Pineal melatonin level disruption in humans due to electromagnetic fields and ICNIRP limits.

The International Agency for Research on Cancer (IARC) classifies electromagnetic fields (EMFs) as 'possibly carcinogenic' to humans that might transform normal cells into cancer cells. Owing to high utilisation of electricity in day-to-day life, exposure to power-frequency (50 or 60 Hz) EMFs is unavoidable. Melatonin is a natural hormone produced by pineal gland activity in the brain that regulates the body's sleep-wake cycle. How man-made EMFs may influence the pineal gland is still unsolved. The pineal gland is likely to sense EMFs as light but, as a consequence, may decrease the melatonin production. In this study, more than one hundred experimental data of human and animal studies of changes in melatonin levels due to power-frequency electric and magnetic fields exposure were analysed. Then, the results of this study were compared with the International Committee of Non-Ionizing Radiation Protection (ICNIRP) limit and also with the existing experimental results in the literature for the biological effect of magnetic fields, in order to quantify the effects. The results show that this comparison does not seem to be consistent despite the fact that it offers an advantage of drawing attention to the importance of the exposure limits to weak EMFs. In addition to those inconsistent results, the following were also observedfrom this work: (i) the ICNIRP recommendations are meant for the well-known acute effects, because effects of the exposure duration cannot be considered and (ii) the significance of not replicating the existing experimental studies is another limitation in the power-frequency EMFs. Regardless of these issues, the above observation agrees with our earlier study in which it was confirmed that it is not a reliable method to characterise biological effects by observing only the ratio of AC magnetic field strength to frequency. This is because exposure duration does not include the ICNIRP limit. Furthermore, the results show the significance of disruption of melatonin due to exposure to weak EMFs, which may possibly lead to long-term health effects in humans.

[1]  S. Michaelson,et al.  Electric field exposure alters serum melatonin but not pineal melatonin synthesis in male rats. , 1994, Bioelectromagnetics.

[2]  S. Armstrong.  Melatonin and circadian control in mammals , 1989, Experientia.

[3]  M. Papp,et al.  Effects of melatonin in a place preference conditioning depend on the time of administration , 2010, Pharmacological reports : PR.

[4]  Priyan Mendis,et al.  Measurement and analysis of electromagnetic fields from trams, trains and hybrid cars. , 2010, Radiation protection dosimetry.

[5]  M. Mirmiran,et al.  Development of fetal and neonatal sleep and circadian rhythms. , 2003, Sleep medicine reviews.

[6]  M Feychting,et al.  A pooled analysis of magnetic fields and childhood leukaemia , 2000, British Journal of Cancer.

[7]  T. Shigemitsu,et al.  Horizontal or vertical 50-Hz, 1-μT magnetic fields have no effect on pineal gland or plasma melatonin concentration of albino rats , 1994, Neuroscience Letters.

[8]  T. Shigemitsu,et al.  Circularly polarized 50-Hz magnetic field exposure reduces pineal gland and blood melatonin concentrations of Long-Evans rats , 1994, Neuroscience Letters.

[9]  D. Cardinali,et al.  Effects of melatonin in elderly patients with sleep disturbance: a pilot study , 1997 .

[10]  J. Herman,et al.  The development of circadian rhythms in a human infant. , 1999, Sleep.

[11]  Con Stough,et al.  Does evening exposure to mobile phone radiation affect subsequent melatonin production? , 2006, International journal of radiation biology.

[12]  P. Lavie,et al.  Melatonin replacement therapy of elderly insomniacs. , 1995, Sleep.

[13]  J. Reif,et al.  Reduced excretion of a melatonin metabolite in workers exposed to 60 Hz magnetic fields. , 1999, American journal of epidemiology.

[14]  Vijayalaxmi,et al.  Melatonin: from basic research to cancer treatment clinics. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  P. Polychronopoulos,et al.  Chronotypology and melatonin alterations in minimal hepatic encephalopathy , 2009, Journal of circadian rhythms.

[16]  Robert Kavet,et al.  The relationship between electromagnetic field and light exposures to melatonin and breast cancer risk: A review of the relevant literature , 1999, Journal of pineal research.

[17]  N. Wertheimer,et al.  Adult cancer related to electrical wires near the home. , 1982, International journal of epidemiology.

[18]  S. Daniels,et al.  Blood pressure‐lowering effect of melatonin in type 1 diabetes , 2004, Journal of pineal research.

[19]  Pawel Majewski,et al.  Bidirectional communication between the pineal gland and the immune system. , 2003, Canadian journal of physiology and pharmacology.

