Are the young more sensitive than adults to the effects of radiofrequency fields? An examination of relevant data from cellular and animal studies

It has sometimes been assumed that children are more sensitive than adults to the effects of radiofrequency (RF) fields associated with cellular wireless telephones. However, relatively few in vitro or animal models have examined this possibility.In vitro studies have used several cell types, from both humans and rodents, including primary cells, embryonic cell lines, undifferentiated cancer cell lines, and stem cells. Overall, the balance of evidence does not suggest that field-related effects occur in any cell type: gene and protein expression were not significantly changed by exposure in nine out of 15 studies; genotoxicity was evaluated in 13 papers and in most, of these studies, no damage to DNA was detected; eight studies failed to demonstrate induction of apoptosis; and three studies reported lack of oxidative stress induction by RF-exposures. Five of eight studies investigating the effects of combined exposures to RF fields and chemical or physical agents reported a lack of field-related effects.In addition, few papers have been published on the effects of low level exposure of immature animals. The available results are very limited, both in terms of signals used and biological endpoints investigated, but the evidence does not indicate that prenatal or early postnatal exposures are associated with acute adverse responses or the development of detrimental changes in the long-term. Overall, this suggests that young animals may not be significantly more sensitive than adults, but there is clearly a need for further studies to be carried out.     

Rapporteur report: implications for exposure guidelines

There is a paucity of information regarding the long-term health effects associated with exposure to static magnetic fields. Perceptual and other acute effects have been demonstrated above a threshold of about 2 T, and these form the basis for human exposure standards at present. Exposures well above this threshold are increasingly becoming more common as the technology associated with magnetic resonance imaging advances. Therefore, priority should be given to assessing the health risks associated with exposures to such fields. Studies should include a prospective cohort study investigating cancer risks of workers and patients exposed to fields in excess of 2 T, a study investigating effects on human cognitive performance from repeated exposures, and a molecular biology study investigating acute changes in genomic responses in volunteers exposed to fields of up to 8 T. Studies investigating the effects of long-term exposure on cancer, and on neurobehavioural development are also recommended using animals, where the use of transgenic models is encouraged. In addition, dosimetric studies should be conducted using high-resolution male, female and pregnant voxel phantoms, as should theoretical studies investigating the local currents induced in the eye and in the heart by movement during exposure. Finally, studies are recommended to investigate further the ability of static magnetic fields to significantly affect radical pair reactions in biological systems.     

Reproductive toxicity in boron exposed workers in Bandirma, Turkey

Boric acid and sodium borates have been considered as being “toxic to reproduction and development”, following results of animal studies with high doses. However unfavorable effects of boron exposure on reproduction and development have not been proved in epidemiological studies so far. The aim of the present study was to investigate the reproductive toxicity indicators in highly exposed workers employed in a boric acid production plant in Band?rma, Turkey. Two hundred and four workers participated in this study. The mean blood boron concentration of the high exposure group of workers was 223.89 ± 69.49 (152.82–454.02) ng/g. Unfavorable effects of boron exposure on the reproductive toxicity indicators were not observed.     

A review of bioeffects of static magnetic field on rodent models

This review is aimed to summarize the experimental researches in the influences of static magnetic field on laboratory rodent models, reported by laboratory scientists, experimental technicians, clinical surgeons, animal veterinarians, and other researchers. Past studies suggested that static magnetic field-singly applied or used combined with other physical or chemical substances-significantly relieved some pains and ameliorated certain diseases in different organ systems, e.g. hypertension, osteoporosis, neuralgia, diabetes and leukemia etc. But on the other hand, some harmful events have also been observed in a number of investigations, from cellular level to fetal development. So exposure to static magnetic field might have dual effects on experimental rodent in various environments, viz. there are potentially therapeutic benefits, as well as adverse effects from it. The positive effect may relate to moderate intensities, while negative influence seems to be in connection with acute strong static magnetic fields. In addition, different orientations of static magnetic field exert different degrees of impact. Thus, the bioeffects of static magnetic field exposure on mice/rats depend on magnetic field intensities, durations and directions, though the exactly relationship between them is still vague. Further researches need to perform with appropriate methodologies, ingenious designs repeatedly and systemically, not only in animal models, but also in human volunteers and patients.     

