IEEE Committee on Man and Radiation-COMAR Technical Information Statement: Health and Safety Issues Concerning Exposure of the General Public to Electromagnetic Energy from 5G Wireless Communications Networks.

This COMAR Technical Information Statement (TIS) addresses health and safety issues concerning exposure of the general public to radiofrequency (RF) fields from 5G wireless communications networks, the expansion of which started on a large scale in 2018 to 2019. 5G technology can transmit much greater amounts of data at much higher speeds for a vastly expanded array of applications compared with preceding 2-4G systems; this is due, in part, to using the greater bandwidth available at much higher frequencies than those used by most existing networks. Although the 5G engineering standard may be deployed for operating networks currently using frequencies extending from 100s to 1,000s of MHz, it can also operate in the 10s of GHz where the wavelengths are 10 mm or less, the so-called millimeter wave (MMW) band. Until now, such fields were found in a limited number of applications (e.g., airport scanners, automotive collision avoidance systems, perimeter surveillance radar), but the rapid expansion of 5G will produce a more ubiquitous presence of MMW in the environment. While some 5G signals will originate from small antennas placed on existing base stations, most will be deployed with some key differences relative to typical transmissions from 2-4G base stations. Because MMW do not penetrate foliage and building materials as well as signals at lower frequencies, the networks will require "densification," the installation of many lower power transmitters (often called "small cells" located mainly on buildings and utility poles) to provide for effective indoor coverage. Also, "beamforming" antennas on some 5G systems will transmit one or more signals directed to individual users as they move about, thus limiting exposures to non-users. In this paper, COMAR notes the following perspectives to address concerns expressed about possible health effects of RF field exposure from 5G technology. First, unlike lower frequency fields, MMW do not penetrate beyond the outer skin layers and thus do not expose inner tissues to MMW. Second, current research indicates that overall levels of exposure to RF are unlikely to be significantly altered by 5G, and exposure will continue to originate mostly from the "uplink" signals from one's own device (as they do now). Third, exposure levels in publicly accessible spaces will remain well below exposure limits established by international guideline and standard setting organizations, including ICNIRP and IEEE. Finally, so long as exposures remain below established guidelines, the research results to date do not support a determination that adverse health effects are associated with RF exposures, including those from 5G systems. While it is acknowledged that the scientific literature on MMW biological effect research is more limited than that for lower frequencies, we also note that it is of mixed quality and stress that future research should use appropriate precautions to enhance validity. The authorship of this paper includes a physician/biologist, epidemiologist, engineers, and physical scientists working voluntarily and collaboratively on a consensus basis.

Influence of blood flow and millimeter wave exposure on skin temperature in different thermal models.

Recently we showed that the Pennes bioheat transfer equation was not adequate to quantify mm wave heating of the skin at high blood flow rates. To do so, it is necessary to incorporate an "effective" thermal conductivity to obtain a hybrid bioheat equation (HBHE). The main aim of this study was to determine the relationship between non-specific tissue blood flow in a homogeneous unilayer model and dermal blood flow in multilayer models providing that the skin surface temperatures before and following mm wave exposure were the same. This knowledge could be used to develop multilayer models based on the fitting parameters obtained with the homogeneous tissue models. We tested four tissue models consisting of 1-4 layers and applied the one-dimensional steady-state HBHE. To understand the role of the epidermis in skin models we added to the one- and three-layer models an external thin epidermal layer with no blood flow. Only the combination of models containing the epidermal layer was appropriate for determination of the relationship between non-specific tissue and dermal blood flows giving the same skin surface temperatures. In this case we obtained a linear relationship between non-specific tissue and dermal blood flows. The presence of the fat layer resulted in the appearance of a significant temperature gradient between the dermis and muscle layer which increased with the fat layer thickness.

Millimeter wave reflectivity used for measurement of skin hydration with different moisturizers.

