Effects of Electromagnetic Fields on Organs and Tissues
Introduction
A large body of literature
exists on the response of tissues to electromagnetic fields, primarily in the
extremely-low-frequency (ELF) and microwave-frequency ranges. In general, the
reported effects of radiofrequency (RF) radiation on tissue and organ systems
have been attributed to thermal interactions, although the existence of
nonthermal effects at low field intensities is still a subject of active
investigation. This chapter summarizes reported RF effects on major
physiological systems and provides estimates of the threshold specific
absorption rates (SARs) required to produce such effects. Organ and tissue
responses to ELF fields and attempts to characterize field thresholds are also
summarized. The relevance of these findings to the possible association of
health effects with exposure to RF fields from GWEN antennas is assessed.
Nervous
System
The effects of radiation on
nervous tissues have been a subject of active investigation since changes in
animal behavior and nerve electrical properties were first reported in the
Soviet Union during the 1950s and 1960s.1 RF
radiation is reported to affect isolated nerve preparations, the central
nervous system, brain chemistry and histology, and the blood-brain barrier.
In studies with in vitro nerve
preparations, changes have been observed in the firing rates of Aplysia neurons
and in the refractory period of isolated frog sciatic nerves exposed to
2.45-GHz microwaves at SAR values exceeding 5 W/kg.2,3,4 Those
effects were very likely associated with heating of the nerve preparations, in
that much higher SAR values have not been found to produce changes in the
electrical properties of isolated nerves when the temperature was controlled.5, 6Studies
on isolated heart preparations have provided evidence of bradycardia as a
result of exposure to RF radiation at nonthermal power densities,7 although
some of the reported effects might have been artifacts caused by currents
induced in the recording electrodes or by nonphysiological conditions in the
bathing medium.8,9,10 Several
groups of investigators have reported that nonthermal levels of RF fields can
alter Ca2+ binding to the surfaces of nerve cells in isolated
brain hemispheres and neuroblastoma cells cultured in vitro (reviewed by the
World Health Organization11 and
in Chapters 3 and 7 of this report). That phenomenon,
however, is observed only when the RF field is amplitude-modulated at extremely
low frequencies, the maximum effect occurs at a modulation frequency of 16 Hz.
A similar effect has recently been reported in isolated frog hearts.12 The
importance of changes in Ca2+ binding on the functional
properties of nerve cells has not been established, and there is no clear
evidence that the reported effect of low-intensity, amplitude-modulated RF
fields poses a substantial health risk.
Results of in vivo studies of
both pulsed and continuous-wave (CW) RF fields on brain electrical activity
have indicated that transient effects can occur at SAR values exceeding 1 W/kg.13,14Evidence
has been presented that cholinergic activity of brain tissue is influenced by
RF fields at SAR values as low as 0.45 W/kg.15 Exposure
to nonthermal RF radiation has been reported to influence the
electroencephalograms (EEGs) of cats when the field was amplitude-modulated at
frequencies less than 25 Hz, which is the range of naturally occurring EEG
frequencies.16 The
rate of Ca2+ exchange from cat brain tissue in vivo was
observed to change in response to similar irradiation conditions.17 Comparable
effects on Ca2+ binding were not observed in rat cerebral
tissue exposed to RF radiation,18 although
the fields used were pulsed at EEG frequencies, rather than
amplitude-modulated. As noted above, the physiological significance of small
shifts in Ca2+binding at nerve cell surfaces is unclear.
A wide variety of changes in
brain chemistry and structure have been reported after exposure of animals to
high-intensity RF fields.19 The
changes include decreased concentrations of epinephrine, norepinephrine,
dopamine, and 5-hydroxytryptamine; changes in axonal structure; a decreased
number of Purkinje cells; and structural alterations in the hypothalamic
region. Those effects have generally been associated with RF intensities that
produced substantial local heating in the brain.
Extensive studies have been
carried out to detect possible effects of RF radiation on the integrity of the
blood-brain barrier.20,21 Although
several reports have suggested that nonthermal RF radiation can influence the
permeability of the blood-brain barrier, most of the experimental findings
indicate that such effects result from local heating in the head in response to
SAR values in excess of 2 W/kg. Changes in cerebral blood flow rate, rather
than direct changes in permeability to tracer molecules, might also be
incorrectly interpreted as changes in the properties of the blood-brain barrier.
