increased general anxiety about possible adverse heaith effects of such
exposures. The classification of RF EMF as 'possibly carcinogenic in humans'
by the International Agency for Research on Cancer (lARC) in 2012 has further
sparked these fears. This classification was primarily based on epidemiological
data, with additional support from animal studies.
The Electromagnetie Fields Committee of the Health Council of the Netherlands
decided to perform an independent systematic review of both the epidemiological and experimental data, taking into account the scientific quality of the
studies. The anaiysis of the epidemiological data has been published in a report
issued in 2013. The current report contains the anaiysis of the data on
carcinogenesis in experimental animals.

Systematic search
The systematic literature search performed by the Committee revealed a
substantial body of 54 animal studies on the carcinogenesis of exposure to RF

Summary

19

fields. In 23 studies the effect of exposure to RF EMF alone has been
investigated. A variety of animal models and tumour types has been used, as well
as a number of different types of RF signals, although the focus has been on the
types of signals used in modern mobile telecommunication. Exposure has been
from several weeks up to two years, and the follow-uptimegenerally lifelong. In
addition, 24 studies investigated the modulating effects of RF exposure on
carcinogenesis induced by various well-known carcinogenic compounds, and
another seven studies the effect of RF exposure on the growth of implanted
tumours. These data cover a wide range of experimental situations and may thus
provide a reasonably well insight into the effects of RF exposure on
carcinogenesis in rodents.

No effect in most studies
The anaiysis of the quality of the studies, as reflected in the possibility that the
internal or external validity of the studies could be affected, showed that most of
the studies are of adequate design. However, in seven studies various issues
resulted in a negative appraisai and these studies were consequently excluded
from the overall anaiysis. Of the remaining 47 studies, five showed an inerease in
the incidence of several types of tumours. Four of these were closely linked and
performed by the same research group. They used rather high exposure levels
and could not exclude thermal effects. The fifth study found an increased
incidence of chemically-induced lung tumours, but lacked a proper control
group. The authors consider it to be a preliminary study that needs to be
replicated. The Committee has given it a low weight in the overall anaiysis. A
further three studies found a decreased rate of tumour growth in RF EMF
exposed animals. There is no logical explanation for this, and therefore these are
considered to be chance results. This might also be the case for the positive
associations observed in the studies described above. In the majority of the
studies, however, 39 in total, deseribing experiments on a range of tumour types
and in different species, no effect on carcinogenesis has been observed.

Conclusions
This has led the Committee to eonelude that, on the basis of the results of the
animal studies presented in this systematic review, it is highly uniikely that longterm continuous or repeated exposure to RF EMF may have initiating or
promoting effects on the development of cancer.

20

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

The Committee considers it not useful at this time to propose further animal
studies into RF carcinogenesis. There is currently a large, well-designed animal
carcinogenesis study ongoing in the USA. Before recommending further
research, the outcome of this study, expected in 2016, has to be awaited.

Summary

21

22

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Chapter

1
Introduction

The fast and extensive growth of mobile telephony and the resulting change in
exposure of people to radiofrequency electromagnetie fields (RF EMF) has
sparked the fear of possible adverse effects resulting from such exposure.
Especially dreaded are possible carcinogenic effects. Many studies into this have
been performed in the past decades, and on the basis of the available results the
Intemational Agency for Research on Cancer (lARC) of the World Health
Organization (WHO) has classified RF EMF in 2010 as 'possibly carcinogenic
for humans' (class 2B).' This classification was primarily based on the results of
epidemiological studies into the relation between mobile phone use and the risk
of various types of brain tumours, and on some data of experimental studies with
animals.2
The Electromagnetie Fields Committee of the Health Council of the Netheriand
(designated further in this report as 'the Committee') decided to perform its own,
independent, systematic review of the literature on this subject. In a first report it
has described the epidemiological data^, while the present report discusses the
outeomes of experimental animal studies. Data collection, extraction, and
anaiysis have been done in a predetermined systematic way.

Introduction

23

Exposure
Exposure to RF EMF is usually expressed in terms of the SAR, the Specifie
Absorption Rate. This is the rate of energy absorption by an exposed object per
unit of mass. It is expressed in watts per kilogram (W/kg). Energy absorption in
the body can lead to heating, and too much heating can be a heaith hazard.
Therefore exposure limits have been developed. In the Netherlands generally the
limits of the International Commission for Non-ionizing Radiation Protection
(ICNIRP) are observed.^^ -phe exposure limits for the frequency range of 100
kHz - 10 GHz are based upon limitation of heating of the body, and therefore
expressed in terms of SAR. For exposure of the entire body, the limit for the
general population is an SAR of 0.08 W/kg. This roughly compares to the
amount of heating induced by drinking a cup of hot liquid every 2 hours and will
not lead to an inerease in the core temperature of the body. For local exposure,
higher SAR values are allowed. The most relevant for the use of a mobile phone
is the SAR limit of 2 W/kg for exposure of the head. Use of a mobile phone will
lead to an inerease in SAR which is highest close to the antenna of the phone.
The SAR specifications of a mobile phone provide the maximum SAR that can
be obtained averaged over a 10 g volume of tissue, when the phone is operating
at maximum power. Sustained exposure to an SAR of 2 W/kg (a situation that in
practice virtually never oceurs) will lead to a local temperature inerease in the
head of approximately 0.2 °C.63 Whole body exposure of rodents to an SAR of 25 W/kg can lead to the induction of thermoregulatory mechanisms^, but due to
differenees between rodents and humans in temperature regulation, dimensions
and frequency-dependent resonance effects this cannot be easily extrapolated to
humans.
This report
In Chapter 2 the literature search is described. Chapter 3 provides the methods
used in the data anaiysis. In Chapter 4 the results are presented, and Chapter 5
contains the discussion of the results.
The composition of the Committee at the time of writing of this report is given in
Annex A.
Annex B contains the items used in the validity assessment. In Annex C the
experimental details of the included studies are provided. Annex D gives a list of
the abbreviations used in this report.

24

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Cliapter

Literature search

A literature search in PubMed was performed into the effect of exposure to
radiofrequency electromagnetie fields on the formation and growth of cancer,
using the foliowing search strategy:
(radiofrequency OR radio waves OR radio-waves OR cellphone* OR cell
phone* OR cellular *phone* OR mobile phone* OR cellular phone[MeSH
Terms] OR telephone, cellular[MeSH Terms]) AND (animal OR rat OR mouse
OR rats OR mice OR murine) AND (cancer OR carcinogen* OR tumour* OR
tumor* OR neoplasm* OR benign OR malignant OR malignancy) NOT ("in
viuo"[Publication Type] OR "in viü-o"[All Fields] OR hyperthermia OR ablaUon
OR imaging)
There were no restrictions on date and language. The search was performed on
September 13, 2012.
The total number of papers retrieved was 376. An additional search using
Related papers in PubMed brought up another 4 papers, which increased the total
number of papers to 380. Of these, 42 were on in vitro studies, 95 on therapy, 42
were reviews, 144 dealt with other subjects, 1 was in Chinese with only an
abstract available in English, 5 were comments, 1 was a reanalysis of another
paper, and 1 was a background paper. This left 49 papers to be included in the
anaiysis.

Literature search

25

A search in the EMF Portal using the key words 'Mobile Phone', 'cancer' and
'animal' did not produee any thus far undetected studies.
A search in Web of Science using the same keywords as with PubMed resulted in
132 papers. Of these, 10 were on in vitro studies, 1 was on therapy, 32 were
reviews, 6 were conference proceedings, 1 was a book and 51 were classified as
'other'. That left 31 relevant papers, of which 30 had already been retrieved with
PubMed.
One paper was obtained from another source.
So the total number of papers included in the anaiysis of this report is 51, divided
over different tumour types as listed in Table 1 (one paper includes two separate
studies).
Table I Number of studies per tumour type.
Type of tumour Number of
Number of
studies using
studies using
wildtype
wildtype
animals and no animals and
chemical orUV chemical orUV
induction
induction
Lymphoma
Skin tumour
Mammary
tumour
Liver tumour
CNS tumour
Sarcoma
Colon mmour
Multiple
tumours

26

Number of
studies using
tumour-prone
animals
(wildtype and
transgenic)
10
I
3

Number of
studies using
implanted
tumours in
wildtype
animals

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Total number
of studies

10

2
11
3
1
8

Chapter

Data anaiysis

The studies were extracted and analysed using the Gold Standard Publication
Checklist (GSPC) as basis.'* ^ The GSPC addresses a large number of items,
many of which were not considered relevant by the Committee for the current
anaiysis, while some items that are relevant for the specifie type of RF EMF
carcinogenesis studies in this report are missing from the GSPC. The Committee
therefore added a number of items, in particular several pertaining to the
dosimetry. Table 2 lists the items that were extracted from the papers.
Tal)le 2 Items extracted from the smdies.
Bacicground information
Funding sources
Conflicts of interest
Methods
Quarantine and acclimatisation period after
transportation to animal facility
Species
Sex
Age at the start of the experiment
Number of animals per experimental group
Sham, cage and positive controls
Intervention
Day and time of intervention within experiment
Type of intervention
Source of RF exposure

Data anaiysis

(wildtype or mmour-prone)
(altemative; animal weight)
(also power and sample size calculations)

(RF alone or RF + carcinogenic agent or effect
modifier)
(including frequency, pulsed or continuous wave)

27

Exposure duration and sehedule
Exposure system used
Exposure level

(dedicated to exposed target or whole body)
(local or whole-body SAR; extemal field
strength)
(measured or predicted (caleulated))

Determination of exposure level
Account for movement, growth in exposure level
Dmgs
(carcinogenic agent or effect modifier)
Restraint
(similar in exposed and control animals?)
Outcome
Deseription of parameters of interest
(are all parameters mentioned in the Introduction
and Material and Methods sections described?)
Blinding of staff to treatment modality
Deseription of the statisties used
Results
Blinding of staff in anaiysis
Deseription of the main results
Excluded animals
(number. and reasons why they were excluded)

Validity assessment
Internal validity
These data were used to assess the internal validity of the studies according to
five topics:
• Allocation to groups
• Blinding
• Data loss
• Reporting bias
• Other bias.
The assessment was performed by considering for each topic a number of
questions on the information presented in each publication. These questions, that
were formulated by the authors of the GSPC, are listed in Table B1 in Annex B.
External validity
The external validity is used to indicate to what extent the results of the studies
can be extrapolated to humans. For the extemal validation the Committee
developed a table with items to be considered for two topics: Animal
characteristies and Exposure. An important part of this evaluation is the

28

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

assessment ofthe quality of the exposure and exposure characterization. For
instanee, if the exposure is not well-described or the exposure level is not
reported, it is diffieult or even impossible to evaluate the study in terms of
relevance to the situation in humans. In the appraisai of the quality of the
dosimetry the Committee has taken into consideration that there has been
considerable progress in the past decades in the possibilities to aecurately
measure and caleulate the exposure. So the criteria for older studies were more
lenient than for more recent ones. This information is provided in Table B2 in
Annex B.
Both the internal and the extemal validity were assessed by two independent
assessors, and conflicts were solved by a third party. For each of the five topics
for internal validity and for each of the two topics for extemal validity the chance
that they would influenee the outcome of the assessment of the results of the
study was estimated as either high, low or unknown. In the next step, these
estimations were combined into an overall assessment for each individual study
of whether there is a chance that either the intemal or the extemal validity would
influenee the conclusions of the study. The results of these assessments were
used in the overall appraisai of the entire dataset.
A brief deseription of each study is given in Chapter 4 and the agreed scores for
the validity assessments are summarized in Table 3 in Chapter 5. They give an
impression of tiie internal and exteraal validity of each of the studies.

Data anaiysis

29

30

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Chapter

Results

In this chapter a brief deseription is given of the results of each of the selected
studies, organized first per treatment modality (RF alone, RF + carcinogenic
agent or implanted tumours) and then per tumour type and per type of animal
(wildtype, tumour-prone or Uansgenic). More details of the studies are provided
in Table Cl in Annex C. The reason for the primary organization per Ueatment
modality is because there is a fundamental difference between treatment with RF
alone, where the carcinogenic potential (cancer induction) of RF is investigated,
and treatment with RF and a carcinogenic agent or RF exposure of an implanted
tumour. The latter studies investigate the modulating potential of RF (cancer
modulation). Some studies fall in more than one category, either because they
investigate more than one tumour type, or because they study both exposure to
RF alone and exposure to a carcinogenic agent and RF. These studies are
diseussed under each heading.
4.1

RF alone

4.1.1

Lymphoma
Transgenic tumour-prone animals
Repacholi et al. (1997)* exposed transgenic lymphoma-prone female C57BL/
6NTac (suain ppG64 uansgenic for E[i-Piml) mice to a GSM 900 MHz signal.