[20]  C E Minder,et al.  Effects of exposure to 16.7 Hz magnetic fields on urinary 6‐hydroxymelatonin sulfate excretion of Swiss railway workers , 1996, Journal of pineal research.

[21]  R. Wurtman,et al.  Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Penafiel,et al.  The effect of pulsed and sinusoidal magnetic fields on the morphology of developing chick embryos. , 1997, Bioelectromagnetics.

[23]  B Claustrat,et al.  Daytime 50 Hz magnetic field exposure and plasma melatonin and urinary 6‐sulfatoxymelatonin concentration profiles in humans , 2001, Journal of pineal research.

[24]  R. Stevens,et al.  Inverse association between breast cancer incidence and degree of visual impairment in Finland , 1999, British Journal of Cancer.

[25]  Vijayalaxmi,et al.  Melatonin and radioprotection from genetic damage: in vivo/in vitro studies with human volunteers. , 1996, Mutation research.

[26]  M R Cook,et al.  Human melatonin during continuous magnetic field exposure. , 1997, Bioelectromagnetics.

[27]  W T Kaune,et al.  Residential magnetic fields, light-at-night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women. , 2001, American journal of epidemiology.

[28]  J. Reif,et al.  Melatonin metabolite levels in workers exposed to 60-Hz magnetic fields: work in substations and with 3-phase conductors. , 2000, Journal of occupational and environmental medicine.

[29]  D. House,et al.  Effect of ac and dc magnetic field orientation on nerve cells. , 1996, Biochemical and biophysical research communications.

[30]  Simona Negro,et al.  Is newborn melatonin production influenced by magnetic fields produced by incubators? , 2012, Early human development.

[31]  D. A. Chathurika,et al.  Analysis of biological effects and limits of exposure to weak magnetic fields , 2010, 2010 Fifth International Conference on Information and Automation for Sustainability.

[32]  Yasutaka Osada,et al.  Residental magnetic fields, light-at-night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women. Davis, S., Kaune, W.T., Mirick, D. K., Chen, C., and Stevens, R.G.: Am. J. Epidemiol., 154(7): 591-600, 2001.(Abstracts of foreign literature) , 2002 .

[33]  R. Reiter,et al.  A review of the multiple actions of melatonin on the immune system , 2005, Endocrine.

[34]  D. Kennaway,et al.  PLASMA MELATONIN LEVELS , 2005 .

[35]  W. Löscher,et al.  Magnetic field exposure increases cell proliferation but does not affect melatonin levels in the mammary gland of female Sprague Dawley rats. , 2002, Cancer research.

[36]  R. Reiter,et al.  Neurotoxins: Free Radical Mechanisms and Melatonin Protection , 2010, Current neuropharmacology.

[37]  Parviz Abdolmaleki,et al.  Comparing performances of logistic regression and neural networks for predicting melatonin excretion patterns in the rat exposed to ELF magnetic fields , 2009, Bioelectromagnetics.

[38]  C. Graham,et al.  All‐night exposure to EMF does not alter urinary melatonin, 6‐OHMS or immune measures in older men and women , 2001, Journal of pineal research.

[39]  R. Reiter,et al.  Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: Two years' experience , 1997, Journal of pineal research.

[40]  M R Cook,et al.  Examination of the melatonin hypothesis in women exposed at night to EMF or bright light. , 2001, Environmental health perspectives.

[41]  M. Peres,et al.  Melatonin in the Preventive Treatment of Chronic Cluster Headache , 2001, Cephalalgia : an international journal of headache.

[42]  V. V. Novikov,et al.  Effect of weak combined static and extremely low‐frequency alternating magnetic fields on tumor growth in mice inoculated with the Ehrlich ascites carcinoma , 2009, Bioelectromagnetics.

[43]  L. Brusco,et al.  Possible therapeutic value of melatonin in mild cognitive impairment: a retrospective study , 2007, Journal of pineal research.

[44]  R. Hahn,et al.  Profound bilateral blindness and the incidence of breast cancer. , 1991, Epidemiology.

[45]  M. Azarnia,et al.  PROTECTIVE EFFECT OF MELATONIN ON SPINAL CORD DAMAGE AFTER GAMMA IRRADIATION , 2009 .

[46]  Masamichi Kato,et al.  Effects of exposure to a circularly polarized 50-Hz magnetic field on plasma and pineal melatonin levels in rats. , 1993, Bioelectromagnetics.

[47]  Vijayalaxmi,et al.  Melatonin and protection from whole-body irradiation: survival studies in mice. , 1999, Mutation research.