Effects of pulsed and
sinusoidal ELF fields on the electrical activity of the nervous system have
also been studied extensively.22,23 In
general, only high-intensity sinusoidal electric fields or rapidly pulsed
magnetic fields induce sufficient current density in tissue (around 0.1-1.0 A/m2 or
higher) to alter neuronal excitability and synaptic transmission or to produce
neuromuscular stimulation. Somewhat lower thresholds have been observed for the
induction of visual phosphenes (discussed in the next section) and for
influencing the electrical activity of Aplysia pacemaker neurons when the
frequency of the applied field matched the endogenous neuronal firing rate.24Those
effects, however, have been observed only with ELF frequencies and would not be
expected to occur at the higher frequencies associated with GWEN transmitters.
Recent studies with human volunteers exposed to 60-Hz electric and magnetic
fields with intensities comparable with those of high-voltage power lines have
shown no consistent effects on the EEG.25 Minor
changes were observed in reaction time and heart rate, but the variations were
within normal ranges.
Visual
System
Cataract development as a
result of exposure of the eye to high-intensity RF radiation has been studied
for more than 30 years. Extensive experiments have been carried out with
rabbits to determine the dependence of cataractogenesis on the frequency and
intensity of RF fields and on exposure time.26-28 In
general, the lowest thresholds for cataract induction have been observed with
near-field exposure at 1-10 GHz, and a power density greater than 100 mW/cm2 applied
for at least an hour is required. Most of the evidence indicates that the
mechanism of injury leading to lens opacity is thermal, and pulsed and CW
microwave fields appear to have similar thresholds for producing cataracts.19 Multiple
subthreshold exposures do not lead to cataracts if the time between exposures
is long enough to permit the tissue to return to its normal temperature.1 At
frequencies where the wavelength of the RF field is not well matched to the
dimensions of the eye, cataracts are not produced even at extremely high power
densities approaching the lethal levels. Although it is difficult to
extrapolate results from laboratory animals to humans, the threshold power
density required to produce cataracts is expected to be similar in rabbits and
humans because of the structural similarities and comparable dimensions of the
eyes in these species.
Results of recent studies with
monkeys have indicated that vascular leakage can increase at relatively low
power densities of pulsed 2.45-GHz radiation when the eye is pretreated with
timolol maleate, which decreases intraocular pressure by reducing the
production of aqueous humor. A power density as low as 1 mW/cm2,
corresponding to an intraocular SAR of 0.26 W/kg, has been observed to produce
the effect.29 Those
findings might have implications for RF ocular damage in humans being treated
with timolol maleate for glaucoma. However, the threshold power density at 2.45
GHz is still well in excess of the intensity of the RF fields produced by GWEN
antennae in areas accessible to the general public.
A visual phenomenon associated
with exposure to ELF fields that has been studied for nearly a century is the
induction of a flickering illumination known as phosphenes. Time-varying
magnetic fields with either pulsed or sinusoidal waveforms and frequencies
below 100 Hz have been shown to produce phosphenes when the time rate of change
of the field exceeds 1.3 T/sec.30 The frequency most likely to produce
magnetophosphenes with sinusoidal fields is 20 Hz; the threshold flux density
for eliciting the visual effect is 8 mT.31 A
similar frequency dependence has been observed for electrophosphenes produced
by placing electrodes in contact with the forehead near the eyes.32 The
locus of the effect is in the retina, and available evidence suggests that
induced currents in the retina elicit visual responses similar to those
resulting from photic stimulation.30Changes
in visually evoked potential (VEP) have also been reported in response to ELF
magnetic fields with flux densities that are 5-10 times greater than those
required to produce phosphenes.3Because
phosphenes and VEP alterations are observed only with fields below 100 Hz, such
phenomena are not expected to occur in response to the low-frequency fields
associated with GWEN antenna.
