Limites de radiação não ionizante

Limites de radiação não ionizante

(Parte 3 de 13)

Studies on mammary cancer development in rodents treated with a chemical initiator have suggested a cancerpromoting effect of exposure to power-frequency magnetic fields in the range 0.01–30 mT (Beniashvili et al. 1991; Loscher et al. 1993; Mevissen et al. 1993, 1995; Baum et al. 1995; Loscher and Mevissen 1995). These observations of increased tumor incidence in rats exposed to magnetic fields have been hypothesized to be related to field-induced suppression of pineal melatonin and a resulting elevation in steroid hormone levels and breast cancer risk (Stevens 1987; Stevens et al. 1992). However, replication efforts by independent laboratories are needed before conclusions can be drawn regarding the implications of these findings for a promoting effect of ELF magnetic fields on mammary tumors. It should

502 Health Physics April 1998, Volume 74, Number 4 also be noted that recent studies have found no evidence for a significant effect of exposure to ELF magnetic fields on melatonin levels in humans (Graham et al. 1996, 1997; Selmaoui et al. 1996).

Indirect effects of electric and magnetic fields

Indirect effects of electromagnetic fields may result from physical contact (e.g., touching or brushing against) between a person and an object, such as a metallic structure in the field, at a different electric potential. The result of such contact is the flow of electric charge (contact current) that may have accumulated on the object or on the body of the person. In the frequency range up to approximately 100 kHz, the flow of electric current from an object in the field to the body of the individual may result in the stimulation of muscles and/or peripheral nerves. With increasing levels of current this may be manifested as perception, pain from electric shock and/or burn, inability to release the object, difficulty in breathing and, at very high currents, cardiac ventricular fibrillation (Tenforde and Kaune 1987). Threshold values for these effects are frequencydependent, with the lowest threshold occurring at frequencies between 10 and 100 Hz. Thresholds for peripheral nerve responses remain low for frequencies up to several kHz. Appropriate engineering and/or administrative controls, and even the wearing of personal protective clothing, can prevent these problems from occurring.

Spark discharges can occur when an individual comes into very close proximity with an object at a different electric potential, without actually touching it (Tenforde and Kaune 1987; UNEP/WHO/IRPA 1993). When a group of volunteers, who were electrically insulated from the ground, each held a finger tip close to a grounded object, the threshold for perception of spark discharges was as low as 0.6–1.5 kV m21 in 10% of cases. The threshold field level reported as causing annoyance under these exposure conditions is about 2.0–3.5 kV m21. Large contact currents can result in muscle contraction. In male volunteers, the 50th percentile threshold for being unable to release a charged conductor has been reported as 9 mA at 50/60 Hz, 16 mA at 1 kHz, about 50 mA at 10 kHz, and about 130 mA at 100 kHz (UNEP/WHO/IRPA 1993).

The threshold currents for various indirect effects of fields with frequencies up to 100 kHz are summarized in Table 2 (UNEP/WHO/IRPA 1993).

Summary of biological effects and epidemiological studies (up to 100 kHz)

With the possible exception of mammary tumors, there is little evidence from laboratory studies that power-frequency magnetic fields have a tumorpromoting effect. Although further animal studies are needed to clarify the possible effects of ELF fields on signals produced in cells and on endocrine regulation— both of which could influence the development of tumors by promoting the proliferation of initiated cells—it can only be concluded that there is currently no convincing evidence for carcinogenic effects of these fields and that these data cannot be used as a basis for developing exposure guidelines.

Laboratory studies on cellular and animal systems have found no established effects of low-frequency fields that are indicative of adverse health effects when induced current density is at or below 10 mA m22. At higher levels of induced current density (10–100 mA m22), more significant tissue effects have been consistently observed, such as functional changes in the nervous system and other tissue effects (Tenforde 1996).

Data on cancer risk associated with exposure to ELF fields among individuals living close to power lines are apparently consistent in indicating a slightly higher risk of leukemia among children, although more recent studies question the previously observed weak association. The studies do not, however, indicate a similarly elevated risk of any other type of childhood cancer or of any form of adult cancer. The basis for the hypothetical link between childhood leukemia and residence in close proximity to power lines is unknown; if the link is not related to the ELF electric and magnetic fields generated by the power lines, then unknown risk factors for leukemia would have to be linked to power lines in some undetermined manner. In the absence of support from laboratory studies, the epidemiological data are insufficient to allow an exposure guideline to be established.

