The effects of extremely low-frequency magnetic fields on melatonin and cortisol, two marker rhythms of the circadian system

Dialogues Clin Neurosci. 2012;14:381-399.

In the past 30 years the concern that daily exposure to extremely low-frequency magnetic fields (ELF-EMF) (1 to 300 Hz) might be harmful to human health (cancer, neurobehavioral disturbances, etc) has been the object of debate, and has become a public health concern. This has resulted in the classification of ELF-EMF into category 2B, ie, agents that are “possibly carcinogenic to humans” by the International Agency for Research on Cancer. Since melatonin, a neurohormone secreted by the pineal gland, has been shown to possess oncostatic properties, a “melatonin hypothesis” has been raised, stating that exposure to EMF might decrease melatonin production and therefore might promote the development of breast cancer in humans. Data from the literature reviewed here are contradictory. In addition, we have demonstrated a lack of effect of ELF-EMF on melatonin secretion in humans exposed to EMF (up to 20 years' exposure) which rebuts the melatonin hypothesis. Currently, the debate concerns the effects of ELF-EMF on the risk of childhood leukemia in children chronically exposed to more than 0.4 μT. Further research is thus needed to obtain more definite answers regarding the potential deleterious effects of ELF-EMF.

Author Affiliations: 
Chronobiology Unit, Foundation A. de Rothschild, Paris, France (Yvan Touitou); INERIS, Department of Experimental Toxicology, Verneuil-en-Halatte, France (Brahim Selmaoui) 
Address for correspondence: 
yvan.touitou@chronobiology.fr 

Introduction

We are continuously exposed in our environment to electromagnetic fields (EMF) which are either of natural origin (geomagnetic field, intense solar activity, thunderstorms) or manmade (factories, transmission lines, electric appliances at work and home), magnetic resonance imaging, medical treatment, etc. Electric and magnetic fields which exist wherever electricity is generated, transmitted, or distributed correspond to three frequency ranges: the extremely low frequency (ELF) range includes the frequencies (50 Hz in Europe, 60 Hz in North America) of the electric power supply and of electric and magnetic fields (EMF) generated by electricity power lines and electric/electronic appliances; intermediate frequency (IF, 300 Hz to <10 MHz) is used in computer monitors, industrial processes, and security systems; and finally, radiofrequency range (RF, 10 MHz to 300 GHz) includes radars, and radio and television broadcasts and telecommunications.

Biological effects of ELF-EMF and their consequences on human health have become the subject of important and recurrent public debate. The growth of electric power use in industrialized countries and the parallel increase of environmental exposure to ELF-EMF resulted in a widespread concern that ELF-EMF may have harmful effects in humans, a concern stimulated in the past decades by a number of epidemiologic studies reporting deleterious effects of ELF-EMF on human health. Wertheimer and Leeper[1],[2] published the first report, conducted in the Denver area, on the association between childhood cancer and exposure to ELF-EMF, with the conclusion of a higher risk of childhood leukemia at higher residential ELF-EMF exposure. Savitz et al[3] gave support to this assertion with the publication of similar results in the same area (Denver). From then, several epidemiologic papers have reported a possible link, without any experimental evidence, however, between exposure of humans to ELF-EMF and diseases such as leukemia and other cancers,[4],​[5],​[6] depression, and suicide,[7] and neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis.[8],​[9],​[10],​[11] All these results, though some of them were conflicting, resulted in a “melatonin hypothesis” as a tentative explanation, with the idea that those potential ELF-EMF deleterious effects might be a consequence of an inhibitory effect of ELF-EMF on the production of melatonin,[12] a hormone whose secretion has been shown to be altered (concentration decline and/or alteration of its circadian rhythm) in some diseases including cancers (review in Hill et al, ref 13), depressive disorders,[14],​[15],​[16] and disorders of the circadian time structure.[17],[18]

The concern regarding public health resulted in reports on this matter of official organizations, the most recent reports being those of the International Agency for Research on Cancer (IARC) in 2002 and the World Health Organization in 2007.[19] Of special interest, the IARC published in 2002 an evaluation of the carcinogenic risks of ELF to humans.[20] The agency classified ELF electric fields into category 3, which in the classification corresponds to “inadequate evidence” of deleterious effects, and classified ELF magnetic fields into category 2B, corresponding to the category of agents that are “possibly carcinogenic to humans.” A classification into group 2B is “usually based on evidence in humans which is considered credible, but for which other explanations could not be ruled out.” It has to be noted that these extremely-low-frequency electric and magnetic fields are separate entities.

Whether or not ELF magnetic field exposure is causally related to increased health risks has led many scientists to examine the potential mechanisms by which ELF magnetic fields might affect human health. It is known that cancer and neurobehavioral alterations may be associated with circadian rhythm disruption and/or effect on melatonin secretion.[21],​[22],​[23],​[24] Theoretically, melatonin could be a good mechanistic candidate to explain potentially deleterious effects of EMF since: i) its secretion is dramatically inhibited by light,[25],​[26],​[27],​[28] which is the visible part of EMF; ii) the circadian pattern of the hormone is phase-advanced or -delayed by light according to the time of exposure, which is known as the phase response curve or PRC,[29] and this property might occur with exposure to EMF; iii) the oncostatic properties of melatonin have been described,[30],​[31],​[32] which resulted in the hypothesis that a decrease in the secretion of melatonin by the pineal gland might promote the development of breast cancer in humans[12]; iv) and last, its association with depressive, disorders has been put forward.[14],​[15],​[16]

Since both melatonin and cortisol are major markers of the circadian system, we reviewed data from the literature on these two marker rhythms, in search of deleterious effects of EMF on both their blood levels and abnormalities in their circadian profiles, eg, a phase-advance or a phase-delay which would point out a rhythm desynchronization of the organism, ie, a situation that occurs when the biological clock is no longer in step with its environment.[17],[33]

Rationale for studying the effects of ELF-EMF on melatonin and cortisol secretions

Melatonin (N-acetyl 5- methoxytryptamine), a neurohormone produced by the pineal gland, is characterized by a prominent circadian rhythm with high levels at night and very low levels during the daytime, whatever the age.[34],[35] Its secretory pattern has a strong endogenous component and is physiologically controlled by light. Melatonin is therefore considered as a marker rhythm of the circadian temporal structure. A marker rhythm is a physiological rhythmic variable, whose circadian pattern is highly reproducible on an individual basis and as a group phenomenon, which thus allows characterization of the timing of the endogenous rhythmic time structure and provides information on the synchronization of individuals (Figure 1.).[36] Besides melatonin, the most frequent marker rhythms used both in humans and animals are the core body temperature circadian pattern[37] and the cortisol circadian rhythm, since they are also highly reproducible.[36],[17]

Cortisol also displays a robust and highly reproducible circadian rhythm that does not respond rapidly to minor and transient environmental changes, as they are part of daily life, which also makes it a good candidate as a marker rhythm.[36] Since a relationship between the pineal gland and the adrenal gland has been documented in vitro,[38] and considering the hypothesis of the alteration of melatonin by EMF, it can be useful to look at their potential effects on cortisol, another rhythm marker of the circadian system, and to obtain an additional argument for a circadian desynchronization of the organism.

Figure 1. Reproducibility of the circadian patterns of plasma cortisol and melatonin in young healthy men. The circadian rhythms of the two hormones are highly reproducible from a day to another. Both are useful circadian markers of the time structure. Reproduced from ref 36: Selmaoui B, Touitou Y. Reproducibility of the circadian rhythms of serum cortisol and melatonin in healthy subjects. A study of three different 24-h cycles over six weeks. Life Sci. 2003;73:3339-3349. Copyright © Pergamon Press 2003

ELF-EMF effects on melatonin

Animal studies

For the sake of clarity, we present in two different tables the reports on ELF-EMF effects on melatonin. Table Ia displays the reports showing an alteration of melatonin secretion in different animal species, mainly rodents, after exposure to ELF-EMF. Table Ib deals with all of the studies reporting no effect of ELF-EMF on melatonin secretion in the different species under study.

The very first data on the topic deal with electric fields (not magnetic fields), and date back to 1981, with the report on the reduction of pineal melatonin and N-acetyltransferase (NAT), the key enzyme for melatonin synthesis, in rats exposed to electric fields 20 h/day for 30 days.[39],[40] Other reports, however, failed to find any effect, or were inconclusive or contradictory.[41],[42] Then the interest shifted from electric to magnetic fields, with a large number of studies devoted to the effects of ELF-EMF on melatonin levels in different animal species.[43],[44]

Yellon[45],[46] and Wilson et al,[47] documenting the effects of magnetic fields, were the first to report a reduction of both in pineal and plasma melatonin in Djungarian hamsters with a short exposure to a sinusoidal 100-μT magnetic field. In addition, Wilson et al[47] also reported an increase in the concentration of norepinephrine in the suprachiasmatic nuclei, the central rhythm-generating system.

The majority of laboratory studies were then carried out on rats. Kato et al,[48] in exposing male Wistar-King rats for 6 weeks to a 50-Hz circularly polarized sinusoidal magnetic field using increasing intensities, showed a decrease in pineal and plasma melatonin concentrations without any dose-response relationship. With the same protocol of exposure and species, but with a horizontal or vertical magnetic field, the same authors failed to find any effect on melatonin levels:[49] Suspecting a possible interference of pigmentation, Kato et al[50],[51] then documented in Long-Evans rats the same intensities of a circularly polarized magnetic field and did indeed show a reduction of pineal and plasma melatonin concentrations. Other studies on rats or mice,[52],​[53],​[54],​[55] baboons,[56] and hamsters[57],[58] also showed a reduction in the nighttime peak of melatonin. The same team reported a phase delay in the nocturnal peak time of melatonin in hamsters,[46],[57],[58] though they acknowledged in one paper that they were unable to replicate these findings, which make them inconclusive.[58] Some authors have reported an increase in nighttime melatonin levels.[59],​[60],​[61]

With the aim of comparing short-term and long-term exposure effects, Selmaoui and Touitou[62] used male Wistar rats housed in a 12:12 light:dark schedule and submitted to a 50-Hz sinusoidal magnetic field of 1, 10, or 100 μT intensity, either once for 12 h or repeatedly 18 h per day for 30 days. While a single 12-h exposure to a 1- or 10-μT magnetic field had no effect on plasma melatonin levels or NAT and hydroxyindole-O-methyltransferase (HIOMT) pineal activities, a 100-μT exposure significantly decreased 30% plasma concentrations of melatonin and depressed 23% pineal NAT activity (HIOMT activity unchanged) when compared with sham-exposed rats. In turn, the 30 days' repeated exposure showed that while the 1-μT intensity showed no effects on pineal function, both the 10- and 100-μT intensities resulted in an approximately 42% decrease of plasma melatonin levels. NAT activity was also decreased, and HIOMT activity remained unchanged. This study showed that a sinusoidal magnetic field alters plasma melatonin levels and pineal NAT activity, and that the sensitivity threshold varies with the duration of exposure, thus suggesting that magnetic fields may have a cumulative effect upon pineal function. This melatonin and NAT activity decrease was able to be replicated in adult rats in another study by Selmaoui and Touitou,[63] while they also reported that aged rats were not affected by ELF-EMF. Löscher et al[53] studied the effects of a 24 h/day, 7 days/week, and 3-month exposure to magnetic fields on female rats bearing DMBA-induced mammary tumors; the field intensities were similar to the domestic exposures recorded close to electric power facilities. Whereas a significant decrease of blood melatonin concentrations was observed with 1 μT, no influence on the development of the mammary tumors could be put in evidence.

