Assessment of Health Effects from
Exposure to Power-Line Frequency
Electric and Magnetic Fields
Working Group Report**This report represents the views and expert opinions of the Working Group
which met in Brooklyn Park, Minnesota, 16-24 June 1998

The Working Group was organized by the NIEHS with support of the
EMF Research and Public Information Dissemination (EMFRAPID) Program throughthe
United States Department of Energy
and theNational Institute of Environmental Health Sciences/National Institutes of HealthChristopher J. Portier, Ph.D.
Mary S. Wolfe, Ph.D.
EditorsNational Institute of Environmental Health Sciences
U.S. National Institutes of Health
U.S. Department of Health and Human Services, Public Health Service
PO Box 12233
Research Triangle Park, NC 27709
NIH Publication No. 98-3981
Printed in the United States of America
August 1998

This report is available at the NIEHS EMFRAPID Program world-wide-website:www.niehs.nih.gov/emfrapid/home.htm and in hard copy or CD-ROM on request by
mail: EMFRAPID Program/LCBRA, NIEHS, NIH, PO Box 12233, MD A3-06,
Research Triangle Park, NC 27709; by fax: 919-541-1479; or by e-mail: emfrapid@niehs.nih.gov

Preface
The National Institute of Environmental Health Sciences was charged by
Congress to prepare and submit an evaluation of the potential human healtheffects from exposure to extremely low frequency electric and magnetic fields(ELF EMF). To evaluate the quality of the science and the strength of theevidence on EMF, the NIEHS organized a comprehensive review of the data
which included three science symposia and a working group meeting. The goal of
the Working Group meeting was to perform a critical review and evaluation of
the research data on ELF EMF exposures and potential biological and/or healtheffects.
Scientists both within and outside of EMF research were selected as members of
the Working Group representing a wide range of disciplines including,engineering, epidemiology, cellular and molecular biology, medicine,mathematics, neurobiology, pathology, physics, statistics, and toxicology. This
diversity helped to ensure a cross-disciplinary discussion of the experimental
findings and broad scientific perspective.
The Working Group Report presented here draws conclusions on the strengthand robustness of the experimental data related to ELF EMF and its
implications for human health and disease etiology. The summaries used todefine the strength of the evidence in any one area have definitions which, toproperly understand the report, should be read carefully (Appendix A). The
Report was completed during the 16-24 June 1998 meeting in Brooklyn Park,
Minnesota and the information contained within this report reflects thedeliberations and discussions of the Group. Following the meeting, the Report
was reviewed and edited by a science writer for clarity and put into a common
format. Systeme International (SI) units are used throughout the document.
Some attempt was made to check the accuracy of references and data prior to
the Report being printed; however, there was only limited time for this prior to
its release to the public so there are likely to be some minor technical errors
within the document.
The deliberations and summarization of the scientific data regarding possible
health effects from exposure to ELF EMF are critical to the NIEHSÕ hazard
evaluation project. This document represents the first step in a risk assessment
for potential health effects of ELF EMF in human populations. The final
categorizations represent strength of the evidence for a hazard and do not reflect
the degree of that hazard. While there is no short summary of the results, thefinal discussions in Chapter 5 are sufficiently short and informative to give someindication of the overall strength of this evidence. The only way a reader can beiiicertain they understand these decisions is to read the appropriate sections in thebook.
Preparation of the Working Group Report in a nine-day period was amonumental undertaking. There was a vast literature to cover in a short period,
and the members responded to this challenge with diligence and long hours. The
30 members of the Working Group contributed approximately 1200 personhours prior to the meeting and 3000 person-hours while at the meeting. Adding
to this, the contribution of NIEHS staff and contractors shows that the
document represents approximately 3 person-years of effort focused on thisproblem in a very short period. This effort was greatly enhanced by thesummaries from the three science symposia which would add another 4 personyears to this effort.
We wish to thank the members of the Working Group for their contributions to
the meeting, their dedication, and their open-minded approach to preparation of
the report. We greatly appreciate the efforts of the participants in the science
symposia who highlighted areas of concerns and identified key research findings
for the Working Group. We also wish to thank the staff and contractors of the
EMFRAPID Program for their technical support in preparation of the report.
Finally, we also wish to thank our families and friends who have shown us
continuing support throughout this effort.
Mary S. Wolfe, Ph.D.
Christopher J. Portier, Ph.D.
Research Triangle Park, North Carolina, USA
July 24, 1998

iv

Contents
PARTICIPANTS ..............................................................................................................1
1 INTRODUCTION ........................................................................................................7
2 OCCURRENCE AND MEASUREMENT OF EXTREMELY LOWFREQUENCY ELECTROMAGNETIC FIELDS ........................................................92.1 What are electromagnetic fields? ...........................................................................9
2.2 Measurements, unit conventions, and sources....................................................14
2.3 Exposure assessment...........................................................................................172.3.1 Instrumentation..........................................................................................172.3.2 Exposure metrics........................................................................................192.3.3 Exposure environments..............................................................................222.3.4 Exposure assessment for epidemiological studies......................................23
2.4 Occupational exposure........................................................................................24
2.4.1 General occupational environments ...........................................................24
2.4.2 Visual display terminal operators ..............................................................31
2.5 Residential exposure............................................................................................32
2.5.1 Direct measurements..................................................................................33
2.5.2 Calculated historical fields..........................................................................39
2.5.3 Wire codes as an exposure surrogate..........................................................42
2.6 Exposure in transport..........................................................................................43
2.7 Exposure in schools.............................................................................................44
2.8 Exposure from appliances...................................................................................45
2.9 Laboratory exposure systems.............................................................................47
2.10 Summary ...........................................................................................................49
3 INTERNAL DOSIMETRY.........................................................................................79
3.1 Electric field dosimetry for human exposure.......................................................79
3.2 Low-frequency magnetic field dosimetry............................................................80
3.2.1 Magnetic fields induced in the body by external magnetic fields...............80
3.2.2 Magnetic fields induced in the body by external magnetic fields...............80
3.3 Scaling between different organisms, assuming that an observed effect isdue to induced electric fields ...............................................................................81
3.4 Considerations for in vitro dosimetry................................................................82
3.4.1 Electric field dosimetry ..............................................................................82
3.4.2 Magnetic field dosimetry ...........................................................................83
3.5 Summary ............................................................................................................83
4 BIOLOGICAL DATA RELATING TO THE TOXICITY OF EXTREMELY
LOW-FREQUENCY ELECTROMAGNETIC FIELDS............................................85
4.1 Carcinogenicity in animals...................................................................................85
4.1.1 One- and two-year bioassays.....................................................................86v

4.1.2 Multistep carcinogenesis............................................................................89
4.1.2.1 Mammary Cancer..............................................................................89
4.1.2.2 Skin tumor models.............................................................................95
4.1.2.3 Liver cancer models...........................................................................98
4.1.2.4 Leukemia/lymphoma model ..............................................................98
4.1.3 Summary ..................................................................................................101
4.2 Epidemiological studies of carcinogenicity in adults.........................................107
4.2.1 Occupational exposure.............................................................................1084.2.1.1 All cancers combined.......................................................................109
4.2.1.2 Leukemia .........................................................................................111
4.2.1.3 Brain cancer.....................................................................................117
4.2.1.4 Breast cancer ...................................................................................1194.2.1.5 Lung cancer......................................................................................123
4.2.1.6 Other cancers...................................................................................124
4.2.1.7 Central nervous system cancers in the offspring of parents
exposed to electromagnetic fields....................................................125
4.2.1.8 Meta-analyses of brain cancer and leukemia...................................127
4.2.1.9 Summary .........................................................................................129
4.2.2 Residential exposure.................................................................................133
4.2.2.1 All cancers.......................................................................................133
4.2.2.2 Leukemia .........................................................................................134
4.2.2.3 Breast cancer ...................................................................................140
4.2.2.4 Tumors of the central nervous system............................................143
4.2.2.5 Summary .........................................................................................144
4.3 Epidemiological studies of carcinogenicity in children......................................167
4.3.1 Effects of power lines ..............................................................................167
4.3.2 Effects of appliances................................................................................178
4.3.3 Meta-analyses of studies of effects of power lines .................................183
4.3.4 Summary .................................................................................................184
4.4 Non-cancer health effects in experimental animals............................................209
4.4.1 Immunological effects...............................................................................209
4.4.1.1 Magnetic and electric fields.............................................................209
4.4.1.2 Magnetic fields................................................................................210
4.4.1.3 Magnetic fields and 7,12-dimethylbenz[a]anthracene ....................211
4.4.1.4 Summary .........................................................................................212
4.4.2 Hematological effects ...............................................................................216
4.4.2.1 Magnetic and electric fields.............................................................216
4.4.2.2 Summary .........................................................................................217
4.4.3 Effects on the nervous system.................................................................217
4.4.3.1 Field detection.................................................................................217
4.4.3.2 Avoidance and aversion...................................................................218
4.4.3.3 Learning and performance ...............................................................2214.4.3.4 Neurophysiology ............................................................................224
4.4.3.5 Electrophysiology...........................................................................227
4.4.3.6 Summary .........................................................................................229
4.4.4 Reproductive and developmental effects .................................................237vi

4.4.4.1 Birds................................................................................................237
4.4.4.2 Mice ................................................................................................238
4.4.4.3 Rats .................................................................................................239
4.4.4.4 Hamsters .........................................................................................240
4.4.4.5 Summary .........................................................................................240
4.4.5 Effects on melatonin.................................................................................244
4.4.5.1 Electric fields...................................................................................244
4.4.5.2 Exposure to magnetic fields for < 1 h..............................................245
4.4.5.3 Exposure to magnetic fields for 1Ð24 h...........................................247
4.4.5.4 Exposure to magnetic fields for > 24 h............................................248
4.4.5.5 Exposure to electric and magnetic fields..........................................251
4.4.5.6 Summary .........................................................................................251
4.4.6 Bone and tissue repair and adaptation .....................................................256
4.4.6.1 Clinical bone healing with pulsed electromagnetic fields.................256
4.4.6.2 Experimental studies .......................................................................260
4.4.6.3 Summary .........................................................................................269
4.5 Epidemiological studies of non-cancer health effects in humans.......................272
4.5.1 Occupational exposure.............................................................................272
4.5.1.1 Reproductive effects .......................................................................272
4.5.1.2 Neurodegenerative diseases.............................................................276
4.5.1.3 Suicide and depression ....................................................................282
4.5.1.4 Cardiovascular disease.....................................................................283
4.5.1.5 Summary .........................................................................................284
4.5.2 Environmental exposure...........................................................................287
4.5.2.1 Pregnancy outcome .........................................................................287
4.5.2.2 Neurodegenerative diseases and neurobiological disorders..............292
4.5.2.3 Summary .........................................................................................292
4.6 Laboratory studies of non-cancer health effects in humans..............................301
4.6.1 Sensation and perception .........................................................................302
4.6.1.1 Field perception ..............................................................................302
4.6.1.2 Visual effects...................................................................................302
4.6.2 Central nervous system............................................................................303
4.6.2.1 Electroencephalographic spectral analysis......................................303
4.6.2.2 Event-related potential....................................................................305
4.6.2.3 Sleep electrophysiology..................................................................306
4.6.2.4 Cognition and performance .............................................................308
4.6.3 Cardiovascular system .............................................................................308
4.6.3.1 Heart rate.........................................................................................308
4.6.3.2 Heart-rate variability.......................................................................309
4.6.4 Other effects.............................................................................................311
4.6.4.1 Melatonin........................................................................................311
4.6.4.2 Neuroendocrinology........................................................................313
4.6.4.3 Immune system...............................................................................313
4.6.5 Mood disturbances...................................................................................314
4.6.6 Electromagnetic hypersensitivity.............................................................314
4.6.7 Summary ..................................................................................................316vii

4.7 In vitro and mechanistic studies........................................................................326
4.7.1 Genotoxicity and regulation of gene expression.......................................326
4.7.1.1 Genotoxicity....................................................................................327
4.7.1.2 Transcription...................................................................................330
4.7.1.3 Translation and protein synthesis...................................................332
4.7.1.4 Summary .........................................................................................333
4.7.2 Signal transduction and proliferation........................................................334
4.7.2.1 Calcium homeostasis and flux .........................................................335
4.7.2.2 Receptor-mediated signaling pathways...........................................337
4.7.2.3 Cell proliferation .............................................................................338
4.7.2.4 Enzyme synthesis and activity.......................................................340
4.7.2.5 Apoptosis .......................................................................................341
4.7.2.6 Summary .........................................................................................342
4.7.3 Induction of cytological markers..............................................................342
4.7.3.1 Embryonic staging...........................................................................343
4.7.3.2 Matrix synthesis and extracellular interactions...............................345
4.7.3.3 Cell surface markers ........................................................................346
4.7.3.4 Matrix interactions: Adhesion, morphology, and motility .............348
4.7.3.5 CellÐcell communication and gap junctions.....................................351
4.7.3.6 Summary .........................................................................................352
4.7.4 Summary ..................................................................................................354
4.8 Biophysics of interactions of ELF EMF with biological systems...................355
4.8.1 Biologically important interactions at the molecular level .......................358
4.8.1.1 Forces and torques on ions and molecules ......................................358
4.8.1.2 Perturbation of chemical reactions ..................................................359
4.8.1.3 Temporal averaging and time-dependent processes........................360
4.8.2 Comparison of changes induced by EMF and competing physicalprocesses ..................................................................................................361
4.8.2.1 Comparison with the geomagnetic field ..........................................361
4.8.2.2 Comparison with endogenous electric fields...................................361
4.8.2.3 Comparison with thermal noise ......................................................362
4.8.2.4 Comparison with shot and 1/f noise................................................365
4.8.2.5 Magnitude of competing thermal effects.........................................366
4.8.3 Proposed physical mechanisms ...............................................................368
4.8.3.1 Effects of electric fields on cell surface structures and cellattachment .......................................................................................368
4.8.3.2 Cyclotron resonance and ion parametric resonance ........................371
4.8.3.3 Biological electron transfer..............................................................375
4.8.3.4 Effects on biogenic magnetite..........................................................376
4.8.3.5 Magnetochemistry: Effects of magnetic fields on free-radical
reactions ..........................................................................................377
4.8.3.6 Non-linear dynamics and application of stochastic resonance........380
4.8.4 Summary ..................................................................................................382
5 FINAL SUMMARY AND EVALUATION...........................................................395
5.1 Carcinogenicity in humans ................................................................................396viii

5.1.1 Evidence from epidemiological studies to support the evaluation...........396
5.1.2 Evidence from studies of carcinogenicity in experimental animals
in vivo to support the evaluation.............................................................397
5.1.3 Mechanistic and in vitro evidence to support the evaluation ..................398
5.1.4 Discussion................................................................................................399
5.2 Non-cancer health effects.................................................................................399
5.2.1 Non-cancer adverse health effects............................................................399
5.2.2 Other biological effects.............................................................................401
5.3 Overall evaluation..............................................................................................402
6 REFERENCES...........................................................................................................403
7 ABBREVIATIONS ...................................................................................................467
8 GLOSSARY...............................................................................................................471
APPENDIX A - IARC Monographs Programme on the Evaluation of Carcinogenic
Risks To Human - Preamble ..............................................................479
APPENDIX B - Minority Statement on Animal Carcinogenicity................................505ix

Figures
Figure 2.1 Electromagnetic spectrum showing extremely low frequency and otherbands...............................................................................................................55
Figure 2.2 Field-particle interactions: ÒclassicalÓ forces, torques, and energies.............56
Figure 2.3 Illustration of Òcross-productÓ (equations (a), (C) and (c) in Figure 2.2:
The resulting vector c = aCb is in a direction perpendicular to the plane
defined by a and b and its magnitude is equal to the product of theirmutually perpendicular components: c = a×b sin f). ....................................57
Figure 4.1 Equivalent circuit for an array of N membrane channels with conductive
media on each side of the membrane. Resistance value is associated witheach channel (RG) and with each of the access resistances (RA and RB)near the channel mouths. All resistors in the circuit produce voltage
noise, and these sources (VGi, VAi, and VBi) are completely independentand uncorrelated. When circuit analysis techniques with the proper
methods are used for summing incoherent signals, the net noise voltage
across an arbitrary channel (V1 in this figure) can be calculated. Note thatthe noise voltage of interest (V1) is that occurring across the channel, andnot across the series combination of the channel and access resistances.
The model assumes that any voltage gating mechanism is inside thechannel or at the channel mouth. From Gailey (Gailey, 1996)....................385
Figure 4.2 Normalized correlation coefficients for thermal electrical noise occurring
across an ion channel as a function of the number of channels in themembrane (Electrical parameters used in this calculation apply to gapjunction channels with a channel resistance of 6.5 GW and an access
resistance of 0.33 GW.). The coherence or correlation between noise
signals occurring in different channels decreases by a factor of 10 per
decade with increasing number of channels. From Gailey (Gailey, 1996)....386
Figure 4.3. Improvement in signal-to-(thermal) voltage noise ratio due to lack ofcorrelation between noise signals occurring in different open channels in
the membrane (The x axis is the absolute value of the slope of the closing
rate constant divided by the slope of the opening rate constant. The solidline was generated from equation 4.15 with equal opening and closing rate
constants and assuming no effect of thermal voltage noise on the closing
rate constants (g = 0, No ®ì)). When the slight correlation between
voltage noise in the open channels and the effect of the uncorrelated noisein these channels is included, the dashed line is obtained for a membranewith 50,000 open channels. From Gailey (Gailey, 1996). ...........................387
Figure 4.4. Voltage noise spectra of a frog node of Ranvier at various membranepotentials. From Verveen and DeFelice (Verveen & DeFelice, 1974);
reproduced by Barnes (Barnes, 1986)..........................................................388xFigure 4.5. Effect of magnetic fields on radical-pair energy levels (Electron spins in
the three sub-levels of the triplet state: T+1 spins parallel in the directionof the magnetic field, T-1 spins parallel in the direction opposite to themagnetic field, T0 spins antiparallel but in phase in the field direction.). S,
singlet state From Polk (Polk, 1992a). .........................................................389
Figure 4.6. Maximum change in escape probability and maximum relative change areshown as a function of cage retainment time for an increment of 5 mT toan external field of 50 mT (The recombination probability for electrons ina relative singlet state is taken as twice the escape probability and theinternal field magnitudes and directions are selected from Monte Carloprocedures, as is the direction of the external field. The variation of
escape probability with cage time of radicals with fields chosen so as tomaximize the escape at a cage time of 10 ns, is also shown.) From Adair(Adair, 1997). ...............................................................................................390xi

Tables
Table 2.1 Field meter characteristics.............................................................................58
Table 2.2 Magnetic field exposure metrics used in epidemiological studies .................59
Table 2.3 Standard occupational classification codes and job categories of"electrical jobs"..............................................................................................60
Table 2.4 Electrical occupations derived from job titles with TWA magnetic field
exposures.......................................................................................................61
Table 2.5 Occupational exposure measurements in occupational studies.....................73
Table 2.6 Distribution of wire code categories of control subjectsÕ homes in sevenstudies in the USA ........................................................................................75
Table 2.7 Measured magnetic fields and Wertheimer-Leeper wire codes in six
studies in the USA ........................................................................................76
Table 2.8 Comparison of the percentage of homes in wire code categories > 0.2 or
0.3 mT in four studies in the USA.................................................................77
Table 2.9 Estimated median magnetic fields in the 1000 homes survey .......................36
Table 2.10 Average magnetic flux densities in schools in Canada...................................45
Table 2.11 Magnetic fields associated with use of appliances........................................47
Table 3.1 Typical average electric fields in bone marrow in numerical dosimetricstudies of uniform conditions of exposure to electric or magnetic fields
at 60 Hz.........................................................................................................80
Table 3.2 Calculated average induced electric fields in selected tissues in a humanadult from a 1.0 mT, 60 Hz magnetic field orientated from shoulders
and assumed tissue conductivities.................................................................81
Table 4.1 Results of long term chronic bioassays in rodents exposed to EMF..........103
Table 4.2 Assays of co-initiation and of promotion of: mammary cancer..................104
Table 4.3 Incidences of mammary gland lesions in female rats exposed to 10 mg
DMBA plus sham exposure or exposure to magnetic fields.........................94
Table 4.4 Studies of promotion and co-promotion of skin cancer..............................105
Table 4.5 Studies of promotion and co-promotion of liver cancer..............................106
Table 4.6 Studies of promotion of: Lymphoma/leukemia...........................................106
Table 4.7 Lymphoma incidence in mice treated with ionizing radiation and EMF.......99
Table 4.8 Leukemia/lymphoma in transgenic mice exposed to 60 Hz magnetic
fields............................................................................................................101xii

Table 4.9 Minimal exposure assessment required for a study to be included inthis review...................................................................................................109
Table 4.10 Epidemiological studies of exposure to EMF and cancer at all sites...........146
Table 4.11 Epidemiological studies of leukemia with full-shift measurements ofmagnetic fields.............................................................................................147
Table 4.12 Epidemiological studies of brain cancer with full-shift measurements ofmagnetic fields.............................................................................................151
Table 4.13 Cohort studies of breast cancer and occupational exposure to EMF..........154
Table 4.14 Case-control studies of male breast cancer and occupational exposure
to EMF........................................................................................................155
Table 4.15 Case-control studies of female breast cancer and occupational studies
of EMF........................................................................................................157
Table 4.16 Epidemiological studies of lung cancer with full-shift measurements ofmagnetic fields.............................................................................................158
Table 4.17 Central nervous system tumors in offspring of EMF-exposed parents .....159
Table 4.18 Design of studies of leukemia and residential exposure to EMF ................161
Table 4.19 Results of studies of leukemia and residential exposure to EMF ...............164
Table 4.20 Summary of epidemiological studies on childhood cancers.........................190
Table 4.21 Childhoodleukemia.....................................................................................196
Table 4.22 Results for childhood nervous system tumors............................................200
Table 4.23 Results for childhood lymphoma................................................................202
Table 4.24 Summary of appliance studies ....................................................................203
Table 4.25 Summary of meta-analysis results ..............................................................205
Table 4.26 Summary of NIEHS meta-analysis .............................................................207
Table 4.27 Summary of immunological studies of exposure to EMF inexperimentalanimals ...................................................................................213
Table 4.28 Perception in experimental animals exposed to EMF.................................230
Table 4.29 Summary of experiments assessing aversion in experimental animals
fields............................................................................................................231
Table 4.30 Learning and performance in experimental animals exposed to EMF.........232
Table 4.31 Neurophysiological effects of EMF in experimental animals .....................234
Table 4.32 Electrophysiological effects of EMF in experimental animals....................236
Table 4.33 Studies on EMF exposures and reproductive and developmental effects
of EMF in experimental animals and birds..................................................241xiii

Table 4.34 Studies of the effect of exposure to EMF on melatonin in experimental
animals.........................................................................................................253
Table 4.35 Minimal exposure assessment required for a study to be included inthis review...................................................................................................272
Table 4.36 Adverse pregnancy outcomes and maternal exposure to EMF...................293
Table 4.37 Alzheimer disease and dementia in association with exposure to EMF .....295
Table 4.38 Amyotrophic lateral sclerosis in association with exposure to EMF.........297
Table 4.39 Suicide and depression in association with exposure to EMF....................299
Table 4.40 Mortality from cardiovascular disease in relation to exposure tomagnetic fields (Savitz et al., 1998c)...........................................................300
Table 4.41 Effects on exposure to EMF on measures of electrical activity inhuman brain.................................................................................................318
Table 4.42 Laboratory studies of the effects of magnetic fields onelectroencephalographic measures of human sleep .....................................320
Table 4.43 EMF effects of exposure to EMF on human cognition and performance...321
Table 4.44 Effects of exposure to EMF on heart rate and heart rate variability inhuman volunteers ........................................................................................323
Table 4.45 Effects of exposure to EMF on melatonin and its metabolite in humans ...324
Table 4.46 Maximum numbers of turnovers of some enzymes....................................391
Table 4.47 Cells showing Ca++ oscillations...................................................................391
Table 4.48 Average endogenous fields due to heart activity induced field (Hz)...........391
Table 4.49 Experimental papers reporting resonance depending on the static
magnetic fields (BDC)...................................................................................392
Table 8.1 Units............................................................................................................477

xiv

Participants
Members
L. E. Anderson, Research Scientist, Battelle, Pacific Northwest National RRCLA Annex Bldg.,
Rm. 104; MS K4-28, P.O. Box 999, 902 Battelle Blvd., Richland, WA 99352
J. D. Bowman, Research Industrial Hygienist, National Institute for Occupation Safety and
Health, Taft Laboratories, MS C-27, 4676 Columbia Parkway, Cincinnati, OH 45226
A. L. Brown, Emeritus Dean and Professor, University of Wisconsin at Madison, Department of
Pathology and Laboratory Medicine, 28228 Marshall Ct., Madison, WI 53705 (Vice-Chair)
E. Cardis, Chief, Unit of Radiation and Cancer, International Agency for Research on Cancer, 150
Cours Albert-Thomas, 69372 Lyon Cedex 08, France
F. M. Dietrich, Principal Engineer, Electric Research and Management, Inc., 2140 William Pitt
Way, Pittsburgh, PA 15238
M. L. Dubocovich, Professor, Northwestern University Medical School, Department of
Molecular Pharmacology and Biological Chemistry, Tarry Bldg., Rm. 7-701, 303 E. Chicago
Ave., Chicago, IL 60611
J. S. Felton, Division Leader, Molecular and Structural Biology Division, University ofCalifornia, Biology and Biotechnology Research Program, Lawrence Livermore National
Laboratory, Bldg. 361, Rm. 1065, MS-452, P.O. Box 808, 7000 East Ave., Livermore, CA
94550
M. Feychting, Epidemiologist, Institute of Environmental Medicine, Karolinska Institute,
Division of Epidemiology, Box 210, Doktorsringen 16 C, S-17177 Stockholm, Sweden
P. C. Gailey, Director, Electric and Magnetic Fields Bioeffects Research Program, Oak Ridge
National Laboratory, Energy Division, Bldg. 3147, Rm. 108, MS-6070, 1 Bethel Valley
Rd., Oak Ridge, TN 37831-6070
M. A. Gallo, Director and Professor, NIEHS Center of Excellence, UMDNJ-Robert WoodJohnson Medical School, Department of Environmental and Community Medicine, EOHSI
Bldg., Rm. 408, 170 Frelinghuysen Rd., Piscataway, NJ 08854-8020 (Chair)
C. Graham, Senior Advisor for Life Sciences, Midwest Research Institute, Department of Life
Sciences, 425 Volker Blvd., Kansas City, MO 64110
G. J. Harry, Neurotoxicology Group Leader, National Institute of Environmental Health
Sciences, Laboratory of Toxicology, Bldg. 101; C-142; MD C1-04, P.O. 12233, Research
Triangle Park, NC 27709

1

L. I. Kheifets, Senior Scientist, EPRI, Stanford, 12570 Roble Ladera Rd., Los Altos Hills, CA
94022
R. A. Luben, Associate Dean for Research, University of California at Riverside, Department of
Biomedical Sciences, Statistics/Computer Bldg., Rm. B600, East Campus Dr., Riverside,
CA 92521-0121
M-O. Mattsson, Associate Professor, UmeŠ University, Department of Cellular andDevelopmental Biology, Bldg. L, UmeŠ S-901 87, Sweden
K. J. McLeod, Associate Professor, State University of New York at Stony Brook, Departmentof Orthopaedics, Health Science Center T18, Rm. 030, Stony Brook, NY 11794-8181
S. C. Miller, Director, Signal Transduction Program, SRI International, Pharmaceutical Discovery
Division, 333 Ravenwood Ave., Menlo Park, CA 94025
M. Misakian, Physicist, National Institute of Standards and Technology, Bldg. 220 Rm. B344,
Gaithersburg, MD 20899
C. Polk, Professor Emeritus, University of Rhode Island, Department of Electrical and Computer
Engineering, Kelley Hall Rm. A-123, 4 East Alumni Ave., Kingston, RI 02881
C. J. Portier, Chief, Laboratory of Computational Biology and Risk Analysis and Coordinator,
EMF Hazard Evaluation, National Institute of Environmental Health Sciences, P.O. Box12233, Research Triangle Park, NC 27709 (Meeting Coordinator)
W. R. Rogers, Associate Professor of Environmental Sciences, University of Texas School of
Public Health, Department of Family Practice, 7703 Floyd Curl Dr., San Antonio, TX
78284-7976
A. Sastre, Principal Scientist, Midwest Research Institute, Health Assessment and ResearchCenter, 425 Volker Blvd., Kansas City, MO 64110
C. D. Sherman, Assistant Professor, San Francisco State University, Department ofMathematics, 1600 Holloway Ave., San Francisco, CA 94132
L. E. Slesin, Editor, Microwave News, 155 East 77th St., Suite 3D, New York, NY 10021
R. G. Stevens, Staff Scientist, Battelle, Pacific Northwest National Laboratory, Department of
Molecular Biosciences, P.O. Box 999, 902 Battelle Blvd., Richland, WA 99352
L. Tomatis, Scientific Director, Istituto Per LÕInfanzia, Via Dell ÔIstria 65/1, Trieste 34137, Italy
D. Wartenberg, Associate Professor, EOHSI UMDNJ-Robert Wood Johnson Medical School,
Department of Environment and Community Medicine, EOHSI Bldg., Rm. 234, 170
Frelinghuysen Rd. Piscataway, NJ 08855

2

J. R. Williams, Professor of Oncology, Johns Hopkins University, Department of Radiation
Oncology, Oncology Bldg., Rm. 2-121, 600 N. Wolfe St., Baltimore, MD 21287-5001
H. Yamasaki, Chief, Unit of Multistage Carcinogenesis, International Agency for Research on
Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France
M. G. Yost, Associate Professor, University of Washington, Department of Environmental
Health, Box 357234, Seattle, WA 98195-7234
P. L. Zweiacker, Environmental Permitting Manager, Texas Utilities Services, Energy Plaza Bldg.,
Rm. 09-002, 1601 Bryan St., Dallas, TX 75201-3411
Contributors to First Draft
L. E. Anderson, Research Scientist, Battelle, Pacific Northwest National RRCLA Annex Bldg.,
Rm. 104; MS K4-28, P.O. Box 999, 902 Battelle Blvd., Richland, WA 99352
G. M. Blumenthal, Research Fellow, National Institute of Environmental Health Sciences,
Laboratory of Toxicology, Bldg. 101, Rm. E123, MD E1-05, P.O. 12233, Research Triangle
Park, NC 27709
J. D. Bowman, Research Industrial Hygienist, National Institute for Occupation Safety and
Health, Taft Laboratories, MS C-27, 4676 Columbia Parkway, Cincinnati, OH 45226
E. Cardis, Chief, Unit of Radiation and Cancer, International Agency for Research on Cancer, 150
Cours Albert-Thomas, 69372 Lyon Cedex 08, France
C. Graham, Senior Advisor for Life Sciences, Midwest Research Institute, Department of Life
Sciences, 425 Volker Blvd., Kansas City, MO 64110
M-O. Mattsson, Associate Professor, UmeŠ University, Department of Cellular andDevelopmental Biology, Bldg. L, UmeŠ S-901 87, Sweden
K. J. McLeod, Associate Professor, State University of New York at Stony Brook, Departmentof Orthopaedics, Health Science Center T18, Rm. 030, Stony Brook, NY 11794-8181
J. E. Morris, Senior Research Scientist, Battelle, Pacific Northwest National Laboratories,
RRCLA Annex Bldg.; MS K4-28, 902 Battelle Blvd., Richland, WA 99352
C. Polk, Professor Emeritus, University of Rhode Island, Department of Electrical and Computer
Engineering, Kelley Hall Rm. A-123, 4 East Alumni Ave., Kingston, RI 02881
W. R. Rogers, Associate Professor of Environmental Sciences, University of Texas School of
Public Health, Department of Family Practice, 7703 Floyd Curl Dr., San Antonio, TX
78284-7976

3

C. D. Sherman, Assistant Professor, San Francisco State University, Department ofMathematics, 1600 Holloway Ave., San Francisco, CA 94132
M. G. Yost, Associate Professor, University of Washington, Department of Environmental
Health, Box 357234, Seattle, WA 98195-7234
National Institute of Environmental Health Sciences Staff
K. Olden, Director
G. W. Lucier, Director, Environmental Toxicology Program (ETP)
N. J. Bernheim, Biologist, Office of Special Programs, ETP
G. A. Boorman, Associate Director for Special Programs, ETP
M. J. Galvin, Health Scientist Administrator, Division of Extramural Research and Training
W. M. Grigg, Director of Communications
S. V. Lange, Director, National Toxicology Program, Liaison and Scientific Review Office
C. J. Portier, Chief, Laboratory of Computational Biology and Risk Analysis and Coordinator,
EMF Hazard Evaluation
M. S. Wolfe, Associate Coordinator, EMF Hazard EvaluationOAO Corporation
J. A. Fleming, Technical Training Specialist
F. M. Parham, Information Technology Technical Specialist II

Personal Communication Services Inc.
Diana Phillips, President

U.S. Department of Energy
I. Gyuk, EMF Program Manager, U.S. Department of Energy, EE-14, 1000 Independence Ave.,
Washington, DC 20585

4

National EMF Advisory Committee
S. D. Linde, Chairperson, National Electric Magnetic Fields Advisory Committee, 2733 Manning
Ave., Los Angeles, CA 90064
Science Writer
E. Heseltine, Associate Professor, Universit‚ Lumiere Lyon II, Lajarthe, 24290 St. Leon-surVezere, France
Observers
L. Anderson, Federal Energy Regulatory Commission
C. Axness, Northern States Power Co.
R. S. Banks, Robert S. Banks Associates, Inc.
D. G. Bannerman, National Electrical Manufacturers Association
R. L. Beavers, Private Citizen
M. Gluck, Private Citizen
N. N. Hankin, U.S. Environmental Protection Agency
D. Hoolihan, IEEE-EMC Society
J. C. Lathrop, EMF Health and Safety Digest
M. Lehrman, Caring Technologies, Inc.
R. Lindholm, Minnesota PowerR. M. Loughery, Edison Electric Institute
P. Lumnitzer, Watson & Renner
C. G. Lynch, Robert S. Banks Associates, Inc.
M. T. Marron, Office of Naval Research
I. Nishimura, Central Research Institute of Electric PowerG. Novak, Edison Electric Institute
K. M. Shanley, United Illuminating
5

6

1

Introduction
Electric power is used all over the world. In the United States, the generation,transmission, and use of electric energy is associated with the production of weak electricand magnetic fields (EMF) which oscillate 60 times per second (power-line frequency).
These fields are a fact of daily life: they are emitted by power lines, transformers, service
wires, and electrical panels as well as by home appliances (such as electric blankets,waterbeds, clocks, shavers, and televisions). Electricity has been used, to great advantage,for 100 years without society being aware of any adverse health effect, other than thermal
injury and electrocution.
Thus, when Wertheimer and Leeper reported in 1979 that children living near power lines
had an increased risk for developing cancer, the concern was immediate, and acontroversial area of research was born. Yet, despite a multitude of studies, there remains
considerable debate over what, if any, health effects result from exposure to EMF. Thereis still no clear answer to the question, ÒCan exposure to electric and magnetic fields
resulting from the production, distribution, and use of electricity promote cancer or
initiate other health problems?Ó
Faced with growing concern on the part of the public about whether EMF might be
adverse to human health, Congress mandated the Electric and Magnetic Fields Researchand Public Information Dissemination (EMFRAPID) Program in the 1992 Energy Policy
Act, Public Law 102-104. The National Institute of Environmental Health Sciences(NIEHS) and the Department of Energy (DOE) were given the responsibility for directing
and managing the program. This five-year effort, jointly funded by Federal and matchingprivate funds, was designed to improve our understanding of the potential adverse healtheffects of exposure to extremely low frequency (ELF) EMF, especially those producedby the generation, transmission, and use of electricity. The EMFRAPID Program sought
to explain any links between EMF exposures and human health and any special
conditions under which cause-effect relationships might occur. The 1992 Energy Policy
Act requires a report from the NIEHS Director outlining the possible human health risks
upon completion of the Program.
As part of its strategy for preparation of the report, the NIEHS developed a novel
program that brought together diverse areas of science. The program involved large
numbers of research scientists with diverse expertise both within and outside the EMF
research field. With the aid of the National EMF Advisory Committee and the EMF
Interagency Committee, the NIEHS used its existing peer-review grants process, worked
with the DOE to characterize and improve methods for measuring exposure, andconducted a two-year study of carcinogenicity in experimental animals.
As the program entered its last two years, the NIEHS enacted a two-tiered process forcollecting and evaluating information for the Director's report: Science Review Symposia

7were held in which open public debate was encouraged with regard to key researchfindings on EMF; and a rigorous, multi-disciplinary, scientific assessment of available
data on the health effects of EMF was conducted by a Working Group. This publication
represents the output of the Working Group. The process was publicly open, scholarly,
objective, and sufficiently flexible to accommodate the changing face of EMF research andpublic health concerns.
In the first step of the process, with the aid of their advisory committees and scientists inthe field, the NIEHS opened the review on the interaction of ELF EMF with biologicalsystems by holding the first Science Review Symposium in Durham, NC, in March 1997.
The participants addressed specific questions concerning the mechanisms governing theinteractions of ELF EMF with biological systems in vitro and using biophysical theories.
The participants included engineers, molecular biologists, toxicologists, physiologists,
epidemiologists, mathematicians, and physicists, some specialized in EMF and othersfrom different fields. The report of the discussions has been published (Portier & Wolfe,
1997). Two further symposia were held, one on the epidemiology of exposure to ELF
EMF in San Antonio, Texas, in January 1998 (Portier & Wolfe, 1998a), and the other on
in-vivo/clinical investigations in Phoenix, Arizona, in April 1998 (Portier & Wolfe,
1998b). Through this series of three symposia, the NIEHS identified the key aspects ofscience that should be used in making any decision about health effects.
In the second step of the process, a Working Group was selected carefully after screening
by the NIEHS and discussions with its two standing external advisory boards. The
members of the Group represented a wide range of scientific disciplines, with and withouta particular interest in EMF. During a nine-day working session in Brooklyn Park,
Minnesota, they conducted a careful, thorough scientific review of all of the evidence
related to health effects associated with exposure to ELF EMF. Certain members of theGroup developed drafts in advance of the meeting to be used as the basis for discussion
on specific aspects of research on ELF EMF. At the meeting, subgroups read, modified,and rewrote the drafts to reflect the consensus of the Group.
The attached document is the report of the Working Group on the health effects of
exposure to ELF EMF. The evaluations of carcinogenicity were reached following theguidelines used in the International Agency for Research on Cancer (IARC) Monographson the Evaluation of the Carcinogenic Risk of Chemicals to Humans, with minor
modifications (see footnotes, Appendix A). Evaluations of other health end-points
followed the same criteria, with minor exceptions relating to final evaluations (seefootnotes, Appendix A).

8

2

Occurrence and Measurement of Extremely Low Frequency
Electromagnetic Fields

2.1

What are electromagnetic fields?
Wherever electricity is generated, transmitted, or used, electric and magnetic fields (EMF)
are created, due to the presence and motion of electric charges. Generally, these fields aretime-varying vector quantities characterized by a number of parameters, including theirfrequency, phase, direction, and magnitude. A simple analogy provides some insight into
the complexity of summarizing an exposure variable.
Consider the motion of an airplane in flight. A time-varying vector describes the velocity(km/h) of the passengers as the plane travels between two cities. At a particular time, themagnitude of the velocity vector gives the passengersÕ speed without regard to theheading. The three directional components (x, y, z) of the velocity vector at some time
will give the speed with respect to its position in space, described by a position vector in
altitude, longitude, and latitude coordinates. Over time, a variety of measures could bechosen to summarize the passengersÕ time-varying velocity vector. For example, theaverage vector magnitude would describe their average speed, or the average vertical
position would give their average altitude. We could even choose some measure of change
in the vector components with time to describe features such as the rate of descent or
acceleration. All of these summary measures are equally valid in a physical sense but
describe qualitatively different aspects of the passengersÕ motion that may not be equallyimportant in relation to a biological response.
The challenge for exposure assessment is to choose a summary measure that is physicallymeaningful and biologically relevant. To illustrate this point, the average speed of thepassengers may be useful for deciding how long their trip will take but is essentiallyuseless for predicting whether the passengers will become airsick; however, anothersummary measure, describing velocity fluctuations up and down, would probably be avery good predictor of possible air sickness during a flight. A different summary measure,
involving the directional components of the motion, would be needed to predict anotherbiological response such as jet lag. Thus, the choice of summary measure depends on boththe physical characteristic to be described and the biological response of interest.
An electromagnetic field is composed of two components, the electric and the magnetic
fields. The electric field is created by the presence of an electric charge. It describes themagnitude and direction of the force it exerts on a positive electric charge. The magnitudeof the electric field depends on the difference in potential between charge-carrying bodies,including conductors, regardless of the amount of current that is flowing in them. In
contrast, a magnetic field is created by the motion of electric charges. Typically, thismotion is represented by a flow of charge in the form of an electric current, which gives

9the number of charges per second passing through the conductor. The magnetic field acts
only on other electric charges in motion. Thus, a magnetic field is created by an electric
current and describes the magnitude and direction of the force exerted on a nearby current(moving charges). The magnitude of the magnetic field is proportional to the current flow
in a conductor, regardless of the voltage present.
The discussion in this document focuses primarily on magnetic fields but will include
electric fields when possible because of their inherently close association with electric
power systems. Voltage and current determine the magnitude of the electric and themagnetic fields at a location, respectively, with the source geometry and distance from thesource to the measurement location. The strength of an electric field is usually measured
in volts per meter (V/m) or sometimes in kilovolts per meter (1 kV/m = 1000 V/m).
Magnetic fields can be designated by either magnetic flux density (B) or magnetic fieldstrength (H); both are proportional to the magnitude of the current. B is measured in thecentimeter-gram-second unit, the gauss (G), or the unit of the Systeme Internationale (SI),the tesla (T); 1 mG = 1 x 10Ð3 G = 0.1 mT. H is measured in SI units of amperes/meter(A/m). B and H are related through the equation: B = m0H, where m0 = 1.26 x 10Ð6
henry/m is the magnetic permeability of a vacuum. To a close approximation, m0 remains
the same for air and body tissues, and only one of the variables, B or H, need bemeasured. In practice, B is the usual measured quantity, and, for the purpose of thisdocument, Ômagnetic fieldÕ refers to the magnetic flux density in microtesla (mT; 1 mT =1 x 10Ð6 T). Unless otherwise stated, all voltage, current, and magnetic flux values are rms(root mean square), as defined in equation 2.4.
EMF can be arranged in an orderly fashion in an electromagnetic spectrum, according totheir frequency (f) or wavelength (l), where l = c/f and c is the velocity of light. The
electromagnetic spectrum spans an enormous range of frequencies (Figure 2.1), more than
15 orders of magnitude. This document focuses principally on EMF resulting from theuse and distribution of electric power, allowing a great deal of simplification as thesefields vary rather slowly over time. The frequency of EMF depends on the power-line
source; in North America, power systems operate at a frequency of 60 cycles per second,or 60 hertz (Hz). Generally, these power-line fields fall in the extremely low frequency(ELF) region of the electromagnetic spectrum, which is defined by frequencies from 3 to3000 Hz (Poole & Ozonoff, 1996). The alternating current flowing in the electric powersystem has dominant sinusoidal voltage and current waveforms; however, although 60 Hz
is the predominant fundamental frequency, humans are exposed to a mixture of
frequencies, and much higher frequencies can arise. For example, switching events cangenerate abrupt spikes in voltage and current waveforms, leading to high frequency
ÔtransientsÕ, which can extend into radio frequencies above several megahertz (1 MHz =106 Hz). Nonlinear characteristics in electrical devices can generate harmonics at integer
multiples of the fundamental frequency extending up to several kilohertz (1 kHz = 103
Hz). EMF frequencies from some electronic equipment, like televisions and visual display
terminals (VDT), can routinely extend up to 50 kHz.

