Journal of Occupational & Environmental Medicine:
Melatonin Metabolite Levels in Workers Exposed to 60-Hz Magnetic Fields: : Work in Substations and with 3-Phase Conductors
Burch, James B. PhD; Reif, John S. DVM; Noonan, Curtis W. PhD; Yost, Michael G. PhD
From the Department of Environmental Health, Colorado State University, Fort Collins, Colo. (Dr Burch, Dr Reif, Dr Noonan); and the Department of Environmental Health, University of Washington, Seattle, Wash. (Dr Yost).
Address correspondence to: James B. Burch, MS, PhD, Department of Environmental Health, Colorado State University, Fort Collins, CO 80523; e-mail: firstname.lastname@example.org.
Melatonin suppression by 50/60-Hz magnetic fields represents a plausible biological mechanism for explaining increased health risks in workers. Personal exposure to magnetic fields and ambient light, and excretion of the melatonin metabolite 6-hydroxymelatonin sulfate (6-OHMS), were measured over 3 consecutive workdays in electric utility workers. There was a magnetic field–dependent reduction in adjusted mean nocturnal and post-work 6-OHMS levels among men working more than 2 hours per day in substation and 3-phase environments and no effect among those working 2 hours or less. No changes were observed among men working in 1-phase environments. The results suggest that circular or elliptical magnetic field polarization, or another factor linked to substations and 3-phase electricity, is associated with magnetic field induced melatonin suppression in humans.
The issue of whether exposure to power frequency (50/60-Hz) electric and magnetic fields (EMFs) is associated with health effects in humans remains uncertain in part because human biological responses to EMF exposure have not been reproducibly characterized. The hormone, melatonin, has oncostatic, 1–2 immunological, 3–4 and antioxidant properties 5–6; thus its suppression by EMFs represents a biologically plausible mechanism for increased cancer risks that have been observed in electric utility workers. 7–8
Melatonin synthesis and secretion follow a diurnal pattern synchronized by ambient light, thereby exerting significant effects on circadian physiology. 9–10 Peak melatonin concentrations occur in the dark phase (0200 to 0400 hours), and lowest concentrations occur during the light phase (1200 to 1800 hours) of the 24-hour light–dark cycle. 9–10 Circulating melatonin levels are age dependent, although only small differences have been reported in subjects between the ages of 20 and 60 years. 11–12 Urinary concentrations of the major metabolite, 6-hydroxymelatonin sulfate (6-OHMS), are well correlated with circulating melatonin, and overnight 6-OHMS excretion represents an integrated measure of nocturnal melatonin production. 13–14
In experimental animals, exposure to 50/60-Hz magnetic fields has been associated with reduced circulating and pineal melatonin concentrations, although these effects have not been observed consistently. 15–16 Differences in genetic composition; the timing, duration, or intensity of exposure; field polarization; lighting conditions; or other factors may explain divergent findings among laboratory species. Epidemiological studies of human melatonin levels in response to EMF exposure have been performed in male utility workers, 17–18 healthy women, 19 male railway workers, 20 electric blanket users, 21 and workers using video display terminals. 22 There was wide variation in the exposure conditions; the duration, precision, and type of measures obtained; the presence of possible confounders (light at night, shift work), and the general characteristics of participants among these studies. Although the response to individual exposure metrics was not always consistent, each study showed some decrement in urinary 6-OHMS excretion. 23
Reasons for the inconsistency among the various human and animal studies remain to be elucidated. One potential explanation is that EMFs have no effect on melatonin production and that some unidentified factor produced a number of false positives. 16 Alternatively, one or more critical factors that can modify the effects of EMFs on melatonin may not have been carefully considered in all studies. 16 Kato and coworkers 24–27 reported that circularly polarized fields or elliptical fields with a small axial ratio were most effective at suppressing nocturnal melatonin production in rats, whereas linearly polarized fields or elliptical fields with a large axial ratio had little or no effect. Although numerous investigations of melatonin levels in response to 50/60-Hz EMF exposure have been performed subsequently in rodents, no other studies used circularly or elliptically polarized magnetic fields. Magnetic fields in close proximity to energized 3-phase conductors (eg, 3-phase distribution lines and substations) have circular or elliptical polarization, 28 whereas those associated with single phase conductors are linearly polarized. Exposure monitoring in substations as well as in residential settings has confirmed the presence of elliptically polarized fields. 29 The purpose of this analysis was to test the hypothesis that the effect of 60-Hz magnetic field exposure on 6-OHMS excretion was greatest among utility employees working in substations or in the vicinity of energized 3-phase conductors, and that work around 1-phase conductors had little or no effect on 6-OHMS excretion.