There have been reports of an increased risk of certain types of cancer, such as leukemia, nervous tissue tumors, and, to a limited extent, breast cancer, among electrical workers. In most studies, job titles were used to classify subjects according to presumed levels of magnetic field exposure. A few more recent studies, however, have used more sophisticatedmethodsof exposureassessment; overall, these studies suggestedan increasedrisk of leukemiaor braintumorsbut werelargelyinconsistentwith regardto the type of cancerfor whichrisk is increased.The data are insufficient to provide a basis for ELF field exposureguidelines.In a large number of epidemiological studies, no consistent evidence of adverse reproductive effects have been provided.

Measurement of biological responses in laboratory studies and in volunteers has provided little indication of adverse effects of low-frequency fields at levels to which people are commonly exposed. A threshold current density of 10 mA m22 at frequencies up to 1 kHz has been estimated for minor effects on nervous system functions. Among volunteers, the most consistent effects

Table 2. Ranges of threshold currents for indirect effects, including children, women, and men.

Indirect effect

Threshold current (mA) at frequency:

50/60 Hz 1 kHz 100 kHz

Touch perception 0.2–0.4 0.4–0.8 25–40 Pain on finger contact 0.9–1.8 1.6–3.3 3–5 Painful shock/let-go threshold 8–16 12–24 112–224 Severe shock/breathing difficulty 12–23 21–41 160–320

503Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields ● ICNIRP GUIDELINES of exposure are the appearance of visual phosphenes and a minor reduction in heart rate during or immediately after exposure to ELF fields, but there is no evidence that these transient effects are associated with any long-term health risk. A reduction in nocturnal pineal melatonin synthesis has been observed in several rodent species following exposure to weak ELF electric and magnetic fields, but no consistent effect has been reported in humans exposed to ELF fields under controlled conditions. Studies involving exposures to 60-Hz magnetic fields up to 20 mT have not reported reliable effects on melatonin levels in blood.

BIOLOGICAL BASIS FOR LIMITING EXPOSURE (100kHz –300 GHz)

The following paragraphs provide a general review of relevant literature on the biological effects and potential health effects of electromagnetic fields with frequencies of 100 kHz to 300 GHz. More detailed reviews can be found elsewhere (NRPB 1991; UNEP/WHO/IRPA 1993; McKinlay et al. 1996; Polk and Postow 1996; Repacholi 1998).

Direct effects of electromagnetic fields

Epidemiological studies. Only a limited number of studies have been carried out on reproductive effects and cancer risk in individuals exposed to microwave radiation. A summary of the literature was published by UNEP/WHO/IRPA (1993).

Reproductive outcomes. Two extensive studies on women treated with microwave diathermy to relieve the pain of uterine contractions during labor found no evidence for adverse effects on the fetus (Daels 1973, 1976). However, seven studies on pregnancy outcomes among workers occupationally exposed to microwave radiation and on birth defects among their offspring produced both positive and negative results. In some of the larger epidemiological studies of female plastic welders and physiotherapists working with shortwave diathermy devices, there were no statistically significant effects on rates of abortion or fetal malformation (Kallen et al. 1982). By contrast, other studies on similar populations of female workers found an increased risk of miscarriage and birth defects (Larsen et al. 1991; Ouellet-Hellstrom and Stewart 1993). A study of male radar workers found no association between microwave exposure and the risk of Down’s syndrome in their offspring (Cohen et al. 1977).

Overall, the studies on reproductive outcomes and microwave exposure suffer from very poor assessment of exposure and, in many cases, small numbers of subjects. Despite the generally negative results of these studies, it will be difficult to draw firm conclusions on reproductive risk without further epidemiological data on highly exposed individuals and more precise exposure assessment.

Cancer studies. Studies on cancer risk and microwave exposure are few and generally lack quantitative exposure assessment. Two epidemiological studies of radar workers in the aircraft industry and in the U.S. armed forces found no evidence of increased morbidity or mortality from any cause (Barron and Baraff 1958; Robinette et al. 1980; UNEP/WHO/IRPA 1993). Similar results were obtained by Lillienfeld et al. (1978) in a study of employees in the U.S. embassy in Moscow, who were chronically exposed to low-level microwave radiation. Selvin et al. (1992) reported no increase in cancer risk among children chronically exposed to radiation from a large microwave transmitter near their homes. More recent studies have failed to show significant increases in nervous tissue tumors among workers and military personnel exposed to microwave fields (Beall et al. 1996; Grayson 1996). Moreover, no excess total mortality was apparent among users of mobile telephones (Rothman et al. 1996a, b), but it is still too early to observe an effect on cancer incidence or mortality.

