Elson, E. Biologic Effects of Radiofrequency and Microwave Fields: In Vivo and in Vitro Experimental Resultsand .

The Biomedical Engineering Handbook: Second Edition.

Ed. Joseph D. Bronzino
Boca Raton: CRC Press LLC, 2000

92
Biologic Effects of
Radiofrequency and
Microwave Fields:
In Vivo and In Vitro
Experimental Results
92.1
92.2
92.3
92.4
92.5

Edward Elson
Walter Reed Army Institute
of Research

92.6
92.7

Cellular and Molecular Biology

Reproduction, Growth, and Development
Effects on the Nervous System
Behavioral Effects
Effects on the Cardiovascular and Hematopoietic
Systems
Auditory and Ocular Effects
Conclusion

Radiofrequency radiation (RFR), defined by the Institute of Electrical and Electronics Engineers (IEEE)
as extending from 3 kHz to 300 GHz, is absorbed by biologic systems, which are water-dominated
dielectrics richly endowed with electrolytes and intricately packaged polar and nonpolar molecules. At
sufficiently high RF intensities, thermal energy is generated that can quickly produce morbidity and, after
thermoregulatory mechanisms are overwhelmed, mortality. In recent years, work has focused on possible
effects at nonthermal levels or under conditions in which physiologic temperature can be maintained
by regulatory mechanisms of living systems.
The human perception of microwave heating has been studied [1,2]. Although the human is the
ultimate test object, the bulk of research has been on animals. This requires an understanding and
appreciation of biophysical principles and comparative medicine. Such studies require interspecies scaling, [3-7] the selection of biomedical parameters that reflect basic physiologic functions, and differentiation of adaptational or compensatory changes from pathologic manifestations. In comparing results
of experiments performed in the same or different laboratories, standardization of conditions is important
and, unfortunately, all too often not attained.
Even by using approaches where absorbed energy patterns in a test animal are set to approximate as
closely as possible the patterns that may exist in humans under certain exposure conditions, the intrinsic
physical and physiologic dissimilarities between species further confound the problem of extrapolating
between animals and humans. In addition to the obvious external geometric differences, the differences

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in internal vascular anatomy and mechanisms of heat dissipation in fur-bearing animals compared with
humans must be taken into considerations.
Johnson [8] has described factors that affect absorption of electromagnetic energy in animals. This
absorption is dependent on the size and geometry of the animal relative to the wavelength and polarization. The wavelength-to-animal size relationship (/a, where a is the longest axis dimension of the body
and the electric field vector is parallel to the longest axis) is a critical factor in the relative absorption
cross section (RAC). The RAC is the ratio of the absorbed power to the power incident on the geometric
cross-sectional area of the animal [9]. This produces the immediate result that at a given frequency and
power density, the specific absorption rate (SAR) is vastly different in animals depending on size. To
produce an identical whole-body average SAR, one must scale from one frequency to another. It is of
practical importance to realize that experiments on biologic effects at 2.45 GHz on small animals, such
as mice and rats, do not scale to humans at 2.45 GHz but to effects on humans at approximately 100 MHz.
In recent years, much modeling and experimental measurement has been done on the variation of
localized absorption in animals and humans [10].

92.1 Cellular and Molecular Biology

The mutagenic potential of microwave energy has been evaluated by various techniques, including point
mutations in bacterial assays [11], the dominant lethal test in mammalian systems [12], and genetic transmission in Drosophila [13], with inconsistent results. Two studies reported effects of RFR on sister chromatid
exchange [14,15]. Such changes as were seen appeared to be related to temperature elevations rather than
RF exposure. From many studies there is little evidence that exposure to RF radiation induces mutations in
bacteria, yeasts, fruit flies, or mammals. One study reported cytogenetic effects at 200 W/m2 [16], but its
finding was contradicted by another study [17] that failed to find any cytogenetic effects at 2 to 5 kW/m2.
There is a consensus among students of the subject that RF radiation does not initiate carcinogenesis
by inflicting direct damage on the genome by any mechanism resembling the effect of ionizing radiation.
This is evident from the low photon energies involved. RF radiation as part of a compound stress on
intact animals has been studied with conflicting results. Fibroblasts in tissue culture were exposed to
benzpyrene and the promoter 12-o-tetradecanoylphorbol with and without 2.45-GHz microwaves, SAR
4.4 W/kg. Microwave exposure produced a several-fold increase in transformation frequency [18].
In a study of long-term, low-level microwave exposure of rats, Chou et al. [19] compared 100 rats
exposed to 2.45-GHz pulsed microwaves, average SAR 0.15 to 0.4 W/kg, 21 hours per day for 25 months
with suitable controls. No adverse effects were found. An increase in malignancies of specific type in
exposed animals was found, but a significant increase in malignancies of all types was not found. This
was interpreted as minimal evidence of carcinogenic action.