Endocrine
System
Many studies with rodents and
monkeys have demonstrated that exposure to thermogenic levels of RF radiation
produces endocrine alterations, the most consistent change being an increase in
plasma corticosterone.1, 34 SAR
values in excess of 3 W/kg produce an increase in plasma corticosterone in rats
that depends on secretion of adrenocorticotropic hormones by the pituitary.35Decreased
thyroid hormone levels have also been observed in response to thermogenic
levels of RF radiation, and this response has been associated with an
inhibition of thyrotropin secretion by the pituitary.36,37 In
general, the alteration of hormone concentrations is reversible after
termination of the RF exposure. Those findings indicate that RF heating alters
the complex interactions of the hypothalamic, pituitary, adrenal, and thyroid
systems that are important in the maintenance of homeostasis.19 It
is noteworthy that a 2-yr exposure of rats to nonthermogenic pulsed 2.45-GHz
microwaves did not produce detectable endocrine alterations.37
Studies on the possible
endocrine effects of ELF electric and magnetic fields have yielded inconsistent
results.22 Increases,
decreases, and no change in plasma steroid hormones have been reported. Results
of studies with dogs and rats suggest that the threshold 60-Hz electric field
required to produce changes in blood concentrations of corticosterone or
testosterone is in excess of 10 kV/m.38-40 Results
of experiments with monkeys exposed to 60-Hz electric and magnetic fields at
intensities typical of those in the vicinity of high-voltage transmission lines
indicated that a decrease in neurotransmitter concentrations occurs during
chronic exposure.41 However,
there were no other observations of behavioral or physiological changes in the
exposed animals.
The most widely studied effect
of ELF fields on the endocrine system is an apparent depression in the
nocturnal rise of pineal melatonin.42 Changes
in pineal melatonin have reportedly occurred after 2-3 wk of exposure to
electric fields with intensities exceeding 1.7 kV/m in air. The effect is
reversible, with a return of nocturnal pineal melatonin to control values
within 3 d of termination of exposure. A similar effect on pineal melatonin has
been observed after exposure of rodents to a 0.05 mT static magnetic field that
was continuously switched on and off in 5-min cycles for 1 h beginning 3.5 h
after the onset of darkness.43 Interest
in this phenomenon has centered around the effects of melatonin on cell
proliferation and its possible carcinostatic effects.44-46 A
major problem in the interpretation of the results of studies is lack of
quantitative information on the threshold fields required to alter melatonin
concentration. It is also unclear whether ELF fields directly alter pinealocyte
functions or whether the reported alteration in pineal melatonin production is
secondary to effects of the fields on the nervous system. Further studies are
needed to assess the possible influence of field-induced changes in pineal
melatonin on physiological regulation and the risk of endocrine-dependent
cancers. It is not now possible to extrapolate the available information
obtained with 60-Hz fields or intermittent DC magnetic fields to the possible
effects of fields with higher frequencies.
Immune
System
Effects of RF-field exposure on
cellular components of the immune system have been reported with both in vitro
and in vivo test systems.1 Lymphoblast
transformation and changes in responsiveness to mitogens have been reported,
although the effects observed in different laboratories have been quite variable.
It appears from available information that the threshold SAR for altering
lymphocyte responses to mitogens exceeds 4 W/kg with both pulsed and CW
microwaves.47-49Thermogenic
levels of exposure have been found to decrease natural killer cell activity and
to activate macrophages.50, 52 The
changes observed in components of the immune system at RF power densities that
produce tissue heating are consistent with the expected effects of increased
release of steroid hormones into the circulation.1,52,53 In
one study involving a 2-yr exposure of rats to a nonthermal level of pulsed 2.45-GHz
microwaves (SAR, 0.4 W/kg), no significant irreversible changes were found in
the concentrations of lymphocytes or their responses to mitogen stimulation.
Numerous studies have been
carried out to determine the effects of ELF electric and magnetic fields on
components of the immune system. In general, sinusoidal ELF fields have been
found to have no significant effects on immune competence after in vivo
exposure of laboratory animals.22,25 However,
reduced mitogen responses and decreased target-cell toxicity have been reported
for lymphocytes exposed in vitro to pulsed magnetic fields or 60-Hz
amplitude-modulated RF fields.55-57 These
effects might have resulted from the relatively high current densities induced
in the cell suspensions. In a study involving 60-Hz electric and magnetic
fields with a sinusoidal waveform and intensities comparable with those of the
fields near high-voltage power lines, no effects were observed on the
immunologic functions of peripheral human and canine lymphocytes obtained from
donors that either were normal or had been challenged with specific antigens.58
Hematologic
and Cardiovascular Systems
Several studies have been
performed to assess the effects of both thermogenic and nonthermogenic levels
of RF radiation on blood chemistry and blood-cell counts.