BACKGROUND/AIMS: A new non-invasive method for determining the free water content in human skin has been developed. The method analyzes the reflection of millimeter (mm) wavelength electromagnetic waves. The amount of reflection of mm waves depends on an electrical property (namely, the permittivity) of the skin, and this depends upon the free water content of the various skin layers. The aim of the present study was to use the mm wave reflectometry method for determination of free water content in healthy skin treated with different hydrating substances. METHODS: Skin lotion, pure water, glycerol, and petroleum jelly (an occlusive substance) were used for hydration of skin. The amount of free water was calculated using the permittivity values of skin layers found from fitting a three layer skin model to measured reflection data. The skin model consisted of (1) the stratum corneum (SC), (2) the viable epidermis plus the dermis, and (3) fat layers. RESULTS: Mm wave reflection was significantly affected by the water content of the thick SC of the palm but not by the very thin SC of the forearm. Treatment of the forearm and palm skin with different hydrating substances produced notable changes of the free water content in the SC, but not in the viable epidermis or dermis. The greatest hydration was produced by pure water and skin lotion, and the lowest by petroleum jelly. However, petroleum jelly produced prolonged retention of water in the SC following its hydration by other moisturizers. The content of free water was found to return to its baseline value after removal of moisturizers in as short a time as 8.3 min. CONCLUSION: The study shows that mm wave reflectometry can be used as a sensitive technique for the non-invasive determination of water content in living skin.

Reflection and penetration depth of millimeter waves in murine skin.

Millimeter (mm) wave reflectivity was used to determine murine skin permittivity. Reflection was measured in anesthetized Swiss Webster and SKH1-hairless mice in the 37-74 GHz frequency range. Two skin models were tested. Model 1 was a single homogeneous skin layer. Model 2 included four skin layers: (1) the stratum corneum, (2) the viable epidermis plus dermis, (3) fat layer, and (4) muscle which had infinite thickness. We accepted that the permittivity of skin in the mm wave frequency range results from the permittivity of cutaneous free water which is described by the Debye equation. Using Fresnel equations for reflection we determined the skin parameters best fitting to the reflection data and derived the permittivity of skin layers. The permittivity data were further used to calculate the power density and specific absorption rate profiles, and the penetration depth of mm waves in the skin. In both murine models, mm waves penetrate deep enough into tissue to reach muscle. In human skin, mm waves are mostly absorbed within the skin. Therefore, when extrapolating the effects of mm waves found in animals to humans, it is important to take into account the possible involvement of muscle in animal effects.

Millimeter wave dosimetry of human skin.

To identify the mechanisms of biological effects of mm waves it is important to develop accurate methods for evaluating absorption and penetration depth of mm waves in the epidermis and dermis. The main characteristics of mm wave skin dosimetry were calculated using a homogeneous unilayer model and two multilayer models of skin. These characteristics included reflection, power density (PD), penetration depth (delta), and specific absorption rate (SAR). The parameters of the models were found from fitting the models to the experimental data obtained from measurements of mm wave reflection from human skin. The forearm and palm data were used to model the skin with thin and thick stratum corneum (SC), respectively. The thin SC produced little influence on the interaction of mm waves with skin. On the contrary, the thick SC in the palm played the role of a matching layer and significantly reduced reflection. In addition, the palmar skin manifested a broad peak in reflection within the 83-277 GHz range. The viable epidermis plus dermis, containing a large amount of free water, greatly attenuated mm wave energy. Therefore, the deeper fat layer had little effect on the PD and SAR profiles. We observed the appearance of a moderate SAR peak in the therapeutic frequency range (42-62 GHz) within the skin at a depth of 0.3-0.4 mm. Millimeter waves penetrate into the human skin deep enough (delta = 0.65 mm at 42 GHz) to affect most skin structures located in the epidermis and dermis.

Electromagnetic millimeter wave induced hypoalgesia: frequency dependence and involvement of endogenous opioids.

Millimeter wave treatment (MMWT) is based on the systemic biological effects that develop following local skin exposure to low power electromagnetic waves in the millimeter range. In the present set of experiments, the hypoalgesic effect of this treatment was analyzed in mice. The murine nose area was exposed to MMW of "therapeutic" frequencies: 42.25, 53.57, and 61.22 GHz. MMWT-induced hypoalgesia was shown to be frequency dependent in two experimental models: (1) the cold water tail-flick test (chronic non-neuropathic pain), and (2) the wire surface test (chronic neuropathic pain following unilateral constriction injury to the sciatic nerve). Maximum hypoalgesic effect was obtained when the frequency was 61.22 GHz. Other exposure parameters were: incident power density = 13.3 mW/cm(2), duration of each exposure = 15 min. Involvement of delta and kappa endogenous opioids in the MMWT-induced hypoalgesia was demonstrated using selective blockers of delta- and kappa-opioid receptors and the direct ELISA measurement of endogenous opioids in CNS tissue. Possible mechanisms of the effect and the perspectives of the clinical application of MMWT are discussed.