10

Most devices that have electric wires, e.g. electric motors, electric equipment such as
electric power lines, residential appliances, and industrial equipment, are potential sourcesof EMF. Residential exposures are dominated by ELF sources but also include exposure
to very low frequencies, 3Ð30-kHz radio frequencies, and microwave sources.
The Earth also produces EMF. Unlike the fields from power lines and other alternating
current sources, the EarthÕs fields are largely ÔstaticÕ, that is they do not change over time.
In contrast, EMF from power lines and other alternating current sources have a periodic
component. The EarthÕs magnetic field has a magnitude of about 50 mT over most of the
USA and is oriented toward magnetic North; the vertical field component accounts forabout two-thirds of the total vector magnitude. Devices that operate on direct current(DC) also produce static magnetic fields, and some occupational environments, such asaluminum smelting, can have extremely strong static fields.
For the most part, researchers have focused on ELF magnetic fields resulting from powerlines, appliances, and occupational exposures. In the broader context of human exposuresand epidemiological studies, it should be remembered that typical exposures to EMF
occur over a wide range of frequencies and in conjunction with static fields.
ELF electric fields at relatively high intensities can have acute biological effects. Nerve andmuscle stimulation results in an immediate behavioral response in humans and othervertebrates (Malmivuo & Plonsey, 1995; Reilly, 1992). Extremely strong electric fields
can permanently or transiently damage cell membranes (Weaver & Chizmadzhev, 1996)
and produce burn injuries (Tropea & Lee, 1992). Stimulation of peripheral nerves at
power frequencies in humans generally requires electric current densities in muscle tissue
in the order of 1.0 A/m2, which corresponds roughly inside tissues with an electric
conductivity of s ÷ 1 S/m to internal electric fields on the order of 1.0 V/m. Production ofsuch currents inside living tissue at 60 Hz requires either direct, electrically conductive
contact with a source of electric power or the presence of an electric field in thesurrounding air in the order of several 100 kV/m. Without conductive contact, the electricfield outside body tissues (EOUT) must be much larger than the field inside (EINS). Thisrequirement is a consequence of the physical laws of conservation of electric charge andcontinuity of electric displacement. In the case of steady-state sinusoidal electric fields offrequency f at a plane boundary between Ôsemi-infiniteÕ media, the ratio of the external
electric field over the internal field is described by the relation (Polk, 1986):

EOUT
s
»
EINS weEq. 2.1

where w = 2pf, e is the dielectric permittivity of air and s is the conductivity of tissue » 1
S/m. Since for dry air e » 8.84 x 10Ð12 F/m, the ratio given by equation 2.1, which
describes the attenuation of an external electric field relative to the apparent field inside
the body, is roughly 100 million. Distortion of the field in air by the presence of a11ÔconductingÕ body, air moisture, contact with an electrically conducting earth, andvariation of s within the body, can reduce this ratio somewhat, but it will never be muchless than 10 million. Details of current and field distributions that take into account bodyorientation and in homogeneity have been given, for example, by Kaune (Kaune &Forsythe, 1985) and Dawson (Dawson et al., 1996).
Typical 60 Hz electric fields in homes rarely exceed 100 V/m (Barnes et al., 1989) and are
not more than 10 kV/m near ground level directly underneath a very high-voltage (~ 500kV) transmission line. It is clear that the only persons who will experience internal electricfields in the order of even 10Ð3 V/m due to an external electric field are utility workers in
the immediate vicinity of high-voltage wires.
Time-varying magnetic fields induce electric fields into any material, according toFaradayÕs law:¶B

ò E × dl = - òò ¶ t × ds

Eq. 2.2

The term on the left-hand side of the equation indicates the electric field integrated over a
closed boundary; the term on the right-hand side is the integral of the rate of change of themagnetic flux density, B, perpendicular to and integrated over the area enclosed by thecontour designated on the left-hand side . The integral òò B × ds is also called the magnetic
flux f. For a reasonably long, cylindrical body of radius r, eq. 2.2 leads to (Polk, 1986):

E=pfBr

Eq. 2.3

where B is the magnetic flux in tesla and r is in meters, which is frequently used toestimate the average electric field induced by a time-varying magnetic field. Since the lefthand side of equation 2.2 gives only the induced electric field summed over a closed
contour, equation 2.3 applies only to an electrically homogeneous medium; however, inelectrically inhomogeneous tissue, this induced field can vary locally, giving rise to muchlarger or smaller values than the average (Polk, 1992c).
The magnetic permeability (m) of living tissue (with very few, localized exceptions) ispractically equal to that of free space. Consequently, the magnetic flux density inside thebody is nearly equal to that outside. Equation 2.3 then indicates that a 60 Hz field of 100
mT oriented along the head-to-feet axis of a human, with an average radius of 15 cm, will
induce near the periphery of the body an average electric field of 2.8 x 10Ð3 V/m. In
comparison, the average electric field near the rim of a petri dish, with a radius of 3 cm,
induced by a vertical 60 Hz, 100-mT magnetic field will be about 0.56 x 10Ð3 V/m.

12

These magnetically induced internal electric fields are very much larger than those due to a
100-V/m external electric field in air. A 100-V/m electric field represents the upper limit ofthose found in typical homes; however, induced electric fields are still much smaller thaninternal electric fields associated with nerve and muscle stimulation. The average electricfield induced by a 0.3-mT 60 Hz field near the surface of a human with a 15-cm radius isonly 8.5 x 10Ð6 V/m. Thus, typical magnetic fields encountered in epidemiological studies
of residences induce internal currents and electric fields that are roughly one million times
smaller than the currents required to produce acute nerve and muscle stimulation.
The basic laws derived from ÔclassicalÕ physics, which can operate either directly or
indirectly and at either the macroscopic or the microscopic (molecular) level in fieldÐ
biosystems interactions, are summarized in Figures 2.2 and 2.3; quantum mechanicalconsiderations are discussed in Section 4.7.5. Forces and torques are given for bothelectric fields and magnetic flux densities. Individual electric charges, electric dipoles, andmagnetic dipoles or magnetic moments are considered. These equations indicate thatstationary or moving individual electric charges will undergo translatory motion in the
direction of an applied electric field. In comparison, only charges that are already moving
at some velocity, v, will be subjected to a magnetic or ÔLorentzÕ force in a magnetic flux
density, B, that is perpendicular to both v and B (as indicated by the cross-product). This
perpendicular force on electric charges in a magnetic field leads to a circular motion andthe Ôcyclotron resonanceÕ phenomenon (Liboff, 1985), which will appear only when theprobability of collisions with stationary or randomly moving particles is extremely small(Durney et al., 1988). Translatory motion of electric dipoles, ÔdielectrophoresisÕ (Pohl,
1978), and of magnetic moments requires very large spatial field gradients (Barnes, 1986).
The appearance of torques, producing rotation, requires either the pre-existence of dipole
moments or their generation by an applied field. This includes phenomena at the atomic
level, where the nuclear magnetic moment and nuclear angular momentum are responsible
for nuclear magnetic resonance at frequencies determined by an applied DC magnetic field.
Various biophysical mechanisms have been proposed to account for the effects of EMF(see section 4.8). Some mechanisms predict a strong (or weak) dependence on thefrequency content, magnitude, or spatial direction of the fields. Some mechanisms
proposed for the interaction of magnetic field with tissues suggest a response from boththe time-varying and static-field components or specify a unique combination of the staticand time-varying field vectors for a particular target molecule. Also, we cannot ignore thepossible role of the state of the biological system, for example awake or sleeping, which
could make the timing of exposure important. A great variety of possible exposure factors
could be considered, none of which can be excluded a priori, and several different
mechanisms have been postulated. Assumptions must thus be made when measuring
EMF and constructing a few simple summary measures of exposure for the purposes ofhealth assessment.

13

2.2

Measurements, unit conventions, and sources
In the power distribution system, the line voltage or current is usually designated by therms value. To compute the rms value, the instantaneous values are squared and averaged
and the square root is taken. Mathematically, the rms magnetic flux density is describedby:Brms =

1 t =T
B(t ) 2 dt
T òt = 0

Eq. 2.4

where B(t) is the instantaneous magnetic flux density and T is the time for an integral overa number of periods of the fundamental frequency.
For a pure sinusoidal waveform, the rms value is related to the instantaneous peak value
by a factor of Ö2, i.e. Bpeak = Ö2 Brms. Similar formulas apply for computing the rms
voltage. The rms value is always positive and can be related to the average power in watts(energy per unit time), where watts are defined by the instantaneous product of voltage
and current delivered to a load. Note that ultimately it is the integral of power with time(i.e. watt-hours or kilowatt-hours) that represents the amount of energy delivered by autility to a customer.
The measurements of EMF used in most studies are records of the magnitude of the field;
they do not retain information on the directional orientation in space or changes in
direction over time. This is accomplished by measuring the rms value of three orthogonal
spatial components (x, y, and z), and then combining these three values to find themagnitude of the rms. This value, sometimes referred to as the rms resultant, is computedas:B res = B x2 + B y2 + B z2

Eq. 2.5

where Bx , By, and Bz are the orthogonal magnetic flux density spatial components.
Throughout this document, the quantity Bres is referred to as the magnitude of themagnetic field or vector. As noted above, the magnitude does not depend on the directionof the field vector in space. Therefore, Bres provides an isotropic measure that does notdepend on the orientation of the coordinate system for the measuring device. This is aconvenient property for personal exposure meters, in which the spatial orientation
constantly changes as the subject moves about.
In many studies, instruments have been used to measure or estimate the time-weighted
average (TWA) magnitude of the magnetic field. The TWA is computed from theequation:

14

T

1
BTWA = ò B(t )dt
T0

Eq. 2.6

where T is the averaging time.
Note that for a series of measurements uniformly spaced over time, the TWA reduces tothe simple average (mean) of the values over T, the time interval. The TWA is by far thecommonest exposure metric. It represents a measure of field magnitude, averaged overtime. These definitions have been given in terms of magnetic field components, but similar
quantities can be derived for electric fields.
The electric power system in North America is arranged in a series of building blocks orsegments, with power lines connecting generating stations via a network of transmission
lines, intermediate substations, and switching points to the local distribution lines, andultimately to utility customers. By design, the voltage in a given portion of the systemremains nearly constant; large transmission lines typically operate at > 35 kV, andprimary distribution lines operate at about 4Ð35 kV. These higher voltages on thetransmission lines are stepped down at local substations by transformers to produce thevoltages for the primary distribution lines. The primary distribution lines are further
reduced by transformers at other points to a correspondingly lower voltage and higher
current for residential or commercial use. Typically, residential service operates at 120
and 240 V. Roughly speaking, the power delivery in each segment of the electric systemis the product of the voltage and current load. So power is delivered by creating highvoltage at moderate current in the transmission segments and transforming this into highcurrent at moderate voltage for residential distribution. An important consequence of this
distribution system is that transmission lines are usually larger sources of electric fields,
because of the high line voltage. In most cases, transmission lines carry larger load
currents than primary distribution lines but are located farther away from residences;
however, in some cases transmission lines carry load currents similar to those of primary
distribution lines. Thus, overall, commercial and residential power distribution systems
can be a more significant source of magnetic fields than transmission lines but are usually
not a very significant source of large electric fields.
Although the voltage in a given segment of the power system remains nearly constant, thecurrent in each portion is highly variable over time, depending on the changing demand forelectric power. As a result, in the absence of other changes (such as introducing shielding
materials) at locations near power lines, electric fields remain fairly constant, whilemagnetic fields generally vary significantly over time. Interestingly, residential
measurements of magnetic fields show appreciable morning and evening peaks (Dovan etal., 1993) and a seasonal component which varies by geographic region and closely
follows the electrical use patterns of urban residents. Consequently, the timing of
measurements during a day or season can lead to systematic bias in estimates of 24-h orannual average exposures (Bracken et al., 1993).

15

Calculations of EMF frequently involve a spatial arrangement of one or more charge orcurrent elements, known as multipoles (Lorrain & Corson, 1970). A monopole consists ofa single positive or negative electric point charge; a small displacement of this point charge
and replacement of the original charge element by a charge of equal magnitude but
opposite sign creates an electric dipole. A magnetic dipole represents the basic elementthat describes the magnetic field from a current loop. A small displacement of a dipole andreplacement of the original by a dipole of equal magnitude and opposite sign creates aquadrupole. This concept can be extended indefinitely to describe the spatial extent offields in terms of a general multipole expansion of order 2n, where n is the number ofpoles. The magnetic field produced at a distance R by a multipole of order n can be
described by the equation:
Bn = mMf (f )
R n +1

Eq. 2.7

with field in mT, distance in meters, and multipole in Amn, where M is the multipole
vector term describing the source current. At a given frequency, the magnitude anddirection of M are a function of the source current magnitude and geometry, f is the angle
between the direction of M and R, and f(f) designates a function of f. Both M and B canbe elliptically polarized, that is the vectors rotate in space, describing an ellipse overevery cycle of the power frequency. As the distance R increases, the field produced byhigher-order multipoles becomes less important. At most practical distances for exposure
assessment, significant fields are produced only by terms associated with monopoles anddipoles, with order n = 1 or 2 for power lines and up to order n = 3 for appliances, withwhich people are nearly in contact when exposed. Magnetic monopoles do not actuallyexist but are a useful approximation near one pole of a large dipole.
A consequence of this dependence on geometry is that the magnitude of the magnetic field
decreases fairly rapidly with movement away from an isolated source; the magnitude falls
at least inversely with distance and often with the square of distance or more. A worker
standing next to a magnetic field source such as a small motor might experience a fieldmagnitude of 100 mT, but by moving a few feet away the magnitude may fall tobackground levels of < 0.1 mT. Naturally, the decrease in field strength with distancedepends on the magnetic field source, and the pattern is different for a small motor and fora power line. A small motor or computer monitor is essentially a point source, in that thefields originate from a small defined area. In contrast, a power line is a line source which
may decrease in strength much more slowly with distance and contribute exposure over amuch larger area. Field strength at the source is only one consideration in assessing thecontribution of a source to exposure to magnetic field; equally important is theindividualÕs proximity to the source and the amount of time spent near it. Together, thesefactors determine the relative contribution of a source to the individualÕs total exposure tomagnetic fields.

16

2.3

Exposure assessment

2.3.1 Instrumentation
Exposure assessment may be broadly defined as the task of estimating, for an individual
or group of individuals, the magnitude, frequency of occurrence, and length of time anagent is present and available to the target receptor. Exposure in this sense refers to thejoint presence of some biologically active agent with a person in space and time (Sussman,1995). Exposure is distinct from dose in that it usually refers to the external measure of
the agent, whereas dose usually refers to the amount reaching an internal target organ or
tissue.
Exposure to EMF is assessed for many purposes, including compliance withrecommended standards or regulatory limits, to evaluate the prevalence of EMF in someenvironment, or for use in epidemiological studies of possible health effects. The
underlying purpose of the monitoring often affects the kind of information gathered, thechoice of instrumentation, and the quality of the survey.
Data collected for a specific purpose may not be useful in another context. For example,
data collected at a workplace in a non-random fashion or specifically to identify a worstcase exposure scenario for compliance with a standard may not provide any meaningful
information on typical exposures in those jobs. The study design also must allow a
sufficient sample size to achieve the desired level of precision. Another consideration is
the use of assessment procedures that have been used in previous studies in order toobtain comparable results. If other data are available from the literature and consistentcollection methods are used, it may be possible to combine data on exposure from several
sources so as to draw broader conclusions.
As noted earlier, describing EMF with a summary measure involves many assumptions.
All instruments selectively measure certain aspects of field, usually ignoring others.
Consequently, no single instrument or study captures all aspects of potential human
exposure to EMF. Without guidance from studies of the biomechanisms of EMF, theinstrument makers made the following implicit assumptions (Heroux, 1991); (Bracken etal., 1993) :·Magnetic fields are a higher priority for research than electric fields. Most
monitors measure the magnetic field well, but only a few have a built-in electricfield sensor.

·

The important frequencies are those of electric power (50Ð60 Hz) and harmonics
up to about 500 Hz generated by common electrical appliances and industrial

17equipment. The low-frequency response should be limited to approximately 35
Hz in order to filter out signals due to movement in the geomagnetic field.
·

Exposure is best summarized by the rms magnitude of the ELF magnetic field
vector averaged over several cycles.

·

As temporal variation in the magnitude of the magnetic field may be important,many instruments can log data.

·

The location of a measurement on the body is of secondary importanceIn general, exposure to magnetic fields can be estimated with a personal exposure meter,with a fixed location monitor, or by taking spot measurements. In some studies, fixedlocation monitoring or spot measurements are made at multiple locations in order tocapture spatial variability. More recent studies have emphasized personal measurementsof exposure to magnetic fields by the use of data-logging meters, but some researchers
contend that spot measurements can be used to classify such exposure as well as personalmeasurements in some residential situations (Delpizzo et al., 1991); (Dovan et al., 1993).
Personal exposure monitoring was made possible by the availability of reliable compact
instruments, notably the AMEX-3D, EMDEX-C, EMDEX II, EMDEX Lite, andPositron meters. All of these meters measure the rms magnitude of the magnetic field,
thus sacrificing most of the information about the fieldÕs frequency content, spatial
orientation, and polarization. Magnetic fields are easier to measure for personal exposure
than electric fields because they are not perturbed by the body and other conductive
objects; however, some meters, like the Positron and the EMDEX-C, include both electricand magnetic field sensors and provide some indication of both components. Table 2.1
summarizes the characteristics of various common exposure meters.
The EMDEX II (Electric and Magnetic Digital Exposure meter), like many other datalogging meters, measures the near 60 Hz rms directional components of the magnetic field,
has some ability to distinguish higher-frequency harmonics, and can be used to monitor
electric fields when fitted with a sensor. The EMDEX II covers a frequency range ofabout 40Ð800 Hz. Sahl et al. argued that these frequencies probably contain information
about the biologically relevant characteristics of EMF, but biological support for that
assertion is limited (Sahl et al., 1994). The simplest meter, the AMEX-3D (Average
Magnetic Exposure), measures only the average magnetic field (i.e. the TWA) over time
(Kaune et al., 1992). All of the personal exposure meters except the AMEX-3D provide
data logging to capture temporal variation in exposures. Data loggers store measurements
at regular intervals, ranging from 1 s to 1 min. Investigators may explore various exposure
metrics in addition to the TWA, such as the geometric mean (GM) and the fraction of
measurements that exceed a threshold. In addition to personal exposure meters, many
hand-held survey meters are available for taking single spot readings of magnetic fields. A

18

comparison of many magnetic field meters showed that most are reasonably accurate
when properly calibrated (Misakian et al., 1991; Olsen et al., 1991).
EMF monitors typically have electronic filters to restrict measurement to bandwidths in
the ELF range. Most instruments have inductive coil sensors which cannot measure static
magnetic fields and which can produce a low-frequency signal (around 3Ð30 Hz), createdby motion through static field gradients, which is usually filtered out. Higher frequencies,
above 1 kHz in the very low-frequency band, from induction heaters, VDT, and othersources are also filtered out. Some exceptions exist: the portable MultiWave system hasflux gate sensors and captures both static magnetic fields and alternating fields up to about
3 kHz; the Positron meter includes a controversial high-frequency Ôtransient EMFÕ sensor
which detects radio-frequency electric field signals around 5Ð20 MHz (Deadman et al.,1988); (Heroux, 1991).
In studies in which measurement of personal exposure to magnetic fields is part of the
exposure assessment, hip-worn exposure meters are by far the most commonly used. As
some investigators have shown that exposure to magnetic fields varies with elevation, it
may be desirable to design monitors that could take measurements near potential target
organs (when known). Fortunately, monitors on the waist are close to the reproductive
organs and the pelvis, the largest reservoir of bone marrow and the presumed origin of
leukemiacells.
The efficacy of hip-worn and chest-worn exposure meters for estimating exposure of thewhole body and head was examined in detail by DelPizzo (DelPizzo, 1993). The
participants wore six exposure meters at a time, positioned at various locations on the
body. Over a 2-h period, they engaged in one of the following activities: office work(without a VDT), work on a VDT, mechanical work (excluding welding), and electronics
work. While DelPizzo found that hip-worn exposure meters consistently underestimatedwhole-body average and head exposure, the measurements were highly correlated (R =0.91 for whole body average, R = 0.83 for head exposure). Chest-worn exposure metersprovided better estimates of whole-body and head exposure than those worn on the hip.

2.3.2 Exposure metrics
Assessment of exposure to EMF has a number of challenging features. First, thisexposure is not perceptible by humans at typical nonoccupational intensities, so that it isdifficult to assess past exposure from questionnaires or other elicitation tools. Second, thesources of EMF are ubiquitous in modern urban life, and the contribution of manysources is only starting to be recognized. For example, currents flowing in the electricalgrounding systems of buildings or on water pipes can be an important source of magnetic
fields (Lanera et al., 1997). It is thus difficult to predict circumstances that might lead toparticularly high exposures or to identify situations in which little or no exposure will
occur. Third, EMF are highly variable in space and time and can fluctuate systematically19with electric power use (Bracken et al., 1993). Thus, measurements can be subject to large
random variation, and a carefully designed sampling plan may be needed to avoid poor
precision or systematic bias in the sample estimates. Fourth, there is no generally
accepted biophysical mechanism for the biological effects of EMF and no establishedbiomarkers of exposure or response. It is therefore very difficult to determine whichfeatures should be measured.
In exposure assessment, a way must be found to summarize the characteristics of
exposure across time, within groups of individuals, and between many exposure
environments. A variety of exposure metrics has been developed to capture the various
physical aspects of fields and to provide a summary measure of exposure characteristics
that can be aggregated across individual measurements.
A complete description of EMF is possible only with vector mathematics to describe themagnitude and direction in space of the fields over time. A large variety of summary
variables can be used to describe a time-varying EMF vector. These variables, called
exposure metrics, are intended to capture some particular aspect of the field; however, at
this time there is great uncertainty about which exposure metrics (if any) are related tobiological responses, and studies have been based mainly on the TWA magnetic field.
Some studies also have measured the magnitude of the electric field, and others have
explored exposure metrics related to the TWA, such as the geometric mean or percent
time exposed to > 0.2-mT threshold, but not in great detail. Consequently, the problem ofdefining and measuring a biologically relevant exposure to EMF is complex and largely
unresolved.
Valberg summarized many of the features of exposure to magnetic fields that can beconsidered in defining exposure metrics (Valberg et al., 1995). He identified some 18 field
attributes related to exposure in laboratory experiments (see below), but the list is also
applicable to human exposure assessment. The attributes fall into four major categories:(1)Êcharacteristics of exposure intensity and timing, (2) frequency domain characteristics,(3) spatial characteristics, and (4) combined EMF exposure characteristics. The firstcategory describes the magnitude and history of exposure, which is most often the focusof studies of exposure to EMF . The second category describes the frequency domain
aspects of exposure, such as harmonic content, intermittence, and switching transients,
which have been poorly characterized in most cases. The third category describes thecharacteristics of the vectorÕs spatial orientation, such as field polarization (periodic
rotation of the vector) and the spatial uniformity of the fields. The fourth category
describes the characteristics arising from combined vector fields, such as the joint
occurrence or orientation of alternating and static fields or the joint occurrence of electricand magnetic fields. These four categories represent a hierarchy of increasing complexity
in exposure assessment, and increasing levels of mechanistic detail are needed in order tospecify an appropriate summary exposure metric.

20

Despite the uncertainty about biologically meaningful metrics, assessment of exposure to
EMF has considerably advanced understanding of the sources and conditions that
contribute to EMF in daily life. A variety of factors have been hypothesized tocontribute to possible harmful effects of magnetic fields: TWA exposure, percent of timeexceeding a certain threshold, frequency harmonics, intermittent exposures, highly variable
and constant exposures, and peak exposures are just a few possible metrics considered.
To some extent, most time-dependent exposure metrics are correlated with the TWA fieldmagnitude, which is universally measured. Various EMF exposure metrics have been
compared in at least two studies, and many of the alternatives were found to be highly
correlated with the TWA magnitude of the magnetic field (Armstrong et al., 1990); (Savitz
et al., 1994). The high degree of intercorrelation among exposure metrics argues thatstudies in which TWA field magnitude is used as the primary exposure metric would
probably produce similar results, even with another metric of field magnitude; however,these two studies examined only a limited range of exposure metrics that are closely
related to the characteristics of exposure magnitude and timing (category 1 above). These
exposure metrics can be expected to be well correlated with the TWA field magnitude. No
studies have broadly addressed exposure metrics spanning all four of the above categories.
Some examples indicate that exposure metrics for other categories outlined by Valberg
may be only weakly correlated and inadequately assessed by relying on the TWA fieldmagnitude. For example, the magnitude of the electric field appears to be largely
uncorrelated with the magnitude of the magnetic field in the studies of Armstrong et al.
(Armstrong et al., 1990) and Savitz et al. (Savitz et al., 1994), which represent
comparisons involving combined EMF exposure characteristics (category 4). Breysse etal. (Breysse et al., 1994b) studied various measures of temporal variability, including
first-lag autocorrelation, and found that these exposure metrics ranked the exposures oftelephone workers quite differently than the TWA, suggesting a low degree of correlation.
Table 2.2 lists a variety of candidate metrics for exposure to magnetic fields which havebeen used in epidemiological studies. The Table summarizes the characteristics of each
metric in terms of its relation to five attributes of the measured magnetic field: magnitude,frequency content, time variability, spatial characteristics, and relationship to thegeomagnetic field. The measures of variation include metrics of both short-term andoverall variation, where short-term variation describes some measure of change in fieldmagnitude between two or more successive samples recorded in the data logger. The
variation measures are usually dependent on the sampling rate selected for the data logger:higher sampling rates usually show higher overall variation.
A number of epidemiological studies (see Section 4, and Section 2.3.4) have addressed theissue of adverse health effects and exposure to ELF magnetic fields and have used avariety of methods to evaluate power-frequency magnetic fields in residential
environments. The primary exposure metric measured has been the average magnitude of
the magnetic field. Other surrogate measures of exposure, such as wiring codes and job
titles, have also been used. Assessments of past exposure to magnetic fields have focused
primarily on the residential environment and on specialized occupations, such as electrical21

utility workers; however, these jobs are relatively rare in the general population, and far
more people are employed in other services, business, or industry, where there may also
may be high exposures (NIOSH, 1996).

2.3.3 Exposure environments
Assessment of exposure to EMF has tended to focus not just on the individual but also
on the environment in which the exposure takes place. This approach is useful for two
reasons: first, from the standpoint of defining homogeneous exposure groups it helps to
identify common sources and attributes of exposure or appropriate surrogates; second,studies focused on just one environment can derive greater detail for a particular study
population.
Four main groupings of exposure environments can be drawn from work on theassessment of exposure to EMF: studies of residential, occupational, school, andtransport environments. Together, these environments describe a large cross-section of
the US population. Occupational environments have been extensively studied in thecontext of specific industries and worker populations, particularly the electric utility
industry where high exposure to EMF was anticipated. Residential studies haveaddressed the exposures to children and adults, usually as part of population-based orcaseÐcontrol epidemiological investigations in selected cities. A nationwide survey ofresidences has been completed that provides a broad overview of sources of EMF in
homes. Exposure has also been assessed in schools and transport, but the literature is lessextensive.
Most of these studies have a cross-sectional design. In evaluating them, it must berecognized that the results reflect defined study populations over a particular time.
Extrapolating the results of one study to other groups or other periods necessarily
involves assumptions about the trends over time and how representative the results arefor other populations. Various surrogates and measurement techniques may be used, suchas job titles, spot readings, personal exposure measurements, and stationary monitoring.
These techniques may not always produce comparable estimates of exposure and may
have dissimilar errors or bias. Finally, the underlying purpose of the studies may differ:some are designed to characterize the exposures of particular individuals and others to
identify and characterize sources, appliances, or unique machinery in an industrial setting.
Many studies in the occupational environment are designed to characterize particular jobs
or work activities that may be used as surrogates of exposure, such as the exposures ofutility lineman or electrical power-line repair maintenance workers.

222.3.4 Exposure assessment for epidemiological studies
Direct measurements of relevant exposure for studies of health effects are often difficult
or impossible to obtain, particularly for chronic diseases. Sometimes, the exposure ofinterest occurred years earlier, the actual circumstances of exposure cannot be recreated,
access and cooperation of subjects cannot be obtained, or insufficient details are available.
For this and a variety of other reasons, it is frequently necessary to use surrogates insteadof direct measures. Exposure surrogates are individual or group attributes that can be used
to arrive indirectly at a ranking of the true exposure or to assign a numerical estimate of
the true exposure to an agent. Two primary surrogates have been widely used in research
on EMF: job titles in occupational studies and wiring configuration coding (wire codes) inresidential studies. These two surrogates and the validity of the methods are discussed indetail below. It should be noted that a direct measure of EMF may be considered an
exposure surrogate if the measured quantity does not capture the biologically meaningful
signal.
The concept of homogeneous exposure within groups is the underlying basis for exposure
assessment in most epidemiological studies. Ideally, when homogeneous exposure groups
exist, all members within the group have an essentially comparable exposure, and all
variation in exposure occurs between groups. Although this ideal situation never occurs, it
can be approximated. The exposure can be characterized by partitioning the total
exposure variation in an analysis of variance (ANOVA) model. The goal of the exposure
assessment is to identify a method of grouping individuals in which a large fraction of thetotal variation is between the groups and a small fraction remains within the groups.
Much effort has been devoted over the past 10 years to methods for identifying exposuregroupings and applying this concept to exposure surveys (Rappaport et al., 1993).
A frequent problem in epidemiological exposure assessment is defining the characteristics
that can be used to define exposure group membership. A variety of historical exposure
estimates have been used, such as field readings at some point in time (spotmeasurements), survey measurements in a residence or workplace, and personalmonitoring, but more often other factors, such as work, school, or residential
environment, duties performed at a work site, job title, or occupational history, are used
as grouping factors. These factors become useful exposure surrogates to the extent thatthey provide reliable, meaningful partitioning of the exposure variation in the study
population.
If measurements have large errors, the surrogates are not specific, or the data areotherwise unreliable, the exposure of study subjects to EMF may be misclassified.
Misclassification is often essentially random, leading to switching of individuals between
exposure groups. Misclassification may also have a systematic effect that affects certain
groups more than others. The effects of random exposure misclassification are usually todecrease the precision of an epidemiological study, making it more difficult to observe anassociation with disease. When there are multiple exposure groupings, random

23

misclassification can lead to spurious associations in the results (Flegal et al., 1986). The
usual effect of systematic misclassification is to bias the risk estimates, possibly creatinga specious association or masking a real one.

2.4

Occupational exposure

2.4.1 General occupational environments
A variety of methods for exposure assessment have been devised and applied toepidemiological studies of the effects of EMF in occupational settings. The methods range
from rather crude job-classification methods, to sophisticated jobÐexposure matrix (JEM)
modeling based on personal exposure measurements and reconstruction of past exposure.
The methods have their potential strengths and weaknesses and at best allow only an
estimate of the true exposure of the study population. In the following, except whereindicated, the assumed exposure metric is the TWA rms field or a closely related measureof ÔaverageÕ field magnitude.
The main features of the exposure assessment methods used in epidemiological studies
can be summarized by three terms: sensitivity, specificity, and potential bias (Lilienfeld& Stolley, 1994). The first two characteristics usually affect individual exposure
estimates relative to a group classification, while the last affects group estimates.
Sensitivity is the ability of the method to classify correctly an individual who is truly
exposed. Specificity refers to the methodÕs ability to classify accurately an individual
who is truly not exposed. Bias is the potential for shifting or skewing of exposure
estimates away from the true values. Consequently, a biased assessment method may
either systematically overestimate or underestimate desired exposure features for groups
of individuals in the study population. Bias can be introduced in many ways but mostoften stems from fundamental limitations of the study design or from limited access to a
portion of the study population. Bias can also be introduced by flaws in the samplingstrategy used in the exposure assessment, particularly when random sampling or
systematic sampling (stratified or cluster sampling) plans are not used.
Considerable emphasis has been placed on the use of personal monitoring for studies ofoccupational exposure to EMF. Personal monitoring relies on an exposure meter, which iscarried on a subjectÕs body to capture spatial and temporal variation in exposure as aseries of measurements over time. The individual is the sampling unit, which has theadvantage that both within-subject and between-subject exposure variation can becharacterized and homogeneous exposure groups can be formed. In some cases, spotmeasurements may provide a reasonable alternative to personal measurements. In
retrospective studies, it is impossible to measure the exposure of the same worker forwhom occupational information was gathered; subjects may be untraceable, dead, or
inaccessible for reasons of confidentiality or may be in a different exposure circumstance.

24

In such situations, it may be necessary to rely on contemporary measurements ofpersonal exposure from a different, surrogate worker. Contemporary measurements are
based on the premise that work practices and sources have remained relatively constantover time. If the spot measurements can capture relevant differences in exposures
between jobs, then use of surrogate workers is not necessarily any more meaningful thanspot measurements in a work area.
An occupational or work history is a body of data obtained for a study subject, whichcontains information on the jobs that the subject held throughout his or her working life.
Such information is often obtained through questionnaire interviews or databases such ascompany records. Work histories usually contain information on self-reported job andindustry title, company name, a brief job description, how long each job was held, andhours worked per week. In addition, medical records may be obtained from healthmaintenance organizations, doctorsÕ offices, and disease registries. Death certificates havealso been used to obtain information on occupations (Lin et al., 1985).
Job and industry titles are commonly used as surrogates for exposure to EMF and othertypes of exposure in epidemiological studies. As investigators often have no prior direct
measurements of the subjectsÕ past exposures, an entire occupational history must be recreated for each study subject and used to infer past exposure. Usually, researchers
cannot obtain individual measurements of exposure for all subjects in a study;
consequently, researchers have developed various ways of estimating the exposure ofgroups of individuals, by re-creating their occupational history and quantifying the related
workplace exposures.
Many coding schemes are available, including the Standard Industrial Classification,
Standard Occupational Classification (Table 2.3), US census codes, The Dictionary of
Occupational Titles, and international occupational codes. Although these codes provide
standardized classification methods for jobs or industries, most of these systems were
derived for economic or statistical recording purposes and not for the purpose of
exposure groupings. Consequently, the coding may not efficiently aggregate similar
exposures or even logically classify workers who perform similar tasks and have similar
exposures. The Standard Occupational Classification coding system has been widely usedin the USA for epidemiological studies. This coding provides a hierarchy of classificationthat at least tends to keep similar jobs in neighboring groups. This feature is useful whenaggregating data from many studies or for clustering jobs held over a working lifetime.
A JEM is a convenient way of organizing data that link job titles or an occupational
history to exposure. In a JEM, occupational classification is shown along one axis. Job
titles, industry categories, or a combination of these factors are included on this axis. The
exposure agent appears across the other axis. Where the rows and columns intersect in the
body of the matrix, a level of exposure is displayed. A degree of confidence is often added
to the level of exposure, or a percentage of the population exposed may be incorporated.
Early versions of JEMs can be traced back to the 1940s, but the first modern JEM wasreported in 1980 (Hoar et al., 1980). Although use of JEMs in occupational epidemiology
25

is relatively recent, it has gained wide acceptance in caseÐcontrol studies (Smith, 1987).
The main advantage is the possibility of collapsing many job titles into a smaller numberof homogeneous exposure groups. Combining workers into homogeneous groups allows
analysis and comparison of data exposure between groups, so that differences in jobÐexposure and doseÐresponse relationships can be explored. A JEM also can help toeconomize future research by combining data from many sources; JEMs are often used in
hypothesis-generating studies to re-analyze existing data.
Exposure level can be represented in several different ways in a JEM. The most basic
JEM simply indicates the presence or absence of a particular exposure for a particular job
title. If more information is available, exposure may be ranked, for instance as high,medium, or low. Numerical data from actual measurements is the most desirable source
for creating a JEM. In this case, each cell in the JEM ideally contains a group mean value
for the exposure metric and some measure of within-group variability.
Although early developments focused on exposure to chemicals, detailed data on personal
exposure make it possible to create a JEM for EMF. Today, JEMs incorporating
measurements are probably the best approach for assessing exposure to EMF in
occupational studies. JEMs allow merging of quantitative measurements with information
on job title, industry, and work site to arrive at a grouped estimates of exposure; however,
the availability of historically accurate information on exposure to EMF remains achallenge. In general, it is easier to assess past exposures agents such as solvents, because
exposure to them is much more memorable to workers or supervisors, and some groups
can be identified a priori as having little or no exposure. This is not true for EMF, sincevirtually everyone is exposed to some degree, and typical exposures are not memorable.
In addition, there are usually many more potential sources of EMF than chemicals in aworkplace (Savitz, 1993).
An alternative to measuring exposure for a JEM is asking a panel of experts to assign
exposure. Such experts should have background knowledge of the tasks in a job, sourcesof EMF, and specific exposure situations (Loomis et al., 1994a). Job and industry titles
may be insufficient to classify the exposures of workers in the absence of specificinformation on actual work sites. Expert judgment can incorporate this kind of sitespecific information, resulting in a better exposure assessment for a particular occupation
when information is obtained from a work history or from questionnaires (Post et al.,1991); (Kromhout, 1992). Often, an expert panel is made up of current or former
company employees, such as plant workers, supervisors, and industrial hygienists ormedical staff.
JEMs used in epidemiological studies of EMF are often specific to a certain industry or
location, such as electric power utilities, and may focus solely on occupational exposures.
The rational for ignoring residential exposures in occupational studies is the assumptionthat occupational exposures dominate the total daily or annual exposure to such an extent
that other sources are unimportant. This assumption has several potential flaws. First, it
presumes that the magnitude of the field is the appropriate measure of disease risk.
26

Second, it assumes that all exposures are additive in time. Third, it assumes that
residential sources are much less intense than occupational sources. Fourth, it assumes
that the timing of exposure and circadian effects (for example, exposure during sleep,
which is not typical on the job) play no role in defining a biologically meaningful
exposure. To some extent, all of these assumptions are questionable for EMF, but the last
two in particular are not supported by recent studies of EMF. TWA measures ofresidential exposure can be at least equal to those received in many jobs, and residential
appliances can contribute intense (but usually brief) exposure.
Job and industry title can be used as surrogates for exposure to EMF because they allow
assumptions to be made about the workersÕ duties. Certain tasks can be associated withhigh or low exposure to EMF. For instance, a worker employed as a welder is likely to be
exposed to high levels; in contrast, an agricultural worker picking fruit will probably havelittle exposure to EMF.
Retrospective exposure assessment from job titles can present problems. Workers withthe same job title or workers in the same industry today may not be have the same
exposures as workers had 20 or 30 years ago, and some job titles that were common in thepast may have been rendered obsolete by changing technology. For example, Ôkeypunch
operatorÕ was a common job in the computer industry but has essentially disappeared.
Another example is secretarial and administrative work: 30Ð40 years ago most such
workers probably sat at a desk with a telephone and a manual typewriter. Today, it iscommon for secretaries to have computers, fax machines, and photocopiers within armÕs
reach of their desks. The addition of these appliances may greatly increase average daily
exposure to EMF.
The classifications Ôelectrical jobsÕ and Ônon-electrical jobsÕ were developed by Milham
to dichotomize workers into exposed and unexposed groups (Milham, 1985). This
classification found wide use in early mortality and morbidity studies of EMF. Although
this grouping probably leads to considerable misclassification and does not allow
derivation of quantitative exposureÐresponse relationships, it makes few assumptions
about the nature of exposure to EMF. A three-level classification indicating a degree of
exposure to EMF, by background, intermittent, and continuous exposure, was used byGuŽnel et al. (GuŽnel et al., 1993).
Measurements of exposure to magnetic field have been collected in a number ofoccupational studies. Table 2.4 shows the exposures to EMF assigned to different job
titles in the occupational epidemiological studies reviewed in this document. The
occupations in which exposure to EMF is assumed to be above ÔbackgroundÕ levels arelisted in order of the arithmetic mean of the TWA magnetic field measured. These
exposures have been summarized in a JEM (Yost et al., 1997). When the standard
deviations are greater than the arithmetic mean, the distribution is skewed, and thearithmetic mean is not necessarily the best statistic for the central tendency (althoughmany investigators report nothing better). To give perspective, the Table includes
magnetic fields measured in some common occupations not considered to involve27

exposure to EMF and also includes percentiles from a distribution of TWA exposures
measured in a population-based study of male workers (Floderus et al., 1996).
Magnetic fields experienced in a variety of categories of jobs, homes, and offices wereassessed by Bowman et al. (Bowman et al., 1988) (see Table 2.5). They found significant
increase in exposure to EMF in electrical jobs overall. At the work sites examined, spotmeasurements were taken as close to the worker as possible in the direction of the most
likely field sources. In the residences, spot measurements were taken in the center of theliving room, bedroom, kitchen, and backyard, under conditions of both low and normal
power. The magnetic fields observed at work sites ranged from 0.003 mT(microelectronics assembler) to 10 mT (electrician in industrial power supply). Only a
few measurements were taken in the office environment: one secretary using a VDT had ageometric mean exposure of 0.31 mT. Three secretaries who did not use VDTs had ageometric mean exposure of 0.11 mT. In the 18 residences measured, a geometric mean
exposure of 0.06 mT was found.
Using personal exposure meters, Deadman et al. (Deadman et al., 1988) assessed theoccupational and residential exposure of a group of electrical utility workers and acomparison background group over one week. The study cohort consisted of 20 workers
from six electric utility occupations and 16 workers from two office buildings. Exposures
at work and away from work were determined for the two groups. The geometric mean
exposure was 1.7 mT for the exposed group and 0.16 mT for the background group atwork and 0.31 mT for the exposed and 0.19 mT for the background group away fromwork. The authors proposed that the difference was due to misclassification of somework as non-work. The background group had slightly higher exposure to magnetic fields
away from work than at work (0.19 vs. 0.16 mT). This difference was presumed to be dueto the greater use of hand-held and other electrical appliances at home.
In a study of exposures to magnetic fields in the electric utility work environment (Sahl etal., 1994), exposure to magnetic fields was obtained for 770 work days for the following
occupational categories: office staff, meter readers, mechanics, groundmen, lineman,splicers, laborers, plant operators, welders, technicians, machinists, substation operators,
and electricians. The fraction of exposures exceeding a 0.5 mT summary measure was used
to classify occupations into three main groups. The high-exposure group included
electricians and substation operators with mean exposures of 2.1 and 1.8 mT,
respectively; the low-exposure group included office staff, meter readers, and groundmen;
and the remaining craft occupations made up the medium-exposure group. The mean
exposure for three classifications of office workers (n = 73 workdays) was 0.1, 0.18, and0.23 mT.
Barroetavena et al. (Barroetavena et al., 1994) compared electric and magnetic fields
measured at 132 locations in three pulp and paper mills. The median magnetic field28

strengths in the three facilities were 0.12, 0.33, and 0.15 mT, respectively, which were
statistically significantly different (p = 0.006), on the basis of the overall electricalconsumption at each facility. Differences in measured magnetic fields were also observed
in offices at the facilities, with median measurements of 0.05 mT in two offices in one
facility, 0.18 mT in three offices in another facility, and 0.26 mT in five offices in thethird.
In Denmark, Skotte (Skotte, 1994) studied the 24-h exposure of electric utility workers,
office workers, industrial workers, and people living near high power lines to powerfrequency electromagnetic fields . A total of 396 measurements were gathered from 301
subjects, 55 of whom were office workers outside the utility companies. The geometricmean exposure observed for office workers was 0.09 mT (geometric standard deviation[GSD] 1.8). In normal residences, defined as those not near high-voltage transmission
lines, the geometric mean exposure of all study participants was 0.05 mT (GSD, 2.1).
Breysse et al. (Breysse et al., 1994b) measured ELF magnetic fields in officeenvironments by taking spot and personal measurements of magnetic field in a large
payroll department. Personal exposure was collected for 15 female employees with either
an EMDEX C or EMDEX II exposure meter. The spot measurements revealed exposure
to 0.13Ð2.7 mT for work with office equipment such as VDTs and photocopiers. The
highest measured flux density was attributed to an electrical utility duct. The TWA
personal work exposures were 0.1Ð0.65 mT (mean, 0.32 ± 0.15 mT).
Burch et al. (Burch et al., 1998) compared exposure to magnetic fields and light withurinary melatonin metabolites in 194 utility workers in northern Colorado, USA. This
study is unique because it related exposure to magnetic fields to a short-term change in ahuman biomarker. Magnetic field and light readings were collected from personal exposure
meters for full 24-h periods over five consecutive days. Post-shift and overnight urine
samples were used to follow melatonin metabolite excretion. A variety of exposure
metrics was used, including a measure of rate of change to describe temporal changes in
the field readings and a standardized rate of change metric to measure temporal stability.
The standardized metric closely predicted decreased melatonin excretion for both workand night exposures, the values being 0.64 ± 0.04 at work and 0.5 ± 0.04 during sleep for
distribution workers and 0.73 ± 0.03 at work and 0.58 ± 0.04 during sleep for office andadministrative workers. The TWA exposures over the same intervals showed noassociation with melatonin, unless combined with the standardized rate of change metric.
This result suggests that it may be important to characterize the temporal characteristics
of exposure to magnetic fields .
The EMDEX project, conducted by Bracken et al. (Bracken et al., 1995b), was one of thefirst to document personal exposure for a broad group of utility workers. The exposure ofvolunteers were collected from utility employees in 13 job classifications at 59 sites infour countries over one year. Uniform sampling procedures and data collection protocols

29were used at all sites. The volunteers kept diaries of the work and non-workenvironments they occupied while wearing an exposure meter. Approximately 50 000 hof exposure to magnetic fields taken at 10-s intervals were obtained, about 70% of whichwere from work environments. Exposure and time spent in environments were analyzed
by primary work environment, by occupied environment, and by job classification. The
utility-specific job classifications were typically associated with higher exposures; the jobclassifications with the highest (median workday mean) exposure were substation
operators (0.7 mT) and electricians (0.5 mT). Total variance also tended to be largest for
utility-specific job classifications, while the contributions of between-worker and withinworker variation to total variance were about the same. Estimates of time-integrated
exposure indicated that in utility-specific job classifications approximately one-half of thetotal exposure was received on the job. The distributions of non-work exposure werecomparable for workers in all job categories, with a median non-workday mean of about
0.09 mT.
Savitz et al. (Savitz & Loomis, 1995) studied exposure to magnetic fields in relation tomortality from leukemia and brain cancer among a cohort of 138 905 electric utility
workers at five companies in the USA. An extensive personal sampling protocol was used
to develop a JEM for exposure reconstruction. Randomly selected workers within
occupational categories wore a time-integrating magnetic-field meter (AMEX-3D) so thatdaily exposure could be estimated for job categories. The mean TWA exposures ranged
from 0.12 to 1.27 mT for the various categories. Exposure was estimated by linking
individual work histories to a JEM based on 2842 work-shift magnetic fieldmeasurements. The JEM was optimized to partition variance into between-day (thelargest contributor), within occupational categories, and between occupational categories.
Kromhout et al. (Kromhout & Loomis, 1997) examined the effectiveness of six alternative
grouping strategies for assessing cumulative exposure to magnetic fields in this study
population. The quantitative relationship between cumulative exposure to magnetic fields
and mortality from brain cancer was sensitive to the choice of grouping scheme, theoptimized grouping scheme indicating a stronger relationship than standard grouping
based only on job titles.
ThŽriault et al. (ThŽriault et al., 1994) conducted a large study of occupational exposure
to magnetic fields in relation to cancer risks among three cohorts of electric utility workers
in Ontario and Quebec, Canada, and France. A JEM was constructed after monitoring ofcontemporary occupations to link exposure to 50Ð60 Hz EMF to the occupational
histories of workers at three electric utilities: ElectricitŽ de FranceÐGaz de France,
170Ê000 men; Ontario Hydro, 31Ê543 men; and Hydro-QuŽbec, 21, 749 men. EachparticipantÕs cumulative exposure to magnetic fields was estimated from measurements ofthe current personal exposure of 2066 workers who performed tasks similar to those ofworkers in the cohorts. Past exposure was estimated from knowledge of current loading,work practices, and usage. The median cumulative exposure to magnetic fields was 3.1
mT-years, and the 90th percentile was 15.7 mT-years.

