Biological effects of radiofrequency radiation: concepts and criteria.

The radiofrequency (RF) portion of the electromagnetic radiation spectrum between 0.5 MHz and 100 GHz is a significant factor in numerous industrial and military as well as consumer and medical applications. Certain organ and organ systems can be affected by RF energy absorption. Biological reactions are a response to thermal energy conversion. To understand the fundamental factors in the response to RF energy absorption, it is necessary to utilize accepted principles of dosimetry, biologic experimentation and interpretations, as well as differentiation between effect and hazard. Analysis of the relevant literature leads one to conclude that there are no unequivocal pathophysiologic changes in humans exposed to levels up to 4 W kg-1.

Influence of 60-Hertz magnetic fields on leukemia.

Female DBA/2 mice at 8 weeks of age were implanted with P388 leukemia cells in groups of ten mice and exposed to a 60-Hz 1.4-microT, 200-microT, or 500-microT magnetic field 2-3 hours after the implant for 6 hours daily, 5 days/week until all the exposed P388-treated and nontreated mice died. Parallel exposed groups of non-P388-treated mice and P388-treated mice exposed at 0 microT were included for study. No statistically significant differences (P greater than .05) in survival, spleen weight, or body weight resulted between P388-treated or nontreated mice from exposure to the magnetic field. No effect on the incidence or progression of P388 leukemia was apparent.

Mitogen responsiveness after exposure of influenza virus-infected human mononuclear leukocytes to continuous or pulse-modulated radiofrequency radiation.

Data are available regarding interactions of radiofrequency radiation (RFR) with normal human mononuclear leukocytes. However, no data have emerged regarding effects of RFR on human leukocytes already challenged by a commonly encountered alternate agent, such as a virus. Therefore, in these studies, uninfected (control) and in vitro influenza virus-infected human mononuclear leukocytes were exposed to 2450 MHz RFR as continuous waves or pulse-modulated at 60 or 16 Hz, at a specific absorption rate of 4 mW/ml. Such exposures produced no significant effects on leukocyte viability or on mitogen-stimulated DNA synthesis by either uninfected or influenza virus-infected leukocytes when compared to sham-RFR-exposed of cells.

Effects of microwaves on three different strains of rats.

Confounding factors influencing the sensitivity of biological indicators of microwave exposure--lethality, colonic temperature (Tco), decreased body mass (dW), corticosterone (CS), thyrotropin (TSH), thyroxine (T4), free thyroxine (FT4), and prolactin (PRL) concentration--were studied in Long-Evans (LE), Wistar-Kyoto (WKY), and spontaneous hypertensive (SHR) rats. The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Test power density ranged from 1 to 50 mW/cm2 for 2 h. In contrast to the LE and WKY rats, the SHR rats were characterized by intolerance (death) between 40 and 50 mW/cm2 (9.2 to 11.5 W/kg). The lowest lethal Tco was 41.1 degrees C. Survivors including all the LE and WKY rats were capable of maintaining Tco lower than 41.0 degrees C. In general, strain of rat seemed to influence other bioindicators and to interact with power density on these bioindicators. Except for Tco and PRL, baseline for the various bioindicators varied among the different strains of rats. Responses of T4 and FT4 were limited in magnitude and inconsistent among strains of rats. In general, the magnitude of Tco increase was more pronounced in SHR than in WKY. Differences between SHR and LE, however, could be noted only at 1, 10, and 50 mW/cm2. Increased Tco, increased magnitude of Dw, increased CS, decreased TSH, and increased PRL (stress reactions) could be noted in rats exposed to 30 mW/cm2 (approximately 6 W/kg) or higher, irrespective of strain. At least two of three strains of rats (WKY and SHR) exposed to 20 mW/cm2 (approximately 4 W/kg) showed changes in Tco, CS, TSH, and PRL. At 10 mW/cm2 (2 W/kg), increased Tco could be found in all three strains of rats accompanied by changes in dW and TSH in LE, TSH in WKY, and dW and CS in SHR. At 1 mW/cm2 (0.2 W/kg), increased Tco could be noted in two of three strains (LE and SHR) and increased PRL in LE only. The smallest Tco increases for a consistent response (increased magnitude of response with power density) were 1.59 degrees C for dW, 0.70 degrees C for CS, 0.24 degrees C for TSH, and 0.97 degrees C for PRL. Tentatively, the threshold intensity for response to microwave exposure for rats could be considered as 2 W/kg or a 0.24 degrees C increase at 24 degrees C ambient temperature.