Results

31

The animals were free roaming in their cages during exposure and the individual
SAR could vary (~500-fold!) from 0.008-4.2 W/kg. An inerease in lymphoma
incidence was observed in the exposed group, with an odds ratio of 2.4 (95%
confldence interval: 1.3-4.5). [The Committee notes that histopathology of
lymphoma was only performed on animals that died before the end of the
experiment. The lymphoma incidence in surviving animals is unknown, and this
is thus also the case for the overall lymphoma incidence.]
Two repetition studies were performed. These studies were not exact
replications, since in these studies the mice were restrained to obtain a more
uniform and better defined exposure and histopathological anaiysis was
performed on all animals. Utteridge et al. (2002)^ exposed female mice of the
same transgenic strain and of a wildtype strain to a GSM 900 MHz signal.
Instead of two exposure sessions of 30 min per day they had only one session
of 1 h, because of the effort to put the animals in the restrainers and the stress this
imposed on the mice. Exposure was at four SAR levels: 0.25, 1.0, 2.0 and 4.0
W/kg, neither of which resulted in any effects on lymphoma incidence in either
transgenic or wildtype mice.
The second repetition study was by Oberto et al. (2007).* They exposed male
and female mice from again the same transgenic strain to a GSM 900 MHz signal
using SARs of 1.4 or 4.0 W/kg. No effect on survival and on the incidence of
lymphomas or other tumours was observed.
Non-transgenic tumour-prone animals
Sommer et al. (2004)' exposed non-transgenic female AKR/J mice with a high
spontaneous lymphoma incidence to a GSM 900 MHz signal. The animals were
free roaming and the SAR of 0.4 W/kg therefore had rather large variations of +
40%. No effect of exposure was observed on lymphoma incidence and survival.
Using a similar study design, Sommer et al. (2007)'° exposed female AKR/J
mice to an UMTS signal, also at an SAR of 0.4 W/kg + 40%. Again no difference
in lymphoma incidence and survival was observed.
Lee et al. (2011)" also used the same mouse strain and exposed them
simultaneously to a CDMA and a WCDMA signal. The SAR was 4.0 W/kg, but
since the animals were free roaming, there was likely a considerable variation.
They also observed no difference in lymphoma incidence and survival.
Anghileri et al. performed several studies using female Ieo:OFI mice, a nontransgenic strain with a high spontaneous lymphoma incidence. In the first study
(Anghileri et al., 2005)'2 they exposed the mice to a GSM 800 MHz signal and
observed a decreased survival and increased lymphoma incidence.

32

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

In the second study (Anghileri et al. 2006)they exposed the mice to GSM
800 MHz or to a ferric-ATP complex (FeATP). FeATP is used by this group as a
promoter of carcinogenesis because it increases cellular calcium ion influx. A
similar aeeeleration of carcinogenesis by RF EMF and by FeATP was observed.
In the third study (Anghileri et al, 2009)''* the animals were injected with
calcium chloride, aluminium lactate or aluminium ciü-ate and exposed to a GSM
800 MHz signal. The chemical substances influenced the intracellular calcium
ion balance. A decreased survival and more lymphoma were observed in animals
exposed to RF and each of the substances, compared to exposure to the
substances alone. [The Committee notes that important data such as the exposure
level is missing from these studies; they are therefore diffieult to interpret.]
4.1.2

Skin tumour
Non-transgenic animals
Sanchez et al. (2006)'5 exposed hairless female rats (IFFA Creda) to GSM 900 or
1800 MHz signals, at SARs of 2.5 and 5 W/kg. In contrast to the control group
that was exposed to UV radiation, no histological alterations were observed in
the skin of the RF exposed animals.
In an experiment that was primarily aimed at studying the effect of RF
exposure on chemically-induced skin cancer (see 4.2.2), Paulraj and Behari
(2011)'6 exposed male Swiss mice to either 112 MHz EMF, amplitude
modulated at 16 Hz, at an SAR of 0.75 W/kg, or to 2.54 GHz at an SAR of 0.1
W/kg without the chemical induction. Neither type of exposure resulted in any
effect on skin tumours. [The Committee notes that the number of animals in this
study is not clear: the authors use an unspecified 'effective' number of animals in
their anaiysis.]

4.1.3

Mammary tumour
Non-transgenic tumour-prone animals
Szmigielski et al. (1982)''' exposed female C3H/HEA mice with a high
spontaneous mammary cancer incidence to 2450 MHz RFfieldswith a power
density of 5 or 15 mW/cm^, eorresponding to whole-body SAR levels of 2-3 and
6-8 W/kg, respectively. They observed a dose-dependent aeeeleration of
mammary cancer development resulting in shortening of life time. The authors
could not exclude thermal effects. [The Committee notes that whole-body

Results

33

exposure to the highest SAR level can certainly result in heating of the animals,
but also an SAR of 2 W/kg is already a significant systemic challenge.]
Three publications from the same US research group report on experiments
with mammary tumour-prone female CjH/HeJ mice. Toleret al. (1997)'*
exposed them to pulsed 435 MHz EMF at an SAR of 0.32 W/kg, Frei et al.
(1998)'9 and Frei et al. (1998)20 to 2,450 MHz EMF at SARs of 0.3-1.0 W/kg.
No effects on the number and growth of tumours were observed.
Jauchem et al. (2001)2' exposed the same mammary tumour-prone female
CjH/HeJ mice to an ultra wide band signal with a 40 kV/m peak, but an SAR of
only 0.0098 W/kg. They observed no effects of this exposure on mammary
tumour incidence and survival.
4.1.4

Central nervous system (CNS) tumour
Wildtype animals (not tumour-prone)
Adey et al. (1999)^2 exposed male and female Fischer 344 rats before and after
birth to an NADC 835 MHz signal at SARs of 0.33-0.53 W/kg. They observed a
redueed incidence of CNS tumours in the RF-exposed group.
In similar experiments but using another type of signal, FM 836 MHz at
SARs of 1.0 or 1.2 W/kg, Adey et al. (2000)23 ^id not observe any effect of RF
exposure on survival and CNS tumour incidence.
In an experiment primarily aimed at studying the effect of chemicallyinduced neurogenic tumours (see below) Zook and Simmens (2001)2'* exposed
male and female Sprague Dawley rats without the induetive agent to 860 MHz
pulsed or continuous-wave RF EMF, at SARs of 1.0 ± 0.2 W/kg. They observed
no effect of this exposure on the incidence of neurogenic or other tumours.
La Regina et al. (2003)25 investigated exposure of male and female Fischer
344 rats to an FDMA 835 MHz or CDMA 847 MHz signal at SARs of 1.3 ± 0.5
W/kg in the brain. No effect of either signal on CNS and other tumours was
observed.
Anderson et al. (2004)26 exposed male and female Fischer 344 rats before
and after birth to an 1.6 GHz Iridium* signal, at an SAR in the brain of 0.16 W/kg
(perinatal) and 0.16 or 1.6 W/kg (postnatal). No effect on survival was observed
in males, but in females survival was lower in the cage-controls. No effects were
observed on brain or other tumours.

Iridium; a mobile telecommunication signal used by the Iridium satellite system.

34

Mobile phones and eancer / Part 2. Animal studies on carcinogenesis

4.1.5

Multiple tumours
Wildtype animals (not tumour-prone)
Chou et al. (1992)2^ exposed male Sprague Dawley rats to 2450 MHz pulsed
EMF at SARs of 0.15-0.4 W/kg. They observed no overall effect on tumour
development, but found somewhat more primary malignant tumours in exposed
animals. There was no effect on benign tumours and on overall survival.
Ivanov et al. (2005)2* exposed inbred albino mice and adult C57B1/6 mice
(sex not specified) to 37 GHz RF EMF, at a power density of <10 mW/cm2. They
observed a decreased survival in C57B1/6 adults and offspring, and tumour
formation in albino mice. [The Committee notes that important information is
missing, such as the exposure level and why some animals are not included in the
anaiysis. Some groups had been exposed in previous, unspecified experiments.
Therefore this study cannot be interpreted.]
Smith et al. (2007)29 exposed male and female Han Wistar rats to GSM 900
MHz or DCS 1800 MHz signals at SARs of 0.44, 1.33 or 4.0 W/kg. They
observed no effect on survival and carcinogenesis.
Tillmann et al. (2007)3° exposed male and female B6C3F1/Cri BR mice to
GSM 902 MHz or DCS 1747 MHz signals at SARs of 0.4, 1.3 or 4.0 W/kg. They
observed no effect of the GSM signal, but a decreased number of tumours after
DCS exposure. These were, however, within the tumour rates of historical
controls.
Jin et al. (2011)3' exposed male and female Sprague Dawley rats
simultaneously to CDMA 848.5 MHZ and WCDMA 1950 MHz signals. The
SAR for each signal was 2 W/kg, so the combined SAR was 4 W/kg. There was
no effect of this exposure on carcinogenesis.
Transgenic animals
Saran et al. (2007)32 exposed transgenic, X-ray tumour-prone mice (CD-1
heterozygous for Patchedl) to GSM 900 MHz fields at a SAR of 0.4 W/kg. No
effect on survival and carcinogenesis was observed.

4.2

RF + carcinogenic agent
Unless indicated, studies listed in this section are all using non-transgenic
animals.

Results

35

4.2.1

Lymphoma
RF + X-rays
Heikkinen et al. (2001)33 exposed female CBA/S mice to X-rays to induce
lymphomas and other tumours. Restrained animals were subsequently exposed to
an NMT 902 MHz signal at an SAR of 1.5 W/kg, or to a GSM 902 MHz signal at
an SAR of 0.35 W/kg. No effects of these exposures on X-ray induced
lymphomas, other neoplasms or survival were observed.

4.2.2

Skin tumour
RF + 3,4 benzopyrene (BAP)
Szmigielski et al. (1982)'^ exposed male Balb/c mice treated with the skin
carcinogen 3,4 benzopyrene (also known as benzo(a)pyrene) (BAP) to 2450
MHz RFfieldswith a power density of 5 or 15 mW/cm2, eorresponding to
whole-body SARs of 2-3 and 6-8 W/kg, respectively. They observed aeeeleration
of skin cancer growth and mortality with both SAR levels. For simultaneous
treatment with RFfieldsand BAP this was dose-dependent. For treatment with
RFfields3 months prior to BAP treatment dose-dependence is not clear. The
authors could not exclude the oceurrenee of thermal effects. [Whole-body
exposure to the highest SAR level can certainly result in heating of the animals,
but also an SAR of 2 W/kg is already a significant systemic challenge.]
Szudinski et al. (1982)34 apparendy reported the same data as Szmigielski et
al. (1982)''' of exposures to power densities of 5 or 15 mW/cm2 (eorresponding
to SARs of 2-3 and 6-8 W/kg) during BAP application, and additionally exposed
groups of male Balb/c mice to a power density of 10 mW/cm2 (eorresponding to
an SAR of 4 W/kg) during 1, 2 or 3 months before BAP application. They report
an exposure duration-dependent aeeeleration of skin cancer development. [The
Committee notes that the highest SAR level could have resulted in heating of the
animals, but also an SAR of 2 W/kg is already a significant systemic challenge.]
RF + 7,12-dimethybenz[a]anthracene (DMBA)
A number of studies investigated the effect of RF exposure on skin cancer
induced by DMBA.