The study population was comprised of male workers from six utilities who were engaged in electric power generation (power plant operators, mechanics, electricians), distribution (linemen, meter readers, substation operators), and comparison (utility administrative and maintenance) activities. Data collection was performed between January and September 1997, using procedures similar to those reported previously. 17–18 Serial biological monitoring of urinary 6-OHMS excretion was combined with concomitant measurement of personal exposure to 60-Hz magnetic fields and ambient light. Magnetic field and light exposures were recorded at 15-second intervals over the first 3 days of the subjects’ workweek using EMDEX II meters (Enertech Consultants, Campbell, CA) worn at the waist. The light sensor was adapted to the EMDEX via the external sensor jack. A custom computer program was developed to calculate magnetic field and light exposure metrics. Work-related activities (work in substations, in the vicinity of 3-phase or 1-phase conductors, office, and travel) were recorded in 30-minute increments in a log kept by each participant. Subjects were instructed to log their activities if they had been within approximately 1 meter (arm’s length) of an energized conductor (3-phase, 1-phase, or within a substation) for at least 30 minutes.
Melatonin production was assessed by radioimmunoassay of urinary 6-OHMS concentrations (CIDtech, Mississagua, Ontario, Canada). 30–31 Participants provided overnight urine samples, combining any voids after bedtime with the first morning void on each day of participation. Daily post-work urine samples were also collected. Total overnight 6-OHMS excretion was estimated as the product of the overnight urine volume and the 6-OHMS concentration in each sample. Nocturnal and post-work 6-OHMS concentrations normalized to creatinine (6-OHMS/cr) were also analyzed. The interassay coefficient of variation for 6-OHMS was 8% at 10.5 ng/mL; within-assay variability ranged from 4% to 10% (mean, 6%); and the limit of detection was 0.1 ng/mL.
Data analyses were performed by using the Proc Mixed procedure for repeated measures in version 6.12 of the Statistical Analysis Software computer package (SAS Institute Inc, Cary, NC). Workplace exposure metrics based on either field intensity (time-weighted geometric mean) or temporal stability (standardized rate of change metric [RCMS]) were calculated for each workday of participation. 17–18 The RCMS estimates first-lag serial autocorrelation of personal magnetic field exposures; low values of RCMS represent temporally stable exposures. 32 Ambient light exposure was summarized using the workshift arithmetic time-weighted average. Analyses were performed using log-transformed values of overnight 6-OHMS, 6-OHMS/cr, ambient light, and geometric mean magnetic field exposures (RCMS was untransformed). Mean values were back-transformed for presentation in the tables.
Subjects were first grouped into tertiles of workplace magnetic field exposure and then into groups who spent more than 2 hours, or 2 hours or less, per day in substations or 3-phase environments. Because substation and 3-phase environments were both expected to have circularly or elliptically polarized magnetic fields, these activities were combined. Mean magnetic field exposures among subjects with more than 2 hours, or 2 hours or less, of work in substation or 3-phase environments were compared statistically within each tertile by using the least significant differences method in SAS. Least-squares means of 6-OHMS excretion (adjusted for the effects of age, ambient light exposure, and month of participation) were then calculated by exposure tertile in groups with more than 2 hours, or 2 hours or less, of work in substations and in 3-phase environments. Adjusted mean 6-OHMS levels in the high and low exposure tertiles were compared statistically for each group. The study population was then reclassified on the basis of work in the vicinity of 1-phase conductors, and analyses of mean 6-OHMS excretion in groups with more than 2 hours, or 2 hours or less, per day of 1-phase work were performed in the same manner. Additional analyses were performed using 0.5-, 1.0-, and 1.5-hour periods to assess cut point bias. There were insufficient worker-days of exposure to assess outcomes using cut points above 2 hours. Results of separate analyses incorporating potential confounding variables obtained from questionnaires, including personal, occupational, medical, and lifestyle factors, were consistent with those presented below.
Complete data were available for 149 of 161 subjects; the mean age was 44 ± 9 years; and approximately 91% were Caucasian and non-Hispanic. There were 60 (40%) electric power distribution, 50 (33%) generation, and 39 (26%) comparison workers. Geometric mean magnetic field exposures for subjects working in substations and in the vicinity of 3-phase conductors were similar among subjects in the first and second exposure tertiles (Table 1). For subjects in the highest exposure tertile, geometric mean magnetic field exposures were greater for those with more than 2 hours of work in substations and in 3-phase environments (Table 1). Magnetic field exposures among men working more than 2 hours in substation/3-phase environments were more temporally stable than those with 2 hours or less (Table 1). For those working in 1-phase environments, there were no statistically significant differences in geometric mean or RCMS magnetic field exposures among those with more than 2 hours, or 2 hours or less, of work (Table 1).