There has been a report of increased cancer risk among military personnel (Szmigielski et al. 1988), but the results of the study are difficult to interpret because neither the size of the population nor the exposure levels are clearly stated. In a later study, Szmigielski (1996) found increased rates of leukemia and lymphoma among military personnel exposed to EMF fields, but the assessment of EMF exposure was not well defined. A few recent studies of populations living near EMF transmitters have suggested a local increase in leukemia incidence (Hocking et al. 1996; Dolk et at. 1997a, b), but the results are inconclusive. Overall, the results of the small number of epidemiological studies published provide only limited information on cancer risk.

Laboratory studies. The following paragraphs provide a summary and critical evaluation of laboratory studies on the biological effects of electromagnetic fields with frequencies in the range 100 kHz–300 GHz. There are separate discussions on results of studies of volunteers exposed under controlled conditions and of laboratory studies on cellular, tissue, and animal systems.

Volunteer studies. Studies by Chatterjee et al. (1986) demonstrated that, as the frequency increases from approximately 100 kHz to 10 MHz, the dominant effect of exposure to a high-intensity electromagnetic field changes from nerve and muscle stimulation to heating. At 100 kHz the primary sensation was one of nerve tingling, while at 10 MHz it was one of warmth on the skin. In this frequency range, therefore, basic health protection criteria should be such as to avoid stimulation of excitable tissues and heating effects. At frequencies from 10 MHz to 300 GHz, heating is the major effect of absorption of electromagnetic energy, and temperature rises of more than 1–2 °C can have adverse health effects such as heat exhaustion and heat stroke (ACGIH 1996). Studies on workers in thermally stressful environments have shown worsening performance of simple tasks as

504 Health Physics April 1998, Volume 74, Number 4 body temperature rises to a level approaching physiological heat stress (Ramsey and Kwon 1988).

A sensation of warmth has been reported by volunteers experiencing high-frequency current of about 100– 200 mA through a limb. The resulting SAR value is unlikely to produce a localized temperature increment of more than 1°C in the limbs (Chatterjee et al. 1986; Chen and Gandhi 1988; Hoque and Gandhi 1988), which has been suggested as the upper limit of temperature increase that has no detrimental health effects (UNEP/WHO/ IRPA 1993). Data on volunteers reported by Gandhi et al. (1986) for frequencies up to 50 MHz and by Tofani et al. (1995) for frequencies up to 110 MHz (the upper limit of the FM broadcast band) support a reference level for limb current of 100 mA to avoid excessive heating effects (Dimbylow 1997).

There have been several studies of thermoregulatory responses of resting volunteers exposed to EMF in magnetic resonance imaging systems (Shellock and Crues 1987; Magin et al. 1992). In general, these have demonstrated that exposure for up to 30 min, under conditions in which whole-body SAR was less than 4Wk g21, caused an increase in the body core temperature of less than 1°C.

Cellular and animal studies. There are numerous reports on the behavioral and physiological responses of laboratory animals, including rodents, dogs, and nonhuman primates, to thermal interactions of EMF at frequencies above 10 MHz. Thermosensitivity and thermoregulatory responses are associated both with the hypothalamus and with thermal receptors located in the skin and in internal parts of the body. Afferent signals reflecting temperature change converge in the central nervous system and modify the activity of the major neuroendocrine control systems, triggering the physiological and behavioral responses necessary for the maintenance of homeostasis.

Exposure of laboratory animals to EMF producing absorption in excess of approximately4Wk g21 has revealed a characteristic pattern of thermoregulatory response in which body temperature initially rises and then stabilizes following the activation of thermoregulatory mechanisms (Michaelson 1983). The early phase of this response is accompanied by an increase in blood volume due to movement of fluid from the extracellular space into the circulation and by increases in heart rate and intraventricular blood pressure. These cardiodynamic changes reflect thermoregulatory responses that facilitate the conduction of heat to the body surface. Prolonged exposure of animals to levels of microwave radiation that raise the body temperature ultimately lead to failure of these thermoregulatory mechanisms.

Several studies with rodents and monkeys have also demonstrated a behavioral component of thermoregulatory responses. Decreased task performance by rats and monkeys has been observed at SAR values in the range 1–3Wk g21 (Stern et al. 1979; Adair and Adams 1980; de Lorge and Ezell 1980; D’Andrea et al. 1986). In monkeys, altered thermoregulatory behavior starts when the temperature in the hypothalamic region rises by as little as 0.2–0.3°C (Adair et al. 1984). The hypothalamus is considered to be the control center for normal thermoregulatory processes, and its activity can be modified by a small local temperature increase under conditions in which rectal temperature remains constant.

