Neuroscience Letters 361 (2004) 13–16 www.elsevier.com/locate/neulet
Mini-review
Diseases of modern living: neurological changes associated with mobile phones and radiofrequency radiation in humansq Roderick Westermana,*, Bruce Hockingb a
Epworth Hospital, Healthcheck, 89– 91 Bridge Road, Richmond, VIC 3121, Australia b 9 Tyrone Street, Camberwell, VIC 3124, Australia
Abstract Health effects of radiofrequency radiations (RFR) including mobile phone technology and the adequacy of their safety standards remain uncertain. Case reports of peripheral neurological effects of RFR describe mainly disturbances of noxious sensation (dysaesthesia). Cases associated with other RFR sources as well as mobile phone technology are examined seeking insights into neurophysiological mechanisms and safety levels. Cases have arisen after exposure to much of the frequency range (low MHz to GHz). In some instances symptoms are transitory, but may be lasting in others. After very high intensity exposures nerves may be grossly injured. However, after lower intensity exposures which may result in dysaesthesia, ordinary nerve conduction studies demonstrate no abnormality although current perception threshold studies may. Only a small proportion of similarly exposed persons develop symptoms. The role of modulations (e.g. pulses) needs clarification. Some of these observations are not consistent with the prevailing hypothesis that all health effects of RFR arise from thermal mechanisms. It is concluded that RFR from mobile phones can cause peripheral neurophysiological changes in some persons. The effects occur at exposure levels below the present safety levels for RFR. Possible non-thermal mechanisms are discussed and may point to future directions of research. q 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Radiofrequency radiations; Mobile phones; Safety standards; Clinical symptoms; Dysaesthesia; Pathophysiological mechanisms
As discussed in Hocking and Westerman [11], most safety standards for radiofrequency radiations (RFR) exposure (3 KHz to 300 GHz) are based on either the avoidance of heating effect sufficient to harm tissue due to frequencies . 10 MHz, or electrostimulatory effects of frequencies , 10 MHz [2,12,27]. The fundamental restrictions of the standard are based on RFR energy deposition into tissue expressed as W/kg (watts per kilogram of tissue). Based upon no consistent health effects having been observed at exposures below 4 W/kg, and allowing a ten-fold safety factor, exposure standards are based on limiting exposures to less than 0.4 W/kg for occupational exposures. A further safety factor of 5 is used to protect the public to give a whole body exposure limit of 0.08 W/kg. These data are then translated into ‘reference levels’, i.e. exposure levels expressed in mW/cm2 (or V/m or A/m) for compliance purposes, e.g. 1 mW/cm2 for occupational or 0.2 mW/cm2 for public
exposures at 300 MHz. The underlying assumption is that no health effects will occur other than those with a thermal or electrostimulatory basis and that RFR does not cause harmful effects due to other means. Empirical confirmation of the hypothesis that no effects will occur in humans exposed below the safety levels, and/or from other mechanisms than heating or electrostimulation, has mainly come from epidemiological studies of cancer which have not found clear evidence of any harmful effect. Another source of data is case reports and there have been many regarding peripheral neurological effects, mainly dysaesthesia. These are examined in this minireview in order to provide insights into neurophysiological mechanisms and hence safety levels. First several case reports are briefly described in the context of our ongoing research into health effects of mobile phones, and then their implications are discussed.
q This paper is dedicated to Manfred Zimmermann in celebration of his 70th birthday. It also honours his Foundation Editorship of Neuroscience Letters for 30 years and his many significant contributions to sensory physiology and pain research. * Corresponding author. Tel./fax: þ 61-3-9859-1443. E-mail address:
[email protected] (R. Westerman).
