ID Number		2282
Study Type		Literature Review, Letter, Book Chapt., Report
Model		Review papers from an international workshop entitled Thermal Aspects of Radio Frequency Exposure convened in Gaithersburg, Maryland, USA in January 2010 (and more recent papers).
Details		AUTHORS' ABSTRACT: Foster and Morrissey (2011) (IEEE #5190): This special issue contains papers presented at an international workshop entitled Thermal Aspects of Radio Frequency Exposure convened in Gaithersburg, Maryland, USA on 11-12 January 2010, and co-sponsored by the Mobile Manufacturers Forum, the GSM Association, and the US Food and Drug Administration. The goals of the workshop were to (1) identify appropriate health endpoints associated with thermal hazards and their time-dependence thresholds, and (2) outline future directions for research that might lead to an improved understanding of health and safety implications of human exposure to radiofrequency energy and design of improved exposure limits for this energy. This present contribution summarises some of the major conclusions of the speakers, and offers comments by one of the present authors on proposed research priorities and the implications of the material presented at the workshop for setting improved thermally based limits for human exposure to RF energy. AUTHORS' ABSTRACT: Yarmolenko, Dewhirst et al. (2011) (IEEE #5191): The purpose of this review is to summarise a literature survey on thermal thresholds for tissue damage. This review covers published literature for the consecutive years from 20022009. The first review on this subject was published in 2003. It included an extensive discussion of how to use thermal dosimetric principles to normalise all time-temperature data histories to a common format. This review utilises those same principles to address sensitivity of a variety of tissues, but with particular emphasis on brain and testis. The review includes new data on tissues that were not included in the original review. Several important observations have come from this review. First, a large proportion of the papers examined for this review were discarded because timetemperature history at the site of thermal damage assessment was not recorded. It is strongly recommended that future research on this subject include such data. Second, very little data is available examining chronic consequences of thermal exposure. On a related point, the time of assessment of damage after exposure is critically important for assessing whether damage is transient or permanent. Additionally, virtually no data are available for repeated thermal exposures which may occur in certain recreational or occupational activities. For purposes of regulatory guidelines, both acute and lasting effects of thermal damage should be considered. AUTHROS' ABSTRACT: Beachy and Repasky (2011) (IEEE #5192): There is interest in understanding the health impact of thermal effects as a result of exposure of humans to radiofrequency/microwave (RF/MW) fields. Immune cells and responses are affected by modest changes in temperature and it is important to quantify these effects and establish safety thresholds similar to what has been done with other tissue targets. Since previous summaries of thresholds for thermal damage to normal tissues have not focused much attention to cells of the immune system, this summary highlights recent studies which demonstrate positive and some negative effects of temperature shifts on human immune cells. We emphasise literature reporting adverse immunological endpoints (such as cell damage, death and altered function) and provide the temperature at which these effects were noted. Whereas there have been many in vitro studies of adverse temperature effects on immune cells, there has been limited validation of these temperature effects in vivo. However, data from heat stress/stroke patients do provide some information regarding core temperatures (40°C) at which thermal damage to immunological processes can begin to occur. We conclude that there is considerable need for more quantitative time temperature assessments using relevant animal models, more complete kinetic analyses to determine how long immunological effects persist, and for analysis of whether frequency of exposure has impact on immune function. To date, no attempt to categorise effects by using cumulative thermal dose measurements (e.g. cumulative equivalent minutes at a given temperature) has been conducted for cells or tissues of the immune system, representing a major gap in this field. AUTHORS' ABSTRACT: Wetsel (2011) (IEEE #5193): This review focuses upon the past 8 years of research on hyperthermic effects on behavior. Heat stress and heat stoke become severe conditions when body temperatures exceed 40°C as this can lead to delirium, convulsions, coma, and death. The animal literature indicates that hyperthermia can increase glutamatergic and decrease GABAergic neurotransmission. Interestingly, µ-opiate receptor antagonists can attenuate the morphological and biochemical changes in brain, as well as, ameliorate some behavioral deficits induced by heart stress. In humans, heat stress can produce detrimental effects on motor and cognitive performance. Since most cognitive tasks require a motor response, some cognitive deficiencies may be attributed to decreased motor performance. Although hyperthermia may exert more deleterious effects on complex than simple cognitive tasks, systematic studies are needed to examine the effects of different levels and durations of hyperthermia (irrespective of dehydration) on cognition. Additionally, body temperatures should be carefully monitored where controls are run for baseline or brief exposures to a hyperthermic environment. Acute radiofrequency exposure can disrupt behavior when body temperatures increase >1°C with whole body SAR between 3.28.4 W/kg and time-averaged power densities at 8140 mW/cm2. Effects of lower levels of radiation are conflicting and some experiments fail to replicate even with the original investigators. This suggests either that brief exposure to the radiation is at a threshold where some individuals are affected while others are not, or that these levels are innocuous. Nevertheless, thermal changes appear to account for almost all of the behavioral effects reported. AUTHORS' ABSTRACT: Ziskin and MOrrissey (2011) (IEEE #5194): The human embryo and foetus may be especially vulnerable to chemical and physical insults during defined stages of development. In particular, the scheduled processes of cell proliferation, cell migration, cell differentiation, and apoptosis that occur at different times for different organ structures can be susceptible to elevated temperatures. With limited ability to regulate temperature on its own, the developing embryo and foetus is