30

Baris and Armstrong (Baris et al., 1996b) conducted a substudy to investigate how
closely the exposures to magnetic fields based on the last job held compared with
exposures based on the workersÕ entire employment history within the company. The
correlations between exposure indices based on the last job and on all jobs varied between
0.75 and 0.78. The mean exposure of all workers was slightly lower when only the last
job was considered; however, the last job was particularly useful for identifying the mosthighly exposed people: the 90th percentile cut-point for the last job had a sensitivity =0.69, a specificity = 0.97, and a concordance = 0.66 in comparison with all jobs held.
These results indicate that use only of the last job to classify exposures results in agreater loss of information than a complete history. Although not all workers starting inhighly exposed jobs stayed in them, those who ended their working life in highly exposedjobs had been in these jobs for an extended period. [This finding may be limited to workwithin the same company.]
Floderus et al. (Floderus et al., 1996) conducted a large population-based study ofoccupational exposure to EMF (50 Hz) in relation to adult leukemia in Sweden. The
exposure assessment was based on a JEM derived from extensive measurements ofpersonal exposure in 1015 workplaces. The JEM derived from these data covered 100 of
the commonest occupations in Sweden, with a minimum of four measurements for each
occupation. The median workday mean was 0.17 mT, and the 95th percentile was 0.66
mT. Median workday means for occupations with low exposure were 0.04 mT for earthmover operators and 0.05 mT for concrete workers; the corresponding value for electricaland electronics engineers and technicians and welders was 0.19 mT. Overall, the workday
mean in the population was 0.28 mT with a standard deviation of 0.62. This data set isperhaps the most extensive to date for exposure of the general population to EMF.

2.4.2 Visual display terminal operators
Some studies have investigated VDTs as a source of exposure to EMF, particularly inconnection with adverse reproductive outcomes. VDTs are relatively unique EMF
sources in that they produce a broad range of ELF frequencies and VLF harmonics
ranging from about 50 Hz up to 50 kHz. VDT sources are often directional and havecomplicated time-varying vector properties. Measuring these sources requires carefulattention to instrumentation if the desired field parameters are to be captured. Many
studies of VDT operators have relied on surrogate exposure measures such as time spentin front of a VDT, distance to the VDT, and job titles. Sometimes, spot measures of fieldmagnitude over a limited portion of the ELF band at a fixed distance in front of the VDT
are used to estimate exposure. Haes and Fitzgerald (Haes & Fitzgerald, 1995) obtained
measurements of VLF magnetic fields from 140 VDTs and electric field measurementsfrom 40 devices over a three-year period. They compared measurements 50 cm from thecenterline of the screen with readings taken 30 cm above the seat, at the approximate
location of the reproductive organs of a seated female user. The results demonstrate little
correlation between the two locations.

31

The validity of various exposure surrogates for describing exposure to EMF in office
VDT users was examined by Abdollahzadeh et al. (Abdollahzadeh et al., 1996). They
compared 8-h TWA personal exposures to 30Ð1000 Hz magnetic fields at waist levelwith a variety of surrogates including: measurements of magnetic fields at 40Ð1000 Hz ata fixed distance from the VDTs; reported hours of VDT use; and reported distance
between the VDT and the subjectÕs waist. The results showed a weak correlation between
the 8-h TWA exposure of a VDT user and the magnetic field measured 46 cm from the
VDT (R = 0.52, n = 67, p < 0.001). They found no association between self-reported
hours of VDT use or self-reported distance between waist and VDT and the averagemagnetic field. Moreover, individualsÕ average exposure to magnetic fields did not seem tobe affected by other variables such as the position of the VDT on the desk, hours of deskuse, and the VDT type (color vs. monochrome).
Nair and Zhang (Nair & Zhang, 1995) also examined a variety of exposure metrics for
VDTs by a method based on effects function, to determine the extent to which VDTs canbe distinguished from other common sources. They found that that VDT exposure may
be of consequence if exposure depends on certain types of time variation of the field.
Their work demonstrates that the choice of an exposureÐresponse relationship (i.e. theeffects function) can determine if a source will make a small or large contribution to thetotal exposure.
A study by Lindbohm et al. (Lindbohm et al., 1992) of exposure to VDTs in connection
with spontaneous abortions incorporated both measurements and exposure surrogates.
They assessed the type of VDT used and the duration of use by questionnaires andemployer information. ELF and VLF magnetic field measurements on a representative
sample of VDT units in a laboratory provided the exposure information. A relatively highthreshold of 0.4 mT (ELF) was used for VDT readings to define the low-exposure group;
the high-exposure group was defined as receiving > 0.9 mT. This grouping scheme made it
likely that VDTs would be a strong contributor to exposures, although validation could
not be made with personal exposure readings. Electric fields were measured with an active
dipole antenna which had a frequency response extending up to 10 Mhz (see Table 2.1).
The electric fields 30 cm from the screen were in the range 1.8Ð22 V/m.
These studies point out the difficulties of conducting a study of VDT operators due tothe many possible sources of exposure and the problems in defining an exposure metricthat captures the unique characteristics of VDTs.

2.5

Residential exposure
The exposure assessment method known as wiring configurations or Ôwire codingÕ
developed by Wertheimer and Leeper (Wertheimer & Leeper, 1979) in a study ofchildhood leukemia deserves special mention because of its place in the literature on
EMF. Wire coding was developed in Denver, Colorado, USA, to provide a surrogate
32measure of exposure to EMF, with a relatively simple scheme for ranking possible
exposures by assigning residences into wiring configuration categories. The originalclassification had only two categories, but this was expanded later to five categories:
underground wiring, very low current configuration, ordinary low current configuration,
ordinary high current configuration, and very high current configuration (VHCC) homes(Wertheimer & Leeper, 1982). The classification scheme is based on the identifying
characteristics of the power lines visible from outside a home and the distance from thehome to the wires. Therefore, it does not require access to the home or instruments, and it
can be used to assess exposure in current and previous residences, thus largely avoiding
participation bias.
Wire coding is also a historically stable metric because the type of power distributionlines outside a house do not in general change much over the years. This method is often
used in retrospective studies, in which historical stability is important; however, othertypes of error such as misclassification of wires may be introduced. Wire coding may also
introduce confounding or bias that has not been fully understood. Researchers havecontinued to measure residential exposures with methods such as wire coding, despite thelimitations of this method and the modest association with measurements of magnetic
fields taken in residences. Wire coding does not provide an estimate of exposure to electricfields within homes (Savitz, 1993).
Table 2.6 shows the distribution of wire codes from seven studies conducted in the USA
over the past 15 years. The prevalence of homes with VHCC varies markedly across thestudies, from 3% in Denver to 12% in Los Angeles. As some studies excluded
underground wiring in homes, the proportions in the remaining categories are somewhat
inflated. Table 2.7 shows measured magnetic fields with wire code categories in six studies
conducted in the USA since 1982. Measures of central tendency were selected from thoseavailable in the studies. Considerable variation can be seen in the measures in eachcategory and particularly in the highest VHCC wire code category, probably reflecting thevarying ability of wire codes to capture higher exposures. Table 2.8 shows the percentage
of homes in various wire code categories with measured values above a 0.2 or 0.3 mTthreshold and indicates that the usefulness of wire codes for identifying high field values
in homes varies widely. The proportions in categories in studies from which undergroundhomes were excluded should be interpreted with caution since they are inflated relative tothe others.

2.5.1 Direct measurements
One of the earliest residential studies in which direct magnetic field measurements wereused in addition to wiring configurations was the study of childhood cancer conducted in
Denver, Colorado, by Savitz et al. (Savitz et al., 1988). The authors relied on spotmeasurements of the field magnitude taken inside the residence to assess potential
exposure to EMF. Although the study showed an association between wire codes and33

magnetic fields, it found no association between wire codes and electric fields (see Table
2.7).
DelPizzo et al. (Delpizzo et al., 1991) tested the usefulness of spot measurements forclassifying residential levels of magnetic fields. Spot measurements were compared withdata collected from stationary 24-h monitors. Homes with mean 24-h magnetic fields >0.075 mT were classified as exposed, and those with mean levels < 0.075 mT wereclassified as unexposed. They found that a single spot measurement had at least an 80%
chance of classifying a house in agreement with the classification based on the 24-h meanmagnetic field and concluded that a small number of readings collected manually over
several points within a home can serve to characterize the magnetic field as well as
stationary monitoring. DelPizzo and Salzberg (Delpizzo & Salzberg, 1992) found that
averaging four or five spot measurement readings over time instead of using a single point
in time measurements resulted in a dramatic improvement in the observed-to-true ratio forclassifying residential fields; however, these studies were limited because the stationary
24-h measurements in the homes were used as the measure of ÔtrueÕ exposure. The
authors did not measure personal exposures and could not assess the effects of personal
activity and use of appliances on exposure classification.
Spot measurements were the basis of a standardized protocol for measuring magnetic
fields in homes for a large study of reproductive toxicity conducted in northern California(Yost et al., 1992). A pilot study, which involved taking 252 spot measurements in 24
San Francisco Bay Area homes, was conducted to identify an appropriate samplingstrategy. Measurements were taken in multiple locations (center, front right, front left,back right, and back left) in the kitchen, living room, and bedroom of each home, underboth low-power (all electrical devices turned off/unplugged) and normal-power
conditions. They found that the center normal-power spot measurement wasrepresentative of those in other locations. In addition, 79% of the variation in home spotmeasurements was due to differences between homes (p < 0.00001). The differences
between rooms were also significant (p < 0.01). In this protocol spot measurements weretaken at the front door and in the center of the kitchen, living room, and bedroom undernormal-power conditions. Under that protocol, no more than 45% (and probably
considerably less) of the variance would result from within homes. The authors pointed
out that London et al. (London et al., 1991), using a similar spot measurement protocol,
reported that 19% of the variance was within homes.
In an earlier study, Silva et al. (Silva et al., 1989) reported the spatial distributions of thevertical magnetic field in five types of room found in residences: living rooms, dining
rooms, bedrooms, kitchens, and bathrooms. Scatter plots of the vertical field component
in the various rooms showed correlation coefficients between center-of-roommeasurements and elsewhere within the same room that ranged from 0.64 to near 0.8.
Although measurements were performed in 81 residences, they were limited because onlya single field component was recorded.

34

The Electric Power Research Institute (EPRI) conducted a survey of 996 residences todetermine the levels and sources of residential power-frequency magnetic fields(Zaffanella, 1993). The survey, often called the ÔEPRI 1000 homes studyÕ, involved arandom two-stage cluster sampling plan to achieve a statistically representative sample of
EPRI utility customers nationwide. This unique survey, although not designed to describe
individual exposures, provides a snapshot of residential fields and the results are probably
reasonably representative of residential conditions. An extensive measurement protocol
was used, including spot measurements inside the rooms, field recordings in the home,
Wertheimer-Leeper wiring codes, measurements of field profiles from wiring outside thehome, measurements of household appliances, and measurement of fields from currents inthe electrical grounding system. The overall average spot magnitude of the magnetic field
inside the surveyed residences was 0.09 mT. The median value for the average spot
magnetic field reading was 0.06 mT and exceeded 0.29 mT in 5% of all measured
residences. The survey results were corrected by reference to the sample base population
representative of national residences. About 28% (95% CI = 22Ð34) of the homes
nationwide exceeded an average interior magnetic field magnitude of 0.1 mT, about 3.3%
(95% CI = 1.7Ð5%) exceeded 0.25 mT, and 0.3% (95% CI = 0.1Ð0.6) of residences
exceeded 0.5 mT.
The 1000 homes study included extensive engineering investigations to identify possible
determinants of residential magnetic fields. In most residences, currents in outside powerlines and currents flowing in the electrical grounding system were the dominant
contributors. Power lines contributed most to the background average magnitude of themagnetic field distributed over the entire residence over the course of a day. Thus, powerlines were identified as a significant source of the background fields in the homeenvironment. Currents flowing in the electrical grounding system, in contrast, produced
larger variations in magnetic fields over space and time. In some cases, specific features ofthe electrical system in the residence could be linked to higher magnetic fields: groundingof electrical sub-panels contributed in 4.6% of residences, multiple three-way switches in
5.2% of homes, electric ceiling heat in 2% of homes, and old-style wiring (knob and tube
wiring) in 7% of homes. Other more general characteristics of the homes were also
associated with higher fields. For example, fields were typically higher in older residences,
homes with grounding to a metallic water line, and in duplex or apartment residences.
Factors found to be unrelated to interior magnetic fields were household electric energy
consumption, construction materials, presence of electric heating (other than radiantceiling heat), and the presence of children in the home.
One goal of the survey was to evaluate various measurement methods to reliably classify
residences with regard to interior magnetic fields. Previous studies had involved a variety
of protocols, such as 24-h recordings and spot measurements taken in several rooms, tomeasure magnetic fields. One comparison of considerable interest concerns the usefulnessof spot magnetic field measurements to correctly identify high-field residences. The
protocol of the 1000 homes survey was similar to the California protocol describedabove, with spot measurements taken at the center of several rooms in the home. In the1000 homes survey, 24-h measurements were also made of both power-line fields and35

grounding-system fields and they were combined to estimate median fields in theresidences. The results are shown in Table 2.9. Remarkably, the median spot readings
obtained with the two methods agree quite well. This shows that spot measurements
could be used as a first approximation for characterizing magnetic fields in homes.
Table 2.9. Estimated median magnetic fields in the 1000 homes survey
60 Hz magnetic field spot measurements (mT)a% of homes inwhich values
were exceeded

Kitchen

50
25
15
5
1

0.07
0.12
0.24
0.35
0.64

Bedrooms

0.05
0.1
0.2
0.29
0.77

Highest24-h combined fieldfrom power-line andground system(median)b

All rooms

0.11
0.21
0.38
0.56
1.22

Average

Median

0.06
0.11
0.21
0.3
0.66

0.05
0.1
0.17
0.26
0.58

0.05
0.10
0.18
0.26
0.55

a

Data from 992 residences
Data from 986 residencesc
Room with highest spot readingb

Kavet et al. (Kavet et al., 1992) assessed the exposure of adults in Maine who lived either
near or far from overhead transmission lines. The assessment included 24-h personal
exposure measurements, spot measurements in three rooms of every residence, and a 24-h
fixed location bedroom measurement. They found greater home and total exposure forsubjects residing near highly loaded transmission lines than for subjects living far awayfrom power lines. Both the room spot measurements and 24-h fixed-site bedroom
measurement were correlated with home exposure (R = 0.70 and 0.68, respectively).
Similarly, in another residential study, Kaune et al. (Kaune et al., 1987) found that spotand 24-h magnetic field measurements were associated, with a correlation coefficient of
0.5.
Kaune et al. (Kaune et al., 1994) also studied 29 children four months to eight years of age
to determine whether area (spot and/or 24-h) measurements of power-frequency magnetic
fields in residences and schools could be used to predict measured 24-h personal
exposures. The average 24-h personal exposure observed was 0.1 mT (geometric mean).
Greater variation between subjects was found for home exposure than for school
exposure. The TWA spot measurements in the home were highly correlated withresidential personal exposure (R = 0.9). On the basis of these findings, they established a
protocol for measuring residential exposures to magnetic fields. This protocol, like theCalifornia protocol developed by Yost et al. (Yost et al., 1992) calls for the following
measurements: spot measurements inside the home (center of the subjectÕs bedroom,
kitchen, and one other room occupied most frequently by the subject), spot36

measurements taken immediately outside the front door, and a 24-h fixed measurement in
the subjectÕs bedroom.
The repeatability of assessments of residential magnetic fields and wiring codes was
examined by Dovan et al. (Dovan et al., 1993) in a study widely known as the Ôback to
DenverÕ study. The purpose of the study was to evaluate the long-term stability of wire
codes and residential spot magnetic field readings in classifying residential magnetic fields.
Wiring code and magnetic field measurements obtained in Colorado homes in 1985 as partof the Savitz study were compared with measurements taken more than five years later.
The wire code measurements were in agreement for 73 of 81 homes (90%), and thecorrelation between spot magnetic field measurements taken in 56 homes in 1985 andmeasurements taken in 1990 was R = 0.7. A diurnal trend was observed when the averagehome spot measurements were compared over 24 h, the highest magnetic fields being
observed in the late afternoon or early evening and the lowest in the early morning.
London et al. (London et al., 1991) investigated the relationship between childhood
leukemia and measurements of EMF in homes or exposure assessed by surrogates such as
wiring configurations and self-reported use of appliances in Los Angeles County,
California. They recorded detailed measurements of the magnetic field in the childÕs
bedroom over more than 24 h (164 cases and 144 controls), spot measurements of EMF(140 cases and 109 controls), and wiring configurations. The 24-h average magnetic fieldrecorded for the controls was reported as 0.12 ± 0.16 mT and the 90th percentile was 0.19
± 0.3 mT. The average electric field in the bedrooms of controls was reported as 8 ± 12
V/m. A gradient in the average magnetic field readings was observed for increasing wiringconfiguration categories: homes with underground wiring, 0.05 mT, and VHCC homes,
0.12 mT. The measurements were similar to those reported by Savitz in Denver, but theprevalence of VHCC homes was higher (11% of control homes in Los Angeles and 3.1%
in Denver).
The correlation between magnetic fields and exposure over time was also examined by
Kaune and Zaffanella (Kaune & Zaffanella, 1994). Their exposure assessment
incorporated spot measurements, stationary 24-h measurements in two locations, andpersonal exposure measurements for 35 children living in western Massachusetts andnorthern California. Measurements were taken in the spring of 1990 and again in thewinter of 1990Ð1991. They found a poor correlation between personal exposure
measured at the two times (R = 0.1) but fair correlations between spot measurements
repeated twice (R = 0.7) and between stationary 24-h measurements repeated twice (R =0.8).
Kleinerman et al. (Kleinerman et al., 1997) reported on assessment of exposure tomagnetic fields for a nine-state residential study of childhood leukemia. Residential
magnetic fields were measured in 1354 current and former homes of cases and controls inthe study . The TWA magnitude of the magnetic field weighted by the length of time thesubject lived in each home was the main exposure metric. The TWA for subjects wasestimated by a weighted average of the 24-h bedroom reading with spot readings taken in37

other rooms. They found that 24-h bedroom measurements adequately characterized theresidential exposure of children and that measurements in other rooms contribute only
slightly . The mean value for the TWA magnetic field in the homes was 0.11 mT, with astandard deviation of 0.11. All of the spot readings were highly correlated with the 24-h
bedroom average; the rank correlations ranged from 0.83 in the bedroom to 0.66 forkitchen locations. Front-door spot measurements provided useful information wheninterior measurements were missing. The rank correlation of the front-door spot reading incomparison with the 24-h reading in the childÕs bedroom was 0.72; this improved to 0.79
when compared with the estimated TWA for the whole residence. [This study indicatesthat contemporary spot measurements or front-door readings are reasonably reliablepredictors of other contemporary measures of residential magnetic field magnitude.]Friedman et al. (Friedman et al., 1996) provided the basis for the residential magnetic fieldsurvey methods reported by Kleinerman. They compared 24-h stationary measurements
in a bedroom with personal exposure measurements for 64 children aged 2Ð14 years
during a typical weekday. The information recorded in activity diaries indicated that thechildren spent more than 40% of the 24 h in their bedrooms and 68% of their time athome. For children under nine, the levels of exposure at home were highly correlated withtotal personal exposure (R = 0.94); the correlation was lower in older children (R = 0.59).
The 24-h bedroom measures correlated well with personal exposure at home (R = 0.76)
for all of the children combined. [These results indicate that 24-h bedroom measurement isa good predictor of both residential and total personal exposure, particularly for younger
children.]
Zaffanella et al. (Zaffanella & Kalton, 1998) made a US nationwide random-sample
survey of 1000 individuals to provide a more comprehensive picture of exposure tomagnetic fields. This study is the first serious effort to evaluate a cross-section of
exposure to magnetic fields in the general population. Although somewhat limited by the
response rates and potential participation bias, the study provides valuable insight into
total exposure to magnetic fields. The preliminary results of this survey were released at a
symposium on engineering research into magnetic fields organized by the DOE. The
subjects for the survey were recruited by telephone, and those who agreed to participate
were mailed a packet with instructions, a time-activity diary, and a personal exposure
meter that recorded the magnetic field resultant at a 0.5-s sampling rate. The following
conclusions were drawn from the interim analysis of 853 individuals:¥

The distribution of 24-h TWA exposure in the population is approximately lognormal with a geometric mean of 0.09 mT (95% CI, 0.085Ð0.096) and a geometricstandard deviation of 2.2 (95% CI, 2.1Ð2.3).

¥

Approximately 15% (95% CI, 12Ð18%) of the population was estimated to be have
24-h TWA exposure exceeding 0.2 mT, about 2.4% (95% CI, 1.5Ð3.9%) to have
exposures exceeding 0.5 mT, and about 0.4% to have exposures exceeding 1.0 mT. The

38

last value indicates that about 1 million people in the USA have an average 24-h
exposure greater than 1.0 mT.
¥

Some variation in 24-h exposures was found by age: the geometric mean exposure forworking-age people was about 0.1 mT, and that for retirement-age people was 0.08
mT. The geometric mean exposure for school-age children was about 0.08 mT, and thatfor pre-school children, 0.06 mT.

¥

About 0.5% of the population have an estimated maximum (peak) exposure tomagnetic fields of 100 mT.

2.5.2 Calculated historical fields
Feychting and Ahlbom (Feychting & Ahlbom, 1993) conducted a study of leukemia inchildren living near high-voltage transmission lines in Sweden. An important feature ofthis study was that a computer model was used to calculate magnetic fields from thetransmission lines in homes around the time of diagnosis, rather than relying oncontemporary measurements. Those calculations of the magnetic fields from thetransmission lines that took into account distance from the home, the power-line
geometry, and the current load on the line are reliable for transmission lines because of thetechnical characteristics of those lines and the availability of the necessary data.
Information about historical current loads on the power lines was used to calculate themagnetic fields for the year closest to the time to diagnosis. The model was evaluated bycomparing calculations based on contemporary transmission line currents with
contemporary spot measurements of the magnetic field. The calculated fields showed
good agreement with spot measurements in single-dwelling homes. For example, in thehighest measurement category (> 0.2 mT), only 15% of the calculations underestimatedthe contemporary measurements. The calculated values showed poorer agreement withmeasurements in apartments; for example, in the highest measurement category (> 0.2mT), 47% of the calculations underestimated the contemporary measurements. The
overall discrepancies between calculations and spot measurements for single homes andapartments were 11% and 32%, respectively. [While information on historical load
currents permitted estimations of past exposure to magnetic fields in this study, thecalculated values did not capture contributions to the field from local sources. Also, thecalculated values can only be as good as the quality of the load current data.] The
historical currents were known to within 100 A increments, and the average historical load
current was 300 A (Kaune et al., 1998). [The effect of the above factors on the amount of
exposure misclassification cannot be estimated from the available information.]
The Swedish study of transmission-line fields represented an important advance overprevious studies that were based on distribution-line wiring configurations in that itprovides a method for estimating historical fields. The calculations are based on
established laws of physics and on available physical and operational data rather than on
39

empirical classifications, as for the Denver wiring codes. The calculation method can not
be reliably applied to distribution lines because of fundamental differences in the designand operation of the lines and the lack of historical data on load for distribution lines.
Consequently, only the magnetic field contribution of the transmission lines can bereliably evaluated. Feychting et al. (Feychting & Ahlbom, 1993) applied the magnetic
field calculation method to distribution lines near an unreported number of residenceswhere the distribution line was judged to be a potentially important source of exposure tomagnetic fields. [The questionable validity of the calculated field levels near distributionlines may have contributed to some of the inconsistency between contemporary
measurements and contemporary calculations discussed above.]
Feychting and Ahlbom (Feychting & Ahlbom, 1994) conducted a study of adult cancers
in relation to calculated historical fields. The exposure assessment method was virtually
identical to that used by the same authors in their study of childhood cancer (Feychting &Ahlbom, 1993), except that one of the dose metrics calculated was cumulative exposure
during the 15 years before diagnosis.
Li et al. (Li et al., 1997) conducted a study of adult cancers in relation to calculated
historical fields in Taiwan. They considered in some detail the locations of transmission
lines (five voltage categories, from 69 to 345 kV) and homes, with distance readings
derived from maps. The stated distance resolution was ± 10 m. The exposure fields were
calculated from formulas based on the Biot-Savart law, accounting for line height, phasing,and other factors. No adjustment was made for local distribution lines or local sources,
although for apartments the assumed building height was raised to 15 m. The historical
average annual load currents, distances from homes to conductors, height of conductors,
current phase, and geographic resistivity were provided by the Department ofTransmission and Substation Project. Data on the resolution and accuracy of the line
current used for historical measurements were not provided. The model calculations werevalidated by comparing contemporary calculations and measurements, with mixed results:
with fields partitioned into three categories < 0.1, 0.1Ð0.2, and > 0.2 mT, the comparisons
showed a concordance of 0.64 between the two exposure estimates. Measurements andcalculations for the category > 0.2 mT, with cut-points 0.5 and 1 mT had a concordance of
0.82. The model calculations appeared to have the best predictive value for the highest
exposure categories. [The discrepancy between calculations and measurements may be
due in part to a contribution of local magnetic field sources to the field, but no indication
was provided that the discrepancy is due to the presence of measured fields that were toohigh or too low. The ± 10-m precision of distance could have had a significant impact on
calculations for residences within 20 m of the power lines but would contribute less error
for points further away from the transmission line.]
Valjus et al. (Valjus et al., 1995) conducted a detailed analysis of historical field modelingcalculations for a study of cancer in Finland. They examined the uncertainty in model
calculated fields from transmission lines with considerable thoroughness. For example, theerror distributions of power-line and building locations, hourly measurement records ofload currents, tower dimensions, variations in conductor height, phase of currents, non-40

parallel lines, and unbalanced currents were considered in a Monte Carlo analysis. The
estimated precision of historical load data was examined by comparison of the estimate tocurrents calculated from power measurements. The estimate and the calculated value werehighly correlated (R2 ~ 0.85). The resolution reported for distance was ± 10 m. [Despite
the completeness of the analysis, it is remarkable that no measurements of the magnetic
field were performed as part of a verification process for the calculations.]
Olsen et al. (Olsen et al., 1993) calculated magnetic fields to estimate human exposure
from power lines and substations for a study of cancer in Denmark. The input parameters
for the calculation include distance of the dwelling from source, type of line, dates of
construction and reconstruction, average current for year, and ordering phases. [Theproblems with this study include: only estimates of historical load currents wereavailable, which were provided by experts experienced in the planning and operation of
the Danish transmission system; there was no experimental verification of thecalculations; and the geometry of substations is much more complicated than that oftransmission lines, entailing greater uncertainties. The use of experts is probably not aserious flaw, since they probably had information on historical annual currents fromplanning surveys.]
In a follow-up analysis of their study of childhood leukemia, Feychting et al. (Feychting
et al., 1996) investigated the importance of short-term variability in the time interval ofmeasurement and other factors in residential exposure assessment. They evaluated thevalidity of contemporary spot measurements and the relative importance of distance frompower transmission lines, and, when estimating past exposure to magnetic fields,
calculated them with a computer model. Spot measurements were taken 5Ð31 years after
diagnosis, with a median of 16 years. Their study showed that distance was not a simple
surrogate for exposure, as first suggested. The relative risks for measurements at the timeof the study (contemporary annual average fields, spot calculations, and spotmeasurements) were all close to or below unity. Neutra and DelPizzo (Neutra &DelPizzo, 1996) noted that spot readings appeared to have poor sensitivity, specificity,and predictive value, even though historical fields were reasonably well correlated with
contemporary spot readings (R = 0.7).
[Together, these studies suggest that it is important to account for the historical
relationship between exposure and disease outcomes. Contemporary spot or daily
readings may introduce enough random and systematic error to obscure or enhance a
possible association with disease risk.]
Zaffanella et al. (Zaffanella et al., 1997) studied the use of computer modeling to estimate
residential exposures, which could be useful for assessing exposure when access toresidences is not possible or when planning a residential development. They used the
RESICALC computer program to model magnetic fields due to currents on arbitrary
configurations of electric transmission lines, primary and secondary distribution lines, andground-return currents in neighborhoods based on residential loads and impedance.

41

Experiments conducted at the Magnetic Field Research Facility in Lenox, Massachusetts,
simulated a residential electric distribution system. The results showed that the program
could accurately model magnetic fields from both supply and ground currents. In somecases, the estimated fields were sensitive to impedance values assigned to the groundnetwork. [Computer modeling for distribution lines requires intensive effort for input datacollection, such as careful mapping of power lines, residential coordinates, acquiring load,and grounding data. These input values are critical if the model is to give valid estimates of
exposure; however, because these input data are not routinely available and would require
special instrumentation to be installed by the electric utility, widespread use of thiscomputer model would be difficult.]
Bowman et al. (Bowman et al., 1997) studied magnetic fields in residences using aphysically based multipole model. The model parameters were determined by nonlinear
regression techniques in order to fit the 24-h magnitude of the magnetic field recorded in achildÕs bedroom. The predictions were better correlated with the bedroom readings (R =0.4) than with Wertheimer-Leeper wire codes (R = 0.27). [Since this model has not beentested in other locations, its generalizability is unknown.]

2.5.3 Wire codes as an exposure surrogate
Kheifets et al. (Kheifets et al., 1997c) examined data on wire codes and spot magnetic
field measurements from seven studies to determine the distribution of wire code
categories among residences in different parts of the country. The percentage of homes
falling within the VHCC category varied markedly among the data sets, but all fell within
the range observed between controls in the study of Savitz (~ 3%) and in the study of
London (~ 12%). Of the five studies with intermediate values, all showed less than ~ 8%homes with VHCC, except for the control homes in the study of Preston-Martin (11%)
which was conducted in the same city as that of London. The number of homes in the
two lowest categories was markedly smaller in Los Angeles (London et al., 1994; PrestonMartin et al., 1996b) than in the areas with predominantly lower-category homes. The
authors also examined the distribution of spot-measured magnetic fields within each of thewire code categories in four of the data sets. All showed a monotonic trend for increasing
median field with increasing wire code in the ordinary low current configuration, ordinaryhigh current configuration , and VHCC categories, but the 10Ð90 percentile ranges in eachcategory overlapped widely. The range of fields measured in each wire code category weresimilar in the data from the 1000 homes study and the EMDEX residential data sets(measured at numerous locations throughout the country) to that in the Savitz data set
but markedly larger (spanning higher values) than that in the London data set. [Thesefindings suggest that the relationship between wire codes and spot magnetic fields are in
general similar throughout the country to that observed by Savitz in Denver but markedly
different in the Los Angeles area.]
Kheifets et al. (Kheifets et al., 1997c) also reviewed the historical stability of spotmeasurements and concluded that they are sufficiently stable over a period of five years
42

to make them suitable for estimating past exposure. In another data set, they examined theusefulness of various surrogates (wire codes, stationary measurements, spotmeasurements, and personal exposure measurements) for estimating personal exposure
measured approximately four months earlier. Contemporary two-day personal exposure
measurements were the best indicator of personal exposure, and wire codes were thepoorest. The percent variability in exposure explained by the surrogate was 15% for wire
codes, 46% for 24-h recordings, 54% for spot readings, and 66% for personal exposures.
Contemporary spot and 24-h stationary measurements were similarly effective for
estimating past exposure and intermediate between contemporary personal exposure andwire codes in effectiveness. The authors concluded that the potential for exposure
misclassification when using wire codes is similar to or greater than that forcontemporaneously measured magnetic fields.
Tarone et al. (Tarone et al., 1998) examined the relationship between wire code category
and 24-h magnetic field measurements on a state-by-state basis over a nine-state study
area. There were insufficient data from Wisconsin for its inclusion in the analysis. Moremean measured fields were in the VHCC category than in other categories in six states;
two states in which there was no strong trend for increasing fields with wire code
(Michigan and Minnesota) were among those with the fewest VHCC homes (four andthree homes, respectively). Thus, the aberrant relationship between high wire code andfield is probably a result of random variation due to small numbers. [This conclusion is
supported by the observation that in the other state with few VHCC homes, the highest
mean field was found in those homes.]
Tarone et al. (Tarone et al., 1998) also looked at the distribution of homes with different
wire codes, the distribution of mean and median fields within wire codes, and thepercentage of homes with exposure > 0.2 and 0.3 mT within a wire code category. While
wire codes did not differentiate among measured values, as in the study of Savitz, they
were more effective than in the London study. The effectiveness of using wire codes wascomparable to or better than that for measured data in other areas examined by Kheifets etal. (Kheifets et al., 1997c). Tarone et al. (Tarone et al., 1998) also looked at the reliabilityof wire coding in a subgroup of homes where replicate wire coding was done for quality
control. Inconsistent determinations were reported for 15 of the 187 homes examined(8%). Of the discrepancies, seven involved distance and only two of the inconsistencies
involved VHCC homes.

2.6

Exposure in transport
Wenzl (Wenzl, 1997) studied exposure to ELF magnetic fields among rail maintenanceworkers near Philadelphia, Pennsylvania. The workers were exposed to 25 Hz magnetic
fields from electrified rail lines in addition to 60 Hz fields from other sources. Because of
the mix of frequencies expected, spot readings of the magnetic fields were taken with a
Multiwave system and fast Fourier transform to analyze for the frequency components.
Personal exposure monitoring was also conducted. [The instrument response was limited43

to frequencies in the range 40Ð1000 Hz, which would not include exposure to 25 Hz.]
Current flowing in the overhead catenary lines was the primary source of magnetic fields
when a train was near the maintenance work site. The peak magnetic fields were 3.4Ð19
mT near a transformer, while the medians at five other locations were 0.7Ð4 mT. TWA
personal exposures were estimated by combining spot measurements at occupied
locations with estimates of the amount of time spent at each location; the values were0.3Ð1.8 mT, depending on the location and how frequently trains passed the work site.
Comparisons between the spot measurements in the 40Ð1000 Hz frequency range and thepersonal exposure readings showed reasonably good agreement. [Further characterizationof personal exposures in this environment may be justified, since workers and passengers
on trains may be more highly exposed and for longer times.]
Electrified mass transit systems are found in many US cities. A US Department ofTransportation study (USDT, 1993) of electrified transport systems showed that the
average ELF magnetic fields in passenger coaches of trains ranged from approximately 0.5
mT in diesel-powered trains to 13.4 mT in electric-powered trains operating between
Washington DC and New York. The maximum fields were found to be approximately fivetimes larger than the average fields. Magnetic fields within the passenger coaches of masstransit systems (subways, trolleys, light rail transit systems) were highly dependent on
the vehicle propulsion control system. The average magnetic fields in the passenger
coaches of most trolleys and subways were 0.3Ð0.9 mT, but one system was found tohave an average field of 17.8 mT. The principal frequency of the magnetic fields in mosttransport systems was other than 60 Hz, and, for many systems, the principal fieldcomponents were at frequencies less than 50 Hz. Consequently, personal exposure
measurements with existing exposure monitors do not accurately assess exposure to ELF
magnetic fields. The electric fields were small within the coaches of all transport systems
tested. Electric fields from external power supply circuits did not significantly penetrate
the metallic passenger compartments. The magnitude of EMF in the driversÕ
compartments of the transport vehicles examined was generally comparable to or lower
than the average fields within the passenger coaches.

2.7

Exposure in schools
Exposure to EMF in schools has recently received more attention because of concern
raised in studies indicating associations between childhood cancer and EMF in residences.
Children can spend a substantial amount of time in school, and this environment accounts
for most of their daily activity away from residences. Like residences, school buildings
may be located near electrical utility lines that can contribute to indoor EMF. Unlike
residences, however, schools may also have extensive electrical bus networks, largetransformers, and other EMF-generating equipment inside the buildings, similar to large
office complexes and industrial settings.
Sun et al. (Sun et al., 1995) conducted a survey of EMF in 79 schools in Canada for theCarlton Board of Education. They found that the typical magnitude of the magnetic field44

in classrooms was lower than those in many occupational settings, with a mean of 0.08
mT (Table 2.10). They also attempted to identify possible sources of EMF, such asexternal wiring and building attributes that contribute to EMF in classrooms. Two-story
buildings produced higher fields (geometric mean, 0.08 mT ) than did one-story structures(geometric mean, 0.056 mT). Wiring in the floors of classrooms was the most frequently
identified local source, while electric typewriters and computers were also common.
Outside wiring was a contributing source, but transmission lines were not common
enough to be identified as a contributing factor. [Overall, the levels reported in the study
were similar to those in many residential and office environments.]
Table 2.10. Average magnetic flux densities in schools in Canada
Type of school
Elementary
Intermediate
SecondaryAll

No. ofschools

Mean (mT)GM

GSD%> 0.2mTa

95% CI for
GM

57
7
15
79

0.085b0.072
0.084
0.082b

0.065b
0.061
0.072
0.066

2.0
1.9
1.8
1.9

8.1
8.3
7.3
7.8

0.054Ð0.078
0.037Ð0.099
0.054Ð0.096
0.057Ð0.077

GM, geometric mean; GSD, geometric mean standard deviationaPercent of all readings greater than 0.2 mTbSummary value calculated from data in the text

The California Public Health Foundation is performing a statewide measurement surveyof EMF in California schools in order to determine the range of EMF in California publicschools. Measurements are to be made in a random sampling of about 90 public schools
to identify and characterize the sources of the magnetic fields and to evaluate possible
mitigation techniques. The measurements will include a survey of classrooms and outdoor
activity areas, identification and characterization of magnetic field sources, 24-h fieldrecordings, wire code classification, and identification of nearby outdoor electricalfacilities. Preliminary results from the pilot study were presented at the 1996 DOE EMF
Contractors Review Meeting in San Antonio, Texas (Neutra et al., 1996). Six schools
were involved in the pilot study, and 163 classrooms were measured. Approximately 4%of the classrooms measured in the study were found to have average magnetic fieldmagnitudes > 0.2 mT; the median value for these classrooms was about 0.08 mT. The
commonest overall source of the magnetic fields was ground currents flowing on water
pipes or electrical conduits, although for classrooms with fields > 0.2 mT outside
distribution lines and ground currents contributed about equally to the number of sources
observed.