92.2 Reproduction, Growth, and Development

The effect of microwaves on the testes has been studied extensively [20-22]. Exposure of the scrotal area
at high power densities (>500 W/m2) results in varying degrees of testicular damage, such as edema,
necrosis of seminiferous tubules, and atrophy, at 2.45, 3, and 10 GHz.
Lebovitz et al. [23] compared pulse-modulated 1.3-GHz microwaves with conventional heating in rats.
The authors stated that all damage could be explained by heating. Although the general consensus is that
damage is thermally mediated, Cleary et al. [24] reported decreases in sperm function in vitro utilizing
suspension of mouse sperm exposed to SARs of 50 W/kg or greater but with stringent temperature control.
Effects on embryonic development have been studied. Thermal stress appears to be the primary
mechanism by which RF energy absorption exerts a teratogenic action. Chernovetz et al. [25] and others
have pointed out evidence that indicates that increases in mortality and resorption are probably related
to peak body temperature and its duration regardless of the method by which the temperature elevation
is elicited. Rugh and McManaway [26] were able to prevent the increase in incidence of teratogenic

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activity, which they had previously reported, by lowering the maternal body temperature through controlled use of pentobarbital anesthesia. The most common result from many studies [27] appears to be
a reduced or retarded gain of body mass, thermally mediated.

92.3 Effects on the Nervous System

Guy and Chou [28] studied response thresholds in rats for short, high-intensity microwave pulses. Rats
were exposed to single 915-MHz RF pulses of 1-s to 300-ms duration. No reaction occurred until the
SAR rose to 29 kJ/kg, which correlated with a temperature rise in the brain of 8C. Seizures occurred
followed by unconsciousness for 4 to 5 minutes. Complete recovery ensued. Postmortem examination
revealed some demyelination of neurons 1 day following exposure and focal gliosis 1 month after
exposure. More intense exposures could produce a fatal outcome. Brown et al. [29] looked for response
thresholds at lower energies, with particular attention to the onset of an involuntary, generalized muscular
contraction that did not appear to be injurious.
Studies of low-level chronic effects, mostly dating to the 1960s and 1970s, have yielded inconsistent
results. Problems of dosimetric measurement and quantitation of reproducible biologic endpoints have
left uncertain whether extended exposure to low-intensity or nonthermal levels of radiofrequency energy
produces effects, adverse or not. Bawin et al. [30] reported that electromagnetic energy of 147 MHz,
amplitude modulated, at brain wave frequencies (8 to 16 Hz), influenced spontaneous and conditioned
EEG patterns in the cat at 10 W/m2. No effects were seen at other modulation frequencies.
At high field intensities, when death is a result of hyperthermia, pathologic changes are identical to
those of hyperthermia. At lower levels of exposure, there are no changes that are specific to RF radiation.
From the work of Albert and DeSantis [31], there appears to be a threshold for permanent histologic
damage to the brain for exposures lasting several hours per day for up to 3 weeks at between 100 and
250 W/m2 at 2.45 GHz CW.
An historically controversial issue has been the effect of radiofrequency radiation on the blood-brain
barrier (BBB). This poorly understood functional barrier provides resistance to movements of largemolecular-weight, fat-insoluble substances from the blood vessels of the brain into brain tissue, presumably to protect the brain from invasion by various blood-borne pathogens and toxic substances. Early
reports asserted that RF radiation reduces the barrier, allowing many substances normally barred from
brain tissue to enter including many drugs. It does appear that gross hyperthermia (brain tissue elevated
to 43C) compromises the barrier [32]. But there is evidence that the level of a drug entering the brain
might actually be reduced at moderate levels of hyperthermia [32].
A number of studies on isolated nerve preparations have been performed. There is no direct production
of a nerve impulse or action potential by CW or PW microwaves, but conduction velocity and amplitude
can be changed, mediated by temperature elevations of at least 1C in the solution. Similar changes can
be produced by ambient changes in temperature [33].