0304-3940/03/$ - see front matter q 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2003.12.028
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Case reports (a) Mobile phone technology Hocking and Westerman [8 – 11] have reported various cases of dysaesthesia associated with mobile phones and base station antennae. Hocking [7] reported a case series of 40 persons who complained of symptoms associated with using a mobile phone. Common symptoms included a burning sensation or dull ache (not an ordinary headache), felt ipsilateral to the side of use of the phone. It occurred minutes after use and lasted minutes to hours. Some cases also reported visual symptoms or not thinking clearly. The mechanism was speculated to be neurological. Because the predominant symptom is dysaesthesia, Hocking and Westerman have used a current perception threshold (CPT) device with fixed frequencies of 2000 Hz, 250 Hz, 5 Hz and a double-blind psychophysical paradigm, so neither the testing neurophysiologist nor the subject are aware of when or whether a stimulus is delivered, to assess patients (see Ref. [17]). CPT is used as a test stimulus to detect excitability changes in different sized nerves that may have been injured. Hocking and Westerman [8] reported a case of a 72-yearold business-man who developed a persistent ‘bruised’ feeling on the scalp after extensive use of a mobile phone. Neurological investigation found no medical cause. On examination by us 1 year later he had altered sensation to cotton wool on the scalp on the affected side. On CPT testing, changes were found for the C3 and trigeminal nerve distributions in the area of his symptoms. Subsequently Hocking and Westerman [10] have studied a 34-year-old journalist who complained of occipital pain on using her mobile phone. She agreed to a provocation study in which her phone was wrapped in thin polystyrene to avoid heating effects. She then spoke continuously into the phone until symptoms occurred (7 min). CPT testing showed marked changes in the nerves of the affected area compared to the opposite side and to her pre-exposure values. (b) Antenna Hocking and Westerman [9] describe the case of a rigger aged 31 years who had accidental exposure of the left side of his face to a 870 MHz Code Domain Multiple Access (CDMA) panel antenna (supposedly turned off). He worked for about 2 h before feeling unwell, and then discovered that the antenna was operating at low power. He developed headache, blurred vision and when examined the next day he had a smaller left pupil and altered sensation to cotton wool on his left forehead. CPT testing found abnormalities of the C-fibres in the left ophthalmic division of the trigeminal nerve, which was again abnormal on re-testing after 1 month, but had returned to normal when tested 6 months later. The exposure to the head was reconstructed and measured to be 0.01 mW/cm2 which is below the whole
body occupational exposure standard of 1 mW/cm2, and similar to that from a mobile phone. Considered together, these cases show that in some cases neurological effects in mobile phone users may arise from the RFR per se, independently of the phone and its alleged effects such as heating of tissues or the position of the head causing compression neuropathy. This suggests that the RFR is causal. (c) Other RFR exposures There have been many reports of RFR exposures causing peripheral neurological effects. Hocking and Westerman [11] identified reports from a Pub Med search, presented in order across the spectrum where the frequency was stated. Kolmodin-Hedman et al. [13] studied 113 RFR welders (25 –30 MHz; the exposures varied but more than 50% of measurements of the machines exceeded the Swedish ceiling exposure level of 25 mW/cm2). They found that 40% had symptoms of dysaesthesia compared to only 22% of 23 non-exposed controls, matched for manual manipulative work. Two-point discrimination was significantly diminished in welders (39/113) compared to controls (1/23). Nerve conduction studies did not find significant abnormalities between 38 symptomatic welders (12/38) and the controls (5/23, possibly CTS). This study shows that the exposures caused symptoms not detectable on ordinary nerve conduction tests in 26/38 welders. Schilling [23,24] has provided two reports of several cases of RFR overexposure. Some of the cases have had neurological effects of the central, peripheral and autonomic nervous systems. Schilling [23] also described three men overexposed to ultra-high frequency (UHF) TV who have had persistent headaches, fatigue and dysaesthesia but no clinical abnormalities on investigation. Scott et al. [25] described 10/200 (5%) patients who were receiving 915 MHz hyperthermia treatment in association with ionizing radiation for superficial cancers, and developed dysaesthesia in adjacent nerves. They considered that the ten patients had a syndrome of non-specific burning, tingling and numbness in a specific nerve. The effect was patient specific occurring in over two-thirds of the nominal ten to 12 treatment sessions of those affected, but the large majority of patients were unaffected. The symptoms saturated at the minimal power density available from the applicator (14 mW/cm2). Once the symptoms developed they were associated with the application of power without a time lag, and ceased at the instant of power removal. The authors concluded that the symptoms were a “direct result of the microwave field and not a thermal effect”, when a time lag due to thermal inertia would be expected. However, a thermal effect cannot be excluded. Reeves [22] has reviewed the medical records of 34 patients seen at United States Air Force (USAF) clinics after overexposure (approximately 25 – 2500 mW/cm2) to RFR between 1973 and 1985. He found little evidence of tissue
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damage after medical examination and a screen of blood tests including full blood examination and liver function tests. Some developed dysaesthesia which the author described as ‘real’ but no abnormality was found on nerve conduction studies. Several cases of dysaesthesia have been reported [16,22] after accidental exposures in faulty microwave ovens (2.45 GHz). This can result in a very large energy deposition into the hand/s and adjacent body from the 600 W source. There may be frank injury to nerves resulting in muscle fibrillation being detected on EMG studies, as well as effects on sensory nerves.