Health effects of static magnetic fields--a review of the epidemiological evidence

Potential health effects of static magnetic fields have received far less attention than, for example, power frequency or radiofrequency fields. Static fields are found in certain occupational settings, e.g. in the aluminium and chloralkali industries, in arc-welding processes, and certain railways systems. Magnetic resonance imaging (MRI) for medical diagnosis is another source. This paper summarizes the epidemiological evidence of static magnetic field exposure and long-term health effects. There are only a few epidemiological studies available, and the majority of these have focused on cancer risks. There are some reports on reproductive outcomes, and sporadic studies of other outcomes. Overall, few occupational studies have focused specifically on effects of static magnetic field exposure, and exposure assessment have consequently been poor or non-existent. Results from studies that have estimated static magnetic field exposure have not indicated any increased cancer risks, but they are generally based on small numbers of cases and crude exposure assessment. Control of confounding has been limited, and it is likely that the “healthy worker” effect have influenced the results. A few studies have reported results on reproductive outcomes among aluminium workers and MRI operators, but limitations in study designs prevent conclusions. A problem in epidemiological studies of static magnetic fields is that workers in exposed occupations are also exposed to a wide variety of other potentially harmful agents, including some known carcinogens. In conclusion, the available evidence from epidemiological studies is not sufficient to draw any conclusions about potential health effects of static magnetic field exposure.     

Static magnetic field effects on human subjects related to magnetic resonance imaging systems

Goal: This paper reviews recent studies evaluating human subjects for physiologic or neuro-cognitive function adverse effects resulting from exposure to static magnetic fields of magnetic resonance imaging systems.

Materials and Methods: The results of three studies are summarized. Two studies evaluated exposure to a maximum of 8 Tesla (T). The first series studied 25 normal human subjects’ sequential vital signs (heart rate, blood pressure, blood oxygenation, core temperature, ECG, respiratory rate) measured at different magnetic field strengths to a maximum of 8 T. A second series of 25 subjects were studied at 0.05 and 8 T (out and in the bore of the magnet), performing 12 different standardized neuro-psychological tests and auditory–motor reaction times. The subjects’ comments were recorded immediately following the study and after a three-month interval. The third study contained 17 subjects, placed near the bore of a 1.5 T magnet, and it used six different cognitive, cognitive–motor, or sensory tests.

Results: There were no clinically significant changes in the subjects’ physiologic measurements at 8 T. There was a slight increase in the systolic blood pressure with increasing magnetic field strength. There did not appear to be any adverse effect on the cognitive performance of the subjects at 8 T. A few subjects commented at the time of initial exposure on dizziness, metallic taste in the mouth, or discomfort related to the measurement instruments or the head coil. There were no adverse comments at 3 months. The 1.5 T study had two of the four neuro-behavioral domains exhibiting adverse effects (sensory and cognitive–motor).

Conclusions: These studies did not demonstrate any clinically relevant adverse effects on neuro-cognitive testing or vital sign changes. One short-term memory, one sensory, and one cognitive–motor test demonstrated adverse effects, but the significance is not clear.     

Effects of static magnetic fields at the cellular level

There have been few studies on the effects of static magnetic fields at the cellular level, compared to those of extremely low frequency magnetic fields. Past studies have shown that a static magnetic field alone does not have a lethal effect on the basic properties of cell growth and survival under normal culture conditions, regardless of the magnetic density. Most but not all studies have also suggested that a static magnetic field has no effect on changes in cell growth rate. It has also been shown that cell cycle distribution is not influenced by extremely strong static magnetic fields (up to a maximum of 10 T). A further area of interest is whether static magnetic fields cause DNA damage, which can be evaluated by determination of the frequency of micronucleus formation. The presence or absence of such micronuclei can confirm whether a particular treatment damages cellular DNA. This method has been used to confirm that a static magnetic field alone has no such effect. However, the frequency of micronucleus formation increases significantly when certain treatments (e.g., X-irradiation) are given prior to exposure to a 10 T static magnetic field. It has also been reported that treatment with trace amounts of ferrous ions in the cell culture medium and exposure to a static magnetic field increases DNA damage, which is detected using the comet assay. In addition, many studies have found a strong magnetic field that can induce orientation phenomena in cell culture.     