[48]  Francine Laden,et al.  Epidemiology of urinary melatonin in women and its relation to other hormones and night work. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[49]  A. Swerdlow.  Shift work and breast cancer : a critical review of the epidemiological evidence , 2003 .

[50]  L. Chacón.  50-Hz SINUSOIDAL MAGNETIC FIELD EFFECT ON IN VITRO PINEAL N-ACETYLTRANSFERASE ACTIVITY , 2000 .

[51]  F. Fraschini,et al.  Melatonin Versus Placebo in the Prophylaxis of Cluster Headache , 1996, Cephalalgia : an international journal of headache.

[52]  R. Reiter,et al.  Do magnetic fields cause increased risk of childhood leukemia via melatonin disruption? , 2005, Bioelectromagnetics.

[53]  J. Trinder,et al.  Inhibition of melatonin secretion onset by low levels of illumination , 1996, Journal of sleep research.

[54]  J. Reif,et al.  Nocturnal excretion of a urinary melatonin metabolite among electric utility workers. , 1998, Scandinavian journal of work, environment & health.

[55]  Masamichi Kato,et al.  Recovery of nocturnal melatonin concentration takes place within one week following cessation of 50 Hz circularly polarized magnetic field exposure for six weeks. , 1994, Bioelectromagnetics.

[56]  N. Wertheimer,et al.  Electrical wiring configurations and childhood cancer. , 1979, American journal of epidemiology.

[57]  H. Ra.  Does blindness protect against cancers , 1998 .

[58]  Y. Touitou,et al.  Is Melatonin the Hormonal Missing Link Between Magnetic Field Effects and Human Diseases? , 2006, Cancer Causes & Control.

[59]  Malka N. Halgamuge,et al.  Comparison Between Two Models for Interactions Between Electric and Magnetic Fields and Proteins in Cell Membranes , 2009 .

[60]  Malka N. Halgamuge,et al.  Behavior of Charged Particles in a Biological Cell Exposed to AC-DC Electromagnetic Fields , 2011 .

[61]  K. Anderson,et al.  REM sleep behaviour disorder treated with melatonin in a patient with Alzheimer's disease , 2008, Clinical Neurology and Neurosurgery.

[62]  J. Bakos,et al.  One week of exposure to 50 Hz, vertical magnetic field does not reduce urinary 6‐sulphatoxymelatonin excretion of male wistar rats , 2002, Bioelectromagnetics.

[63]  R. Stevens,et al.  Electric power use and breast cancer: a hypothesis. , 1987, American journal of epidemiology.

[64]  J. Parkes,et al.  Delayed sleep phase syndrome response to melatonin , 1991, The Lancet.

[65]  M. Nazıroğlu,et al.  Melatonin modulates wireless (2.45GHz)-induced oxidative injury through TRPM2 and voltage gated Ca2+ channels in brain and dorsal root ganglion in rat , 2012, Physiology & Behavior.

[66]  W. Löscher,et al.  Study on pineal function and DMBA-induced breast cancer formation in rats during exposure to a 100-mG, 50 Hz magnetic field. , 1996, Journal of toxicology and environmental health.

[67]  K. H. Mild,et al.  Chromosomal aberrations in peripheral lymphocytes of train engine drivers , 2001, Bioelectromagnetics.

[68]  Malka N. Halgamuge,et al.  Reply to Comment on “Behavior of Charged Particles in a Biological Cell Exposed to AC-DC Electromagnetic Fields” and on “Comparison Between Two Models of Interaction Between Electric and Magnetic Fields and Proteins in Cell Membranes” , 2011 .

[69]  L. E. Anderson,et al.  Nocturnal 6‐hydroxymelatonin sulfate excretion in female workers exposed to magnetic fields , 2000, Journal of pineal research.

[70]  G. Bubenik,et al.  Melatonin and aging: prospects for human treatment. , 2011, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[71]  Benita Middleton,et al.  Measuring melatonin in humans. , 2008, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[72]  P. Semm.  Pineal Function in Mammals and Birds is Altered by Earth-Strength Magnetic Fields , 1992 .

[73]  R Ohtsuka,et al.  Chronic exposure to ELF magnetic fields during night sleep with electric sheet: effects on diurnal melatonin rhythms in men. , 2001, Bioelectromagnetics.

[74]  G. Brown,et al.  60 Hz magnetic field exposure and urinary 6-sulphatoxymelatonin levels in the rat. , 1998, Bioelectromagnetics.

[75]  P. Lissoni,et al.  Enhancement of the efficacy of cancer chemotherapy by the pineal hormone melatonin and its relation with the psychospiritual status of cancer patients , 2010, Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.