Table lb presents data on different animal species reporting the lack of effect of ELF-EMF on the concentrations of pineal or blood melatonin and on the urinary concentration of 6-sulphatoxymelatonin, the main metabolite of the hormone. These reports were either inconsistent or failed to show any effect of ELF-EMF in species as different as rats or mice,[64],​[65],​[66],​[67],​[68],​[69],​[70],​[71],​[72],​[73] sheep,[74],[75] baboons,[76] Djungarian hamsters,[58],[77] cows or heifers,[78],​[79],​[80] and kestrels.[81],[82]

The comparison of Table la (effects on melatonin) and Table lb (lack of effects on melatonin) clearly shows that a number of these studies resulted in inconsistent data, even when the data were replicated by the same team with the same protocol and characteristics of exposure.[48],[49],[57],[58],[83],[84]

Last, some authors studying the effects of exposure to ELF-EMF of various biological systems such as isolated pineal glands[85],​[86],​[87],​[88],​[89],​[90] or MCF-7 cells[91],​[92],​[93],​[94],​[95],​[96] were unable to arrive at definite conclusions (Table II).

Reference of the study Species Exposure characteristics Timing of exposure Fluid or pineal Sampling time Effect on melatonin secretion
Wilson et al, 1981[39] Adult rats 60 Hz- 1.7-1.9 kV/m 20 h/day for 30 days Pineal Mel and NAT activity Day/night Decrease in pineal Mel and NAT activity
Wilson et al, 1986[40] Adult rats 60 Hz- 65 kV/m (39 kV/m effective) 20 h/day for 3 weeks Pineal Mel and NAT activity Day/night Decrease in pineal Mel and NAT activity within 3 weeks
Reiter et al, 1988[41] Adult rats 50 Hz- 10, 65 or 130 kV/m During gestation and 23 days postnatally Pineal Mel Nighttime Decreased and delayed nighttime peak
Martinez Soriano et al, 1992[52] Adult rats 50 Hz- 5 mT 30 min during the morning for 1, 3, 7, 15 and 21 days Ser Mel Nighttime Decrease in Ser Mel on day 15
Kato et al, 1993[48] Adult rats 50 Hz- 1, 5, 50 or 250 μT 6 weeks Pineal and Pl Mel Nighttime Decrease in serum and pineal melatonin
Yellon, 1992, 1994[46] Djungarian hamsters 60 Hz- 100 μT 18 h/ day for one week Pineal and Ser Mel Nighttime Decreased and delayed nighttime peak
Grota et al, 1994[42] Adult rats 60 Hz- 10 or 65 kV/m 20 h/day for 30 days Pineal Mel and NAT activity, Ser Mel Nighttime Decrease in Ser Mel after exposure to 65 kV/m but no effect on nighttime pineal Mel and NAT
Kato et al, 1994[51] Adult albino rats 50 Hz- 1 μT, circularly polarized 6 weeks Pineal and Ser Mel Day/night Decrease in nighttime peneal and Ser Mel Recovery 1 week after cessation of exposure
Kato et al, 1994[50] Adult pigmented rats 50 Hz- 1 μT, circularly polarized 6 weeks Ser Mel 12 h and 24 h Decrease at night
Löscher et al, 1994[53] Adult rats 50 Hz- 0.3-1 μT 24 h/day, 7 days/ week 91 days Ser Mel Nighttime Decrease in nocturnal Ser Mel
Rogers et al, 1995[76] Baboons 60 Hz- 6 kV/m and 50 μT or 30 kV/m and 100 μT irregular and intermittent sequence 6 weeks Ser Mel Nighttime Decrease in Ser Mel
Selmaoui and Touitou, 1995[62] Adult rats 50 Hz- 1, 10 or 100 μT 12 h, or 18 h per day for 30 days Ser Mel and pineal NAT activity Nighttime Decrease in Mel and NAT activity after 100 μT (acute) and 10 and 100 μT (chronic)
Truong et al, 1996[57] Young Djungarian hamsters 60 Hz- 100 μT 15 min, 2 h before dark; over 3-weeks Pineal and Ser Mel Nighttime Decreased and delayed nighttime peak though not replicated in the same paper = inconclusive
Yellon, 1996[58] Djungarian hamsters 60 Hz- 100 μT 15 min, 2 h before dark; over 3-weeks Pineal and Ser Mel Nighttime Decreased and delayed nighttime peak though not replicated in the second part of the paper = inconclusive
Mevissen et al, 1996[71] Adult rats 50 Hz- 10 μT 24 h/day, 7 days/ wk, for 91 days Ser Mel Nighttime Decreased Mel levels
Niehaus et al, 1997[59] Djungarian hamsters 50 Hz- 450 μT sinusoidal or 360 μT rectangular 56 days Pineal and Ser Mel Nighttime Increased nighttime serum melatonin levels after rectangular field exposure
Reiter et al, 1998[83] Adult rats 0 Hz- Pulsed Magnetic field (1s off and on intervals) of 50 to 500 μT 15 to 120 min Pineal Mel and NAT activity, Ser Mel Nighttime Inconsistent results from 15 experiments
Lerchl et al, 1998[60] teleost fish, the brook trout (Salvelinus fontinalis) 1 Hz- maximum 40 μT (200 ms on, 800 ms off) 45 min: exposure started at 22 h45 Pineal and Ser Mel At 23:30 Increase
Selmaoui and Touitou, 1999[63] Aged rats 50 Hz- 100 μT 18 h per day for one week Ser Mel and Pineal NAT Nighttime Decrease of Mel and NAT activity in young but not aged rats
Wilson et al, 1999[52] Siberian hamsters 50 Hz- 100 or 500 T, continuous and/or intermittent 30 min or 2 h before onset of darkness and for up to 3 h up to 42 days Pineal Mel Nighttime Decrease of pineal Mel and NAT activity in short photoperiod
Fernie et al, 1999[81] Kestrel 60 Hz- current created a magnetic field of 30 μT and an electric field of 10 kV/m. For one or two breeding season Pl Mel 08 h-11 h (Males) and 13-15 h (females) Effect in adult males but not females. Long-term, but not short-term, MF exposure of adults suppressed in their fledglings. Seasonal shift
Huuskonen et al, 2001[54] Female adult rats 50 Hz- 13 or 130 μT 24 h/day from day 0 of pregnancy; and killed during light and dark periods between 70 h and 176 h after ovulation Ser Mel Nighttime Decrease of Ser Mel concentration by 34 and 38% at 13 and 130 μT
Burchard et al, 2004[84] Holstein heifers 60 Hz- 10kV/m 22h/day for 4 weeks Ser Mel 9 h, 10 h, 11 h, and 12 h Inconsistent results between 2 replicates
Kumlin et al, 2005[55] Female mice 50 Hz- at 100 μT 52 days Urinary aMT6s Nocturnal urine was collected 1, 3, 7, 14, 16 and 23 days after beginning of exposure Significant day-night difference in the aMT6s levels. No effect on the total 24 h
Dyche et al, 2012[61] Adult rats 60 Hz- 1000 mG 1 month Urinary aMT6s Urine collected for the last 3 days of the exposure period Mild increase of nighttime aMT6s
Table Ia Magnetic field reports on the modification of melatonin secretion in different animal species. Mel, melatonin; Pl, plasma; Ser, serum; aMT6s, 6 sulfatoxymelatonin; MF, magnetic field; NAT: serotonin N-acetyl transferase
Reference of the study Species Exposure characteristics Timing of exposure Fluid or pineal Sampling time Effect on melatonin secretion
Kato et al, 1994[49] Adult rats 50 Hz- 1 μT, horizontally or vertically oriented MF 6 weeks Pineal and Pl Mel 12 h and 24 h No effect
Lee et al, 1993, 1995[74],[75] Suffolk sheep 60 Hz- 6 kV/m and 4 μT Overhead power lines (10 months) Ser Mel 8 x 48 h periods No effect
Rogers et al, 1995[56] Baboons 60 Hz- 6 kV/m and 50 μT 6 weeks 30 kV/m and 100 μT, 3 weeks Ser Mel Nighttime No effect
Kroeker et al, 1996[68] Rats 0 Hz- 800 gauss between 12 hours and 8 days Pineal and Ser Mel Nighttime No effect
Yellon, 1996[58] Adult Djungarian hamsters 60 Hz- 100 μT 15 min, 2 h before dark Pineal and Ser Mel Nighttime No effect
Mevissen et al, 1996[72] Adult rats 50 Hz- 50 μT 24 h/day, 7 days/week, for 91 days Ser Mel Nighttime No effect on DMBA-treated rats
Bakos et al, 1995; 1997[64],[65] Adult rats 50 Hz- 1, 5, 100 or 500 μT 24 h Urinary aMT6s Day/night No effect
Löscher et al, 1998[69] Adult rats 50 Hz- 100 μT 18 h per day for one week Ser Mel Nighttime (3 samples) No effect
Yellon and Truong, 1998[77] Adult Siberian hamster 60 Hz- 100 μT 15 min per day Up to 21 days Pinel and Ser Mel Nighttime No effect
Burchard et al, 1998[78] Holstein cows 60 Hz- 10 kV/m and a uniform horizontal magnetic field of 30 μT Up to 56 days of exposure Pl Mel every 0.5 h for 14 starting at 17 h No effect
John et al, 1998[70] Adult rats 60 Hz, 1 mT 20 h/day for 6 weeks Urinary aMT6s Circadian pattern No effect in 3 experiments out of 4
de Bruyn et al, 2001[73] Mice 50 Hz- between 0.5 and 77 μT with an average of 2.75 μT 24 h/day from conception until adult age Pl Mel 23 h-01 h30 No effect
Fedrowitz et al, 2002[67] Adult rats 50 Hz- 100 μT 24 h/day for 2 weeks Pineal Mel at 9 h30, 10h30, 12h30, 1h30 No effect
Bakos et al, 2002[66] Adult rats 50 Hz- 100 or 50 microT 8 h/day for 1 week Urinary aMT6s Nighttime No effect
Rodriguez et al, 2004[80] Holstein cows 60 Hz- vertical electric field of 10 kV/m and a horizontal magnetic field of 30 μT for 16 h/day for 4 weeks Pl Mel Over 24 h No effect during dark period. Daytime mel low
Burchard et al, 2007[79] Holstein heifers 60 Hz- 30 μT 20 h/day for 4 weeks Ser Mel 09 h, 10 h, 11 h No effect
Dell'omo et al, 2009[82] Eurasian kestrels 50 Hz-power lines high voltage: 4-8 μT Breeding season Ser Mel NG No effect
Table Ib Reports on the lack of effect of magnetic field on melatonin secretion in different animal species. Mel, melatonin; Pl, plasma; Ser, serum; aMT6s, 6 sulfatoxymelatonin; MF, magnetic field; NAT, serotonin N-acetyl transferase; NG, not given
Reference of the study Exposure characteristics End point Effect of MF on melatonin
Studies on rat and hamster isolated pineal glands
Lerchl et al, 1991[85] 33.7 Hz - 44 μT for 2.5 h NE stimulation of Mel production in rat Decreased production and release
Richardson et al, 1992[86] 0 Hz- 1 h to a pulsed 0.4-G static MF NAT activity and Mel in rat Decrease of NAT activity and Mel content
Rosen et al, 1998[87] 60 Hz- 50 μT NE stimulation of Mel release in rat Decreased release
Brendel et al, 2000[88] 50 Hz or 16.7 Hz- 86 μT for 8 h Isoproterenol stimulation of Mel production in Djungarian hamster Decrease in Mel concentration
Lewy et al, 2003[89] 50 Hz- 1 mT for 4 h NE stimulation of Mel production in rat Increased release
Tripp et al 2003[90] 50 Hz- 500 microT for 4 h Mel release in rat pineal glands No effect
Studies on MCF-7 cell growth
Liburdy et al, 1993[91] 60 Hz- 1.2 μT for 7 days Mel inhibition of MCF-7 cell growth Decrease in growth inhibition
Harland and liburdy, 1997[92] 60 Hz- 1.2 μT for 7 days Tamoxifen and Mel inhibition of MCF-7 cell growth Decrease of Mel and Tamoxifen's inhibitory action
Blackman et al, 2001[93] 60 Hz- 1.2 μT for 7 days Tamoxifen and Mel inhibition of MCF-7 cell growth Decrease of Mel and Tamoxifen's inhibitory action
Ishido, 2001[94] 50 Hz- 1.2 or 100 μT for up to 7 days Mel inhibition of cAMP and DNA synthesis in MCF-7 cells Decrease of inhibition induced by Mel
Leman et al, 2001[95] 2 Hz- 0.3 mT, 1h/day for 3 days Mel inhibition of breast cancer cells No effect
Girgert et al 2010[96] 50 Hz- 1.2 mT for 48 h Signal transduction of the Mel receptor MT1 in MCF-7 Signal transduction involving MT1 was disrupted in MCF-7
Table II. Effects of magnetic fields on various biological systems in vitro. NE, norepinephrine; Mel: melatonin