Interaction of static and extremely low frequency electric and magnetic fields with living systems: health effects and research needs

An international seminar was held June 4-6, 1997, on the biological effects and related health hazards of ambient or environmental static and extremely low frequency (ELF) electric and magnetic fields (0-300 Hz). It was cosponsored by the World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), the German, Japanese, and Swiss governments. Speakers provided overviews of the scientific literature that were discussed by participants of the meeting. Subsequently, expert working groups formulated this report, which evaluates possible health effects from exposure to static and ELF electric and magnetic fields and identifies gaps in knowledge requiring more research to improve health risk assessments. The working groups concluded that, although health hazards exist from exposure to ELF fields at high field strengths, the literature does not establish that health hazards are associated with exposure to low-level fields, including environmental levels. Similarly, exposure to static electric fields at levels currently found in the living and working environment or acute exposure to static magnetic fields at flux densities below 2 T, were not found to have demonstrated adverse health consequences. However, reports of biological effects from low-level ELF-field exposure and chronic exposure to static magnetic fields were identified that need replication and further study for WHO to assess any possible health consequences. Ambient static electric fields have not been reported to cause any direct adverse health effects, and so no further research in this area was deemed necessary.     

A magnetic field exposure facility for evaluation of animal carcinogenicity

Several animal studies have been carried out at the Institut Armand Frappier (IAF) to determine whether chronic exposure to 60 Hz linearly polarized sinusoidal magnetic fields might increase the risk of cancer development of female Fisher rats. The magnetic field exposure facility was developed to meet the requirements of the study protocol for chronic exposure of large number of animals to field intensities of sham < 0.2 microT, 2 microT, 20 microT, 200 microT, and 2000 microT. At each exposure level, including sham, the animals are distributed in a group of four exposure units. Each exposure unit contains two exposure volumes having uniform distribution of magnetic fields for the animals, while the magnetic field external to the unit falls off rapidly due to the "figure-eight" coil topography used. A program of "shake down" tests, followed by verification and calibration of the exposure facility, was carried out prior to starting the animal experiments. Continuous monitoring of the magnetic field and other environmental parameters was an important part in the overall quality assurance program adopted.     

Animal studies on growth and development

Despite the fact that no plausible biological mechanism has yet been identified how electromagnetic fields below recommended exposure limits could negatively affect health of animals or humans, many experiments have been performed in various animal species, mainly mice and rats, to investigate the possible effects on growth and development. While older studies often suffered from sub-optimal exposure conditions, recent investigations, using sophisticated exposure devices and thus preventing thermal effects, have been performed without these limitations. In principle, two types of studies can be addressed: those which have investigated the carcinogenic or co-carcinogenic effects of exposure in developing animals, and those which have been done in developing animals without the focus on carcinogenic or co-carcinogenic effects. In both areas, the vast majority of publications did not show adverse effects. The largest study so far has been done in normal mice which have been chronically exposed to UMTS signals up to 1.3 W/kg SAR, thus 16 times higher than the whole-body exposure limit for humans. Even after four generations, no systematic or dose-dependent alterations in development or fertility could be found, supporting the view that negative effects on humans are very unlikely. Ongoing experiments in our laboratory investigate the effects of head-only exposure in rats (up to 10 W/kg local SAR) which are exposed from 14 days of age daily for 2 h. A battery of behavioral tests is performed in young, adult, and pre-senile animals. The results will help to clarify possible effects of exposure on brain development.     

Exposure assessment of boron in Bandırma boric acid production plant

Boric acid and sodium borates have been considered as being “toxic to reproduction and development”, following results of animal studies with high doses. Experimentally, a NOAEL of 17.5 mg B/kg-bw/day (corresponds to ～2020 ng boron/g blood) has been identified for the (male) reproductive effects of boron in a multigenerational study of rats, and a NOAEL for the developmental effects in rats was identified at 9.6 mg B/kg-bw/day (corresponds to 1270 ng boron/g blood). These values are being taken as the basis of current EU safety assessments. The present study was conducted to assess the boron exposure under extreme exposure conditions in a boric acid production plant located in Band?rma, Turkey. The mean blood boron concentrations of low and high exposure groups were 72.94 ± 15.43 (48.46–99.91) and 223.89 ± 60.49 (152.82–454.02) ng/g respectively. The mean blood boron concentration of the high exposure group is still ～6 times lower than the highest no effect level of boron in blood with regard to the developmental effects in rats and ～9 times lower than the highest no effect level of boron in blood with regard to the reprotoxic effects in male rats. In this context, boric acid and sodium borates should not be considered as toxic to reproduction for humans in daily life.     