92.4 Behavioral Effects

Studies have been conducted on the effects of RFR on performance of trained tasks or operant behavior
by rats and rhesus and squirrel monkeys [34,35]. All the studies indicated that the exposure would result
in suppressed performance of the trained task and that an energy/dose threshold for achieving the
suppression existed. Depending on duration and other parameters of exposure, the threshold power
density for affecting trained behavior ranged between 50 and 500 W/m2. Lebovitz [36] and Akyel et al.
[37] were unable to find any specific effect attributed to pulse power and noted that interference with
behavior appeared to be of thermal origin. Raslear et al. [39] and Akyel et al. [38] later found performance
deficits at very high peak, short-pulse powers at low repetition rates, such that no measurable temperature
changes occurred in the brains of rats. Peak brain SAR was reported to be 7 MW/kg for 80-ns-wide
pulses with an average brain SAR of 0.07 W/kg.

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92.5 Effects on the Cardiovascular

and Hematopoietic Systems
At nonthermalizing levels of exposure, both bradycardia and tachycardia have been found in different
studies of different animals and with inconsistent results in the same animal. The specific conditions of
exposure, biologic variability, and other sources of error could account for the findings.
Hyperthermia of RFR or non-RFR origin produces tachycardia and a decrease in total peripheral
resistance caused by vasodilation, a heat dissipating response to the thermal burden. Variations from this
general principle have been found in unusual circumstances, including the application of localized pulse
power to the head, neck, and thoracic region [40].
Changes in the concentrations of circulating white blood cells have been observed in a number of
animal species exposed to microwave energy. The changes were not consistent within or between species
and depended on exposure conditions and thermal changes in tissue. A number of mechanisms have
been proposed to explain changes in cellular dynamics, including stimulation of synthesis at thermal
levels, recirculation of sequestered cells, and increased hypothalamic-hypophysial-adrenal function following thermal stress. Such changes may be related to changes in immune function noted by a number
of investigators [41].

92.6 Auditory and Ocular Effects

Microwave hearing, the perception of a clicking or buzzing in the presence of pulsed microwave energy
(but not CW) at low power densities [42], has been attributed to thermoelastic transduction of pulsed
microwaves in the head, with detection by the sensory epithelium of the cochlea. The process, familiar
to occupationally exposed workers, appears not to be harmful at energies commonly encountered [43].
A threshold for cataract production in the lens of the rabbit eye has been found for 2.45-GHz
microwaves at 1.5 kW/m2 for 100 minutes. An intraocular temperature elevated to at least 45C appears
to be required [44]. For exposures lower than this there does not appear to be a cumulative effect from
microwave exposure, i.e., no pathologic damage following many exposures with time, for which each
individual exposure produces no detectable damage.

92.7 Conclusion
Elucidation of the biologic effects of RF exposure requires study of the available literature. Evaluating
the research is a difficult task even for scientists specializing in the field. The possible sources of error of
the biologic sciences are coupled with the sources of error associated with RF engineering and dosimetry.
It is often difficult to make meaningful comparisons between studies. The issue of effects or even hazards
at nonthermal levels of exposure stimulates continuing debate and research that may affect existing
consensus safety standards. Whether existing standards are adequate frequently rests on a determination
of whether documented effects constitute actual hazards at energy levels not producing morbidity. The
research of the future will continue to affect the issue of safe levels of exposure.

Acknowledgments
I wish to thank Mrs. Doris Michaelson for her support and permission to base this review on Dr. S.
Michaelsons monograph that appeared in the Handbook of Biological Effects of Electromagnetic Fields,
published by CRC Press in 1986. The opinions or assertions contained are private views of the author
and are not to be construed as reflecting the official views of the Department of the Army or the
Department of Defense.

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Defining Terms
Blood-brain barrier: An anatomical and physiologic barrier to the movement of large-molecularweight, fat-insoluble substances from the blood vessels of the brain into brain tissue.
Bradycardia: An abnormal slowness of the heartbeat, as evidenced by slowing of the pulse rate to 60 or
less.
Radiofrequency radiation (RFR): Defined by the Institute of Electrical and Electronics Engineers
(IEEE) as that part of the electromagnetic spectrum extending from 3 kHz to 300 GHz.
Relative absorption cross section (RAC): The ratio of the absorbed power to the power incident on
the geometrical cross-sectional area of an animal.
Tachycardia: An excessive rapidity in the action of the heart, usually applied to a pulse rate above
100 per minute.

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Further Information
The reader is encouraged to consult the Handbook of Biological Effects of Electromagnetic Fields, edited
by C. Polk and E. Postow, (CRC Press). Bioelectromagnetics, the journal of the Bioelectromagnetics Society
and the Society for Physical Regulation in Biology and Medicine, is the leading publication of contemporary research on the biologic effects of electromagnetic radiation.

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