In previous research, we found that rats acutely (2 hr) exposed to a 60-Hz sinusoidal magnetic field at intensities of 0.1-0.5 millitesla (mT) showed increases in DNA single- and double-strand breaks in their brain cells. Further research showed that these effects could be blocked by pretreating the rats with the free radical scavengers melatonin and N-tert-butyl-alpha-phenylnitrone, suggesting the involvement of free radicals. In the present study, effects of magnetic field exposure on brain cell DNA in the rat were further investigated. Exposure to a 60-Hz magnetic field at 0.01 mT for 24 hr caused a significant increase in DNA single- and double-strand breaks. Prolonging the exposure to 48 hr caused a larger increase. This indicates that the effect is cumulative. In addition, treatment with Trolox (a vitamin E analog) or 7-nitroindazole (a nitric oxide synthase inhibitor) blocked magnetic-field-induced DNA strand breaks. These data further support a role of free radicals on the effects of magnetic fields. Treatment with the iron chelator deferiprone also blocked the effects of magnetic fields on brain cell DNA, suggesting the involvement of iron. Acute magnetic field exposure increased apoptosis and necrosis of brain cells in the rat. We hypothesize that exposure to a 60-Hz magnetic field initiates an iron-mediated process (e.g., the Fenton reaction) that increases free radical formation in brain cells, leading to DNA strand breaks and cell death. This hypothesis could have an important implication for the possible health effects associated with exposure to extremely low-frequency magnetic fields in the public and occupational environments.

Magnetic-field-induced DNA strand breaks in brain cells of the rat.

Results The attributable fraction of work-related mortality in the relevant disease and age categories was estimated to be 7% (10% for men and 2% for women), and for all diseases and ages the fraction was 4%. For the main cause-of-death categories, the attributable fraction became 12% for circulatory system diseases, 8% for malignant neoplasms, 4% for respiratory system diseases, 4% for mental disorders, 3% for nervous system diseases, and 3% for accidents and violence. The following estimates were obtained for specific important diseases: 24% for lung cancer, 17% for ischemic heart disease, 12% for chronic obstructive pulmonary disease, and 11% for stroke. Based on these fractions, the total number of work-related deaths that occurred in Finland in 1996 was calculated to be on the order of 1800 (employed work force of 2.1 million); 86% involved men. Conclusions High-quality epidemiologic studies and national survey data are essential for obtaining reliable estimates of the proportion of deaths attributable to occupational factors. The magnitude of work-related mortality is an insufficiently recognized contributor to total mortality in Finland, especially from circulatory diseases and other diseases caused by exposure to agents other than asbestos. Key terms attributable fraction, burden of disease, epidemiologic methods, health statistics, occupational exposure.

Epidemiologic estimate of the proportion of fatalities related to occupational factors in Finland.

Exposures to extremely low-frequency electric and magnetic fields (EMF) emanating from the generation, transmission, and use of electricity are a ubiquitous part of modern life. Concern about potential adverse health effects was initially brought to prominence by an epidemiologic report two decades ago from Denver on childhood cancer. We reviewed the now voluminous epidemiologic literature on EMF and risks of chronic disease and conclude the following: a) The quality of epidemiologic studies on this topic has improved over time and several of the recent studies on childhood leukemia and on cancer associated with occupational exposure are close to the limit of what can realistically be achieved in terms of size of study and methodological rigor. b) Exposure assessment is a particular difficulty of EMF epidemiology, in several respects: i) The exposure is imperceptible, ubiquitous, has multiple sources, and can vary greatly over time and short distances. ii) The exposure period of relevance is before the date at which measurements can realistically be obtained and of unknown duration and induction period. iii) The appropriate exposure metric is not known and there are no biological data from which to impute it. c) In the absence of experimental evidence and given the methodological uncertainties in the epidemiologic literature, there is no chronic disease for which an etiological relation to EMF can be regarded as established. d) There has been a large body of high quality data for childhood cancer, and also for adult leukemia and brain tumor in relation to occupational exposure. Among all the outcomes evaluated in epidemiologic studies of EMF, childhood leukemia in relation to postnatal exposures above 0.4 microT is the one for which there is most evidence of an association. The relative risk has been estimated at 2.0 (95% confidence limit: 1.27-3.13) in a large pooled analysis. This is unlikely to be due to chance but, may be, in part, due to bias. This is difficult to interpret in the absence of a known mechanism or reproducible experimental support. In the large pooled analysis only 0.8% of all children were exposed above 0.4 microT. Further studies need to be designed to test specific hypotheses such as aspects of selection bias or exposure. On the basis of epidemiologic findings, evidence shows an association of amyotrophic lateral sclerosis with occupational EMF exposure although confounding is a potential explanation. Breast cancer, cardiovascular disease, and suicide and depression remain unresolved.