[76]  Y. Touitou,et al.  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. , 1996, Life sciences.

[77]  H. Wachtel,et al.  Case-control study of childhood cancer and exposure to 60-Hz magnetic fields. , 1988, American journal of epidemiology.

[78]  P. Konturek,et al.  The pilot study of 3-month course of melatonin treatment of patients with nonalcoholic steatohepatitis: effect on plasma levels of liver enzymes, lipids and melatonin. , 2010, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[79]  J. Hansen,et al.  Light at night, shiftwork, and breast cancer risk. , 2001, Journal of the National Cancer Institute.

[80]  R. Wurtman,et al.  Improvement of sleep quality by melatonin , 1995, The Lancet.

[81]  M Feychting,et al.  Reduced Cancer Incidence among the Blind , 1998, Epidemiology.

[82]  L. E. Anderson,et al.  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. , 1988, Life sciences.

[83]  K. Borowicz,et al.  Melatonin in experimental seizures and epilepsy , 2011, Pharmacological reports : PR.

[84]  H D Cohen,et al.  Nocturnal melatonin levels in human volunteers exposed to intermittent 60 Hz magnetic fields. , 1996, Bioelectromagnetics.

[85]  K. Jokela,et al.  ICNIRP Guidelines GUIDELINES FOR LIMITING EXPOSURE TO TIME-VARYING , 1998 .

[86]  J. Bakos,et al.  Urinary 6-Sulphatoxymelatonin Excretion of Rats is not Changed by 24 Hours of Exposure to A Horizontal 50-HZ, 100-μT Magnetic Field , 1999 .

[87]  R D Phillips,et al.  Chronic exposure to 60-Hz electric fields: effects on pineal function in the rat. , 1981, Bioelectromagnetics.

[88]  D Stratakis,et al.  On the uncertainty estimation of electromagnetic field measurements using field sensors: a general approach. , 2009, Radiation protection dosimetry.

[89]  John A. Robertson,et al.  Light alters nociceptive effects of magnetic field shielding in mice: intensity and wavelength considerations , 2009, Journal of The Royal Society Interface.

[90]  N. Zisapel,et al.  Improvement of sleep quality in elderly people by controlled-release melatonin , 1995, The Lancet.

[91]  J. Bakos,et al.  Urinary 6-sulphatoxymelatonin excretion is increased in rats after 24 hours of exposure to vertical 50 Hz, 100 microT magnetic field. , 1997, Bioelectromagnetics.

[92]  H. Shinohara,et al.  Relationship between circadian salivary melatonin levels and sleep–wake behavior in infants , 2011, Pediatrics international : official journal of the Japan Pediatric Society.

[93]  R. Reiter,et al.  Melatonin Suppression by Static and Extremely Low Frequency Electromagnetic Fields: Relationship to the Reported Increased Incidence of Cancer , 1994, Reviews on environmental health.

[94]  A. Wood,et al.  Effects of 50 Hz magnetic fields on human physiology: plasma melatonin levels , 1998, Proceedings of the 2nd International Conference on Bioelectromagnetism (Cat. No.98TH8269).

[95]  L. E. Anderson,et al.  Evidence for an Effect of ELF Electromagnetic Fields on Human Pineal Gland Function , 1990, Journal of pineal research.

[96]  L. E. Anderson,et al.  60-Hz electric-field effects on pineal melatonin rhythms: time course for onset and recovery. , 1986, Bioelectromagnetics.

[97]  P. Torrigiani,et al.  Extremely low frequency weak magnetic fields enhance resistance of NN tobacco plants to tobacco mosaic virus and elicit stress‐related biochemical activities , 2007, Bioelectromagnetics.

[98]  Richard G. Stevens,et al.  Relation between residential magnetic fields, light-at-night, and nocturnal urine melatonin levels in women: Volume 1 -- Background and purpose, methods, results, discussion. Final report , 1997 .

[99]  Scott Davis,et al.  Residential magnetic fields and the risk of breast cancer. , 2002, American journal of epidemiology.

[100]  M. Bourdages,et al.  Effects of electric and magnetic fields from high-power lines on female urinary excretion of 6-sulfatoxymelatonin. , 2001, American journal of epidemiology.

[101]  M. Persinger.  Differential Numbers of Foci of Lymphocytes Within the Brains of Lewis Rats Exposed to Weak Complex Nocturnal Magnetic Fields During Development of Experimental Allergic Encephalomyelitis , 2009, The International journal of neuroscience.