36

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Imaida et al. (2001)35 exposed female CD-1 mice to a 1.5 GHz TDMA signal
at an SAR of 2.0 W/kg and found no effect of this Ueatment on skin tumours.
Mason et al. (2001)3*^ u-eated female SENCAR mice with single or repeated
very short (10 sec) exposures to high-power 94 GHzfields(0.333 or 1 W/cm2).
No effect of these RF treatments on skin tumours were observed.
Huang et al. (2005)3'' exposed male ICR mice to a 849 or 1763 MHz signal at
an SAR of 0.4 W/kg. They also found no effect on skin tumours.
In an experiment of which the RF-alone exposure has been described above,
Paulraj and Behari (2011)'6 exposed DMBA-Ueated male Swiss mice to either
112 MHz EMF, amplitude modulated at 16 Hz, at an SAR of 0.75 W/kg, or to
2.54 GHz at an SAR of 0.1 W/kg. Neither type of exposure resulted in any effect
on skin tumours. [The number of animals in this study is not clear: the authors
used an unspecified 'effective' number of animals in their anaiysis.]
RF + ultraviolet (UV) radiation
Heikkinen et al. (2003)3* studied female K2 mice, either wildtype or transgenic
for omithine deearboxylase (ODC), an enzyme involved in carcinogenesis. The
transgenie sUain had been shown to be more sensitive to chemical tumour
promotion.39 The animals were exposed to two different types of signal: GSM or
DAMPS. The SAR in both cases was 0.5 W/kg. They observed a non-significant
aeeeleration of growth of skin tumours induced by UV radiation, especially in
the non-transgenic mice.
4.2.3

Mammary tumour
RF -I- 7,12-dimethylbenz[a]anthracene (DMBA)
Mammary tumours can be induced in rats by administration of DMBA. Using
this paradigm, Bartsch et al. (2002)"*" exposed female Sprague Dawley rats to
GSM 900 MHz signals at an SAR of maximally 0.08 W/kg. No effects on
tumour latency and incidence were observed. [The authors observed a significant
effect in the first of three series of experiments, but could not reproduce that in
subsequent experiments.]
Anane et al. (2003)"*' exposed female Sprague Dawley rats to GSM 900
MHz EMF, at SARs of 0.1,0.7, 1.4, 2.2 or 3.5 W/kg. They observed no effect on
tumour latency, volume, and multiplicity. In the first of two experiments they
found an inverse dose relation for tumour incidence which could not be
satisfaetorily explained.

Results

37

Yu et al. (2006)42 exposed female Sprague Dawley rats to GSM 900 MHz
signals at SARs of 0.44, 1.33 or 4.0 W/kg. They observed no effect on tumour
latency, size, multiplicity and incidence; the incidence and latency were higher in
the cage controls than in the sham controls and the exposed groups.
Hruby et al. (2008)^3 used a GSM 902 MHz signal to exposé female Sprague
Dawley rats to SARs of 0.4, 1.3 or 4.0 W/kg. They found inconsistent effects on
tumour number and incidence. Also in this study the tumour incidence was
higher in cage controls than in the sham controls and the exposed groups.
4.2.4

Liver tumour
RF + diethylnitrosamine
Imaida et al. (1998) performed two experiments with liver tumours induced in
male and female Fischer 344 rats by application of diethylnitrosamine. In the
first study the animals were exposed to a 929 MHz TDMA signal at SARs of
1.7-2.0 W/kg.''4 In the seeond study exposure was to a 1439 MHz TDMA signal
at SARs of 0.937-1.91 Wlkg.*^ In both cases they observed no effect on the
number and size of liver foei, but they did found an inerease in serum hormones.
The inerease in adrenoeorticotropic hormone (ACTH) and corticosterone could
in part be explained by stress due to the confinement during exposure, but the
inerease in melatonin was unexpected and unexplained by the investigators.

4.2.5

Central nervous system (CNS) tumour
RF + ethylnitrosourea (ENU)
In a study described above, where Adey et al. (1999)22 exposed male and female
Fisher 344 rats before and after birth to an NADC 835 MHz signal at SARs of
0.33-0.53 W/kg, they also induced CNS tumours by injection of ENU. As with
the spontaneous CNS tumours, they also observed a reduction in the incidence of
ENU-induced tumours in the RF-exposed group.
In similar experiments (also described above) but using another type of
signal, FM 836 MHz at SARs of 1.0 or 1.2 W/kg, Adey et al. (2000)23
„ot
observe any effect of RF exposure on survival and the incidence of ENU-induced
CNS tumours.
Zook and Simmens (2001)24 treated pregnant female Sprague Dawley rats
with ENU and exposed the offspring to 860 MHz pulsed or continuous-wave RF

38

Mobile phones and eaneer / Part 2. Animal studies on carcinogenesis

EMF, at SARs of 1.0 + 0.2 W/kg. They observed no effect of exposure on ENUinduced neurogenic or other tumours.
In a replication of the previous study, Zook and Simmens (2006)46 exposed
the offspring of ENU-treated Sprague Dawley rats to 860 MHz pulsedfieldsat
an SAR of 1.0 ± 0.2 W/kg. Again, no effect of this exposure on the incidence of
neurogenic tumours was observed.
Shirai et al. (2005)4^ exposed male and female Fischer 344 rats born from
ENU-treated mothers to a 1439 MHz TDMA signal at SARs of 0.67 or 2.0 W/kg.
They observed a lower incidence of pituitary tumours in males after the higher
SAR, but no other RF effect on neurogenic (including CNS tumours) or other
tumours and semm hormones.
In a study with a similar design but another type of signal, 1.95 GHz
WCDMA at SARs of 0.67 or 2.0 W/kg, Shirai et al. (2007)4*foundno effects of
exposure on neurogenic or other tumours.
4.2.6

Colon tumour
RF -t- demethylhydrazine (DMH)
Wu et al. (1994)49 investigated DMH-induced colon tumours in male and female
Balb/e mice. They exposed the animals to 2450 MHz RF EMF at SARs of 10-12
W/kg but did not observe any effects.

4.2.7

Sarcoma
RF + 3,4 benzopyrene (BAP)
Chagnaud et al. (1999)5» treated female Sprague Dawley rats injected with BAP
to induce sarcomas with a GSM 900 MHz signal at SARs of 0.075 ± 0.025 or
0.27 + 0.09 W/kg. No effects on tumour development or growth, on survival and
on semm autoantibodies were observed.

4.2.8

Multiple tumours
Heikkinen et al. (2006)^1 investigated in female Wistar rats the effect of
combined exposure to the mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy2(5H)-furanone (MX) and a GSM 900 MHz signal at SARs of 0.3 or 0.9 W/kg.
No effects of RF EMF exposure on survival and carcinogenesis were seen.

Results

39

Tillmann et al. (2010)^2 exposed female B6C3F1 mice before and after
birth to ethylnitrosourea (ENU), ENU + an UMTS signal at a power density of
4.8 W/m2, or an UMTS signal of 48 W/m2. They observed an increased number
of malignant lung tumours and benign liver tumours in the UMTS+ENU group
compared to the ENU-only group. High rates of benign liver tumours were found
in all groups and might be related to infection with Helicobacter hepaticus. The
lack of an ENU+sham exposure group makes it diffieult to draw definitive
conclusions . No effect were seen for other tumours.
4.3

Implanted tumours

4.3.1

Skin tumour
Santini et al. (1988)^3 exposed female C57B1/6J mice with an implanted
melanoma to pulsed or continuous 2450 MHz RF EMF. The SAR was 1.2 W/kg.
No effect was observed on melanoma growth and on survival.

4.3.2

Central nervous system (CNS) tumour
Salford et al. (1993, 1997)54 55 pairwise implanted male and female Fischer 344
rats with brain tumour cells. One animal was sham exposed and one exposed to a
915 MHz RF field either continuous or pulse modulated at 4, 8, 16, 50 or 200 Hz.
The output of the pulses was kept constant, therefore the SAR varied from
0.0077 to 1.67 W/kg. In some pairs tumour growth in the exposed animal was
faster than in the sham control, but overall there was no significant effect of
exposure on tumour growth. [The animals used in these studies were not welldefined; they had a range of body weights and presumably of ages. The use of
inoculated cells with varying viability resulted in a large variation in tumour
growth. Consequently the experimental conditions show too much variation for a
meaningful anaiysis.]
Higashikubo et al. (1999)5^ implanted male Fischer 344 rats with CNS
tumour cells and exposed them to an 835 MHz continuous wave FM signal or a
847 MHz CDMA signal at SARs of 0.75 + 0.25 W/kg. They observed no effect
of RF exposure on survival, independent of the number of cells injected.

4.3.3

Ascites tumour
Paulraj and Behari (2011)'^ injected ascites carcinoma cells in male Swiss mice
and subsequently exposed them to either 112 MHz EMF, amplitude modulated at

40

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

16 Hz, at an SAR of 0.75 W/kg, or to 2.54 GHz at an SAR of 0.1 W/kg. Neither
type of exposure resulted in any effect on the growth of the ascites tumour.
4.3.4

Sarcoma
Preskora et al. (1978)5'' injected sarcoma cells in male and female CWF mice
that had been repeatedly exposed in utero and, in one experiment, also after birth
to thermal levels of 2450 MHz fields. They observed a lower tumour incidence
and longer survival in animals both with and without tumour.
Szmigielski et al. (1982)''' intraveneously injected lung sarcoma cells in male
Balb/c mice and exposed them to 5 or 15 mW/cm2 2450 MHz RF fields,
eorresponding to SAR levels of 2-3 and 6-8 W/kg, respectively. They observed a
dose-dependent inerease in the number of sarcoma nodules in the lungs. The
authors could not exclude the oceurrenee of thermal effects. [Whole-body
exposure to the highest SAR level can certainly result in heating of the animals,
but also an SAR of 2 W/kg is already a significant systemic challenge.]

Results

41

42

Mobile phones and eancer / Part 2. Animal studies on carcinogenesis

Chapter

Quality assessment

The agreed scores for the assessment of the intemal and extemal validity of the
included studies is presented in Table 3. For each study, threats to the intemal or
extemal validity were estimated as either high (coded red), low (coded blue) or
unknown (coded yellow). Studies that considered multiple endpoints and that are
described in different sections of the preeeding chapter are listen only once in the
table, except for the paper by Paulraj and Behari (2011)'*, that describes two
very distinet experiments.
Table 3 Overview of the scores for the intemal and external validity of each of the studies.
Authors
Brief results
Internal validity
External validity
Influenee
Comment
Influenee
Comment
RF alone
Lymphoma, transgenic tumour-prone animals
Repacholi et al.
increased lymphoitia
incomplete
(1997)*
histopathology
Utteridge et al. (2002)' no effect
Replication of
Repacholi et al.
(1997)*
Oberto et al. (2007)8
effect
Replication of
Repacholi et al.
(1997)*'

Quality assessment

43

Lymphoma, non-transgenic tumour-prone animals
Sommer et al. (2004)'' no effect
Sommer et al. (2007)") no effect
Lee et al. (2011)1'
no effect
Anghileri et al.
decreased survival,
increased lymphoma
(2005) 12
Anghileri et al.
(2009)1^

decreased survival,
increased lymphoma

Anghileri et al.
(2006) 14

aeeeleration of
carcinogenesis

very incomplete data
on experimental
design
very incomplete data
on experimental
design
very incomplete data
on experimental
design

no exposure level, no
sham exposure
no exposure level, no
sham exposure
no exposure level, no
sham exposure

Skin tumour, non-transgenic animals
Sanchez et al (2006)' 5 no effect

Mammary tumour, non-transgenic tumour-prone animals
Szmigielski et al.
acceleratlon of mammary
(1982)17
cancer
Toler et al. (1997)"
no effect
Frei et al. (1998)'''
no effect
Frei et al. (1998)™
no effect
Replication of Frei et
al. (1998)"
Mammary tumour, non-transgenic animals
Jauchem et al. (2001)-! noeffect
CNS tumour, non-transgenic animals
La Regina et al.
no effect
(2003) '-5
no effect
Anderson et al.

possibly thermal effect

(2004) 26

Multiple tumours, non-transgenic animals
Chou et al. (1992)^'
more primary malignant
tumours in exposed; no
effect on benign tumours
and overall survival
Ivanov et al. (2005)2» decreased survival in
C57B1/6, tumour
formation in albino
Smith et al. (2007)2''
Tillmann et al.
(2007)30
Jin et al. (2011)3'

44

too much data on
experimental design
missing to draw any
conclusions

no dosimetry, no
specification of
tumours

effect
noeffect
noeffect

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

human relevance of
tumour types
questionable

Multiple tumours, transgenic animals
Saran et al. (2007)32

effect

human relevance of
tumour types
questionable

RF+initiator
Lymphoma. non-transgenic animals
Heikkinen et al.
no effect
(2001)33
SIcin tumour, non-transgenic

animals

Szmigielski et al.
(1982)1''and
Szudzinski et al.
(1982)3-1

aeeeleration of skin
cancer

Imaida et al. (2001)35

no effect

Mason et al. (2001 )36

no effect

Huang et al. (2005)3'
Paulraj & Behari
(2011)16

no effect
no effect

induced tumours not
relevant for humans;
thermal dose
unclear about number
of animals used

