European Foundation of Oncology and Environmental Sciences “B. Ramazzini”

1. The potential carcinogenic risks of electromagnetic fields: what we know and what we still must learn European Foundation of Oncology and Environmental Sciences “B. Ramazzini” Cesare Maltoni Cancer Research Center Bologna Summer Event June 28 2007

2. Power frequency EMF: what we know

3. Power frequency EMF: epidemiological evidence • The first epidemiological study of childhood cancer and EMF was published in 1979. • Since then more than 20 studies have been conducted • The present position on EMF and the epidemiology of childhood leukemia is summarized in a pooled analysis of measurement and calculated field studies published by Ahlbom et al (3247 cases in total).

4. Pooled results from Ahlbom et al Relative risks (and 95% confidence intervals) Numbers of subjects Study 0.1-<0.2 µT 0.2-<0.4 µT ≥ 0.4 µT ≥ 0.4 µT Observed Expected Measurement studies Canada Germany New Zealand UK USA 1.29 1.24 0.67 0.84 1.11 1.39 1.67 4 cs/0 ct 0.98 1.01 1.55 2.00 0 cs/0 ct 1.00 3.44 13 2 0 4 17 10.3 0.9 0 4.4 4.7 Calculated field studies Denmark Finland Norway Sweden 2.68 0 cs/19 ct 1.75 1.75 0 cs/8 ct 4.11 1.06 0.57 2 cs/0 ct 6.21 0 cs/10 ct 3.74 2 1 0 5 0 0.2 2.7 1.5 Summary Measurements studies Calculated field studies All studies 1.05 (0.9-1.3) 1.58 (0.8-3.3) 1.08 (0.9-1.3) 1.15 (0.9-1.5) 0.79 (0.3-2.3) 1.11 (0.8-1.5) 1.87 (1.1-3.2) 2.13 (0.9-4.9) 2.00 (1.3-3.1) 36 8 44 20.1 4.4 24.2

5. Power frequency EMF: experimental evidence Authors Animals Treatment Comments Result Species/strain No. Exposure Duration Only 1 sex (male); short duration (32 weeks) Margonato et al., Rats 256 males 0; 5 µT 32 weeks No evidence of 1995 S.D. per group (50 Hz) (22 h/day) carcinogenic effect Yasui et al., Rats F344 48 females 0;0,5; 5 mT 2 years No evidence of Only 1 sex (male); short duration (104 weeks) 1997 per group (50 Hz) (22 h/day) carcinogenic effect Mandeville et al., Rats F344 50 males and 0; 2; 20; 200; 2 years, GLP No evidence of Few animals; short duration (104 weeks) 1997 50 females 2000 µT (20 h/day) carcinogenic effect per group (60 Hz) NTP, 1998 Rats F344 100 males and 0; 2; 200; 2 years, GLP Equivocal evidence Short duration (104 weeks) Mice B6C3F1 100 females 1000 µT (18.5 h/day) of carcinogenic effect per species and for thyroid C cell per group tumour in male treated with 2 or 200 µT

6. Present position on power frequency EMF (part I) There is an association between childhood leukemias and EMF exposure in the study populations. However, it is not yet possible to establish a cause-correlation for two reasons: 1) the absence of a plausible mechanism 2) lack of support from laboratory evidence

7. Present position on power frequency EMF (part II) • These factors led IARC to classify power frequency EMF as a possible carcinogen in 2001 • Were there an accepted mechanism of action or robust supporting evidence from the laboratory, it is probable that EMF would have instead been classified as an established carcinogenic agent.