2.8

Exposure from appliances
To date, there have been no extensive studies of the relationship between use of
appliances and personal exposures to EMF. The sampling strategies must be refined inorder to assess the contributions of appliances to total exposure to EMF. Fields in thevicinity of appliances have been quantified in most studies.
45

Gauger (Gauger, 1985) studied the magnetic fields from appliances as a function of
distance. The levels near hand-held hair-dryers were 0.3Ð2 mT at 10 cm. Vacuum cleaners,
microwave ovens, and small hand-held appliances were identified as projecting the highest
fields and/or projecting the furthest distance; 95% of the maximum observed magnetic
fields from appliances were < 0.1 mT at a distance of 1.5 m.
Mader and Peralta (Mader & Peralta, 1992) demonstrated that the magnitude of magnetic
fields drops off at a rate inversely proportional to distance cubed. They presented amethod for assessing magnetic fields and a model for predicting the exposure of body
extremities. Like Gauger, they found that proximity to the appliance was an importantfactor. They concluded that appliances do not contribute significantly to whole-body
exposure although they may be a dominant source of exposure of the extremities.
Florig and Hoburg (Florig & Hoburg, 1990) modeled and measured magnetic fields fromelectric blankets. They estimated that the volume-average whole-body exposure for adults
was 1.9Ð2.2 mT; the corresponding values for an eight-year-old child were 2.6Ð2.7 mT.
The magnetic field estimated at the mid-sagittal line 10 cm above the bed wasapproximately 1 mT. Wilson et al. (Wilson et al., 1996) reported the results of a validation
study of a protocol for measuring magnetic fields from electric blankets in homes. The
average field over seven spots 10 cm above the bed was 0.45 ± 0.05 mT. The values
obtained by Wilson et al. are within a factor of 2 of those reported by Florig and Hoburg.
DelPizzo (Delpizzo, 1990) proposed a model for exposure to electric blankets, mattresspads, and other appliances. He suggested that cumulative exposure to magnetic fields of >400 mT-h per year would be necessary to add significant exposure over background levels.
In the EPRI 1000 homes study, Zaffanella (Zaffanella, 1993) examined a variety ofhousehold sources. Appliances were found to produce the highest magnetic fields near thesource, but the fields typically decreased rapidly with distance. For example, 13 electric
can openers had a median magnetic field magnitude of about 20 mT at 20 cm from thesource, but this fell to 0.3 mT at a distance of 117 cm; microwave ovens had a median
power-frequency magnetic field magnitude at 25 cm of 3.7 mT, which fell to 1 mT at 56
cm. The results for some other appliances in the survey are included in Table 2.11.

46

Table 2.11. Magnetic fields associated with use of appliances
Appliance

Non-ceiling fan
Can opener
Clock-radio (digital)
Clock-radio (analog)
Ceiling fan
Electric range
Microwave oven
Color TV
Refrigerator

2.9

Distance = 25 cm

Distance = 56 cm

95thpercentile

5th
percentile

Median95th
percentile

5th
percentile

9.2
32.5
0.3
2.5
1.6
1.9
6.7
1.2
0.5

0.03
1.2
0.1
0.3
0.03
0.2
1.7
0.4
0.2

0.3
21.0
0.1
1.5
0.3
0.9
3.7
0.7
0.3

1.6
3.2
0.1
0.4
0.3
0.3
1.7
0.3
0.3

0.2
0.01
0.1
< 0.01
0.04
0.5
0.1
0.1

Median
0.04
2.4
0.02
0.2
0.1
0.2
1.0
0.2
0.1

Laboratory exposure systems
The operating constraints of systems designed for laboratory experiments of exposure
characterization are very different from those of observational exposure measurements. In
the laboratory setting, the operational goal is to provide a precise, known, consistentcondition of exposure to EMF with as much control over environmental factors as
possible. In recent years, laboratory systems both in vitro and in vivo have grown insophistication and complexity.
The prototype of a laboratory apparatus for exposure to magnetic fields is a Helmholtz
coil, consisting of a pair of circular coils aligned along their open center axis and separated
by a distance of one radius. A pair of conductive parallel plates forming an air capacitor isfrequently used for exposure to electric fields. Both of these devices produce a reasonably
uniform magnetic or electric field around the geometric centerline; the magnitude of the
field depends on the physical dimensions, number of turns in the coil, and current (orvoltage) applied to the system. In the case of magnetic fields, calibration requires carefulattention to construction details and precise control of the current flow in the coils. The
uniform region in the center of a Helmholtz coil is rather small, and for large-scale
experiments more complex coil designs may have advantages. Kirschvink (Kirschvink,
1992b) described several superior designs with three, four, or five coils which provide
highly uniform fields over a large volume. Other exposure systems include solenoids(Merritt et al., 1983; Mullins et al., 1993) or a current sheet to produce uniform magnetic
fields.
A common goal in EMF experimentation is to provide a matched control condition that is
identical to the exposure in every way except for the desired field exposure. To attainthis, a sham exposure is usually set up with an identical apparatus but some modificationof the current flow pathway. One method is simply to interrupt the current flow of theHelmholtz pair or the voltage to the parallel plates. This method has the disadvantage thatany heat produced by the energized coil is not reproduced in the sham condition. This is
not of material concern if the coils are constructed with sufficiently large wire to produce
47

negligible heating. A superior system consists of bifilar windings around the coils, with aparallel pair of insulated wires (Kirschvink, 1992b). In normal operation, parallel currents
in the windings yield an external magnetic field. In the sham (ÔbuckedÕ) condition, currents
flow in anti-parallel directions, so that the magnetic fields generated by each strand cancel
and yield virtually no external magnetic field. The double-wrapped sham produces thesame ohmic heating and largely controls for temperature effects. Differences in vibration
between the sham and exposed conditions may still occur, but these are usually controlled
by careful isolation of the experimental subjects and solid construction of the coils.
Identical and interchangeable sham and exposure systems facilitate the conduct of truly
double-blind experimental protocols, because the same apparatus can be used for bothexperimental and control groups, with a simple switch to change the operating conditions.
Another problem encountered in laboratory systems is that stray fields produced by the
exposure apparatus or other equipment can contribute to background exposure in thesham controls. Stuchly et al. (Stuchly et al., 1991) devised a system consisting of aquadrupole-coil configuration with four square-wound Merritt coils to minimize straymagnetic fields from the exposure system. The system provides a uniform field within avolume occupied by 16 animal cages and produces a mean flux density of 2 mT which
varies by < 10% over the cages. The flux density decreases to < 0.1 mT at 2 m from thecoils.
Sometimes, incubators, heaters, motors, and other laboratory equipment can produce large
stray fields. To limit these fields, magnetic shielding boxes made of highly permeable
materials such as mu-metal may be used. These boxes can reduce stray fields by morethan 30-fold and also reduce DC fields. [The biological significance of removing thegeomagnetic fields has not been thoroughly studied.] When used inside incubators, shieldboxes can degrade temperature control, degrade gas exchange in the culture system, anddegrade the field uniformity from theoretical calculated values. Coupling of the magnetic
field to the shield box can produce significant mechanical forces, leading to greater
vibration in the system.
Some experiments require exposure to combinations of AC and DC fields or control of themagnetic field vector (such as circular polarization) (Shigemitsu et al., 1993). To achievethis, the exposure apparatus is made up of multiple coil windings or sets of orthogonalcoils arranged to produce the desired vector components. Careful alignment of the coils
and phasing of the currents is needed to produce the desired results (Doynov et al., 1998).
[DC magnetic fields are often not controlled in large exposure systems and can vary
substantially.]
Another important aspect of laboratory system design is the control of external
environmental factors, such as changes in temperature and humidity, light intensity,
lighting spectrum, and noise or air-flow distribution inside the animal housing due to airconditioning equipment. These environmental factors can provide subtle cues to animals
or humans and may also alter cell culture conditions. These concerns have led toexperimental designs in which assignment between sham and experimental conditions is48

randomized or counterbalanced. Sometimes it is desirable to randomize cage assignments
and periodically rotate cage positions to account for such environmental factors. Light
exposure and timing must be controlled especially in experiments involving circadianchanges in hormones or behavior. Light intensity, timing, and duration are frequently
controlled, but the spectral distribution of the light is often overlooked (Prato et al.,1997).
Careful measurement, spatial mapping, and periodic checking of exposure conditions in
the laboratory are necessary for engineering documentation and quality control. Usually, acomplete set of engineering measurements is collected before the experiments begin. This
includes mapping of field uniformity and measurements of possible frequency harmonics
in magnetic field readings. It is also important to characterize any switching transients orother anomalies arising from infrequent operating conditions that may occur during anexperiment, such as the effect of opening an incubator door. In the past, there has beenstrong emphasis on reducing switching events that produce a high rate of change in themagneticfield.
In in vitro experiments with EMF, cultures are routinely exposed to a uniform external
magnetic flux density. Initially, many researchers did not measure or estimate the resulting
induced electric field strength or current density in the sample medium. The magnitude
and spatial distribution of the induced electric field are highly dependent on the sample
geometry and the relative orientation of the culture medium with respect to the magnetic
field (Misakian, 1997; Misakian & Kaune, 1990). Bassen et al. (Bassen et al., 1992)
studied the electric fields induced in several of the most frequently used laboratory culture
dishes and flasks under various exposure conditions. They developed a set of simple,
quantitative tables to predict the induced electric fields and currents which were based on
measurements and calculations of the electric field distributions in the aqueous sample
volume subjected to a uniform, sinusoidal magnetic field of known strength andfrequency. The electric field and current density can also be calculated numerically from
relatively simple but flexible spreadsheet models (Hart, 1996).
These studies highlight the need for careful engineering design and evaluation of laboratory
exposure systems, since all laboratory systems have potential strong points andweaknesses and involve engineering compromises. Researchers should understand these
design elements in order to use the exposure apparatus to the best advantage. Close
collaboration between engineers and laboratory scientists is necessary, and can result inclever adaptations of exposure systems to focus on a desired experimental test. Several
funding agencies have made external site reviews for quality control.

2.10 Summary
Assessment of exposure to electromagnetic fields (EMF) is the subject of an extensive
literature, much of it relating to exposure to power-frequency magnetic fields. In many of49

the epidemiological studies of adults, personal exposure measurements were used toevaluate magnetic fields in the workplace or in residences on the basis of the timeweighted average (TWA) magnitude. Relatively few studies have addressed electric field
exposures or investigated alternative metrics for exposure to magnetic fields, such as
vector polarization, high frequency transients, and frequency harmonics.
Personal exposure has been estimated in the residential setting in order to study childrenÕs
exposure. Kleinerman (Kleinerman et al., 1997) estimated the exposure of 1633 children <14 years of age and found that their daily mean exposure was about 0.11 ± 0.11 mT.
These values are not based on direct personal monitoring but do attempt to account for
total exposure.
Studies of occupational exposure have focused on electrical and utility workers; only
recently have data become available on the exposure of the general population. Studies in
the general population indicate that the median of the daily mean occupational exposure
for adults is about 0.17 mT. Zaffanella et al. (Zaffanella & Kalton, 1998) estimated thatthe distribution of 24-h TWA exposure in the general US population was log-normal,
with a geometric mean of 0.09 mT and a geometric standard deviation of 2.2. Thus, about
15% of the population have 24-h exposures exceeding 0.2 mT, about 2.4% are exposed to> 0.5 mT, and 0.5% to > 1 mT.
When they are practical, direct personal measurements of magnetic fields are generally thepreferable method of exposure assessment. Direct measurements provide a quantitative
estimate of exposure to a clearly defined field. Even direct measurements, however, may
not allay substantial uncertainty about classification of the exposure, as factors such as
seasonal variation, changes in work tasks, intermittent use of appliances or tools, changing
current loads, and variable proximity to wiring can contribute to large day-to-day
variation in measurements. The time of data collection during a day or a season can lead tosystematic bias in estimates of daily or annual average exposure. Personal exposure
monitors can also be intrusive, so that people may alter their usual activities because they
are wearing the meter. Because of the wide variation in exposure to magnetic fields, very
many measurements must be made in order to obtain reasonably precise estimates of
exposure. It should also be noted that the TWA fails to reflect a large number ofpotentially relevant exposure parameters, such as time above thresholds, intermittency,
and transients.
Many studies of EMF have been based on measurements at one point in time (spotmeasurements), stationary monitoring over time, or area measurements involving mappingof the spatial characteristics of fields. While offering a quantitative estimate of fields, suchmeasures also lead to substantial uncertainty about exposure classification. These typesof measurements have several disadvantages, including the fact that they ignore personal
activity patterns such as mobility and use of tools or appliances; they do not reflect past
exposure; and they exclude possible parameters of exposure such as specific frequency
content, polarization, and static magnetic fields. These types of measure do, however,
have the advantage of simplicity and can provide reasonable estimates of human exposure
50when mobility is restricted to a particular room or residence. With additional equipment,
stationary monitoring can be used to capture a wider range of EMF characteristics,
providing a greater variety of potential exposure metrics. Contemporary spotmeasurements are useful for checking the validity and appropriateness of calculations formagnetic fields from power lines in some situations.
The value of contemporary spot measurements as surrogates for past exposure remains
uncertain. The limited data indicate that spot measurements are reasonably well correlated(R » 0.7) with similar measurements over several years. Dovan (Dovan et al., 1993)
found that contemporary spot measurements taken within wire code categories remainedcorrelated with home average readings collected five years earlier (R » 0.7 for low power).
Dovan purposely oversampled high-field very high frequency and case homes from thedata set of Savitz et al. (Savitz et al., 1988), so this may overstate the predictive value ofspot measurements somewhat. The relationship between spot measurements andpersonal exposure is less clear. Kaune and Zaffanella (Kaune & Zaffanella, 1994) foundessentially no correlation over time for the personal exposure of children in residences;
Koontz (Koontz et al., 1992), in a study of childrenÕs exposure, found a significant
correlation over a few days but not across seasons. In residences, the combination of 24-h
bedroom measurements with spot measurements in several other rooms appears to be agood method for determining the contemporary TWA household exposures of children.
The correlation improves as the age of the child decreases.
Assessment of exposure to EMF for studies of human health effects is difficult because
direct measurements often cannot be obtained, particularly for studies of chronic diseases,
as the exposure of interest may have occurred years previously, and the actual
circumstances of exposure cannot be recreated. In such studies, therefore, all assessmentsof exposure, including direct measurements, are surrogates for the exposure of interest.
The surrogates most widely used are contemporary measurements, job titles, proximity
to electrical equipment, calculated historical fields, and wiring configuration coding (wirecodes).
Occupational histories are often incomplete and lack sufficient detail on actual work
activities for past exposures to be reconstructed. As exposures to EMF are notmemorable, questionnaires are of limited value. Contemporary measurements of similar
workplaces may account for all sources but may be poor surrogates for past exposures.
Classification of exposure on the basis of Ôelectrical jobsÕ provides a crude but useful tool
for studies of EMF. The wide variation in EMF intensity results in considerable overlap
and misclassification. This classification scheme, however, includes few assumptions
about the exposure metric used.
An alternative method is use of a jobÐexposure matrix (JEM) to obtain quantitative
estimates of exposure to electric or magnetic fields. In modern occupational studies, theJEM appears to provide the most flexible, stable tool for reconstructing exposure. A JEM
can be constructed for almost any desired exposure if measurements are available,
although it still relies fundamentally on occupational titles to classify exposure. The
51

absence of complete data on exposures in a wide variety of occupations remains alimitation in studies of occupational exposure.
Many different surrogates for exposure have been used in studies of residential exposure,including wire coding, spot measurements, 24-h bedroom measurements, personalmonitoring, and calculations based on physical models. All of these techniques have some
limitations, and all of them result in misclassification of exposure. Measurements have theadvantage that they capture all sources of exposure. Yet, as noted above, contemporary
measurements may be poor predictors of past exposures. Estimates based on wiringconfigurations or model calculations are of historical value, but these techniques accountonly for external sources of EMF such as transmission and distribution power lines.
These methods also result in misclassification of exposure, perhaps non-randomly, andtend to lead to underestimates of total exposure as many local sources are not taken into
account.
The system of wire codes was developed by Wertheimer and Leeper (Wertheimer &Leeper, 1979) to predict residential magnetic fields from the distance and configuration oftransmission and distribution lines near residences. The validity of wire codes has beenquestioned because the different wire code categories for contemporary measured fields
overlap widely. Several studies have shown that wire codes can be used consistently torank homes crudely according to the median magnetic field intensity. Dovan (Dovan et al.,1993) showed that wire codes change little over time, but their usefulness for predicting
past exposures remains an open question. The strengths of the wire code method include
the following:·

A correlation exists between wire codes and median magnetic fields in residences.

·

The codes are probably related to historical magnetic fields since the physicalcharacteristics of power lines usually change little over time.

·

Wire codes may indicate high magnetic fields in some cases.

·

Wire codes make it possible to estimate fields in residences without subject
participation.

The weaknesses of the wire code method include the following:·

The values for contemporary fields are widely dispersed around the median for eachcategory, resulting in overlap among categories.

·

The historical stability of wire codes, which are based on the physical characteristics
of power lines, may not be a reliable indicator of the stability of magnetic fields.

52

·The relationship between wire codes and field intensities varies with different wiring
practices.

·

Exposure to local sources of magnetic fields in residences (i.e. electrical appliances,building wiring, and ground currents) and away from the residence (perhaps importantfor older occupants) are not captured.

Wire codes also are not a simple surrogate for the TWA magnetic field and may be related
in a complex way to various field parameters. Little information is available on therelationship between wire codes and other candidate parameters of exposure such as
frequency, polarization, and ÔtransientsÕ. Homes with VHCC may have a greater
tendency for high-frequency transients. Kheifets et al. (Kheifets et al., 1997c) examinedseveral candidate metrics but found no clear relationship with wire codes.
In an alternative method for assessing residential exposure, physics-based calculations areused to estimate past fields. Generally, retrospective residential exposure assessment
based on calculations of magnetic fields from nearby transmission lines on the basis ofhistorical load currents should be more accurate than either wire codes orcontemporaneous measurements, especially for single-family homes sufficiently close to atransmission line to ensure that the fields originated mainly from that source. In those
homes, failure to account for fields from local sources should have less impact because
transmission line fields dominate over most local field sources. The calculations for
distribution lines are less reliable owing to the presence of ground currents and fluctuatingloads; however, this method may be better than wire codes. Calculations for apartments,
where local field sources might still dominate, are also uncertain. In some cases, themethods of calculation have been validated against contemporary spot measurements, andthis has helped to establish the predictive value of the models in study populations.
Calculations of historical magnetic fields are most applicable when the geometry of thepower-line sources is relatively simple, e.g. transmission lines, provided there are
adequate data on load currents. Limited resolution in the measurement of distance to theresidence can dominate the uncertainty in field estimates near the line. Close proximity tohigh-voltage transmission lines may also be an indication of substantial exposure to bothmagnetic and electric fields. The availability of high-quality data on load currents is also
critical for this approach to succeed, although in some cases it may be possible to obtainreasonable estimates from informed experts. With the deregulation of utilities in the USA,it may become more difficult to obtain data on load currents because of proprietaryinterests. The strengths associated with modeling historical fields are the possibilities of
estimating:·

TWA magnetic fields in homes that are not accessible;·

TWA past exposures over extended periods;

53

·short-term variations in fields from power lines (with good data on load current); and·polarization and other metrics (with good data on load current).

Weaknesses associated with calculations of historical magnetic fields include:·

the inability to capture fields from local sources;·

the inability to capture non-residential exposures;·difficulty in applying the method to distribution lines; and·the limited availability of historical load current data.

Good instrumentation for measuring TWA exposures to EMF is available, but thecomplex field vector still cannot be measured completely with personal exposure meters.
Some of the various exposure meters used in studies of EMF are designed for spotmeasurements or stationary monitoring. The currently available exposure meters have avery limited ability to detect frequency harmonics or transient fields and cannot be used
to measure combined AC and DC fields or vector polarization. None of these aspects of
exposure to EMF can be adequately assessed with present-day personal monitoring
instruments. Consequently, the summary measures of exposure described in existing
epidemiological studies involve many assumptions, and the existing exposure measures
can be regarded as surrogates for the underlying ideal exposure metric. Thus, the available
instrumentation has somewhat limited the ability of researchers to explore alternative
magnetic field metrics in human population studies. Even if instrumentation can be
improved, however, biologically based exposure metrics should be identified. Assessmentof the highly variable, complex, ubiquitous exposures to EMF for studies of health effects
thus requires considerable effort.

54

55

Figure 2.1 Electromagnetic spectrum showing extremely low frequency and other bands

Figure 2.2 Field-particle interactions: ÒclassicalÓ forces, torques, and energies
Electric fields(A)

F = qE

(B)

F=p

(C)

T = pxE

(D)

We =

(E)

Wp = p · E

Magnetic fields

F = q(vxB)

dE
dx

dB
dx

(b)

T = mxB

(c)

F=m

1
e 0e r E 2
2

(a)

1 B2
2 m0 mr(d)

Wm = m · B

(e)

Wm =

For explanation of the Òcross-productÓ in equations (a), (C) and (c), see Figure 2.2. The Òdot-productÓ or scalar product of two vectors a
and b (equations. (E) and (e)) is equal to ab cos f where f is the angle between the vectors a and b.

56

Figure 2.3 Illustration of Òcross-productÓ (equations (a), (C) and (c) in Figure 2.2: The resulting
vector c = aCb is in a direction perpendicular to the plane defined by a and b and its magnitude isequal to the product of their mutually perpendicular components: c = a×b sin f).

(

c

f

a
b

57

Table 2.1 Field meter characteristics
MeterName

FieldsSensorNo. ofAxes

Frequency
Response (Hz)aMaximum Full
Scale Rangea (mT)

OutputFunction

Amex
Amex-3D
Emdex C

B
B
B,E

C
C
C,P

1
3
3,1

-------25 Hz -1.2 kHz
40-400 Hz

12.5
15
2550

TWA
TWA
D,DL

AVG
AVG
AVG

P
P
P

Emdex II

B

C

3

40-800 Hz

300

D,DL

RMS

P

Positron

B,E,HF

C,P,F

3,1

50/60 Hz

50

D,DL

PEAK

P

Monitor Ind.
Multiwave

B
B

C
C, FG

1
3

40 Hz -1 kHz
0-10 kHz

250
500

A
D,DL

RMS
RMS

S
S

Power frequency
Meter MOD120
STAR
MAG 01IREQ
Heitanen &Jokela, 1990
Juutilainen &Saali, 1986b
Sydkraft

B,E

C,P

1

35-600 Hz

3000

A

AVG

S

B
B
B
B,E

C
FG
C
D

3
1
3
1,1

60 Hz
0-10 Hz
40 Hz - 1 kHz
25 Hz -10 Mhz

51
200
100
---

D,DL
D
D,DL
---

RMS
--RMS
---

S
S
S
S

B

C

1

< 50 Hz -25 kHz

380

A

RMS

S

B

C

3

50-60 Hz

20

D,DL

AVG

S

Comment

Built-in E
field
Has harmonic
capability
Built-in E
field
Waveform
captureOscilloscope
output(Bowman et al., 1998; Feychting & Ahlbom, 1993; Heitanen & Jokela, 1990; Juutilainen & Saali, 1986b; Olsen et al., 1991)
E, electric; B, magnetic; HF, high frequency; C, coil; P (function), plate; F, conductive foam; FG, flux gate; D (sensor), active dipole; D (output), digital spot; A, analog spot; DL, data logging; TWA, single readout of
TWA; AVG, average; RMS, root-mean-square; P (function), personal monitor; S, survey
a Frequency response and maximum range refer only to the magnetic field measurement channel

58

Table 2.2 Magnetic field exposure metrics used in epidemiological studies
Abbreviation

Reference

Arithmetic mean (TWA)
Geometric mean
Median (50th percentile)
Peak (maximum) value
99th or Nth upper percentile
Percent of time > threshold
Percent of time < threshold
Percent of time in window
Total harmonic distortion

Exposure Metric

TWA
GM
B50 Med
Bpeak
B99
Tn
Tn
Tw
THD

High frequency electric transients
Average absolute sequential
differenceFirst lag autocorrelation

HFET
AASD

Standardized rate of change
Jaggedness index
RMS Rate of changeStandard deviation
Geometric standard deviation

RCM
Jag
RC
SD
GSD

All
All
All
All
Armstrong
Armstrong
Armstrong
Armstrong
Zaffanella 1993,
Breysse 1997
Deadman
Breysse 1994
Zaffanella 1993
Breysse 1994
Thomas 1996
Birch et.al.
WenzelWilson et.al.
Armstrong, etc
Armstrong, etc

TWA, time-weighted average; rms, root mean square

59

Measures
Magnitude
Magnitude
Magnitude
Magnitude
Peak magnitude% magnitude > limit% magnitude < limit% magnitude > limit1 & < limit2
Frequency B-field
Frequency, E-Field
Short term variability
Short term correlation
Short term correlation
Short term variability
Short term variability
Time variability
Time variability

Table 2.3 Standard occupational classification codes and job categories of "electrical jobs"
Code
1633

7714
1636
1712
3650
3971
4732
4752
6881
7830

Job category
Electrical and electronic engineers
Electrical and electronic technicians
Broadcast equipment operators
Electronic repair, communications & industrial equipment workers
Data processing equipment repairers
Household appliance and power tool repairers
Telephone line installers and repairers
Telephone installers and repairers
Miscellaneous electrical and electronic equipment repairers
Supervisors, electricians and power installers, and repairers
Electricians
Electricians apprentices
Electric power installers and repairers
Power plant operators
Motion picture projectionists
Electric power wire and cable workers
Power station operators
Welders and cutters
Television and radio repairman
Computer engineers
Computer systems analysts
Radiological technologists and technicians
Programmers, business
Telephone Operators
Production and planning clerks
Precision inspectors, testers, and graders
Production testers

60

Table 2.4 Electrical occupations derived from job titles with TWA magnetic field exposures
Occupation

Industry orcompany

Engine driver

Railroad

Driver of electric vehicle

Railroad

Railroad engineer
Railroad engine driver
Cable joiner andlineman
Electric power line
installers and repairers

LinemanPower-line worker

Electric company

Electrician
Sewing-machine
operators
Dressmakers,
seamstresses and tailors

So. Cal. Edison
Garment industry

Dressmakers and tailors
Machinist
Forestry and logging
jobs
Welder

So. Cal. Edison

Epidemiologicalstudy(Floderus et al.,
1994)
(Sobel et al.,
1995)
(Sobel et al.,1996)(GuŽnel et al.,
1993)
(Lin et al., 1985)(Tynes et al.,
1992)
(Fear et al., 1996)(Milham, 1985)(Deapen &Henderson,
1986)(Demers et al.,
1991)
(Loomis et al.,1994b)(Savitz et al.,
1994)
(Spitz & Johnson,
1985)(Nasca et al.,
1988)
(Wilkins &Wellage, 1996)(Savitz et al.,1998b)(Lin et al., 1985)(Tynes et al.,
1992)
(Sahl et al., 1993)
None(Sobel et al.,
1995)
(Sobel et al.,
1996)
(Coogan et al.,
1996)
(Sahl et al., 1993)
NONE(Lin et al., 1985)

61

Exposure

TWA magnetic field
(mT)
AM

SD

4.03

NR

Continuous

4.03

NR

A (definite)
Intermediate

4.03
4.03

NR
NR

3.61

10.92

3.61

10.92

3.61
3.61

10.92
10.92

3.01
3.00

NR
0.28

3.00a

0.28

3.00

0.28

2.69
2.48

NR
7.70

2.00

4.01

A (definite)
Heavy EMF

Low

B (probable)

Table 2.4 (continued)

Occupation

Industry orcompany

Welders and flame
cutters(Milham, 1985)(Deapen &Henderson,
1986)(Demers et al.,
1991)
(Spitz & Johnson,
1985)(Nasca et al.,
1988)
(Wilkins &Wellage, 1996)(Rosenbaum etal., 1994)(Coogan et al.,
1996)
(Sobel et al.,
1996)
(Sobel et al.,
1995)
(Davanipour etal., 1997)(Sobel et al.,
1996)
(Sobel et al.,
1995)
(Fear et al., 1996)

Welders and flame
cutters
WelderElectrical fitter

Electrical and electronic
production fitter
Electrician

Electric power

Electrician
Electrician

Industry
Steel millElectrician

Manufacturer ofelectricalmachinery

Electrician, power
supplyCable splicer

5 US electricutilities

Power station operator

Power plant operator
WorkerEpidemiologicalstudy

Sewing factory(GuŽnel et al.,
1993)
(Lin et al., 1985)(Davanipour etal., 1997)(GuŽnel et al.,1993)
(Tynes et al.,
1992)
(Savitz &Loomis, 1995)(Milham, 1985)(Deapen &Henderson,
1986)(Tynes et al.,
1992)
(Loomis et al.,1994b)(Savitz et al.,
1994)
(Wilkins &Wellage, 1996)(Fear et al., 1996)(Savitz et al.,1998a)(Demers et al.,
1991)
(Sobel et al.,62

Exposure

TWA magnetic field
(mT)
AM

SD

2.00

4.01

Medium

2.00

4.01

High

2.00

4.01

1.56

1.63

1.56

1.63

Continuous

1.56

1.63

A (definite)
High

1.56
1.56

1.63
1.63

Continuous

1.56

1.63

Heavy EMF

1.56

1.63

1.50

3.12

1.43

2.24

1.43

2.24

1.40

1.47

Group 1

Table 2.4 (continued)

Occupation

Relay technician

Industry orcompany

5 US electricutilities

Sheet metal worker

Technician
Electrician
Power plant operator
LinemanWelderSouthern
California
Edison5 US electricutilities
Southern
California
EdisonSouthern
California
EdisonSouthern
California
EdisonMotion picture
projectionist

Substation operator
WelderElectric generation
plant operator
Mechanic
Machinist
95th percentile of males
Lineman

5 US electricutilities
5 US electricutilities
5 US electricutilities
Southern
California
Edison5 US electricutilities
5 US electricutilities

Dental hygienist
Conductor

Railroad

Railroad assistants andRailroad

Epidemiologicalstudy

Exposure

TWA magnetic field
(mT)
AM

SD

1.34

2.34

1.34

4.19

1.32

NR

(Savitz &Loomis, 1995)(Sahl et al., 1993)

1.11

2.18

1.08

NR

(Sahl et al., 1993)

1.03

NR

(Sahl et al., 1993)

1.02

NR

(Milham, 1985)(Deapen &Henderson,
1986)(Loomis et al.,1994b)(Savitz et al.,
1994)
(Sobel et al.,
1996)
(Sobel et al.,
1995)
(Wilkins &Wellage, 1996)(Savitz et al.,1998a)(Savitz &Loomis, 1995)(Savitz &Loomis, 1995)(Savitz &Loomis, 1995)(Sahl et al., 1993)

0.80

0.68

0.80

1.13

0.80

1.08

0.79

2.34

0.77

NR

(Savitz &Loomis, 1995)

0.72

1.95

0.66
0.65

1.59

0.64

1.65

0.61

NR

0.59

NR

1996)
(Sobel et al.,
1995)
(Savitz &Loomis, 1995)(Sobel et al.,
1996)
(Sobel et al.,
1995)
(Sahl et al., 1993)(Savitz &Loomis, 1995)(Davanipour etal., 1997)(Floderus et al.,
1994)
(Floderus et al.,63

MediumTable 2.4 (continued)

Occupation

Industry orcompany

linemanRailroad track walker
Tram driver
Conductors andmotormen, urban railtransitElectrical andelectronics assembler

Employee

Utilities

Employee

Utilities

Electrical and electronicequipment repair

Electrical andelectronics apparatus
mechanics and installers
Electrical equipment
repairer
Electrical equipment
repairman
Household applianceand power tool repairers
Household applianceinstallers and mechanics
Painter

5 U.S. electricutilities

Office machine repairer
LinemanTelephone technician
Mail and message
distributing
occupations

Telephonecompany

Epidemiological
study

1994)
(Tynes et al.,
1992)
(Tynes et al.,
1992)
(Milham, 1985)(Deapen &Henderson,1986);(Coogan et al.,
1996)
(Wilkins &Wellage, 1996)(Johnson & Spitz,
1989)(Fear et al., 1996)(Sobel et al.,
1996)
(Sobel et al.,1995)
(Rosenbaum etal., 1994)(Spitz & Johnson,
1985)(Nasca et al.,1988)
(Loomis et al.,1994b)(Savitz et al.,
1994)
(Savitz et al.,1998b)(Johnson & Spitz,
1989)(Coogan et al.,
1996)
(Spitz & Johnson,
1985)(Nasca et al.,
1988)
(Wilkins &Wellage, 1996)(Deapen &Henderson,
1986)(Savitz &Loomis, 1995)(Deapen &Henderson,
1986)(Lin et al., 1985)(Demers et al.,
1991)
None

64

Exposure

TWA magnetic field
(mT)
AM

SD

Weak EMF

0.59

NR

Intermediate

0.57

0.61

0.57

0.61

0.57

0.25

0.57

1.51

0.57

1.51

0.51

0.61

0.51

0.61

Medium

0.51

0.61

Broad
definition

0.51

0.61

0.46

0.52

0.46

0.52

0.45

0.45

0.44

0.74

A (definite)

0.43

0.05

Group 4

0.43

0.10

0.43

0.41

Narrowdefinition
Broaddefinition

Table 2.4 (continued)

Occupation

Groundskeepers andgardeners
BoilermakerService worker
Serviceman
Instrument and control
technicians
RiggerElectriciana

Industry orcompany

5 U.S. electricutilities
5 U.S. electricutilities
Electric company
5 U.S. electricutilities
5 U.S. electricutilities

Electrician
Electrician
Electrician
Electrician andapprenticeElectrician,Electrician;installation
Non-industrial

installation

Electrician
Factory hand and otherunskilled worker
Factory hand and otherunskilled worker
TV and radio repairman

TV repairer

Iron and steel
works
Iron foundries

Epidemiologicalstudy

Exposure

TWA magnetic field
(mT)
AM

SD

None

0.41

0.90

(Savitz &Loomis, 1995)(Savitz &Loomis, 1995)(Lin et al., 1985)(Savitz &Loomis, 1995)(Savitz &Loomis, 1995)(Sobel et al.,1995) (Sobel etal., 1996)(Davanipour etal., 1997)(Demers et al.,1991)(GuŽnel et al.,
1993)
(Lin et al., 1985)(Milham, 1985)(Deapen &Henderson,
1986)(Loomis et al.,1994b)(Savitz et al.,
1994)
(Spitz & Johnson,1985) (Johnson& Spitz, 1989)(Nasca et al.,
1988)
(Wilkins &Wellage, 1996)(Fear et al., 1996)(Rosenbaum etal., 1994)(Savitz et al.,1998b)(Tynes et al.,
1992)
(Coogan et al.,1996)(GuŽnel et al.,
1993)(GuŽnel et al.,
1993)
(Milham, 1985)(Deapen &Henderson,
1986)(Tynes et al.,
1992)
(Fear et al., 1996)(Davanipour etal., 1997)

0.41

1.05

0.41

0.69

0.41
0.40

0.69
1.12

0.38

0.37

Medium

0.37

0.32

Group 1

0.37

0.32

Continuous

0.37

0.32

B (probable)

0.37
0.37

0.32
0.32

65

A (definite)

Medium

0.37

0.32

Continuous

0.36

0.43

Continuous

0.36

0.43

0.36

0.23

0.36

0.23

MediumTable 2.4 (continued)

Occupation

Industry orcompany

Repairman for radio, TV,and electronic
appliancesHousehold applianceand power tool repairer(Lin et al., 1985)

Commercial andindustrial electronicequipment repairer
Technical worker

5 U.S. electricutilities

Traffic, shipping, andreceiving clerks
Electrical engineering
technician

Electrical engineering
technician
Electrical engineering
technician
Telecommunication
technician
Electrical and electronicengineers

Electrical and electronicengineers
Electrical andelectronics engineers
Electrical andelectronics engineers
Electrical and electronic

Epidemiologicalstudy

5 U.S. electricutilities

Industrial(Dennis et al.,1991)
(Savitz et al.,1994)
(Demers et al.,1991)
(Wilkins &Wellage, 1996)(Savitz &Loomis, 1995)
NONE(Milham, 1985)(Deapen &Henderson,
1986)(Loomis et al.,1994b)(Savitz et al.,
1994)
(Wilkins &Wellage, 1996)(Sobel et al.,
1995)
(Sobel et al.,
1996)
(Savitz et al.,1998b)(Coogan et al.,1996)
(Demers et al.,1991)
(Savitz &Loomis, 1995)(Milham, 1985)(Deapen &Henderson,
1986)(Loomis et al.,1994b)(Savitz et al.,
1994)
(Johnson & Spitz,
1989)(Wilkins &Wellage, 1996)(Savitz et al.,1998b)(Coogan et al.,1996)
(Demers et al.,1991)
(Lin et al., 1985)(Fear et al., 1996)

66

Exposure

TWA magnetic field
(mT)
AM

SD

0.36

0.23

0.36

0.23

0.36

0.23

0.36

0.62

0.36

0.30

0.35

0.27

High

0.35

0.27

Group 4

0.35

0.27

0.35

0.55

0.33

0.67

High

0.33

0.67

Group 4

0.33

0.67

A (definite)

0.33

0.67

0.33

0.67

B (probable)

Group 2

Table 2.4 (continued)

Occupationengineers (professional)
Electrical engineer (sodescribed)
Other electronic
maintenance engineers
EngineerEngineerEngineer

Industry orcompany

Electric power
Electric company
Telephonecompany

Telecommunications
engineer
Maintenance mana
AC, heating, andrefrigeration repairman
Mechanic, Power plant
Mechanic, utility
services
Programmer, systems
planner
Station master and train
dispatcher
Electronics wireman
Precision inspectors,
testers and related
workers
Tool and die maker

Pipe coverer

EDP services
Railroad

5 U.S. electricutilities

Farmer
75th percentile of males
Electrical equipment
salesmanElectrical goods andappliance salesman
Sales occupations, retailComputer programmer
Computer programmer

Electrician, other
Other electrical worker
Engineer (nonspecified)

Other engineers

Electric,
electronic,
aerospace, andtelecommunication

Epidemiologicalstudy

Exposure

TWA magnetic field
(mT)
AM

SD

(Fear et al., 1996)

0.33

0.67

(Fear et al., 1996)

0.33

0.67

(GuŽnel et al.,
1993)
(Lin et al., 1985)(Lin et al., 1985)

Continuous

0.33

0.67

A (definite)
A (definite)

0.33
0.33

0.67
0.67

(Lin et al., 1985)

A (definite)

0.33

0.67

(Lin et al., 1985)(Deapen &Henderson,
1986)(Johnson & Spitz,
1989)(Johnson & Spitz,
1989)(GuŽnel et al.,
1993)
(Floderus et al.,
1994)
(Fear et al., 1996)(Coogan et al.,
1996)

C (possible)

0.32
0.31

0.31
0.27

0.30

0.23

0.30

0.23

0.30

0.55

0.30

NR

0.29
0.29

0.39
0.39

0.28

0.40

0.28

0.44

0.27
0.27
0.26

0.54

0.26

0.14

0.26
0.25

0.14
0.28

0.25

0.28

Intermediate

0.25

0.18

Weak

0.25

0.18

B (probable)

0.25

0.41

Medium

0.25

0.41

Continuous

Medium(Sobel et al.,
1996)
(Sobel et al.,
1995)
(Savitz &Loomis, 1995)
NONE(Spitz & Johnson,
1985)(Johnson & Spitz,
1989)
NONE
(Coogan et al.,
1996)
(Loomis et al.,1994b)(Savitz et al.,1998b)(Tynes et al.,
1992)
(Tynes et al.,
1992)
(Lin et al., 1985)(Coogan et al.,
1996)

67

Broad
definition

Medium0.14

Table 2.4 (continued)

Occupation

Repairman
Craft supervisor
ForemanSupervisors,
electricians, and power
installers and repairers

Mechanic

Industry orcompany

Telecommunicati
ons
5 U.S. electricutilities
Electric company

5 U.S. electricutilities

Industrial engineer
Food and beverage
preparation and service
Carpenter
Carpenter

Receptionist
Clothing cutter

Heavy equipment
operator
Operating engineer
Woodworking, textile,and shoe machine
operators
Computer systemengineer
Computer systems
analysts / scientists
Engineering technician
Telephone fitter
Telephone line
installers and repairers

Garment industry

Epidemiological
study(Lin et al., 1985)(Savitz &Loomis, 1995)(Lin et al., 1985)(Loomis et al.,1994b)(Savitz et al.,
1994)
(Wilkins &Wellage, 1996)(Savitz et al.,1998b)(Savitz &Loomis, 1995)(Davanipour etal., 1997)
NONE

Exposure

TWA magnetic field
(mT)
AM

SD

0.25

0.03

0.24

0.47

0.24
0.24

0.47
0.47

0.23

0.30

0.23

0.23

0.22

0.13

0.22
0.22

0.14
0.14

0.21
0.21

0.47
0.25

Medium

0.21

0.16

Low

0.21

0.16

B (probable)

A (definite)

Medium(Lin et al., 1985)(Davanipour etal., 1997)(Sobel et al.,
1996)
(Sobel et al.,
1995)
NONE
(Sobel et al.,
1996)
(Sobel et al.,
1995)
(Davanipour etal., 1997)(Coogan et al.,
1996)
(Coogan et al.,
1996)

C (possible)
Medium

Low

0.21

0.15

(Davanipour etal., 1997)(Coogan et al.,
1996)
(Coogan et al.,
1996)
(Fear et al., 1996)(Milham, 1985)(Deapen &Henderson,
1986)(Loomis et al.,1994b)(Savitz et al.,
1994)
(Wilkins &Wellage, 1996)(Sobel et al.,
1996)
(Sobel et al.,Medium

0.21

0.41

High

0.21

0.41

Medium

0.20

0.60

0.20
0.20

0.13
0.13

68

Table 2.4 (continued)

Occupation

Industry orcompany

1995)(Savitz et al.,1998b)(Demers et al.,
1991)
NONE

Telephone line
installers and repairers
Supervisors, sales
occupations, insurance,
real estate, and businessservices
Computer equipment
operator
Machine molder
Printing machine
operator
Serviceman

Epidemiological
study

Iron foundries

Telephonecompany

Lathe worker(Loomis et al.,1994b)(Savitz et al.,1998b)(GuŽnel et al.,
1993)
(Coogan et al.,
1996)
(Lin et al., 1985)(Davanipour etal., 1997)(Sobel et al.,
1996)
(Sobel et al.,
1995)
(Lin et al., 1985)(Coogan et al.,
1996)
(Lin et al., 1985)
None

Machinist

Machinist
Machinists / tool anddie makers
Toolmaker
Janitors and cleaners
50th percentile of males
Telephone installer
Telephone installers andrepairers

Authors and technicalwriters
Data processing
equipment repairer
EDP equipment repairer
Assembler

Assembler

Householdappliances

Assembler

Radio, TV andcommunications
equipment(Tynes et al.,
1992)
(Deapen &Henderson,
1986)(Wilkins &Wellage, 1996)(Savitz et al.,1994)
(Rosenbaum etal., 1994)(Coogan et al.,
1996)
(Wilkins &Wellage, 1996)(Coogan et al.,
1996)
(Sobel et al.,
1996)
(Sobel et al.,
1995)
(Deapen &Henderson,
1986)(Deapen &Henderson,
1986)

69

Exposure

TWA magnetic field
(mT)
AM

SD

0.20

0.13

0.20

0.08

0.18

0.24

Continuous

0.18

0.09

Low

0.18

0.09

A (definite)

0.17

0.02

Medium

0.17

0.06

0.17

0.06

C (possible)
Medium

0.17
0.17

0.06
0.06
0.06
0.09

Weak

0.17
0.17
0.17
0.16
0.16

0.09

0.15

0.17

0.15

0.64

0.15

0.64

0.15

0.02

0.15

0.02

0.15

0.02

Group 1

Low

High

0.09

Table 2.4 (continued)

Occupation

Assembler
Assembler
ChemistCoil winder
Data processing
machine repairman

Highway patrolman
Mechanics, computersand business machines
General officeoccupations
Teacher
Accountant
Accountant
Billing, posting andcalculating machine
operators
Dispatcher
Dispatcher
Air traffic controller

Broadcast equipment
operator

Radio/telegraphoperator
Radio and TV performer
Radio announcer
Telegraph operator
Telegrapher

Industry orcompany

Electricalmachinery andsupplies (NEC)Electricalequipment (notspecified)

Epidemiological
study(Deapen &Henderson,
1986)(Deapen &Henderson,
1986)(Davanipour etal., 1997)(Fear et al., 1996)(Deapen &Henderson,
1986)(Savitz et al.,
1994)
(Lin et al., 1985)(Johnson & Spitz,
1989)
NONE
NONE
(Davanipour etal., 1997)(Coogan et al.,
1996)
(Coogan et al.,
1996)
(Lin et al., 1985)(Demers et al.,1991)
(Demers et al.,
1991)
(Loomis et al.,1994b)(Savitz et al.,1998b)(Demers et al.,
1991)
(Loomis et al.,1994b)(Savitz et al.,
1994)
(Wilkins &Wellage, 1996)(Savitz et al.,1998b)(Tynes et al.,1992)
(Rosenbaum etal., 1994)(Johnson & Spitz,
1989)(Demers et al.,
1991)
(Milham, 1985)(Rosenbaum etal., 1994)(Demers et al.,70

Exposure

TWA magnetic field
(mT)
AM

SD

0.15

0.02

0.15

0.02

0.15

0.06

0.15
0.15

0.02
0.64

0.15
0.15

0.09
0.64

0.15

0.18

Medium

0.15
0.14

0.09
0.10

Low

0.14

0.10

Medium0.14

0.13

B (probable)
Group 3

0.14
0.14

0.23
0.23

Group 3

0.14

0.23

Group 3

0.14

0.23

RF

0.14

0.23

0.14

0.23

0.14

0.23

0.14

0.23

0.14

0.23

MediumB (probable)

Group 3

Group 3

Table 2.4 (continued)

Occupation

Industry orcompany

1991)(Coogan et al.,
1996)
(Loomis et al.,1994b)(Savitz &Loomis, 1995)(Demers et al.,1991)
(Wilkins &Wellage, 1996)
None

Communications
equipment operator
Other communications
operators
Electrical and electronicequipment repair(miscellaneous)
Stock handlers andbaggers
Medical technologian
ForemanTelephonecompany

Chief communications
operator
25th percentile of males
Brickmason
Shop assistantDairy products
and bread

Insurance

Aluminumindustry

Military
communications worker
Air Force pilot
Blue-collar jobs (nonservice)

Data entry keyers

EDP and card punch
operators
Electrical andelectronics workers
Electronics workers(Davanipour etal., 1997)(Lin et al., 1985)

Exposure

Aluminum andnon-ferrous metal
production,
smelting andrefiningNone(GuŽnel et al.,
1993)
(Loomis et al.,1994b)(Savitz et al.,1998b)(GuŽnel et al.,
1993)
(Coogan et al.,
1996)
None
(Milham, 1985)(Demers et al.,1991)
(Davanipour etal., 1997)(Rosenbaum etal., 1994)(Loomis et al.,1994b)(Sobel et al.,
1995)
(Sobel et al.,
1996)
(Savitz et al.,1998b)(GuŽnel et al.,
1993)
(Spitz & Johnson,
1985)(Nasca et al.,71

TWA magnetic field
(mT)
AM

SD

0.14

0.23

0.14

0.23

0.14

0.19

0.14

0.08

Medium0.13

0.19

A (definite)

0.13

0.15

0.13

0.15

0.12
0.11
0.11

0.05
0.02

0.10

0.01

Continuous

0.10

0.10

Medium

0.10

0.05

0.09
NR

0.02
NR

Group 3NR

NR

Medium /
high

NR

NR

NR

NR

NR

NR

Continuous

NR

NR

Narrowdefinition
Narrow

NR

NR

NR

NR

MediumGroup 2

(Loomis et al.,1994b)(Savitz et al.,1998b)

Telephone operator

Programmer, systems
planner
Statisticians andscientists
Social worker
Employee

Epidemiologicalstudy

ContinuousTable 2.4 (continued)

Occupation

Fork-lift operators
Heat-treating,equipment, furnace, kiln,
and oven operators
Radar operator
Radio operators

Industry orcompany

Epidemiological
study

1988)
(Wilkins &Wellage, 1996)(Coogan et al.,
1996)
(Davanipour etal., 1997)(Johnson & Spitz,
1989)

NR, not reportedaNumbers in italics are approximate

72

Exposure

TWA magnetic field
(mT)
AM

SD

NR

NR

Low

NR

NR

High

NR

NR

NR

NR

definition

Table 2.5 Occupational exposure measurements in occupational studies
SourceClass

Measurement Method

Field(Bowman et al.,1988)

Non-office electrical
work sites

Spot measurement as close
to worker as possible, in
direction of most likely
field source
Spot measurement as close
to worker as possible, in
direction of most likely
field source
Spot measurements atseveral sites; both low &high power conditions

0.07 mT ( microelectronics
assemblers);
10 mT ( electricians)

Geometric mean

0.31 mT (one secretary with
VDT);
0.11 mT (3 secretaries w/o
VDT)
0.06 mT

Geometric mean

Exposure measured over 7day period for both workand non-work using
personal dosimeters
Exposure measured over 7day period for both workand non-work using
personal dosimeters

1.7 mT at work, 0.31 mT for
non-work

Geometric mean

0.16 mT for work, 0.19 mT for
non-work

Geometric mean

Electricians &substation operators

Exposure obtained for 770
workdays

Mean

Office staff, meter
readers, &groundmen

73 workdays of data for 3
classifications of office
workers

2.1 mT (electricians);
1.8 (subs. ops.); these werehigh exposure group0.1, 0.18, 0.23 mT for threeclassifications of office
workers(Barroetavena et al.,1994)

3 pulp and paper
mills (facilities A, B,
and C0Measurements made at totalof 132 locations, and in
offices

Facility A - 0.12 mT
Facility B - 0.33 mTMedian(Skotte, 1994)

Power frequency MF
in elect. util., office,& industrial.
workers, & in people
living near highpower lines

301 subjects, total of 396
24-hr measurements; 55
subjects were office
workers not from utility
companies

0.09 mT (1.8) office workers;
0.05 mT (2.1) residences notnear high voltage lines

Geometric mean
(geometric standard
deviation)

Offices

Residences (18)(Deadman et al.,1988)

20 workers from 6
electric utilities
16 workers from 2
office buildings(Sahl et al., 1994)

73

Metric

Notes

Geometric mean

Mean

Possible misclassification of some work
time as non-work

Occupations studied were classified into
3 groups using fraction of exposures withsummary measure > 0.5 mT
Occupations studied were classified into
3 groups using fraction of exposures withsummary measure > 0.5 mT
Difference in non-office levels attributed
tot al electric consumption

Table 2.5 (continued)
Source(Breysse et al.,1994a)Class
ELF MF in large
payroll department.