At levels of absorbed electromagnetic energy that cause body temperature rises in excess of 1–2°C, a large number of physiological effects have been characterized in studies with cellular and animal systems (Michaelson and Elson 1996). These effects include alterations in neural and neuromuscular functions; increased bloodbrain barrier permeability; ocular impairment (lens opacities and corneal abnormalities); stress-associated changes in the immune system; hematological changes; reproductive changes (e.g., reduced sperm production); teratogenicity; and changes in cell morphology, water and electrolyte content, and membrane functions.

Under conditions of partial-body exposure to intense

EMF, significant thermal damage can occur in sensitive tissues such as the eye and the testis. Microwave exposure of 2–3 h duration has produced cataracts in rabbits’ eyes at SAR values from 100–140 W kg21, which produced lenticular temperatures of 41–43°C (Guy et al. 1975). No cataracts were observed in monkeys exposed to microwave fields of similar or higher intensities, possibly because of different energy absorption patterns in the eyes of monkeys from those in rabbits. At very high frequencies (10–300 GHz), absorption of electromagnetic energy is confined largely to the epidermal layers of the skin, subcutaneous tissues, and the outer part of the eye. At the higher end of the frequency range, absorption is increasingly superficial. Ocular damage at these frequencies can be avoided if the microwave power density is less than 50 W m22 (Sliney and Wolbarsht 1980; UNEP/WHO/IRPA 1993).

There has been considerable recent interest in the possible carcinogenic effects of exposure to microwave fields with frequencies in the range of widely used communications systems, including hand-held mobile telephones and base transmitters. Research findings in this area have been summarized by ICNIRP (1996). Briefly, there are many reports suggesting that microwave fields are not mutagenic, and exposure to these fields is therefore unlikely to initiate carcinogenesis (NRPB 1992; Cridland 1993; UNEP/WHO/IRPA 1993). By contrast, some recent reports suggest that exposure of rodents to microwave fields at SAR levels of the order of 1Wk g21 may produce strand breaks in the DNA of testis and brain tissues (Sarkar et al. 1994; Lai and Singh 1995, 1996), although both ICNIRP (1996) and Williams (1996) pointed out methodological deficiencies that could have significantly influenced these results.

In a large study of rats exposed to microwaves for up to 25 mo, an excess of primary malignancies was noted in exposed rats relative to controls (Chou et al. 1992). However, the incidence of benign tumors did not differ between the groups, and no specific type of tumor

505Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields ● ICNIRP GUIDELINES was more prevalent in the exposed group than in stock rats of the same strain maintained under similar specificpathogen-free conditions. Taken as a whole, the results of this study cannot be interpreted as indicating a tumor-initiating effect of microwave fields.

Several studies have examined the effects of microwave exposure on the development of pre-initiated tumor cells. Szmigielski et al. (1982) noted an enhanced growth rate of transplanted lung sarcoma cells in rats exposed to microwaves at high power densities. It is possible that this resulted from a weakening of the host immune defense in response to thermal stress from the microwave exposure. Recent studies using athermal levels of microwave irradiation have found no effects on the development of melanoma in mice or of brain glioma in rats (Santini et al. 1988; Salford et al. 1993).

Repacholi et al. (1997) have reported that exposure of 100 female, Em-pim1 transgenic mice to 900-MHz fields, pulsed at 217 Hz with pulse widths of 0.6 ms for up to 18 mo, produced a doubling in lymphoma incidence compared with 101 controls. Because the mice were free to roam in their cages, the variation in SAR was wide (0.01–4.2 W kg21). Given that the resting metabolic rate of these mice is 7–15 W kg21, only the upper end of the exposure range may have produced some slight heating. Thus, it appears that this study suggests a non-thermal mechanism may be acting, which needs to be investigated further. However, before any assumptions can be made about health risk, a number of questions need to be addressed. The study needs to be replicated, restraining the animals to decrease the SAR exposure variation and to determine whether there is a dose response. Further study is needed to determine whether the results can be found in other animal models in order to be able to generalize the results to humans. It is also essential to assess whether results found in transgenic animals are applicable to humans.