Influence of power frequency electric and magnetic fields on human health.

Several reports have appeared in the last ten years in which the authors suggest an association between cancer/leukemia and exposure to electric and magnetic fields in the workplace or in the vicinity of distribution lines from overhead transmission systems. Several of these reports are reviewed and critiqued. The reports of clinical effects of electric and/or magnetic fields among human populations present serious difficulties which stem from the many publications in which pertinent material is not presented, and the data are variable or internally inconsistent. The reports presented so far are not very probing. The numbers of subjects are small, the epidemiologic methodologies are often weak, measurements of intensity of field are absent, and the statistical analyses utilized are not always appropriate. Although suggestive associations of electric/magnetic fields and cancer or leukemia have been made, no one has established a causal relationship between these fields and cancer or leukemia. All the reports on human exposure have numerous deficiencies which include: lack of or imprecise measurements of electric or magnetic field intensities, questionable subject identification, lack of statistical significance, confounding with uncontrolled variables such as socioeconomic differences, smoking, X rays, drugs, population mobility, and the unreliability of occupational classification. Nevertheless the possibility of a link between leukemia and cancer and exposure to electric and magnetic fields has been raised and only responsible research can refute or confirm these reports.

The biological effects of radiofrequency radiation: a critical review and recommendations.

Exposure of the general public and in particular certain occupational groups to radiofrequency radiation (RFR) is ubiquitous and of growing concern. No clear and widely accepted understanding of the biological effects and health implications of such RFR exposure has emerged. This paper reviews the data available, including reports of RFR effects on single cells or cell components, on genetic composition or development, on developed organs, tissues, or cell systems, and on integrative and regulatory biological systems. Reports of RFR effects on the immunological system, with consideration of the influence of neuroendocrine responses, are critically reviewed in greater detail to illustrate important points regarding data acquisition and assessment, and understanding and application of the RFR bioeffects literature in general. Factors affecting RFR bioeffects research are reviewed, and recommendations for future studies are provided.

Effects of microwaves on the adrenal cortex.

Six-hundred-and-one male Long-Evans rats were used to study the effect of microwaves on adrenocortical secretion. Power density ranged from 0.1 to 55 mW/cm2 (SAR 0.02 to 11 W/kg). The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Serum corticosterone (CS) concentration was used as an index of adrenocortical function. Ten different exposure protocols were used to identify confounding factors influencing the sensitivity of adrenal cortex to microwave exposure. Increases in CS concentration were proportional to power density or colonic temperature and inversely proportional to the baseline CS. Increased CS concentration was never observed without increased colonic temperature and was not persistent 24 h after exposure. Acclimation (reduction in magnitude of response) could be noted after the tenth exposure. Facilitated heat loss attenuated the magnitude of CS increases by limiting the degree of hyperthermia. Ethanol enhanced the hyperthermic response and desensitized the adrenal response to microwave hyperthermia by increased baseline CS. Ether stimulated adrenal secretion irrespective of previous microwave exposure or adrenal stimulation induced by microwaves. Minor inhibition was also noted occasionally as decreased CS concentration at lower intensity (less than 20 mW/cm2) and decreased postexposure urinary CS excretion at 40 mW/cm2. Adrenal stimulation required minimally a 20 mW/cm2 (4 W/kg) or 0.7 degrees C increase in colonic temperature. An SAR lower than 4 W/kg may stimulate adrenal secretion by potentiating the hyperthermic effect if the ambient temperature is well above 24 degrees C.

The relationship of decreased serum thyrotropin and increased colonic temperature in rats exposed to microwaves.