Review of the epidemiologic literature on EMF and Health.

Electric and magnetic fields are ubiquitous in the modern society, and concerns have been expressed regarding possible adverse effects of these exposures. This review covers epidemiologic research on health effects of exposures to static, extremely low-frequency (ELF), and radio frequency (RF) fields. Research on ELF fields has been performed for more than two decades, and the methodology and quality of studies have improved over time. Studies have consistently shown increased risk for childhood leukemia associated with ELF magnetic fields, whereas ELF fields most likely are not a risk factor for breast cancer and cardiovascular disease. There are still inadequate data for other outcomes. More recently, focus has shifted toward RF exposures from mobile telephony. There are no persuasive data suggesting a health risk, but this research field is still immature with regard to the quantity and quality of available data. This technology is constantly changing and there is a need for continued research on this issue. Almost no epidemiologic data are available for static fields.

Emf and health

The burden of Alzheimer's disease (AD) falls more heavily on women than men. It is hypothesized that plummeting levels of circulating estrogens after the menopause increase a woman's risk for this disorder and, conversely, that estrogen replacement therapy may lower the risk for dementia due to AD. A number of estrogenic properties support the biological credibility of this hypothesis. Estrogen interacts with neurotrophins and neurotransmitter systems relevant to AD and in some model systems estrogen modulates synaptic plasticity. Effects on beta-amyloid and apolipoprotein E may be especially germane to putative effects. Estrogen also may blunt neurotoxic consequences of the stress response mediated by the hypothalamic-pituitary-adrenal axis, augment cerebral glucose utilization, and enhance cerebral blood flow. Clinical studies of postmenopausal women suggest beneficial estrogen effects on specific cognitive skills, and small preliminary trials of estrogen replacement in women with AD support claims of clinical meaningful efficacy. Consistent with the estrogen hypothesis, cross-sectional studies imply that postmenopausal estrogen use could be associated with a lower risk for AD. Several recent epidemiologic studies in which information on estrogen replacement therapy was collected prospectively further support this contention, with a dose-response relation evident in some reports. Because estrogen users tend to differ from nonusers in a number of lifestyle characteristics, convincing demonstration of putative protective effects could best some from randomized, placebo-controlled, primary intervention trials. For the present, however, the issue of estrogen efficacy in lowering a woman's risk for AD remains unsettled.

The epidemiology of estrogen replacement therapy and Alzheimer's disease

The authors present analyses of data from three independent clinical series and controls indicating an association between working in occupations with probable medium to high exposure to extremely low frequency ( 10 mG intermittently) to high (> 10 mG or > 100 mG intermittently) exposed cases were seamstress, dressmaker, and tailor. The results appear to be independent of education, and the sex-combined odds ratios for the three series are quite homogeneous: 2.9, 3.1, and 3.0. The odds ratio for the three series analyzed together is 3.0 (p < 0.001), with a 95% confidence interval of 1.6-5.4. The odds ratio for women is 3.8 (p < 0.001), with a 95% confidence interval of 1.7-8.6. The most obvious, possibly etiologically relevant exposure is that of electromagnetic fields, which may have biologic plausibility because they may adversely influence calcium homeostasis and/or inappropriately activate immune system cells such as microglial cells, initiating events that result in neuronal degeneration.