An electrophysiological study on the effects of pH on olfaction in mature male Atlantic salmon (Salmo salar) parr

The olfactory responses of mature male Atlantic salmon ( Salmo salar L.) parr to known odorants were studied after exposure of the olfactory epithelia to water of varying pH. Electrophysiological recordings from the olfactory epithelia indicated that the responses of fish to both testosterone and urine from ovulated female Atlantic salmon were significantly reduced at pH 5·5 and 4·5 and abolished at pH 3·5. Concentration response studies indicated that at pH 5·5 and 6·5 significantly higher concentrations of testosterone and urine were required to produce the same amplitude responses as controls. Both testosterone and urine have previously been shown to be important chemical cues eliciting behavioural and physiological responses in Atlantic salmon. The results are therefore discussed in relation to the possible sublethal effects of acidification on reproduction and behaviour of Atlantic salmon and the effects on salmonid stocks.     

A newly designed and constructed 20 kHz magnetic field exposure facility for in vivo study

Exposure to man-made electromagnetic fields has increased over the past century. As a result of exposure to these fields, concerns have been raised regarding the relationship between electromagnetic fields and human health. Interest in the biological and health effects of intermediate frequency (IF) magnetic fields has grown recently because of the increase in public concern. In order to investigate whether IF magnetic fields have biological effects, we have developed a 20 kHz (IF) magnetic field exposure system for in vivo studies. The exposure facility was designed to study the biological effects of IF magnetic field on laboratory animals. The facility consists of a 9 m x 9 m x 5 m high room containing seven separate rooms including a 5.3 m x 4.5 m x 3 m high specific-pathogen free exposure room. The dimensions of the exposure system are 1.6 m x 1.6 m x 1.616 m high located inside this exposure room. The system is designed to provide magnetic fields up to 200 microT at 20 kHz with the uniformity within +/-5% over the space occupied by animals. After constructing the facility, performance tests were carried out. As a result, it was confirmed that our facility met requirements for evaluation of the biological effects of IF magnetic field on small animal experiments. In this paper, the design, construction, and results of evaluation of an animal exposure facility for the in vivo biological effects of an IF magnetic field are described.     

Quantification of risk from fetal exposure to diagnostic ultrasound

Biomedical ultrasound may induce adverse effects in patients by either thermal or non-thermal means. Temperatures above normal can adversely affect biological systems, but effects also may be produced without significant heating. Thermally induced teratogenesis has been demonstrated in many animal species as well as in a few controlled studies in humans. Various maximum ‘safe’ temperature elevations have been proposed, although the suggested values range from 0.0 to 2.5° C. Factors relevant to thermal effects are considered, including the nature of the acoustic field in situ, the state of perfusion of the embryo/fetus, and the variation of sensitivity to thermal insult with gestational stage of development. Non-thermal mechanisms of action considered include acoustic cavitation, radiation force, and acoustic streaming. While cavitation can be quite destructive, it is extremely unlikely in the absence of stabilized gas bodies, and although the remaining mechanisms may occur in utero, they have not been shown to induce adverse effects. For example, pulsed, diagnostic ultrasound can increase fetal activity during exposure, apparently due to stimulation of auditory perception by radiation forces on the fetal head or auditory structures. In contrast, pulsed ultrasound also produces vascular damage near developing bone in the late-gestation mouse, but by a unknown mechanism and at levels above current US FDA output limits. It is concluded that: (1) thermal rather than nonthermal mechanisms are more likely to induce adverse effects in utero, and (2) while the probability of an adverse thermal event is usually small, under some conditions it can be disturbingly high.     

