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

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

Electromagnetic Fields Associated with Commercial Solar Photovoltaic Electric Power Generating Facilities.

The southwest region of the United States is expected to experience an expansion of commercial solar photovoltaic generation facilities over the next 25 years. A solar facility converts direct current generated by the solar panels to three-phase 60-Hz power that is fed to the grid. This conversion involves sequential processing of the direct current through an inverter that produces low-voltage three-phase power, which is stepped up to distribution voltage (∼12 kV) through a transformer. This study characterized magnetic and electric fields between the frequencies of 0 Hz and 3 GHz at two facilities operated by the Southern California Edison Company in Porterville, CA and San Bernardino, CA. Static magnetic fields were very small compared to exposure limits established by IEEE and ICNIRP. The highest 60-Hz magnetic fields were measured adjacent to transformers and inverters, and radiofrequency fields from 5-100 kHz were associated with the inverters. The fields measured complied in every case with IEEE controlled and ICNIRP occupational exposure limits. In all cases, electric fields were negligible compared to IEEE and ICNIRP limits across the spectrum measured and when compared to the FCC limits (≥0.3 MHz).

The relationship between residential magnetic fields and contact voltage: a pooled analysis.

It has been suggested that residential exposure to contact currents may be more directly associated with the potential for an increased risk of leukemia in childhood than magnetic fields. Contact current exposure occurs when a child contacts a bathtub's water fixtures, which are usually contiguous with a residence's electrical ground, and when the drainpipe is conductive. The Northern California Childhood Leukemia Study (NCCLS) is the only epidemiological study known to address whether contact current may confound the reported association between residential magnetic fields and childhood leukemia. The study contributed contact voltage and magnetic-field data for over 500 residences of leukemia cases and control children. We combined these data with the results of previous measurement studies of contact voltage in other communities to conduct an analysis of the relationship of magnetic fields with contact voltage for a total sample of 702 residences. The Spearman correlation of magnetic field with contact voltage was 0.29 (Spearman, P < 0.0001). Magnetic-field and contact voltage data were both divided into tertiles, with an upper magnetic-field cutpoint of 0.3 µT suggested by values used in epidemiological results and an upper contact voltage cutpoint of 60 mV based on dosimetric considerations. Expressed as an exposure odds ratios (EOR), we report an association of contact voltage with magnetic fields of 15.1 (95% CI 3.6-61) as well as a statistically significant positive trend across magnetic-field strata (EOR of 4.2 per stratum with 95% CI 2.4-7.4). The associations appear to be large enough to support the possibility that contact current could be responsible for the association of childhood leukemia with magnetic fields.

Future needs of occupational epidemiology of extremely low frequency electric and magnetic fields: review and recommendations.

The occupational epidemiological literature on extremely low frequency electric and magnetic fields (EMF) and health encompasses a large number of studies of varying design and quality that have addressed many health outcomes, including various cancers, cardiovascular disease, depression and suicide, and neurodegenerative diseases, such as Alzheimer disease and amyotrophic lateral sclerosis (ALS). At a 2006 workshop we reviewed studies of occupational EMF exposure with an emphasis on methodological weaknesses, and proposed analytical ways to address some of these. We also developed research priorities that we hope will address remaining uncertainties. Broadly speaking, extensive epidemiological research conducted during the past 20 years on occupational EMF exposure does not indicate strong or consistent associations with cancer or any other health outcomes. Inconsistent results for many of the outcomes may be attributable to numerous shortcomings in the studies, most notably in exposure assessment. There is, however, no obvious correlation between exposure assessment quality and observed associations. Nevertheless, for future research, the highest priorities emerge in both the areas of exposure assessment and investigation of ALS. To better assess exposure, we call for the development of a more complete job-exposure matrix that combines job title, work environment and task, and an index of exposure to electric fields, magnetic fields, spark discharge, contact current, and other chemical and physical agents. For ALS, we propose an international collaborative study capable of illuminating a reported association with electrical occupations by disentangling the potential roles of electric shocks, magnetic fields and bias. Such a study will potentially lead to evidence-based measures to protect public health.