Human studies

Much of the evidence for the melatonin hypothesis is based on data obtained in rodents with a 25% to 40% reduction in the hormonal concentration, though, as shown above, results on the effects of ELF-EMF in rodents and higher mammals provided controversial results. Since the 1990s several research papers have documented the effects of ELF-EMF on the secretion of melatonin in humans. Most research published has involved an acute exposure (from 30 min to 4 days on average) of healthy volunteers to ELF-EMF with different exposure characteristics (Tables IIIa and IIIb). The data on humans are controversial, since of the papers published about one third reported a decrease in melatonin secretion[97],​[98],​[99],​[100],​[101],​[102],​[103],​[104],​[105],​[106],​[107] with, however, some comments to be mentioned such as the lack of evidence for a dose-response,[97] or a decrease not exclusively related to ELF-EMF and found in some particular subgroups[98],​[99],​[100],​[101],​[102],​[103],​[104],​[105],​[106],​[107] (Table IIIa). In contrast to the previous ones, two thirds of the reports failed to find any effect of ELF-EMF on melatonin secretion in humans ( Table IIIb). [108],​[109],​[110],​[111],​[112],​[113],​[114],​[115],​[116],​[117],​[118],​[119],​[120],​[121],​[122],​[123],​[124],​[125],​[126],​[127],​[128],​[129],​[130]Most work published on humans dealt with short-term exposure for evident ethical reasons. Taking into account the data we have shown on rats of potentially cumulative effects of ELF-EMF,[62] we performed a study in workers chronically exposed daily for 1 to 20 years, both in the workplace and at home, since the workers were housed near the substations. We showed no alteration in their melatonin secretion (plasma level or circadian profiles) which strongly suggests that ELF-EMF do not have cumulative effects on melatonin secretion in humans, and thus clearly rebuts the melatonin hypothesis that a decrease in blood melatonin concentration (or a disruption in its secretory pattern) explains the occurrence of clinical disorders or cancers possibly related to ELF-EMF.[125]

Reference of the study Subjects (N) Sex Age (years) Exposure characteristics Timing of exposure Fluid or pineal Sampling time Effect on melatonin secretion
Pfluger and Minder, 1996[97] 108 M NG 16 Hz- ~ 20 μT mean value in engine drivers 30 min - 4 h Urinary aMT6s Morning and evening samples Decrease of aMT6s in evening; No evidence for a dose-response
Arnetz and Berg, 1996[98] 47 NG NG 1 day exposure to video display unit (VDU) 1 day Ser Mel Morning and afternoon samples Decrease but exposure not exclusively related to 50/60 Hz
Wood et al, 1998[99] 44 M 18-49 50 Hz- 20 μT, sinusoidal or square wave field, intermittent 19 h-21 h Pl Mel 20 min, 30 min, or hourly at night Delay and decrease of Mel in subgroup
Burch et al, 1998[100] 142 M 22-60 60 Hz- 0.1-0.2 μT Occupational exposure Urinary aMT6s Morning urine samples No effect at work, urinary aMT6s decreased at home
Burch et al, 1999[101] 142 M 22-60 60 Hz- occupational exposure Occupational exposure over a week Urinary aMT6s Overnight urine samples Decrease in aMT6s excreation in workers exposed to more stable fields during work.
Burch et al, 2000[102] M NG 60 Hz- occupational exposure (electric utility worker), from 950 nT to 1.05 μT (exposure for < 2 h/day or > 2 h day) 3 consecutive days monitored Urinary aMT6s Overnight aMT6s Decrease in aMT6s excretion in workers exposed for > 2 h
Juutilainen et al, 2000[103] 60 F mean age ~ 44 50 Hz- 0.3-1 μT and > 1 μT and 0.15 μT Occupational exposure Urinary aMT6s Nighttime and morning urine collection aMT6s excretion lower in exposed workers compared with office workers
Davis et al, 2001[104] 203 F 20-74 60 Hz- domestic exposure. Half of the subjects had mean levels of < 0.04 μT residential 72 h Urinary aMT6s Nighttime samples Decrease, primarily in subgroup using medication
Burch et al, 2002[105] 226 electric utility workers M 18-60 60 Hz- occupational exposure occupational exposure: measures on 3 consecutive work days Urinary aMT6s Overnight aMT6s Decrease in aMT6s associated with mobile phone use
Davis et al, 2006[106] 115 F 20-40 60 Hz- 5 to 10 mG At night for 5 consecutive nights Urinary aMT6s Overnight samples Decrease
Burch et al, 2008[107] 153 M Mean age = 44 0 Hz- 15nT to 30 nT + 60 Hz 3 h, 24 h, 36 h Urinary aMT6s Overnight aMT6s Decrease in aMT6s associated with elevated geomagnetic activity
Table IIIa. Magnetic field reports on a melatonin secretion decrease in humans. Mel, melatonin; aMT6s, 6 sulfatoxymelatonin; M, male; F: female; MF, magnetic field; NG, not given
Reference of the study Subjects (N) Sex Age (years) Exposure characteristics Timing of exposure Fluid Sampling time Effect of MF on melatonin secretion
Wilson et al, 1990[108] 42 F, M NG CPW electric blanket. 0.2-0.6 μT 8 weeks Urinary aMT6s Urine voidings No effect
Schiffman et al, 1994[109] 9 M 22-34 0 Hz- Magnetic resonance imaging. 1.5 T 01 h Pl Mel Nighttime (2 samples) No effect
Selmaoui et al, 1996[110] 32 M 20-30 50 Hz- 10 μT, to continuous or intermittent MF 23 h-08 h Ser Mel and urinary aMT6s Every 2 h during the daytime, hourly during the nighttime No effect
Graham et al, 1996[111] 33 M 19-34 60 Hz- 1 or 20 μT, intermittent 23 h-07 h Pl Mel Hourly at night No effect
Graham et al, 1997[112] 40 M 18-35 60 Hz- 20 μT, continuous 23 h-07 h Pl Mel Hourly at night No effect
Akerstedt et al, 1999[113] 18 F, M 18-50 50 Hz- 1 μT 23 h-08 h Pl Mel At 23 h 02h30 h, 05 h, and 08 h No effect
Graham et al, 2000[114] 30 M 18-35 60 Hz- 28.3 μT 4 consecutive nights from 23 h - 07 h Urinary aMT6s Overnight urine samples No effect
Crasson et al, 2001[115] 21 M 20-27 50 Hz- 100 μT, continuous or intermittent 30 min at 13 h30 and 16 h30 Ser Mel and Urinary aMT6s Hourly from 20 h to 07 h No effect
Graham et al, 2001[116] 24 M 19-34 60 Hz- 127 μT, continuous or intermittent 23 h - 07 h Ser Mel and Urinary aMT6s Hourly from 24 to 07 h No effect
Graham et al, 2001[117] 46 F, M 40-60 60 Hz-28.3 μT 23 h - 07 h Urinary aMT6s Morning urine samples No effect
Griefahn et al, 2001[118] 7 M 16-22 16.7 Hz- 200 μT 18h - 02 h Sal Mel Hourly for 24 h No effect
Haugsdal et al, 2001[119] 11 M 23-43 0 Hz- 2-7 mT, 9 h 22 h - 07 h Urinary aMT6s 4 samples / 24 h No effect
Hong et al, 2001[120] 9 M 23-37 50 Hz-1-8 μT, electric 'sheet' over the body 11 weeks at night Urinary aMT6s 5 times a day No effect
Levallois et al, 2001[121] 416 F 20-74 50 Hz- between 0.1 and 0.3 μT Residential exposure Urinary aMT6s Overnight urine samples No effect except in subgroup of women with high BMI
Griefahn et al, 2002[122] 7 M 16-22 16.7 Hz, 0.2 mT 17 h-01 h Sal Mel Hourly for 24 h No effect
Youngstedt et al, 2002[123] 242 F, M 50-81 60 Hz- Mean of one week exposure = 0.1 μT Residential exposure within bed Urinary aMT6s Fractional urine No effect
Kurokawa et al, 2003[124] 10 M 20-37 50 Hz- 20 μT 20 h-08 h Ser Mel Hourly from 20 h to 08 h No effect
Touitou et al, 2003[125] 30 M 31.5-46 50 Hz- mean fields of 0.1-2.6 μT Occupational and residential exposure (1 to 20 years) Ser Mel and urinary aMT6s Hourly from 20 h to 08 h No effect
Warman et al, 2003[126] 19 M 18-35 50 Hz- 200 or 300 μT 2- H exposure between 17 h and 23 h Sel Mel 17 h and 10 h No effect
Cocco et al, 2005[127] 51 F, M Mean age 56.6 50 Hz- from 0.0045 μT to 0.148 μT Residential Urinary aMT6s At 22 h and 08 h No effect
Gobba et al, 2006[128] 59 F, M Mean age 42 and 46 60 Hz- low exposed (≤0.2 μT) or higher exposed (>0.2 μT) 3 consecutive days recorded for workers Urinary aMT6s Morning urine No effect
Juutilainen and kumlin, 2006[129] 60 F Mean age 40 to 53 50 Hz- from 0.1 to 2.5 μT 3 consecutive weeks Urinary aMT6s Morning urine No effect Inconclusive results with light exposure
Clark et al, 2007[130] 127 F 12 to 81 60 Hz- 20 nT to 130 nT and RF 0.04 μW/cm2 to 1.4 μW/cm2 Residential for 2.5 days Urinary aMT6s Overnight No effect
Table IIIb. Magnetic field reports on the lack of effect on melatonin secretion in humans. Mel, melatonin; Pl, plasma; Ser, serum; Sal, saliva; aMT6s, 6 sulfatoxymelatonin; M, male; F, female; BMI, body mass index; MF, magnetic field; RF, radio frequency; NG, not given

