Low-level exposure to radiofrequency electromagnetic fields: Health effects and research needs

The World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), and the German and Austrian Governments jointly sponsored an international seminar in November of 1996 on the biological effects of low-level radiofrequency (RF) electromagnetic fields. For purposes of this seminar, RF fields having frequencies only in the range of about 10 MHz to 300 GHz were considered. This is one of a series of scientific review seminars held under the International Electromagnetic Field (EMF) Project to identify any health hazards from EMF exposure. The scientific literature was reviewed during the seminar and expert working groups formed to provide a status report on possible health effects from exposure to low-level RF fields and identify gaps in knowledge requiring more research to improve health risk assessments. It was concluded that, although hazards from exposure to high-level (thermal) RF fields were established, no known health hazards were associated with exposure to RF sources emitting fields too low to cause a significant temperature rise in tissue. Biological effects from low-level RF exposure were identified needing replication and further study. These included in vitro studies of cell kinetics and proliferation effects, effects on genes, signal transduction effects and alterations in membrane structure and function, and biophysical and biochemical mechanisms for RF field effects. In vivo studies should focus on the potential for cancer promotion, co-promotion and progression, as well as possible synergistic, genotoxic, immunological, and carcinogenic effects associated with chronic low-level RF exposure. Research is needed to determine whether low-level RF exposure causes DNA damage or influences central nervous system function, melatonin synthesis, permeability of the blood brain barrier (BBB), or reaction to neurotropic drugs. Reported RF-induced changes to eye structure and function should also be investigated. Epidemiological studies should investigate: the use of mobile telephones with hand-held antennae and incidence of various cancers; reports of headache, sleep disturbance, and other subjective effects that may arise from proximity to RF emitters, and laboratory studies should be conducted on people reporting these effects; cohorts with high occupational RF exposure for changes in cancer incidence; adverse pregnancy outcomes in various highly RF exposed occupational groups; and ocular pathologies in mobile telephone users and in highly RF exposed occupational groups. Studies of populations with residential exposure from point sources, such as broadcasting transmitters or mobile telephone base stations have caused widespread health concerns among the public, even though RF exposures are very low. Recent studies that may indicate an increased incidence of cancer in exposed populations should be investigated further. Bioelectromagnetics 19:1–19, 1998. © 1998 Wiley-Liss, Inc.     

Bioeffects of chronic exposure to radiofrequency electromagnetic fields of low intensity (standardization strategy)

A retrospective analysis of the experimental researches on the effect of radio frequency electromagnetic fields (EMF) on human health, carried out in the USSR, is presented. The results of chronic exposure of laboratory animals to EMF have been considered. Apparently, EMF in the range of 1750-2750 MHz with power density up to 100-500 W/cm2 caused in immune globullin fractions, and a development of autoimmune processes. The changes in parameters of reproductive functions and posterity, the increase in embryo mortality were found. The standartization strategy used in the USSR and currently applied in Russia has been discussed.     

Genotoxic potential of ethinylestradiol in cultured mammalian cells

Ethinylestradiol, a steroidal estrogen, is widely used with various progestogens in oral contraceptives formulations. There are sufficient evidences for the carcinogenicity of ethinylestradiol in experimental animals. The reports on the genotoxic potential of ethinylestradiol are contradictory. Here in the present study we have tested the genotoxicity of ethinylestradiol in human lymphocytes using chromosomal aberrations (CAs), mitotic index (MI) and sister chromatid exchanges (SCEs) as a parameter. The study was carried out in the absence, as well as in the presence, of rat liver microsomal fraction, with and without NADP. Ethinylestradiol was studied at three different concentrations (1, 5 and 10 microM) and was found non-genotoxic in the absence of metabolic activation (S9 mix) and in S9 mix without NADP. Ethinylestradiol was found to be genotoxic at 5 and 10 microM in the presence of S9 mix with NADP. To study the possible mechanism of the genotoxicity of ethinylestradiol, superoxide dismutase (SOD) and catalase (CAT) were used separately and in combination along with 10 microM of ethinylestradiol at different doses. SOD treatment increased CAs and SCEs and decreases MI as compared with treatment with 10 microM of ethinylestradiol alone in the presence of S9 mix with NADP at both of the tested doses. CAT treatment decreased the frequencies of CAs and SCEs and increased MI, as compared with treatment with 10 microM of ethinylestradiol alone in the presence of S9 mix with NADP. CAT treatment in combination with SOD also decreased the frequencies of CAs and SCEs and increased MI suggesting a possible role of reactive oxygen species for the genotoxic damage.     