Magnetic field exposure and long-term survival among children with leukaemia.

We examined the association between magnetic field (MF) exposure and survival among children with acute lymphoblastic leukaemia (ALL) treated at 51 Pediatric Oncology Group centres between 1996 and 2001. Of 1672 potentially eligible children under treatment, 482 (29%) participated and personal 24-h MF measurements were obtained from 412 participants. A total of 386 children with ALL and 361 with B-precursor ALL were included in the analysis of event-free survival (time from diagnosis to first treatment failure, relapse, secondary malignancy, or death) and overall survival. After adjustment for risk group and socioeconomic status, the event-free survival hazard ratio (HR) for children with measurements >/=0.3 muT was 1.9 (95% confidence interval (CI) 0.8, 4.9), compared to <0.1 muT. For survival, elevated HRs were found for children exposed to >/=0.3 muT (multivariate HR=4.5, 95% CI 1.5-13.8) but based on only four deaths among 19 children. While risk was increased among children with exposures above 0.3 muT, the small numbers limited inferences for this finding.

Evaluation of interactions of electric fields due to electrostatic discharge with human tissue.

Electrostatic discharges (ESDs) produce in the human tissue very strong electric fields of short duration. Possible biophysical interactions are evaluated by comparing the fields in subcutaneous fat/skin to the thresholds for peripheral nerve stimulation, and by computations of membrane potential and electric fields in cytoplasm of a typical cell in bone marrow. It is found that a 4-A peak ESD event is capable of stimulation of nerves located in subcutaneous fat of the lower arm of the hand eliciting a spark, with tens of kV/m and pulse duration of approximately 80 ns. For the same ESD event, the transmembrane potential (TMP) reaches 32 mV with a pulse duration of approximately 200 ns (half-width duration). The electric field in the cytoplasm of a bone marrow cell changes from about 8.8 kV/m to--2 kV/m in about 200 ns.

Electric fields in the human body due to electrostatic discharges.

Electrostatic discharges (ESDs) occur when two objects at different electric potentials come close enough to arc (spark) across the gap between them. Such discharges may be either single-event or repetitive (e.g., 60 Hz). Some studies have indicated that ESDs may be a causative factor for health effects in electric utility workers. Moreover, a hypothesis has recently been forwarded imperceptible contact currents in the human body may be responsible for health effects, most notably childhood leukemia. Numerical modeling indicates that the electric fields in human tissue resulting from typical contact currents are much greater than those induced from typical exposures to electric and magnetic fields at power line frequencies. Numerical modeling is used here to compute representative spark-discharge dosimetry in a realistic human adult model. The frequency-domain scalar potential finite difference method is applied in conjunction with the Fourier transform to assess electric fields in selected regions and tissues of interest in the body. Electric fields in such tissues as subcutaneous fat (where peripheral nerves may be excited), muscle and bone marrow are of the order of kilovolts per meter in the lower arm. The pulses, however, are of short duration (approximately 100 ns).

Study of high- and low-current-configuration homes from the 1988 Denver Childhood Cancer Study.

An epidemiological study conducted by Savitz et al. reported that residential wire codes were more strongly associated with childhood cancer than were measured magnetic fields, a peculiar result because wire codes were originally developed to be a surrogate for residential magnetic fields. The primary purpose of the study reported here, known as the Back to Denver (BTD) study, was to obtain data to help in the interpretation of the original results of Savitz et al. The BTD study included 81 homes that had been occupied by case and control subjects of Savitz et al., stratified by wire code as follows: 18 high current configuration (HCC) case homes; 20 HCC control homes; 20 low current configuration (LCC) case homes; and 23 LCC control homes. Analysis of new data acquired in these homes led to the following previously unpublished conclusions. The home-averaged (i.e., mean of fields measured in subjects' bedrooms, family/living rooms, and rooms where meals normally eaten) spot 60 Hz, 180 Hz, and harmonic (i.e., 60-420 Hz) magnetic fields were associated with wire codes. The 180 Hz and harmonic components, but not the 60 Hz component, were associated with case/control status. Measured static magnetic fields were only weakly correlated (rapproximately 0.2) between rooms in homes. The BTD data provide little support for, but are too sparse to definitively test, the 1995 resonance hypothesis proposed by Bowman et al. Case and control homes had similar concentrations of copper in their tap water. Copper concentration was not associated with wire codes nor with the level of electric current carried by a home's water pipe. These results of the BTD study suggest that future case/control studies investigating power frequency magnetic fields might wish to include measurements of 180 Hz or harmonic magnetic fields in order to examine their associations (if any) with disease status.