Design,construction, and validation of a large capacity rodent magnetic field exposure laboratory

A magnetic field exposure laboratory has been constructed to support National Toxicology Program studies for the evaluation of the toxicity and carcinogenicity of pure, linearly polarized, 60 Hz magnetic fields in rodents. This dual corridor, controlled access facility can support the simultaneous exposure of 1200 rats and 1200 mice. The facility contains fully redundant electrical and environmental control systems and was constructed using non‐metallic materials to maintain low levels of background (ambient), stray, and cross‐talk magnetic fields. The exposure module design provides for large uniform exposure volumes with good control of stray and cross‐talk fields, while allowing the use of roll‐around cage racks for simplified animal husbandry. Stray fields and cross‐talk have been further reduced by the inclusion of “steering coils” in each exposure module. Ambient 60 Hz fields (less cross‐talk) in all exposure rooms are <0.1 μT (1 mG), and static magnetic fields have been mapped extensively. Magnetic field strength, waveform, temperature, relative humidity, light intensity, noise level, vibration, and air flow in all animal holding areas are tightly regulated, and are monitored continuously during all studies. Field uniformity in the animal exposure volumes is better than ±10%; a systematic program of cage, rack, and room rotation controls for possible positional effects within the exposure system. Magnetic fields are turned on and off over multiple cycles to prevent the induction of transients associated with abrupt field level changes. Total harmonic distortion is <3% at all field strengths. The facility has been used to study magnetic field bioeffects in rodent model systems in experiments ranging in duration from 8 weeks to 2 years. Bioelectromagnetics 20:13–23, 1999. © 1999 Wiley‐Liss, Inc.     

Cardiovascular response of rats exposed to 60-Hz electric fields

Recently, it has been reported that exposure to high-strength electric fields can influence electrocardiogram (ECG) patterns, heart rates, and blood pressures in various species of animals. Our studies were designed to evaluate these reported effects and to help clarify some of the disagreement present in the literature. Various cardiovascular variables were measured in Sprague-Dawley rats exposed or sham-exposed to 60-Hz electric fields at 80 or 100 kV/m for periods up to four months. No significant differences in heart rates, ECG patterns, blood pressures, or vascular reactivity were observed between exposed and sham-exposed rats after 8 hours, 40 hours, 1 month, or 4 months of exposure. Blood pressure and heart rate measurements, made during exposure to a 100-kV/m electric field for one hour, revealed no significant differences between exposed and sham-exposed groups. In addition, physiologic reserve capacity, measured in rats subjected to low temperature after exposure to 100 kV/m for one month, showed that electric-field exposure had no significant effect on physiological response to cold stress. Our studies cannot be directly compared to the work of other investigators because of differences in animal species and electric-field characteristics. However, our failure to detect any cardiovascular changes may have been the result of 1) eliminating secondary field effects such as shocks, audible noise, corona, and ozone; 2) minimizing steady-state microcurrents between the mouth of the animal and watering devices; and 3) minimizing electric-field-induced vibration of the electrodes and animal cages.     

A note on the effect of gestation housing environment on approach test measures in gilts

Systems’ welfare evaluation, including behavioural testing, is becoming increasingly popular in farm animal assurance schemes. The aims of this study were to investigate whether fairly short-term exposure to gestation housing systems, which varied in physical, environmental and human-input factors, influenced behavioural and physiological measures during a human approach test—often used to identify problems in human–animal interactions. Twenty-four Large White×Landrace gilts were initially subjected to identical human contact and daily husbandry. Forty-two days after service, the gilts were randomly assigned to either an indoor housing system (n=16) or an outdoor housing system (n=8), which differed physically and in the amount of human contact and daily husbandry. The indoor system used an electronic sow feeder (ESF), was more space-limited and thermally-controlled and had human contact centered on cleaning out. The outdoor system was more extensive, had much greater space accessible, was not thermally-controlled and had human contact that centered around feeding. The human approach test was carried out on all gilts 30–44 days after entry to the gestation system. At testing, each individual was fitted with heart rate monitor and then moved into a test arena. After 2 min an unfamiliar human entered the pen and stood motionless for 3 min against one wall and then approached the gilt and touched her snout. Throughout the experimental period, behaviour and sound within the test arena were recorded continuously. During the 2 min familiarisation period, outdoor gilts had lower heart rates (108.2 bpm versus 123.7 bpm, P<0.05) and tended to perform fewer short vocalisations (0.5 calls per min versus 3.4 calls per min, P<0.1). Outdoor-housed gilts also carried out less locomotor behaviour (2.2 sections crossed versus 4.0 sections crossed, P<0.05) and tended to perform fewer short (1.4 calls per min versus 5.0 calls per min, P<0.1) and long vocalisations (0.2 calls per min versus 1.8 calls per min, P<0.1) over the 3 min test period. Outdoor gilts tended to be slower to approach within 0.5 m of the human (69.9 s versus 19.3 s, P<0.1) but they then took less extra time to make physical contact (3.3 s versus 52.7 s, P<0.1). Mean heart rate was significantly lower in outdoor sows over the whole 3 min period (99.5 bpm versus 115.5 bpm, P<0.05). The results demonstrate that short-term exposure to different housing systems did influence behavioural and physiological measures during a standard human approach test and thus, systems differences should be taken into account before making judgements about the human–animal relationship on any commercial farm, based on results of behavioural tests of this type.     