Effect of intermittent and continuous exposure to electromagnetic fields on cultured hippocampal cells

This study was designed to assess the effect of 50 Hz electromagnetic fields (EMFs) on hippocampal cell cultures in the presence or absence of either sodium nitroprusside (SNP, a NO donor) or Fe2+ induced oxidative stress. One week old cultured rat hippocampal cells were exposed to either intermittent EMFs (IEMFs, 50 Hz, 0-5 mT, 1 min ON/OFF cycles, repeated 10 times every 2 h, 6 times/day during 48 h) or continuous EMFs (CEMFs, 50 Hz, 0-5 mT for 48 h). In a second set of experiments, the effect on such EMFs applied in combination with oxidative stress induced by 0.5 microM Fe2+ or SNP was estimated. At the end of both sets of experiments, cell mortality was assessed by lactate dehydrogenase measurements (LDH). Neither type of exposure to EMFs was observed to modify the basal rate of cell mortality. The exposure to CEMFs in presence of either NO or Fe2+ did not induce any significant increase in cell death. However, when cells were exposed to EMFs in the presence of NO, we observed a significant increase in cell death of 11 and 23% (P<0.001) at 2.5 and 5 mT, respectively. This effect had some specificity because IEMFs did not modify the effect of Fe2+ on cell mortality. Although the effects of IEMFs reported in this study were only observed at very high intensities, our model may prove valuable in trying to identify one cellular target of EMFs.     

Cell physiological effects of radiofrequency electromagnetic fields

Ovarian and body cavity eggs from R. temporaria were exposed to radiofrequency (rf) electromagnetic fields in the frequency range 10-27 MHz with specific absorption rates (SAR) up to 800 W/kg. The effect of the exposure was investigated by measurement of the water-related cell physiological parameters, isotopic and osmotic water membrane permeability and density of the egg cells. Only the osmotic water permeability, Pf, of ovarian eggs was significantly altered. A decrease of about 30% was seen for SARs of 50 W/kg and exposure times up to 2 h. Tests ruled out that the effect was due to temperature increase during the exposure. The observed decrease of Pf was most likely due to cloudy swelling of the egg cytoplasm resulting from the rf irradiation.     

Stress proteins are not induced in mammalian cells exposed to radiofrequency or microwave radiation

The induction of stress proteins in HeLa and CHO cells was investigated following a 2 h exposure to radiofrequency (RF) or microwave radiation. Cells were exposed or sham exposed in vitro under isothermal (37 ± 0.2 °C) conditions. HeLa cells were exposed to 27- or 2450 MHz continuous wave (CW) radiation at a specific absorption rate (SAR) of 25 W/kg. CHO cells were exposed to CW 27 MHz radiation at a SAR of 100 W/kg. Parallel positive control studies included 2 h exposure of HeLa or CHO cells to 40 °C or to 45 μM cadmium sulfate. Stress protein induction was assayed 24 h after treatment by electrophoresis of whole-cell extracted protein labeled with [³⁵S]-methionine. Both cell types exhibited well-characterized responses to the positive control stresses. Under these exposure conditions, neither microwave nor RF radiation had a detectable effect on stress protein induction as determined by either comparison of RF-exposed cells with sham-exposed cells or comparison with heat-stressed or Cd⁺⁺ positive control cells. Bioelectromagnetics 18:499–505, 1997. © 1997 Wiley-Liss, Inc.     

Epidemiological risk assessment of pathology development in occupational exposure to radiofrequency electromagnetic fields