Discussion The above case reports provide information regarding the peripheral neurological effects of RFR and give insights into the range of mechanisms involved. The widespread independent reporting of cases from UK, USA, Australia and Brazil is persuasive evidence of the reality of the symptoms. The dysaesthesia has been reported after exposure to various forms of RFR across the spectrum. Some effects have been transitory as with hyperthermia treatment and CDMA exposure, whereas others have caused lasting effects, such as after very-high frequency (VHF) exposure or after a microwave oven accident. High exposure such as to a hand in a microwave oven results in frank nerve damage. For lower exposures abnormalities are often not detected using ordinary nerve conduction studies, but can be detected using more sensitive CPT techniques. This indicates that the lower exposures have not grossly injured the nerve but have altered its function. In the case of the ten hyperthermia patients with clear ‘on –off’ symptoms in response to exposure, this is not consistent with a thermal effect, but may reflect an electrostimulatory mechanism at levels , 14 mW/cm2 or another unknown mechanism. In the case of the rigger with symptoms arising from a mobile phone antenna and the two persons with changes after use of mobile phones, the exposure was less than the current safety standard indicating that thermal mechanisms are unlikely or the sensitivity of some persons is not accommodated by the standard. It is noted that only some persons exposed to a source develop dysaesthesia. In the hyperthermia cases only 10/200 (5%) developed dysaesthesia, the two men exposed to 4.1 GHz continuous wave (CW) for 90 min did not, and obviously only a small fraction of mobile phone users experience symptoms. This suggests either a specific sensitivity of some persons and/or a few who are at the extreme end of a normal distribution of sensitivity develop symptoms. The importance of modulations in causing effects at low levels of exposure is unclear. Microwave ovens are unmodulated and their effect at high exposure is consistent with thermal mechanisms. It is not known if the cancer
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hyperthermia treatment (915 MHz) was modulated but this is often the case. The absence of effect in the two men exposed to 4.6 mW/cm2 of 4.1 GHz which was known to be unmodulated may be related to this lack of modulation.