A diurnal variation in mean urinary 6-OHMS excretion was observed among all subjects; mean concentrations were 3.0 ng/mg creatinine in the post-work and 18.2 ng/mg creatinine in the overnight samples. Results summarizing 6-OHMS excretion in response to occupational magnetic field exposure and substation/3-phase work activities are presented in Table 2. In workers with more than 2 hours of substation or 3-phase work, there was a clear trend of decreasing nocturnal 6-OHMS/cr excretion with increasing magnetic field exposure using either the geometric mean (P = 0.03) or the temporal stability metric (P = 0.01). Adjusted mean overnight 6-OHMS levels and post-work 6-OHMS/cr concentrations also exhibited a decreasing trend across tertiles of magnetic field exposure for those participating in more than 2 hours of substation and 3-phase activities, although statistically significant differences between the upper and lower tertiles were observed only for the temporal stability metric (Table 2). In contrast, no decrease in 6-OHMS excretion was observed among those with 2 hours or less of substation/3-phase work (Table 2). An increase in overnight 6-OHMS excretion was observed with increasing exposure to temporally stable magnetic fields among those with 2 hours or less of substation/3-phase work. However, statistically significant increases were not observed in this group for any of the other 6-OHMS variables or for magnetic field intensity. When the same analysis was performed for work in 1-phase environments, there were no statistically significant differences in mean 6-OHMS excretion for those with or without 2 hours of 1-phase work when using either the geometric mean or the temporal stability metric (Table 3).
Results obtained among workers with more than 1.0 or 1.5 hours of substation/3-phase work (Table 4) were very similar to those obtained using the 2-hour cut point (Table 3). Differences between the upper and lower tertiles were progressively greater as the duration of time spent in substation/3-phase environments increased. There were no statistically significant differences in mean 6-OHMS excretion among subjects below the chosen cut points for substation/3-phase activities or among those with 1-phase work activities above or below the cut points (results not shown).
Decreased nocturnal or post-work urinary 6-OHMS excretion have been associated with magnetic field exposures in studies of electric railway workers 20 and in our earlier studies of electric utility workers. 17–18 In the present study, another population of male electric utility workers had decreased overnight 6-OHMS levels as well as lower nocturnal and post-work 6-OHMS/cr concentrations with increasing exposure to 60-Hz magnetic fields in substations or near energized 3-phase conductors. Differences in mean 6-OHMS excretion between the upper and lower exposure tertiles became progressively greater as the cut point for the amount of time spent in substations and in 3-phase environments increased from 0.5 to 2 hours. These findings are consistent with the hypothesis that magnetic fields with circular or elliptical polarization are more effective at suppressing melatonin production than linearly polarized fields. 24–27 The lack of effects observed in those with 2 hours or less of substation/3-phase work or among those with 1-phase exposures further supports the hypothesis. Alternatively, this classification scheme may have simply selected those with more intense and temporally stable exposures. However, if intensity or temporal stability was the critical parameter, then one might also expect to observe a trend of decreasing mean 6-OHMS excretion among those with 2 hours or less of substation/3-phase work or among those with 1-phase exposures. A trend of decreasing mean 6-OHMS excretion was observed only among those with more than 2 hours of substation/3-phase work, even though a gradient of exposure across tertiles and similar magnitudes of magnetic field intensity or temporal stability were observed among subjects in each group of substation/3-phase and 1-phase activity. Clearly, further investigation of magnetic field exposures in substations and in the vicinity of 3-phase and 1-phase conductors is needed. The intensity, temporal stability, and degree of magnetic field polarization in each environment should be quantitatively assessed along with other potentially relevant magnetic field parameters, such as high frequency transients and harmonic content.