Most were conducted with
2.45-GHz microwaves, and the results indicate that power densities producing an
average whole-body SAR of less than 2.5 W/kg do not produce significant
alterations in hematologic indexes.59 In
one chronic-exposure study with rabbits subjected to 2.45-GHz microwaves 23 h/d
for 180 d, a small decrease was observed in eosinophil count, serum albumin
concentration, and calcium concentration.60 None
of the other 38 blood characteristics measured in the study were found to
change in response to chronic RF exposure.
At high levels of RF exposures
of mice leading to rectal temperature increases of 2-4ºC, decreased lymphocyte
counts and increased neutrophil counts were observed.61 It
was suggested that the release of adrenal steroids into the blood as a result
of heat stress could have produced the changes in blood-cell counts.52,53 Thermogenic
levels of pulsed or CW microwaves might also affect the cellular composition
and proliferative capacity of bone-marrow cells.62,63 Both
bradycardia and tachycardia have been observed in laboratory animals exposed to
thermogenic levels of RF radiation with SAR values in excess of 2.5 W/kg.64,65 In
general, the effects on cardiac dynamics were transient and consistent with
effects expected from body heating.
As reviewed by several authors,22,54, 66 the
threshold ELF fields for producing significant cardiovascular and hematologic
alterations are high. For example, cardiovascular indexes were not affected by
exposure to 60-Hz, 100-kV/m fields.67 Acute
human exposures to ELF electric fields up to 200 kV/m and magnetic fields up to
5 mT have also failed to show any consistent hematologic or cardiovascular
effects.68,69
Animal
Carcinogenesis
A few studies have investigated
the carcinogenic potential of microwave radiation in whole animals. Male Swiss
albino mice were exposed to a radar transmitter with 9.27-GHz frequency
modulated with 2-µsec pulses at a pulse repetition frequency of 500/sec
for 59 wk, 5 d/wk and 4.5 min/d.70 The
power used (1 kW/m2) caused a temperature rise of 3.3ºC. There was
no difference between exposed and control animals in a number of
characteristics examined, including body weight, red-cell and white-cell counts,
and body temperature. Testicular degeneration occurred in 23 of 57 (40%) of
treated animals and in 3 of 37 (8.1%) of the controls. Monocytic or lymphatic
organ tumors or myeloid leukemia was seen in 21 of 60 (35%) treated and 4 of 40
(10%) control animals. However, that increase was seen in the animals killed at
16 mo—I mo after cessation of treatment—but not at 19 mo. In addition, there
has been considerable criticism of the experimental methods (e.g., definition
of leukosis as an increase in circulating leukocytes, which could have been due
to infection) and statistical analysis.71, 72 Thus,
the study is of questionable use for supporting an increase in cancer risk. The
incident power density was approximately 100 times greater than the highest
relevant GWEN levels.
Female RFM mice were exposed to
0.8-GHz microwave radiation for 2 h/d, 5 d/wk for 35 wk at 430 W/m.73 Red
and white cell counts, hemoglobin, hematocrit, activity, body weight, and
survival were measured, but no histopathologic examinations, were carried out.
The only statistically significant finding was an increase in body weight of
animals older than 86 wk in exposed mice over control animals.
A University of Washington
study on male Sprague-Dawley rats was designed to simulate the maximum absorbed
power (0.4 W/kg) of 0.45-GHz radiation.74 The
frequency was chosen as typical of a midrange radar system. Rats were exposed
at 2.45 GHz, because it yielded a ratio of wavelength to maximum body dimension
similar to that of children exposed at 0.45 GHz. Benign pheochromocytoma of the
adrenal medulla was the only lesion with a statistically significant increase
in incidence. However, that incidence was not higher than that seen in control
rats of other colonies. The time for appearance of first tumor was also shorter
in treated animals (457 d) than in control animals (540 d). When all malignant
tumors observed at all sites are combined, there is a statistically significant
increase in incidence in the exposed animals. That holds true for carcinomas,
but not for sarcomas.