Skin tumour, transgenic and non-transgenic
Heikkinen et al.
(2003)38

possibly thermal effect

animals

no effect

Mammary tumour, non-transgenic animals
Bartsch et al. (2002)^

no effect

Anane et al. (2003)''i

noeffect

Yu et al. (2006)42

„o effect

Hruby et al. (2008)43

inconsistent

Liver tumour, non-transgenic

effect

animals

Imaida et al. (1998)44

no effect

Imaida et al. (1998)45

no effect

CyV5 tumour, non-transgenic

dosimetry data
missing

animals

Adey et al. (1999)22

redueed tumour incidence

Adey et al. (2000)23

no effect

Zook & Simmens
(2001)24

no effect

Zook & Simmens
(2006)46
Replication of Zook &
Simmens (2001)24
Shirai et al. (2005)47

no effect

lower incidence pituitary
tumours in males
Shirai et al. (2007)4»
no effect
Colon tumour, non-transgenic animals
Wu et al. (1994)4''

gffgct

Quality assessment

thermal exposure level

45

Sarcoma, non-transgenic animals
Chagnaud et al.
no effect
(1999)50
Multiple tumours, non-transgenic

animals

Heikkinen et al.
(2006)51

no effect

Tillmann et al.
(2010)52

increased number of lung
tumours; no effect other
tumours

Implanted tumours
Skin tumour
Santini et al. (1988)53

no effect

CA'5 tumour
Salford et al. (1993)54

no effect

Salford et al. (1997)55

no effect

Higashikubo et al.
(1999)56

no effect

Ascites tumour
Paulraj and Behari
(2011)16
Sarcoma
Preskom et al.
(1978)57
Szmigielski et al.
(1982)17

46

data on experimental
animals missing
data on experimental
animals missing

dosimetry data
missing

no effect

tumour not relevant
for humans

increased survival

tumour not relevant
for humans;
incomplete dosimetry
possibly thermal effect

increased number of lung
sarcoma nodules

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Chapter

Conclusions

The systematic literature search performed by the Committee revealed a
substantial body of animal studies on the carcinogenesis of exposure to RF fields.
A total of 23 studies have been published that investigated the effect of exposure
to RF EMF alone. A variety of animal models and tumour types has been
investigated, as well as a number of different types of RF, although the focus has
been on the types of signals used in modem mobile telecommunication.
Exposure has been from several weeks up to two years, and the follow-up time
generally lifelong.
In addition, 24 studies investigated the modulating effects of RF exposure on
carcinogenesis induced by various well-known carcinogenic compounds and
another seven studies the effect of RF exposure on the growth of implanted
tumours.
These data cover a broad range of experimental situations and may thus
provide a reasonably well insight into the effects of RF exposure on carcinogenesis in rodents. An overview is presented in Figure 1. Studies in which an
effect was observed and studies in which this was not the ease are presented
separately and are ordered by type of exposure (RF only, RF -i- effect modifier or
RF and implanted tumour). In four studies the effect observed was a positive one,
i.e. a decrease in tumour incidence or an inerease in survival. This is indicated as
an inhibiting effect. The colour codes indicate the score for the intemal (upper)
and extemal validity (lower). Red means that there is a chance that the outcome
of the study has been influenced by the issues diseussed with the intemal and

Conclusions

47

Stimulating effect

Inhibiting effect

RF only

RF*
modifier

RF+iniptjnted
tumour

RF only
modifier

RF^fim planted
tumour

RF only

RFt
modifier

RF+lmplanted
tumour

Figure 1 Overview of the studies included in this systematic anaiysis, ordered by effect outcome and type of exposure, and
colour coded for internal (upper) and external validity (lower).

extemal validity. Such studies have not been included in the overall appraisai by
the Committee. A blue colour means that the chance for an influenee of the
intemal or extemal validity issues on the outcome is minimal or absent and
yellow means that this is unknown. Studies that are coded with blue and yellow
are included in the overall appraisai.
Some issues warrant a further discussion here. The first one is the Repacholi
et al. (1997)^ study in which the authors found an effect of a mobile phone-type
signal on lymphoma incidence. However, histopathology was only performed on
animals that died before the end of the experiment. It is thus unknown whether
there was any non-fatal lymphoma in the surviving animals, and thus the overall
lymphoma incidence is also unknown. This is the main reason for concluding
that the outcome might have been influenced by the study design and thus for
giving a red code for the intemal validity. No effects have been found in studies
designed as repetitions of the Repacholi study. These studies were no exact
replications because the animals were restrained instead of free roaming in order
to improve dosimetry and the daily exposure was given in one session instead of

48

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

two for practical reasons. Other studies applying lifelong exposure to free
roaming or resUained animals with SAR values up to 4 W/kg did not find any
effect on lymphoma incidence or survival. In view of theflawsin the Repacholi
study and the results of the repetition studies, the conclusion of the Committee is
that an effect of long-term exposure to mobile phone signals on the incidence of
lymphomas has not been demonstrated. Also, since transgenie animals were used
in these studies with an increased spontaneous lymphoma incidence, the direct
relevance of this model for humans is questionable.
No effects of various types of RF signals on skin tumour development or
growth have been observed, with the exception of the results of the research
group of Szmigielski and colleagues.'^ ^^ However, they employed exposures
with SAR levels of 2-8 W/kg and it cannot be excluded that the growthaccelerating influenee of exposure at the these levels could be explained by
thermal effects^S'S^, although not all tumours seem to respond similarly to
moderate heating.^o Even a whole-body SAR of 2 W/kg is a significant systemic
challenge to a mouse with a metabolic rate of 4-7 W/kg under thermal neutral
conditions.
With respect to mammary tumours, the study by Szmigielski et al. (1982)'^
was again the only one showing aeeeleration of tumour development. They
exposed the animals for 2 hours per day to SAR levels that may result in
increased body temperatures. Studies of two other groups exposing the animals
ofthe same mouse suain to various frequencies for up to 22 hours per day, but to
a maximum SAR of 1 W/kg, did not observe any influenee on mammary tumour
development.'8-20 The committee considers it likely that the effects observed by
Szmigielski et al. were the result of thermal challenge and not a direct effect of
the RF field.
There are only few data on the influenee of RF EMF on liver tumours, and
they come from only one research group, but they do not indicate any effect.
There are no indications that exposure to RF EMF has any influenee on the
development or growth of CNS or other neurogenic tumours. Although Adey et
al. (1999)22 observed less CNS tumours after longterm RF exposure, and Shirai
et al. (2005)"'^ found less pituitary tumours after RF exposure of male offspring
from mothers that had been treated with a carcinogen, there is no rational
biological explanation for these observations, and they might be chance results.
Even at very high SAR levels that could induce thermal effects, no influenee
of RF EMF on colon tumour growth was observed. However, these data only
come from one single publication.
Long-term exposure to RF EMF up to a SAR of 4 W/kg does not seem to
have any effect on other spontaneous or carcinogen-indueed tumours, with the

Conclusions

exception of an inerease in ENU-induced lung tumours observed by Tillman et
al. (2010)52 aftei- U M T S exposure. This is, however, a single study that has not
been followed up or replicated. It also lacks an ENU-sham exposed control
group.The Committee therefore gives it a low weight in the overall anaiysis.
The systematic anaiysis of the quality of the studies, reflected in the
indications of the internal and extemal validity, has shown that most studies are
of sufficiënt quality and ean be included in the overall anaiysis. There are some
studies, however, that suffer from a very poor deseription of the experimental
design and/or poor dosimetry. They are, therefore, of limited or no value in the
overall anaiysis.
Overall the studies diseussed in this report show that no effects of long-term
exposure to RF EMF on the development or growth of tumours in general, or on
specifie types of tumours, have been demonstrated in rodents. Thefindingsof the
few studies that did indicate effects have either not been observed in repetition
studies, or might be explained by thermal effects. It is also possible that they
were chancefindings.This can also only be the conclusion for the few observed
proteetive effects of RF exposure.
An important issue is also whether the animal models and exposures used in
these studies have predietive value for the situation in humans. In general the
exposure of small laboratory animals to RFfieldsresults in a different energy
deposition than in humans. Because of their smaller size, the exposure of rats and
mice results much easier in whole-organ or whole-body exposure. This means
that the action of any compensating mechanisms will be much redueed compared
to in humans, where only parts of the body and organs will be exposed when
using communication deviees such as mobile phones. Whole-body exposure
does occur in humans, of course, by the RFfieldsemanating from mobile phone
base stations and other antennas, but the exposure levels in such situations are
considerably lower than in the animal studies, that tend to employ as much as
possible worse-case situations. This can also be said of the animal models that
use either transgenic animals with an increased spontaneous incidence of
tumours, or models that use chemical or physical carcinogens. These create also
worse-ease situations that - except for UV exposure - people usually do not
encounter in daily life. So in general the animal studies provide worse-ease
situations with respect to RF exposure, and when no effects are observed on the
induction or promotion of tumours in such models the Committee considers this
a strong indication that such effects are improbable in humans.

50

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

The final conclusion of the Committee is therefore that, on the basis of the results
ofthe animal studies presented in this systematic review, it is uniikely that longterm continuous or repeated exposure to RF EMF may have initiating or
promoting effects on the development of eaneer.
The Committee deems further animal studies into RF carcinogenesis not useful
at thistime.There is currently a large, well-designed animal carcinogenesis
study ongoing in the USA in which two species, rats and mice, are being longterm exposed to various levels of RFfields.^'Before recommending further
research, the outcome of this study, expected in 2016, has to be awaited.
In general, the Committee wishes to make the point that, for experimental studies
to be of value, the design has to be well-conceived and described, the tumour
model and exposure sehedule used should be relevant for humans, and there
should be a good deseription of the dosimetry and exposure levels. Foliowing the
recommendations of the Gold Standard Publication Checklisr* ' can be helpful.

Conclusions

^'

52

Mobile phones and eancer / Part 2. Animal studies on carcinogenesis

References

Baan R, Grosse Y, Lauby-Secretan B, e.a. Carcinogenicity of radiofrequency electromagnetie fields.
Lancet Oncol, 2011; 12(7): 624-626.
lARC - Intemational Agency for Research on Cancer. lARC Monographs on the Evaluation of
Carcinogenic Risks to Humans. Non-ionizing radiation. Part 2: Radiofrequency elecü-omagnetic
fields. Volume 102. Internet: http://monographs.iarc.fr/ENG/Monographs/voI102/index.php. Access
date 23-4-2013.
HCN - Health Council of the Netheriands. Mobile phones and cancer. Part I : Epidemiology of
tumours in the head. The Hague: Health Couneil of the Netherlands, 2013; Publication nr 2013/11.
Hooijmans CR, Leenaars M, and Ritskes-Hoitinga M. A gold Standard publication checklist to
improve the quality of animal studies, to ftilly integrate the Three Rs, and to make systematic reviews
more feasible. Altem Lab Anim, 2010; 38(2): 167-182.
Hooijmans CR, de Vries R, Leenaars M, e.a. Improving planning, design, reporting and scientific
quality of animal experiments by using the Gold Standard Publication Checklist, in addition to the
ARRIVÉ guidelines. Br J Pharmacol, 2011; 162(6): I259-I260.
Repacholi MH, Basten A, Gebski V, e.a. Lymphomas in Em-Piml transgenic mice exposed to pulsed
900 MHz electromagnetie fields. Radiat Res, 1997; 147(5): 631-640.
Utteridge TD, Gebski V, Finnie JW, e.a. Long-term exposure of E-ji-Piml ü^ansgenic mice to 898.4
MHz microwaves does not inerease lymphoma incidence. Radiat Res, 2002; 158(3): 357-364.
Oberto C Rolfo K, Yu P, e.a. Carcinogenicity study of 217 Hz pulsed 900 MHz electromagnetie
fields in PimI transgenic mice. Radiat Res, 2007; 168(3): 316-326.

References

9

Sommer AM, Streckeit J, Bitz AK, e.a. No effects of GSM-modulated 900 MHz electromagnetie
fields on survival rate and spontaneous development of lymphoma in female AKR/J mice. BMC
Cancer, 2004; 4: 77.

10

Sommer AM, Bitz AK, Streckert J, e.a. Lymphoma development in mice chronically exposed to
UMTS-modulated radiofrequency electromagnetie fields. Radiat Res, 2007; 168(1): 72-80.