Alternative magnetic field exposure metrics: relationship to TWA, appliance use, and demographic characteristics of children in a leukemia survival study.

The ongoing Childhood Leukemia Survival Study is examining the possible association between magnetic field exposure and survival of children with newly diagnosed acute lymphocytic leukemia (ALL). We report the results of the first year 24 h personal magnetic field monitoring for 356 US and Canadian children by time weighted average TWA and alternative exposure metrics. The mean TWA of 0.12 microT was similar to earlier personal exposure studies involving children. A high correlation was found between 24 h TWA and alternative metrics: 12 h day TWA, 12 night TWA, geometric mean, 95th percentile value, percentage time over 0.2 and 0.3 microT, and an estimate of field stability (Constant Field Metric). Two measures of field intermittency, rate of change metric (RCM) and standardized rate of change metric (RCMS), were not highly correlated with TWA. The strongest predictor of TWA was location of residence, with highest TWAs associated with urban areas. Residence in an apartment, lower paternal educational level, and residential mobility were also associated with higher TWAs. There were no significant differences in the appliance use patterns of children with higher TWA values. Children with the highest field intermittency (high RCM) were more likely to sit within 3 feet of a video game attached to the TV. Our results suggest that 24 h TWA is a representative metric for certain patterns of exposure, but is not highly correlated with two metrics that estimate field intermittency.

Magnetic-field exposures of cable splicers in electrical network distribution vaults.

The purposes of the research reported here were to quantify the power-frequency magnetic-field exposures of cable splicers while they were performing tasks in energized network distribution vaults and to compare these exposures with occupational exposure guideline levels. Network vaults supply electricity to commercial and residential urban areas as well as to large buildings. Participating workers wore a personal exposure monitor at the waist, kept a simple diary to record their work location, and recorded information about the vaults and tasks performed. To capture temporal variability, a stationary meter was deployed in the vault during a task. Load current in the vault was measured. To examine temporal variability over long time periods, stationary meters were deployed in selected vaults for one month. Data were collected during 77 tasks in 69 vaults for 191 person-tasks, representing approximately 400 hours of in-vault personal exposure data. Highest exposures were observed in tasks performed near secondary conductors. Personal exposure variability arises principally from worker movement and activities in the vaults, not from load variability during a task. Maximum field during a person-task exceeded the International Committee on Non-Ionizing Radiation Protection (ICNIRP) (0.42 millitesla) and the American Conference of Governmental Industrial Hygienists (ACGIH) (1.0 millitesla) guideline levels during 14 percent and 8 percent of the person-tasks, respectively. The mean of measurements during a person-task exceeded those guideline levels during 4 percent and 2 percent of the person-tasks, respectively. A large number of person-tasks (40%) had measured fields above the ACGIH recommended limit of 0.1 millitesla for workers with pacemakers or other implanted devices. Based on the frequency and duration of their high exposures, cable splicers working in network distribution vaults are one of the most highly exposed groups in the electric utility industry. Selective assignment of work location and task could minimize the likelihood of exposures for vault workers exceeding guideline limits for wearers of pacemakers or other implanted devices. Scheduling vault tasks during off-peak hours (nights and weekends) may reduce exposures. However, even during these periods exposures in certain vaults can still exceed guideline levels.

Mortality patterns by occupation in a cohort of electric utility workers.

