Electromagnetic Fields and Our Health 20th22nd October 2003

A Review of Completed and Ongoing RF Bioeffects Research Relevant To Cancer Risk Assessment
J.J. Morrissey1, J. Elder1, M.L. Swicord1 and K.H. Joyner2 1Motorola Florida Research Labs, 8000 West Sunrise Blvd., Ft. Lauderdale, Florida, USA, 33322. 2Motorola Australia 10 Wesley Court, Tally Ho Business Park, East Burwood, Victoria, Australia, 3151 KEYWORDS Mobile Phones, Cancer, WHO database INTRODUCTION Over 180 studies have been initiated using human, animal, and cell culture experimental models to investigate whether exposure to radiofrequency (RF) emissions, specifically from mobile telephony, can cause or promote cancer (Table 1). One hundred fifteen of these studies are now complete, with the vast majority reporting no association with cancer endpoints. A list of these studies including details of exposure, test model, and author's conclusions can be obtained from the WHO website at http://www.who.int/pehemf/ research/database/en/. The results of cancer related studies from this database will be used by the International Agency for Research on Cancer (IARC) in 2004/05 to evaluate RF emissions as a potential human carcinogen. In addition, the results of non-cancer related studies from this database will be used by the WHO in 2005/06 to evaluate RF emissions for adverse human health effects other than cancer. In such evaluations, epidemiological studies will carry the most weight. Animal studies will play an important role when epidemiological studies are weak or not definitive. In vitro studies will generally have a supporting or clarifying role. OBSERVATIONS Twelve relevant epidemiological studies have been completed and report on the potential for mobile telephone RF exposure to cause brain and other forms of cancer (Table 2). In addition, two studies have been completed that looked at associations between cell phone use and eye melanoma. The majority of these studies report no association with cancer, and although two studies do report marginal effects, these are inconsistent in their findings when compared with each other and with the rest of the studies in the database. A large number of epidemiological studies, many funded by the EU 5th Framework program and organized through IARC, are currently ongoing to provide further data. In addition, 15 long-term animal bioassays, 20 cancer-initiated animal assays, and 2 tumor cell line injection bioassays have been initiated to look at mobile phone-type RF exposure and cancer (Table 3). Of these
Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003

2 animal studies, only one by Repacholi et al (1997) has reported positive results, and this study had a number of shortcomings in the experimental design. The Repacholi study has been unable to be replicated/verified (Utteridge et al 2002) and is currently being replicated in another independent laboratory. Finally, there are a large number of short-term animal and in vitro studies addressing various endpoints related to cancer. The majority of these again report no association between mobile phone-type RF exposure and cancer endpoints, and those that do report positive findings either have not, or cannot, be independently replicated. CONCLUSIONS The majority of studies investigating potential carcinogenicity of mobile telephony RF emissions show no effects. This has lead numerous expert panels (see Table 4) to conclude that no evidence exists to support RF exposure as an agent that can either initiate or promote cancer. Sporadic studies that have reported an association between mobile telephone RF emissions and various cancer-relevant endpoints do not support one another in any obvious common mechanism, and have all either failed to be replicated in independent laboratories or replication attempts have not been completed to date. No plausible biological mechanism exists to explain how RF energy might interact non-thermally with biological tissue to initiate or promote cancer. If current ongoing studies continue to report no association between RF exposure and cancer endpoints, the available data contained within the WHO database should be more than sufficient for the IARC to make a conclusive carcinogenic evaluation of RF exposure from mobile telephony devices. Table 1. List of current and completed studies looking at the potential biological effects of exposure to mobile phone-type RF signals.

Type of Study Completed Ongoing Total Cancer relevant or related Epidemiological studies 12 24 36 Standard bioassays 8 7 15 Sensitized in-vivo studies 13 7 20 Acute in-vivo studies 23 8 31 In-vitro studies 57 25 82 Total Cancer Studies 115 69 184 Non-cancer studies Epidemiology 10 1 11 Acute in-vivo studies 37 10 47 In-vitro studies 15 7 22 Human studies 50 21 71 Total Non-Cancer Studies 112 39 151 Grand Totals 225 110 335
Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003

Completed and ongoing epidemiological studies. The WHO ID denotes the access number to the study description in the WHO database at http://www.who.int/pehemf/research/database/en/

Case Control Studies: PI End Point Status WH IARC 900 & 1800 MHz (analog &
Ongoing170, 171, 172,

Inskip & Linet Brain tumor, acoustic neuroma & meningioma incidence in humans (n=700) and cellular telephone use (USA). No Effect Observed N Engl J Med (2001) 344:79-86 168