ELF-EMF effects on cortisol and corticosterone

In contrast to the number of studies on the effects of ELF-EMF on melatonin secretion, few data are available in the literature on the pituitary adrenal axis. The hormones under study (corticosterone for rats, cortisol for other mammals), exposure characteristics (short- and long-term), and timing and duration of exposure (1 to 6 months) in different animal species are detailed in Table IV.

While the majority of papers failed to find any effect,[131],​[132],​[133],​[134],​[135],​[136],​[137] others have reported either an increase in the hormonal concentrations[138],​[139],​[140],​[141],​[142],​[143],​[144] or a decreased concentration.[145] The results of these studies are thus inconsistent and contradictory. Comparison between studies revealed that the discrepancy in the results might be due in part to the difference in the animal species used (rabbit, ewe lambs, cows, rats, or mice), class of age, and duration and intensity of exposure. Another factor that should be taken into account is that glucorticoids (ie, cortisol or corticosterone) levels are sensitive to many stressors that might affect hormone levels. It is well known that handling or bleeding animals increase corticosterone, a stress marker, and it is thus important to ensure that any external confounding stressor has to be controlled.

Overall, these data suggest that no consistent effects have been seen in the stress-related hormones of the pituitary-adrenal axis in a variety of mammalian species. Data on ELF-EMF effects on cortisol in humans are scarce. We have found 7 papers on the matter (Table V).[109],[124],​[146],​[147],​[148],​[149] All of these papers report only on short exposure of adult volunteers to ELF-EMF, and all failed to find any effect.

Reference of the study Species Exposure characteristics Timing of exposure Fluid or pineal Sampling time Effect of MF on melatonin secretion
Papers reporting no effect
Free et al, 1981[131] Rats 60 Hz- 100 kV/m 20 h/day for 30 or 120 days (adults) or from 20 to 56 days of age (young) Ser corticosterone 08 h30-12 h30 No effect
Quinlan et al, 1985[132] Rats 60 Hz- 100 kV/m; continuous or intermittent 1 or 3 h Ser corticosterone 11 h or 13 h No effect
Portet and Cabanes, 1988[133] Rabbits and rats 50 Hz- 50 kV/m Rabbit: 16 h/day from last 2 weeks of gestation to 6 weeks after birth. Rat: 8h/day for 4 weeks Ser cortisol (rabbits) and corticosterone (rats) Nighttime No effect
Thompson et al, 1995[134] Ewe lambs 60 Hz- 500-kV transmission line (mean electric field 6 kV/m, mean magnetic field 40 mG) Up to 43 weeks Ser cortisol 48 h sampling (3-h intervals at daylight and hourly at night No effect
Burchard et al, 1996[135] Dairy cows (Holstein) 60 Hz- 10 kV/m and 30 μT Up to 56 days of exposure Pl cortisol Twice weekly No effect
Szemerszky et al, 2010[136] Rats 50 Hz-0.5 mT for 5 days, 8 h daily (short) or for 4-6 weeks, 24 h daily (long) Ser corticosterone NG No effect
Martinez-Samano et al, 2012[137] Rats 60 Hz - 2.4 mT 2 hours (12 h-14 h) Pl corticosterone NG No effect
Papers reporting an effect
Hackman and Graves, 1981[138] Rats 60 Hz- 25 or 50 kV/m 15 min per day up to 42 days Ser corticosterone Before and after exposure Increase in serum levels at onset of exposure
Gorczynska and Wegrzynowicz, 1991[139],[140] Rats 1 and 10 mT 1 h daily for 10 days Ser cortisol Nighttime Increase
de Bruyn and de Jager, 1994[141] Mice 60 Hz- 10 kV m-1 22 h per day for 6 generations Ser corticosterone Day/night Elevated daytime but no effect on night-time levels
Picazo et al, 1996[142] Mice 50 Hz- 15 μT 14 weeks prior to gestation and 10 weeks post-gestation Ser cortisol Circadian Circadian rhythm Altered
Bonhomme-Faivre et al, 1998[145] Mice 50 Hz- 5 μT After 90 and 190 days Ser cortisol Morning On day 190, exposed animals showed a decrease in the cortisol
Marino et al, 2001[143] Mice 60 Hz- 500 μT For 1-175 days Ser corticosterone Nighttime Changes in Ser corticosterone
Mostafa et al, 2002[144] Rats 50 HZ-200 μT Up to 2 weeks Pl corticosterone NG Increase of plasma corticosterone
Table IV. Effects of EMF on cortisol or corticosterone secretion in different animal species. Pl, plasma; Se, serum; NG, not given
Reference of the study Subjects (N) Sex Age (years) Exposure characteristics Timing of exposure Fluid Sampling time Effect of MF on melatonin secretion
Maresh et al, 1988[146] 11 M 21-29 60 Hz-9 kV/m and 20 μT 2 hours of exposure Pl cortisol 10, 30, 60, 90 and 120 No effect
Gamberale et al, 1989[147] 26 M 25-52 50 Hz- 2.8 kV/m and 23.3 μT 4.5 h during working day 10 h-12 h, 12h30-14 h30 Ser cortisol 06 h45-07 h, 12 h-12 h10, 16 h30-17 h10 No effect
Selmaoui et al, 1997[148] 32 M 20-30 50 Hz- 10 μT, continuous or intermittent 23 h -08 h Ser cortisol Every 2 h during the daytime, hourly during the nighttime No effect
Akerstedt et al, 1999[113] 18 F, M 18-50 50 Hz- 1 μT 23 h -08 h Pl cortisol At 23 h 02 h30, 05 h, and 08 h No effect
Kurokawa et al, 2003[124] 10 M 20-37 50 Hz- 20 μT 20 h-08 h Ser cortisol Hourly from 20 h to 08 h No effect
Ghione et al, 2004[149] 10 M Mean age: 41 3 7 Hz- 80 μT 1 hour of exposure between 9 h and 12h Pl cortisol 2 samples: one 15 min befor the start of the study and one after the end of exposure period No effect
Table V. Magnetic field reports on cortisol secretion in humans. Ser, serum; Pl, plasma; M, male; F, female; MF, magnetic field

Conclusion

We are all exposed to electric and magnetic fields of weak intensity. The levels of exposure of the general population range from 5 to 50 V/m for electric fields and from 0.01 to 0.2 μT for magnetic fields. The possible risk on health with exposure to electromagnetic fields became a concern to the public, which led to numerous studies by scientists on the topic. We have shown in this review that the reported studies are largely contradictory with regard to epidemiologic studies (about half of the studies found a relationship and the other half failed to find any), to the potential biological effects of ELF-EMF, and to the potentially mechanisms put forward; no clear explanations exist for these contradictory results. The relative risk (RR) which establishes the relation between exposure to ELF-EMF and cancer, is approximately 2 to 3. In the absence of clear explanation(s) a number of hypotheses have been raised. The characteristics of the magnetic field (linear or circular polarization, duration, timing), the animal species and, within a species, the strain appears to have a role in determining the biologic response obtained. Therefore, great care must be given when comparing data obtained in different animal species, even within a group as rodents, since differences have been described between rodent species and even between pigmented and albino breeds.