Measurement Method
Spot measurements
Personal data for 15 female
employees

Field

Metric0.13 to 2.7 mT for officeequipment
0.32 ± 0.15 mT, with rangeof 0.1-0.65 mT

Range

Notes

Mean of personal
TWAs, range of
personal TWAs

(Burch et al., 1998)

194 utility workers

MF & light measured bypersonal dosimeters 24 h/dfor 5 consecutive days;
melatonin metabolite
excretion measured in urine
samples

Distribution workers -0.64 ±0.04 at work, 0.5±0.04 during sleep;
Office and administrative
workers -- 0.73 ± 0.03 atwork, 0.58 ±0.04 during
sleep

RCMS

Standardized rate of change metric (RCMS)
for MF was predictor of decreased
melatonin excretion(Bracken et al.,
1995b)

Utility workers in
13 job classes at 59
sites in 4 countries

50,000 hrs of MF datataken at 10s intervals by
dosimeter; 70% were fromwork environments

Substation operators 0.7
mT; electricians 0.5 mTMedian workday
mean

These two groups had highest exposure
by this metric. Utility-specific jobclassifications had about 1/2 of timeintegrated exposure on the job.

All work categories, while
not working 0.09 mT
Means in exposure
categories 0.12 to 1.27 mTMedian nonworkday mean
TWA

(Savitz & Loomis,
1995)

138 905 electricutility workers at 5
US companies(ThŽriault et al.,1994)

3 cohorts of electricutility workers in
Ontario, Quebec, andFrance

JEM constructed fromcurrent occupations andlinked to occupational
histories

3.1 mT-years (median)15.7 mT-years (90thpercentile)

Cumulative exposure(Floderus et al.,1996)

Swedish workers

At least 4 personal
exposuremeasurements/occupationfor 100 common
occupations at 1015
workplaces; used to form
JEM

0.04 mT (earth mover
operators); 0.05 mT(concrete workers); 0.19 mT(electrical and electronics
engineers and technicians
and welders); 0.28 mT(overall); 0.17 mT (median ofoccupations)

Workday mean

74

No measurements given in Section 2.3

90th percentile cut-point for last job wasgood predictor of 90th percentile cutpoint for total job history

Table 2.6 Distribution of wire code categories of control subjectsÕ homes in seven studies in theUSA
Study location(reference)

Homes in indicated category (%)
UG

VLCC
a

OLCC

OHCC

VHCC

56

25

6

Denver area
(Wertheimer &Leeper, 1982)

None

13

Denver area
(Savitz et al.,
1988)

34

7

39

17

3

Seattle area
(Severson etal., 1988)

None

45a

33

16

6

Los Angeles
area (London
et al., 1991)

5

13

37

33

12

Los Angeles
area (PrestonMartin et al.,1996b)

7

13b

28 b

42

10

Seattle area
(Gurney et al.,
1996)

40

26

13

15

7

Nine states in
USA (Linet etal., 1997)

18c

26 c

28

22

6

UG, underground wiring; VLCC, very low current configuration; OLCC, ordinary low current configuration; OHCC, ordinary high current
configuration; VHCC, very high current configurationaDesignated as Òend poleÓ in this studyb
Authors reported only the combined percentage of homes in the VLCC and OLCC as 41%. That number is divided between the twocategories in accordance with the ratio of all study subjects in those two categories.
cAuthors reported only the combined percentage of homes in the UG and VLCC categories as 44%. That number is divided between the twocategories in accordance with the ratio of all study subjects in those two categories.

75

Table 2.7 Measured magnetic fields and Wertheimer-Leeper wire codes in six studies in the USA
Study location(reference)

Magnetic field (mT)

Reported measure ofcentral tendency

UG

VLCC

OLCC

OHCC

VHCC

(Wertheimer & Leeper,
1982)
Median of spotmeasurements next tohome at point near line

excluded< 0.05< 0.050.12

0.25(Savitz et al., 1988)
Low power spotmeasurement in home:
Mean

0.049

0.053

0.071

0.12

0.21

Median

0.030

0.030

0.051

0.09

0.22

(Severson et al., 1988)
Median of a small
subsample

excluded

.032

.048

.11

.17

(London et al., 1991)
Geometric mean of low
power spotmeasurements

.017

0.017

0.022

.0029

0.060

Geometric mean of 24-h
medians

0.045

0.042

0.058

0.066

0.11

(Preston-Martin et al.,1996b)
Mean of 24-h mean in
bedroom

0.078

0.076

0.10

0.12

0.18

ibid., Mean of 24-h
median in bedroom

0.047

0.057

0.043

0.060

0.11

(Tarone et al., 1998)
Mean of 24-h means

0.064

0.077

0.12

0.14

0.21

Median of 24-h means

0.046

0.049

0.075

0.098

0.13

UG, underground wiring; VLCC, very low current configuration; OLCC, ordinary low current configuration; OHCC, ordinary high current
configuration; VHCC, very high current configuration76

Table 2.8 Comparison of the percentage of homes in wire code categories > 0.2 or 0.3 mT in fourstudies in the USA
Study Location(reference)

Wire code category (%)

Reported measure

UG

VLCC

OLCC

OHCC

VHCC

(Wertheimer & Leeper,
1982)
Outdoor spotmeasurements > 0.3 mT

excluded

0

1

10

29

(Savitz et al., 1988)
Spot measurement > 0.2
mT

3

0

6

21

60

(Severson et al., 1988)
24-h mean > 0.2 mT out ofa small subsample

excluded

0

6

11

50

(Tarone et al., 1998)24-h mean > 0.2 mT

3

6

15

20

40

24-h mean > 0.3 mT

0

3

6

10

23

UG, underground wiring; VLCC, very low current configuration; OLCC, ordinary low current configuration; OHCC, ordinary high current
configuration; VHCC, very high current configuration

77

78

3

Internal Dosimetry
In chemical toxicology, the delivered dose of a xenobiotic is the concentration of thesubstance at the cell or tissue of interest. When the toxicant is a chemical, the dose can bemeasured using analytical devices. With EMF, current knowledge indicates that the
combination of the geomagnetic field, AC magnetic fields, and electric fields and currents
induced on or in the body may affect biological processes. Because the exact mechanisms
by which these potential effects are produced have not been identified, however, it is
impossible to clearly define which aspects of EMF constitute the dose. In studies of
EMF, description of the relationships between external EMF and the EMF and currents
induced in the body is called ÔdosimetryÕ. The dosimetry of EMF can be estimated using
the standard analytical techniques of electromagnetics, although the significance ofparameters other than intensity must be considered. First, as EMF can be applied
separately at low frequencies (< 100 kHz), specifying whether the applied field is electricor magnetic is essential. Second, because EMF are vectors, it is essential to specify not
only magnitudes but also field directions with respect to the individual object (axial ortransverse). For electric fields, the shape of the exposed object greatly affects the induced
currents, and for magnetic fields the cross-sectional dimensions of the individual are
critical. In addition, for both electric and magnetic fields it must be known whether the
exposed object was electrically insulated or electrically grounded.
The wave shape or frequency content of the applied signal also influences delivered dose
significantly. If the signal is purely sinusoidal and is applied continuously, only thefrequency and the duration of exposure need to be specified; however, if pulsed fields areused, then specification of wave shape, the rise time, decay time, duration of individual
pulses, and pulse repetition rate is essential. In general, the wave shapes of appliedmagnetic and induced electric pulses are radically different.
Finally, a description of exposure to EMF should include measured values of backgroundfields, since these fields vary widely between laboratories. These include the geomagnetic
field, which is essentially static.

3.1

Electric field dosimetry for human exposure
Equation 2.1 in section 2 provides a rough approximation of the electric fields inside andoutside an individual subjected to an external electric field. An electric field that is initially
uniform becomes distorted in the immediate vicinity of a person. Whether the individualis electrically grounded or is standing on an insulating platform also will significantly
affect the field distribution (Table 3.1). Finally, for human exposure, the interest isusually not in the average electric field within the body but rather in the field and current
density distribution within parts of the body. The in homogeneity of electric properties(e.g. bone vs. muscle conductivity) and variations in the cross-section of the limbs and79trunk determine the exact current density distribution. Extensive model calculations andmeasurements have been made on ÔphantomsÕ (saline body models) (Dawson et al., 1997;
Kaune & Forsythe, 1985). Thus, the maximum current densities in a human standing onelectrically conducting ground in a 10-kV/m, 60 Hz electric field are 0.03 A/m2 in the leg
and 0.004 A/m2 in the neck.
Table 3.1. Typical average electric fields in bone marrow in numerical dosimetric studies
of uniform conditions of exposure to electric or magnetic fields at 60 Hz
Vertical electric field (1 kV/m)Organ-averaged electric field(mV/m)

Grounded man
Insulated 14.4 mm above
groundFree space

3.0
1.8
1.0

From Dawson et al. (1997)
Values are given for the tissues with the highest organ-averaged electric fields for each exposure condition

Differences in shape, body size, and body orientation result in substantial differences in
induced electric field intensity with equal exposure to external electric fields. Thus, rats ina cage must be exposed to a 30-kV/m, vertical, 60 Hz electric field in order to obtainroughly the same current densities within the rat body as inside a human standing uprightin a 10-kV/m, 60 Hz field (Kaune & Phillips, 1980).

3.2

Low-frequency magnetic field dosimetry

3.2.1 Magnetic fields induced in the body by external magnetic fields
The ELF magnetic flux density, B(t), inside living tissues is approximately equal to theexternal field. This relationship is a consequence of two conditions. First, the magnetic
permeability of tissue and cells is approximately equal to that of free space. Second, therelatively low electric conductivity (at most on the order of 1 S/m) of living matter, incomparison with that of metallic structures (»107 S/m), guarantees that the magnitude of
the secondary magnetic field produced by the induced eddy currents is negligible (Polk,
1990). Therefore, the applied magnetic field can be measured externally without need tocorrect for the presence of an individual in the field.

3.2.2 Magnetic fields induced in the body by external magnetic fields
A time-varying magnetic field vector B also creates an electric field E according toFaradayÕs law, such that

80

¶B

ò Ed1 = - ò ò ¶t ds

Eq. 3.1

where d1 is a vector element of length and ds is a vector element of area.
When a magnetic flux density B is applied parallel to the axis of an infinitely long,electrically homogeneous, circular, cylindrical body, equation 3.1 reduces to
Ef = pfBr

Eq. 3.2

where Ef is the circumferentially directed electric field, f is frequency, and r is the radial
distance from the center of the cylinder. This last relation is frequently employed inestimating induced electric fields in animal bodies and cell cultures but will give only
approximate results because biological tissue is neither cylindrical nor electricallyhomogeneous. Table 3.2 nevertheless shows that a 60 Hz, 1 mT magnetic flux density B,
orientated from the front to the back of an individual will induce an electric field on theorder of 100 mV/m near the periphery of the body. Detailed calculations are necessary toestimate induced field intensities in organ systems (Dawson et al., 1997).
Table 3.2. Calculated average induced electric fields in selected tissues in a human adult from a 1.0
mT, 60 Hz magnetic field orientated from shoulders and assumed tissue conductivities
Organ
Brain
Cerebrospinal fluid
Lungs
KidneyProstate

Tissue conductivity s (S/m)
0.1Ð0.17
1.5Ð2.0
0.07Ð0.09
0.27
0.11Ð0.4

Induced electric field (mV/m)
11Ð12
2.8Ð5
21Ð28
14Ð24
17Ð22

From Dawson et al. (1997)

Depending on the biological interaction mechanism, either the internal magnetic field or
the induced electric field is the appropriate applied dose.

3.3

Scaling between different organisms, assuming that an observed
effect is due to induced electric fields
Equations 3.1 and 3.2 indicate that the magnetic flux density B would have to be varied ininverse proportion to the radius r (in a plane perpendicular to the direction of B) if thesame induced electric field is to be obtained in different preparations or organisms. Thus,
assuming that a particular physiological system is similar in mice and humans, a 10 mT,
horizontal, 60 Hz magnetic field in a mouse of 2.5-cm diameter and a 1 mT, vertical 60 Hz
magnetic field in a human of 25-cm mean body diameter would produce similar effects.

81Because the electric properties of biological substances can change substantially over ascale of nanometers (for example when a membrane is present), predictions of the electricfield at every point in a tissue are therefore accurate on a micro-scale only when regions oftissues are correctly represented.
Electric fields inside the human or animal body induced by time-varying ELF magnetic
fields will not necessarily produce the same biological effects as internal electric fields due
to externally applied magnetic fields. Scaling between different organisms or from in-vitro
to in-vivo conditions will differ widely for external electric and magnetic fields, even if themagnetic field exerts its physiological effect only through induced electric fields or current
densities. In the absence of detailed numerical micro-scale models, equation 3.2 must be
used for first-order scaling.

3.4

Considerations for in vitro dosimetry
Several experiments (Blackman et al., 1994; Liboff et al., 1987) have shown that certain
biological effects depend on synergism between static and time-varying magnetic fields,suggesting that both magnitude and relative field direction are important. Inside a steelframe building or a laboratory incubator, the ÔstaticÕ magnetic field may differ
substantially in both magnitude and direction from the field in free space and may also
vary from point to point. Specifying the characteristics of the background field at the
exposure location is therefore essential when biological effects of weak (microtesla)magnetic fields are investigated. Similar considerations are not needed for electric fields
because they are substantially lower in saline than in air.

3.4.1 Electric field dosimetry
Culture media generally have an electric conductivity on the order of 1 S/m, similar to thatof fluid-saturated living tissue. A material is considered to be an electric conductor, as
opposed to an insulator or dielectric, if the ratio of conduction current density, sE , todisplacement current density, e(¶E/¶t), is much greater than 1, where s is the electric
conductivity, E is the electric field, and e is the dielectric permittivity. For a field thatvaries sinusoidally in time at a frequency of w/2p, this relationship is:

s
>> 1
we

Eq. 3.3

The dielectric permittivity is given by e = e1e0, where e0 is the permittivity of free space,which is equal to 8.84 x 10Ð12 F/m, and e1 is the relative dielectric constant. Below 100
Hz, the e1 of living tissue can be as large as 106; nevertheless, equation 3.3 still gives a82

value of 180 at 100 Hz with s = 1 S/m and er = 106. Thus, at ELF, culture media can beconsidered to be electrically conducting fluids. Electric fields are therefore most easily
introduced into cell cultures by contact and by measuring the series current, I. If theelectrodes are large enough and their shape is relatively simple, or if the field is calculated
at a point in the field at a distance that is relatively far in comparison with the electrodesize, then the electric current density, J, is given by I/A, where A is the cross-sectional
area of rectangular electrodes or of rectangular vessels. The electric field can then be
calculated from J = sE if the conductivity is measured.
All such calculations are based on the assumption that the culture medium of cells andtissues is electrically homogeneous. This approximation is reasonable for freely floating
cells at relatively low density. If cells are plated at the bottom of a culture vessel andbecome confluent, or nearly so, the culture fluid and cell system must be considered a
two-layer medium, in which the bottom (cell) layer may have vastly different (and at ELF
usually lower) electric conductivity than the fluid. Current density and field evaluation
then require more complex calculations.
Electrodes must be introduced cautiously into biological fluids in order to avoid chemical
reactions at the electrode surfaces and consequent contamination of the fluid. The mostsuccessful method is use of agar bridges. Another method for introducing an electric field
into a culture medium is capacitive coupling (Polk, 1995).

3.4.2 Magnetic field dosimetry
A key question in exposure to magnetic fields is the magnitude of the induced electricfield. Here, the orientation of a culture dish or any other object within the magnetic field
will have major consequences because only the component of the magnetic field that isperpendicular to a surface contributes to the induced electric field in the plane of that
surface; different orientations of the magnetic field to the culture dish result insignificantly different induced electric field magnitudes and distributions. In the immediate
vicinity of a high-voltage transmission line, the electric field induced in a human by theelectric field of the line will generally be larger than the electric field induced by the lineÕs
magnetic field. Conversely, inside a home or even near a secondary distribution line, theelectric field induced inside the body will usually be due to the external time-varying
magnetic field (King, 1998; King & Wu, 1995).

3.5

Summary
The occurrence of static and dynamic EMF in the environment will result in the inductionof magnetic and electric fields in the body. Because of the low permeability of living
tissues, both static and dynamic magnetic fields within the body will be similar to the83magnetic fields outside the body. Conversely, the induction of electric fields in the bodydue to either time-varying electric or magnetic fields requires careful numerical calculations
which incorporate size, shape, and organ conductivity. Peak induced electric fields in thehuman body due to exposure to a 60 Hz, 1 mT magnetic field can exceed 0.1 mV/m.
Similar computational techniques can be used to determine induced fields in laboratory
experiments.

84

4

Biological Data Relating to the Toxicity of Extremely Lowfrequency Electromagnetic Fields

4.1

Carcinogenicity in animals
Although the interaction of an agent with humans is of prime importance and concern,many areas of biological investigation are more efficiently and appropriately conductedwith animal species. Studies in laboratory animals provide an integrated system in which
experimental variables can be controlled, specific hypotheses can be explored, andexposure can be precisely assessed. Given the uncertainty and the relatively low power of
epidemiological studies of EMF to ascertain the relationship between exposure andpossible adverse health effects, studies in experimental animals are especially important inevaluating whether there is an association with cancer. These studies have, however,limitations for risk assessment. In several instances, identification of cancer-inducing
agents in animals preceded their identification in humans.
Studies of a possible association between exposure to EMF and cancer are challenged byunidentified intensity and/or frequency parameters that can result in reproducible
biological responses and dosimetric differences between animals and humans. The effects
of EMF have usually been studied at intensities of exposure that are much higher thanenvironmental levels, in order to determine if effects occur. Another approach, not yet
used to any great extent, is to focus on exposure parameters at levels commonly
experienced by humans. Several designs and animal models have been used in laboratory
studies of cancer. The choice of model depends largely on the hypothesis for a particularunderlying mechanism. Few carcinogenic agents exert their full effect after a single, brief
exposure, and most agents act only after an extended exposure. During that time, exposure
to other possibly confounding agents must be kept to a minimum. The long-term bioassay
is designed to address this issue. In this design, the animals are observed for most of their
lifetime, and the number, type, and time of appearance of tumors are the critical endpoints. This type of study should include several doses and a relatively large number ofanimals, particularly if the natural incidence of the tumor type is low. As might besurmised, studies of complete carcinogenicity are expensive, due to both the length oftime and the number of animals involved. One potential problem in such studies is theinadequacy of present knowledge about what aspects of the EMF signal are biologically
active.
A consideration in using animal models to investigate the effects of EMF on cancer
development is the appropriateness of the model itself in relation to human disease. For
example, the rat mammary carcinoma model has been thought to be reasonably relevant inmany ways for investigating human breast cancer (Russo et al., 1990), as many of thefactors that promote tumors in the animal model also increase breast cancer risk inhumans. Nevertheless, other aspects of the rodent model may not be directly relevant to85human disease. Another commonly used animal cancer model is mouse skin. This
represents a convenient, well-developed way of investigating mechanistic questions in
multistage carcinogenesis. Although it allows the study of potential risk factors on theprocess of cancer development, its results may not translate easily into information on
the specific cancer type in humans. Other models, specifically for investigating the risk
for leukemia, are valuable because a variety has been developed. Thus, considerable
information is available about leukemia and lymphoma and its carcinogenic process inanimals, and some similarities exist between the development of the disease in thesemodels and in humans (Pattengale & Taylor, 1983).

4.1.1 One- and two-year bioassays
Lifelong studies of EMF as a complete carcinogen have been conducted in experimental
animals in Canada, Japan, and the United States. The results are summarized in Table 4.1.
The results of long-term bioassays can provide a general assessment of whether an agent
is carcinogenic in an animal model. This type of study is therefore relevant to theinitiation, promotion, and progression phases of cancer development, although it may notcontribute much information on biological mechanisms. As indicated above, few have been
carried out on exposure to EMF because of the time and the cost of such assays.
The most comprehensive study to date of EMF as a potential carcinogen was conductedat the IIT Research Institute for the National Toxicology Program (NTP, 1998b). In thisstudy, which was conducted according to good laboratory practice (GLP), groups of 100
Fischer 344 rats and 100 B6C3F1 mice of each sex were exposed to one of several
magnetic field conditions: 2 200, or 1000 mT continuously or 1000 mT intermittently (1 hon, 1 h off), 60 Hz linearly polarized magnetic fields; one group received sham exposure.
Neither exposed nor control animals were exposed to transients. Exposure began when the
animals were 6Ð7 weeks of age and continued for 18.5 h/d for two years. The animals
were monitored and evaluated over the course of their lifetime for survival, body weight,
and clinical signs of neoplasia. At death (average age, 112Ð113 weeks), all animals
underwent complete necropsy and histopathological evaluation.
The survival of exposed rats (47Ð59% of males and 58Ð68% of females) was no different
from that of control animals (57% males and 59% females). There were no exposurerelated clinical findings. The only significant increase in tumor incidence in field-exposed
rats was for thyroid gland C-cell adenomas and carcinomas combined in male rats, withincidences of 16% in sham-exposed controls, 31% in those at 2 mT (p < 1.01), 30% in
those at 200 mT (p < 0.01), 25% in those at 1000 mT continuously (p = 0.06), and 22% in
those at 1000 mT intermittently (p = 0.15). The incidence of mononuclear-cell leukemia inmales was 50, 44, 47, 50, and 36% (p < 0.05, intermittent group) for the five groups,
respectively.

86

The survival of exposed mice (72Ð84% in males and 74Ð79% in females) was similar tothat of control animals (76% males and 70% females), except for male mice exposed to1000 mT which had significantly reduced survival (62/100, p = 0.037) in comparison with
control mice (76/100). There were no exposure-related clinical findings. Significant
differences in the incidence of neoplasms between field-exposed and sham-exposed mice
included decreased incidences of alveolar/bronchiolar adenoma in males exposed to 2 mT
(11/99, p = 0.007) or 200 mT (9/100, p < 0.001) and in female mice exposed to 200 mT(0/99, p = 0.002). The incidences of adenoma and carcinoma combined were significantly
lower in males (19/100, p = 0.041) and females (29/99, p = 0.008) exposed to 200 mT thanin controls (males, 30/100; females, 11/95). The incidence of malignant lymphoma infemale mice exposed intermittently to 1000 mT was significantly lower (20/100, p =0.035) than that observed in the controls (32/100).
The authors concluded that under the conditions of these two-year studies with wholebody exposure there was equivocal evidence for the carcinogenic activity of 60 Hz
magnetic fields in male Fischer 344/N rats, on the basis of the increased incidences ofthyroid gland C-cell neoplasms in male rats exposed at 2 or 200 mT . There was noevidence of carcinogenic activity in female rats or in male or female B6C3F1 mice exposed
to 2, 200, or 1000 mT continuously or to 1000 mT intermittently.
A study similar to that described above was conducted in Canada (Mandeville et al.,1997). In this study, groups of 50 female Fischer 344/N rats were exposed to 2, 20, 200,
or 2000 mT 60 Hz, linearly-polarized magnetic fields; there were also groups of shamexposed and cage controls. The authors carefully excluded transients. Exposure began twodays before birth and continued for 20 h/d for two years. The animals were monitored andevaluated over the course of their lifetime for survival, body weight, and clinical signs ofneoplasia. At death, all of the animals were subjected to complete necropsy andhistopathological evaluation of 50 organs and tissues from each animal, with specificattention to the incidences of mononuclear-cell leukemia, brain tumors, and mammary
tumors.
The survival of rats at the end of the study was significantly lower among the shamexposed controls (19/50, p = 0.03) and animals exposed to low field intensities (16/50, p =0.005 for both 2 and 20 mT groups) than in cage controls (30/50). The survival rates were
not different for exposed and sham-exposed animals (16/50, 16/50, 24/50, and 25/50 inrats at 2, 20, 200, and 2000 mT, respectively, versus 19/50 in sham-exposed). There were
no consistent exposure-related clinical findings.
The two control groups had higher overall tumor incidences (45/50 in cage controls and46/50 in sham-exposed) than exposed rats (42/50, 43/50, 43/50, and 41/50 in rats at 2, 20,
200, and 2000 mT). In all groups of animals, the commonest tumor types were pituitaryadenomas, mammary gland fibroadenomas, and mononuclear-cell leukemia. Following thepattern for overall tumor incidence, that of pituitary adenomas in the exposed animals
varied between 40% (2 mT; 20/50, p = 0.04) and 44% (2000 mT; 22/50, p = 0.07) and was87statistically significantly lower than in the controls (31/49 in cage controls, 29/49 in shamexposed). When the sham-exposed animals were compared with the exposed rats for
mammary gland fibroadenomas, there was no significant difference (28/50 for shamexposed and mice at 2 mT versus 27/50, 24/49, and 21/50 for those at 20, 200, at 2000 mT
respectively). Mammary gland adenocarcinomas were rare in all groups of animals. The
incidence of mononuclear-cell leukemia was relatively low and not significantly different
in any group.
The authors concluded that there was no evidence for the carcinogenic activity of 60 Hz,
linear sinusoidal, continuous waves at intensities of 2, 20, 200, or 2000 mT in female
Fischer 344 rats, suggesting lack of carcinogenicity. There were also no statisticallysignificant, consistent, dose-related trend in the number of tumor-bearing animals per
study group that could be attributed to exposure to magnetic fields.
The results of a carefully conducted, well-documented study to determine the
carcinogenic effect of 50 Hz sinusoidal magnetic fields in rats throughout their lifetime
have been reported (Yasui et al., 1997). Groups of 48 Fischer 344/DuCrj rats of each sex
were exposed to flux densities of 500 or 5000 mT or sham fields from 5 to 109 weeks ofage. The high dose was much higher than those used in the other two studies. The
exposure design eliminated transients, and exposure was for 22.6 h/d day for two years.
The animals were monitored and evaluated over their lifetime for survival, body weight,
and clinical signs of neoplasia. At death, all animals underwent complete necropsy andhistopathological evaluation.
The survival of exposed rats was no different from that of control animals. There were no
exposure-related clinical findings. The only significant difference between exposed andsham-exposed rats in the incidence of neoplasms was an increase in fibroma of the
subcutis in males at 5 mT (9/48 versus 2/48 in controls, p = 0.05). This increase in theincidence of a benign tumor was not significant in a comparison with historical controls.
The incidences of leukemia, lymphoma, and brain and of adenomas of the pituitary andthyroid (changes noted in other animal studies) were no different between field- andsham-exposed animals.
Marganato et al. (Margonato et al., 1995) investigated the exposure of groups of 256
animals male Sprague-Dawley rats to a 50 Hz field over 32 weeks. Exposure was for 22
h/d to 5 mT magnetic fields or sham exposure. Although this study was not designed toaddress the issue of cancer per se, the biological end-points included hematologicalexaminations for each animal and morphological and histological evaluation of the liver,heart, mesenteric lymph nodes, and testes. In two identical sets of experiments involving
128 rats per group per experiment, no significant difference in the investigated variables
was found between exposed and sham-exposed animals. Although certain parameters
differed between the two experiments, the exposure conditions were the same. The
authors concluded that the results did not indicate any harmful effects of prolonged
exposure to magnetic fields comparable to those measured close to power lines. [This88conclusion is limited to a selected number of markers within the portion of the life span of
the animal corresponding to a high growth rate but not to the early developmental phase.]
Few long-term bioassays have been performed of the exposure of mice or rats to 50- or 60
Hz magnetic fields. In the largest and most comprehensive of the studies (Mandeville etal., 1997; NTP, 1998b; Yasui et al., 1997), few significant effects (both increases anddecreases) of exposure on cancer development were seen, with the exception of isolated
thyroid C-cell adenomas and carcinomas in male rats in the NTP study.

4.1.2 Multistep carcinogenesis
Carcinogenesis is a multistep, multifactorial process. The experimental approach mostcommonly used is the two-phase protocol, based on the two-stage hypothesis, which canbe used to verify whether the agent of interest acts as an initiator or a promoter.
ÔInitiationÕ is considered to involve a genotoxic event in which the carcinogen interacts
with target cells to affect DNA. ÔPromotionÕ is associated with a number of subcellular
events that are generally nongenotoxic and is responsible for the conversion or clonal
expansion of initiated cells to a cancer. When EMF is be investigated for possible
promotional effects, animals are treated with a known initiator (e.g. ionizing radiation or achemical carcinogen such as 7,12-dimethylbenz[a]anthracene, DMBA) and subsequently
exposed to EMF over a long period (months). InitiationÐpromotion approaches have theadvantage of involving fewer animals, shorter time, and less cost. This approach may also
provide information on doseÐresponse relationships or answer questions about biologicalmechanisms. An initiationÐpromotion study may provide only general information on thespecific effect of EMF on cancer development. A given model is usually limited toevaluating a specific type of cancer that may or may not be relevant to the agent ofinterest.
Neither the long-term studies of spontaneous tumor development studies summarized
above nor shorter studies have given any indication that EMF are mutagenic. For thisreason, investigations based on the multistage nature of carcinogenesis have focused on
the promotional phases of the cancer process. The studies summarized below addressed
the specific question of whether EMF acts as a promoter or co-promoter of tumorigenesis
in models of mammary, skin, liver, and brain cancer and of lymphoma/leukemia and as anenhancer in a rat leukemia progression model.
4.1.2.1 Mammary Cancer
Several studies have been conducted to examine mammary cancer and exposure tomagnetic fields (Table 4.2), because of the importance of breast cancer to the public andon the basis of a possible biological mechanism involving the hormone melatonin (Stevens,
1987) and EMF (Wilson & Matt, 1997).

89

(a) Initiation with N-methyl-N-nitrosourea
In the earliest reported study of this type, Beniashvili et al. (Beniashvili et al., 1991)
induced mammary tumors in five groups of 50 female rats by an intravenous injection of
N-methyl-N-nitrosourea (MNU; 50 mg/kg body weight) at 55 days of age. Afteradministration of the MNU, one group served as cage controls, and two groups were
exposed to a 20 mT, 50 Hz magnetic field for 30 or 180 min. each day, and exposure
continued for the lifetime of the animals. Animals exposed to the 50 Hz field for 180
min/d had a higher incidence (p < 0.05) of mammary tumors than cage controls (43/46 vs.
27/46) and a larger number (p < 0.05) of total tumors (75 vs. 31 in controls). In addition,
the mean latent period was shorter in the exposed animals (45.5 d) than in the MNUinjected controls (74.4 d). No differences were observed for the animals exposed tomagnetic fields for 0.5 h/d.
As part of this study, 25 female rats were exposed to 50 Hz magnetic fields for 0.5 or 3
h/d with no MNU treatment. At the conclusion of the study after two years, limited
information was collected at necropsy and histological examination. A significant increase(p < 0.05) in the incidence of mammary gland tumors was observed in rats exposed to 20
mT for 3 h/d (7/25 animals) in comparison with those exposed for 0.5 h/d (1/25) and with
unexposed animals (0/50). The latency for tumor appearance was 74 ± 15 d for controls,
65 ± 1 d for 0.5-h exposure, and 46 ± 12 d for 3-h exposure.
Anisimov et al. (Anisimov et al., 1996), conducted a replication experiment in whichgroups of 40 outbred white rats were field- or sham-exposed to 50 Hz, 20 mT magnetic
fields for life (generally less than five months). Rats received 50 mg/kg MNU
intravenously at three-week intervals with either magnetic field exposure or sham
exposure for 3 h/d. Mammary adenocarcinomas (identified histologically) were found in
7/22 sham-exposed and 15/33 field-exposed (not significant). The mean latent period fortumor development was 166 ± 4 d for sham-exposed and 125 ± 7 (p < 0.05) for fieldexposed.
[The inadequate reporting of the method and experimental details prevents an assessmentof the significance of either result.](b) Initiation with 7,12-dimethylbenz[a]anthracene
A fairly comprehensive series of studies of mammary tumor initiation and promotion was
conducted by Lšscher and Mevissen (Lšscher et al., 1993; Lšscher et al., 1994; Mevissen
et al., 1998a; Mevissen et al., 1993). In all of their studies, female Sprague-Dawley rats
were initiated by intragastric administration of DMBA in sesame oil at 52 days of age bya fractionated dosage of 5 mg per animal given over four weeks (4 x 5 = 20 mg, total dose
DMBA). In all of the experiments, animals were exposed for 13 weeks, 24 h/d, to 50 Hz
horizontal magnetic fields. [No transients were expected from the design of the system.]90

In the initial study (Mevissen et al., 1993), female rats were exposed after DMBA
administration to 30 mT (50 Hz) magnetic fields. The average mammary tumor incidenceswere 66% (range, 55Ð75%) in reference controls and 61% (range, 50Ð78%) in shamexposed controls. Exposure to magnetic fields resulted in tumors in 19/36 sham-exposedand 20/33 field-exposed animals, and the total number of tumors was 51 in treated animals
and 36 in sham-exposed (not statistically significant). When the latter experiment was
repeated with only eight or nine animals per group, no difference was found between the
exposed and control groups. When groups of 36 DMBA-treated rats were exposed to a
gradient (0.3Ð1.0 mT) 50 Hz field, no difference in tumor incidence was seen, and theexposed animals had 47 tumors versus 60 in the sham-exposed (not statisticallysignificant) (Lšscher et al., 1994; Mevissen et al., 1993). The authors concluded that theseexperiments indicate that magnetic fields at high flux densities act as a promoter or copromoter of breast cancer. [This conclusion must be considered only tentative because of
the limitations of this study, particularly the small sample size used for exposure tomagnetic fields.]
In the next set of experiments, a much larger number of animals (99 rats/group) was used
(Lšscher et al., 1993). All rats received the four weekly doses of 5 mg DMBA beginningat 52 days of age. One group of 99 rats was then exposed to magnetic fields at a flux
density of 100 mT, while another group of 99 rats served as sham-exposed controls. After
three months of exposure, the number of tumor-bearing animals (macroscopically visible
tumors at necropsy) was 34 in the sham-exposed group and 51 in the exposed animals (p< 0.05). The tumors were not significantly larger (p = 0.08) in the exposed group (median,
707 mm3; interquartile range, 168Ð1885) than in the controls (367 mm3; 101Ð1178; p =0.07), and no difference was found in the number of tumors per tumor-bearing rat. The
authors stated that the data demonstrate that long-term exposure of DMBA-treatedfemale rats to an alternating magnetic field of low flux density promotes the growth andincreases the incidence of mammary tumors. [The study is well documented andadequately addresses the problem of the earlier study. No histopathological data arepresented.]
An extension of the previous study was conducted in which a complete histopathologicalexamination was performed (Baum et al., 1995). Histological examination of the tumors
from the previous experiment revealed more tumors than were detected by palpation, theincidence of histologically verified DMBA-induced lesions being 57/99 in sham-exposed
controls and 65/99 in animals exposed to magnetic fields. When tumors and hyperplasia
were combined [an unusual combination], the numbers were 74/99 in sham-exposed
controls and 65/99 in field-exposed rats; the incidence did not significantly differ between
the groups. The authors concluded that exposure did not alter the incidence of mammary
lesions but accelerated tumor growth, consistent with a co-promoting effect of EMF.
There was a significant increase (p < 0.05) in the number of adenocarcinomas in exposed
animals (62/99 in field-exposed versus 49/99 in sham-exposed controls). [Adenocarcinoma
are not normally separated from carcinoma in situ for evaluation in the mammary gland.]After assessing the histological data, the authors concluded that long-term exposure of
DMBA-treated female rats to EMF promotes the size and progression of mammary

91

tumors (treated: median, 733 mm3; interquartile range, 183Ð2994; controls: 367 mm3;
101Ð1178; p < 0.05), while tumor incidence is not affected.
In the next experiments in this series of studies (Mevissen et al., 1996a), an effort wasmade to determine if a doseÐresponse relationship exists with field intensity. Ninety-nine
animals per group were exposed to 10 mT for 13 weeks. DMBA induced palpable tumorsin 55/99 of sham-exposed and 60/99 field-exposed animals. At autopsy, these numbers
were 61 and 67%, respectively; neither was statistically significant. The size, number per
animal, incidence, and latency of tumors were similar in the two groups. The authors
concluded that at this field intensity, magnetic fields had no effect.
In the next experiment in this series (Mevissen et al., 1996b), groups of 99 rats were
exposed to 50 mT. At autopsy, 55% of sham-exposed controls and 69% (p < 0.05) of
those exposed to magnetic fields had tumors, but the size and the number of tumors per
animal were similar in the two groups. The author concluded that at this field intensity,
magnetic fields had no effect.
Mevissen et al. (Mevissen et al., 1998a) conducted a replication experiment in which 99
female Sprague-Dawley rats were field-exposed or sham-exposed to a 100 mT, 50 Hz
magnetic field. All of the rats received a total of 20 mg of DMBA (4 x 5 mg fractionateddose) beginning at 52 ± 2 days of age. After three months of exposure, the rats weresacrificed and mammary tumors identified by macroscopic evaluation at necropsy. Small
tumors were examined histologically to confirm diagnosis as adenocarcinomas.
Macroscopically visible tumors were found in 82 field-exposed and 61 sham-exposed rats(p < 0.05). The total number of tumors was 230 in controls and 297 in exposed animals;
no difference was observed in the number of tumors per animal or in tumor size.
[In this series of studies of DMBA-initiated breast cancer in Sprague-Dawley rats
promoted with 10Ð100 mT magnetic fields, a higher number of total tumors was found infield-exposed groups in most studies. These effects often did not reach statisticalsignificance, and in none of the studies was there a difference between field-exposed andsham-exposed animals in the number of tumors per tumor-bearing rat. The exposure
resulted in a decreased latency in several but not all studies, and this effect was often seen
only during part of the study. Increased tumor size was seen with exposure to magnetic
fields but not consistently across the studies. Although the rats were initiated with a very
high dose of DMBA (20 mg/rat), the 34Ð61% tumor incidence in the controls is much
lower than would have been expected in Sprague Dawley rats in US studies. This may
reflect a differences in the rat strain.]In an effort to replicate these results (NTP, 1998a), Battelle Pacific Northwest
Laboratories attempted to simulate the design and experimental method of the studies as
closely as possible, with four weekly doses of 5 mg DMBA beginning at 52 days of age
given by intragastric intubation to female Sprague-Dawley rats. Exposure was for 18.5
h/d, 7 d per week for 13 weeks at field intensities of 100 and 500 mT (50 Hz) and 100 mT

92

(60 Hz) linearly polarized horizontal sinusoidal magnetic fields. The study was conductedunder GLP conditions and included documentation of fields and exposure characteristics.
A 26-week study at a lower single dose of 10 mg DMBA was also conducted. As all rats
given DMBA in the first 13-week study had mammary gland neoplasms at incidences,
determined by palpation, > 80%, a second 13-week study was conducted with four
weekly doses of 2 mg DMBA.
Additional groups were included which were exposed at 500 mT (50 Hz) and 100 mT (60Hz) for 18.5 h/d; all environmental conditions (temperature, light, relative humidity, andnoise) were regulated and monitored continuously. Full gross pathological analysis andcomplete histopathological examination of mammary tumors were conducted.
In the first 13-week study, no difference in the onset of tumors or tumor size was foundby gross palpation. The skin and the mammary glands were transluminated to identify all
potential lesions; all gross lesions were counted, measured in two directions and sampled
for histology. The incidences of mammary gland carcinomas were 92% in sham-exposed
rats, 86% in those at 100 mT 50 Hz, 96% in those at 500 mT 50 Hz, and 96% in those at
100 mT 60 Hz magnetic fields. The numbers of mammary gland carcinomas verified
histologically were 691 in sham-exposed and 528 (p < 0.05 negative trend), 651 (notsignificant), and 692 (not significant) for rats at 100 and 500 mT 50 Hz and 100 mT 60
Hz, respectively.
The high tumor incidence in all groups (86Ð94%) seen with the same dosing regime asused in the L”scher studies decreased the sensitivity of the first 13-week study to detecta promoting effect. In the second 13-week study, at 8 mg DMBA (2 mg x 4 weekly
doses), the mean body weights and clinical findings (attributable to DMBA
administration) were not different between field-exposed and sham-exposed groups.
There was no difference in the time to onset of tumors or in tumor size by gross
palpation. The incidences of mammary gland carcinomas were 43, 48, and 38% for the
sham-exposure and for exposure to 100 or 500 mT, 50 Hz magnetic fields, respectively,
and the numbers of mammary gland carcinomas verified histologically were 102, 90, and79, respectively. At necropsy, > 99% of the palpated tumors were shown histologicallyto be mammary gland carcinomas. The tumor incidence, total number of tumors, numberof tumors per tumor-bearing rat (average, 1.7Ð2), and tumor size were not increased byexposure.
In the 26-week study, survival was similar in the sham- and field-exposed groups. In
addition, no consistent differences in clinical findings were seen between groups exposed
to DMBA plus magnetic fields and DMBA controls. Mammary gland carcinomas andmultiple carcinomas were observed in all groups, but the rats exposed to magnetic fields
had consistently fewer mammary tumors than the DMBA controls (Table 4.3); the 100
mT, 60 Hz group had a significantly lower incidence than controls (p < 0.05). The
numbers of tumors per tumor-bearing animal showed a similar pattern, the 100 mT, 60 Hz
group having lower values than controls. Most of the palpable tumors in all groups were93

shown histologically to be mammary gland carcinomas and fibroadenomas. The numbersof mammary gland carcinomas verified histologically were 649 (sham-exposed), 494 (100mT, 50 Hz) (p < 0.05 negative trend for poly-3 test), 547 (500 mT, 50 Hz), and 433 (100mT 60 Hz) (p < 0.05 negative trend for poly-3 test). The tumor sizes were similar in allgroups.
Table 4.3. Incidences of mammary gland lesions in female rats exposed to 10 mg DMBA
plus sham exposure or exposure to magnetic fields
LesionSham-exposed

Hyperplasia
Adenoma
Carcinoma
Fibroadenoma
a
*

50 Hz

50 Hz

60 Hz

100 mT

500 mT

100 mT

1
0
90
76

0
0
95
73

1
0
85*
68

1
2
96
71

100 animals/exposure groupp < 0.05 (decrease)

In both the 26-week and the 13-week studies, the authors found no evidence thatmagnetic fields promote the development of mammary gland neoplasms. [The rats
exposed to EMF showed a decrease in the number of tumors and in the incidence of
DMBA-initiated tumors. Because of the large number of tumors generated by the dose of
DMBA used in the first 13-week study, the sensitivity of the assay to pick-up small
promotor effects was limited.]
A further study was conducted to examine the effects of magnetic fields on mammary
tumor development in rodents (Ekstršm et al., 1998). Although the intensities of themagnetic fields used in this study were similar to those in the studies described above,
250 and 500 mT at 50 Hz, there were also some significant differences. In this study, atransient-producing, intermittent field was used (15 s on, 15 s off). In addition, the fields
were used in a strictly ÔpromotionalÕ design, exposure beginning one week after DMBA
administration rather than simultaneously with the DMBA. Fifty-two-day-old SpragueDawley female rats were treated with DMBA (7 mg/animal) and, once started, theexposures continued for 19Ð21 h/d for 25 weeks. As in the other studies, the end-points
were tumor incidence, number of tumors per animal, and tumor volume and weight.
This incidences of tumors were 43/60, 42/60, and 42/60 for the sham-exposed, 250 mT
and 500 mT 50 Hz groups, respectively. The numbers of tumors and tumors per animal
were also similar between all the groups, with 111 tumors in the DMBA controls and 102
at 250 mT and 90 at 500 mT in the exposed groups. The rate of tumor appearance andtumor volume were the same in all groups. The authors concluded that magnetic fields had
no effects in this study. [The interpretation of these results is made uncertain by the lackof histopathological data.]