'1

Lee HJ, Jin YB, Lee JS, e.a. Lymphoma development of simultaneously combined exposure to two
radiofrequency signals in AKR/J mice. Bioelectromagnetics, 2011; 32(6): 485-492.

12

Anghileri U , Mayayo E, Domingo JL, e.a. Radiofrequency-induced carcinogenesis; cellular calcium
homeostasis changes as a triggering factor. Int J Radiat Biol, 2005; 81(3): 205-209.

13

Anghileri LJ, Mayayo E, Domingo JL, e.a. Evaluation of heaith risks caused by radio frequency
accelerated carcinogenesis: the importance of processes driven by the calcium ion signal. Eur J
Cancer Prev, 2006; 15(3): 191-195.

14

Anghileri LJ, Mayayo E, and Domingo JL. Aluminum, calcium ion and radiofrequency synergism in
aeeeleration of lymphomagenesis. Immunopharmacol Immunotoxicol, 2009; 31(3): 358-362.

15

Sanchez S, Masuda H, Billaudel B, e.a. Effect of GSM-900 and -1800 signals on the skin of hairless
rats. II: I2-week chronic exposures. Int J Radiat Biol, 2006; 82(9): 675-680.

16

Paulraj R and Behari J. Effects of low level microwave radiation on carcinogenesis in Swiss Albino
mice. Mol Cell Biochem, 20II; 348(1-2): I9I-I97.

17

Szmigielski S, Szudzinski A, Pietraszek A, e.a. Accelerated development of spontaneous and
benzopyrene-induced skin cancer in mice exposed to 2450 MHz microwave radiation.
Bioelectromagnetics, 1982; 3: I79-I9I.

18

Toler JC, Shelton WW, Frei MR, e.a. Long-term, low-Ievel exposure of mice prone to mammary
tumors to 435 MHz radiofrequency radiation. Radiat Res, 1997; 148(3): 227-234.

19

Frei MR, Berger RE, Dusch SJ, e.a. Chronic exposure of cancer-prone mice to low-level 2450 MHz
radiofrequency radiation. Bioelectromagnetics, 1998; 19(1): 20-31.

20

Frei MR, Jauchem JR, Dusch SJ, e.a. Chronic. low-level (1.0 W/kg) exposure of mice prone to
mammary cancer to 2450 MHz microwaves. Radiat Res, 1998; 150(5): 568-576.

21

Jauchem JR, Ryan KL, Frei MR, e.a. Repeated exposure of C3H/HeJ mice to ultra-wideband
electromagnetie pulses: lack of effects on mammary tumors. Radiat Res, 2001; 155(2): 369-377.

22

Adey WR, Byus CV, Cain CD, e.a. Spontaneous and nitrosourea-induced primary tumors of the
central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves.
Radiat Res, 1999; 152(3): 293-302.

23

Adey WR, Byus CV, Cain CD, e.a. Spontaneous and nitrosourea-induced primary tumors of the
central nervous system in Fischer 344 rats exposed to frequency-modulated microwavefields.Cancer
Res, 2000; 60(7): 1857-1863.

24

Zook BC and Simmens SJ. The effects of 860 MHz radiofrequency radiation on the induction or
promotion of brain tumors and other neoplasms in rats. Radiat Res, 2001; 155(4): 572-583.

54

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

25

La Regina M, Moros EG Pickard WF, e.a. The effect of chronic exposure to 835.62 MHz FDMA or
847.74 MHz CDMA radiofrequency radiation on the incidence of spontaneous tumors in rats. Radiat
Res, 2003; 160(2): 143-151.

26

Anderson LE, Sheen DM, Wilson BW, e.a. Two-year chronic bioassay study of rats exposed to a 1.6

27

Chou CK, Guy AW, Kunz LL, e.a. Long-term, low-level microwave irradiation of rats.

28

Ivanov VB, Subbotina Tl, Khadartsev AA, e.a Exposure to low-intensive superhigh frequency

GHz radiofrequency signal. Radiat Res, 2004; 162(2): 201-210.
Bioelectromagnetics, 1992; 13(6): 469-496.
electromagnetie field as a factor of carcinogenesis in experimental animals. Buil Exp Biol Med,
2005; 139(2): 241-244.
29

Smith P, Kuster N, Ebert S, e.a. GSM and DCS wireless communication signals: combined chronic
toxicity/carcinogenicity study in the Wistar rat. Radiat Res, 2007; 168(4): 480-492.

30

Tillmann T, Emst H, Ebert S, e.a. Carcinogenicity study of GSM and DCS wireless communication
signals in B6C3F1 mice. Bioelectromagnetics, 2007; 28(3): 173-187.

31

Jin YB, Lee HJ, Seon LJ, e.a. One-year, simultaneous combined exposure of CDMA and WCDMA

32

Saran A, Pazzaglia S, Mancuso M, e.a. Effects of exposure of newbom patchedl heterozygous mice

radiofrequency electromagnetie fields to rats. Int J Radiat Biol, 2011; 87(4): 416-423.
to GSM, 900 MHz. Radiat Res, 2007; 168(6): 733-740.
33

Heikkinen P, Kosma VM, Hongisto T, e.a Effects of mobile phone radiation on X-ray-induced
tumorigenesis in mice. Radiat Res, 2001; 156(6): 775-785.

34

Szudzinski A, Pietraszek A, Janiak M, e.a. Aeeeleration of the development of benzopyrene-induced

35

Imaida K, Kuzutani K, Wang J, e.a. Lack of promotion of 7,12-dimethylbenz[a]anthracene-initiated

skin cancer in mice by microwave radiation. Arch Dermatol Res. 1982; 274(3-4): 303-312.
mouse skin carcinogenesis by 1.5 GHz electromagnetie near fields. Carcinogenesis, 2001; 22( 11):
1837-I84I.
36

Mason PA, Walters TJ, DiGiovanni J, e.a. Lack of effect of 94 GHz radio frequency radiation
exposure in an animal model of skin carcinogenesis. Carcinogenesis, 2001; 22(10): I70I-I708.

37

Huang TQ, Lee JS, Kim TH, e.a. Effect of radiofrequency radiation exposure on mouse skin
mmorigenesis initiated by 7,I2-dimethybenz[aIpha]anthracene. Int J Radiat Biol, 2005; 81(12): 861867.

38

Heikkinen P, Kosma VM, Alhonen L, e.a Effects of mobile phone radiation on UV-induced skin
tumourigenesis in omithine deearboxylase transgenic and non-transgenic mice. Int J Radiat Biol,
2003; 79(4): 221-233.

39

Halmekytö M, Syrjanen K, Janne J, e.a. Enhanced papilloma formation in response to skin tumor
promotion in transgenic mice overexpressing the human omithine deearboxylase gene. Biochem
Biophys Res Commun, 1992; 187(1): 493-497.

40

Bartsch H, Bartsch C, Seebald E, e.a. Chronic exposure to a GSM-like signal (mobile phone) does
not stimulate the development of DMBA-induced mammary tumors in rats: results of three
consecutive studies. Radiat Res, 2002; 157(2): 183-190.

References

41

Anane R, Dulou PE, Taxile M, e.a. Effects of GSM-900 microwaves on DMBA-induced mammary

42

Yu D, Shen Y, Kuster N, e.a. Effects of 900 MHz GSM wireless communication signals on DMBA-

gland mmors in female Sprague-Dawley rats. Radiat Res, 2003; 160(4): 492-497.
induced mammary tumors in rats. Radiat Res, 2006; 165(2): 174-180.
43

Hruby R, Neubauer G, Kuster N, e.a. Smdy on potential effects of "902-MHz GSM-type Wireless
Communication Signals" on DMBA-induced mammary tumours in Sprague-Dawley rats. Mutat Res,
2008:649(1-2): 34-44.

44

Imaida K, Taki M, Yamaguchi T, e.a. Lack of promoting effects of the electromagnetie near-field
used for cellular phones (929.2 MHz) on rat liver carcinogenesis in a medium-term liver bioassay.
Carcinogenesis, 1998; 19(2): 311-314.

45

Imaida K, Taki M. Watanabe S, e.a. The 1.5 GHz electromagnetie near-field used for cellular phones
does not promote rat liver carcinogenesis in a medium-term liver bioassay. Jpn J Cancer Res, 1998;
89(10): 995-1002.

46

Zook BC and Simmens SJ. The effects of pulsed 860 MHz radiofrequency radiation on the promotion
of neurogenic tumors in rats. Radiat Res, 2006; 165(5): 608-615.

47

Shirai T, Kawabe M, Ichihara T, e.a. Chronic exposure to a 1.439 GHz electromagnetie field used for
cellular phones does not promote N-ethylnitrosourea induced central nervous system tumors in F344
rats. Bioelectromagnetics, 2005; 26(1): 59-68.

48

Shirai T, Ichihara T, Wake K, e.a. Lack of promoting effects of chronic exposure to 1.95-GHz WCDMA signals for IMT-2000 cellular system on development of N-ethylnitro.sourea-induced central
nervous system tumors in F344 rats. Bioelectromagnetics, 2007; 28(7): 562-572.

49

Wu RY, Chiang H, Shao BJ, e.a. Effects of 2.45-GHz microwave radiation and phorbol ester 12-0tetradecanoylphorbol-I3-acetate on dimethylhydrazine-induced colon cancer in mice.
Bioelecü-omagnetics, 1994; 15(6): 531-538.

50

Chagnaud JL, Moreau JM, and Veyret B. No effect of short-term exposure to GSM-modulated lowpower microwaves on benzo(a)pyrene-induced tumours in rat. Int J Radiat Biol, 1999; 75(10): 12511256.

51

Heikkinen P, Emst H, Huuskonen H, e.a. No effects of radiofrequency radiaüon on 3-chloro-4(dichloromethyl)-5-hydroxy-2(5H)-fijranone-induced tumorigenesis in female Wistar rats. Radiat
Res, 2006; 166(2): 397-408.

52

Tillmann T, Emst H, Streckert J, e.a. Indication of cocarcinogenic potential of chronic UMTSmodulated radiofrequency exposure in an ethylnitrosourea mouse model. Int J Radiat Biol, 2010;
86(7); 529-541.

53

Santini R, Hosni M, Deschaux P, e.a. B16 melanoma development in black mice exposed to low-level
microwave radiation. Bioelectromagnetics, 1988; 9(1): 105-107.

54

Salford LG Bmn A, Persson BRR, e.a. Experimental studies of brain tumor development during
exposure with continuous and pulsed 915 MHz radiofrequency radiation. Bioelectrochem
Bioenerget 1993; 30(1-3): 313-318.

56

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

55

Salford LG Bmn A, and Persson BR. Brain tumor development in rats exposed to electromagnetie
fields used in wireless communication. Wireless-Netw, 1997; 3: 463-469.

56

Higashikubo R, Culbreth VO, Spitz DR, e.a. Radiofrequency electromagnetie fields have no effect on
the in vivo proliferation ofthe 9L brain tumor. Radiat Res, 1999; 152: 665-671.

57

Preskom SH, Edwards WD, and Justesen DR. Retarded tumor growth and greater longevity in mice
after fetal irradiation by 2450-MHz microwaves. J Surg Oncol, 1978; 10(6): 483-492.

58

Dickson JA. The effects of hyperthermia in animal tumour systems. Recent Results Cancer Res,

59

Wile AG Nahabedian MY, and Mason GR. Enhanced tumor growth in experimental whole body

1977; (59): 43-111.
hyperthennia J Surg Oncol, 1983; 24(2): 119-123.
60

Sen A, Capitano ML, Spemyak JA, e.a. Mild elevation of body temperamre reduces tumor interstitial
fluid pressure and hypoxia and enhances efficacy of radiotherapy in murine mmor models. Cancer
Res, 2011; 71(11): 3872-3880.

61

NIEHS - National Institute of Environmental Health Services. Cell Phones. Intemet: http://

62

ICNIRP - Intemational Commission on Non-Ionizing Radiation Protection. Guidelines for limiting

www.niehs.nih.gov/heahh/topics/agents/cellphones/index.cfm. Access date 24-6-2014.
exposure totime-varyingeleetric, magnetic, and electromagnetie fields (up to 300 GHz). Health
Phys, 1998; 74(4): 494-522.
63

Leeuwen G van. Lagendijk JJW, van Leersum B, e.a. Calculation of change in brain temperature due
to exposure to a mobile phone. Phys Med Biol, 1999; 44: 2367-2379.