Muscat et al 800 & 1900 MHz (cell phone use) and glioblastoma, astrocytoma, acoustic neuroma & salivary gland tumor incidence. No Effect Observed Neurology (2002) 58:13041306 JAMA (2000) 284:30013007 220

Hardell et al Brain tumor incidence and cellular telephone use Effect Observed Intl J Oncology (2003) 22:399-407; European J Cancer Prevention (2002) 11:377-386; European J Cancer Prevention (2001) 10:1-7; Med Gen Med (2000) 2(2); Intl J Oncology (1999) 15:113-116 229

Auvinen et al 900 & 1800 MHz (GSM & NMT) phone use and analysis of brain and salivary gland tumors. Marginal Effect Reported Epidemiology (2002) 13:356-359 816

BaumgardtElms 900 & 1800 MHz (GSM) exposure from mobile phones & other sources and testicular cancer (data extracted from a larger case control study). No Effect Observed Cancer Causes and Control (2002) 13:895-902 1040

Warren et al Mobile phone use (all types) and facial tumor incidence. No Effect Observed The Laryngoscope (2003) 113(4):663-667 1071

Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003

Cohort Studies: PI Endpoint Status WHO ID

Morgan et al Total cancer incidence in Motorola employees occupationally exposed to RF. No Effect Observed Epidemiology (2000) 11:118-127 173

Rothman et al 800 & 1900 MHz (cell phone use) and total mortality in the USA. No Effect Observed Epidemiology (1996) 7(3):303-305 174

Johansen et al 900 & 1800 MHz (GSM) cell phone use and cancer incidence and mortality in Denmark No Effect Observed JNCI (2001) 93:203-206 176 Cook et al Ecological correlation study of mobile phone use and brain, head, and neck tumors in New Zealand No Effect Observed The New Zealand Medical Journal (2003) 116: 1-8 1056

Charlton et al Ecological correlation study between smoking and mobile phone use in teenagers Hypothesis Presented (correlation between smoking & mobile phone use) British Med J. (2003) 326:161 1020

De Roos et al Occupational and mobile phone exposure & neuroblastoma in offspring No Effect Observed Epidemiology (2001) 12:508-17; Cancer Causes & Controls (1999) 10:53949 1025

Rothman et al 800 & 1900 MHz (cell phone use) and brain tumor incidence. On hold 175 Ahn, Yoon-Ok Cell phone use in Korea and cancer incidence. Ongoing 837

Elliot et al Pilot study prior to larger 900 MHz (GSM) cohort in England. Ongoing 891

Ahn, Yoon-Ok Cell phone use in Korea and cancer incidence. Ongoing 837

Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003

Eye Melanoma Studies PI Endpoint Status WHO ID

Stang et al 900 & 1800 MHz (GSM) cell phone & two-way radio exposures. Case control study of uveal melanoma (eye cancer). Marginal Effect Reported Epidemiology (2001) 12:712 643 Johansen et al 900 & 1800 MHz (GSM) cell phone & two-way radio exposures and incidence of melanoma in the eye. No Effect Observed British J Cancer (2002) 86:348-349 900 Mitchell & Rose 900 MHz (AMPS, CDMA, GSM) effects on visual and auditory pathology in humans. Ongoing 721

Table 3. Current completed and ongoing long term animal studies. The WHO ID denotes the access number to the study description in the WHO database at http://www-nt.who.int/pehemf/ database.htm. TwoYear Bioassays: PI Endpoint Status WHO ID

Adey et al 836.55 MHz (TDMA) exposure in standard rat 2-year bioassay. No increased tumor formation Rad. Res. (199) 152:293302 1

Adey et al 836.55 MHz (FM) exposure in standard rat 2-year bioassay. No increased tumor formation Cancer Res. (2000) 60:1857-63 788

Zook et al 860 MHz (MiRS/TDMA) exposure in standard rat 2-year bioassay. No increased tumor formation Rad. Res. (2001) 155:572583 6

Zook et al 860 MHz (FM) exposure in standard rat 2-year bioassay. No increased tumor formation Rad. Res. (2001) 155:572583 789

Spalding 800 MHz (CW) exposure on RFM mice. No increased tumor formation 423

Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003

Health Phys. (1971) 20:421-424 Roti, Roti et al 835.62 MHz (FM) exposure in standard rat 2-year bioassay. No increased tumor formation BEMS 2002 9

Roti, Roti et al 847.74 MHz (CDMA) exposure in standard rat 2-year bioassay. No increased tumor formation BEMS 2002 790

Anderson et al 1616 MHz (IRIDIUM) exposure in standard rat 2-year bioassay. No increased tumor formation BEMS 2002 11

Dasenbrook et al 900 MHz (GSM) RF exposure for 2 years to B6C3F1 mice. Ongoing 244

Dasenbrook et al 1800 MHz (DCS) RF exposure for 2 years to B6C3F1 mice. Ongoing 944