Pathophysiological mechanisms Some of these observations confirm current views of RFR mechanisms such as thermal effects from microwave ovens but others raise questions about our current understanding of health effects of RFR. The effect on nerve tissue to alter its function reversibly rather than destroy it as with the provocation study is not consistent with a simple thermal mechanism. In the hyperthermia cases exposed to 915 MHz, once the symptoms developed they were associated with the application of power without a time lag, and ceased at the instant of power removal. The authors concluded that the symptoms were a “direct result of the microwave field and not a thermal effect”. The occurrence of an electrostimulatory effect at these frequencies and power levels is unexpected and raises questions about the underlying neurophysiological mechanism of these effects, although a contribution from heating cannot be finally excluded. There are few studies on nerve conduction in laboratory preparations and studying dysaesthesia is not possible with animals since they are a subjective phenomena. Chou and Guy [5] found that strong pulsed or CW 2.45 GHz radiation was not able to elicit action potentials in isolated frog nerves. Pakhomov [20] found that nerve velocities did not change but potential amplitudes decreased using 915 MHz pulsed waves. Aplysia, a sea snail, permits monitoring of firing in identified sensory neurons in the mollusc’s brain and Seaman and Wachtel [26] observed increased firing rates of Aplysia ganglia exposed to 1.5 and 2.5 GHz CW radiation, which further increased when pulsed. Bolshakov and Alekseev [3] used Lymnea, a fresh water snail, to record and monitor neuronal firing patterns. They found that 900 MHz pulsed (but not CW) increased bursts of firing of Lymnea neurons. The relationship of these observations to dysaesthesia is unknown, but they demonstrate that RFR may affect neuronal excitability in molluscs. In humans exposed to RFR, the often transitory paraesthesia suggests that a reversible mechanism is operating. Earlier studies of Ng, Burke et. al. [19] showed that paraesthesia occurred during the supernormal phase of excitability, with reduced latency and increased supernormality during limb warming. This certainly suggests that even subtle warming may affect cutaneous nerve excitability. However, changes in ion channels offer a more likely mechanism for RFR changes. Burke and colleagues [6,14,15,18] have measured changes in neuronal excitability in various experimental and clinical situations using elegant threshold tracking techniques which might be applied to the study of RFR effects. Sodium channel blockage and/or changes in their gating and blocking of voltage-dependent
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potassium channels are included in their explanation of the different effects of ischaemia and hyperventilation on cutaneous nerve excitability. Lin et al. [15] have shown that nerve activity itself affects excitability of cutaneous afferents, even brief trains of impulses producing hypoexcitability, probably by effects on slow K þ conductances. Finally, Adey [1] has shown that weak amplitude modulated microwave fields may affect calcium efflux from awake cat cerebral cortex. Finally, at the molecular level the DNA/Genetox Expert Panel has produced a recent review of the data from over 100 studies suggesting that RFR is not directly mutagenic, and that adverse effects from high frequencies and high power intensities of RFR are predominantly the result of hyperthermia [4]. They cannot exclude some subtle indirect effects on the replication and/or transcription of genes under relatively restricted exposure conditions.
Conclusions The occurrence of effects in a few persons at levels below current safety standards or from unexplained mechanisms as in the hyperthermia cancer treatment cases indicates that while the standards are adequate for most there is a fraction of persons who may develop symptoms. The importance of these studies on peripheral nerves is partly that sometimes the injury is debilitating and partly because they may give insight into possible effects on the central nervous system [21]. The data we have briefly reviewed here endorse the need for replication of biological effects from low-level RFR exposure and caution in the application of the standards.
References [1] R. Adey, Effects of weak amplitude modulated microwave fields on calcium efflux from awake cat cerebral cortex, Bioelectromagnetics 3 (1982) 295–307. [2] Australian Standard (Interim) Radiofrequency Fields Part 1: Maximum exposure levels 3 kHz to 300 GHz, Standards Australia, Homebush, 1998. [3] M. Bolshakov, S. Alekseev, Bursting responses of Lymnea neurons to microwave radiation, Bioelectromagnetics 13 (1992) 119–126. [4] D. Brusick, R. Albertini, D. McRee, D. Peterson, G. Williams, P. Hanawalt, J. Preston, Genotoxicity of radiofrequency radiation. DNA/ Genetox Expert Panel, Environ. Mol. Mutagen. 32 (1998) 1–16. [5] C.K. Chou, A. Guy, Effects of electromagnetic fields on isolated nerve and muscle preparations, IEEE Trans. Microwave Theory Tech. 26 (1978) 141–147. [6] J. Grosskreutz, C. Lin, I. Mogyoros, D. Burke, Changes in excitability indices of cutaneous afferents produced by ischaemia in human subjects, J. Physiol. 518 (1999) 301 –314.