8. Radio frequency EMF (RFEMF): what we know

9. RFEMF: epidemiological evidence (part I) 1978-1995: Various epidemiological studies conducted on military personnel exposed to radar waves and on children living near radio-television aerials indicate a possible increase in limphomas/leukaemia 2001-2002: Initial epidemiological data on tumours of acustic nerves have been reassuringly negative

10. RFEMF: epidemiological evidence (part II) 2004: Preliminary results of an epidemiological study condicted in Sweden report an increase in tumours of the acustic nerve in population exposed to cellular telephones (RFEMF) (Ahlbom, 2004) • 2006: Pooled analysis of two case-control studies on use of cellular and cordless telephones showed an increase risk of malignant brain-tumours diagnosed in 1997-2003, highest in the group with > 10 years latency period

11. RFEMF: experimental evidence Authors Animals Treatment Comments Result Species/strain No. Exposure Duration Only 1 sex (male); short duration (110 weeks) Chou et al., Rats 100 males 25 months Excess of primary 1992 S.D. per group (2,450MHz) (21.5 h/day) malignant tumors Repacholi et al., Mice Em-Pim1 100 females 18 months Increase risk of lymphomas Only 1 sex (female); short duration (78 weeks) 1997 per group (900 MHz) (1h/day) Mice Em-Pim1; w.t. Utteridge et al., 120 females 2 years Only 1 sex (male); short duration (104 weeks) No evidence of (900 MHz) 2002 per group (1h/day) carcinogenic effect Rats Bartsch et al., 60 females (900 MHzand DMBA) (23 h/day) Few animals short duration (sacrificed within 1 year) No evidence of S.D. per group 2002 carcinogenic effect for mammary tumors

12. Present position on RFEMF • Use of cell phones for < 10 years have not demonstrated an increase in cancer • There is however some evidence regarding long-term use and lengthy latency period • absence of evidence ≠ • absence of risk

13. EMF and RFEMF: what we still must learn

14. Diffused carcinogenic risks EMF and RFEMF represent what are known as diffused carcinogenic risks. We use this term to describe carcinogenic risks of low potency, but to which almost the entire population of the planet may be exposed.

15. Examples of diffused carcinogenic risks 1) agents which are slightly carcinogenic at any dose; 2) low or extremely low doses of strong carcinogenic agents; 3) mixtures of small doses of any carcinogenic agents.

16. Tools for identifying diffused carcinogenic risks In the case of diffused carcinogenic risks, it is not sufficient to follow the standard protocol used in ordinary experiments, but rather it is necessary to conduct what we define as mega-experiments.

17. Characteristics of mega-experiments • reproduce the various conditions of human exposure • use vast numbers of animals per group, in order to express variations in the effects more sharply • are conducted until the natural death of the rodents, to allow an agent to express its full carcinogenic potential • evaluate all neoplastic and non-neoplastic pathologies

18. 35 years of mega-experiments at the ERF agent # rodents vinyl chloride > 7,000 vitamins > 8,000 coca-cola > 2,000 gamma radiation > 10,000 irradiated food > 2,000 electromagnetic fields > 9,000 extremely low frequency > 7,000 radiofrequency > 2,000

19. Integrated project of the European Ramazzini Foundation (ERF)

20. ERF mega-experiments to evaluate EMF (50Hz) Experiment Age at start Number of animals (M+F) Treatment Duration 50Hz-magnetic field Lifespan BT 1 CEM embryo 5,029 50Hz-magnetic field and formaldehyde Lifespan embryo 805 BT 2 CEM embryo 657 50Hz-magnetic field and 10 gamma rads Lifespan BT 3 CEM embryo 642 50Hz-magnetic field and aflatoxin B1 Lifespan BT 4 CEM TOTAL 7,133

21. ERF mega-experiment on EMF (50Hz)

22. ERF mega-experiment to evaluate RFERF (1.8 GHz) Experiment BT 1 CEMRF Group number Age at start Number of animals (M+F) Treatment (Volt/meter) Duration Lifespan I embryo 409 50 Volt/meter Lifespan II 411 25 Volt/meter embryo III embryo 811 5 Volt/meter Lifespan 0 Volt/meter (control) Lifespan IV embryo 817 TOTAL 2,448

23. ERF mega-experiment on RFEMF (1.8 GHz)

24. Conclusions • The epidemiological evidence concerning EMF and long-term exposure to RFEMF show there are reasonable grounds for concern for the possibility of adverse effects • The absence of epidemiologicalevidence concerning short-term exposure RFEMF ≠ the absence of risk • While we await the results of the experiments currently underway (2009-2011), the precautionary principle guides us to “undertake provisional risk management measures…without having to wait until the reality and seriousness of those adverse effects become fully apparent”