entirely dependent upon the mother's thermoregulatory capacity. As a general rule, maternal core body temperature increases of 2°C above normal for extended periods of time, 22.5°C above normal for 0.51 h, or e4°C above normal for 15 min have resulted in developmental abnormalities in animal models. Significant differences in thermoregulation and thermoneutral ambient temperatures make direct extrapolation of animal data to humans challenging, and the above temperatures may or may not be reasonable threshold predictions for adverse developmental effects in humans. Corresponding specific absorption rate (SAR) values that would be necessary to cause such temperature elevations in a healthy adult female would be in the range of e15 W/kg (whole body average or WBA), with 4 W/kg required to increase core temperature 1°C. However, smaller levels of thermal stress in the mother that are asymptomatic might theoretically result in increased shunting of blood volume to the periphery as a heat dissipation mechanism. This could conceivably result in altered placental and umbilical blood perfusion and reduce heat exchange with the foetus. It is difficult to predict the magnitude and threshold for such an effect, as many factors are involved in the thermoregulatory response. However, a very conservative estimate of 1.5 W/kg WBA (1/10th the threshold to protect against measurable temperature increases) would seem sufficient to protect against any significant reduction in blood flow to the embryo or foetus in the pregnant mother. This is more than three times above the current WBA limit for occupational exposure (0.4 W/kg) as outlined in both IEEE C95.1-2005 and ICNIRP-1998 international safety standards for radiofrequency (RF) exposures. With regard to local RF exposure directly to the embryo or foetus, significant absorption by the mother as well as heat dissipation due to conductive and convective exchange would offer significant protection. However, a theoretical 1-W/kg exposure averaged over the entire 28-day embryo, or averaged over a 1-g volume in the foetus, should not elevate temperature more than 0.2°C. Because of safety standards, exposures to the foetus this great would not be attainable with the usual RF sources. Foetal exposures to ultrasound are limited by the US Food and Drug Administration (FDA) to a maximum spatial peak temporal average intensity of 720 mW/cm2. Routine ultrasound scanning typically occurs at lower values and temperature elevations are negligible. However, some higher power Doppler ultrasound devices under some conditions are capable of raising foetal temperature several degrees and their use in examinations of the foetus should be minimised. AUTHORS' ABSTRACT: Wetsel (2011) (IEEE #5195): The past decade has witnessed the cloning of a new family of ion channels that are responsive to temperature. Six of these transient receptor potential (TRP) channels are proposed to be involved in thermosensation and are located in sensory nerves and skin. The TRPV1, TRPV2, TRPV3, and TRPV4 channels have incompletely overlapping functions over a broad thermal range from warm to hot. Deletion of the individual TRPV1, TRPV3, and TRPV4 channels in mice has established their physiological role in thermosensation. In all cases thermosensation is not completely abolished  suggesting some functional redundancy among the channels. Notably, the TRPV2 channel is responsive to hot temperatures in heterologous systems, but its physiological relevance in vivo has not been established. Cool and cold temperatures are sensed by TRPM8 and TRPA1 family members. Currently, the pharmaceutical industry is developing agonists and antagonists for the various TRP channels. For instance, TRPV1 receptor agonists produce hypothermia, while antagonists induce hyperthermia. Recent investigations have found that different regions of the TRPV1 receptor are responsive to temperature, nociceptive stimuli, and various chemical agents. With this information, it has been possible to develop a TRPV1 compound that blocks responses to capsaicin and acid while leaving temperature sensitivity intact. These channels have important implications for hyperthermia research and may help to identify previously unexplored mechanisms in different tissues that are responsive to thermal stress. AUTHORS' ABSTRACT: Van Rhoon et al. (2011) (IEEE #5196): The Health Council of the Netherlands (HCN) and other organisations hold the basic assumption that induced electric current and the generation and absorption of heat in biological material caused by radiofrequency electromagnetic fields are the only causal effects with possible adverse consequences for human health that have been scientifically established to date. Hence, the exposure guidelines for the 10 MHz10 GHz frequency range are based on avoiding adverse effects of increased temperatures that may occur of the entire human body at a specific absorption rate (SAR) level above 4 W/kg. During the workshop on Thermal Aspects of Radio Frequency Exposure on 1112 January 2010 in Gaithersburg, Maryland, USA, the question was raised whether there would be a practical advantage in shifting from expressing the exposure limits in SAR to expressing them in terms of a maximum allowable temperature increase. This would mean defining adverse timetemperature thresholds. In this paper, the HCN discusses the need for this, considering six points: consistency, applicability, quantification, causality, comprehensibility and acceptability. The HCN concludes that it seems unlikely that a change of dosimetric quantity will help us forward in the discussion on the scientific controversies regarding the existence or non-existence of non-thermal effects in humans following long duration, low intensity exposure to electromagnetic fields. Therefore, the HCN favours maintaining the current approach of basic restrictions and reference levels being expressed as SAR and in V/m or µT, respectively.
Findings		Effects (only at thermal levels)
Status		Completed With Publication
Principal Investigator		Duke University Medical School - dewhirst@radonc.duke.edu
Funding Agency		FDA, MMF and GSMA
Country		UNITED STATES
References		Foster, KR et al. International Journal of Hyperthermia., (2011) 27:307-319 Yarmolenko, PS et al. International Journal of Hyperthermia., (2011) 27:320-343 Beachy, SH et al. International Journal of Hyperthermia , (2011) 27:344-352 Wetsel, WC International Journal of Hyperthermia., (2011) 27:353-373 Ziskin, MC et al. International Journal of Hyperthermia., (2011) 27:374-387 Wetsel, WC International Journal of Hyperthermia. , (2011) 27:388-398 van Rhoon, GC et al. International Journal of Hyperthermia. , (2011) 27:399-404 Hylander, BL et al. Trends Cancer., (2016) 2:166-175
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