A possible change in the spatial structure of the photoreceptor pigment rhodopsin due to the electric field induced by the magnetic field has been proposed. Magnetic fields might also change either the electrical activity of the pinealocytes or their ability to produce melatonin, or both. With regard to the numerous studies performed on the effects of ELF-EMF on melatonin, the differences observed in animals and humans in these effects may be due to the differences in anatomical location and configuration of the pineal gland, and also the difference in the rest-activity cycle between rodents and humans. A different sensitivity to ELF-EMF could also be part of the explanation. Some human subjects may have greater sensitivity to ELF-EMF, but this is difficult to demonstrate because of the important interindividual variability in plasma concentration of melatonin. As far as melatonin is concerned, we have shown a lack of effect of ELF-EMF on melatonin (concentration and circadian rhythm) in workers exposed daily for up to 20 years in their workplace and at home, which strongly suggests that chronic ELF-EMF exposure appears to have no cumulative effects in human adults; this rebuts the “melatonin hypothesis” raised as an explanation for the deleterious sanitary effects of ELF-EMF.[125]

In the same way, the application of high-throughput omics technologies to investigate the influences of ELF-EMF is confronted with the heterogeneity among the biological materials investigated, which are as different as blood cells/vessels, tissue cells, nerves, and bacteria, and this makes it difficult to compare data and to arrive at firm conclusions on the potential effects of ELF-EMF on biological systems.[150] As an example, most breast tumors become, resistant to tamoxifen, and it has been shown that ELF-EMF reduce the efficacy of tamoxifen in a manner similar to tamoxifen resistance. By exposing cells of the breast cancer line MCF-7 to ELF-EMF, it has been found that ELF-EMF alter the expression of estrogen receptor cofactors, which in the authors' view may contribute to the induction of tamoxifen resistance in vivo.[151]

Currently, the debate concerns the effects of ELF-EMF on children, with some data published in the literature pointing out the risk of childhood leukemia in relation to residential exposure, and underlining that this risk (the RR is around 2) can exist when children are chronically exposed to more than 0.4 μT.10 Large-scale collaborative studies are still needed to fill the gaps in our knowledge and provide answers to these numerous questions not yet resolved. Last, the deleterious risk of ELF-EMF on frail populations such as children and aged people may be greater and should be documented, at least for their residential exposure.