An effect on the process of
carcinogenesis has been reported in several studies that used injected tumor
cells or animals treated with low doses of a known carcinogen. The effects of
2.45-GHz microwave radiation at 50 and 150 W/m2 in an anechoic chamber was
determined.75 Lung
sarcoma cells were injected intravenously into Balb/C mice, and the lung-cancer
colonies were counted after 1, 2, and 3 mo of treatment. After 3 mo, the
numbers of lung nodules were 3.6 ±2.2. 7.7 ± 2.0, 6.1± 8, and 10.8 ± 2.1 in
control animals, chronically stressed animals, animals exposed at 50 W/m2,
and animals exposed at 150 W/m2, respectively. The time to
appearance of spontaneous breast tumors in 50% of C3H/HeA mice decreased in
animals treated with chronic stress, 50 W/m2, and 150 W/m2 (255,
261, and 219 d, respectively, compared with 322 d in controls). The time of
appearance of skin tumors induced by benzo[a]pyrene was also shortened when
irradiation for 1 or 3 mo preceded carcinogen application or when radiation and
carcinogen were given at the same time.75 Again,
stress closely duplicated the effect of 50-W/m2 radiation, and,
although the results of 150 W/m2 were significantly greater
than those of stress or 50 W/m2, thermal effects might be
responsible for the results at 150 W/m2. The power density of 50 W/m2 is
approximately 7 times the low-frequency power density at the GWEN site
boundary.
Negative and beneficial results
of exposure have also been reported. The effect of continuous or pulsed waves
of 2.45 GHz (10 W/m2; SAR, 1.2 W/kg) was studied in black C57/6J mice
with B16 melanoma.76 No
significant effects on tumor development or survival times were observed.
Beneficial effects of induced hyperthermia have been observed after treatment
with microwave radiation.77,78 Lung
sarcoma cells injected into Balb/C mice demonstrated temporary regression after
exposure to 2.45-GHz radiation. After radiation exposure was stopped, tumor
volumes increased and lung metastases exceeded those in untreated animals.77 Sarcoma
cells were implanted on postpartum day 16 into CFW mice that had been
irradiated in utero with 2.45-GHz microwaves (35 W/kg) during days 11-14 of
gestation; the mice were then subjected to additional exposure to microwave
radiation. Fetal exposure to radiation that increased the dam's colonic
temperatures by an average of 2.2ºC decreased tumor incidence (13%, with 46% in
controls). Both tumor-bearing and tumor-free animals that were irradiated as
fetuses lived longer, on the average, than controls. Enhanced immunocompetence
related to increases in temperature was suggested as an explanation.
In summary, several studies
have provided some evidence of possible carcinogenic potential, and others have
shown no effect. Consistent reproducible studies demonstrating a dose-response
relation in animals are lacking, and the interpretation of several studies is
complicated by thermally induced stress. All studies were conducted with
electromagnetic fields larger than the relevant GWEN fields.
Considerable interest has
arisen concerning a possible role of electromagnetic fields as cocarcinogens or
cancer promoters. Results of cellular studies that support such speculation are
discussed in Chapter 7. Studies by McLean et al.79 have
begun to explore directly the possible role of 60-Hz magnetic fields as cancer
promoters. In their studies, cancers in SENCAR mice—known for their sensitivity
to the promoting effects of 12-O-tetradecanoylphorbol-13-acetate (TPA)—were
initiated with dimethylbenzanthracene and then promoted with TPA, a 2-mT
magnetic field, or a combination of TPA and a magnetic field. Tumor development
was then observed for 20 wk. There was no significant difference in tumor
development between those promoted with TPA alone and those promoted with TPA
and a magnetic field. However, recent results of another experiment by the same
group of investigators suggest that a 60-Hz magnetic field acts as a
co-promoter. Additional studies are required to substantiate those findings.
Beniashvili et al.80 treated
rats with nitrosomethyl urea and then exposed them to either a 0.2 G static or
50-Hz magnetic field for either 0.5 or 3 h/d for up to two years. They found an
increased incidence and number of mammary tumors in the groups exposed to the
magnetic fields, with the ac field being more active than the static one. They
also reported an increased tumor response in rats exposed to the 50-Hz field alone.
.
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