A cross-sectional study of working conditions and health of the personnel of the civil aircraft radar-tracking system has been conducted based on periodical health examinations. The personnel was divided into three occupational groups. Group I was exposed to EMF EHF, group II--to EMF HF and UHF and group III was not exposed to EMF (reference group). The groups didn't differ in any occupational and non-occupational parameters. Health status of 250 workers was examined. High prevalence rate of cardiovascular diseases (ICD-X I00-I99) was found in the exposed groups. Odds ratio (OR) was 3.78 (95% CI 1.96-7.27) in group I and 2.13 (95% CI 1.13-4.03) in group II. High prevalence rate of cardiovascular diseases is explained by arterial hypertension (ICD-X I10-I15) (OR = 1.96 95% CI 1.04-3.70 in group I and OR = 1.80 95% CI 0.93-3.50 in group II) and ischemic heart disease (ICD-X I20-I25) (OR = 7.9 95% CI 3.48-18.06 in group I; OR = 3.0 95% CI 1.23-7.33--in group II). In the exposed groups cardiovascular diseases were developed in young age. OR was 7.04 (95% CI 1.64-30.19) in group I and 4.33 (95% CI 0.96-19.65) in group II in 30-39 age sub groups. Myocardium infarction was found in 2 out of 16 persons of this age in the group exposed to EMF.     

Calibration and uncertainties in personal exposure measurements of radiofrequency electromagnetic fields

In the past 5 years radiofrequency personal exposure meters have been used to characterize the exposure during daily activities. We found from calibration tests for the 12 frequency bands of the EME Spy 121 exposimeter in a Gigahertz Transverse Electromagnetic cell and an Open Area Test Site, that these measurements tend to underestimate the actual exposure. Therefore, a maximum frequency‐dependent correction factor of 1.1–1.6 should be applied to the electric field. This correction factor consists of three multipliers correcting for calibration, elevation arrival angle, and influence of the body. The calibration correction factor should be determined per exposimeter, as the maximum range of response between exposimeters in a frequency band is 2.4 dB. Since the range of response for different elevation angles could reach 10.2 dB, a strict protocol for wearing the exposimeter during fieldwork should be followed to be able to compare and combine measurements made by different persons in the same microenvironments. Because the influence of the body depends on the azimuth angle of arrival, it may lead to an over‐ or underestimation. Thus, the body correction factor is an average over the angles and should only be applied in activities involving movement through the full 360° range of random angles of arrival. Bioelectromagnetics. Bioelectromagnetics 32:652–663, 2011. © 2011 Wiley Periodicals, Inc.     

Genotoxic activity of caramel on Salmonella and cultured mammalian cells

The genetic activity of 2 commercial caramel preparations, manufactured either by heating the malt sugar solution directly (non-ammoniated caramel) or by heating it with ammonia (ammoniated caramel) was studied in the Salmonella mutagenicity test and UDS assay in cultured mammalian cells. The non-ammoniated caramel was found to be mutagenic to S. typhimurium TA100, while the ammoniated one was genetically active in all the tester strains used, namely TA100, TA97 and TA98. It was also demonstrated that non-ammoniated caramel was capable of inducing UDS in cultured human amnion FL cells, but for the ammoniated one, no such activity was observed. Furthermore, based on the results obtained in the DNA synthesis inhibition assay, it was suggested that the DNA synthesis inhibition seen in our experiments with the ammoniated caramel was probably not of DNA damage in origin. These data indicate that the mutagenic fractions formed during ammoniated and non-ammoniated caramelization were quite different.     

Investigation of co-genotoxic effects of radiofrequency electromagnetic fields in vivo

We investigated the possible combined genotoxic effects of radiofrequency (RF) electromagnetic fields (900 MHz, amplitude modulated at 217 Hz, mobile phone signal) with the drinking water mutagen and carcinogen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). Female rats were exposed to RF fields for a period of 2 years for 2 h per day, 5 days per week at average whole-body specific absorption rates of 0.3 or 0.9 W/kg. MX was given in the drinking water at a concentration of 19 microg/ml. Blood samples were taken at 3, 6 and 24 months of exposure and brain and liver samples were taken at the end of the study (24 months). DNA damage was assessed in all samples using the alkaline comet assay, and micronuclei were determined in erythrocytes. We did not find significant genotoxic activity of MX in blood and liver cells. However, MX induced DNA damage in rat brain. Co-exposures to MX and RF radiation did not significantly increase the response of blood, liver and brain cells compared to MX exposure only. In conclusion, this 2-year animal study involving long-term exposures to RF radiation and MX did not provide any evidence for enhanced genotoxicity in rats exposed to RF radiation.     