[102]  O. Gandhi.  Biological effects and medical applications of electromagnetic energy , 1990 .

[103]  Y. Touitou,et al.  Age-related differences in serum melatonin and pineal NAT activity and in the response of rat pineal to a 50-Hz magnetic field. , 1999, Life sciences.

[104]  Jacques Lambrozo,et al.  Magnetic fields and the melatonin hypothesis: a study of workers chronically exposed to 50-Hz magnetic fields. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[105]  Adair,et al.  Constraints on biological effects of weak extremely-low-frequency electromagnetic fields. , 1991, Physical review. A, Atomic, molecular, and optical physics.

[106]  K. Kugiyama,et al.  Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men. , 2001, American heart journal.

[107]  W. Löscher,et al.  Exposure of DMBA-treated female rats in a 50-Hz, 50 microTesla magnetic field: effects on mammary tumor growth, melatonin levels, and T lymphocyte activation. , 1996, Carcinogenesis.

[108]  P. Zee,et al.  Treatment of Shift Work Disorder and Jet Lag , 2010, Current treatment options in neurology.

[109]  D. B. Lyle,et al.  A 0.5 G, 60 Hz magnetic field suppresses melatonin production in pinealocytes. , 1998, Bioelectromagnetics.

[110]  J. Reif,et al.  Melatonin metabolite excretion among cellular telephone users , 2002, International journal of radiation biology.

[111]  Stephen D. Gedney,et al.  High-Order NystrÖm Solution of the Volume - EFIE for TE-Wave Scattering , 2001 .

[112]  J. S. Røtnes,et al.  A single nocturnal exposure to 2-7 millitesla static magnetic fields does not inhibit the excretion of 6-sulfatoxymelatonin in healthy young men. , 2001, Bioelectromagnetics.

[113]  D. House,et al.  The influence of 1.2 microT, 60 Hz magnetic fields on melatonin- and tamoxifen-induced inhibition of MCF-7 cell growth. , 2001, Bioelectromagnetics.

[114]  Eka Swadiansa.  The hypothesis , 1990 .

[115]  V. Lednev,et al.  The influence of extremely weak alternating magnetic fields on the regeneration of planarians and the gravitropic response of plants , 2010 .

[116]  J. Bakos,et al.  Sinusoidal 50 Hz, 500 microT magnetic field has no acute effect on urinary 6-sulphatoxymelatonin in Wistar rats. , 1995, Bioelectromagnetics.

[117]  B. Arnetz,et al.  Melatonin and adrenocorticotropic hormone levels in video display unit workers during work and leisure. , 1996, Journal of occupational and environmental medicine.

[118]  Y. Touitou,et al.  Sinusoidal 50-Hz magnetic fields depress rat pineal NAT activity and serum melatonin. Role of duration and intensity of exposure. , 1995, Life sciences.

[119]  A. Wakatsuki,et al.  Maternal‐fetal transfer of melatonin in pregnant women near term , 1998, Journal of pineal research.

[120]  D. Tan.  Melatonin and Brain , 2010, Current neuropharmacology.

[121]  J. Arendt,et al.  Circularly polarised MF (500 μT 50 Hz) does not acutely suppress melatonin secretion from cultured Wistar rat pineal glands , 2003, Bioelectromagnetics.

[122]  H. Ehrenreich,et al.  Melatonin as a candidate compound for neuroprotection in amyotrophic lateral sclerosis (ALS): high tolerability of daily oral melatonin administration in ALS patients , 2002, Journal of pineal research.

[123]  H. Pons,et al.  Melatonin protects mice infected with Venezuelan equine encephalomyelitis virus , 1997, Cellular and Molecular Life Sciences CMLS.

[124]  Charles Graham,et al.  Multi‐night exposure to 60 Hz magnetic fields: Effects on melatonin and its enzymatic metabolite , 2000, Journal of pineal research.

[125]  D. House,et al.  Frequency-dependent interference by magnetic fields of nerve growth factor-induced neurite outgrowth in PC-12 cells. , 1995, Bioelectromagnetics.

[126]  Jerome CJ Fryer.  Is a purpose of REM sleep atonia to help regenerate intervertebral disc volumetric loss? , 2009, Journal of circadian rhythms.

[127]  J. Reif,et al.  Geomagnetic disturbances are associated with reduced nocturnal excretion of a melatonin metabolite in humans , 1999, Neuroscience Letters.

[128]  D. Cardinali,et al.  Time-dependent melatonin analgesia in mice: inhibition by opiate or benzodiazepine antagonism. , 1991, European journal of pharmacology.