ELF magnetic fields: animal studies, mechanisms of action

Animal studies can contribute to addressing the issue of possible greater health risk for children exposed to 50–60 Hz extremely low frequency (ELF) magnetic fields (MFs), mostly in terms of teratological effects and cancer.Teratology has been extensively studied in animals exposed to ELF MFs but experiments have not established adverse developmental effects.Childhood leukaemia has been the only cancer consistently reported in epidemiological studies as associated with exposure to ELF MFs. This association has been the basis for the classification as “possibly carcinogenic to humans” by the International Agency for Research on Cancer in 2002. Animal experiments have provided only limited support for these epidemiological findings. However, none but one study used an animal model for acute lymphoblastic leukaemia (ALL), the main form of childhood leukaemia, and exposures to ELF MFs were not carried out over the whole pregnancy period, when the first hit of ALL is assumed to occur.Moreover, there are no generally accepted biophysical mechanisms that could explain carcinogenic effects of low-level MFs. The radical pair mechanism and related cryptochromes (CRY) molecules have recently been identified in birds and other non-mammalian species, as a sensor of the geomagnetic field, involved in navigation. The hypothesis has to be tested in mammalian models. CRY, which is part of the molecular circadian clock machinery, is a ubiquitous protein likely to be involved in cancer cell growth and DNA repair.In summary, we now have some clues to test for a better characterization of the interaction between ALL and ELF MFs exposure.     

Fission in Convolutriloba longifissura: asexual reproduction in acoelous turbellarians revisited

Studies of the asexual reproduction of Convolutriloba longifissura (Acoela, Acoelomorpha) revealed that there is no longitudinal fission of the whole animal as has been described by Bartolomaeus and Balzer (1997) . Instead, the first step is a transverse fission. This results in the detachment of the caudal fourth of the mother animal. The detached part forms what we call the butterfly stage, which initially has no mouth and no eye fields. This stage gives rise to two new individuals by a longitudinal fission. Within 2–3 days the eye fields and a mouth develop in each of the two progenies formed in this way. In the meantime the mother individual grows and develops the three typical caudal lobes. The mother animal can repeat this process resulting in three individuals every fourth day. The finding of this new pattern of reproduction in the Acoela has prompted us to review the various ways by which asexual reproduction occurs in the group. The peculiar combination of few cases but high diversity of asexual reproduction in the Acoela is discussed from an evolutionary point of view.     

Thirty-five years in bioelectromagnetics research

For 35 years, I have been involved in various bioelectromagnetics research projects including acute and long-term radiofrequency (RF) bioeffects studies, dosimetry, exposure systems, MRI safety, cancer studies involving hyperthermia and electrochemical treatment, development of RF exposure and measurement standards, and product compliance. My first study demonstrated that effects on isolated nerve and muscle preparations were due to thermal effects of RF exposure. The recording of cochlear microphonics in animals shows the mechanical nature of the microwave auditory effect. In 1992, we published the results of a large-scale lifetime study in which 100 rats were sham-exposed and 100 rats were exposed for 21 h/day for 25 months to a pulsed RF signal. In dosimetry studies, human models were employed as well as many animal species including mice, rats, rabbits, monkeys, and birds of many sizes. Cancer hyperthermia studies demonstrated that knowledge of temperature distribution was crucial for successful treatment. Research on electrochemical treatment of tumors with direct current involved cellular, animal, and clinical studies. Over the past few decades, there has been rather extensive investigation of the public health impact of RF exposure. In my opinion, future research in bioelectromagnetics should place greater emphasis on medical applications.