Growth of mammalian multicellular tumor spheroids.

The in vitro growth of small (0.05 to 3 mm diameter) avascular multicellular tumor spheroids from six rodent and two human tumor lines has been analyzed. Surprisingly, the radial increase of multicellular tumor spheroids is linear with time after a brief initial period of geometric growth. These multicellular tumor spheroids are shown to have a constant thickness of proliferative outer crust and of middle nonproliferative but viable mantle. An analytical model for their growth is developed which explains the growth pattern. This constant crust thickness model leads to a progressively diminishing growth fraction as radius increases and should be applicable to such early growth of micrometastases in vivo. The model also provides a procedure for determining cell cycle time.

Cardiac volume measurement errors.

Measurements of cardiac volumes based on biplane radiographic data exhibit a cyclical variation as the heart is rotated with respect to the radiologic instrumentation. This study develops a theoretical basis for evaluating the measurement errors due to orientation, that explains the cyclical variation. Since this type of measurement error is always one of overestimation, better accuracy will be obtained if several views are performed at varying orientations and the smallest of the resulting values is used as the measurement.

Continuous millimeter-wave radiation has no effect on lipid peroxidation in liposomes.

The effect of millimeter waves on lipid peroxidation was studied in the presence and absence of melanin. Irradiation of liposomes with continuous millimeter electromagnetic waves at frequencies of 53.6, 61.2 and 78.2 GHz and incident power densities of 10, 1 and 500 mW/cm2, respectively, did not show an enhancement in the formation of lipid peroxides compared to unirradiated samples. Liposomes exposed to 254 nm UVC radiation at 0.32 mW/cm2 and 302 nm UVB radiation at 1.12 mW/cm2 served as positive controls. No increment in the formation of lipid peroxides was observed when irradiation of liposomes was carried out in the presence of ADP-Fe+3 and EDTA-Fe+3. Direct irradiation of melanin with millimeter waves did not exhibit an increased formation of superoxide or hydrogen peroxide. The present results indicate that millimeter waves of the above frequencies and intensities do not cause lipid peroxidation in liposomal membranes.

Effect of WR-2721 on fetal development in the rat.

The radioprotector WR-2721 has been shown to radioprotect all tissues studied except the central nervous system. However, it has not yet been used to radioprotect the fetus. In this study we determined that [14C]WR-2721 injected into pregnant rats quickly passed the placenta and was concentrated by the fetus. In addition, we evaluated the toxicity of WR-2721 (2.5-600 mg/kg) to pregnant rats and their fetuses during the period of major organogenesis at Days 9, 11, and 14 postconception. Pregnant animals were only slightly more (10%) sensitive (LD50, 580 mg/kg) to WR-2721 than nonpregnant cohort animals (LD50, 640 mg/kg). At concentrations of 50 mg/kg or less there was a small but statistically significant increase in fetal deaths, while at doses greater than 300 mg/kg a larger degree of fetal mortality occurred. Maximal fetal weight loss, to about 84% of control, was found at 500 mg/kg. No changes in head dimensions or gross malformations of the surviving fetuses were detected at any time or concentration. Of all the parameters measured in this study none demonstrated a predilection for any specific period of major organogenesis. The results of this study indicate that while WR-2721 demonstrates a dose-related embryotoxicity it is not teratogenic.

Transdermal absorption of radioprotectors using permeation-enhancing vehicles.

Radioprotectors are not currently used clinically due to concerns regarding toxicity and uncertainties regarding tumor protection. Topical radioprotection of skin might find clinical applications with protectors such as WR-2721, but laboratory studies in which protectors have been applied in water have not been promising. We have studied the absorption of 14C-WR-2721 and [14C]cysteine dissolved in skin permeation-enhancing vehicles through the skin of hairless mice and compared the absorption to that in water. Skin concentration of WR-2721 was increased most by dimethylformamide (DMF), but only propylene glycol increased absorption as far as the dermis, as measured by plasma concentration. Skin concentration of cysteine was improved by DMF, 2-pyrrolidone (2-P), and methyl-2-pyrrolidone (M-2-P); only dimethylsulfoxide (DMSO) resulted in increased plasma levels of the protector. Pretreating skin with DMSO before application of WR-2721, irrespective of the vehicle, improved its concentration within the skin. Plasma levels were improved (10 and 12 times) only with 2-P and DMF. Therefore, by choosing the appropriate vehicle, it is possible to breach the barrier of the stratum corneum and enhance the presence of the protector in all layers of the skin.