Although decreased serum thyrotropin (TSH) concentration has been found to be part of the endocrine response pattern in rats exposed to microwaves and other stimuli, the response of individual endocrine organs was not activated simultaneously by a given irradiance. Therefore, analytical evaluation of the function of endocrine organs individually as well as collectively is required to characterize the extent of biological involvement in microwave exposure. We have studied the changes in TSH concentration in unanesthetized rats exposed to 2.45 GHz amplitude modulated (120 Hz) microwaves in the far field for 2 and 4 h, between 0 and 55 mW/cm2, and from 1 to 10 times to demonstrate any possible cumulation, acclimation, or sensitization process. Ether inhalation was administered to test the responsiveness of TSH in groups of rats that failed to respond to microwave exposure by lowering TSH concentration. In addition, groups of rats were sampled 24 h after microwave exposure to test the persistency of the microwave effect on serum TSH concentration. Results showed that TSH concentration decreased in rats after microwave exposure. Influence of microwave exposure on serum TSH concentration was independent of the number of exposures indicating absence of cumulation, acclimation, or sensitization. The microwave effect on serum TSH could be dependent on duration of exposure. Decreased TSH concentration was usually accompanied by increased colonic temperature. For 4-h exposure, the lowest irradiance was 20 mW/cm2 or a 0.3 degree C increase in colonic temperature independent of the number of exposures. For 2-h exposure, the lowest irradiance was 30 mW/cm2 or a 1.1 degree C increase in colonic temperature regardless of the number of exposures. All the rats exposed at 10 mW/cm2 for 2 h had a lower TSH concentration than those of sham-exposed rats. Occasionally, significant reduction in TSH concentration could not be found in rats exposed to 20 or 25 mW/cm2 for 2 h. None of the rats exposed at an irradiance lower than 10 mW/cm2 had any change in TSH concentration. Failure of change in TSH concentration in response to microwave exposure was not a reflection of a deficiency since these rats responded to ether inhalation by lowering their TSH concentration. The effect of microwave exposure on TSH concentration was not persistent after exposure. The relation between TSH concentration and colonic temperature was curvilinear (exponential). From these results, two mechanisms and their implications for man were discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Hyperthermia and human leukocyte functions: DNA, RNA, and total protein synthesis after exposure to less than 41 degrees or greater than 42.5 degrees hyperthermia.

Hyperthermia is being used clinically in the treatment of neoplasms, and mononuclear leukocytes are commonly present in a heated tumor or in surrounding tissues. Therefore, we examined the effects of exposure of human mononuclear leukocytes to less than 41 degrees or greater than 42.5 degrees hyperthermia for 2 h. The ability of the cells to exclude dyes, used as a measurement of leukocyte viability, was not altered by such exposures. Exposure of the cells to less than 41 degrees hyperthermia generally did not alter unstimulated or mitogen-stimulated DNA, RNA, or total protein synthesis. In contrast, exposure to greater than 42.5 degrees hyperthermia resulted in decreased unstimulated RNA and total protein synthesis, as well as delayed synthesis of DNA, RNA, and total protein in response to stimulation with the optimal concentration of mitogen and decreased synthesis in response to suboptimal concentrations of mitogen.

Serum-thyroxine levels in microwave-exposed rats.