Biological effects of prolonged exposure to ELF electromagnetic fields in rats: III. 50 Hz electromagnetic fields

Groups of adult male Sprague Dawley rats (64 rats each) were exposed for 8 months to electromagnetic fields (EMF) of two different field strength combinations: 5μT - 1kV/m and 100μT - 5kV/m. A third group was sham exposed. Field exposure was 8 hrs/day for 5 days/week. Blood samples were collected for hematology determinations before the onset of exposure and at 12 week intervals. At sacrifice, liver, heart, mesenteric lymph nodes, bone marrow, and testes were collected for morphology and histology assessments, while the pineal gland and brain were collected for biochemical determinations. At both field strength combinations, no pathological changes were observed in animal growth rate, in morphology and histology of the collected tissue specimens (liver, heart, mesenteric lymph nodes, testes, bone marrow), and in serum chemistry. An increase in norepinephrine levels occurred in the pineal gland of rats exposed to the higher field strength. The major changes in the brain involved the opioid system in frontal cortex, parietal cortex, and hippocampus. From the present findings it may be hypothesized that EMF may cause alteration of some brain functions. Bioelectromagnetics 19:57–66, 1998. © 1998 Wiley-Liss, Inc.     

2.45 GHz radiofrequency fields alter gene expression in cultured human cells

The biological effect of radiofrequency (RF) fields remains controversial. We address this issue by examining whether RF fields can cause changes in gene expression. We used the pulsed RF fields at a frequency of 2.45 GHz that is commonly used in telecommunication to expose cultured human HL-60 cells. We used the serial analysis of gene expression (SAGE) method to measure the RF effect on gene expression at the genome level. We observed that 221 genes altered their expression after a 2-h exposure. The number of affected genes increased to 759 after a 6-h exposure. Functional classification of the affected genes reveals that apoptosis-related genes were among the upregulated ones and the cell cycle genes among the downregulated ones. We observed no significant increase in the expression of heat shock genes. These results indicate that the RF fields at 2.45 GHz can alter gene expression in cultured human cells through non-thermal mechanism.     

Lyn and syk tyrosine kinases are not activated in B-lineage lymphoid cells exposed to low-energy electromagnetic fields.

Exposure of B-lineage lymphoid cells to a 100 microT 60 Hz AC magnetic field has been reported to stimulate the rapid activation of Lyn and Syk tyrosine kinases and the induction of protein tyrosine phosphorylation. These findings are significant because of the critical role played by these B cell signaling events in the control of growth and differentiation, and therefore the potential of electromagnetic field (EMF) exposure to induce cancer. We report the first study carried out with the aim of reproducing the reported EMF effects on Lyn and Syk tyrosine kinases. The system used enabled EMF exposure conditions to be carefully controlled and also allowed experiments to be performed blind. The effects of a 100 microT 60 Hz AC magnetic field on protein tyrosine phosphorylation and on Lyn and Syk tyrosine kinase activities were investigated in Nalm-6 and DT40 B cells in the absence and presence of a 46 microT DC magnetic field. However, no significant effects of low-energy electromagnetic fields on tyrosine kinase activities or protein phosphorylation were observed.     

Dual effects of thymic substance(s) on growth of cultured mammalian cells

Saline extracts from thymus glands of mice, or thymocyte suspensions, had stimulatory and inhibitory influences on the growth of mammalian cells in vitro. The stimulatory effect appeared at high extract concentrations as amounts of Lowry-positive substance, and at high suspension densities. The inhibitory effect was observed at low concentrations of the extract and at low densities of the suspension. The thymus extract not only affected the initiation of cell proliferation but also influenced proliferation of their descendants. The tissue fragments obtained from normal mouse exhibited the inhibitory action and the one from mice irradiated with 700 R showed the stimulatory effect on the colony formation. These facts may suggest that two different substances responsible for affecting cell growth are produced by different types of cells in the thymus. It was also found that the suspension prolonged the generation time of the cells and that calf serum was antagonistic to those dual actions. Moreover, the loss of inhibitory activity with trypsin treatment strongly suggests that the thymic materials contain a protein as an active site.     