Occupations with Exposure to Electromagnetic Fields: A Possible Risk Factor for Alzheimer's Disease

A few studies have investigated a possible relationship between Alzheimer's disease (AD) and occupations with extremely low frequency magnetic field (MF) exposure The purpose of this study was to further evaluate this possible association in a large patient population with expert diagnoses Subjects came from the 8 of the 9 California Alzheimer's Disease Diagnostic and Treatment Centers not previously used in an earlier study Cases had probable or definite AD; controls primarily had a dementia-related problem other than vascular dementia (VaD) and some were not demented upon expert examination Occupations were classified as having low, medium or high MF exposure, based upon previous research, replicating the exposure methodology used in our previous published studies Occupational information was available for 986% of the 1527 cases and 985% of the 404 controls with age-at-initial examination known to be at least 65 Among cases, 21% and 54% had high and medium occupational MF exposure, respectively, while among controls the percentages were 08% and 30% In univariate analyses, the odds ratio (OR) for subjects with medium or high MF exposures combined was 21 (p < 001), while for high exposure alone the OR was 29 (p < 008) Two models were used in multivariate analyses, with gender, stroke, and either age-at-onset or age-at-initial examination as covariates The ORs for MF exposure varied little between the two models: 22 (p < 002) and 19 (p < 003) for medium or high exposure; 27 (p < 011) and 32 (p < 012) for high exposure OR estimates for females were higher than for males, but not significantly higher There were no material differences between the ORs resulting from univariate and multivariate analyses Elevated occupational MF exposure was associated with an increased risk of AD Based on previous published studies, the results likely pertain to the general population

https://link.springer.com/content/pdf/10.1186%2F1471-2377-7-13.pdf

A case-control study of occupational magnetic field exposure and Alzheimer's disease: results from the California Alzheimer's Disease Diagnosis and Treatment Centers.

AIMS This report is the first study of the possible relationship between extremely low frequency (50-60 Hz, ELF) magnetic field (MF) exposure and severe cognitive dysfunction. Earlier studies investigated the relationships between MF occupational exposure and Alzheimer's disease (AD) or dementia. These studies had mixed results, depending upon whether the diagnosis of AD or dementia was performed by experts and upon the methodology used to classify MF exposure. STUDY DESIGN Population-based case-control. PLACE AND DURATION OF STUDY Neurology and Preventive Medicine, Keck School of Medicine, University of Southern California, 2 years. METHODOLOGY The study population consisted of 3050 Mexican Americans, aged 65+, enrolled in Phase 1 of the Hispanic Established Population for the Epidemiologic Study of the Elderly (H-EPESE) study. Mini-Mental State Exam (MMSE) results, primary occupational history, and other data were collected. Severe cognitive dysfunction was defined as an MMSE score below 10. The MF exposure methodology developed and used in earlier studies was used. RESULTS Univariate odds ratios (OR) were 3.4 (P< .03; 95% CI: 1.3-8.9) for high and 1.7 (P=.27; 95% CI: 0.7-4.1) for medium or high (M/H) MF occupations. In multivariate main effects models, the results were similar. When interaction terms were allowed in the models, the interactions between M/H or high occupational MF exposure and smoking history or age group were statistically significant, depending upon whether two (65-74, 75+) or three (65-74, 75-84, 85+) age groups were considered, respectively. When the analyses were limited to subjects aged 75+, the interactions between M/H or high MF occupations and a positive smoking history were statistically significant. CONCLUSION The results of this study indicate that working in an occupation with high or M/H MF exposure may increase the risk of severe cognitive dysfunction. Smoking and older age may increase the deleterious effect of MF exposure.