94

(c) Comments
Several studies have been conducted in rats to examine the effect of 50 and 60 Hz
magnetic fields on mammary tumor promotion. In all of these studies, mammary gland
carcinomas were initiated by treating female rats with a known chemical carcinogen; they
were then exposed to various intensities of magnetic fields. Since promotion is generally aprocess of long duration, the short duration of these experiments greatly limits thepossibility of detecting a potential modifying effect of EMF on the action of a strong
carcinogen such as DMBA. The series conducted by Mevissen and Lšscher appear tosuggest that mammary cancer promotion in the rodent model is enhanced by exposure tomagnetic fields. Although there was an apparent increase in the tumor incidence, thenumber of tumors per rat did not increase with exposure to magnetic fields. There isconcern about the lack of consistency of the data, the lack of a doseÐresponse to exposure
to EMF in the individual studies, the low carcinogenic response to DMBA, and the lackof histological detail. The NTP study, specifically designed to replicate the Lšscher
studies, produced some results similar to those of Lšscher but could not verify apromotional effect of exposure to EMF because of lack of sensitivity in one experiment.
Conditions that might account for these results are the source of animals and feed, thequality of DMBA, possible exposure to field transients, different length of exposure.
Within the limits of the experimental model used, the results of the ensemble ofexperiments do not provide convincing evidence for a promoting effect of EMF on
chemically induced mammary cancer.
4.1.2.2 Skin tumor models
Skin tumor development in mice is a well-accepted, convenient model for the study ofmultistage carcinogenesis. Although human epidemiological studies do not indicate thatskin tumors occur as a result of exposure to EMF, this model is useful for exploring
general cancer development. In the most highly developed, two-stage model, the protocol
involves DMBA treatment of the skin on the back of mice as an initiator and thentreatment with an active phorbol diester, 12-O-tetradecanoyl phorbol 13-acetate (TPA),
which is used as a promoter. Selected mouse strains, e.g. SENCAR (SENsitive to
CARcinogenesis) mice, are used. After initiation and repeated application of TPA,
morphological changes are observed. The main tumor type is squamous-cell papilloma,
which begins to appear after five or six weeks of TPA treatment. Many substances havebeen found to act as promoters or co-promoters in this model (DiGiovanni, 1992).
Studies with this model to examine EMF as a possible promoter or co-promoter are
outlined in Table 4.4.
Skin tumor promotion after initiation with DMBA was examined in groups of 32 female
mice exposed to a 2000 mT, 60 Hz continuous magnetic field for 6 h/d five days per week
for up to 21 weeks (McLean et al., 1991). Mice were initiated with DMBA (10 nmol in
200 ml of acetone) on the dorsal skin and were then exposed to the magnetic field with orwithout TPA promotion (1 mg per week for 21 weeks). As none of the field-exposed or95sham-exposed mice developed papillomas in the absence of TPA, the authors concluded
that magnetic fields did not act as a tumor promoter. A slight, nonsignificant decrease in
the time of appearance of tumors was observed in animals treated with TPA plus EMF,
in comparison with animals treated with TPA and sham exposed. [The number of animals
with tumors at 21 weeks was extremely high (> 90% in both exposed and control groups)
and essentially precluded a judgment as to whether EMF could affect the incidence ofskin papillomas.]
In a second study, two groups of 48 mice were similarly initiated with DMBA andpromoted with 0.3 mg (4.9 nmol) TPA for 23 weeks, with or without magnetic field
exposure (Stuchly et al., 1992). The onset of tumor development occurred earlier in mice(p < 0.05 for weeks 16, 17, and 18) that were treated with TPA plus magnetic fields whencompared with the TPA plus sham-exposed mice. Although a difference in the cumulative
number of mice with tumors was observed during the experiment, neither the number ofanimals affected nor the number of tumors per animal was statistically different between
the two groups at the end of the study.
In a third study, the protocol was similar to that in the study described above, except thatsham or field exposure continued for 52 weeks, whereas TPA treatment was discontinued
after week 23. McLean et al. (McLean et al., 1995) reported that while there was no
overall increase in total tumors associated with exposure to fields, more field-exposed
animals had malignant tumors (8/48) than sham-exposed animals (1/48, p < 0.03). [Noindication of the number of tumors per animal was given.] A review of three independentstudies involving a total of 288 SENCAR mice used to study the effects of 60 Hz
magnetic fields on the growth and development of skin tumors showed mixed results: inone study, more tumors were seen in field-exposed (86) than sham-exposed mice (48),while two studies showed the opposite effect (33 magnetic field-exposed versus 50 shamexposed and 27 magnetic field-exposed versus 86 sham-exposed; p = 0.01). The authors
concluded that the results did not support a role of magnetic fields as tumor co-promoters(McLean et al., 1997).
In a lifespan study of skin carcinogenesis in NMRI/HAN mice exposed to sinusoidal
magnetic fields, no evidence was found that magnetic fields promote the formation of skintumors (Rannug et al., 1993a). Groups of 30 mice were initiated with DMBA (25.6 mg
applied topically to the shaved dorsal skin of each mouse) and exposed from seven weeks
of age to either 50 Hz sinusoidal magnetic fields with flux densities of 50 or 500 mT for
103 weeks for 19Ð21 h/d or sham conditions. There was no increase in tumor promotion
with exposure to magnetic fields. [The flux densities used in this study were lower thanthose used by McLean et al.] (McLean et al., 1995)
As part of this study, a group of animals was exposed to fields for two years in theabsence of treatment with DMBA or TPA and were then monitored and evaluated overthe course of their lifetime for survival and the appearance of skin tumors; at death, they
were assessed by complete necropsy and histopathological evaluation of skin tumor

96

types. The survival of mice treated with DMBA and TPA but exposed to 500 mT was
shorter than that of controls or 50 mT-treated animals (median survival, 74 versus 94.5
and 87.5 weeks, respectively). There were no skin tumors in either control or fieldexposed groups, and no significant differences were observed between sham-exposed andfield-exposed groups in the incidences of other neoplastic lesions or leukemia.
In a second study, this group investigated the tumor promoting effects of continuous andintermittent magnetic fields in sensitive female SENCAR mice (Rannug et al., 1994).
Groups of 40 mice were treated with DMBA (2.6 mg) one week before exposure tocontinuous and intermittent (15 s on/off) 50 Hz horizontal, AC fields with flux densitiesof 50 and 500 mT for 19 or 21 h/d for 104 weeks. Untreated, DMBA-treated, and TPApromoted control groups were included. No tumors were found in animals treated with
DMBA with no co-promotion by TPA and exposed to continuous fields of 50 or 500
mT. Four tumors in four animals were found at 50 mT and 13 tumors in five animals at
500 mT given intermittently, with two tumors in DMBA-treated sham-exposed animals.
These increases were not significantly different when the two intermittent exposuregroups were compared with the sham-exposed group. The time to first tumor was
shortened in the intermittently exposed animals when compared with the DMBA-treatedcontrols. [There were far fewer tumors in the field-exposed groups (< 5%) than in the
TPA-treated positive control animals (> 97%). No hyperplastic response was seen withthe magnetic field exposures. The results did not support the hypothesis that magnetic
fields promote skin carcinogenesis in SENCAR mice at flux densities of 50 and 500 mT.]±A further study was conducted in SENCAR mice (Sasser et al., 1998) as a collaborative
effort between Battelle and the M.D. Anderson Cancer Center. Mice were exposed to
DMBA (10 nmol in 200 mL acetone) and then to TPA at 0.85, 1.7, or 3.4 nmol. They
were then exposed to 2000 mT, 60 Hz magnetic fields for 23 weeks. Skin tumor incidence
and multiplicity were monitored, and the tumors were histologically evaluated at the endof the study. Papillomas were seen in 15 of 48 field-exposed and 10 of 48 sham-exposed
mice. These differences were not significantly different. The overall conclusion of theauthors was that, within the sensitivity limits imposed by the animal model and theexposure parameters employed, no co-promotional effect of field could be demonstrated.
[Several studies of promotion and co-promotion have been conducted in mice to examine
the effect of 50 and 60 Hz magnetic fields on the development of skin carcinomas andpapillomas. In all of these studies, skin carcinomas were initiated by treating the animals
with a known chemical carcinogen; they were then exposed to various intensities ofmagnetic field or combinations of magnetic fields with a known chemical promoter (TPA).
Within the constraints of all five studies, there were no significant promotional effects ofmagnetic fields on skin tumor development.]974.1.2.3 Liver cancer models
Rat liver is the most commonly used experimental model for investigating multistage
carcinogenesis in tissues other than the epidermis (Dragan & Pitot, 1992). The protocol
used in these studies typically requires a mitogenic stimulus, often a partial hepatectomy,
in tandem with a subcarcinogenic dose of an initiator (usually N-nitrosodiethylamine,
NDEA). The inclusion of a promoter (e.g. phenobarbital) is necessary to obtain
expression of liver foci. The basis of using the rat liver model to study EMF exposure issimilar to that for the skin tumor model: to determine whether EMF will promote or copromote liver tumors. Two studies of this type have been conducted, as described below(Table 4.5).
In a series of experiments, Rannug et al. (Rannug et al., 1993b; Rannug et al., 1993c)
investigated the possibility that magnetic fields interact with known initiators or
promoters of cancer to induce preneoplastic lesions in rats. They used partiallyhepatectomized male Sprague-Dawley rats treated with NDEA to initiate tumor
development. The animals were then exposed to magnetic fields for 12 weeks, beginningone week after initiation, to determine whether growth of enzymatically altered fociwould be promoted in liver cells. In two studies, groups of nine to 10 rats were initiatedwith NDEA and then promoted with 50 Hz horizontal magnetic fields with flux densities
of 0.5 or 50 mT (experiment 1) or 5 or 500 mT (experiment 2). A slight increase in staining
for g-glutamyltranspeptidase was reported in the first experiment at 50 mT (p < 0.01) but
not in the second experiment.
In a third study, groups of 10 rats were exposed to magnetic fields with flux densities of
0.5 or 500 mT both during initiation with NDEA and throughout co-promotion withphenobarbital (300 ppm in diet) (Rannug et al., 1993c). The magnetic field inhibited,
although not significantly, the size and number of focal lesions. The authors concluded
that there was no evidence of a promotional or co-promotional role of magnetic fields.
4.1.2.4 Leukemia/lymphoma modelTwo types of study have been conducted: exposure to EMF after induction ofleukemia/lymphoma by initiation with X-rays or DMBA or progression of the disease
under the influence of EMF after introduction of leukemia cells into the animal. Thesestudies are summarized in Table 4.6.
(a) Mice
In the largest of these studies, over 2000 C57Bl/6J mice were exposed to fractionateddoses of ionizing radiation (cobalt-60) at 0, 350, 475, or 600 rads (Babbitt et al., 1998)
Eight groups of 195Ð450 male and female mice were exposed to a circularly polarizedmagnetic field of 1.4 mT from the first day of irradiation, continuing for 18 h/d for the98two-year duration of the study. This study was conducted under GLP, and extensive
monitoring of exposure parameters was conducted; no transients were present duringexposure. The incidence of lymphoma was not affected by exposure to magnetic fields(Table 4.7). A full morphological and histopathological evaluation and analysis was
performed on all animals. No statistically significant, consistent effects of exposure werereported at any dose of ionizing radiation. Evaluation of the various lymphoma subsets
produced similar conclusions. The authors reported no significant effects of exposure tomagnetic fields over the natural lifespan of this strain of mouse with regard to either theincidence of all leukemias/lymphomas at death or the rate of death withleukemia/lymphoma present. [This study should have been sensitive enough to detect
small differences due to exposure to magnetic fields.]
Table 4.7. Lymphoma incidence in mice treated with ionizing radiation and EMF
Percent lymphomas
Ionizing radiation (rads)

Sham-exposeda

60 Hz 1.4 mTb

0

35 ± 737 ± 5350

40 ± 734 ± 5475

38 ± 741 ± 5600

52 ± 746 ± 5a

190 control mice per ionizing radiation group (760 total)b
380 exposed mice per ionizing radiation group (1520 total)

As an addition to the study of Babbitt et al. (Babbitt et al., 1998), sections of brain were
examined from mice exposed to 0, 350, 475, or 600 rads of ionizing radiation in four
fractionated doses with and without subsequent exposure to 1.4 mT of circularly
polarized 60 Hz magnetic fields. Hematoxylin and eosin-stained sections were preparedof the brain and were reviewed for primary proliferative lesions. Seven primary brain
tumors or hamartous lesions (lipomas) were found in treated animals, with no apparent
correlation with exposure to either radiation or magnetic fields. The authors concluded
that this study provides no evidence of an effect of magnetic fields on primary brain
tumors in female C57BL/6 mice (Kharzi, submitted manuscript).
[The sensitivity of this mouse model for agents that cause brain cancer has not been
established, and ionizing radiation did not affect brain tumor incidence.]
A study in which DMBA was used as an initiator was conducted in newborn male andfemale Swiss-Webster mice (Shen et al., 1997). Each pup received a subcutaneous
injection of 35 mg DMBA within 24 h of birth. Two weeks later, the mice were separated
into either a sham-exposed group or a group exposed to a 1 mT, 50 Hz magnetic field.
Exposure was continued for 3 h/d, 6 d per week for 16 weeks. The percentages of animals
with thymic lymphomas and lymphomatous leukemia were 30% (50/165) of fieldexposed and 30% (46/155) of sham-exposed mice. The authors reported no evidence for a
promotional effect of a 1 mT, 50 Hz magnetic field on lymphoma/leukemia induced by
DMBA in mice.
99

(b) Rats
A study of the progression of disease was conducted in Fischer rats with large granularlymphocytic leukemia cells (Anderson et al., 1997; Sasser et al., 1996). Spleen cells
shown to be predominately with large granular lymphocytic leukemia cells were takenfrom diseased, aged Fischer 344 rats and transplanted into young male rats. The leukemia
developed into full-blown disease within six to eight weeks, as indicated by enlarged
palpable spleens and various hematological parameters. In the first study (Sasser et al.,1996), 72 rats were randomly assigned to four treatment groups as follows: 1 mT, shamexposure, ambient controls, and positive controls exposed to 5 Gy whole-body girradiation (cobalt-60). At initiation of field or sham exposure, all rats were injected
intraperitoneally with 2.2 x 106 fresh leukemia cells. Magnetic fields were present for 20
h/d seven d per week for approximately 18 weeks. An additional 18 rats per group (fieldor sham-exposed) bled serially to evaluate hematological indicators of disease progression.
In general, no significant or consistent differences were seen between rats exposed tomagnetic fields and ambient-field controls, in either the size of palpated spleens or thehematological parameters evaluated for leukemia. The 1 mT, continuous 60 Hz field did
not significantly alter the clinical progression of the disease.
In the second study (Anderson et al., 1997), a similar protocol, exposure, and end-points
were used. Leukemia cells were inoculated at 2.2 x 106 or 2.2 x 105, and intermittent fieldpresentation (3 min on, 3 min off) was added, with replication of the continuous field
exposures. Again, no significant exposure-related differences were observed forcontinuous fields at either level of cell inoculum or for intermittent fields at the lower cell
inoculum; however, with intermittent fields at the higher inoculum an apparent decrease in
the latency to disease (from 60 to 45 days) was observed in comparison with the shamexposed animals. The authors reported that, taken together, the results for both inoculae
argue for a lack of effect of magnetic fields on the progression of leukemia in this model.
There remains, however, the slight effect of intermittent exposure, particularly when inanimals with a higher load of injected leukemia cells.
(c) Transgenic animal models[Neither studies in which an initiating event such as g-irradiation or a chemical carcinogen
was used nor studies of progression of leukemia after injection of viable leukemic cells
showed an effect of exposure to magnetic field at a variety of intensities. The absence ofan increased incidence of leukemia/lymphoma in the long-term bioassay is consistent withthese results.](c) Transgenic animal models
Pim mice, which carry the pim-1 oncogene, are highly sensitive to N-ethyl-N-nitrosourea(ENU)-induced lymphoma. Groups of 30 male and female Pim mice were treated with
ENU (25 mg/kg bw) and then exposed to 0 (sham exposure), 2 200, or 1000 mT, 60 Hz
100

magnetic fields for 23 weeks. Histological evaluation revealed no differences in lymphoma
incidence between field- and sham-exposed mice. In a second experiment, groups of 30
male and female TSG-p53 heterozygote transgenic mice were exposed to 0 (shamexposure) or 1000 mT, 60 Hz magnetic fields for 23 weeks. There was no evidence of aeffect of magnetic fields on the lymphoma incidence (McCormick et al., 1998; Table 4.8).
[The usefulness of transgenic mice for detecting environmental carcinogens has not been
established. It was also noted that the p53 transgenic mice were evaluated at only one
field intensity, and the low tumor incidence in the p53 controls suggest that the study
may have been too short for this model.]Table 4.8. Leukemia/lymphoma in transgenic mice exposed to 60 Hz magnetic fields
No. of affected micea
Strain
Pim1
Pim1
p53
p53

Sex

Sham

2 mT

200 mT

1000 mT

1000 mT(I)b

Male
FemaleMale
Female

15
14
1
1

14
13
NT
NT

13
13
NT
NT

7*
14
0
2

17
16
NT
NT

NT, not testedaNumber of mice diagnosed with leukemia/lymphoma; 30 mice/groupbIntermittent exposure for 1 h on, 1 h off during the 18.5-h exposure period*p < 0.05 vs sham-exposed

Groups of approximately 100 Em-Pim1 transgenic mice were exposed to 50 Hz magnetic
fields at intensities of 0, 1, 100, or 1000 mT for up to 18 months (Harris et al., 1998).
Animals that died during the study were subjected to histological evaluation. No
difference in lymphoma incidence was seen between field- and sham-exposed mice. The
authors concluded that long-term exposure to 50 Hz magnetic fields had no tumorigenic
effect in the lymphoma-prone mice. The authors assumed that the animals did not haveleukemia.
[Transgenic mouse models have not been fully evaluated for their predictive value fortesting carcinogens. The design is also unusual in that the ÔhealthyÕ animals (nearly 50%of the animals) were discarded at the end of the study without examination. It was further
noted that during the in-life portion of the study more than 7% of the animals wereautolysed and discarded without diagnoses.]

4.1.3 Summary
Two long-term bioassays demonstrated no carcinogenic response, and one showed anequivocal response at one tumor site in animals of one sex of one species. Within thelimits of the experimental model of multistage mammary carcinogenesis, the results of theensemble of experiments do not provide convincing evidence for a promoting effect of
EMF on chemically induced mammary cancer. In another commonly investigated model,

101skin carcinogenesis, exposure to magnetic fields had no effect. EMF did not promoteleukemia or lymphoma in mice or rats in several studies.
In several long-term bioassays, no association was found between exposure to magnetic
fields and brain cancer; however, the sensitivity of rodent models for assaying brain
cancer has not been well established.
Most of the investigations carried out until now have followed the pattern of the
traditional testing of chemical agents suspected to be carcinogenic. While additional
traditional studies are fully justified and may produce useful results, it is conceivable thatinvestigations of the role of the factors involved in the multistep, multifactorial
carcinogenesis process (perhaps including EMF) may require different approaches thanthose used until now.
The overall conclusion of the Working Group is that most of the studies suggest a lack ofcarcinogenicity, and the few with borderline positive results are inadequate to conclude
that exposure to magnetic fields at the magnitude and field configurations at which they
were investigated increases the incidence of cancer in rodents.
There is inadequate evidence in experimental animals for carcinogenicity from exposure to
extremely low frequency electromagnetic fields.
[This conclusion was supported by 19 members of the Working Group; there were 8
votes for ÔlackÕ of carcinogenicity, 1 abstention and 1 absent.][There was a minority report written on this opinion; this report is in Appendix B]

102

Table 4.1 Results of long term chronic bioassays in rodents exposed to EMF
Species/Strain

No. of animals

EMF exposure(NTP, 1998b)

Reference

F344 rats
B6C3F1 mice

100 males, 100
females/species/
group

2, 200, 1000 mT
continuously(60 Hz) & 1 mT
intermittently(60 Hz, 1 hour on, 1 houroff)

2 years, GLP(18.5 h/d)

Time/otherNo increase in carcinogenesis (brain, mammary
gland, or leukemia) in male or female rats ormice(Mandeville et al.,1997)

F344/N rats

50 females/group2, 20, 200, 2000 mT (60 Hz)

2 year,
GLP (20 h/d)

No increase in carcinogenesis(Yasui et al., 1997)

F344 rats

48 females/group0.5, 5 mT (50 Hz)

2 year chronic,(22.6 h/d)

No increase in carcinogenesis(Margonato et al.,
1995)

Sprague-Dawley
albino rats

256 males/group

5 mT (50 Hz)

32 weeks (22 h/d)

No increase in carcinogenesis

GLP, good laboratory practice103

Results reported by authors

Table 4.2 Assays of co-initiation and of promotion of: mammary cancer
Species / strain No. of animals

Initiator(Beniashvili et al.,1991)

Referencerats

50
females/group

MNU

20 mT (50 Hz);EMF exposure

lifelong(0.5, 3 h/d)

Increase incidence, decreased latency of
mammary tumors in rats exposed for 3 h/d;
more malignant tumors(Mevissen et al.,
1993)

Sprague- Dawley 18
rats
females/group

DMBA

30 mT (50 Hz)(homogeneous field)

13 weeks (24 h/d)

Increase tumor number per animal (66 vs.
61%); not reproduced upon repeat(Lšscher et al.,
1994)

Sprague- Dawley 36
rats
females/group

DMBA

0.3 - 1.0 mT (50 Hz)(gradient field)

13 weeks (24 h/d)

No significant differences in histopathology;
nocturnal melatonin significantly lower in
exposed animals(Lšscher et al.,
1993)

Sprague- Dawley 99
rats
females/group

DMBA

0.1 mT (50 Hz)(homogeneous field)

13 weeks (24 h/d)

50% increase in mammary tumor incidence(51% exposed vs. 34% in sham-exposed)(Baum et al., 1995)

Sprague- Dawley 99
rats
females/group

DMBA

0.1 mT (50 Hz)

13 weeks (24 h/d)

No effect on incidence of mammary tumors;significant increase in malignant tumor sizein exposed(Mevissen et al.,1996a)

Sprague- Dawley 99
rats
females/group

DMBA

10 mT (50 Hz)(homogeneous field)

13 weeks (24 h/d)

Negative (61% tumor incidence in sham vs.
66% in exposed)(Mevissen et al.,1996b)

Sprague- Dawley 99
rats
females/group

DMBA

50, mT (50 Hz)(homogeneous field)

13 weeks (24 h/d)Significant increase in tumors in exposed
animals (apparent dose-response reported)(Mevissen et al.,1998a)

Sprague-Dawleyrats99
females/group

DMBA

0.1 mT (50 Hz)(homogeneous field)

13 weeks (24 h/d)Significant increase in tumors in exposed
animals; no change in tumor size

(NTP, 1998a)

Sprague- Dawley 100
rats
females/group

DMBA

0.1- 0.5 mT (50 Hz)

13 weeks (18.5h/d)

Negative (43% tumor incidence in sham vs.
48% in 0.1 mT exposed and 38% in 0.5 mT
exposed)Negative (96% tumor incidence in sham vs
90% in 0.1 mT (50 Hz) exposed and 95% in
0.5 mT exposed)

0.1- 0.5 mT (50 Hz), 0.1
mT (60 Hz)(Ekstršm et al.,1998)

Sprague- Dawley 60
rats
females/group

DMBA

0.25 - 0.5 mT (50 Hz)(intermittent, 15 s,
on/off)

MNU, N- methyl - N - nitrosourea; DMBA, 7, 12-dimethylbenz [a] anthracene

104

Time / other26 weeks (18.5h/d)
25 weeks (19-21
h/d)Results reported by authors

Negative (71% tumor incidence in sham vs.
70% in exposed; exposure 1 week after
DMBA)

Table 4.4 Studies of promotion and co-promotion of skin cancer
ReferenceSpecies / strain

No. of animals

Initiator /promoter

EMF exposure

Time other

Results reported by authors(McLean et al.,
1991)

SENCAR mice

32 females/group

DMBA ñ TPA(1 mg/week)

2 mT (60 Hz)

21 weeks ( 6h/d)

Negative at 22 weeks(Stuchly et al.,
1992)

SENCAR mice

48 females/group

DMBA/TPA(0.3 mg/week)

2 mT (60 Hz)

21 weeks (6 h/d)

Decreased tumor latency,
increased tumor incidence(McLean et al.,
1995)

SENCAR mice

48 mice/group

DMBA/TPA(0.3 mg/week)

2 mT (60 Hz)

52 weeks (6 h/d)

Increased fraction withmalignant tumors in exposed;
non-significant increase in
overall tumor incidence(Rannug et al.,1993a)NMR/HAN mice

30 females/group

DMBA

50, 500 mT (50 Hz)(continuous field)

103 weeks(19-21 h/d)

Negative(Rannug et al.,
1994)

SENCAR mice

50 females/group

DMBA

50, 500 mT (50 Hz;)
continuous orintermittent 15 s on/off

104 weeks(19-21 h/d)

Negative for continuous; dose
trend of increased tumors/tumorbearing animal in intermittently
exposed(Sasser et al., 1998)

SENCAR mice

100 females/group

DMBA/TPA

2 mT (60 Hz)

23 weeks (18.5 h/d)

DMBA, 7,12 dimethylbenz[a]anthracene; SENCAR, SENsitive to CARcinogenesis; TPA, 12-O-tetradecanoyl phorbol 13-acetate

105

Negative

Table 4.5 Studies of promotion and co-promotion of liver cancer
Reference(Rannug et al.,1993b)(Rannug et al.,1993c)

Species / strain

No. of animals

Initiator /promoter

EMF exposure

Time / other

Sprague-Dawleyrats
Sprague-Dawleyrats

10 males/group
10 males/group

Results reported by authors

NDEA

0.5, 5, 50, 500 mT (50 Hz)

12 weeks (19 h/d)

Negative

NDEA
phenobarbital

0.5 and 500 mT

13 weeks (19 h/d)

Exposed and a decrease in no. of foci.
(0.5 mT), mean focus area and volume
of foci

NDEA, N-nitrosodiethylamine

Table 4.6 Studies of promotion of: lymphoma/leukemia
ReferenceSpecies / strain

No. of animals

Initiator / promoter

EMF exposure

Time / other(Babbitt et al.,1998)

C57Bl/6J mice

195-450 males or
females/group

X-irradiation (0, 350,
475, 600 R)

1.4 mT circularly polar. 1
mT horizontal andvertical (60 Hz)

2 year chronic (18h/d)

Negative(Shen et al., 1997)

Swiss-Webstermice

165 exposed 155
sham- exposed

DMBA within 24 h ofbirth

1 mT (50 Hz)

32 weeks (3 h/d,
6 d/week)

No difference inlymphoma/leukemia between
groups; increased liver
infiltration in exposed(Sasser et al., 1996)

Fischer 344 rats

72 males/group

Leukemic cells injected(2.2 x 107)

1 mT (60 Hz) continuous

18 weeks (20 h/d)

Negative(Anderson et al.,1997)

Fischer 344 rats

72 males/groupleukemic cells injected(2.2 x 107 or 2.2 x 106)

1 mT (60 Hz) continuous
and intermittent

18 weekscontinuous andintermittent

Negative for continuous,decrease in latency forintermittent exposure in 107
cell inoculum

106

Results reported byauthors4.2

Epidemiological studies of carcinogenicity in adults
Epidemiological studies are implemented to investigate the associations between healtheffects and exposure to a presumed disease agent. A well-designed and -conductedepidemiological study involves several steps. First, the population base is identified
within which the relationship between the exposure of interest and the disease are to beinvestigated. Identification of the population base includes specifying the study
population and the follow-up period during which disease status is to be assessed. Only
subjects who are free of the disease of interest at the time of enrollment can be included in
the study base. During the follow-up period, all new cases of the disease must be
identified. In observational studies, exposure occurs through the natural course of events.
In a cohort study, information on exposure is collected for the entire study base. In
studies of rare diseases, a caseÐcontrol design is used in which the exposure prevalence isinvestigated in all cases and in a random sample of disease-free individuals (controls) in
the study base. It is crucial that the control sample accurately reflect the prevalence of
exposure in the study base.
Inability to randomly assign exposures means that investigators must design their study
such that the cases resemble the controls, except for exposure, in order to limit possible
bias. Control selection bias is introduced if exposure is related to characteristics thatwould make persons more or less likely to be sampled, or, once sampled, to participate.
In the Nordic countries, comprehensive national population registries can be used forselecting controls. All residents of each country are listed in these population registries,
and participation rates are typically high, such that epidemiological studies of these
populations are not compromised by control selection bias. In the USA, investigators
often use random-digit dialing methods to identify controls, because no comprehensive
registries are available. Random-digit dialing leads to difficulty in identifying, contacting,and recruiting controls of low socioeconomic status. The impact and possible bias
introduced by enrolling fewer controls of low socioeconomic status is described by Pooleand Trichopolous (Poole & Trichopoulos, 1991).
Case selection bias may occur in studies that are based on mortality records (deathcertificates). Studies of mortality rather than incidence are subject to bias if the survival
rate of the exposed and unexposed subjects differs. This may occur if, for example, theexposure is related to socioeconomic status, and different socioeconomic groups havedifferent survival rates for the studied disease. In addition, for diseases that are easily
cured or allow patients to live with the disease for a long time and die of some othercause, use of death certificates leads to severe limitations for the identification of cases.
Apart from limiting the power of the study (a severe limitation in studies of rarediseases), there is a large potential for selection bias in the identification of cases.
The inability to randomly assign exposures also introduces the possibility ofconfounding. Confounding is a mixing of effects between the exposure of interest andextraneous risk factors; it is not a product of the design or conduct of the study but
107results from an association among risk factors (Rothman, 1986). In order to be a
confounder, a risk factor must be related to both the studied exposure and the disease. For
example, consider a study to determine whether alcohol drinkers have a greater incidenceof oral cancer than abstainers. Smoking is related to the incidence of oral cancer; it is also
associated with alcohol consumption, and there is a greater proportion of smokers among
alcohol drinkers than among nondrinkers. Since smoking increases the incidence of oral
cancer, alcohol drinkers will have a greater incidence than nondrinkers, quite apart fromany effect of alcohol drinking itself but simply as a consequence of the greater prevalenceof smoking among alcohol drinkers. Thus, the apparent effect of alcohol drinking is
distorted by the effect of smoking, and smoking is thus a confounding factor.
Confounding can produce bias in either direction, artificially increasing or decreasing
relative risk estimates, depending on the direction of the association between the
exposure, the disease, and the confounder. When identified, confounding can be controlled
through statistical methods.
Another limitation of observational epidemiological studies is that exposure occurs
through the natural course of events rather than being assigned and controlled for by theinvestigator. Thus, determination of exposure is subject to inaccuracies, i.e. exposure
misclassification. Exposure misclassification may distort measures of association seen in
the study and may occur at several levels. For example, in occupational epidemiologicalstudies, errors may occur in assigning job titles. Measurement errors that are dependent
on either disease or exposure are termed Ôdifferential misclassificationÕ, i.e. the exposureassignment differs for diseased and non-diseased subjects or disease classification differs
for exposed and unexposed persons. Information on exposure can be obtained either
prospectively (before the disease has occurred) or retrospectively (after the occurrence ofthe disease). In the former situation, there is no potential for differential misclassificationof the exposure. In the latter situation, the recall of exposures that occurred before
diagnosis may be influenced by the disease, if the patientÕs recollection of the exposure isrequired for its assessment.
In this report, the Working Group critically reviewed observational epidemiologicalstudies of exposure to EMF that were of sufficient quality and reliability in respect of theaforementioned limitations.

4.2.1 Occupational exposure
Epidemiological study of diseases in relation to occupational exposure to EMF has a long
history. Reports of various health problems in high-voltage substations in the former
USSR initially focused attention on ELF electric fields (Asanova & Rakov, 1966). After
Wertheimer and Leeper (Wertheimer & Leeper, 1979) suggested that occupational
exposure to magnetic fields might be carcinogenic, Milham (Milham, 1982) examined theassociation between electrical jobs and leukemia risk. The significant association reported
in his first study led to over 100 epidemiological investigations of workplace exposure to108

EMF and various diseases. The early studies were based on job titles assumed to entail
exposure but lacked measurement-based validation.
After a number of these studies showed associations between cancer and electrical work,
epidemiologists in several countries undertook studies with personal magnetic field
monitors. All of the studies included measurements of exposure to ELF magnetic fields,
and in some studies exposures to ELF electric fields and pulsed EMF (PEMF) at higher
frequencies were studied. Accompanying the improvements in assessment of exposure to
EMF, these newer studies had more reliable epidemiological designs: cohort and caseÐ
control. Since the literature is so voluminous, this review covers only the studies thatmeet the criteria for exposure assessment listed in Table 4.9.
Table 4.9. Minimal exposure assessment required for a study to be included in thisreview
DiseaseExposure assessment

All cancers
Leukemia and brain cancer
Breast cancer
Other cancers
Central nervous system tumors from parental exposure

Full-shift monitoring*
Job titles of electrical workers**
Full-shift monitoring
Job titles of electrical workers* Worker wears personal EMF monitor for a complete work shift** Includes one or more studies with full-shift measurements

4.2.1.1 All cancers combined
Tynes et al. (Tynes et al., 1992) studied a cohort of 37 945 working-age men in Norway
who were identified from the Norwegian Central Bureau of Statistics as having held jobs
in which they could be exposed to EMF. This cohort was linked the Cancer Registry of
Norway to identify 3806 incident cancer cases that occurred between 1961 and 1985.
High exposure to EMF was assumed to occur in 12 electrical jobs (Table 2.4).
Standardized incidence ratios (SIR) for the electrical workers were calculated with theworking population as reference and adjusting for age and calendar period. The SIR was
1.1 (95% CI, 1.0Ð1.1; see Table 4.10) [No field measurements were made in this study.]
Sahl et al. (Sahl et al., 1993) studied a cohort of utility workers in the USA comprising the36 221 permanent employees who had worked for Southern California Edison (Edison)
for at least one year between 1960 and 1988. Vital status was ascertained through the
National Death Index, Social Security Administration, and the California AutomatedMortality Linkage System. Workers were classified as ÔelectricÕ or Ônon-electricÕ workers
on the basis of their longest-held occupation at Edison. Electrical workers were defined asÔcraft occupations who work near energized equipmentÕ; non-electrical workers included
all other non-managerial, non-electrical jobs. The age-adjusted relative risk (RR) for
electrical occupations was calculated for all cancers combined (261) and was not
significant (1.1; 95% CI, 0.92Ð1.3). [The limitations of the study are its relatively small

109sample size and potentially incomplete follow-up of the small percentage of former
employees who left California before 1979.]
Savitz and Loomis (Savitz & Loomis, 1995) conducted a retrospective cohort mortality
study of 138 905 men who had been full-time permanent employees of one of five
participating electric utility companies for at least six months during the period 1950-86.
A complete work history was assembled from company records for each worker. Men
who had worked for their entire career in a utilityÕs nuclear division were excluded fromthe cohort. Vital status to 1988 was determined for more than 99% of the men bysearching Social Security Administration, Death Benefit Records, Health Care Financing
Administration Records, and Drivers License records. Death certificates were obtained for
97% of the deceased. Subjects lost to follow-up were considered lost at the date of thelast record showing they were alive. Exposures, measured with an AMEX-3D, wereassessed for 2842 full shifts for a random sample of workers in 28 occupational
categories. Exposure to potential confounding factors was evaluated by asking industrial
hygienists and expert panels to assess exposures to a number of known or suspectedcarcinogens, including solvents, polychlorinated biphenyls, sunlight, and woodpreservatives. In all analyses, the investigators adjusted for age, calendar year, race, social
class, and work status (active versus inactive).
For total cancers (4833), a slight significant increase in risk was observed in the higher
exposure categories (Table 4.10), adjusted for age, calendar year, race, social class, work
status, and exposure to polychlorinated biphenyls and solvents. [The main limitation is
the reliance on death certificates for diagnosis and the use of a magnetic field meter that
could record only TWA exposures and not other metrics.]
ThŽriault et al. (ThŽriault et al., 1994) examined cancer occurrence in relation to exposure
to magnetic fields among workers at three large electric utility companies: Hydro QuŽbec
and Ontario Hydro in Canada, and ElectricitŽ de France (EDF). A nested caseÐcontrol
approach within these three cohorts was used to study all cancers combined among themale population of the three companies (total: 223 000; EDF, 170 000; Ontario Hydro,
31 543; Hydro QuŽbec, 21 749). The cohorts at the two Canadian companies included
both active and retired workers employed between 1970 and 1988, although the Ontario
Hydro cohort included only retired workers from 1970Ð73. The EDF cohort included
only actively employed workers and covered the period 1978-89. There were 4151 newcases of cancer in the combined cohort between 1970 and 1989. At Ontario Hydro, cases
were ascertained through the Ontario Cancer Registry; at Hydro QuŽbec, ascertainment
was made through the companyÕs medical files, the QuŽbec Tumor Registry and deathcertificates; at EDF, only cancers in active workers were identified through thecompanyÕs specific epidemiological data base of sickness benefits.
To estimate cumulative exposure to magnetic fields, the authors combined the job historyof each case and control with TWA exposure to magnetic fields estimated from a JEM foreach job (see section 2.4). The JEM for each utility was based on an extensive program of
measurements among its employees. For this study, 2066 workers in the three utilities
110wore a Positron exposure to EMF meter for a five-day work week. The Positron
measures ELF EMF and was also thought to measure PEMF (see section 2.3.1). Only thedata on ELF magnetic field were used in this study; the other fields were analyzed insubsequent publications. In the protocol used by Hydro QuŽbec and EDF, workers wereselected for measurements in job categories determined a priori on the basis of EMF
sources, and the sample sizes were representative of the utility's worker distribution
among those categories. In Ontario Hydro's measurement protocol, the sample of workers
was representative of the job titles and work locations of the cases and controls.
Potential confounders examined included smoking and exposure to ionizing radiation,
chemical agents, and sunlight. Data on smoking were available from medical histories forsome subjects at Hydro QuŽbec but not for the other two companies. Information on
cumulative individual occupational dose of ionizing radiation was obtained from company
radiation surveillance records. Occupational hygienists at each of the companies thendeveloped JEMs for chemicals and sunlight. In an approach similar to that used toestimate exposure to EMF, each individualÕs job history was combined with the JEM toobtain a cumulative exposure estimate for each chemical agent. When available, data fromexposure monitoring were used; otherwise, exposure to confounders was assessed byexpert judgment. No association was found between the risk for all cancers combined andcumulative exposure to ELF magnetic fields (Table 4.10), overall (OR, 1.0; 95% CI, 0.91Ð
1.1 for exposures ³ median compared with < median) or in any of the cohorts.
GuŽnel et al. (GuŽnel et al., 1996) reanalyzed the data from this cohort study withinformation on exposure to electric fields. There was a marginally significant decrease inrisk for all cancers combined (Table 4.10). [As a personÕs exposure to electric fields
depends on posture, grounding, and nearby objects, accurate measurement requires moresophisticated instruments and measurement protocols than those used in this and otherepidemiological studies.]
4.2.1.2 Leukemia
Floderus et al. (Floderus et al., 1993) conducted a large population based caseÐcontrol
study of occupational exposure to magnetic fields and leukemia and brain tumors. The
study base was all men (20Ð64 years old in 1980) who were alive at the time ofinvestigation and living in SwedenÕs more densely-populated counties, representing about
half the male population of the country. Cases of leukemia (426) and brain cancer (424)that occurred during 1983-87 were identified from the national cancer registry. Of theleukemia patients, 325 were contacted, and 250 agreed to participate. Two controls,
matched on age and alive at the time of investigation were selected for each case from the1980 census. Full job histories were obtained from responses to questionnaires mailed tothe subjects or proxies (64% of the cases required proxies). The response rates were 77%
for leukemia patients and 72% for controls.