Special considerations for pulsed and amplitude-modulated waveforms

Compared with continuous-wave (CW) radiation, pulsed microwave fields with the same average rate of energy deposition in tissues are generally more effective in producing a biological response, especially when there is a well-defined threshold that must be exceeded to elicit the effect (ICNIRP 1996). The “microwave hearing” effect is a well known example of this (Frey 1961; Frey and Messenger 1973; Lin 1978): people with normal hearing can perceive pulse-modulated fields with frequencies between about 200 MHz and 6.5 GHz. The auditory sensation has been variously described as a buzzing, clicking, or popping sound, depending on the modulation characteristics of the field. The microwave hearing effects have been attributed to a thermoelastic interaction in the auditory cortex of the brain, with a threshold for perception of about 100–400 mJ m22 for pulses of duration less than 30 ms at 2.45 GHz (corresponding to an SA of 4–16 mJ kg21). Repeated or prolonged exposure to microwave auditory effects may be stressful and potentially harmful.

Some reports suggest that retina, iris, and corneal endothelium of the primate eye are sensitive to low levels of pulsed microwave radiation (Kues et al. 1985; UNEP/ WHO/IRPA 1993). Degenerative changes in lightsensitive cells of the retina were reported for absorbed energy levels as low as 26 mJ kg21. After administration of timolol maleate, which is used in the treatment of glaucoma, the threshold for retinal damage by pulsed fields dropped to 2.6 mJ kg21. However, an attempt in an independent laboratory to partially replicate these findings for CW fields (i.e., not pulsed) was unsuccessful (Kamimura et al. 1994), and it is therefore impossible at present to assess the potential health implications of the initial findings of Kues et al. (1985).

Exposure to intense pulsed microwave fields has been reported to suppress the startle response in conscious mice and to evoke body movements (NRPB 1991; Sienkiewicz et al. 1993; UNEP/WHO/IRPA 1993). The threshold specific energy absorption level at midbrain that evoked body movements was 200 J kg21 for 10 ms pulses. The mechanism for these effects of pulsed microwaves remains to be determined but is believed to be related to the microwave hearing phenomenon. The auditory thresholds for rodents are about an order of magnitude lower than for humans, that is 1–2 mJ kg21 for pulses ,30 ms in duration. Pulses of this magnitude have also been reported to affect neurotransmitter metabolism and the concentration of the neural receptors involved in stress and anxiety responses in different regions of the rat brain.

The issue of athermal interactions of high-frequency

EMF has centered largely on reports of biological effects of amplitude modulated (AM) fields under in-vitro conditions at SAR values well below those that produce measurable tissue heating. Initial studies in two independent laboratories led to reports that VHF fields with amplitude modulation at extremely low frequencies (6–20 Hz) produced a small, but statistically significant, release of Ca11 from the surfaces of chick brain cells (Bawin et al. 1975; Blackman et al. 1979). A subsequent attempt to replicate these findings, using the same type of AM field, was unsuccessful (Albert et al. 1987). A number of other studies of the effects of AM fields on Ca11 homeostasis have produced both positive and negative results. For example, effects of AM fields on Ca11 binding to cell surfaces have been observed with neuroblastoma cells, pancreatic cells, cardiac tissue, and cat brain cells, but not with cultured rat nerve cells, chick skeletal muscle, or rat brain cells (Postow and Swicord 1996).

Amplitude-modulated fields have also been reported to alter brain electrical activity (Bawin et al. 1974), inhibit T-lymphocyte cytotoxic activity (Lyle et al. 1983), decrease the activities of non-cyclic-AMP- dependent kinase in lymphocytes (Byus et al. 1984), and cause a transient increase in the cytoplasmic activity of ornithine decarboxylase, an essential enzyme for cell proliferation (Byus et al. 1988; Litovitz et al. 1992). In contrast, no effects have been observed on a wide variety

506 Health Physics April 1998, Volume 74, Number 4 of other cellular systems and functional end-points, including lymphocyte capping, neoplastic cell transformation, and various membrane electrical and enzymatic properties (Postow and Swicord 1996). Of particular relevance to the potential carcinogenic effects of pulsed fields is the observation by Balcer-Kubiczek and Harrison (1991) that neoplastic transformation was accelerated in C3H/10T1/2 cells exposed to 2,450-MHz microwaves that were pulse-modulated at 120 Hz. The effect was dependent on field strength but occurred only when a chemical tumor-promoter, TPA, was present in the cell culture medium. This finding suggests that pulsed microwaves may exert co-carcinogenic effects in combination with a chemical agent that increases the rate of proliferation of transformed cells. To date, there have been no attempts to replicate this finding, and its implication for human health effects is unclear.

(Parte 3 de 13)

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