BACKGROUND: Mortality patterns were examined in a United States cohort of 138,905 male electric utility workers from five companies to help interpret previous studies of health effects in this industry. METHODS: Using Poisson regression techniques, internal cohort analyses examined total mortality, cardiovascular disease, and cancer in relation to duration of employment in each of nineteen occupational categories which comprise utility operations. RESULTS: Relative to workers who were never involved in utility operations (e.g., administrative workers), mortality rate ratios among operations workers were higher for total mortality, cardiovascular disease, and total cancer. Lung cancer risk was consistently elevated, whereas increased mortality for other cancers was less consistent. CONCLUSIONS: The results of this study indicate excess risk of total mortality, cardiovascular disease, and some cancers among electric utility workers, which could be related to both occupational and non-occupational risk factors.

Evaluation of biological effects, dosimetric models, and exposure assessment related to ELF electric- and magnetic-field guidelines.

Several organizations worldwide have issued guidelines to limit occupational and public exposure to electric and magnetic fields and contact currents in the extremely low frequency range (<3 kilohertz). In this paper, we evaluate relevant developments in biological and health research, computational methods for estimating dosimetric quantities, and exposure assessment, all with an emphasis on the power frequency (60 hertz in North America, 50 hertz in Europe). The aim of each guideline is to prevent acute neural effects of induced electric fields. An evaluation of epidemiological and laboratory studies of neurobiological effects identified peripheral nerve stimulation as the response most suitable for establishing a magnetic-field guideline. Key endpoints that merit further study include reversal of evoked potentials; cardiovascular function, as measured by heart rate and heart rate variability; and sleep patterns. High-resolution computations of induced electric fields and current densities in anatomically correct human models are now achieved with finite-difference methods. The validity and limitations of these models have been demonstrated by computations in regular geometric shapes, using both analytic and numeric computations. Calculated values for average dosimetric quantities are typically within a few percent for the two approaches. However, maximum induced quantities are considerably overestimated by numerical methods, particularly at air interfaces. Overestimates are less pronounced for the upper 99th percentile level of a dosimetric quantity, making this measure a more useful indicator of maximum dose. Neural stimulation thresholds are dependent on the electric field around the excitable cell rather than on the current density, making the former preferable for expression of basic restrictions based on nervous system function. Furthermore, modeling data indicate that the induced electric field is much less strongly influenced by tissue conductivity than is the induced current density. In the electric utility industry, most magnetic-field exposures at or near guideline levels occur in highly nonuniform fields. Two methods are described for simplified estimation of induced quantities in such fields, with each method using as input modeling results for uniform field exposure. These methods have practical value for assessing occupational exposures relative to guideline levels.

The possible role of contact current in cancer risk associated with residential magnetic fields.

Residential electrical wiring safety practices in the US result in the possibility of a small voltage (up to a few tenths of a volt) on appliance surfaces with respect to water pipes or other grounded surfaces. This "open circuit voltage" (V(OC)) will cause "contact current" to flow in a person who touches the appliance and completes an electrical circuit to ground. This paper presents data suggesting that contact current due to V(OC) is an exposure that may explain the reported associations of residential magnetic fields with childhood leukemia. Our analysis is based on a computer model of a 40 house (single-unit, detached dwelling) neighborhood with electrical service that is representative of US grounding practices. The analysis was motivated by recent research suggesting that the physical location of power lines in the backyard, in contrast to the street, may be relevant to a relationship of power lines with childhood leukemia. In the model, the highest magnetic field levels and V(OC)s were both associated with backyard lines, and the highest V(OC)s were also associated with long ground paths in the residence. Across the entire neighborhood, magnetic field exposure was highly correlated with V(OC) (r = 0.93). Dosimetric modeling indicates that, compared to a very high residential level of a uniform horizontal magnetic field (10 mu T) or a vertical electric field (100 V/m), a modest level of contact current (approximately 18 mu A) leads to considerably greater induced electric fields (> 1 mV/m) averaged across tissue, such as bone marrow and heart. The correlation of V(OC) with magnetic fields in the model, combined with the dose estimates, lead us to conclude that V(OC) is a potentially important exposure with respect to childhood leukemia risks associated with residential magnetic fields. These findings, nonetheless, may not apply to residential service used in several European countries or to the Scandinavian studies concerned with populations exposed to magnetic fields from overhead transmission lines.