Figure 2. Effects of chronic exposure of male rats to a sinusoidal 50-Hz magnetic field ( from 1 to 100 uT) on nocturnal pineal activity. The rats were exposed every day from 14:00 to 08:00 for 30 days at three different intensities. Only 10 and 1 00 uT were able to depress serum melatonin and pineal activity. No effect was observed on HIOMT activity. The asterisks indicate a significant difference (P<0.05) with the control group (Ctrl). Reproduced from ref 62: Selmaoui B, Touitou Y. Sinusoidal 50-Hz magnetic fields depress rat pineal NAT activity and serum melatonin. Role of duration and intensity of exposure. Life Sci. 1995;57:1351-1358. Copyright© Pergamon Press 1995
Figure 3. Nocturnal plasma melatonin patterns (A) and 6-sulfatoxymelatonin concentration (6SM; B) in the first-void morning urine (20:00 to 08:00). This study was carried out in 15 healthy chronically (in the workplace and at home) exposed men (daily and for 1 to 20 years) to a 50-Hz magnetic field in search of any cumulative effect from those chronic conditions of exposure. Fifteen healthy unexposed men served as controls. As shown here, the exposed subjects experienced no change in the hormone levels or circadian patterns of melatonin. Reproduced from ref 125: Touitou Y, Lambrozo J, Camus F, Charbuy H. Magnetic fields and the melatonin hypothesis: a study of workers chronically exposed to 50-Hz magnetic fields. Am J Physiol Regul Integr Comp Physiol. 2003;284:R1 529-535. Copyright © American Physiological Society 2003
REFERENCES
1. Wertheimer N, Leeper E. Electrical wiring configurations and childhood cancer. Am J Epidemiol. 1979;109:273-284 [ Pub Med ]
2. Wertheimer N, Leeper E. Adult cancer related to electrical wires near the home. Int J Epidemiol. 1982;11:345-355 [ Pub Med ]
3. Savitz DA, Wachtel H, Barnes FA, John EM, Tvrdik JG. Case control study of childhood cancer and exposure to 60-Hz magnetic fields. Am J Epidemiol. 1988;128:21-38 [ Pub Med ]
4. Ahlbom A, Day N, Feychting M, et al. . A pooled analysis of magnetic fields and childhood leukemia. Br J Cancer. 2000;83:692-698 [ Pub Med ]
5. Linet MS, Hatch EE, Kleinerman RA, et al. . Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. N Engl J Med. 1997;337:1-7 [ Pub Med ]
6. McBride ML, Gallagher RP, Theriault G, et al. . Power-frequency electric and magnetic fields and risk of childhood leukemia in Canada. Am J Epidemiol. 1999;149:831-842 [ Pub Med ]
7. Reichmanis M, Perry FS, Marino AA, Becker RO. Relation between suicide and the electromagnetic field of overhead power lines. Physiol Chern Pfiys. 1979;11:395-403 [ Pub Med ]
8. Sobel E, Dunn M, Davanipour Z, Qian Z, Chui H. Elevated risk of Alzheimer's disease among workers with likely electromagnetic exposure. Neurology. 1996;47:1477-1481 [ Pub Med ]
9. Davanipour Z, Sobel E. Long-term exposure to magnetic fields and the risks of Alzheimer's disease and breast cancer: further biological research. Pathophysiology. 2009;16:149-156 [ Pub Med ]
10. Kheifets L, Ahlbom A, Crespi CM, et al. . Pooled analysis of recent studies on magnetic fields and childhood leukaemia. Br J Cancer. 2010;103:1128-1135 [ Pub Med ]
11. Kheifets L, Renew D, Sias G, Swanson J. Extremely low frequency electric fields and cancer: assessing the evidence. Bioelectromagnetics. 2010;31:89-101 [ Pub Med ]
12. Stevens RG, Davies S. The melatonin hypothesis: electric power and breast cancer. Enviro Health Perspect. 1996;104:135-140 [ Pub Med ]
13. Hill SM, Blask DE, Xiang S, et al. . Melatonin and associated signaling pathways that control normal breast epithelium and breast cancer. J Mammary Gland Biol Neoplasia. 2011;16:235-245 [ Pub Med ]
14. Wehr TA, Godwin FK. American Handbook of Psychiatry. Vol 7. 2nd ed. New York, NY: Basic Books 1981:46-74
15. Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Rosenthal NE. Manic depressive patients may be supersensitive to light. Lancet. 1981;106:145-151 [ Pub Med ]
16. Claustrat B, Chazot G, Brun J. A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression. Biol Psychiatry. 1984;19:1215-1228 [ Pub Med ]
17. Touitou Y, Coste O, Dispersyn G, Pain L. Disruption of the circadian system by environmental factors: effects of hypoxia, magnetic fields and general anesthetics agents. Adv Drug Deliv Rev. 2010;62:928-945 [ Pub Med ]
18. Touitou Y. Desynchronisation de l'horloge interne, lumiere et melatonine. Bull Acad Nle Med. 2011;195:1527-1549 [ Pub Med ]
19. World Health Organization. Extremely low frequency fields (Environment health criteria 238). Geneva, Switzerland: World Health Organisation 2007
20. International agency for research on cancer (IARC). Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 80 Non-Ionizing Radiation. Part 1: Static and Extremely Low-Frequency (ELF) Electric and Magnetic Fields.
21. Wilson BW, Stevens RG, Anderson LE. Neuroendocrine mediated effects of electromagnetic-field exposure: possible role of the pineal gland. Life Sci. 1989;45:1319-1332 [ Pub Med ]
22. Touitou Y, Levi F, Bogdan A, Benavides M, Bailleul F, Misset JL. Rhythm alteration in patients with metastatic breast cancer and poor prognostic factors. J Cancer Res Clin Oncol. 1995;121:181-188 [ Pub Med ]
23. Touitou Y, Bogdan A, Levi F, Benavides M, Auzeby A. Disruption of the circadian patterns of serum cortisol in breast and ovarian cancer patients relationships with tumor marker antigens. Br J Cancer. 1996;74:1248-1252 [ Pub Med ]
24. Mormont MC, Langouet AM, Claustrat B, et al. . Marker rhythms of circadian system function: a study of patients with metastatic colorectal cancer and good performance status. Chronobiol Int. 2002;19:141-155 [ Pub Med ]
25. Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP. Light suppresses melatonin secretion in humans. Science. 1980;210:1267-1269 [ Pub Med ]
26. Touitou Y, Benoit O, Foret J, et al. . Effects of 2 hour early awakening and bright light exposure on plasma patterns of cortisol, melatonin, prolactin and testosterone in man. Acta Endocrinol. 1992;126:201-205 [ Pub Med ]
27. Lemmer B, Bruhl T, Pflug B, Kohler W, Touitou Y. Effects of bright light on circadian patterns of cyclic adenosine monophosphate, melatonin and cortisol in healthy subjects. Eur J Endocrinol. 1994;130:472-477 [ Pub Med ]
28. Depres-Brummer P, Levi F, Metzger G, Touitou Y. Light-induced suppression of the rat circadian system . Am J Physiol. 1995;37:R1111-R1116 [ Pub Med ]
29. Touitou Y, Arendt J, Pevet P. Melatonin and the Pineal Gland: from Basic Science to Clinical Applications. Amsterdam, the Netherlands: Elsevier 1993
30. Rodin AE. The growth and spread of walker 256 carcinoma in pinealectomized rats. Cancer Res. 1963;23:1545. Abstract. [ Pub Med ]
31. Das Gupta TK, Terz J. Influence of the pineal gland on growth and spread of melatonin in the hamster. Cancer Res. 1967;27:1306-1311 [ Pub Med ]
32. Tamarkin L, Cohen M, Roselle D, Reichert C, Lippman M, Chabner B. Melatonin inhibition and pinealectomy enhancement of 7, 12-dimethylbenz(a)anthraceneinduced mammary tumors in the rat. Cancer Res. 1981;41:4432-4436 [ Pub Med ]
33. Reinberg AE, Touitou Y. Synchronisation et dyschronisme des rythmes circadiens humains. Pathol Biol. 1996;44:487-495 [ Pub Med ]
34. Touitou Y, Sulon J, Bogdan A, et al. . Adrenal circadian system in young and elderly human subjects: a comparative study. J Endocrinol. 1982;93:201-210 [ Pub Med ]
35. Touitou Y, Sulon J, Bogdan A, Reinberg A, Sodoyez JC, Demey-Ponsart E. Adrenocortical hormones ageing and mental condition: seasonal and circadian rhythms of plasma 18-hydroxy-11 deoxycorticosterone, total and free cortisol and urinary corticosteroid. J Endocrinol. 1983;96:53-64 [ Pub Med ]
36. Selmaoui B, Touitou Y. Reproducibility of the circadian rhythms of serum cortisol and melatonin in healthy subjects. A study of three different 24-h cycles over six weeks. Life Sci. 2003;73: 3339-3349 [ Pub Med ]
37. Mailloux A, Benstaali C, Bogdan A, Auzeby A, Touitou Y. Body temperature and locomotor activity as marker rhythms of aging of the circadian system in rodents. Exp Gerontol. 1999;34:733-740 [ Pub Med ]
38. Touitou Y. Pineal and hypothalamo-pituitary-adrenal axis: in search for interaction. In: Reiter RJ, Pang SF, eds. Advances in Pineal Research. Vol 3. London, UK: John Libbey, 1989:241-246
39. Wilson BW, Anderson LE, Hilton Dl, Phillips RD. Chronic exposure to 60Hz electric fields: effects on pineal function in the rat. Bioelectromagnetics. 1981;2:371-380 [ Pub Med ]
40. Wilson BW, Chess EK, Anderson LE. 60-Hz electric-field effects on pineal melatonin rhythms: time course for onset and recovery. Bioelectromagnetics. 1986;7:239-242 [ Pub Med ]
41. Reiter RJ, Anderson LE, Buschbom RL, Wilson BW. Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth. Life Sci. 1988;42:2203-2206 [ Pub Med ]
42. Grata LJ, Reiter RJ, Keng P, Michaelson S. Electric field exposure alters serum melatonin but not pineal melatonin synthesis in male rats. Bioelectromagnetics. 1994;15:427-437 [ Pub Med ]
43. Touitou Y, Bogdan A, Lambrozo J, Selmaoui B. Is melatonin the hormonal missing link between magnetic field effects and human diseases. Cancer Causes Control. 2006;17:547-552 [ Pub Med ]
44. Lambrozo J, Touitou Y, Dab W. Exploring the EMF-melatonin connection: a review of the possible effects of 50/60-Hz Electric and magnetic fields on melatonin secretion. IntJOccup Environ Health. 1996;2:37-47 [ Pub Med ]
45. Yellon SM, Gottfried L. An Acute 60 Hz exposure suppresses the nighttime melatonin rhythm in the adult djungarian hamster in short days. Annual Review of Research on Biological Effects of Electric and Magnetic Fields from the Generation, Delivery and Use of Electricity. US Department of Energy: A-22, San Diego, California: 1992; November 8-12
46. Yellon SM. Acute 60 Hz magnetic field exposure effects on the melatonin rhythm in the pineal gland and circulation of the adult Djungarian hamster. J Pineal Res. 1994;16:136-144 [ Pub Med ]
47. Wilson BW, Morris JE, Sasser LB, et al. . Changes in the hypothalamus and pineal gland on Djungarian hamsters from short-term exposure to 60 Hz magnetic field. Annual Review of Research on Biological Effects of Electric and Magnetic Fields from the Generation, Delivery and Use of Electricity. US Department of Energy: A-30, Savannah. Georgia. 1993; October 31-November 4
48. Kato M, Honma K, Shigemitsu T, et al. . Effects of exposure to a circularly polarized 50-Hz magnetic field on plasma and pineal melatonin levels in rats. Bioelectromagnetics. 1993;14:97-106 [ Pub Med ]
49. Kato M, Honma K, Shigemitsu T, Shiga Y. Horizontal or vertical 50-Hz, 1-microT magnetic fields have no effect on pineal gland or plasma melatonin concentration of albino rats. Neurosci Lett. 1994;168:205-208 [ Pub Med ]