Transdermal absorption of radioprotectors in the rat using permeation-enhancing vehicles.

Topical radioprotection of rat skin with WR-2721 has not been effective presumably because the drug does not cross the stratum corneum to reach the epidermis and dermis. Earlier, we showed in the mouse that WR-2721 and cysteine dissolved in permeation-enhancing vehicles passed through the skin more readily than when in water. However, the most effective vehicles in the mouse were not necessarily as effective in the rat. Here we report that the most effective transport vehicles in the rat were (1) water with WR-2721, (2) water and dimethylformamide (DMF) with cysteine, and (3) water and DMF with prostaglandin E2 (PGE2). Pretreatment of the skin with dimethylsulfoxide (DMSO) further improved the transfer of the radioprotectors across the skin in most cases. After pretreatment with DMSO, the most effective vehicles were (1) water for WR-2721, (2) water and methyl-2-pyrrolidone (M-2-P) for cysteine, and (3) DMF for PGE2.

Antipruritic effect of millimeter waves in mice: evidence for opioid involvement.

In our previous studies, exposure of mice to millimeter waves (MW) increased the duration of anesthesia caused by either ketamine or chloral hydrate, and this effect was blocked by naloxone. To further characterize the biological effects of MW, we have chosen a new animal model of experimental itch. Male Swiss albino mice were injected s.c. in the rostral part of the back with the pruritogenic agent, compound 48/80, with or without naloxone pretreatment. After a 15-min exposure of mice to MW (frequency, 61.22 GHz; incident power density, 15 mW/cm2), the number of scratches of the injected site was counted for 90 min post-injection. MW inhibited the scratching activity of mice by more than 2 times in comparison with the sham-exposed controls (p<0.005). Pretreatment of animals with (-)-naloxone (0.1-1.0 mg/kg, i.p.) suppressed the antipruritic effect of MW in a dose-dependent manner, while the inactive enantiomer (+)-naloxone at 1 mg/kg did not alter the effect. These results suggest that MW trigger the release of opioids in exposed subjects.

Hypoalgesic effect of millimeter waves in mice: dependence on the site of exposure.

Based on a hypothesis of neural system involvement in the initial absorption and further processing of the millimeter electromagnetic waves (MW) signal, we reproduced, quantitatively assessed and compared the analgesic effect of a single MW treatment, exposing areas of skin possessing different innervation densities. The cold water tail flick test (cTFT) was used to assess experimental pain in mice. Three areas of exposure were used: the nose, the glabrous skin of the right footpad, and the hairy skin of the mid back at the level of T5-T10. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15mW/cm2; and duration = 15 min. The maximum hypoalgesic effect was achieved by exposing to MW the more densely innervated skin areas--the nose and the footpad. The hypoalgesic effect in the cTFT after MW exposure to the murine back, which is less densely innervated, was not statistically significant. These results support the hypothesis of neural system involvement in the systemic response to MW.

Peripheral neural system involvement in hypoalgesic effect of electromagnetic millimeter waves.

In a series of blind experiments, using the cold water tail-flick test (cTFT) as a quantitative indicator of pain, the hypoalgesic effect of a single exposure of mice to low power electromagnetic millimeter waves (MW) was studied. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15 mW/cm2; and duration = 15 min. MW treatment was applied to the glabrous skin of the footpad. Exposure of an intact murine paw to the MW resulted in a statistically significant hypoalgesia as measured in the cTFT. These mice were able to resist cold noxious stimulation in the cTFF more than two times longer than animals from the sham-exposed group. A unilateral sciatic nerve transection was used to deafferent the area of exposure in animals from one of the experimental groups. This surgery, conducted six days before the MW treatment, completely abolished the hypoalgesic effect of the exposure to MW. The results obtained support the conclusion that the MW-skin nerve endings interaction is the essential step in the initiation of biological effects caused by MW. Based on our past and present results we recommend that in order to obtain a maximum therapeutic effect, densely innervated skin areas (head, hands) need to be used preferentially for exposure to MW in clinical practice.