64

Ebert S, Eom SJ, Schuderer J, e.a. Response, thennal regulatory threshold and thermal breakdown
threshold of restrained RF-exposed mice at 905 MHz. Phys Med Biol, 2005; 50(21): 5203-5215.

References

"

58

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

The Committee
B

Items used in the validity assessment
Experimental details

D

Abbreviations

Annexes

59

60

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Annex

The Committee

The membership of the Electromagnetie Fields Committee at the time of
preparation of this advisory report was as follows:

Prof. GC. van Rhoon, chair
Professor of Physical Aspects of Electromagnetie Fields and Health, Erasmus
University Medical CenUe Rotterdam
Prof. A. Aleman
Professor of Cognitive Neuropsychiatry, University of Groningen
Prof. H. Kromhout
Professor of Epidemiology of Health Effects from Exposure to
ElecUomagnetic Fields, Institute for Risk Assessment Sciences, University
of Utrecht
Prof. F.E. van Leeuwen
Professor of Cancer Epidemiology, Free University of Amsterdam,
Epidemiologist, Netherlands Cancer Institute, Amsterdam
Prof. H.FJ. Savelkoul
Professor of Cell Biology and Immunology, Wageningen University
Prof. W.J. Wadman
Professor of Neurobiology, University of Amsterdam

The Committee

61

•

•

•

•

•

•

•

•
•
•

D.H.J. van de Weerdt, physician
Toxicologist and specialist in environmental medicine. Central Gelderland
Municipal Health Services (GGD), Amhem
Prof. A.P.M. Zwamborn
Professor of Electromagnetie Fields and Health, Eindhoven University of
Technology; Physicist, TNO (Netherlands Organisation for Applied
Scientific Research), The Hague
Prof. R.A. Woutersen
Professor of Translational Toxicology, Wageningen University; Toxicologie
pathologist, TNO (Netherlands Organisation for Applied Scientific
Research), Zeist
Dr. G Kelfkens, advisor
Physieist, National Institute for Publie Health and the Environment,
Bilthoven
Prof. I.A. Kreis, advisor
Epidemiologist and specialist in social medicine, Health Council of the
Netherlands, The Hague
Prof. E. Lebret, observer
Professor of Environmental Health Impact Assessment, Institute for Risk
Assessment Sciences, Utrecht University, and Chairman Science fomm,
Knowledge Platform Electromagnetie Fields, Bilthoven
Dr. M.J.M. Pruppers, observer
Physicist, Deputy Executive Direetor, Knowledge Platform Electromagnetie
Fields, Bilthoven
J. Robijns, observer
Ministry of Economie Affairs, The Hague
R.P.R. Schutte, observer
Ministry of Infrastmcture and the Environment, The Hague
Dr. E. van Rongen, scientific secretary
Radiobiologist, Health Council of the Netherlands, The Hague

Assistence with the scoring system for the internal and extemal validity of the
studies and its further development was provided by dr. CR. Hooijmans and
Prof. M. Ritskes-Hoitinga, Radboud University Medical Centre, Nijmegen.

62

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

The Health Council and interests
Members of Health Council Committees are appointed in a personal capacity
because of their special expertise in the matters to be addressed. Nonetheless, it
is precisely because of this expertise that they may also have interests. This in
itself does not neeessarily present an obstaele for membership of a Health
Couneil Committee. Transparency regarding possible conflicts of interest is
nonetheless important, both for the chairperson and members of a Committee
and for the President of the Health Couneil. On being invited to join a
Committee, members are asked to submit a form detailing the functions they
hold and any other material and immaterial interests which could be relevant for
the Committee's work. It is the responsibility of the President of the Health
Council to assess whether the interests indicated constitute grounds for nonappointment. An advisorship will then sometimes make it possible to exploit the
expertise of the specialist involved. During the inaugural meeting the
déclarations issued are diseussed, so that all members of the Committee are
aware of each other's possible interests.

The Committee

63

64

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Annex

B
Items used in the validity assessment

Table BI Items used in the assessment of the intemal validity and the chance of influeneing the outcome.
Allocation to groups
Unknown:
No (high chance):
Yes (low chance):
Was the allocation
sequence adequately
Insufficiënt information
The investigators describe a
The investigators describe a nongenerated and applied?
about the sequence
random component in the sequence
random component in the
generation process to
generation process. Usually, the
sequence generation process
permit judgement of 'Low
such as referring to a random deseription would involve some
systematic, non-random approach, for chance' or 'High chance.
number table. or using a
example:
computer random number
• allocation by judgement or
generator
preference of the investigator
• allocation based on the results of a
laboratory test or a series of tests
• allocation by availability of the
intervention
• sequence generated by odd or
even date of birth
• sequence generated by some mie
based on anima! number/ cage
number

Items used in the validity assessment

65

Were the groups similar at Yes (low chance):
baseline or adjusted for
confounders?
The investigators show /
describe an equal distribution of
all relevant baseline
characteristies and or
confounders. Usually such a
deseription contains:
• the gender, age or weight of
the animals
• baseline values of the
outeomes which are of
interest in the study.

No (high chance):

Unknown:

The authors show that there is an
unequal distribution of relevant
baseline characteristies and/or
confounders and do not adjust for
this imbalance.

Not reported or
insufficiënt information
about the di.stribution of
baseline characteristies or
confounders to pennit
judgement.

Blinding
Were the care givers / and Yes (low chance):
No (high chance):
Unknown:
or investigators during the
course of the experiment All of the foliowing:
Any one of the foliowing:
Insufficiënt information to
adequately blinded from • blinding of care givers and
• no blinding or incomplete
permit judgement of 'Low
knowledge of which
investigators ensured, and
blinding, and the outcome is
chance' or 'High chance'.
intervention each animal
uniikely that the blinding
likely to be influenced by lack of
could have been broken
received?
blinding
• ID cards of individual
• blinding of investigators and
animals, or cage/animal
animal care givers attempted, but
labels are coded and of
likely that the blinding could have
identieal appearanee
been broken, and the outcome is
likely to be influenced by lack of
• another person than the
blinding. For example:
investigator prepares the
intervention
• coloured cage labels (red for
• the circumstances during the
group A, yellow group B)
intervention are specified and
expected differenees in visible
similar in both groups (see
effects between control and
next entry)
experimental groups
housing conditions of the animals
• housing conditions of the
during the experiment are not
animals during the
randomized within the room
experiment are randomized
the person who prepares the
within the room.
experiment is the same as the one
who conducts and analyses the
experiment
circumstances during the
intervention are not similar in
both groups (see next entry).

66

Mobile phones and eaneer / Part 2. Animal studies on carcinogenesis

Unknown:
Not similar (high chance):
Additional criteria to score Similar (low chance):
the similarity of the
The reviewers judge that the
Insufficiënt information to
circum.stances during the The reviewers judge that the
circumstances during the
permit judgement of 'Low
intervention is as similar as
intervention.
intervention differ in such a way that chance' or 'High chance'.
possible between the
experimental and control groups. they inerease the risk of performance
bias. For example:
For example:
• timing of the intervention was • timing of administration of real
and sham exposure are different
similar;
• the control group received a • instmments used to conduet the
experiment differ between real
correct sham treatment;
and sham exposed groups.
• technique and duration
needed to conduet the
intervention is exactly the
same in the experimental
groups.
Unknown:
No (high chance):
Yes (low chance):
Was the outcome
assessment adequately
Insufficiënt information to
Any one of the foliowing:
blinded (with regard to the Any one of the foliowing
permit judgement of 'Low
• no blinding of outcome
• no blinding or incomplete
subjective outeomes)?
chance' or 'High chance'.
assessment. and the outcome
blinding, but the outcome is
measurement is likely to be
not likely to be influenced by
influenced by lack of blinding
lack of blinding, e.g.
• blinding of outcome assessment
mortality
might be attempted, but likely that
• blinding of outcome
the blinding could have been
assessment ensured, and
broken, and the outcome
uniikely that the blinding
measurement is likely to be
could have been broken:
influenced by lack of blinding:
• methods for outcome
• methods for outcome
assessment are the same in
assessment are not the same in
both groups
both groups
• animals were selected at
• animals were not selected at
random during outcome
random during outcome
assessment.
assessment.
Data loss
Were incomplete outcome Yes (low chance):
data adequately addressed?
Any one of the foliowing:
• no missing outcome data
• reasons for missing outcome
data uniikely to be related to
tme outcome
• missing outcome data
balanced in numbers across
intervention groups, with
similar reasons for missing
data across groups
• missing data have been
imputed using appropriate
methods.

Items used in the validity assessment

No (high chance):

Unknown:

Insufficiënt reporting of
Any one of the foliowing:
• reason for missing outcome data attrition/exclusions to
permit judgement of 'Low
likely to be related to tme
outcome, with either imbalance in chance' or 'High chance'
(e.g. number randomized
numbers or reasons for mi.ssing
not stated, no reasons for
data across intervention groups
missing data provided).
• high proportion of missing
outeomes
• potentially inappropriate
application of simple imputation.

67

Reporting bias
Are reports of the study
free of selective outcome
reporting?

Yes (low chance):

Unknown:

Any one of the foliowing:
Any one of the foliowing:
In.sufficient information to
• the study protocol is not
• not all the study outeomes as
permit judgement of 'Low
specified in introduction and
available, but the outeomes of
chance' or 'High chance'.
material and methods sections of
interest as mentioned by the
the paper are described in the
investigators in the
results section
introduction and material and
methods sections are similar
not all of the study's pre-specified
with the outcome measures
primary outeomes have been
described in the results
reported
section
one or more primary outeomes is
• the study protocol is available
reported using measurements,
anaiysis methods or subsets of the
and all of the study's predata (e.g. subscales) that were not
specified (primary and
pre-specified in the protocol
secondary) outeomes thaat
one or more reported primary
are of interest in the review
outeomes were not pre-specified
have been reported in the pre(unless clear ju.stification for their
specified way.
reporting is provided, such as an
unexpected adverse effect)
the study report fails to include
results for a key outcome that
would be expected to have been
reported for such a study.

Other bias
Was the study apparenüy Yes (low chance):
free of other problems that
could put a high risk of
The study appears free of other
bias?
biases.

68

No (high chance):

No (high chance):

Unknown:

There is at least one importantriskof There may be ariskof
bias. For example:
bias, but there is either:
• the smdy suffered from extreme • insufficiënt information
baseline imbalance (evidence for
to assess whether an
failed randomization)
important risk of bias
exists; or
• the conduet of a smdy is affected
by interim results
• insufficiënt rationale or
• author has been claimed to have
evidence that an
been fraudulent
identified problem will
• inappropriate influenee of ftinders introducé bias.
• incorrect statistical methods or
unit of anaiysis error For example
data or animals are assumed to be
independent, but they are not
• some design specifierisksof bias:
• multi-arm study in which different
outeomes are presented per group
(selective outcome reporting)
• multi-arm study in which results
of different arms are combined
(all data should be presented per
group).