50. Kato M, Honma K, Shigemitsu T, Shiga Y. Circularly polarized 50-Hz magnetic field exposure reduces pineal gland and blood melatonin concentrations of Long-Evans rats. Neurosci Lett. 1994;166:59-62 [ Pub Med ]
51. Kato M, Honma K, Shigemitsu T, Shiga Y. Recovery of nocturnal melatonin concentration takes place within one week following cessation of 50 Hz circularly polarized magnetic field exposure for six weeks. Bioelectromagnetics. 1994;15:489-492 [ Pub Med ]
52. Martinez Soriano F, Gimenez Gonzalez M, Armanazas E, Ruiz Torner A. Pineal 'synaptic ribbons' and serum melatonin levels in the rat following the pulse action of 52-Gs (50-Hz) magnetic fields: an evolutive analysis over 21 days. Acta Anat (Basel). 1992;143:289-293 [ Pub Med ]
53. Loscher W, Wahnschaffe U, Mevissen M, Lerchl A, Stamm A. Effects of weak alternating magnetic fields on nocturnal melatonin production and mammary carcinogenesis in rats. Oncology. 1994;51:288-295 [ Pub Med ]
54. Huuskonen H, Saastamoinen V, Komulainen H, Laitinen J, Juutilainen J. Effects of low-frequency magnetic fields on implantation in rats. Reprod Toxicol. 2001;15:49-59 [ Pub Med ]
55. Kumlin T, Heikkinen P, Laitinen JT, Juutilainen J. Exposure to a 50-hz magnetic field induces a circadian rhythm in 6-hydroxymelatonin sulfate excretion in mice. J Radiat Res. 2005;46:313-318 [ Pub Med ]
56. Rogers WR, Reiter RJ, Barlow-Walden L, Smith HD, Orr JL. Regularly scheduled, day-time, slow-onset 60 Hz electric and magnetic field exposure does not depress serum melatonin concentration in nonhuman primates. Bioelectromagnetics. 1995;(suppl 3):111-118 [ Pub Med ]
57. Truong H, Smith JC, Yellon SM. Photoperiod control of the melatonin rhythm and reproductive maturation in the juvenile Djungarian hamster: 60-Hz magnetic field exposure effects. Biol Reprod. 1996;55:455-460 [ Pub Med ]
58. Yellon SM. 60-Hz magnetic field exposure effects on the melatonin rhythm and photoperiod control of reproduction. Am J Physiol. 1996;270:E816-E821 [ Pub Med ]
59. Niehaus M, Bruggemeyer H, Behre HM, Lerchl A. Growth retardation, testicular stimulation, and increased melatonin synthesis by weak magnetic fields (50 Hz) in Djungarian hamsters, Phodopus sungorus. Biochem Biophys Res Commun. 1997;234:707-711 [ Pub Med ]
60. Lerchl A, Zachmann A, AM MA, Reiter RJ. The effects of pulsing magnetic fields on pineal melatonin synthesis in a teleost fish (brook trout, Salvelinus fontinalis). Neurosci Lett. 1998;256:171-173 [ Pub Med ]
61. Dyche J, Anch AM, Fogler KA, Barnett DW, Thomas C. Effects of power frequency electromagnetic fields on melatonin and sleep in the rat. Emerg Health Threats J. Epub 2012 Apr 20.
62. Selmaoui B, Touitou Y. Sinusoidal 50-Hz magnetic fields depress rat pineal NAT activity and serum melatonin. Role of duration and intensity of exposure. Life Sci. 1995;57:1351-1358 [ Pub Med ]
63. Selmaoui B, Touitou Y. Age-related differences in serum melatonin and pineal NAT activity and in the response of rat pineal to a 50-Hz magnetic field. Life Sci. 1999;64:2291-2297 [ Pub Med ]
64. Bakos J, Nagy N, Thuroczy G, Szabo LD. Sinusoidal 50 Hz, 500 microT magnetic field has no acute effect on urinary 6-sulphatoxymelatonin in Wistar rats. Bioelectromagnetics. 1995;16:377-380 [ Pub Med ]
65. Bakos J, Nagy N, Thuroczy G, Szabo LD. Urinary 6-sulphatoxymelatonin excretion is increased in rats after 24 hours of exposure to vertical 50 Hz, 100 microT magnetic field. Bioelectromagnetics. 1997;18:190-202 [ Pub Med ]
66. Bakos J, Nagy N, Thuroczy G, Szabo LD. One week of exposure to 50 Hz, vertical magnetic field does not reduce urinary 6-sulphatoxymelatonin excretion of male wistar rats. Bioelectromagnetics. 2002;23:245-248 [ Pub Med ]
67. Fedrowitz M, Westermann J, Loscher W. Magnetic field exposure increases cell proliferation but does not affect melatonin levels in the mammary gland of female Sprague Dawley rats. Cancer Res. 2002;62:1356-1363 [ Pub Med ]
68. Kroeker G, Parkinson D, Vriend J, Peeling J. Neurochemical effects of static magnetic field exposure. Surg Neurol. 1996;45:62-66 [ Pub Med ]
69. Loscher W, Mevissen M, Lerchl A. Exposure of female rats to a 100microT 50 Hz magnetic field does not induce consistent changes in nocturnal levels of melatonin. Radiat Res. 1998;150:557-567 [ Pub Med ]
70. John TM, Liu GY, Brown GM. 60 Hz magnetic field exposure and urinary 6-sulphatoxymelatonin levels in the rat. Bioelectromagnetics. 1998;19:172-180 [ Pub Med ]
71. Mevissen M, Lerchl A, Loscher W. Study on pineal function and DMBAinduced breast cancer formation in rats during exposure to a 100-mG, 50 Hz magnetic field. J Toxicol Environ Health. 1996;48:169-185 [ Pub Med ]
72. Mevissen M, Lerchl A, Szamel M, Loscher W. Exposure of DMBA-treated female rats in a 50-Hz, 50 microTesIa magnetic field: effects on mammary tumor growth, melatonin levels, and T lymphocyte activation. Carcinogenesis. 1996;17:903-910 [ Pub Med ]
73. de Bruyn L, de Jager L, Kuyl JM. The influence of long-term exposure of mice to randomly varied power frequency magnetic fields on their nocturnal melatonin secretion patterns. Environ Res. 2001;85:115-121 [ Pub Med ]
74. LeeJM Jr, Stormshak F, Thompson JM, Thinesen P, et al. . Melatonin secretion and puberty in female lambs exposed to environmental electric and magnetic fields. Biol Reprod. 1993;49:857-864 [ Pub Med ]
75. LeeJM Jr, Stormshak F, Thompson JM, Hess DL, Foster DL. Melatonin and puberty in female lambs exposed to EMF: a replicate study. Bioelectromagnetics. 1995;16:119-123 [ Pub Med ]
76. Rogers WR, Reiter RJ, Smith HD, Barlow-Walden L. Rapid-onset/offset, variably scheduled 60 Hz electric and magnetic field exposure reduces nocturnal serum melatonin concentration in nonhuman primates. Bioelectromagnetics. 1995;(Suppl 3):119-122 [ Pub Med ]
77. Yellon SM, Truong HN. Melatonin rhythm onset in the adult Siberian hamster: influence of photoperiod but not 60-Hz magnetic field exposure on melatonin content in the pineal gland and in circulation. J Biol Rhythms. 1998;13:52-59 [ Pub Med ]
78. Burchard JF, Nguyen DH, Block E. Effects of electric and magnetic fields on nocturnal melatonin concentrations in dairy cows. J Dairy Sci. 1998;81:722-727 [ Pub Med ]
79. Burchard JF, Nguyen DH, Monardes HG. Exposure of pregnant dairy heifer to magnetic fields at 60 Hz and 30 microT. Bioelectromagnetics. 2007;28:471-476 [ Pub Med ]
80. Rodriguez M, Petitclerc D, Burchard JF, Nguyen DH, Block E. Blood melatonin and prolactin concentrations in dairy cows exposed to 60 Hz electric and magnetic fields during 8 h photoperiods. Bioelectromagnetics. 2004;25:508-515 [ Pub Med ]
81. Fernie KJ, Bird DM, Petitclerc D. Effects of electromagnetic fields on photophasic circulating melatonin levels in American kestrels. Environ Health Perspect. 1999;107:901-904 [ Pub Med ]
82. Dell'Omo G, Costantini D, Lucini V, Antonucci G, Nonno R, Polichetti A. Magnetic fields produced by power lines do not affect growth, serum melatonin, leukocytes and fledging success in wild kestrels. Cornp Biochem Physiol C Toxicol Pharmacol. 2009;150:372-376 [ Pub Med ]
83. Reiter RJ, Tan DX, Poeggeler B, Kavet R. Inconsistent suppression of nocturnal pineal melatonin synthesis and serum melatonin levels in rats exposed to pulsed DC magnetic fields. Bioelectromagnetics. 1998;19:318-329 [ Pub Med ]
84. Burchard JF, Nguyen DH, Monardes HG, Petitclerc D. Lack of effect of 10 kV/m 60 Hz electric field exposure on pregnant dairy heifer hormones. Bioelectromagnetics. 2004;25:308-312 [ Pub Med ]
85. Lerchl A, Nonaka KO, Reiter RJ. Pineal gland “magnetosensitivity” to static magnetic fields is a consequence of induced electric currents (eddy currents). J Pineal Res. 1991;10:109-116 [ Pub Med ]
86. Richardson BA, Yaga K, Reiter RJ, Morton DJ. Pulsed static magnetic field effects on in-vitro pineal indoleamine metabolism. Biochim Biophys Acta. 1992;1137:59-64 [ Pub Med ]
87. Rosen LA, Barber I, Lyle DB. A 0.5 G, 60 Hz magnetic field suppresses melatonin production in pinealocyt.es. Bioelectromagnetics. 1998;19:123-127 [ Pub Med ]
88. Brendel H, Niehaus M, Lerchl A. Direct suppressive effects of weak magnetic fields (50 Hz and 16 2/3 Hz) on melatonin synthesis in the pineal gland of Djungarian hamsters (Phodopus sungorus). J Pineal Res. 2000;29:228-233 [ Pub Med ]
89. Lewy H, Massot O, Touitou Y. Magnetic field (50 Hz) increases N-acetyltransferase, hydroxy-indole-O-methyltransferase activity and melatonin release through an indirect pathway. Int J Radiat Biol. 2003;79:431-435 [ Pub Med ]
90. Tripp HM, Warman GR, Arendt J. Circularly polarised MF (500 micro T 50 Hz) does not acutely suppress melatonin secretion from cultured Wistar rat pineal glands. Bioelectromagnetics. 2003;24:118-124 [ Pub Med ]
91. Liburdy RP, Sloma TR, Sokolic R, Yaswen P. ELF magnetic fields, breast cancer, and melatonin: 60 Hz fields block melatonin's oncostatic action on ER+ breast cancer cell proliferation. J Pineal Res. 1993;14:89-97 [ Pub Med ]
92. Harland JD, Liburdy RP. Environmental magnetic fields inhibit the antiproliferative action of tamoxifen and melatonin in a human breast cancer cell line. Bioelectromagnetics. 1997;18:555-562 [ Pub Med ]
93. Blackman CF, Benane SG, House DE. The influence of 1.2 microT, 60 Hz magnetic fields on melatonin- and tamoxifen-induced inhibition of MCF7 cell growth. Bioelectromagnetics. 2001;22:122-128 [ Pub Med ]
94. Ishido M, Nitta H, Kabuto M. Magnetic fields (MF) of 50 Hz at 1.2 microT as well as 100 microT cause uncoupling of inhibitory pathways of adenylyl cyclase mediated by melatonin 1a receptor in MF-sensitive MCF-7 cells. Carcinogenesis. 2001;22:1043-1048 [ Pub Med ]
95. Leman ES, Sisken BF, Zimmer S, Anderson KW. Studies of the interactions between melatonin and 2 Hz, 0.3 inT PEMF on the proliferation and invasion of human breast cancer cells. Bioelectromagnetics. 2001;22:178-84 [ Pub Med ]
96. Girgert R, Hanf V, Ernons G, Grundker C. Signal transduction of the melatonin receptor MT1 is disrupted in breast cancer cells by electromagnetic fields. Bioelectromagnetics. 2010;31:237-245 [ Pub Med ]
97. Pfluger DH, Minder CE. Effects of exposure to 16.7 Hz magnetic fields on urinary 6-hydroxymelatonin sulfate excretion of Swiss railway workers. J Pineal Res. 1996;21:91-100 [ Pub Med ]
98. Arnetz BB, Berg M. Melatonin and adrenocorticotropic hormone levels in video display unit workers during work and leisure. J Occup Environ Med. 1996;38:1108-1110 [ Pub Med ]
99. Wood AW, Armstrong SM, Sait ML, Devine L, Martin MJ. Changes in human plasma melatonin profiles in response to 50 Hz magnetic field exposure. J Pineal Res. 1998;25:116-127 [ Pub Med ]
100. Burch JB, Reif JS, Yost MG, Keefe TJ, Pitrat CA. Nocturnal excretion of a urinary melatonin metabolite among electric utility workers. ScandJ Work Environ Health. 1998;24:183-189 [ Pub Med ]