The nature of the response of the thyroid gland in animals exposed to microwave irradiation is controversial. An enlarged thyroid and an increase of radioiodine uptake in microwave workers have been reported. Absence of thyroid disorders has also been reported in other exposed populations. Animal experimentation has contributed to the controversy because both increased and decreased thyroid functions have been reported. The thyroxine concentration in rats as representative of thyroid function in animals exposed to 2.45-GHz, 120-Hz amplitude-modulated microwaves has been studied. Comparison was made between thyroxine concentrations in microwave- and sham-exposed rats by Student's t test. After a 1-hr exposure, an increased thyroxine concentration was found in rats exposed at 40 and 70 mW/cm2, but not at 1, 5, 10, 20, 50, or 60 mW/cm2. After a 2-hr exposure, increased thyroxine concentration was noted in rats exposed at 25, 30, and 40 mW/cm2, but not at 1, 5, 10, and 20 mW/cm2. After a 4-hr exposure, thyroxine concentration increased in rats exposed at 1 mW/cm2 and decreased in rats exposed at 20 mW/cm2; but changes were not noted at 5 or 10 mW/cm2. Other experiments included animals that were exposed once for 4 hr (0.1, 1, 10, 25, and 40 mW/cm2), sampled 24 hr after a 4-hr exposure (0.1, 1, 10, 25, and 40 mW/cm2), or exposed for 4 hr 3 times (1, 10, 20, 30, 40, and 55 mW/cm2) and 10 times (1, 10, 20, 25, 30, and 40 mW/cm2), to evaluate the consistency of the thyroxine response. None of the rats in these experiments displayed any alteration of thyroxine concentration, except that decreased thyroxine was noted in rats exposed at 40 mW/cm2 for the third time. These studies covered a long time span; rats from two commercial sources (BS and CR) were used and subjected to different numbers of exposures, and therefore these data were evaluated for their stability. Two factors could influence the result significantly, i.e., source of animal and number of sham exposures. Rats used in the 2-hr exposures were from two different commercial sources; rats from CR had a higher (but normal) thyroxine concentration than did rats from BS. Therefore the data of these animals were separated by commercial source for reevaluation. Instead of increased thyroxine concentration in rats exposed at 25, 30, and 40 mW/cm2, changes were not noted in any microwave-exposed rats. The influence of sham exposure revealed that appropriate concurrent control and specification of animal source are needed in longitudinal studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuroendocrine parameters in the rat exposed to 60-Hz electric fields.

This study was designed to assess the neuroendocrine response of male Long-Evans rats to sustained or intermittent 60-Hz electric fields when exposed for 1 or 3 h at 100 kV/m. No significant differences were noted in corticosterone, prolactin, or thyrotropin levels between exposed and sham-exposed rats. A statistically significant increase (P less than .01) in growth hormone was noted in rats exposed to intermittent electric fields for 3 h. Emphasis was placed on good experimental design and the need to avoid standard laboratory stressors (excessive handling, temperature extremes, transportation, noise, etc.) known to be present in many biomedical studies. The importance of avoiding reactions due to extraneous factors in experiments predicated on investigating physiological function in relation to electric field exposure is discussed.

Epidemiological studies of human exposures to radiofrequency radiation. A critical review.

The health effects to exposure to radiofrequency radiation (RFR) remain undefined and controversial. Epidemiological studies of human exposures to RFR are confounded by difficulties in determining the type and true extent of exposures, in selecting an appropriate control group for comparisons, in determining the existence and influence of many concomitant environmental factors, and in establishing the presence or measuring the frequency or severity of subjective complaints was well as objective findings in the studied populations. This paper reviews reported RFR effects on general health, growth and development, physiological systems such as the cardiovascular and nervous systems, and organs such as the eye. Criteria for reliable epidemiological studies are presented to allow critical analysis of such reports.

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. A. Effect on the permeability to sodium fluorescein.

Significantly elevated levels of sodium fluorescein (MW 376) were found only in the brains of conscious rats made considerably hyperthermic (colonic temperatures greater than 41.0 degrees C) by exposure to ambient heat (42 +/- 2 degrees C) for 90 min or 2450 MHz CW microwave energy at 65 mW/cm2 (SAR approximately equal to 13.0 W/kg) for 30 or 90 min. For microwave-exposed rats, fluorescein levels within the cortex and hypothalamus appeared to increase with increasing duration of exposure. This trend was not apparent in the cerebellum or medulla. Exposure to ambient heat resulted in increased fluorescein with the cortex, hypothalamus and medulla, but not the cerebellum, and, in general, ambient heat was not as effective as microwave energy in raising tracer concentrations within the brain. By far the greatest elevation of fluorescein dye in the brain occurred in those animals whose blood-brain barrier had been opened osmotically by intracarotid injection of 10 M urea. It is suggested that increased levels of sodium fluorescein found in the brain tissue of ambient heat and microwave-exposed rats most likely represent technically derived artifact and not a breakdown of the blood-brain barrier.

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. B. Effect on the permeability to HRP.