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Table B2 Items used in the as.sessment of the extemal validity and the chance of influeneing the outcome.
Unknown chance
Low chance
High chance
Animal characteristies
Age
Cancer type predominantly
found in animals

Cancer type

Age characteristic for age in Non-characteristic age
humans for cancer type
Cancer type typically found in humans

Exposure
Exposure: whole body or local
Exposure: source and level

Not typical for exposure of
humans

Exposure protocol

Not typical for exposure of
humans (non-thermal level,
comparable to exposure with
use of mobile phone or near
antenna)
Exposure: quality of dosimetry, 0-1
rated on a scale of O (very poor) 5 (excellent)

Exposure: level

Items used in the validity assessment

Not relevant for cancer type
Relevant for cancer type
Typical for exposure of
humans
Not typical for exposure of
Typical for exposure of
humans
humans (e.g. low level
continuous, or higher level
intermittent, simulating mobile
phone conversations)
Typical for exposure of
humans

2-5

1-2

69

70

Mobile phones and eancer / Part 2. Animal studies on carcinogenesis

Annex

Experimental details

Table Cl Details of the included studies.
Animal normal Carcinogen Exp source
Authors
Exp time
/ transgenic
Age at start (+:
Exp level
acclimatization
period)
Other tumours

Exp free/ Controls Group
Exp
size
restrained
level:
cortectio
n for
growth

Blinded

Results

RF alone

Lymphoma, transgenic tumour-prone animals
Repacholi female C57BL/ none
GSM 900
yes
MHz
et al.
óNTac mice,
2x30 min/d,
(1997)6
transgenic for
24 mo
En-Piml,
0.008-4.2
lymphoma
W/kg
prone
(individual)
4-6 wk + 10 d
0.13-1.4 W/kg
(in cage)
GSM 898
Utteridge female C57BL/
MHz
6NTac mice,
et al.
I h/d, 5 d/wk,
transgenic for
(2002)7
104 wk
Replica- En-Piml,
0.25, 1.0,2.0,
lymphoma
tion of
4.0 W/kg
Repacholi prone &
wildtype
et al.
4-6 wk + 10 d
(1997)6

Experimental details

free
5 / cage

sham

restrained sham,
cage
control,
positive
control

101
(contr:
IOO)

exposure and higher risk
anaiysis
in exposed
OR=2.4
(1,3-4.5)

120
(exp,
sham,
cage
contr);
30

exposure and no effect in
anaiysis
either
transgenic
or normal

(positive
contr)

71

Oberto
et al.
(2007)»
Replication of
Repacholi
et al.
(1997)6

male and
female C57BL/
6NTac mice,
transgenic for
Eu-Pim 1,
lymphoma
prone
6 wk + 20 d
multiple
tumours

GSM 900
yes
MHz
I h/d, 7 d/wk,
18 mo
0.5, 1.4, 4.0
W/kg

Lymphoma, non-transgenic tumour-prone animals
Sommer female AKR/J none
GSM 900
et al.
mice, wildtype,
MHz
but with high
(2004)'^
continuous,
lymphoma
46 wk
incidence
0.4 W/kg ±
4-5 wk
40%
UMTS
Sommer female AKR/J none
continuous,
et al.
mice, wildtype,
43 wk
(2007)10 but with high
0.4 W/kg +
lymphoma
40%
incidence
8 wk
Lee et al, female AKR/J none
CDMA,
(2011)"
mice, wildtype,
WCDMA
but with high
45 min/d,
lymphoma
5 d/wk, 42 wk
incidence
4.0 W/kg
5 wk
Anghileri female Ico:OFl none
GSM 800
et al,
mice, wildtype,
MHz
(2005) >q but with high
I h/wk, 4 mo
lymphoma
exposure level
incidence
not provided
4-5 wk
Anghileri female Ico:OFI CaCI, AI
GMS 800
et al.
mice, wildtype, lactate
MHz
(2009)1' but with high
1 h/wk, 16 wk
lymphoma
exposure level
incidence
not provided
2 mo
Anghileri female Ico:OFI FeATP
GSM 800
et al.
mice, wildtype,
MHz
(2006)''* but with high
1 h/wk, 4 mo
lymphoma
exposure level
incidence
not provided
4-5 wk

72

restrained sham.
cage
control

IOO (50 yes
m, 50 O

free
sham
6-7 / cage

160

free
sham,
6-7 / cage cage
control

160

free
5 / cage

sham

40

free

sham

20

free

sham

10

no

decreased
survival
and more
lymphoma
in exposed

free

sham

20

no

similar
aeeeleration of
carcinogenesis by
RF&
FeATP

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

no effect
on
survival,
lymphoma
s and other
tumours

exposure and no
anaiysis
difference
in
lymphoma
incidence,
survival
exposure and no
anaiysis
difference
in
lymphoma
incidence,
survival
exposure and no
anaiysis
difference
in
lymphoma
incidence,
survival
no
decreased
survival
and more
lymphoma
in exposed

Skin tumour, non-transgenic animals
Sanchez female IFFA
let al.
Creda rats,
(2006)" hairiess
5 wk + 1 wk

GSM 900
yes
MHz, 1800
MHz
2 h/d, 5 d/wk,
12 wk
2.5, 5 W/kg
Mammary tumour, non-transgenic tumour-prone animals
2450 MHz
no
Szmigiel2 h/d, 6 d/wk,
ski et al. HEA mice,
10.5 mo
(1982)17 wildtype with
2-3,6-8 W/kg
high mammary
cancer
incidence
6wk
435 MHz
Toler et al. female C3H/
pulsed
(1997)1» HeJ mice,
22 h/d, 7 d/wk,
wildtype with
21 mo
high mammary
0.32 W/kg
cancer
incidence
3-4 wk + I mo
2450 MHz
Frei et al. female C3H/
20 h/d, 7 d/wk,
(1998)1'' HeJ mice,
wildtype with
18 mo
high mammary
0.3 W/kg
cancer
incidence
3-4 wk + 10 d
2450 MHz
no
Frei et al female C3H/
20 h/d, 7 d/wk,
(1998)2" HeJ mice,
78 wk
Replica- wildtype with
high mammary
0.3-1.0 W/kg
tion of
Frei et al. cancer
(1998)1'' incidence
3-4 wk + 10 d
UWB
Jauchem female C3H/
HeJ mice,
2 min/wk, 12
et al.
(2001)21 3-4 wk + 10 d
wk
40 kV/m peak;
0.0098 W/kg
CNS tumour, non-transgenic animals
La Regina male and
female Fischer
et al.
344 rats,
(2003)2
wildlype
4+2 wk
CNS & other
tumours

Experimental details

FDMA 835
MHz, CDMA
847 MHz
4 h/d, 5 d/wk,
2y
1.3 + 0.5 W/kg
(brain)

histological
anaiysis

restrained sham,
positive
control
(UV),
cage
control

no effect
RF on skin
histology

dosedependent
acceleratio
n of
mammary
cancer

free
sham
10/cage

40

free

sham

200

histological
anaiysis

no effect
on number
and growth
of tumours

free

sham

100

histological
anaiysis

no effect
on number
and growth
of tumours

free

sham

100

histological
anaiysis

no effect
on number
and growth
of tumours

free

sham

IOO

histological
anaiysis

no effect
on tumour
incidence,
survival

160 (80 histological
m, 80 O anaiysis

no effect
of either
signal on
brain or
other
tumours

restrained sham

73

Anderson male and
female Fischer
et al.
(2004)26
344 rats,
wildtype
4 d before birth
brain and other
tumours

Multiple tumour, non-transgenic animals
Chou et al. male Sprague
(1992)27
Dawley rats,
wildtype
3 + 5 wk

Ivanov et
al.
(2005)2»

Smith et
al.
(2007)2')

inbred albino
mice and adult
C57B1/6 mice
(sex not
specified);
wildtype adults
& progeny
age not
provided
male and
female Han
Wistar rats,
wildtype
4-5 + 2 wk

none; some
groups
exposed in
previous
experiments

Iridium 1.6
yes
GHz
2 h/d, 7 d/wk
(perinatal); 2
h/d, 5 d/wk, 2
y (postnatal)
brain: 0.16 W/
kg (perinatal);
0.16,1.6 W/kg
(postnatal)

free

sham,
cage
control

exp.:
180 (90
m, 90f)
contr:
160 (80
m, 80 0

postnatal
exposure,
histological
anaiysis

males: no
effect
survival;
females:
lower
survival
cagecontrols;
no effect
brain or
other
tumours

2450 MHz,
yes
pulsed
21.5 h/d,
25 mo
0.15-0.4 W/kg

free

sham

100

histological
anaiysis

37 GHz
repeatedly f
or 1 mo, total
exposure 3.5 h
<10mW/cm2

unknown cage
control

unknown

no overall
effect on
tumour
development; more
primary
malignant
tumours in
exposed;
no effect
on benign
tumours
and overall
survival
decreased
survival in
C57BI/6
adults and
Fl; tumour
fomiation
in albino

GSM 900
MHz, DCS
1800 MHz
2 h/d, 5 d/wk,
104 wk
0.44, 1.33,4.0
W/kg
GSM 902
yes
MHz, DCS
1747 MHz
2 h/d, 5 d/wk,
24 mo
0.4, 1.3,4.0
W/kg

restrained sham,
cage
control

130 (65 yes
m,65f)

no effect
on survival
and
carcinogenesis

restrained sham

130 (65 yes
m, 65 f)

no effect
GSM,
decreased
number of
tumours
after DCS

Tillmann
et al.
(2007)30

male and
female
B6C3FI/CrlBR
mice, wildtype
4-5 + 4 wk

74

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Jin et al.
(20II)"

male and
none
female Sprague
Dawley rats,
wildtype
5 + I wk
Multiple tumours, transgenic animals
CD-1 mice
Saran et
heterozygous
al.
(2007)52 for Patched 1,
transgenic, Xray tumour
prone
2d
RF+ initiator
Lymphoma, non-transgenic animals
Heikkinen female CBA/S X-ray
et al.
mice, wildtype
(2001)" 3-5 wk
lymphomas and
other tumours

Skin tumour, non-transgenic animals
BAP
Szmigiel- male Balb/c
ski et al. mice, wildtype
(1982)17 6wk

sham

CDMA,
WCDMA
45 min/d, 5 d/
wk, 12 mo
4.0 W/kg

free

GSM 900
yes
MHz
2x0.5 h/d, 5 d
0.4 W/kg

restrained sham

40
(20 m,

yes

50-63

yes

no effect
on survival
and
carcinogenesis

histological
anaiysis

no effect
on X-ray
induced
lymphomas, other
neoplasms
or survival

(m+O

50

2450 MHz
2 h/d, 6 d/wk,
10.5 mo
2-3,6-8 W/kg

free,
sham
10/cage

40

IOO

Szudzinski et al.
(1982)''»

BAP
male Balb/c
mice, wildtype
adult, age not
provided

2450 MHz
2 h/d, 6 d/wk,
1, 2, 3, 6 mo
2-3, 6-8 W/kg
during BAP;
4 W/kg 1,2,
3 mo before
BAP

free,
BAP+
10 / cage sham

Imaida
et al.
(2001)"

female CD-1
DMBA
mice, wildtype
5 wk

TDMA 1.5
GHz
1.5 h/d, 5 d/
wk, 19 wk
2,0 W/kg

Mason et
al.
(2001)36

DMBA
female
SENCAR mice,
wildtype
4-5 wk + 10 d

94 GHz
10 s
(1 W/cm2);
10 s, 2/wk,
12 wk (0.333
W/cm2)

30,48
restrained sham,
positive
control
(TPA),
cage
control
restrained sham,
27-55
positive
control
(TPA),
infrared,
cage
control

Experimental details

no
difference
in tumour
incidence

20 0

restrained sham,
cage
control

NMT 902
MHz, GSM
902 MHz
1.5 h/d,5 d/
wk, 78 wk
NMT: 1.5
W/kg; GSM:
0.35 W/kg

yes

no

no

dosedependent
aeeeleration of skin
cancer
dosedependent
aeeeleration of skin
cancer; in
part same
data as
Szmigielski et al.
(1982)
no effect
RF on skin
tumour

no effect
RF on skin
tumour

75

Huang et
al.
(2005)"

male ICR mice, DMBA
wildtype
6 wk

849, 1763
MHz
2x45 min/d,
5 d/wk, 19 wk
0.4 W/kg
112 MHz,
Paulraj & male Swiss
DMBA
16 Hz AM;
Behari
mice, wildtype
2.54 GHz
(2011)16 7-8 wk
2 h/d, 3 d/wk,
skin, ascites
16 wk
tumour
112 MHz: 1
mW/cm2, 0.75
W/kg; 2.54
GHz: 0.34
mW/cm2, 0.1
W/kg
Skin tumour, transgenic and non-transgenic animals
Heikkinen female K2
UV
GSM,
yes
mice, wildtype
DAMPS
et al.
1.5 h/d,
(2003)3» and ODC
transgenic mice
5 d/wk, 52 wk
12-15 wk
0.5 W/kg

free

sham,
positive
control
(TPA)

20

free

sham

18

restrained sham,
cage
control

Mammary tumour, non-transgenic animals
Bartsch
GSM 900
female Sprague DMBA
et al.
MHz
Dawley rats,
(2002)*' wildtype
eontinuously
max 0.08
38+13 d; 43+8
W/kg
d;34+I7d

no, but free
sham
decline
in SAR
taken in
consideration
GSM 900
no
restrained sham,
MHz
cage
2 h/d, 5 d/wk.
control
9 wk
0.1,0.7, 1.4,
1.4,2.2, 3.5
W/kg

no effect
RF on skin
tumour

no effect
RF on skin
and ascites
tumour

45-49,
cage
contr:
20

RF sham:
nonhistological significant
acceleraanaiysis
tion of
mmour
growth

60

histological no effect
anaiysis;
on tumour
animal
latency and
control in
incidence
experiment 3