101. Burch JB, Reif JS, Yost MG, Keefe TJ, Pitrat CA. Reduced excretion of a melatonin metabolite in workers exposed to 60 Hz magnetic fields. Am J Epidemiol. 1999;150:27-36 [ Pub Med ]
102. Burch JB, Reif JS, Noonan CW, Yost MG. Melatonin metabolite levels in workers exposed to 60-Hz magnetic fields: work in substations and with 3phase conductors. J Occup Environ Med. 2000;42:136-142 [ Pub Med ]
103. Juutilainen J, Stevens RG, Anderson LE, Hansen NH, Kilpelainen M, Kumlin T, Laitinen JT, Sobel E, Wilson BW. Nocturnal 6-hydroxymelatonin sulfate excretion in female workers exposed to magnetic fields. J Pineal Res. 2000;28:97-104 [ Pub Med ]
104. Davis S, Kaune WT, Mirick DK, Chen C, Stevens RG. Residential magnetic fields, light-at-night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women. Am J Epidemiol. 2001;154:591-600 [ Pub Med ]
105. Burch JB, Reif JS, Noonan CW, Ichinose T, Bachand AM, Koleber TL, Yost MG. Melatonin metabolite excretion among cellular telephone users. IntJ Radiat Biol. 2002;78:1029-1036 [ Pub Med ]
106. Davis S, Mirick DK, Chen C, Stanczyk FZ. Effects of 60-Hz magnetic field exposure on nocturnal 6-sulfatoxymelatonin, estrogens, luteinizing hormone, and follicle-stimulating hormone in healthy reproductive-age women: results of a crossover trial. Ann Epidemiol. 2006;16:622-631 [ Pub Med ]
107. Burch JB, Reif JS, Yost MG. Geomagnetic activity and human melatonin metabolite excretion. Neurosci Lett. 2008;438:76-79 [ Pub Med ]
108. Wilson BW, Wright CW, Morris JE, et al. . Evidence for an effect of ELF electromagnetic fields on human pineal gland function. J Pineal Res. 1990;9:259-269 [ Pub Med ]
109. Schiffman JS, Lasch HM, Rollag MD, Flanders AE, Brainard GC, Burk DL Jr. Effect of MR imaging on the normal human pineal body: measurement of plasma melatonin levels. J Magn Reson Imaging. 1994;4:7-11 [ Pub Med ]
110. Selmaoui B, Lambrozo J, Touitou Y. Magnetic fields and pineal function in humans: evaluation of nocturnal acute exposure to extremely low frequency magnetic fields on serum melatonin and urinary 6-sulfatoxymelatonin circadian rhythms. Life Sci. 1996;58:1539-1549 [ Pub Med ]
111. Graham C, Cook MR, Riffle DW, Gerkovich MM, Cohen HD. Nocturnal melatonin levels in human volunteers exposed to intermittent 60 Hz magnetic fields. Bioelectromagnetics. 1996;17:263-273 [ Pub Med ]
112. Graham C, Cook MR, Riffle DW. Human melatonin during continuous magnetic field exposure. Bioelectromagnetics. 1997;18:166-171 [ Pub Med ]
113. Akerstedt T, Arnetz B, Ficca G, Paulsson LE, Kallner A. A 50-Hz electromagnetic field impairs sleep. J Sleep Res. 1999;8:77-81 [ Pub Med ]
114. Graham C, Cook MR, Sastre A, Riffle DW, Gerkovich MM. Multi-night exposure to 60 Hz magnetic fields: effects on melatonin and its enzymatic metabolite. J Pineal Res. 2000;28:1-8 [ Pub Med ]
115. Crasson M, Beckers V, Pequeux C, Claustrat B, Legros JJ. Daytime 50 Hz magnetic field exposure and plasma melatonin and urinary 6-sulfatoxymelatonin concentration profiles in humans. J Pineal Res. 2001;31:234-241 [ Pub Med ]
116. Graham C, Cook MR, Gerkovich MM, Sastre A. Melatonin and 6-OHMS in high-intensity magnetic fields. J Pineal Res. 2001;31:85-88 [ Pub Med ]
117. Graham C, Sastre A, Cook MR, Gerkovich MM. All-night exposure to EMF does not alter urinary melatonin, 6-OHMS or immune measures in older men and women. J Pineal Res. 2001;31:109-113 [ Pub Med ]
118. Griefahn B, Kunemund C, Blaszkewicz M, Golka K, Mehnert P, Degen G. Experiments on the effects of a continuous 16.7 Hz magnetic field on melatonin secretion, core body temperature, and heart rates in humans. Bioelectromagnetics. 2001;22:581-588 [ Pub Med ]
119. Haugsdal B, Tynes T, Rotnes JS, Griffiths D. A single nocturnal exposure to 2-7 millitesla static magnetic fields does not inhibit the excretion of 6sulfatoxymelatonin in healthy young men. Bioelectromagnetics. 2001;22:1-6 [ Pub Med ]
120. Hong SC, Kurokawa Y, Kabuto M, Ohtsuka R. Chronic exposure to ELF magnetic fields during night sleep with electric sheet: effects on diurnal melatonin rhythms in men. Bioelectromagnetics. 2001;22:138-143 [ Pub Med ]
121. Levallois P, Dumont M, Touitou Y, et al. . Effects of electric and magnetic fields from high-power lines on female urinary excretion of 6-sulfatoxymelatonin. Am J Epidemiol. 2001;154:601-609 [ Pub Med ]
122. Griefahn B, Kunemund C, Blaszkewicz M, Golka K, Degen G. Experiments on effects of an intermittent 16.7-Hz magnetic field on salivary melatonin concentrations, rectal temperature, and heart rate in humans. IntArch Occup Environ Health. 2002;75:171-178 [ Pub Med ]
123. Youngstedt SD, Kripke DF, Elliott JA, Assmus JD. No association of 6sulfatoxymelatonin with in-bed 60-Hz magnetic field exposure or illumination level among older adults. Environ Res. 2002;89:201-209 [ Pub Med ]
124. Kurokawa Y, Nitta H, Imai H, Kabuto M. Acute exposure to 50 Hz magnetic fields with harmonics and transient components: lack of effects on nighttime hormonal secretion in men. Bioelectromagnetics. 2003;24:12-20 [ Pub Med ]
125. Touitou Y, Lambrozo J, Camus F, Charbuy H. Magnetic fields and the melatonin hypothesis: a study of workers chronically exposed to 50-Hz magnetic fields. Am J Physiol Regul Integr Cornp Physiol. 2003;284:R1529-R535 [ Pub Med ]
126. arman GR, Tripp H, Warman VL, Arendt J. Acute exposure to circularly polarized 50-Hz magnetic fields of 200-300 microT does not affect the pattern of melatonin secretion in young men. J Clin Endocrinol Metab. 2003;88:5668-5673 [ Pub Med ]
127. Cocco P, Cocco ME, Paghi L, et al. . Urinary 6-sulfatoxymelatonin excretion in humans during domestic exposure to 50 hertz electromagnetic fields. Neuro Endocrinol Lett. 2005;26:136-142 [ Pub Med ]
128. Gobba F, Bravo G, Scaringi M, Roccatto L. No association between occupational exposure to ELF magnetic field and urinary 6-sulfatoximelatonin in workers. Bioelectromagnetics. 2006;27:667-673 [ Pub Med ]
129. Juutilainen J, Kumlin T. Occupational magnetic field exposure and melatonin: interaction with light-at-night. Bioelectromagnetics. 2006;27:423-426 [ Pub Med ]
130. Clark ML, Burch JB, Yost MG, et al. . Biomonitoring of estrogen and melatonin metabolites among women residing near radio and television broadcasting transmitters. J Occup Environ Med. 2007;49:1149-1156 [ Pub Med ]
131. Free MJ, Kaune WT, Phillips RD, Cheng HC. Endocrinological effects of strong 60-Hz electric fields on rats. Bioelectromagnetics. 1981;2:105-121 [ Pub Med ]
132. Quinlan WJ, Petrondas D, Lebda N, Pettit S, Michaelson SM. Neuroendocrine parameters in the rat exposed to 60-Hz electric fields. Bioelectromagnetics. 1985;6:381-389 [ Pub Med ]
133. Portet R, Cabanes J. Development of young rats and rabbits exposed to a strong electric field. Bioelectromagnetics. 1988;9:95-104 [ Pub Med ]
134. Thompson JM, Stormshak F, LeeJM Jr, Hess DL, Painter L. Cortisol secretion and growth in ewe lambs chronically exposed to electric and magnetic fields of a 60-Hertz 500-kilovolt AC transmission line. J Anim Sci. 1995;73:3274-3280 [ Pub Med ]
135. Burchard JF, Nguyen DH, Richard L, Block E. Biological effects of electric and magnetic fields on productivity of dairy cows. J Dairy Sci. 1996;79:1549-1554 [ Pub Med ]
136. Szemerszky R, Zelena D, Barna I, Bardos G. Stress-related endocrinological and psychopathological effects of short- and long-term 50Hz electromagnetic field exposure in rats. Brain Res Bull. 2010;81:92-99 [ Pub Med ]
137. Martinez-Samano J, Torres-Duran PV, Juarez-Oropeza MA, VerdugoDiaz L. Effect of acute extremely low frequency electromagnetic field exposure on the antioxidant status and lipid levels in rat brain. Arch Med Res. 2012. Epub ahead of print. 2012.04.003.
138. Hackman RM, Graves HB. Corticosterone levels in mice exposed to highintensity electric fields. Behav Neural Biol. 1981;32:201-213 [ Pub Med ]
139. Gorczynska E, Wegrzynowicz R. Glucose homeostasis in rats exposed to magnetic fields. Invest Radiol. 1991;26:1095-1100 [ Pub Med ]
140. Gorczynska E, Wegrzynowicz R. Structural and functional changes in organelles of liver cells in rats exposed to magnetic fields. Environ Res. 1991;55:188-198 [ Pub Med ]
141. de Bruyn L, de Jager L. Electric field exposure and evidence of stress in mice. Environ Res. 1994;65:149-160 [ Pub Med ]
142. Picazo ML, Miguel MP, Romo MA, Varela L, Franco P, Gianonatti C, Bardasano JL. Changes in mouse adrenalin gland functionality under second-generation chronic exposure to ELF magnetic fields. I. males. Electro Magnetobiol. 1996;15:85-98 [ Pub Med ]
143. Marino AA, Wolcott RM, Chervenak R, et al. . Coincident nonlinear changes in the endocrine and immune systems due to low-frequency magnetic fields. Neuroimmunomodulation. 2001;9:65-77 [ Pub Med ]
144. Mostafa RM, Mostafa YM, Ennaceur A. Effects of exposure to extremely low-frequency magnetic field of 2 G intensity on memory and corticosterone level in rats. Physiol Behav. 2002;76:589-595 [ Pub Med ]
145. Bonhomme-Faivre L, Mace A, Bezie Y, et al. . Alterations of biological parameters in mice chronically exposed to low-frequency (50 Hz) electromagnetic fields. Life Sci. 1998;62:1271-1280 [ Pub Med ]
146. Maresh CM, Cook MR, Cohen HD, Graham C, Gunn WS. Exercise testing in the evaluation of human responses to powerline frequency fields. Aviat Space Environ Med. 1988;59:1139-1145 [ Pub Med ]
147. Gamberale F, Olson BA, Eneroth P, Lindh T, Wennberg A. Acute effects of ELF electromagnetic fields: a field study of linesmen working with 400 kV power lines. BrJIndMed. 1989;46:729-737 [ Pub Med ]
148. Selmaoui B, Lambrozo J, Touitou Y. Endocrine functions in young men exposed for one night to a 50-Hz magnetic field. A circadian study of pituitary, thyroid and adrenocortical hormones. Life Sci. 1997;61:473-486 [ Pub Med ]
149. Ghione S, Del Seppia C, Mezzasalma L, Emdin M, Luschi P. Human head exposure to a 37 Hz electromagnetic field: effects on blood pressure, somatosensory perception, and related parameters. Bioelectromagnetics. 2004;25:167-175 [ Pub Med ]
150. Blankenburg M, Haberland L, Elvers HD, Tannert C, Jandrig B. Highthroughput omics technologies: potential tools for the investigation of influences of EMF on biological systems. Curr Genomics. 2009;10:86-92 [ Pub Med ]
151. Girgert R, Grundker C, Emons G, VHant V. Electromagnetic fields alter the expression of estrogen receptor cofactors in breast cancer cells. Bioelectromagnetics. 2008;29:169-176 [ Pub Med ]
152. Wilson BW, Matt KS, Morris JE, Sasser LB, Miller DL, Anderson LE. Effects of 60 Hz magnetic field exposure on the pineal and hypothalamicpituitary-gonadal axis in the Siberian hamster (Phodopus sungorus). Bioelectromagnetics. 1999;20:224-232 [ Pub Med ]