Alteration of blood-brain barrier (BBB) permeability by 2450 MHz CW microwaves was assessed semi-quantitatively after intravenous injection of horseradish peroxidase (HRP) and exposure of conscious, unrestrained rats to incident power densities of 0, 20 or 65 mW/cm2 for 30, 90 or 180 min. Additional rats were exposed to ambient heat (42 +/- 2 degrees C) for 30 or 90 min. None of the brain regions studied, with the exception of the normally leaky pineal gland, showed extracellular HRP leakage attributable to microwave or thermally-induced breakdown of the blood-brain barrier. The mean ratio of HRP-labeled microvessel endothelium/total number of microvessels counted was determined for each brain region. Mean values for the cortex, hypothalamus, cerebellum and medulla of microwave-exposed and heated rats were consistently below those of corresponding sham levels. This decrease appeared to correlate inversely with power density and duration of exposure. Statistically significant deviation (P less than 0.05) from sham mean values occurred in the cortex, hypothalamus, cerebellum and medulla of animals made hyperthermic with ambient heat or exposure to microwaves at 65 mW/cm2 (specific absorption rate approximately equal to 13.0 W/kg) for 30 or 90 min. Additionally, electron microscopic evaluation of ultrathin sections taken from each of the 4 brain regions revealed no significant extravasation of HRP indicative of microwave or ambient heat-induced disruption of the blood-brain barrier.

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. C. Effect on the permeability to [14C]sucrose.

Intravenously injected [14C]sucrose was used as a small molecular weight (342 daltons), hydrophilic tracer for determination of 2450 MHz CW microwave and ambient heat effects on rat blood-brain barrier permeability in the cerebral cortex, hypothalamus, cerebellum and medulla. The tracer was injected 4 min following exposure of conscious, unrestrained rats to microwaves at 0 or 65 mW/cm2 for 30 or 90 min (SAR approximately equal to 13.0 W/kg) or to ambient heat (42 +/- 2 degrees C) for 90 min. Comparison of mean permeability-surface area products (PA) and uptake ratios between sham and microwave-exposed animals revealed a statistically significant (P less than 0.05) decrease of both PA and uptake ratios for the hypothalamus, cerebellum and medulla of rats exposed to microwaves for 30 min. This decrease was not apparent for rats exposed to microwaves for 90 min. A pertinent observation, with regard to this latter group of animals, was the increased circulating levels of the tracer when colonic temperature was raised to approximately 41.4 degrees C or higher.

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. D. Brain temperature and blood-brain barrier permeability to hydrophilic tracers.

Measurement of temperature within the cerebral cortex, hypothalamus, cerebellum and medulla of rats sham-, heat- or microwave-exposed revealed the presence of a thermal gradient within the brain. In all groups, cerebral cortex and the cerebellum were cooler than the deeper hypothalamus and medulla. Exposure to 2450 MHz CW microwaves or ambient heat (42 +/- 2 degrees C) resulted in measurable elevation of regional brain temperature, but without alteration of temperature gradients normally observed within the brain. Exposure to 20 mW/cm2 (SAR approximately equal to 4 W/kg) for 30, 90 or 180 min induced a small, but significantly (U = 0, P less than 0.05) increased temperature of the colon, and in each region of the brain studied. Exposure to an incident power density of 65 mW/cm2 (SAR approximately equal to 13.0 W/kg) for 30 or 90 min or to ambient heat (42 +/- 2 degrees C) for 90 min resulted in a substantially greater thermal response as indicated by higher colonic and brain temperatures. Comparison of regional brain temperature with individual colonic temperatures is expressed as delta T = t degrees Cbrain--t degrees Ccolon. In general delta T values for ambient heat or microwave-exposed rats did not differ significantly from those of sham-exposed animals. Exposure to microwaves or ambient heat did not alter the general relationships between regional brain and colonic temperatures, i.e., cortical and cerebellar temperatures were always below and hypothalamic and medullary temperatures always above corresponding colonic temperatures. The plotted temperature data (brain vs colonic temperature) indicate a linear relationship between brain and colonic temperatures. Levels of sodium fluorescein (NAFl), horseradish peroxidase (HRP) and [14C]sucrose (described in preceding papers) within the brain show a high correlation (P less than 0.05) with brain temperature. Suppression of blood-brain barrier permeability to hydrophilic tracers was most pronounced at brain temperatures exceeding approximately 40 degrees C and is demonstrated to be temperature dependent.