[7] B. Hocking, Preliminary report: symptoms associated with mobile phone use, Occup. Med. 48 (1998) 357–360. [8] B. Hocking, R. Westerman, Neurological abnormalities associated with mobile phones, Occup. Med. 50 (2000) 366 –368. [9] B. Hocking, R. Westerman, Case report: neurological abnormalities associated with CDMA exposure, Occup. Med. 51 (2001) 410–413. [10] B. Hocking, R. Westerman, Neurological changes induced by a mobile phone, Occup. Med. 52 (2002) 413 –415. [11] B. Hocking, R.A. Westerman, Neurological effects of radiofrequency radiation, Occup. Med. 53 (2003) 123–127. [12] International Commission on Non-Ionizing Radiation Protection, Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields (up to 300 GHz), Health Phys. 74 (1998) 494 –522. [13] B. Kolmodin-Hedman, K. Hanson Mild, M. Hagberg, E. Jonsson, M. Andersson, E. Erikson, Health problems among operators of plastic welding machines and exposure to radiofrequency electromagnetic fields, Int. Arch. Occup. Environ. Health 60 (1988) 243–247. [14] C. Lin, J. Grosskreutz, D. Burke, Sodium channel function and the excitability of human cutaneous afferent nerves during ischaemia, J. Physiol. 538 (2002) 435–446. [15] C. Lin, I. Mogyoros, D. Burke, Recovery of excitability of cutaneous afferents in the median and sural nerves following activity, Muscle Nerve 23 (2000) 763–770. [16] P. Marchiori, H. Silva, M. Hirata, A. Lino, M. Scaff, Acute multiple mononeuropathy after accidental exposure to oven microwave, Occup. Med. 45 (1995) 276 –277. [17] E.A. Masson, A. Veves, D. Fernando, A.J.M. Boulton, Current perception thresholds: a new, quick, and reproducible method for the assessment of peripheral neuropathy in diabetes mellitus, Diabetologia 32 (1989) 724–728. [18] I. Mogyoros, M.C. Kiernan, D. Burke, H. Bostock, Excitability changes in human sensory and motor axons during hyperventilation and ischaemia, Brain 120 (1997) 317 –325. [19] A. Ng, D. Burke, A. Al-Shehab, Hyperexcitability of cutaneous afferents during the supernormal period. Relevance to paraesthesiae, Brain 110 (1987) 1015–1031. [20] A. Pakhomov, B. Dubovick, V. Kolupayev, I. Degtyariov, A. Pronkevich, Search for microwave-sensitive structures and functions in the nervous system, Proceedings of the 14th Annual IEEE/EMBS Conference, Paris, IEEE/EMBS, Piscataway, NJ, 1992, p. 297. [21] A. Preece, G. Iwi, A. Davies-Smith, K. Wesnes, S. Butler, E. Lim, A. Varey, Effect of a 915-MHz simulated mobile phone signal on cognitive function in man, Int. J. Radiat. Biol. 75 (1999) 447–456. [22] G.I. Reeves, Review of extensive workups of 34 patients overexposed to radiofrequency radiation, Aviat. Space Environ. Med. 71 (2000) 206 –215. [23] C. Schilling, Effects of acute exposure to ultra high radio-frequency radiation on three antenna engineers, Occup. Environ. Med. 54 (1997) 281 –284. [24] C. Schilling, Effects of exposure to very high frequency radiofrequency radiation on six antenna engineers in two separate incidents, Occup. Med. 50 (2000) 49–56. [25] R.S. Scott, L. Clay, K.V. Storey, R.J. Johnson, Transient microwave induced neurosensory reactions during superficial hyperthermia treatment, Int. J. Radiat. Oncol. Biol. Phys. 11 (1985) 561 –566. [26] R. Seaman, H. Wachtel, Slow and rapid responses to CW and pulsed microwave radiation by individual Aplysia pacemakers, J. Microwave Power 13 (1978) 77 –85. [27] WHO Environmental Health Criteria 137. Electromagnetic Fields 300 Hz-300 GHz, Geneva, WHO, 1994.