Electromagnetic millimeter waves increase the duration of anaesthesia caused by ketamine and chloral hydrate in mice.

BALB/c mice were injected i.p. with either ketamine 80 mg/kg or chloral hydrate 450 mg/kg. Anaesthetized mice were exposed to unmodulated electromagnetic millimeter waves at the frequency of 61.22 GHz with a peak specific absorption rate of 420 W/kg and corresponding incident power density of 15 mW/cm2 for 15 min or sham-exposed. In combination with either of the anaesthetics used, mm waves increased the duration of anaesthesia by approximately 50% (p < 0.05) in a dose (power)-dependent manner. Sham exposure to mm waves did not affect the sleeping time of mice. Pretreatment of mice with naloxone, an opioid antagonist, did not change the duration of anaesthesia caused by the corresponding chemical agent, but completely blocked or decreased the additional effect of mm waves. The data in this study indicates that exposure of mice to mm waves in vivo releases endogenous opioids or enhances the activity of opioid signalling pathway.

Pain relief caused by millimeter waves in mice: results of cold water tail flick tests.

PURPOSE: To find out if millimeter waves can decrease experimental pain response in mice using cold water tail flick test. MATERIALS AND METHODS: Male Swiss albino mice (15 mice per group) were exposed to continuous millimeter waves at a frequency of 61.22 GHz with incident power densities (IPD) ranging from 0.15 to 5.0 mW/cm2 for 15 min or sham exposed. Latency of tail withdrawal in a cold water (1 +/- 0.5 degrees C) tail flick test was measured before the exposure (baseline) and then four times after the exposure with 15 min breaks. RESULTS: The mean latency of the tail flick response in mice exposed to millimeter waves was more than twice that of sham-exposed controls (p<0.05). This effect was proportional to the power of millimeter waves and completely disappeared at an IPD level of < or = 0.5 mW/cm2. Pretreatment of mice with the opioid antagonist naloxone (1 mg/kg i.p.) blocked the effect of millimeter waves. CONCLUSIONS: Results suggest that the antinociceptive effect of millimeter waves is mediated through endogenous opioids.

Biological consequences of hyperthermia.

Because of the potential for certain modalities of clinical ultrasound to cause tissue heating, it was deemed important to survey the literature for reports on temperatures and hyperthermia exposure durations at which biological effects occur in a wide spectrum of organisms. In general the higher the temperature or the longer the hyperthermia exposure, the greater the chance for observing a perturbation to the biological system. Special attention was given to ascertaining temperature exposure conditions below which no biological effects have been reported. The physical mechanism(s) by which heat produces biological effects is(are) not known but substantial quantities of empirically derived data have allowed for the calculation of exposure temperature-duration equivalences. It appears reasonably well established that short exposures to sharply-elevated temperatures result in a protective effect against further thermal insult; the generation of heat shock proteins by cells coincides with the onset of such "thermal protection." The information contained in this review indicates an absence of reported effects in animals below 39 degrees C.

Epidemiology of human exposure to ultrasound: a critical review.

Epidemiologic studies and surveys and widespread clinical usage over 25 years have yielded no evidence of any adverse effect from diagnostic ultrasound. Nonetheless, the inability to find convincing proof of an effect, either from epidemiology or from physicians' experience, does not preclude the possibility of it happening. Statistical reasoning shows that even with large population studies, it is difficult to identify a small increase in the rate of a commonly occurring event. Subtle effects, long-term delayed effects, and certain genetic effects, could easily escape detection.

Geometric and intensity distortion in echography.

Anatomic structures possessing varying sonic propagation velocities refract ultrasonic beams and create distortions in the sonographic image. The distortions consist of inaccurate positioning of echogenic locations (geometric distortions) and of inaccurate display of ultrasonic intensities (intensity distortions). Artifacts of both types occur in the region distal to a structure of circular cross section with an internal sonic propagation velocity lower than that of its surroundings. In an attempt to better understand these distortions, a model is developed from first principles of the production of sonograms of such a region. Assuming a uniform ultrasonic beam and uniform echogenicity of the surrounding tissue, a mathematical expression has been derived for the intensity of the sound arriving at each point and returning to the transducer. Computer simulations of the resulting sonographic image are provided for visualization. In spite of many simplifying assumptions, this model is shown to be consistent with several known artifacts, and provides insight into the mechanisms of their production.