Temporally stable magnetic field exposures that occurred in substation/3-phase environments were more strongly associated with decreased mean 6-OHMS excretion than magnetic field intensity, as measured by the geometric mean. These findings are consistent with previous studies in electric utility workers that indicated decreased 6-OHMS excretion in response to temporally stable magnetic field exposures. 17–18 The importance of temporally stable magnetic field exposures in eliciting biological effects was originally described by Litovitz and coworkers. 33 The basis for the biological activity of temporally stable exposures remains unexplained but may provide a clue as to the fundamental mechanism of interaction between 60-Hz magnetic fields and melatonin production. Kruglikov and Dertinger 34 indicate that a highly correlated exposure is required for stochastic resonance at a cellular level. However, further work is required to determine whether such a mechanism might mediate the effects of temporally stable magnetic field exposures on 6-OHMS excretion in humans.
Studies performed in rats by Kato and coworkers indicated that circularly polarized magnetic fields were more effective at inducing melatonin suppression than linearly polarized fields. 24–27 They observed decreased circulating melatonin concentrations in rats when using 1.4 μT circularly polarized magnetic fields. 24,25,27 The same group reported that chronic exposure to a horizontally polarized magnetic field was effective at a higher intensity of 5 μT but not at 1 μT. 26–27 Linearly polarized 50/60-Hz magnetic fields have been effective at reducing circulating melatonin levels in other rodent studies, 35–38 although results have been inconsistent. 39–42 Sheep penned under a 3-phase transmission line had no noticeable changes in circulating melatonin levels after 6 to 10 months of exposure.42a Field polarization at ground level under the power lines was not reported, although a large axial ratio (ie, close to linear polarization) would have been expected.27–28 Inasmuch as no other laboratory has attempted to evaluate the effects of field polarization on magnetic field induced melatonin suppression in experimental animals, the role of this parameter remains undefined.
Human laboratory-based studies, performed using either circularly43–44 or linearly polarized45 magnetic fields, have generally yielded negative results. However, it is difficult to draw conclusions regarding the effectiveness of circular polarization from these studies owing to questions concerning the timing of exposure. Magnetic field induced delays in human melatonin secretion were observed by using circularly polarized fields when 20-μT exposures of 1.5 to 4.0 hours duration commenced before the nocturnal melatonin onset. 46 Similarly, decreased nocturnal 6-OHMS excretion in utility workers occurred in response to magnetic field exposures occurring at home, or for work and home exposures combined, but not during sleep. 17 Repeated short-term exposure (20 minutes per day for 3 weeks) to a high-intensity, 2900-μT magnetic field delivered before the nocturnal melatonin onset (1000 or 1800 hours) was also associated with reduced nocturnal melatonin production in humans. 47
Kato and Shigemitsu 27 presented theoretical calculations to explain why circularly or elliptically polarized fields would be more effective at suppressing melatonin than linearly polarized fields. These authors indicate that magnetic fields with circular or elliptical polarization are expected to more effectively induce electrical currents in the rat pineal gland. Recent estimates suggest that occupationally relevant electric field exposures (10 kV/m) in humans may result in average induced current densities of 1451 μA/m 2 in the pineal gland compared with average current densities of 6 μA/m 2 attained owing to endogenous electrical activity. 48 However, differences due to field polarization were not addressed.
The characterization of human biological responses to 60-Hz magnetic fields is critical for determining whether concern over potential health effects is warranted. Melatonin suppression is a plausible link to increased cancer risks that have been associated with such exposures. Results from the present analysis suggest that magnetic field induced melatonin suppression seems to be enhanced by work in substations and with energized 3-phase conductors. Failure to characterize magnetic field polarization or other potentially important modifying factors 18,49 may partially explain the inconsistent findings reported to date. Recently developed personal exposure devices are now available to evaluate the role of field polarization and other biologically based exposure parameters on human 6-OHMS excretion. 50 Reduced melatonin secretion may serve as an important model for understanding human biological responses to magnetic field exposures.
The authors gratefully acknowledge the cooperation of the participating utilities, their employees who participated in this study, and their representatives. Urinary 6-OHMS assays were performed under the direction of Dr Terry Nett, Director of the Radioimmunoassay Laboratory for the Colorado State University Animal Research and Biotechnology Laboratories.
In particular, the authors thank Ms Jeanette Haddock for assistance with data collection, Ms Xiao Ming Sha for assistance with the 6-OHMS assay, Drs Lee Wilke and Martin Fettman for assistance with the creatinine assays, and Mr Travers Ichinose and Dr Annette Bachand for assistance with data processing. Dr Scott Davis of the Fred Hutchinson Cancer Research Center provided the design for adaptation of the light meters to the EMDEX monitors. Battelle Pacific Northwest Laboratories and Platte River Power Authority provided light meters. Mr Ken Webster provided computer programming assistance.
This work was supported by research grant no. 1 R01ES08117 from the National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland.
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If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
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