Severe Cognitive Dysfunction and Occupational Extremely Low Frequency Magnetic Field Exposure among Elderly Mexican Americans

Dr. Poole has made a number of useful points about the interpretation of studies of the association of childhood cancers with extremely low frequency magnetic fields (1). We wish to comment on only two of his points. First, Dr. Poole takes issue with the appliance-specific relative risks that were reported in the two papers in this issue (2, 3) and several earlier ones, including another Los Angeles study (4). We agree with his desire for an exposure assessment that consolidates appliances with other sources of magnetic fields, including power lines. However, numerous difficulties preclude doing so at this time. Too little is known about the fields generated by each appliance at the target organs, variations between brands, duration and frequency of use, and other modifying influences needed for a sensible summary index. More important is the uncertainty over the appropriate "exposure metric," a single number that represents a subject's magnetic field environment, including its frequency spectrum, time variation, polarization, spatial orientation, and high-frequency transients. Since fields from appliances and power lines differ in many of these qualities, weighting exposures from various electromagnetic field sources requires an exposure metric that is hypothetically carcinogenic. "Combining apples and oranges" makes sense in dietary epidemiology only because fructose has been identified as an etiologically relevant nutrient! Although summary electromagnetic field exposure indices would be useful, their development clearly poses formidable challenges to epidemiologists, exposure assessors, and biologists. During the present state of ignorance, however, we feel that appliance-specific risk estimates may provide potential clues about etiologically important components of magnetic fields (if any) and may provide some preliminary guidance to individuals and officials in making decisions about their safety. Second, we agree that the best use of household magnetic field measurements is not as a direct cancer risk factor, but in building exposure models from wiring configuration data. Where Dr. Poole uses the measured fields simply to combine categories of the Wertheimer-Leeper wire code (5), we feel that a more powerful application is predicting long-term residential exposures to a variety of magnetic field metrics. For example, we recently developed a regression model for predicting the mean magnetic field from measurements, wire configurations, and physical principles (6). When applied to the data from the Los Angeles childhood leukemia study (3), this model predicted household magnetic fields far better than did the Wertheimer-Leeper code and was significantly associated with leukemia risk, providing new evidence for magnetic field carcinogenicity. However, the predicted fields did not improve upon the Wertheimer-Leeper code in a multivariate risk model, suggesting that the mean magnetic field may not be the appropriate exposure metric (6). Such wire configuration models could be used to evaluate other plausible exposure metrics. Metrics correlated with the Wertheimer-Leeper categories would more likely be associated with cancer. We have identified two such candidates: the field's autocorrelation over time (7) and frequency components that create ionic resonances with the earth's magnetic field (8). We are looking forward to the postpublication phase of the peer-review process that Dr. Poole describes. We hope Dr. Poole's commentary (1) and the responses by Gurney et al. (9) and ourselves to this debate will stimulate further thinking about some of these methodological issues, as well as our substantive conclusions.

/pdf/response-to-evolution-of-epidemiologic-evidence-on-magnetic-4ktafibgq0.pdf

Response to “Evolution of Epidemiologic Evidence on Magnetic Fields and Childhood Cancers”

We assessed the prevalence of headache and psychosocial stress in a group of patients with cerebral ischemia and evaluated hemostatic function in these patients. Headache and preceding psychosocial stress were present in one-third and one-half, respectively, of patients capable of providing an adequate history and answering a standardized psychosocial questionnaire. There were no significant differences in hematocrit, white blood cell count and differential, fibrinogen, and platelet activation peptide s-thromboglobulin, between patients with and without headache and between high- and low-stress patients. Fibrin D-dimer (a fragment of cross-linked fibrin) was significantly lower in high-stress compared to low-stress patients. There was no association between headache and stress level. These findings make unlikely the hypothesis that headache associated with cerebral ischemia is platelet-mediated and suggest that psychosocial stress on a chronic basis is not associated with procoagulant tendencies in this population.

Pey-Jiuan Lee

Papers

Occupations with Exposure to Electromagnetic Fields: A Possible Risk Factor for Alzheimer's Disease

A case-control study of occupational magnetic field exposure and Alzheimer's disease: results from the California Alzheimer's Disease Diagnosis and Treatment Centers.

Severe Cognitive Dysfunction and Occupational Extremely Low Frequency Magnetic Field Exposure among Elderly Mexican Americans

Response to “Evolution of Epidemiologic Evidence on Magnetic Fields and Childhood Cancers”

Hemostasis findings in headache and psychosocial stress associated with cerebral ischemia