Dotti et al 1800 MHz (DCS) RF exposure for 2 years to Wistar rays. Ongoing 245

Dotti et al 900 MHz (GSM) RF exposure for 2 years to Wistar rays. Ongoing 945

Sharai et al 1.5 GHz (PDC) exposure and standard NTP type bioassay Ongoing 328

Yamaguchi et al 1.5 GHz (PDC) exposure and brain tumors Ongoing 329

Chemically, Genetically, and Radiation Initiated Bioassays: PI Endpoint Status WHO I

Adey et al 836.55 MHz (TDMA & FM) exposure in ENU induced rat brain tumor bioassay. No increased tumor formation Rad. Res. (1999) 152:293302; Cancer Res. (2000) 60:1857-63 4 Zook et al 860 MHz (MiRS TDMA & FM) exposure in ENU-induced rat brain tumor bioassay. No Effect Observed Rad. Res. (2001) 155:572583 8

Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003

Zook et al 860 MHz (MiRS/TDMA & FM) exposure in ENU-induced tumor latency bioassay. No Effect Observed Radiation Research (in preparation) 7

Chagnaud et al 900 MHz (GSM) exposure in Benz(a)Pyrene induced rat sarcoma No Effect Observed Int J Radiat Biol (1999) 75(10):1251-6 12

Imaida et al 929 & 1500 MHz (PDC) exposure in DEN induced-GSTp(+) rat hepatoma bioassay. No Effect Observed Carcinogenesis (1998) 19(2):311-314; Jpn J Cancer Research (1999) 89:995-1002 13

Heikkinen et al 902 MHz (GSM) exposure in radiation induced mouse lymphoma bioassay No Effect Observed Radiation Research (2001) 156:775-85 15

Heikkinen et al 900 MHz (GSM) exposure on UV induced skin tumors in ODC transgenic & non-transgenic mice No Effect Observed Int J Radiat. Biol. (2003) 79(4):221-33 16

Bartsch et al 900 MHz (GSM) exposure in DMBA induced rat mammary tumor bioassay No Effect Observed Radiation Research (2002) 157:183-190 17

Anane et al 900 MHz (GSM) exposure in DMBA induced rat mamary tumor bioassay No Effects Observed BEMS 2001, St. PaulMN 18 Repacholi et al 900 MHz (PW) exposure on lymphomas in PIM-1 transgenic mice. Increased mortality Rad. Res. (1997) 147(5):631-640 19

Utteridge et al 900 MHz (PW) exposure on lymphomas in PIM-1 transgenic mice. No Effects Observed Radiation Research (2002) 158:357-364; Radiation Research (2003) 159:274278 20

Sykes, P. et al 900 MHz (GSM simulated) exposure on intra-chrom. recomb. in pKZ-1 transgenic mice. Inconclusive Preliminary Findings Rad. Res. (2001) 156:495502 21

Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003 8 Persson et al 900 MHz (GSM) exposure to GFAP (-/-) knockout mice on tumor development, micronuclei formation, ODC activity & polyamine/histamine levels. No effect BEMS (1999) 287
Imaida, . et al 1.5 GHz (PDC) exposure of mice and promotion o skin tumorogenesis in DMBA initiated model. No effect BEMS (2001) 768 Hruby et al Replication of DMBA initiated mammary tumor bioassay Ongoing 246 Oberto, G. et al Replication of PIM-1 transgenic mouse study for lymphoma development Ongoing 247 Juutilainen et al 900 MHz (GSM) exposure of 3chloro-4-(dichloromethyl)-5hydroxy-2(5H)-furanone initiated mice and analysis of tumor formation Ongoing 323

Chiang Huai 900 MHz (GSM) exposure on DMBA initiated rats and analysis of mammary tumors Ongoing 593

Lee J-S et al 848. 5 MHz and1762. 5 MHz RF exposute to hsp70.1 knockout and p53 knockout mice and analysis of histopathology, gene expression, and stress response Ongoing 994

Shirai et al 2.2 GHz exposure on the promotion of ENU induced brain tumors in rats Ongoing 1050

Tumor Cell Line Injection Studies: PI Endpoint Status WHO ID

Salford, L. et al 915 MHz (FM) exposure on RG2 injected brain tumor progression in rats. No Effect Observed Bioelctrochem. & Bioenergetics (1993) 30:313-318 22

Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003 9
Higashikubo et al 847.74 MHz (CDMA) & 835.62 MHz (FM) exposure on 9L injected brain tumor progression in rats. No Effect Observed Rad. Res. (1999) 152:665671 23