Assessing the potential carcinogenic activity of magnetic fields using animal models.

We update our 1997 publication by reviewing 29 new reports of tests of magnetic fields (MFs) in six different in vivo animal models of carcinogenesis: 2-year, lifetime, or multigeneration exposure studies in rats or mice; and promotion/progression models (rat mammary carcinoma, rat liver focus, mouse skin, several models of human leukemia/lymphoma in rats and mice, and brain cancer in rats). Individual experiments are evaluated using a set of data quality criteria, and summary judgments are made across multiple experiments by applying a criterion of rough reproducibility. The potential for carcinogenicity of MFs is discussed in light of the significant body of carcinogenesis data from animal bioassays that now exists. Excluding abstracts, approximately 80% of the 41 completed studies identified in this and our previous review roughly satisfy data quality criteria. Among these studies, the criterion for independent reproducibility is not satisfied for any positive results but is satisfied for negative results in chronic bioassays in rats and mice and for negative results in both promotion and co-promotion assays using the SENCAR mouse skin model. Results of independent replication studies using the rat mammary carcinoma model were conflicting. We conclude that long-term exposure to continuous 50- or 60-Hz MFs in the range of 0.002-5 mT is unlikely to result in carcinogenesis in rats or mice. Though results of most promotion/progression assays are negative, a weak promoting effect of MFs under certain exposure conditions cannot be ruled out based on available data.

Rate of occurrence of transient magnetic field events in U.S. residences.

Recent interest in the transient magnetic field events produced by electrical switching events in residential and occupational environments has been kindled by the possibility that these fields may explain observed associations between childhood cancer and wire codes. This paper reports the results of a study in which the rate of occurrence of magnetic field events with 2-200 kHz frequency content were measured over 24 h or longer periods in 156 U.S. residences. A dual-channel meter was developed for the study that, during 20 s contiguous intervals of time, counted the number of events with peak 2-200 kHz magnetic fields exceeding thresholds of 3. 3 nT and 33 nT. Transient activity exhibited a distinct diurnal rhythm similar to that followed by power frequency magnetic fields in residences. Homes that were electrically grounded to a conductive water system that extended into the street and beyond, had higher levels of 33 nT channel transient activity. Homes located in rural surroundings had less 33 nT transient activity than homes in suburban/urban areas. Finally, while transient activity was perhaps somewhat elevated in homes with OLCC, OHCC, and VHCC wire codes relative to homes with underground (UG) and VLCC codes, the elevation was the smallest in VHCC and the largest in OLCC homes. This result does not provide much support for the hypothesis that transient magnetic fields are the underlying exposure that explains the associations, observed in several epidemiologic studies, between childhood cancer and residence in homes with VHCC, but not OLCC and OHCC, wire codes.

Morning urinary assessment of nocturnal melatonin secretion in older women.

We evaluated the feasibility of using morning urine samples in epidemiological studies aimed at clarifying the relationship between nocturnal melatonin levels and breast cancer risk. Initially, a laboratory-based study of 29 women (40- 70 yr old) was performed to examine the correlation between plasma melatonin levels in hourly nocturnal blood samples and both melatonin and its major enzymatic metabolite, 6-hydroxymelatonin-sulfate (6-OHMS) in morning urine samples. In a companion field study, morning urine samples were collected from 203 healthy women to assess similarities and differences in laboratory versus field measures. Taken together, our results indicate: 1) levels of melatonin and of creatinine-corrected 6-OHMS in the first morning void urine are strongly correlated with total nocturnal plasma melatonin output (P < 0.001) and also with peak nocturnal melatonin values (P < 0.001); 2) similar ranges for 6-OHMS were found in the laboratory and the field; and 3) neither menopausal status nor hormonal replacement therapy altered 6-OHMS values in morning void urine. The inclusion of morning urine samples in epidemiological studies of cancer could allow cost-effective, widespread testing of the role played by melatonin in human health and disease.