Anane
et al.
(2003)''i

female Sprague DMBA
Dawley rats,
wildtype
55 d

Yu et al.
(2006)''2

female Sprague DMBA
Dawley rats,
wildtype
36+ I2d

76

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

GSM 900
no, but restrained sham,
MHz
variation
cage
4 h/d, 5 d/wk, of 1.93
control
26 wk
dB noted
0.44, 1.33,
4.0 W/kg

histological
anaiysis

16 (cage histological
contr: 8) anaiysis

100

exposure,
histological
anaiysis

no effect on
tumour
latency,
volume,
multiplicity; in
I»'of2
experiments
inverse dose
relation for
incidence
no effect
on tumour
latency,
size,
multiplicity,
incidence;
incidence
and latency
higher in
cage
controls

Hmby
et al.
(2008)''3

female Sprague DMBA
Dawley rats,
wildtype
5 wk+ 12d

Liver tumour, non-transgenic animals
male and
DEN
Imaida
female Fischer
et al.
(1998)'^» 344 rats,
wildtype
5 + I wk

Imaida et
al.
(1998)'*5

DEN
male and
female Fischer
344 rats,
wildtype
5 + I wk

CNS tumour, non-transgenic animals
Adey et al. male and
ENU
(1999)22 female Fischer
344 rats,
wildtype
gestation
d 15 + 3d

ENU
Adey et al. male and
(2000)23 female Fischer
344 rats,
wildtype
gestation
d 15 + 3d
Zook&
Simmens
(2001)2"

male and
ENU
female Sprague (mothers)
Dawley rats,
wildtype
57 + 4d

Experimental details

no, but restrained sham,
GSM 902
cage
lifetime
MHz
control
4 h/d, 5 d/wk, variation
of 1.0 dB
6 mo
noted
0.4, 1.3,4.0
W/kg

100

TDMA 929
MHz
1.5 h/d,
5 d/wk, 6 wk
1.7-2.0 W/kg

restrained sham,
cage
control

4X

TDMA 1439
MHz
1.5 h/d, 5
d/wk, 6 wk
0.937-1.91
W/kg

restrained sham,
cage
control

48

NADC 835
yes
MHz
2 h/d, 7 d/wk
(prenatal),
4 d/wk
(postnatal),
2y
0.33-0.53
W/kg
FM 836 MHz yes
2 h/d, 7 d/wk
(prenat),
4 d/wk
(postnat),
2y
1.0,1.2 W/kg
860 MHz
pulsed, CW
6 h/d, 5 d/wk,
22 mo
1.0 ±0.2 W/kg

sham
free
(prenat),
restrained
(postnat.)

236

histological redueed
anaiysis
incidence
spontaneou
s and
ENUinduced
tumours

sham
free
(prenat),
restrained
(postnat.)

90

histological
anaiysis

noeffect of
RF on
survival,
tumour
incidence

restrained sham,
cage
control

60

histological
anaiysis

no RF
effect on
neurogenic
or other

exposure,
histological
anaiysis

inconsistent effect
on mmour
number,
incidence;
incidence
higher in
cage
controls
no effect
on foei
number
size, but
inerease in
semm
ACTH,
corticosterone,
melatonin
no effect
on foei
number,
size, but
inerease in
semm
ACTH,
corticosterone,
melatonin

77

Zook&
Simmens
(2006)''6
Replication of
Zook &
Simmens
(2001)2"
Shirai
et al.
(2005)"'

Shirai et
al.
(2007)"»

male and
ENU
female Sprague (mothers)
Dawley rats,
wildtype
52 + 2d

860 MHz
pulsed
6 h/d, 5 d/wk,
325 d
1.0 + 0.2 W/kg

restrained sham,
cage
control

30
(serial
killing
experiment)

histological
anaiysis

no RF
effect on
neurogenic
tumours

male and
ENU
female Fischer
344 rats,
wildtype
gestation d 18

TDMA 1439 yes
GHz
90 min/d,
5 d/wk,
104 wk
0.67, 2.0 W/kg

restrained sham,
cage
control

100

histological
anaiysis

male and
female Fischer
344 rats,
wildtype
gestation d 18

WCDMA 1.95 yes
GHz
90 min/d,
5 d/wk,
104 wk
0.67, 2.0 W/kg

restrained sham,
cage
control

100

histological
anaiysis

lower
incidence
pituitary
tumours in
males after
high dose
RF, no
other RF
effect on
neurogenic
or other
tumours
and semm
hormones
no RF
effect on
neurogenic
or other

2450 MHz
3 h/d, 6 d/wk,
5 mo
10-12 W/kg

restrained sham

26-32

no

GSM 900
MHz
2 h/d, 2 wk
0.075 + 0.025,
0.27 + 0.09 W/
kg

restrained sham

6
(contr),
7-9
(exp.)

GSM 900
MHz
2 h/d, 5 d/wk,
104 wk
0.3, 0.9 W/kg

free

72

ENU

Colon tumour, non-transgenic animals
Wu et al. male and
DMH
(1994)49 female Balb/c
mice, wildtype
4-5 wk
Sarcoma, non-transgenic animals
Chagnaud female Sprague BAP
Dawley rats,
et al.
(1999)50 wildtype
2 mo

Multiple tumours
Heikkinen female Wistar MX
et al.
rats, wildtype
(2006)51 7 wk

78

sham,
cage
control

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

noRF
effect

no effect
on mmour
development or
growth, on
survival
and on
semm
autoantibodies
histological
anaiysis

no effect
on survival
and
carcinogenesis

Tillmann
et al.
(2010)52

female B6C3F1 ENU
mice, wildtype
6 d post
conception

UMTS
eontinuously
24 mo
0,4.8,
48 W/m2

yes

free

sham,
ENU
cage
control

54-60

yes

increased
number of
malignant
lung
tumours
and benign
liver
tumours;
no effect
other
tumours;
noENU
+sham
control

Implanted tumours
Skin tumour
female C57B1/
Santini
et al.
6J mice,
(1988)53 wildtype,
implanted
melanoma
5 wk
CNS tumour
Salford et male and
none
al (1993)5" female Fischer
344 rats,
wildtype
age not
provided,
weight 150-250
g

Salford
et al.
(1997)55

male and
female Fiseher
344 rats,
wildtype
age, weight not
provided.

Experimental details

no effect
melanoma
mmour
growth,
survival

2450 MHz,
pulsed, CW
2.5 h/d, 6 d/
wk, lifelong
1.2 mW/kg

free, 15 / sham
cage

915 MGzCW
and pulsed 4,
8, 16,50,217

restrained sham

37

histological
anaiysis

overall no
effect of
exposure
on mmour
growth;
large
variation
due to u.se
of
inoculated
cells

restrained sham

4-29

histological
anaiysis

overall no
effect of
exposure
on tumour
growth;
large
variation
due to use
of
inoculated
cells,
probably
includes
results
from 1993
study

Hz
7 h/d, 5d/wk,
2-3 wk
4 Hz: 0.0077
W/kg; 8 Hz:
0.016 W/kg;
16 Hz: 0.030
W/kg; 50 Hz:
1 W/kg; 217
Hz: 0.4 W/kg;
CW: 1.67
W/kg
915 MHzCW
and pulsed 4,
8, 16, 50,217
Hz
7 h/d, 5d/wk,
9-15 d
4 Hz: 0.0077
W/kg; 8 Hz:
0.016 W/kg;
16 Hz: 0,030
W/kg; 50 Hz:
1 W/kg; 217
Hz: 0.4 W/kg;
CW: 1.67
W/kg

79

Higashi- male Fischer
kubo et al. 344 rats,
(1999)56 wildtype
28 d

FM CW 835
MHz, CDMA
847 MHz
4 h/d, 5 d/wk,
4 wk
0.75 ±0.25
W/kg

restrained sham

112 MHz,
16 Hz AM;
2.54 GHz
2 h/d, 3 d/wk,
16 wk
112 MHZ:
I mW/cm2,
0.75 W/kg;
2.54 GHz:
0.34 mW/cm2,
0.1 W/kg

free

sham

male and
female CWF
mice, wildtype
d 11 gestation

2450 MHz
20 min/d,
3(pre)+36 d
(postnatal); 4 d
prenatal
35 W/kg

free

sham

Szmigiel- male Balb/c
ski et al. mice, wildtype
(1982)17 6wk

2450 MHz
2 h/d, 6 d/wk,
3 mo
2-3,6-8 W/kg

free,
sham,
not
10/cage confine- proviment
ded
stress

Ascites tumour
Paulraj
male Swiss
and Behari mice, wildtype
(2011)16 7.8 wk

Sarcoma
Preskom
et al.
(1978)57

12-67
histological
(sham), anaiysis
1049
(FMCW),
22-38
(CDMA),
groups
from
2 exp.
combined

no effect of
RFon
survival,
independent of
number of
cells
injected

no effect

12

palpationand lower
histological incidence
anaiysis
and longer
survival
with/
without
tumour
after
prenatal
exposure
no
dosedependent
increased
number of
sarcoma
lung
nodules

Abbreviations: OR: odds ratio; SAR: specifie absorption rate
Carcinogens: UV: uUraviolet; BAP: benzo(a)pyrene; DMBA: 7,12-dimethybenz[a]anthracene; TPA: 12-0tetradecanoylphorbol-I3-acetate; DEN: diethylnitrosamine; ACTH: adrenocorticotrope hormone; ENU: ethylnitro.sourea;
DMH: ethylnitrosourea; MX: 3-chIoro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; CaCI: calcium chloride; Fe-ATP: ferricadenosine triphosphate complex; Al lactate: aluminum lactate
RF sources: GSM: Global System for Mobile ommunication; UMTS: Universai Mobile Teleeommunications Signal; CDMA:
Code Division Multiple Access; WCDMA: Wideband Code Division Multiple Access; NMT: Nordic Mobile Telephony; CW:
continuous wave; TDMA: Time Division Multiple Access; DAMPS: Digital Advanced Mobile Phone System; UWB: ultra wide
band; FDMA: Frequency-Division Multiple Access; NADC: North American Digital Cellular; FM: Frequency Modulation;
DCS: Digital Communication Signal.

80

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

Annex

Abbreviations

BAP
CDMA
CNS
DAMPS
DCS
DMBA
DMH
EMF
ENU
FDMA
FM
GHz
GSM

Abbreviations

benzo(a)pyrene or 3,4 benzopyrene, a skin carcinogen
Code Division Multiple Access - a second generation or 20 type
of signal used in mobile telephony (predominantly in the USA and
Japan)
Central Nervous System
Digital Advanced Mobile Phone System - a second generation or
2G type of signal used in mobile telephony in the USA and
Canada
Digital Communication Signal - a second generation or 2G type
of signal used in mobile telephony (similar to GSM, but with a
higher frequency)
7,l2-dimethybenz[a]anthracene, a carcinogen
dimethylhydrazine, a carcinogen
electromagnetie fields
ethylnitrosourea, a carcinogen
Frequency Division Multiple Access - a type of signal used in
mobile telephony, especially in satellite communication
Frequency Modulation: information is transmitted by variations in
the basic frequency of the carrier wave signal
gigahertz: 10^ Hz
Global System For Mobile Communication - a second generation
or 2G type of signal used in mobile telephony

81

GSPC
Hz
lARC
Iridium
MHz
MX
NADC
NMT
ODC
RF
SAR
TDMA
UMTS
UV
WCDMA
WHO
W/kg

82

Gold Standard Publication Checklist
hertz, unit of frequency; 1 Hz equals one cycle per second
International Agency for Research on Cancer
a mobile telecommunication signal used by the Iridium satellite
system
megahertz: 10* Hz
3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, a
mutagen
North American Digital Cellular - a third generation or 3G type of
signal used in mobile telephony in the USA
Nordic Mobile Telephony - a first generation or IG type of signal
used in mobile telephony
omithine deearboxylase, an enzyme involved in carcinogenesis
radiofrequency
Specifie Absorption Rate - the rate of absorption of
radiofrequency electromagnetie energy in a body; used as a
measure of RF EMF exposure
Time Division Multiple Access - a type of signal used in mobile
telephony; GSM and DAMPS are TDMA signals
Universai Mobile Teleeommunications Signal - a third generation
or 3G type of signal used in mobile telephony
ultraviolet (radiation)
Wideband Code Division Multiple Access - a third generation or
3G type of signal used in mobile telephony; similar to UMTS
World Health Organization
Watt per kilogram, the unit in which the SAR is expressed

Mobile phones and cancer / Part 2. Animal studies on carcinogenesis

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