Table 4. Some of the Expert Panels/Government Agencies that conclude no evidence exists to support RF exposure can either initiate or promote cancer. National Radiological Protection Board (NRPB): 1993, 1999, 2003

http://www.nrpb.org.uk/ The International Commission on Non-Ionizing Radiation Protection (ICNIRP): 1996, 1998

http://www.icnirp.de/ European Commission Expert Group: 1996 http://europa.eu.int/ Royal Society of Canada: 1999, 2001 http://www.rsc.ca/ UK Independent Expert Group on Mobile Phones (IEGMP Stewart Report): 2000 French Expert Group (Zmirou): 2001, 2003 http://www.sante.gouv.fr/ Singapore Health Sciences Authority 2001 http://www.hsa.gov.sg/ German Commission for Radiation Protection (SSK): 2001 http://www.ssk.de/ European Committee on Toxicology, Eco-toxicology and the Environment (CSTEE): 2001, 2002

http://www.iegmp.org.uk/ Health Council of the Netherlands: 2000, 2002 http://www.gr.nl/ World Health Organization 2000 http://www.who.int/pehemf/ en/

American Cancer Society 2001 http://www.cancer.org/docr oot/home/index.asp

http://europa.eu.int/ Swedish Radiation Protection Authority: 2002 http://www.ssi.se Australian Radiation Protection & Nuclear Safety Agency 2002

http://www.arpansa.gov.au/ Norwegian Radiation Protection Authority: 2003 http://www.nrpa.no Hong KongOffice of Telecommunications Authority 2003 http://www.ofta.gov.hk US Food and Drug Administration 2003 http://www.fda.gov/cellpho nes/

Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003

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REFERENCES All references, as well as a complete description of the study model and the investigators general conclusions, can be obtained at the WHO database website at http://www.who.int/peh-emf/research/database/en/ by using the WHO ID number. WHO-1 Adey WR, Incidence of Spontaneous and Nitrosourea Induced Primary Tumors of the Central Nervous System in Fischer 344 Rats Chronically Exposed to Modulated Microwaves, Radiation Research (1999) 152:293-302. WHO-4 Adey WR, Spontaneous and Nitrosourea Induced Primary Tumors of the Central Nervous System in Fischer 344 Rats Exposed to a Frequency Modulated Microwave Field, Radiation Research (1999) 152:293-302; Cancer Research (2000) 60:1857-63. WHO-6 Zook, B.C., The Effects of 860 MHz Radiofrequency Irradiation on the Induction or Promotion of Brain Tumors and other Neoplasms in Rats, Radiation Research (2001)155:572-583. WHO-7 Zook, B.C., Possible Promotion of Brain Tumors in Rats by a 860 MHz Pulsed Radiofrequency, Radiation Research (manuscript in preparation). WHO-8 Zook, B.C., The Effects of 860 MHz Radiofrequency Irradiation on the Induction or Promotion of Brain Tumors and other Neoplasms in Rats, Radiation Research (2001) 155:572-583. WHO-9 Roti Roti, J.L., 835.62 MHz (FM) exposure in standard rat 2-year bioassay, Radiation Research (2003) in press. WHO-11 Anderson LE, 1616 MHz (IRIDIUM) exposure in standard rat 2-year bioassay, Radiation Research (2003) in press. WHO-12 Chagnaud, J.L., Veyret, B., No Effect of Short Term Exposure to GSM-Modulated Low Power Microwaves on Benzo(a)Pyrene induced Tumors in Rats, Int J Radiat Biol. (1999) Oct; 75(10):1251-6. WHO-13 Imaida, K. and Shirai, T., Lack Of Promoting Effects Of The Electromagnetic 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; Jpn. J Cancer Research (1999) 89:995-1002. WHO-15 Heikkinen, P. & Juutilainen, J. Effects of Radio Frequency Radiation on the Development of Cancer in Mice. Radiation Research (2001) 156:775-85. WHO-16 Heikkinen, P. & Juutilainen, J. Effect of 900 MHz Radiofrequency Radiation on UV-induced Skin Tumorigenesis in ODC-Transgenic and Non-Transgenic Mice. Int J Radiat. Biol. (2003) 79(4):221-33 WHO-17 Bartsch, C. 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. Radiation Research (2002) 157:183-190 WHO-18 Anane R, Veyret B. Effects of Whole Body Exposure to GSM Microwaves on Rats Bearing DMBA Induced Tumors. BEMS 2001, St. PaulMN WHO-19 Repacholi, M.H., Lymphomas In E(Mu)-Pim1 Transgenic Mice Exposed To Pulsed 900 MHz Electromagnetic Fields., Radiation Research (1997) 147(5):631640.
Proceedings of the International Conference on Non-Ionizing Radiation at UNITEN (ICNIR 2003) Electromagnetic Fields and Our Health 20th22nd October 2003