Determinants of power-frequency magnetic fields in residences located away from overhead power lines.

The Wertheimer-Leeper wire code, originally developed as a surrogate for magnetic-field exposure, has been associated with childhood leukemia in several epidemiologic investigations. However, these and other studies indicate that most between-residence variability in measured magnetic fields remains unexplained by wire codes. To better understand this remaining variability, engineering and demographic data were examined for 333 underground (UG) and very-low current configuration (VLCC) single-family or duplex residences, selected from a database of nearly 1000 residences specifically because their magnetic fields are most likely affected negligibly by overhead power lines. Using linear regression techniques, four factors predictive of the log-transformed residential field were identified: the square-root of the 24-h average net service drop current (this current is equivalent to the current in the grounding system), the log of the number of service drops on the same secondary serving the residence, residence age (four categories), and area type (rural, suburban, or urban). Complete data on ground current and service drops, the two factors with the strongest individual relationships to measured fields, were available for only half of the residences in the sample. However, these data were determined to be "missing at random" according to established statistical criteria. The full-sample or "composite" models thus relied on a method similar to regression imputation, accounting for missing data with binary dummy variables. When applied to the samples from which they were derived, these models accounted for 25% of the variance of the log-spot-measured magnetic field values in the full sample, while models that considered only those residences with complete data (n = 167) explained about 35%. The model validated well against a sample of 201 ordinary low current configuration (OLCC) homes selected from the same database.

Lack of effect of a 60 Hz magnetic field on biomarkers of tumor promotion in the skin of SENCAR mice.

It has been proposed that extremely low frequency magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin carcinogenesis in mice initiated by a single subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Experimentation utilized three different doses of TPA within its dose-response range (0.85, 1.70 or 3.40 nmol) and examined the following early biomarkers of tumor promotion after 1, 2 and 5 weeks of promotion: increases in epidermal thickness and the labeling index of epidermal cells, induction of epidermal ornithine decarboxylase activity and down-regulation of epidermal protein kinase C activity. Mice exposed to a 60 Hz magnetic field having a flux density of 2 mT for 6 h/day for 5 days/week were compared with mice exposed to an ambient magnetic field. Within the sensitivity limits of the biomarker methodology and the exposure parameters employed, no consistent, statistically significant effects indicative of promotion or co-promotion by the magnetic field were demonstrated.

The relationship between electromagnetic field and light exposures to melatonin and breast cancer risk: a review of the relevant literature.

Worldwide, breast cancer is the most common malignancy accounting for 20-32% of all female cancers. This review summarizes the peer-reviewed, published data pertinent to the hypothesis that increased breast cancer in industrialized countries is related to the increased use of electricity [Stevens, R.G., S. Davis 1996]. That hypothesis specifically proposes that increased exposure to light at night and electromagnetic fields (EMF) reduce melatonin production. Because some studies have shown that melatonin suppresses mammary tumorigenesis in rats and blocks estrogen-induced proliferation of human breast cancer cells in vitro, it is reasoned that decreased melatonin production leads to increased risk of breast cancer. To evaluate this hypothesis, the paper reviews epidemiological data on associations between electricity and breast cancer, and assesses the data on the effects of EMF exposure on melatonin physiology in both laboratory animals and humans. In addition, the results on the effects of melatonin on in vivo carcinogenesis in animals are detailed along with the controlled in vitro studies on melatonin's effects on human breast cancer cell lines. The literature is evaluated for strength of evidence, inter-relationships between various lines of evidence, and gaps in our knowledge. Based on the published data, it is currently unclear if EMF and electric light exposure are significant risk factors for breast cancer, but further study appears warranted. Given the ubiquitous nature of EMF and artificial light exposure along with the high incidence of breast cancer, even a small risk would have a substantial public health impact.

Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers.

The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.