111

Exposure to magnetic fields was determined from JEMs for the longest-held job during
the 10 years prior to diagnosis of the case, and 1015 full-shift measurements wereconducted at the subjectÕs job or a similar one. Because measurements were not available
for everyone, all subjects were assigned exposure based on the averages for all
measurements for their job. JEMs were constructed in 169 occupational categories for the
TWA, median, standard deviation (SD), and time exposed to > 0.2 mT, computed fromthese one-day measurements. Exposures to potential confounders were evaluated fromworkplace interviews,.
Age-adjusted odds ratios were calculated from an unmatched analysis of all controls forboth leukemia and brain cancer cases. The relative risks for leukemia were significantly
associated with the estimated TWA exposure to magnetic fields in the job held longest
during the 10 years before diagnosis (Table 4.11). Although no formal testing of the trend
is reported, the relative risks increased with quartiles of exposure, reaching significance forthe highest exposure. For all leukemias combined, the highest risk was seen in the groupwith TWA exposure > 0.41 mT (OR = 1.7; 95% CI, 1.0Ð2.7). Analysis by leukemia
subtype revealed no increased relative risk for acute myeloid leukemia (AML) but anincrease in the risk for chronic lymphocytic leukemia (CLL) with greater exposure. The
odds ratios for CLL in the highest TWA exposure categories were even higher andstatistically significant (TWA ³ 0.41 mT: OR = 3.7; 95% CI, 1.8Ð7.7). The relative risks
for CLL in the highest category of exposure to magnetic fields increased somewhat when
adjusted for exposure to benzene (OR = 4.1; 95% CI, 2.0Ð8.5), solvents (4.2; 1.9Ð9.4),
and ionizing radiation (4.7; 2.2Ð9.7). Because the authors were concerned about a possible
information bias due to the large number of proxy respondents among the cases, they also
carried out analyses based on average daily exposure estimated from occupational
information from the 1980 census. Although the odds ratios were slightly reduced,
increases were observed with increasing exposure category: 1.0 (0.5Ð2.1), 1.9 (1.0Ð3.6),
2.3 (1.2Ð4.3), and 2.6 (1.3Ð5.4), respectively, for exposure to 0.16Ð0.19, 0.20Ð0.28, ³0.29, and ³ 0.41 mT. Concern about a possible bias linked to the high non-response rate
was addressed by repeating the analyses with the occupation stated in the census for theentire population of cases and controls, including non-respondents. The odds ratios were
further reduced, and, although increased, were no longer statistically significant: 0.9 (0.5Ð
1.6), 1.6 (0.9Ð2.7), 1.6 (0.9Ð2.7), and 1.7 (0.9Ð3.3). These results are due to the larger
proportion of unexposed subjects among non-respondents and indicate the presence of adifferential bias.
[This study is unique in assessing EMF cancer risks in the general working population. In
industry, magnetic fields are likely to be more diverse in their characteristics than the
single-frequency fields usually found around electric power facilities. Another uniquefeature of this study is the effort to measure magnetic fields at the same job andworkplace (or a close proxy) where the subjects had worked before their cancer diagnosis.
For logistical reasons, the measurement protocol was changed during the course of thestudy, resulting in more measurements in case work places than in those of controls.
Exposures were not based on an entire work history. The results of analyses during two
different jobs, however, are similar. The analyses based on census occupational112

information, including non-responders, indicate the presence of a bias which could lead toan overestimate of risk among respondents.] (Bowman & Methner, 1998)
Matanoski et al. (Matanoski et al., 1993) conducted a caseÐcontrol study of mortality
from leukemia nested in a cohort of 1 300 000 active workers and 200 000 retirees of theAmerican Telephone & Telegraph Co. (AT&T). Cases of primary leukemia (except CLL)
were determined from AT&TÕs mortality records for 1975Ð80. To be included in the
study, cases had to be in white males who had worked at AT&T for at least two years.
For each case, three controls without leukemia were matched on retirement status at theage of the patientÕs death, gender, date of birth, and date of hire. Sporadic data on thesubjectsÕ employment histories were obtained from AT&T data tapes and from records
of some participating regional phone companies which were separated from AT&T after
the study period. Although 124 matched sets of cases and controls were identified, someanalyses were based on smaller numbers since records specifying the last job could beobtained for only 75 sets of cases and controls (60%), and complete job histories were
found for 35 sets (28%).
Full-shift measurements of magnetic fields were made with an EMDEX-C monitor fromsamples taken on 15-61 present-day workers in four categories of telephone line jobs
(cable splicers, installers, central office technicians, and supervisors) and a sample of nonline jobs. For central office technicians, measurements were taken at switching facilities
where either solid-state techniques or electromechanical relay crossbars were used; thelatter began to be replaced during 1975Ð80. The older relay switching results in higher
exposure than the new solid-state technique. The data on magnetic fields were used toconstruct JEMs with the TWA and peak exposures averaged for each job category. Odds
ratios were calculated by conditional logistic regression for the last job held (relative to
non-line workers) and for cumulative exposure (relative to values below the median). To
assess exposureÐresponse relationships, one-tailed tests for positive trend were
performed on odds ratios for quartiles of cumulative exposure. For cumulative TWA
exposures, the relative risk was elevated but not significant (OR = 2.5; 95% CI, 0.7-8.6),
and there was no exposureÐresponse relationship (p for trend = 0.27; based upon meansof logs of exposures in each quartile). A marginally significant exposureÐresponse
relationship was found among workers using the older style relay switching (p for trend =0.06). [A large fraction of subjects were excluded because of missing job records, which isa potential source of bias and resulted in small sample size.]
Sahl et al. (Sahl et al., 1993) conducted a nested caseÐcontrol study in the cohort of
employees at Southern California Edison (Edison) described in section 4.2.1.1, comprising
44 cases of leukemia identified from death certificates. Ten controls were selected for eachcase, frequency matched on age, gender, and race. For the caseÐcontrol analysis, exposure
to magnetic fields was assessed with a JEM based on 776 person days of exposure
measurements made with an EMDEX II monitor among present-day Edison employees in
35 occupational categories. Several exposure metrics were computed from themeasurements, including the arithmetic mean, geometric mean, 95th and 99th percentiles,
and fraction of time exposed to > 1.0 or 5.0 mT. An exposure score was obtained for each113

subject by summing the product of the exposure metric from the JEM times years of
employment. The odds ratios for leukemia in relation to the various exposure scores wereclose to 1 (Table 4.11) Further analyses at various time windows of exposure and latency
did not reveal positive associations. [The limitations are discussed in section 4.2.1.1.
They also include lack of information on potentially important confounding exposures tochemicals, ionizing radiation, and smoking and a reliance on death certificates fordiagnosis. The failure to track the deaths of subjects outside California could also haveintroduced some slight negative bias.]
London et al. (London et al., 1994) performed a caseÐcontrol study of leukemia which
focused on nine electrical occupations originally suggested by Milham (Milham, 1985);
see Table 2.4. Cases were all 2355 working men, aged 20Ð64, in whom leukemia had been
diagnosed in Los Angeles County during 1972Ð90 and whose last occupation was enteredin the CountyÕs cancer registry. Of these, 121 were electrical workers. The controls were67Ê212 men from the same study base in whom other tumors, except of the central
nervous system (CNS), had been diagnosed. They included 2665 electrical workers.
Exposure to magnetic fields was estimated with a variety of meters from full-shiftmeasurements taken on 278 Los Angeles workers in electric occupations and a random
sample of 105 men in 18 other occupations. TWA magnetic fields were calculated for 24
different tasks with exposure to EMF. The proportion of time that electric workers
usually spent at those tasks was estimated by interviews with expert panels at each
workplace. From these data, task-weighted estimates of mean and standard deviation were
calculated for each electrical occupation, for all electric occupations combined, and for all
non-electrical occupations combined. Exposure to potential leukemogens in theseoccupations was also assessed by the expert panels.
Odds ratios were calculated by logistic regression adjusted for age. Men in electricaloccupations as a whole had significantly greater exposure to magnetic fields than thesample of those in non-electrical jobs (mean TWA = 0.96 ± 0.13 mT vs. 0.17 ± 0.01 mT),
except for electrical engineers. A weak trend in risk for leukemia of marginal significancewas observed with exposure to the TWA magnetic field (OR increase per 1 mT = 1.2;
95% CI, 1.0Ð1.5). The trend with TWA was concentrated in the risk for chronic
myelogenous leukemia (significant) and acute nonlymphocytic leukemia (nonsignificant);
no increase in relative risk was seen for CLL. The limited information on exposure toconfounders did not appear to explain the risk patterns. [The following limitations wereidentified: reliance on the single job specified in the registry to estimate exposure and astudy design based on the proportion of leukemia among all cancers.]
Kheifets et al. (Kheifets et al., 1997b) used the exposure measurements of London et al.
(London et al., 1994) to assess the risks for leukemia associate with exposure to ELF
electric fields. Some of the EMF monitors also had electric field sensors, so that exposure
to electric fields was known for 28% of the Los Angles workers monitored in the original
study. Although no measurements were taken on power line workers in Los Angeles,
they were assigned to have high exposures (> 20 V/m) on the basis of measurements done
elsewhere. The authors noted additional difficulties in assessing exposure to electric fields,114

in particular that a personÕs exposure varies with posture and grounding. [The fraction ofworkers with the electric field sensor was 14Ð93% across occupations, which is a large
potential source of bias.]
In their study of three large electric utility companies, ThŽriault et al. (ThŽriault et al.,1994) carried out a nested caseÐcontrol study of leukemia. No significant association was
found between cumulative exposure to magnetic fields and the risk for leukemia as awhole. In analyses of specific leukemia subtypes, only the risk for acute nonlymphocytic leukemia was found to be related to exposure to magnetic fields (OR = 2.4;
95% CI, 1.1Ð5.4) among workers with TWA exposures above the median compared tothose below the median. When only AML was considered, the odds ratio among the halfof workers with higher exposures increased to 3.2 (95% CI, 1.2Ð8.3). No significant
exposureÐresponse relationship was observed. The association with magnetic fields
greater than or equal to the median was strongest for exposures received 20 or more years
previously (OR = 4.6; 95% CI, 0.22-94), based on seven exposed cases. For otherleukemia subtypes, no significant associations were reported. When analyses for all
leukemias were restricted to individual cohorts, a significant association was observed
between cumulative exposure above the median in Ontario Hydro (OR = 3.1; 95% CI,
1.1Ð9.7) but not in the other cohorts (Hydro QuŽbec, OR = 0.29; 95% CI, 0.04-1.8; EDF,
OR = 1.4; 95% CI, 0.61-3.1). The association was due mainly to AML. [The cohorts
were defined and followed up differently: the EDF cohort included only active workers,
while the Ontario Hydro cohort included only retirees for the first three years of thestudy. The levels of exposure were notably lower in the EDF cohort, probably due to theinclusion of gas workers. The JEMs were derived differently for each cohort, which may
affect the interpretation of the results for the combined cohorts. The small numbers ofcases by leukemia subtypes make interpretation of these results difficult.]GuŽnel et al. (GuŽnel et al., 1996) analyzed exposure to ELF electric fields in the EDF
cohort and found no association with leukemia risk (OR = 0.4; 95% CI, 0.13-1.2). [Seesection 4.2.1.1 for comments on the limitations of this study and that of ThŽriault et al.]Miller et al. (Miller et al., 1996) re-analyzed the data on the Ontario Hydro cohort for
exposure to both ELF electric and magnetic fields. An association with increasing
exposure to electric fields was reported for all leukemias and leukemia subtypes; anincrease was also seen in combination with magnetic fields (see Table 4.11). The JEMs at
Ontario Hydro and the other two utilities were different, as noted above. Miller et al.
found an association when exposures were derived from the JEM of the Ontario Hydro
protocol, which disappeared with the JEM derived from the same measurements with theprotocol used at the other two utilities. [The large 95% confidence intervals on the odds
ratios prevent interpretation of these results.]
In their retrospective cohort study of exposure to magnetic fields and cancer in utility
workers (described in section 4.2.1.1), Savitz and Loomis (Savitz & Loomis, 1995)
identified 164 deaths from leukemia. No association was observed between leukemia risk
and increasing cumulative exposure to magnetic fields (Table 4.11). Analysis by subtype
115

showed no association, although a nonsignificantly increased risk for AML was seen(based on five cases) in the highest exposure category (³ 4.3 mT-year). [Reliance on deathcertificates limits diagnoses, particularly for leukemia subtypes and cancers with longsurvival such as CLL; furthermore, the magnetic field meter used could record only TWA
exposures and not other metrics. See section 4.2.1.1 for other comments on the limitationsof this study.]
In a population-based caseÐcontrol study, Feychting et al. (Feychting et al., 1997)
examined leukemia risk in relation to occupational and residential magnetic fields. They
estimated occupational exposure to magnetic fields from information from census data on
the last job held before cancer diagnosis and from the JEM constructed by Floderus et al.
(Floderus et al., 1996) in another study in Sweden. When analyses were restricted tosubjects with little or no residential exposure, nonsignificant increases in the risk forleukemia as a whole and for AML and CLL were observed for occupational TWA
exposure ³ 0.2 mT. The odds ratio for AML was greater for subjects with both residential
and occupational exposure, based on three exposed cases (Table 4.11). Adjustment forpossible confounding by motor fuel or exhaust, benzene, oil products, and welding fumes
reported to interviewers did not change these associations. [The limitations are use of an
exposure assessment based on a JEM for another population of working males and thelarge percentage of missing information on occupation, particularly for women, and thesmall numbers of subjects in the analysis by subtype and by joint occupational andresidential exposures. See also section 4.2.2.1 for comments on the limitations on theresidential study.]
Johansen & Olsen (Johansen & Olsen, 1998) conducted a retrospective cohort mortality
study of electric utility workers in Denmark. The cohort consisted of 32 006 men andwomen who had been employed for at least three months at any of the 99 electric utilities
in Denmark. Their employment history was obtained from utility records going back to1909. Vital status was obtained from the Central Population Register and the National
Death Certificate files for 1968Ð93, and cancer incidence was obtained from the Cancer
Registry over the same period. A JEM was constructed by a panel of utility engineers
who used 127 magnetic field measurements taken earlier (Skotte, 1994) to assign a TWA
magnetic field exposure category (background, low, high, or unknown) to 475
combinations of job titles and work areas. Each subject was assigned the magnetic field
exposure at their first job because < 1% of the employees had changed occupations within
a utility, according to the company records. The SIRs for leukemia in men were calculated
for different exposure with respect to the Danish male population, with adjustment forage, gender, and calendar year. No association between level of exposure to magnetic fields
and leukemia risk was observed (Table 4.11). [The measurement database is far lesscomprehensive than those of most other studies, which had access to full-shiftmeasurements.]

116

4.2.1.3 Brain cancer
In their large caseÐcontrol study of occupational magnetic fields, Floderus et al. (Floderus
et al., 1993) also studied 346 cases of brain tumor (see section 4.2.1.2) that occurred
during 1983Ð87, which were identified from the National Cancer Registry. The response
rate to the questionnaire was 75% for cases, resulting in 261 cases for analysis. A weakassociation with TWA exposure to magnetic fields for the job held longest during the 10
years before diagnosis (Table 4.12) was observed, with no evidence of a trend. A
significant increase was seen in an intermediate median exposure category (median ³ 0.17
mT: OR = 1.5; 95% CI, 1.1-2.0). [See section 4.2.1.2 for comments on the limitations of
this study.]
Sahl et al. (Sahl et al., 1993) also considered brain cancer in their caseÐcontrol study
nested in the cohort of employees at Southern California Edison (see section 4.2.1.2). The
analyses included 32 deaths from brain cancer. The odds ratios by cumulative exposure
category were close to 1.0. Further analyses at various time windows of exposure andlatency did not reveal any association. [See section 4.2.1.2 for comments on thelimitations of the study.]ThŽriault et al. (ThŽriault et al., 1994) also examined the risk for brain cancer in their caseÐ
control study nested within a cohort of workers at three large electric utility companies(see section 4.2.1.1). In all, 250 cases of brain cancer were included in the study. A nonsignificant increase in risk of brain cancers as a whole was observed for workers withcumulative exposure to magnetic fields greater than the median (3.15 mT-years: OR, 2.0;
95% CI, 0.98Ð3.9) and the 90th percentile (15.7 mT-years: OR, 2.1; 95% CI, 0.80Ð5.7;
see Table 4.12). A significantly increased risk was seen for astrocytoma among workers in
the 90th percentile of cumulative exposure, based on five exposed cases. This association
greatly diminished, however, when exact conditional logistic analyses were used [theappropriate method for analyzing data when such small numbers of cases are observed].
The analyses showed no significant differences across cohorts. [See section 4.2.1.2 forcomments on the limitations of this study.]
In their re-analyses of the EDF cohort, GuŽnel et al. (GuŽnel et al., 1996), found anincreased risk for brain tumors (based on 69 cases) among utility workers exposed toelectric fields. The increase was significant in the group that had exposure to electric fields
in the 90th percentile of the exposure distribution (OR, 3.1; 95% CI, 1.1-8.7). The
association remained significant after adjustment for confounding exposures (including
magnetic fields) and was strongest in workers with ³ 25 yearsÕ employment. [See section
4.2.1.2 for comments about the limitations of this study.]
In their reanalyzes of the Ontario Hydro cohort (see section 4.2.1.2), Miller et al. (Miller
et al., 1996) also considered 69 cases of brain cancer. No association was seen with
exposure to electric fields, based on two exposed cases in the 172Ð344 V/m-year category

117and three in the ³ 345 V/m-year category. [See section 4.2.1.1. for comments on thelimitations of this study.]
In their retrospective cohort study of magnetic fields and cancer in utility workers(described in section 4.2.1.1), Savitz and Loomis (Savitz & Loomis, 1995) estimatedexposure to magnetic fields for 144 workers who had died from malignant neoplasms of
the brain and nervous system. An increased risk was seen in all exposure categories,
which was statistically significant only in the highest category (³ 4.3 mT: RR = 2.3; 95%
CI, 1.2Ð4.6). The RR per mT-year was 1.1 (95% CI, 1.0-1.1). The association wasslightly greater for cumulative exposures received 2Ð10 years previously (RR per mT =1.9; 95% CI, 1.3-2.8). [See section 4.2.1.1 for comments on the limitations of this study.]
Feychting et al. (Feychting et al., 1997) also considered brain cancer in their caseÐcontrol
study of cancer and occupational and residential exposure to magnetic fields in Sweden(see section 4.2.1.2). They identified 223 cases of central nervous system tumors fromthe Swedish Cancer Registry. No association was seen between CNS tumors andoccupational exposure to magnetic fields among people with little or no residential
exposure. Among those with both residential and occupational exposures ³ 0.2 mT, noassociation was seen for CNS tumors as a whole, but a non-significant increase (OR, 2.2;
95% CI, 0.6Ð8.5) was reported for astrocytomas grades III and IV, based on three
exposed cases. [See section 4.2.1.2 for comments on the limitations of this study].
Harrington et al. (Harrington et al., 1997) conducted a caseÐcontrol study of death frombrain cancer nested in a cohort of 84 018 male and female electric utility workers who had
been employed for at least six months between 1972 and 1984 at the Central Electricity
Generating Board in the United Kingdom. The cohort was defined from computerized
employment records, which started at different times over the period 1972Ð79 in various
regions of England and Wales. Deaths from brain cancer were identified from deathcertificates, and 112 diagnoses of primary brain cancer were verified through the National
Cancer Registry. Six controls per case were chosen from the cohort, matched on gender,
who were alive at the time of death of the case and closest in age to the case. WorkersÕ
computerized job histories were coded blindly in terms of 11 job groups by two engineers
with long experience in the industry. Exposure in different jobs and locations wasassessed from measured exposures from a survey of 258 staff in the British electricity
supply industry (Merchant et al., 1994), in which both IREQ and Positron meters wereused. In each job for which measurements were made, exposure was estimated as the
TWA and the time-weighted geometric mean of the measurements made in this job.
Various measures of the exposure of the cases and controls were calculated by combining
job classifications with employment records (when available) and the estimated exposurein the relevant job. Exposure estimates could not be made for 86 subjects (18 cases and 68
controls) because of insufficient employment history. Information on 24 potential
workplace carcinogens and neurotoxic agents was obtained from a JEM generated for thisstudy. Statistical analyses were performed by conditional logistic regression. No
association was observed between brain cancer and cumulative exposure to magnetic fields(measured either as TWA or time-weighted geometric mean) over the total career or over118

the five years before death. A significant increase in risk was, however, observed amongpeople whose exposure was not classifiable owing to insufficient employment history.
No association between exposure to any of the 24 potential confounders and brain cancer
was observed. [The limitations in the exposure assessment resulted in no exposure
estimates for 16% of cases and 10% of controls.]
Johansen and Olsen (Johansen & Olsen, 1998) also considered brain cancer in theirretrospective cohort mortality study of electric utility workers in Denmark (see section
4.2.1.2). No association was seen between death from brain cancer (72 cases) and
exposure to magnetic fields (see Table 4.12). [See section 4.2.1.2 for comments on thelimitations of the study.]
4.2.1.4 Breast cancer
The studies described in this section are summarized in Table 4.13 and 4.14.
(a) MenMatanoski et al. (Matanoski et al., 1991) first reported an excess of male breast cancer,
based on two cases among central office technicians in a cohort of telephone employees.
The peak exposure to magnetic fields of the technicians was a significant risk factor in the
study of leukemia in telephone workers (Matanoski et al., 1993). It was later reported
that these technicians were probably exposed to ionizing radiation from radium gas tubes
which were sometimes carried in their shirt pockets, a clear confounder (Malkin et al.,1994). Nonetheless, this study provided the first anecdotal evidence for a risk for breast
cancer and generated interest in further studies. In another brief communication, Loomis etal. (Loomis, 1992) reported an excess of breast cancer deaths among men under 65, basedon a small number of cases.
Demers et al. (Demers et al., 1991) assessed exposure to EMF for the men in a
population-based caseÐcontrol study of epithelial breast cancer (Jauchem et al., 1992).
The cases were determined from five years of records at cancer registries in six states andfour metropolitan areas in the USA. Controls matched on age were selected by randomdigit dialing for younger subjects and from Medicare records for those over 65. Aninterviewer asked about the subjectÕs two longest-held occupation and possible risk
factors for breast cancer. A subject was considered to have been exposed to EMF if his
longest-held job was in one of five groups (Table 2.4). All exposed men had a twofold
increase in relative risk, which increased in the electric utility trades (OR = 6.0; 95% CI,
1.7-21). Adjustment for known risk factors for breast cancer did not change theseestimates appreciably. The relative risks were further elevated in subjects who were first
exposed before the age of 30 and continued to be exposed for at least 30 years before
cancer diagnosis. [This finding confirms the hypothesis that exposure to EMF is an earlystage carcinogen.] The study is the largest to look at male breast cancer and could
therefore assess the timing of exposure to EMF and possible confounders, both of which119supported the association. [The job titles used as a surrogate for exposure to EMF were
not validated by field measurements in the study population. In addition, the refusal rate
was substantial, especially among controls, and the occupational histories were limited tojobs held the longest.]
Tynes et al. (Tynes et al., 1992) studied a cohort of working-age men in Norway bylinking census data on work histories to cancer registry data covering a 25-year period.
Exposure to EMF was attributed for a list of 13 electrical job titles (Table 2.4). The SIRs
for the electrical workers were calculated from the expected numbers of cancers for theentire cohort. The relative risks for male breast cancer were significantly elevated, being
highest for men with jobs in electrical transport (only four cases), although the exposure
to EMF is generally below the power frequency (e.g. 16.7 Hz for electric railways andDC magnetic fields for tram operators in the three largest Norwegian cities). [The job
titles used as a surrogate for exposure to EMF were not validated by field measurementsin the study population, and no information on potential confounders was available.]GuŽnel et al. (GuŽnel et al., 1993) conducted a population-based study of working men
and women in Denmark, whose cancer incidence was examined from 18 years of data fromthe national registry. To estimate exposure to EMF, 3932 combinations of occupational
and industrial categories were assigned by expert judgment to four exposure categories(none, intermittent ELF, continuous ELF, and other EMF frequencies). The highest
exposure category was ELF magnetic fields continuously above 0.3 mT, which were
attributed to 20 industryÐjob combinations (Table 2.4). Sex-specific cancer risks arecalculated relative to the entire cohort of economically active subjects and are effectively
SIRs. GuŽnel et al. reported relative risks for male and female breast cancer, neither ofwhich were significantly elevated for either intermittent or continuous exposure to ELF
EMF (see Table 4.13). The occupations considered to imply continuous exposure to ELF
magnetic fields is unusual, as it includes jobs such as female shop assistants in the dairy
products and bread industries and omits electric line workers, power station operators,
and welders, who are combined with other metal workers in the Danish job classification
system. The authors noted that these possible misclassifications would tend to lower therisk estimates. [The job titles used as a surrogate for exposure to EMF were not validated
by field measurements in the study population, and no information on potential
confounders was available.]
Rosenbaum et al. (Rosenbaum et al., 1994) conducted a caseÐcontrol study of male breast
cancer in New York State. The cases were all 71 cases of histologically confirmed primarybreast cancer in men from eight counties in western New York state reported to the New
York State Tumor Registry between 1979 and 1988. Controls were 256 men from thesame eight counties who participated in the Prevention-Detection Clinic, a voluntarycancer screening program; they were cancer-free and frequency matched to the cases by
race, year of diagnosis (screening for the controls), and age. The Ôusual occupationÕ was
taken from hospital records (76%) for cases, and information on Ôtype of work doneÕ was
obtained by questionnaire from 95% of the controls before screening. Complementary
information on occupation was obtained from city directories, resulting in occupational120

data for 89% of the cases and 99% of controls. JEMs were constructed for occupational
exposures to heat and EMF (Table 2.4). The risk for breast cancer was elevated for men
exposed to heat but not for those exposed to EMF, based on six exposed cases, and could
be adjusted only for heat exposure, age, and county of residence. [The job titles used as asurrogate for exposure to EMF were not validated by field measurements in the study
population, and no information on potential confounders was available. In addition, thesource and completeness of information on occupation differed for cases and controls, andthe controls may not be representative of the population at risk.]
Floderus et al. (Floderus et al., 1994) analyzed the risk for breast cancer among all
Swedish men who had been employed as railway workers and were aged 20Ð64 in 1960.
The cohort was defined on the basis of data on occupation from the 1960 Swedish census.
Cases of breast cancer were ascertained from the 1960 Cancer Environment Registry,
which comprises information from the Cancer Registry for the period 1960Ð79. SIRs for
specific occupations were calculated with respect to the entire population of working men
from the 1960 census data, adjusted for age in 10-year intervals. No account was made forcancer mortality or incidence during the follow-up period. Data for 1960Ð69 and 1970Ð79
were analyzed separately because changes in railway work practices had reduced the sizeof train crews and how often individuals worked on trains. Exposures were assessed by
the railroad job titles that were associated with high exposure to ELF magnetic fields
according to earlier personal monitoring (Floderus et al., 1993). Significantly increased
relative risks were reported for men in the most exposed occupations (Table 2.4): engine
drivers, engine drivers and conductors, and railway workers in the first decade, based on
two, three, and four cases, respectively (Table 4.13). In the second decade, only fourcases of breast cancer were seen, none of which was in men with the occupations listed
above. The authors discussed the differences between the two time periods and proposedseveral hypotheses, in particular an effect of reduction of exposures. [The very small
number of cases and the improper follow-up of the cohort make interpretation of theseresults difficult.]
In an extension of their previous caseÐcontrol study of leukemia and brain cancer(Floderus et al., 1993), described in section 4.2.1.2, Stenlund and Floderus (Stenlund &Floderus, 1997) also considered male breast cancer and testicular cancer. They identified
56 cases of breast adenocarcinoma from the Swedish Cancer Registry for the period
1985Ð91 from all of Sweden. The 1700 controls used in the study were from the previouscaseÐcontrol study of brain and leukemia. The participation rate was 82% for cases and
72% for controls. Exposure assessment was based on the use of the JEM, as describedabove, which was obtained in the previous caseÐcontrol study on a different study
population (Floderus et al., 1993) and complemented by 15 additional measurements inthis study population. No association was observed between the risk for male breast
cancer and exposure to magnetic fields (see Table 4.14). [The limitations are transporting
JEMs across study populations, the low participation rates, limited information on
potential controls, and the fact that the controls came from a different study and were
therefore not matched on age or region with the cases in this study.]121

(b) Women
Female breast cancer has been the subject of one study in which exposure was assessedby measurements and three studies in which exposure to EMF was assessed by job titles(Table 4.13 and 4.15).
Loomis et al. (Loomis et al., 1994b) used a large database of death certificates in the USA
for the period 1985Ð89. Among 27 814 cases of breast cancer and 112 749 controls, 68
cases and 199 controls had been employed in traditional electrical occupations, resulting
in a small but significantly increased risk (mortality odds ratio = 1.4; 95% CI, 1.0-1.8) inthe electrical occupations originally defined by Milham (Milham, 1982). Since thisrestrictive definition of electrical work applied to only about 0.2% of women, Loomis etal. (Loomis et al., 1994b) examined other occupations in which more women might be
exposed to EMF (Table 2.4), but saw no elevated associations. [The study had thefollowing limitations: reliance on death certificates for occupation and diagnosis, use ofother deaths as controls, assessment of exposure to EMF by a group of electricaloccupations, and an inability to control for other risk factors for breast cancer.]
Cantor et al. (Cantor et al., 1995a) used the same death certificate data set, adding one
more year of follow-up. Exposure to EMF was assessed by an industrial hygienist [nodetails were given]; however, this new classification resulted in twice as many womenbeing defined as 'highly' exposed. They found no association for white women but asignificant increase for black women with medium or high probability of exposure to ELF
fields (see Table 4.15). [The absence of detail about the more liberal ELF exposure
assessment makes evaluation of the differences in results from Loomis et al difficult.]
Coogan et al. (Coogan et al., 1996) studied occupational exposure to 60 Hz magnetic
fields in a large caseÐcontrol study of breast cancer in the USA (Newcomb et al., 1994).
The cases were over 6800 cases of breast cancer diagnosed between 1988 and 1991 among
women 74 years of age or younger from the cancer registries in Maine, Wisconsin, andMassachusetts. The controls were frequency-matched on age from driversÕ license records(if < 65) and the Health Care Financing AdministrationÕs list of Medicare beneficiaries (if65Ð74). The occupation most representative of the subjectÕs career was obtained by
telephone interview, with information on reproductive history and other breast cancer
risk factors. The participation rates were 81% (6888) for cases and 84% (9529) for
controls. Usual occupations were grouped into three categories (low, medium, and high)of potential exposure to 60 Hz magnetic fields above background by an industrial
hygienist (Table 2.4); the remaining occupations were aggregated into a ÔbackgroundÕ
category. Conditional logistic regression stratified on age and state was used to calculate
odds ratios, with adjustment for risk factors for breast cancer. The odds ratios by
category were 1.0 (95% CI, 0.91Ð1.2) for low exposure, 1.1 (0.83Ð1.4) for intermediate
exposure, and 1.4 (0.99-2.1) for high exposure. [There are problems in assessing exposure
to EMF by expert judgment for workers in broad sectors of the economy (see section 2.4
for further discussion).]122

Johansen and Olsen (Johansen & Olsen, 1998) also considered breast cancer in women in
their retrospective cohort mortality study of electric utility workers in Denmark (seesection 4.2.1.2). No association was seen between death from breast cancer (96 cases) and
exposure to magnetic fields, based on very small numbers of exposed cases: two in the
low-exposure category (0.1Ð0.29 mT), none in the intermediate category, and one in thehighest category (³ 1.0 mT). [No information on risk factors for breast cancer wasavailable. See section 4.2.1.2 for comments on the limitations of the study.]
4.2.1.5 Lung cancer
The Positron meter used by ThŽriault et al. (ThŽriault et al., 1994) also measured
exposures to ELF electric fields and high-frequency EMF transients (or PEMF; seesection 2.3.1). They examined the risk for lung cancer in their caseÐcontrol study nested
within the cohort of workers at three large electric utility companies (see section 4.2.1.1).
In all, 772 cases of lung cancer were included in the study. No association between risk
for lung cancer and cumulative exposure to magnetic fields greater than the median (³ 3.2
mT-years: OR, 0.92; 95% CI, 0.70Ð1.2; Table 4.16). [See section 4.2.1.2 for comments on
the limitations of this study.]
Armstrong et al. (Armstrong et al., 1994) examined the associations between exposure to
PEMF and cancer among the Hydro QuŽbec and EDF cohorts included by ThŽriault et al.
(ThŽriault et al., 1994). This analysis was based on about 1000 personÐweeks ofmeasurements of exposure to these high-frequency electromagnetic transients, 508 lungcancer cases, and 508 controls. Smoking status was available from medical histories forsome of the subjects at Hydro QuŽbec but not at EDF. A significant association wasobserved between the risk for lung cancer and cumulative exposure to PEMF (OR, 3.1;
95% CI, 1.6-6.0 among workers with exposure > 90th percentile). This association was
confined to the Hydro QuŽbec workers (OR, 2.4; 95% CI, 1.1-5.3 for PEMF exposures >median and OR, 5.6; 95% CI, 2.0-16 for exposures > 90th percentile), despite a low
standardized mortality ratio (SMR, 0.85) for lung cancer in that cohort. The association
among Hydro QuŽbec workers became stronger after adjustment for current smoking
status and exposure to asbestos and other occupational agents (OR = 10; 95% CI, 3.2-31
for the highest exposure). The authors noted that the levels of exposure to both PEMF
and ELF magnetic fields were considerably lower among EDF workers than among HydroQuŽbec workers. They also noted the incomplete and apparently incorrectcharacterization of the PositronÕs PEMF channel, which is more sensitive toradiocommunication signals (see section 2.3.1) (Heroux, 1991). [The information on
smoking was incomplete.]
Miller et al. (Miller et al., 1996) also analyzed the risk for lung cancer in the Ontario
Hydro cohort of ThŽriault et al. in relation to exposure to both ELF electric and magnetic
fields (see description of study in section 4.2.1.2). No significant association was seen
between the occurrence of lung cancer (263 cases) and exposure to electric or magnetic

123

fields. [See section 4.2.1.2 for comments on the limitations of this study; in addition,
there was no information on smoking.]
Savitz et al. (Savitz et al., 1997) subsequently re-examined the cohort from the study offive US utilities of Savitz and Loomis (Savitz & Loomis, 1995) in order to test theassociation between lung cancer and exposure to PEMF reported by Armstrong et al.
(Armstrong et al., 1994). A total of 1692 deaths from lung cancer had occurred over the
study period. The PEMF JEM from the CanadaÐFrance study was adapted with someapproximation to the job categories of the five US utilities. No association was seen
between the risk for lung cancer and exposure to 60 Hz magnetic fields. The risks
associated with exposure to PEMF were slightly but significantly elevated in all exposure
categories (Table 4.16); there was no indication of a trend with exposure. No data on
smoking were available. The risk for lung cancer was still significantly elevated after
adjustment for socioeconomic status. [Transposition of a JEM from the CanadaÐFrance
study to this population is problematic.]
4.2.1.6 Other cancers
A number of studies based on job titles alone have investigated the occurrence of various
cancer types. Sporadic reports of elevated risks for malignant melanoma, have come out,
but interpretation of these results is difficult because of the lack of measurements and the
problem of multiple comparisons. The studies are therefore not described here.
In the caseÐcontrol study described above (section 4.2.1.3), Stenlund and Floderus(Stenlund & Floderus, 1997) also used the Swedish JEM to analyze the relative risks fortesticular cancer. A total of 144 cases (94 seminomas and 50 non-seminomas) wereidentified from the Swedish Cancer Registry for the period 1985Ð87 in central Sweden. A
small increase in risk was observed in all quartiles of TWA exposure to magnetic fields.
The analyses were adjusted for age, education, and exposure to solvents. The odds ratios
were 1.3 (95% CI, 0.7-2.4) for TWA exposure in the range 0.16Ð0.19 mT, 1.4 (0.8Ð2.7)
for 0.20Ð0.28 mT, and 1.3 (0.7Ð2.5) for ³ 0.29 mT. The risk was significantly increased
among workers with exposures > 90th percentile (³ 0.41 mT: OR = 2.1; 1.0Ð4.3),
particularly among men under the age of 40 (OR = 3.9; 95% CI, 1.4Ð11). A significantly
increased risk in the 90th percentile was seen for non-seminomas in men below the age of40 (OR = 16; 2.7Ð95, based on seven exposed cases and overall when workers were also
probably exposed to solvents (OR = 3.8; 95% CI, 1.1Ð13.1). The authors regretted theirinability to test for confounding by exposure to heat, a possible risk factor for testicularcancer. [See section 4.2.1.3 for comments on the limitations of this study.]ThŽriault et al. (ThŽriault et al., 1994) also examined the occurrence of a number of othercancer types in relation to exposure to magnetic fields in a caseÐcontrol study nested
within the cohort study of workers at three large electric utility companies (see section
4.2.1.1). No association was seen with lymphoma, multiple myeloma, melanoma, or anyof the other 13 cancer groupings considered. No association with exposure to electric

124

fields was seen for cancers other than those of the brain and lung cancer by Miller et al.
(Miller et al., 1996). [See section 4.2.1.1 for comments on the limitations of thesestudies.]Schroeder and Savitz (Schroeder & Savitz, 1997) studied mortality from lymphoma andmultiple myeloma in association with the JEM for magnetic fields and the cohort
mortality data from Savitz and Loomis (Savitz & Loomis, 1995). In total, 154 deaths
from non-HodgkinÕs lymphoma, 87 from CLL (classified as low and intermediate or highgrade), 29 from HodgkinÕs disease, and 84 from multiple myeloma occurred during thestudy period. No association was found between levels of exposure to magnetic fields andthe risk for CLL, HodgkinÕs disease, or multiple myeloma. An association was found for
non-HodgkinÕs lymphoma, however, which was significant in the two intermediate
exposure categories. The relative risks, adjusted for exposure to solvents, were 1.5 (0.9Ð
2.4), 1.8 (1.1Ð2.9), 1.8 (1.1Ð3.1), and 1.3 (0.7Ð2.8) for cumulative exposure categories of
0.6 £ 1.2, 1.2 £ 2.0, 2.0 £ 4.3, and ³ 4.3 mT-years, respectively. No association was seen
for cumulative exposures in the previous 2Ð10 years. [Information on other risk factors
for lymphomas was lacking. See also section 4.2.1.1 for comments on the limitations of
the Savitz and Loomis study.]
4.2.1.7 Central nervous system cancers in the offspring of parents exposed toelectromagnetic fields
Seven studies have addressed the risks for cancers of the central nervous system (CNS)
among children of parents exposed to EMF (Table 4.17). Six are population-based caseÐ
control studies in which exposure to EMF was assessed by job titles, and the seventh is acohort study that included childhood cancers in a study of male reproductive effects.
In an exploratory study, Spitz and Johnson (Spitz & Johnson, 1985) investigated deathfrom neuroblastoma. The jobs of controls and parents were obtained from the Texas birthcertificate registry. Controls were selected so as to match the caseÕs birth year
distribution. Exposure to EMF was assigned to electrical jobs, with both a ÔnarrowÕ and aÔbroadÕ definition (see Table 2.4). The relative risks were elevated with both definitions of
exposure but reached significance only with the broad definition. [The broad definition
included electrical equipment salesmen and repairmen, who are unlikely to have highexposure to magnetic fields. No adjustment was made for potential confounding
exposures.]
The same Texas records were examined by Johnson and Spitz (Johnson & Spitz, 1989)
for mortality from all CNS tumors (intracranial and spinal cord), which include theneuroblastomas studied by Johnson and Spitz (Spitz & Johnson, 1985). The methods
were similar to those of the earlier study, except that controls were frequency-matched on
gender and race as well as birth year. The relative risks in electrical occupations were notsignificantly elevated. [Their new definition of electrical occupations is perhaps the most125

questionable devised, as it includes jobs such as radio and television performer andelectrical goods and appliance salesmen.]
Nasca et al. (Nasca et al., 1988) conducted a study of the incidence of CNS tumors;
controls were selected from birth certificates for the same geographical region and werematched on gender, race, and year of birth. Parental job histories were obtained by
telephone interviews with the mothers (85% participation rate for cases and 70% forcontrols). Exposures to EMF and ionizing radiation were assigned to industryÐoccupation
combinations (see Table 2.4). Some increase in risk was observed among children whoseparents were employed in industries with exposure to ionizing radiation, and they were
excluded as controls in the EMF analysis. The relative risks from exposure to EMF were
not significantly elevated for either the broad or narrow definition. Power calculations
indicated that the sample sizes were large enough to permit detection of relative risks as
low as 2.5Ð2.8.
Bunin et al. (Bunin et al., 1990) studied the incidence of neuroblastomas in comparison
with controls selected by random-digit dialing and with occupational histories ascertainedby phone interviews. The controls were matched to cases on race, date of birth, and thefirst five digits of their telephone numbers (i.e. locality). Exposure to EMF was assigned
to the electrical occupations defined by Spitz and Johnson (Spitz & Johnson, 1985). No
increase in risk was observed.
Wilkins and Hundley (Wilkins & Hundley, 1990) studied the incidence of neuroblastomas
in Columbus, Ohio. Controls and parental occupations were determined from birthcertificates, and controls were matched on birth year, race, gender, and motherÕs county ofresidence. Electrical occupations of the fathers were defined in several ways, including
those of Deapen and Henderson (Deapen & Henderson, 1986) and Lin et al. (Lin et al.,1985). No significant associations were seen with any definition.
Wilkins and Wellage (Wilkins & Wellage, 1996) studied the same population in Ohio forthe association between exposure to EMF and risks for CNS tumors. Random-digit
dialing was used to recruit controls, who were matched on gender and race (but not
telephone exchange). Occupational histories and exposures to potential risk factors wereascertained by interviewing both biological parents. Exposure of the fathers to EMF was
ascribed for a group of electrical occupations (Table 2.4). No association was seen withtumor risk. When welders were analyzed separately, the relative risk, based on only six
cases, was marginally significant (OR = 3.8; 95% CI, 0.95-16). No evidence was seen forconfounding by childhood or maternal exposure to X-rays, parental smoking, orhousehold pesticides. [Confounding from welding fumes and solvents is a potential
explanation for the association.]
Tornqvist (Tornqvist, 1998) examined cancers in the children of members of retrospective
and prospective cohorts of electrical workers in the power industry. Details of the study
design are given in section 4.5.1. The retrospective study found an equal number of126

cancers among children of fathers who had had electrical jobs in the censuses before andafter the birth (ÔexposedÕ) and the remainder of the cohort (ÔunexposedÕ). [On the basis of
the number of cancers expected in the paper, the Working Group calculated the risk ratio
as 0.75 (95% CI, 0.24-2.3), showing no association with the fatherÕs apparent electrical
work at the time of conception.] Six of the 12 cancers were located in the CNS and werealso found equally in exposed and unexposed children. No cancers were reported among
the children in the prospective study. [As the paper did not report the number of cancers
expected in this population, this finding is hard to interpret.]
4.2.1.8 Meta-analyses of brain cancer and leukemia
Kheifets et al. (Kheifets et al., 1997a; Kheifets et al., 1995) have explored the patterns of
the brain cancer and leukemia in relation to exposure to EMF in meta-analyses andcombined their results to obtain pooled risk estimates.
(a) Brain cancer
Kheifets et al. (Kheifets et al., 1995) identified 52 studies of occupational exposure to
EMF and brain cancer through an English-language literature search. The criteria forinclusion in the meta-analyses were as follows:·

For studies that were updates or re-analyses of previously reported studies, only thestudy with the most inclusive study population was selected, unless more specificinformation on exposure or disease was used for a subset. Six studies were excluded
on the basis of this criterion.