Short-duration exposure to radiofrequency electromagnetic radiation alters the chlorophyll fluorescence of duckweeds (Lemna minor)

Plants growing in natural environments are exposed to radiofrequency electromagnetic radiation (EMR) emitted by various communication network base stations. The environmental concentration of this radiation is increasing rapidly with the congested deployment of base stations. Although numerous scientific studies have been conducted to investigate the effects of EMR on the physiology of humans and animals, there have been few attempts to investigate the effects of EMR on plants. In this study, we attempted to evaluate the effects of EMR on photosynthesis by investigating the chlorophyll fluorescence (ChF) parameters of duckweed fronds. During the experiment, the fronds were tested with 2, 2.5, 3.5, 5.5 and 8?GHz EMR frequencies, which are not widely studied even though there is a potentially large concentration of these frequencies in the environment. The duckweed fronds were exposed to EMR for 30?min, 1?h and 24?h durations with electric field strength of 45–50?V/m for each frequency. The results indicated that exposure to EMR causes a change in the non-photochemical quenching of the duckweeds. The changes varied with the frequency of the EMR and were time-varying within a particular frequency. The temperature remained unchanged in the duckweed fronds upon exposure to EMR, which confirms that the effect is non-thermal.     

Lymphoma development in mice chronically exposed to UMTS-modulated radiofrequency electromagnetic fields

There are public concerns regarding possible carcinogenic or cancer-promoting effects of electromagnetic fields (EMFs) from mobile phones and base stations. The objective of the present study was to investigate whether chronic exposure to EMFs of the UMTS (Universal Mobile Telecommunication System) influences the development of lymphoma in a lymphoma animal model, the AKR/J mouse. Unrestrained mice were chronically sham-exposed (n = 160) or exposed (n = 160) in identical exposure systems (radial waveguides) to a generic UMTS test signal (24 h per day, 7 days per week, 0.4 W/kg SAR). Additionally, 30 animals were kept as cage controls. Animals were checked visually each day and were weighed and palpated weekly to detect swollen lymph nodes. Starting at the age of 6 months, blood samples were taken from the tail every 2 weeks to perform differential leukocyte counts and to measure the hematocrit. Visibly diseased animals or those older than 43 weeks were killed humanely, and tissue slices were examined for metastatic infiltrations and lymphoma type. The study was performed in a blinded way. Cage control animals had a significantly lower growth rate than those kept in the radial waveguides. The number of ill animals, the mean survival time, and the severity code of the disease did not differ between the experimental groups. Therefore, the data show no negative effects from exposure and corroborate earlier findings in AKR/J mice exposed to GSM EMF (Sommer et al., BMC Cancer 4, 77-90, 2004).     

Genotoxic effects of occupational exposure to lead and cadmium

This study was designed to assess genotoxic damage in somatic cells of workers in a Polish battery plant after high-level occupational exposure to lead (Pb) and cadmium (Cd), by use of the following techniques: the micronucleus (MN) assay, combined with in situ fluorescence hybridization (FISH) with pan-centromeric probes, analysis of sister chromatid exchanges (SCEs), and the comet assay. Blood samples from 44 workers exposed to lead, 22 exposed to cadmium, and 52 unexposed persons were used for SCE and MN analysis with 5'-bromodeoxyuridine (BrdU) or cytokinesis block, respectively. In parallel, the comet assay was performed with blood samples from the same persons for detection of DNA damage, including single-strand breaks (SSB) and alkali-labile sites (ALS). In workers exposed mostly to lead, blood Pb concentrations ranged from 282 to 655 microg/l, while the range in the controls was from 17 to 180 microg/l. Cd concentration in lead-exposed workers fell in the same range as for the controls. In workers exposed mainly to cadmium, blood Cd levels varied from 5.4 to 30.8 microg/l, with respective values for controls within the range of 0.2-5.7 microg/l. Pb concentrations were similar as for the controls. The incidence of MN in peripheral lymphocytes from workers exposed to Pb and Cd was over twice as high as in the controls (P<0.01). Using a combination of conventional scoring of MN and FISH with pan-centromeric probes, we assessed that this increase may have been due to clastogenic as well as aneugenic effects. In Cd- and Pb-exposed workers, the frequency of SCEs as well as the incidence of leukocytes with DNA fragmentation in lymphocytes were slightly, but significantly increased ( P<0.05) as compared with controls. After a 3h incubation of the cells to allow for DNA repair, a clear decrease was found in the level of DNA damage in the controls as well as in the exposed workers. No significant influence of smoking on genotoxic damage could be detected in metal-exposed cohorts. Our findings indicate that lead and cadmium induce clastogenic as well as aneugenic effects in peripheral lymphocytes, indicating a potential health risk for working populations with significant exposures to these heavy metals.