·

Quantitative information had to be available on exposure and risk. Twelve studies
were excluded on the basis of this criterion.

·

Five studies were not included in most analyses because they were not published orpresented only preliminary results.

Of the studies with results pertaining to occupational exposure to EMF and brain cancer,
29 independent studies were selected for this analysis. [The studies of GuŽnel et al.;Miller et al.; Feychting et al.; Harrington et al.; and Johansen and Olsen, reviewed above,were not included in the meta-analyses as they were published later.] (Feychting et al.,
1997; GuŽnel et al., 1996; Harrington et al., 1997; Johansen & Olsen, 1998; Miller et al.,
1996)
In order to assess heterogeneity, the authors scored 15 individual study characteristics
that were thought to predict the results, including study quality and design. The
characteristics were scored by two independent epidemiologists who were blinded to theauthors and the results of the studies. Because most of the completed studies contained127

limited information on exposure, the authors attempted to evaluate the relationshipbetween exposure and disease by using additional information or measured exposure to
EMF by job classification obtained from several large surveys of exposure in theworkplace. These data were used to rank job categories and to compare exposure to therisk estimates for those job categories. The risk estimates of the 29 studies and various
subsets are summarized by weighted averages in which the weight is the inverse of thevariance of the estimate. A heterogeneity test, q statistic, and random-effects and fixedeffects summaries were computed. To investigate the sensitivity of the results to theweights used, several additional weighting schemes were used.
The pooled odds ratio from the 29 studies for a broad group of electrical occupations was
1.2 (95% CI, 1.1-1.3). [The pooled results for the broad group of electrical occupations
includes data from studies in which no measurements of magnetic fields were made andwhich are therefore not reviewed in this document.] The authors observed lower risks in
the Nordic cohort and incidence-based studies included in the meta-analyses. To assess
exposureÐresponse relationships, the authors pooled the risk estimates for the high,medium, and low categories of exposure from the available studies in which magnetic
fields were measured. These included the results of Floderus et al. (Floderus et al., 1993),
ThŽriault et al. (ThŽriault et al., 1994), and Savitz and Loomis (Savitz & Loomis, 1995).
Although an increased risk was seen in all exposure categories, there was no evidence ofan exposureÐresponse relationship across the three exposure categories. [A limitation ofthis analysis is the combination of results across studies with different exposure
categorizations. For example, the high exposure category in the study of Floderus et al. in
the general industry may correspond to a medium exposure level in an electrical industry,
possibly resulting in exposure misclassification.](b) Leukemia
Using the same methods, Kheifets et al. (Kheifets et al., 1997a) also reviewed 70 studies
on leukemia. The criteria for inclusion were:·

For studies that were updates or re-analyses of previously reported studies, only thestudy with the most inclusive study population was selected, unless more specificinformation on exposure or disease was used for a subset; 15 studies were excluded on
the basis of this criterion.

·

Quantitative information had to be available on exposure and risk. Eleven studies were
excluded on the basis of this criterion.

·

One study was excluded because it was a meta-analysis.

·

Three studies were not included in most analyses because they were not published orpresented only preliminary results.

128

·

One study was not published in English.

Of the studies reporting results pertaining to occupational exposure to EMF andleukemia, 38 independent reports were selected for this analysis; the study of ThŽriault etal. (ThŽriault et al., 1994) was treated as three independent studies. [The studies reviewed
by Kheifets et al. did not include those of London et al., GuŽnel et al., Miller et al.,Feychting et al., and Johansen and Olsen, as the results were not yet available foranalysis.] (Feychting et al., 1997; GuŽnel et al., 1996; Johansen & Olsen, 1998; Kheifets
et al., 1997a; Miller et al., 1996)
The pooled odds ratio from the 38 data sets (in 22 of which exposure was assessed by job
titles alone) for leukemia was 1.2 (1.1-1.3) for a broad group of electrical occupations.
Among the leukemia subtypes, a significant association was seen for both AML (OR =1.4; 95% CI, 1.2Ð1.7) and CLL (OR = 1.6; 95% CI, 1.1Ð2.2). There was no evidence ofheterogeneity of risk across the studies; in particular, the studies judged to have included
better exposure assessment and design did not show a different risk.
In order to assess possible exposureÐresponse relationships, the authors pooled the risk
estimates for the high, medium, and low categories of exposure from studies in whichmagnetic fields had been measured and which were published at that time. The analyses
included results from Floderus et al. (Floderus et al., 1993), ThŽriault et al. (ThŽriault etal., 1994), Savitz and Loomis (Savitz & Loomis, 1995), and Matanoski et al. (Matanoski
et al., 1993) and two studies that included spot measurements (Tynes et al., 1992; Tynes
et al., 1994). For both brain cancer and leukemia, the pooled relative risks showed no
exposureÐresponse relationship across the three exposure categories. An increased risk
was seen in all exposure categories, although there was no evidence of an exposureÐ
response relationship. [See comments on the limitations of these analyses in thediscussion of the meta-analysis of brain cancer, above.]4.2.1.9 Summary
This review focuses on the best of the epidemiological studies that were available to theWorking Group, i.e. those of exposure from full-shift measurements of extremely low
frequency (ELF) magnetic and electric fields. The one exception is the studies of breast
cancer, in which exposure was assessed only by job title.
Leukemia
Leukemia was the first cancer to be associated with occupational exposure to EMF, andat least 70 epidemiological studies have provided evidence relevant to this cancer. Most ofthese were based on job titles, and judgments were made about which occupational
categories involve high exposure to EMF. In a meta-analysis, a small but significantly
increased relative risk for leukemia and its main subtypes was found for a broad group ofelectricity-associated occupations.
129

Separate evaluations were made for the two major leukemia subtypes, chronic
lymphocytic leukemia (CLL) and acute myelogenous leukemia (AML), and for all
leukemias.
Chronic lymphocytic leukemia: The association between exposure to magnetic fields and
CLL was considered in three studies of incidence, two in Sweden (Feychting et al., 1997;
Floderus et al., 1993) and one in Canada and France involving three separate cohorts(ThŽriault et al., 1994), and in one of mortality in the USA (Savitz & Loomis, 1995).
No association was found in the US mortality study. The diagnoses were, however, basedon death certificates, which is problematic for leukemia subtypes and particularly for
CLL, because of the long survival time.
In the CanadaÐFrance incidence study of electric utility workers, a nonsignificantly
increased risk was seen overall and in two of the three cohorts. A significant increase wasseen in both of the Swedish studies. One of these (Feychting et al., 1997) provides uniqueinformation on the potential importance of combining occupational and residential
exposures for adults, but it suffers from small numbers. In addition, their exposure
assessment was based on a jobÐexposure matrix derived from magnetic fieldmeasurements for a different population of male workers, so their occupational exposures
were not validated, especially for female workers. In the other Swedish study (Floderus etal.) of male workers in all occupations, the risk increased with increasing exposure; therisk was particularly strong for the highest exposure category and was increased
somewhat when adjusted for exposure to potential confounders. The refusal rate in thatstudy, however, could have introduced bias into the results.
Although each of these studies has its limitations, the limitations are different acrossstudies, as are the designs and exposure assessment methods. Taken together, the studies
of incidence suggest an association between exposure to magnetic fields and CLL.
Acute myelogenous leukemia: The association between exposure to magnetic fields and
AML was considered in the same studies as for CLL. A nonsignificant increase in risk
was found in the US mortality study, although the use of diagnoses from deathcertificates is problematic, as mentioned above.
In the Canada-France study, a significantly increased risk was seen overall for exposures
above the median; this association is due mainly to a very high risk in one cohort, whereas
a much smaller risk was seen in another cohort. The differences in definition and followup between the three studies, however, limit interpretation of the results. A
nonsignificant increase in risk was seen in the study of Feychting et al. (Feychting et al.,1997), which became significant when restricted to the very small number of subjects who
had both high occupational and high residential exposures. Although the study of
Feychting et al. provides unique information on the potential importance of combining
occupational and residential exposures in adults, it suffers from small numbers and130

weaknesses in exposure assessment, particularly for women. In the study of Floderus etal. (Floderus et al., 1993), no association was seen between exposure to magnetic fields
and the risk for AML.
Leukemia: The association between exposure to magnetic fields and risk for leukemia ingeneral was considered in the same studies. No association was found in either of the two
US studies of mortality. The limitations of death certificate diagnoses mentioned above
are less critical for leukemia in general than they are for specific subtypes. In the CanadaÐ
France study, no significant association was seen overall, although a significant
association was seen in one cohort. The differences in definition and follow-up among
three studies, however, limit interpretation of the results. A marginally significant
association was seen in both Swedish studies; in the study of Feychting et al. (Feychting
et al., 1997), when the analyses were restricted to subjects with high occupational andresidential exposures, a significant elevation in risk was seen, based on nine cases.
Although the study of Feychting et al. provides unique information on the potential
importance of combining occupational and residential exposures in adults, it suffers fromsmall numbers and weaknesses in exposure assessment, particularly for women.
Brain cancer
The association between exposure to magnetic fields and brain cancer was considered in
the same studies.
One US study found a significant association in the highest exposure category andevidence for an exposureÐresponse trend. The smaller US study showed no association.
Both studies are based on diagnoses from death certificates, which is problematic for brain
cancer owing to the difficulty in distinguishing primary cancers from metastases.
A nonsignificant elevation in risk was seen in the CanadaÐFrance study and in each of thecohorts in that study. In the study of Floderus et al. (Floderus et al., 1993), an association
was reported between exposure to magnetic fields and brain cancer, which was significant
only in one of the intermediate exposure categories; no evidence for a doseÐresponse
relationship was observed. No association was observed in the study of Feychting et al.
Although each of these studies has its limitations, the limitations are different acrossstudies, as are the designs and exposure assessment methods. Taken together, the studies
suggest an association between exposure to magnetic fields and brain cancer, although theresults are somewhat inconsistent.
Male breast cancer: The relationship between the risk for male breast cancer andexposure to magnetic fields has been examined in only one study, in Sweden, in which
exposures were assessed with a JEM derived from full-shift measurements of magnetic
fields. No association was observed, although no adjustment for potential confounders
was made.

131

This association was also considered in nine studies in which only job titles were used toclassify workers by exposure. Only one study involved large numbers of cases and took
into account risk factors for male breast cancers. In that study, a two-fold increase ofborderline significance was seen among men in all exposed occupations combined; asignificant increase was seen for the category of workers in electrical trades. The exposure
assessment based on job title was not validated by measurements. The other studies,
which were based on smaller numbers and had various limitations, gave inconsistent
results. Most of these studies were not designed a priori to test this hypothesis.
Female breast cancer: The relationship between the risk for breast cancer in women andexposure to magnetic fields assessed with a JEM derived from full-shift measurements
has been examined in only one study, in Denmark. No association was observed, but noadjustment was made for potential confounders.
Three other studies, in the USA, were based on job titles; in two, these were classified byexperts into categories of probable exposure to EMF. These studies, which havemethodological limitations mainly because they were not designed a priori to test an
association with EMF, had mixed results.
Other cancers
Other cancer outcomes (including cancer in the offspring of exposed workers) wereconsidered in some studies. Increased incidences of specific types of cancers wereobserved in some studies but were not found consistently. Many of the studies sufferfrom methodological limitations, which hamper interpretation of the results.
Cancers at all sites
The risk for cancers at all sites associated with occupational exposure to magnetic fields
were assessed in one US mortality study and one incidence study in Canada and France.
These two studies were based on cohorts of male electric utility workers, and exposures
were assessed by jobÐexposure matrixes derived from contemporary full-shift monitoringof the cohort members. The mortality study reported a very weak but significant
elevation in risk, with an exposureÐresponse relationship. The study of incidence in the
Canadian and French utilities found no increased risk overall, although a small,nonsignificant elevation was observed in the Hydro QuŽbec cohort.
Evaluation
There is limited evidence that occupational exposure to extremely low frequency magnetic
fields is carcinogenic to adults. This evaluation is based on the results of studies ofchronic lymphocytic leukemia.

132[This conclusion was supported by 14 members of the Working Group; there were 11
votes for ÔinadequateÕ evidence, 2 abstentions, and 2 absent.]
There is inadequate evidence for all other cancers.
[This conclusion was supported by 22 Working Group members; there were 2 votes forÔlimitedÕ evidence, 1 vote for ÔlackÕ of evidence, 2 abstentions, and 2 absent.]

4.2.2 Residential exposure
4.2.2.1 All cancers
Wertheimer and Leeper (1987) (Wertheimer & Leeper, 1987) carried out a seminal caseÐ
control study of adult cancer in the towns of Boulder and Longmont and the city andsuburbs of Denver in Colorado, USA. The cases were all deaths from cancer that had
occurred between 1967 and 1975 and were identified from death certificates in Boulder
and Longmont, all survivors in these two towns of Ôlife-threateningÕ cancers from theColorado Cancer Registry diagnosed in the previous five years and alive in 1979, and asample of 1977 cancer deaths from Denver and its suburbs comprising all deaths fromcancers other than lung among people under the age of 62 and half of the deaths from lungcancer and half of the deaths from all cancers in people over the age of 62. Only subjects
for whom an address could be traced in the sampling area for at least four years before
diagnosis were included. Controls for the deaths in Boulder and Longmont were chosenfrom the next three death certificates for non-cancer deaths, matched to the cases forgender, age, year of death, and, in most cases, socioeconomic level. Controls for the cancer
survivors were drawn at random from a list of subjects included in an unrelated random
telephone survey in Longmont and Boulder and matched on gender, age, andsocioeconomic level. Controls for the Denver cancer deaths were chosen at random fromthe 1970 city directory among persons whose addresses were within two blocks of thecase addresses. [It is unclear whether these controls were matched to the cases on thesame factors.] Each residence was categorized by presumed level of EMF exposure on thebasis of wire coding (VHCC, ordinary high and ordinary low current configuration, andEndpole); the same approach was used as for the study of childhood cancer (Wertheimer& Leeper, 1979). In all, 1977 cancer cases were included in the study. The proportion ofcaseÐcontrol pairs for which the wire codes were higher in case residences than in control
residences was significantly elevated overall. There was a tendency for the proportion ofcaseÐcontrol pairs in which the wire codes were higher in case residences than in control
residences to increase with increasing wiring configuration level (40% for Endpole, 49%
ordinary low current configuration, 53% ordinary high current configuration, and 59%
VHCC). [This is an important hypothesis-generating paper; however, its usefulness for
hypothesis testing was compromised because of unblinded assessment of exposure, theunusual statistical method used, potential overmatching for the Denver cases, and theunusual and complex selection of controls.]

133

Verkasalo et al. (1996a) (Verkasalo, 1996) tested the hypothesis of a relationship between
cancer risk and exposure to magnetic fields from high-voltage transmission lines in acohort study in Finland. Information was obtained by linkage between the Finnish Cancer
Registry, data on residential exposure to magnetic fields from the Finnish Transmission
Line Cohort Study, and residential data from the Central Population Register and the1970 Population Census. The study cohort consisted of all persons who had resided in abuilding with a calculated magnetic field of ³ 0.1 mT for any period between 1970 and
1989. Follow-up was from 1 January 1974 to 31 December 1989. Internal analyses werecarried out by Poisson regression on data grouped on age (five-year categories),
cumulative exposure, and social class [cumulative exposure was defined as cumulative
exposure at the end of follow-up and was not treated as a time-dependent variable in theanalysis]. In addition, SIRs were calculated with respect to the Finnish general
population. The study cohort was very large, consisting of 383, 700 persons (189, 300men) who contributed 2.5 million personÐyears of follow-up after age 20. Overall, 8415
cancer cases were observed (4082 in men). There was no association between cumulative
level of exposure and the risk for all cancers (incidence rate ratio, IRR, 0.98 per mT-year;
95% CI, 0.96Ð1.0) or for any specific cancer type studied. The authors reported that skinmelanoma was the only cancer for which the risk was somewhat increased throughout thethree highest cumulative exposure categories: the IRR per mT-year was 0.91 (0.58Ð1.4),
1.5 (1.0Ð2.3), 1.5 (0.80Ð2.9), and 1.3 (0.59Ð2.7) for exposure to 0.2Ð0.39, 0.4Ð0.99, 1.0Ð
1.99, and ³ 2.0 compared with < 0.2 mT, respectively, in people of each sex. A
marginally significant increased IRR was seen for multiple myeloma in men (IRR, 1.2 per
mT-year; 95% CI, 1.0Ð1.5), and a nonsignificant decrease was observed for women (IRR,
0.87 per mT-year; 95% CI, 0.57Ð1.3). A significant increase in the risk for colon cancer
was seen in women (IRR, 1.2 per mT-year; 95% CI, 1.0Ð1.3) but not in men. [Nomeasurements were made to validate the calculated fields, and no distinction was madebetween apartments and single-family dwellings. The lack of information on other sourcesof residential exposure to EMF might have resulted in substantial exposure
misclassification. In addition, no information on other risk factors, apart from age and sex,
was available].
4.2.2.2 Leukemia
The studies summarized in this section are presented in tabular form in Tables 4.18
(design characteristics) and 4.19 (results).
Preston-Martin et al. (Preston-Martin et al., 1988) investigated the risk for leukemia
associated with use of electric blankets (see section 2.1) by including questions inquestionnaires that were being used in two recently started case-control studies of AML
and chronic myelogenous leukemia (CML) in Los Angeles County in the USA. The
patients were residents of the area, aged 20Ð69 years, with histologically confirmed AML
or CML diagnosed between July 1979 and June 1985, identified through the Los Angeles
County population-based cancer registry. Both cases and controls had to be alive and to
be able to be interviewed in English. One neighborhood control was matched individually
to each case on gender, race, and birth year (within five years). The cancer registry134contained 858 eligible cases, of whom 485 were alive. A physicianÕs permission tocontact a patient was obtained for 415. The participation rate of patients was 61% (68could not be located, and 52 refused to be interviewed). [The response rate of controls is
not given.] Controls could not be found in three neighborhoods. In all, 293 matched pairs
were included in the analysis, including 156 cases of AML and 137 cases of CML. As
information on use of electric blankets was included after the beginning of the study, thisinformation was available for only 224 matched pairs. Neither AML nor CML appeared
to be related to any regular use of electric blankets: the ORs were 0.9 (95% CI, 0.5Ð1.6)
for AML and 0.8 (95% CI, 0.4Ð1.6) for CML. Cases and controls did not differ by
average duration of use, year of first regular use, or year since last use. Adjustment forother risk factors found in the study did not change the results. [There was no indicationof whether blankets had been used only for warming the bed or continuously throughout
the night.]
Severson et al. (Severson et al., 1988) carried out a population-based caseÐcontrol studyof ANLL in adults in relation to residential exposure to power-frequency magnetic fields
in King, Pierce, and Snohomish counties in western Washington State in the USA. The
cases were identified through the cancer registry of the Fred Hutchinson Cancer ResearchCenter, which is part of the SEER program. Cases were restricted to those of people aged
20Ð79 in whom ANLL had been diagnosed between 1 January 1981 and 31 December
1984. Both living and deceased patients were included, for a total of 164 cases. Randomdigit dialing was used to select 204 controls in the same three geographical areas, whowere frequency matched to the patients by gender and age (in five-year groups). A
detailed questionnaire was administered to patients (or their next-of-kin if the patients
had died) and controls; the questionnaire covered complete residential history and use ofelectric appliances. Exposure was assessed in three ways. First, the wire coding methodof Wertheimer and Leeper (Wertheimer & Leeper, 1979) was used to classify all
addresses in the study area in which the subject had resided in the previous 15 years. On
the basis of maps of the residences and the wiring configuration, magnetic fields inside theresidence were also estimated by a method developed by Kaune et al. (Kaune et al.,1987). In addition, one-time measurements of the 60 Hz magnetic fields were made insideand outside the residence using a Power-frequency Field Meter Model 111 at the time of
the interview if the subject had lived there for a continuous period of one year or longer
immediately prior to the reference date (date of diagnosis for the cases). The
measurements were made in the kitchen, the subjectÕs bedroom, and the family gatheringroom, in both Ôlow powerÕ and Ôhigh powerÕ configurations (i.e. with all major appliancesthat could conveniently be turned on and off). Finally, 24-h measurements were made in alimited sample of residences.
The response rates were 70% for cases and 65% for controls. For cases, most of the nonresponses were due to physician refusal (17%), and only 4.9% of the subjects refused to
be interviewed. The percentage of refusals among controls was much higher: (27%). The
final analyses included 114 cases, with 91 cases of AML, and 133 controls. The patientstended to be of lower socioeconomic status than the controls and to smoke more; thesefactors were therefore adjusted for in subsequent analyses. There was no association135

between the risk for leukemia and electrical wiring configuration by the Wertheimer andLeeper scheme, either in the residence inhabited the longest in the 3Ð10 years before thereference date or in the residence closest to the reference date. There was also no
association with magnetic fields calculated by the model of Kaune et al. One-timemeasurements were available for only 56% of homes, since many subjects had moved
after the reference date. A non-significant increase in odds ratio was observed for mean
exposures of 0.2 mT or more, in both low-power (OR, 1.5; 95% CI, 0.48-4.7) and highpower conditions (1.6; 0.49-5.0). When weighted mean exposure was considered, theincrease was no longer apparent in low-power conditions and was reduced in high-power
conditions (1.3; 0.35-4.5). No association was found with use of electric blankets, electricwater-bed heater, or electric mattress pads. [The participation rates were low, and thetype of refusal differed between cases and controls. Also, information on electric blanket
use was limited.]
Lovely et al. (Lovely et al., 1994) further analyzed the data obtained in this caseÐcontrol
study, focusing on information obtained by questionnaire on use of motor-driven personal
appliances (electric razors, hair dryers, and massage units), for which it was judged thatuse would represent higher exposures to peak magnetic fields than most other home
appliances. Information was available on whether subjects had ever used such appliances,on the number of years (in the 10 years before diagnosis) they had had such appliances,and on the daily length of reported use. The authors also characterized magnetic fields
produced by several models of hair dryers, electric razors, and massage units and foundthat partial body exposure could exceed 0.5 mT at rates of change exceeding 10 T/s.
Massage units resulted in the highest average peak magnetic flux densities (0.35 mT ±0.15); electric razors were in the middle range (0.19 mT ± 0.17), and hair dyers in thelowest (0.03 mT ± 0.004).
There was no association between ever using one of these appliances and the risk forleukemia (unadjusted OR, 0.71; 95% CI, 0.41Ð1.2 for ever vs. never used). When theappliances were considered individually, massage units had been used more frequently bycases (3.0; 1.4Ð6.3, based on 24 exposed cases), while hair dryers had been used more
frequently by controls (0.38; 0.22Ð0.66). There was a nonsignificantly increased risk forleukemia among ever users of electric razors (1.3; 0.80-2.2). A positive trend (p < 0.05)
was seen for reported daily of use of electric razors; the unadjusted odds ratios were 0.70
(0.32Ð1.5) for use up to 2.5 min/d, 1.6 (0.76Ð3.25) for use 2.5Ð7.5 min/d, and 2.4 (1.1Ð
5.5) for use > 7.5 min/d in comparison with never use. No pattern of risk with length ofuse was seen for massage units [the numbers of exposed cases and controls were quite
small for this analysis] or hair dryers. The authors noted that information on use may
have been limited, since the majority of leukemia patients in the study had died before theinterview and information on reported duration of use was obtained from proxy
respondents.
Data from this study were further analyzed by Sussman et al. (Sussman et al., 1996) toassess the likelihood that the observed association with duration of use of electric razors
was due to a bias related to the fact that proxy respondents had been used only for cases

136and not for controls. Of 110 patients for whom information on duration of use of electricrazors was available, only 24 had provided this information themselves. On the basis of
this small number of cases, there was no association between ever use of electric razors
and the risk for leukemia (OR, 0.7; 95% CI, 0.3-1.7). There was also no association with
reported daily length of use: the odds ratios were 0.6 (0.2Ð2.3; three exposed cases) for
use up to 2.5 min/d, 0.6 (0.1Ð2.6; two exposed cases) for 2.5Ð7.5 min/d, and 0.9 (0.2Ð4.7;
two exposed cases) for > 7.5 min/d in comparison with never use. When analyses wererestricted to proxy respondents, however, the odds ratio for ever use was 1.6 (0.9-2.8),
and a significant trend with daily duration of use was observed. The authors suggested
that the association reported by Lovely et al. was therefore an artifact due to proxy
response. [The number of patients for whom information was obtained directly is too
small to rule out similar odds ratios].
A population-based caseÐcontrol study was carried out in Sweden by Feychting andAhlbom (Feychting & Ahlbom, 1992; Feychting & Ahlbom, 1994) to assess the impact
on the risk for leukemia of exposure to magnetic fields from high-voltage transmission
lines. The methods used were similar to those used in their caseÐcontrol study ofchildhood leukemia (Feychting & Ahlbom, 1993). The study base consisted of all persons
aged 16 years or more who had lived at least one year on a property located within 300 mof any of the 220 and 400 kV transmission lines in Sweden during the period 1960Ð85.
These individuals were identified from maps of the Central Board for Real Estate Data toidentify properties at least partially located on the corridor and the Population Registry
to identify the approximately 400 000 residents of these properties. The caseÐcontrol
study was nested in this study base. Cases of leukemia were identified by record linkage
with the Swedish Cancer Registry for the period 1960Ð85. For each case, two controls
were selected at random from the cohort among those who had lived in the power-line
corridor at least one year before the reference date and who lived near the same power line
as the case. The controls were matched to the case on age (within five years), gender,
parish of residence, and year of the diagnosis.
A detailed description of the exposure assessment method is given in section 2. It
included spot measurements and calculations of fields generated by the power line. For
each case and control, the historical field was then calculated from the average load for the
relevant years preceding the diagnosis. Calculations were made for the year of diagnosis,
or closest to diagnosis if the subject had moved, and for 1, 5, and 10 years before
diagnosis. These estimated levels were used to assign an average magnetic field exposurein microtesla for each year the subject had lived in the power corridor over the previous
15 years. Information on the following confounding factors was available: age, gender,
year of diagnosis, residence in the county of Stockholm or not, type of housing (singlefamily vs. apartment), and socioeconomic status.
A total of 325 cases of leukemia (72 AML, 57 CML, 14 ALL, and 132 CLL) and 1091
controls were included in the analysis. There was no association between the risk for all
leukemia and calculated exposure to magnetic fields closest to the time of diagnosis. For
AML and CML, however, non-significantly increased odds ratios were seen for fields of137

³ 0.2 mT in comparison with £ 0.09 mT (AML: OR, 1.7; 95% CI, 0.8Ð3.5; based on nine
exposed cases; CML: 1.7; 0.7-3.8; based on seven exposed cases). For analyses based on
calculated cumulative exposure during the 15 years preceding the diagnosis, the odds
ratios for all leukemia were 1.0 (0.6Ð1.8) for cumulative exposures of 1.0Ð1.9 mT-years,
1.5 (1.0Ð2.4) for ³ 2.0 mT-years, and 1.5 (0.9Ð2.6) for ³ 3.0 mT-years, in comparison
with £ 0.99 mT-years. Elevated odds ratios were seen at exposure ³ 2.0 mT-years forboth AML (2.3; 1.0Ð4.6) and CML (2.1; 0.9Ð4.7). Although these results were notadjusted for age or socioeconomic status, the authors reported that they were not greatlychanged when adjustment was carried out. The authors also presented the results ofmatched analyses, which were similar to those of the unmatched analyses. The results ofanalyses based on spot measurements yielded odds ratios close to unity for all categories
of exposure and leukemia subtypes, except for CML in the ³ 0.2 mT category (1.5; 0.7Ð
3.2). The authors commented on the small number of cases, which prevented further
analyses of duration of exposure, and on the lack of information on exposure to EMF
from other sources, particularly occupational. [It is difficult to estimate exposures over along period of follow-up.]
In a follow-up to this study, Feychting et al. (Feychting et al., 1997) obtained information
on occupation from the censuses performed by Statistics Sweden every fifth year.
Exposure was assessed from the occupation held in the year prior to the reference date
(date of diagnosis for the cases) and a JEM developed from workday measurements in alarge number of jobs held by a sample of the general male population within theframework of an occupational caseÐcontrol study (see section 4.2.1.2). No information
was available on the occupations of 43% of the women.
No association was seen between the risk for all leukemia and calculated residential
exposure to magnetic fields after exclusion of subjects who were not exposed residentially
but who were exposed to ³ 0.13 mT occupationally. Again, however, elevated odds ratios
were seen for AML (OR, 2.4; 95% CI, 0.9Ð5.7) and CML (2.1; 0.8Ð5.5) among patientsin the highest exposure category (³ 0.2 mT) compared with the lowest (< 0.1 mT). Whenthe analyses were restricted to people who had only residential exposure in the highest
category (compared with ÔunexposedÕ subjects with < 0.1 mT residential and < 0.13 mT
occupational exposure), the odds ratios for AML and CML were no longer elevated(AML: 1.3; 0.4Ð5.0; based on three exposed cases; CML: 0.5; 0.1Ð3.9), although the verysmall number of cases prevents any interpretation of these results. The odds ratios forpatients who had both high occupational and high residential exposure were much higher
than those who had either (6.3; 1.5Ð27 for AML and CML based on three exposed casesof each subtype). [The limitations of the previous study apply here as well. This study isthe first to combine both residential and occupational exposures (see section 4.2.1 formore discussion). The validity of extrapolating occupational information, particularly for
women, is questionable.]
In a very large cohort study in Finland, described in detail in section 4.2.2.1), Verkasalo(Verkasalo, 1996) considered the risk for leukemia associated with calculated exposure tomagnetic fields from transmission lines. These data were analyzed in more detail in caseÐ

138

control analyses [mistakenly referred to as caseÐcohort analyses]. A total of 196 cases ofleukemia were included, with 60 of AML, 12 of ALL, 30 of CML, 73 of CLL, and 21 ofother or unknown subtype. For each case, 10 controls were selected from the cohort andmatched on gender, age at diagnosis (within one year), and whether they were alive in theyear of diagnosis of the case. The statistical analyses were based on conditional logistic
regression, adjusted for type of municipality. Several exposure measures were used:cumulative exposure and exposure 0Ð4, 5Ð9, and ³ 10 years before diagnosis; annual
average magnetic fields 1Ð20 years before diagnosis; highest annual average magnetic field
and in windows of 0Ð4, 5Ð9, and ³ 10 years before diagnosis; and age at first exposure toannual average magnetic field greater than a specified level and duration and time since
exposure to annual averages above that level.
No association was seen between the risk for all leukemia or for specific subtypes andcumulative exposure or highest annual average exposure. Adjustment for type of housing
or for occupational exposure (none vs. possible or probable, based on expert judgment)
did not affect the results. For CLL, a significant increase was seen with dichotomized
cumulative exposures of ³ 0.2 mT-years and ³ 0.4 mT-years for ³ 10 years before
diagnosis and for durations of exposure to fields of ³ 0.10 mT for ³ 12 years, based on
three exposed cases. No association was seen for other types of leukemia. [Thelimitations noted for the study of Verkasalo et al. apply here as well; however, type ofresidence was examined in this analysis.] (Verkasalo, 1996)
In a caseÐcontrol study described in detail in section 4.2.1.2, Li et al. (Li et al., 1997)
studied 1135 histologically confirmed incident cases of leukemia in northern Taiwan
which were identified from the National Cancer Registry between 1987 and 1992.
Controls were chosen among people with cancers other than those potentially related to
exposure to magnetic fields. Eleven caseÐcontrol pairs were excluded after verification of
hospital records and a further 416 because one of the members of the pair resided in oneof the 14 districts for which maps were not availability and therefore exposure could not
be assessed. The addresses of the remaining cases and controls were plotted on detailed
maps with information on utility routes; distance to the nearest transmission line wasthen estimated to within 10 m. Average and maximum residential magnetic fields wereassessed on the basis of distance from the lines and information on distance between
wires, height of wires above the ground, annual and maximum loads on the lines in 1987Ð
92, current phase, and geographical resistivity of earth. The calculated magnetic fields
were validated by direct 30Ð40-min indoor measurements made at low-power conditionsin 407 residences. With results grouped in three categories (< 0.1, 0.1Ð0.2, > 0.2 mT), theagreement (k) between measured and calculated fields was 0.64 (95% CI, 0.5Ð0.78),
which increased to 0.82 (0.79Ð0.86) when analyses used cut off points 0.5-1 mT and
were restricted to houses in which both the measured and the calculated fields were > 0.2
mT. Limited information was available on potential confounders because of restrictions on
interviews for the study.
The odds ratios were increased for patients in the middle and highest categories ofcalculated exposure to magnetic fields in the year of diagnosis: 1.3 (0.8Ð1.9) for 0.1Ð0.2
139mT and 1.4 (1.0Ð1.9) for > 0.2 mT, compared with < 0.1 mT. In analyses by leukemia
subtype, the odds ratios varied between 0.8 and 2.8. [The numbers of exposed cases bysubtype were too small for these results to be interpreted; calculations of magnetic field
were limited to the year of diagnosis because previous addresses were not available (seesection 2 for comments on the exposure assessment in this study). Only limited
information on confounders was available. Although the authors excluded cancer types
thought to be potentially related to exposure to EMF, use of cancer cases as controls is
still a concern.]
4.2.2.3 Breast cancer
In a caseÐcontrol study in western New York, USA, Vena et al. (Vena et al., 1991)
studied the role of electric blankets in postmenopausal breast cancer. The cases were
newly diagnosed, histologically confirmed, in women aged 41Ð85 and admitted tohospitals in the study area (Niagara and Erie counties) between 1987 and 1989. The
controls were randomly selected from the community from the driversÕ license rosters of
the New York State Motor Vehicle Bureau for women under 65 and from the rosters ofthe Health Care Financing Administration for older women, and matched on age. The
participation rate was low: 56% among cases (permission was denied by the physician
for 28%; of the remaining 72%, 18% refused to participate, and 4% were too ill to beinterviewed) and 46% among controls. Detailed home interviews were carried out; thequestionnaire included questions about electric blanket use in the previous 10 years, thefrequency of use by season, and the mode of use. Information was obtained for 382 cases
and 439 controls.
The odds ratio for breast cancer with use of electric blankets was 0.89 when adjusted forage and education and 1.0 after further adjustment for risk factors for postmenopausal
breast cancer: body mass index, age at first pregnancy, number of pregnancies, age at
menarche, family history of breast cancer, and history of benign breast disease. There wasno trend in odds ratio with increasing years or frequency of use. In the analysis of thegeneral mode of use of the electric blankets, a slightly increased risk was found for women
who reported using electric blankets continuously throughout the night compared withnever users (OR adjusted for all risk factors, 1.5; 95% CI, 0.96Ð2.2). Further analyses
showed a slightly increased risk in the heaviest users (only 8% of cases and 6% of
controls), i.e. those who had used electric blankets continuously throughout the night,
daily during the season over the previous 10 years (1.4; 0.77Ð2.4). The authors concluded
that there was no association between use of electric blankets and risk forpostmenopausal breast cancer, although the increased risk among heaviest users should be
investigated further. [Interpretation of this study is complicated by the very low
response rates, particularly among controls, the lack of information on the type and age ofthe electric blankets, and the absence of information on other source of exposure to ELF
EMF.]
In a complementary study, Vena et al. (Vena et al., 1994) also studied the role of electricblankets in women aged 40 or more with premenopausal breast cancer diagnosed between
140

1986 and 1991. Women were considered premenopausal if they were still menstruating or
not menstruating due to medical intervention yet retained one ovary and were under theage of 50. Controls were drawn from the driversÕ license rosters and frequency matchedon age to the cases. The response rates were again low: 66% among cases (72% of
thenon-interviewed cases were due to denial of permission to interview by physician) and
62% among controls. Interviews were carried out at home with a lengthy questionnaire
including questions about electric blanket use. The odds ratio for use of an electric blanket
at any time in the previous 10 years was 1.2 (95% CI, 0.83Ð1.7) after adjustment for age,education, and other risk factors, as in the study of postmenopausal breast cancer. There
was no trend in risk with number of years of use. A slight increase in risk was observed
among women reporting daily use during a season in comparison with never users (1.3;
0.86Ð1.9) and among those who reported using electric blankets continuously throughout
the night (1.4; 0.94-2.2). The odds ratio among the heaviest users (continuously
throughout the night, daily during the season over the previous 10 years) was 1.1 (0.59Ð
2.1). [The interpretation of this study is complicated by the low response rates, the lackof information on the type and age of the electric blankets, and the absence of informationon other sources of exposure to ELF EMF.]
In a letter to the Editor, Stevens (Stevens, 1995) commented on the results of these twostudies. He suggested that they should be combined, thus increasing their statisticalpower and the likelihood that the small increases in risk noted for continuous use
throughout the night in both studies would reach statistical significance. He further
commented on the possible mechanisms by which EMF could affect the risk for breast
cancer, suggesting that if they reversed the oncostatic effect of melatonin at the site ofaction in breast tissue they would be more important for estrogen receptor-positive
tumors. Vena et al. (Vena et al., 1995) responded that pre- and postmenopausal tumors
had been separated because of their different etiologies. The a priori hypothesis of thesestudies was that EMF differentially affect premenopausal and postmenopausal tumors on
the basis of StevensÕ (Stevens, 1987) hypothesis that they affect risk through the pinealÐ
melatonin pathway, which is more relevant for premenopausal women. Vena et al. (Venaet al., 1995) nevertheless presented the results of combined analyses. The odds ratio was
1.1 (95% CI, 0.85Ð1.4) for ever use, 1.2 (0.90Ð1.5) for daily use, and 1.5 (1.1Ð1.9) for
continuous use throughout the night. Analysis by duration of continuous use throughout
the night showed no association. The authors cautioned about over interpretation of theseresults because of the limited capacity of the study to address such issues and theretrospective nature of the exposure assessment.
A caseÐcontrol study of several adult cancers and residential exposure to 60 Hz magnetic
fields from transmission lines was carried out in northern Taiwan by Li et al. (Li et al.,1997) (see section 4.2.2.2). A total of 2407 histologically confirmed incident cases ofbreast cancer reported between 1990 and 1992 were identified from the National Cancer
Registry. The same number of controls were drawn from the registry among women withcancer, excluding leukemia, brain cancer, breast cancer, cancers of the hematopoietic andreticuloendothelial system, skin, ovary, fallopian tube, and broad ligament. They werematched one-to-one to cases on date of birth (within five years) and date of diagnosis

141

(within six months). Twenty-two caseÐcontrol pairs were excluded after verification of
hospital records and a further 823 because one of the members of the pair resided in oneof the 14 districts for which maps were not available, leaving 1562 caseÐcontrol pairs foranalysis. An index of urbanization was derived on the basis of local population density,age, mobility, economic activity, family income, educational level, and sanitation facilities.
There was no association with calculated exposure to magnetic fields in the year of
diagnosis (OR, 1.1 for exposure to > 0.2 or 0.1Ð0.2 mT in comparison with < 0.1 mT).
[See comments on the limitations of this study in section 4.2.2.2.]
In the Finnish cohort study described in section 4.2.2.1, Verkasalo et al. (Verkasalo et al.,1996) also examined the risk for breast cancer in relation to calculated residential exposure
to magnetic fields. Overall, 1229 cases of breast cancer were found among women in thecohort. No association was seen with risk, with SIRs of 1.1 (0.98Ð1.1) for exposure to <0.2 mT, 1.1 (0.88Ð1.3) for exposure to 0.20Ð0.39 mT, 0.89 (0.71Ð1.1) for exposure to0.40Ð0.99 mT, 1.2 (0.89-1.6) for exposure to 1.00-1.99 mT, and 0.75 (0.48-1.1) for
exposure to ³ 2.00 mT. [See comments on the limitations of this study in section 4.2.2.2.]
In their population-based nested caseÐcontrol study described in detail above (section
4.2.2.2), Feychting et al. (Feychting et al., I998) also considered the effect of magnetic
fields from high-voltage transmission lines on the risk for breast cancer, using 699 cases inwomen and nine in men, identified from the Swedish Cancer Registry. Controls wereselected at random from the study base among people who had lived in the power-line
corridor for at least one year before the reference date and who lived near the same powerline as the case. The controls were matched to the cases on age (within five years), gender,
and parish of residence in the year of the diagnosis. Matching was one-to-one for female
breast cancer cases and one-to-eight for male breast cancer cases. A detailed description of
the method of exposure assessment is given in section 4.3.1). Information on the estrogenreceptor status of the tumor was obtained from medical records and was available for only
82 of the 699 cases.
There was no association between the risk for breast cancer in women and calculated
exposure to magnetic fields closest in time to the diagnosis (OR, 1.0; 95% CI, 0.7Ð1.5 for³ 0.2 mT compared with < 0.1 mT). A nonsignificantly elevated risk was observed among
women with cumulative exposures ³ 3.0 mT-years in the six years immediately preceding
diagnosis (1.6; 0.8Ð3.2). A nonsignificant increase was also observed among women aged
< 50 (1.8; 0.7Ð4.3) (³0.2 mT vs. <0.1 mT) and among women who were estrogen
receptor-positive (1.6; 0.6-4.1) (³ 0.1 mT vs. <0.1 mT), with an exposure cut-point of 0.1
mT. Among estrogen receptor-positive women under 50, the odds ratio was 7.4 (1.0Ð180), based on six exposed cases and one exposed control. In males, a nonsignificant
increase in risk was observed (2.1; 0.3Ð14) for calculated exposure to magnetic fields ³ 0.2
mT closest to the time of diagnosis. [In addition to the limitations described in section
4.2.2.1, no information was available on important risk factors for breast cancer, since allof the data were obtained from registry and hospital files. Information on estrogenreceptor status, moreover, was available for only a limited number of cases.]142

4.2.2.4 Tumors of the central nervous system
In their population-based nested caseÐcontrol study, described in detail in section 4.2.2.2,
Feychting and Ahlbom (Feychting & Ahlbom, 1992; Feychting & Ahlbom, 1994) also
considered the effect of exposure to magnetic fields from high-voltage power lines on therisk for tumors of the CNS. Cases were identified from the Swedish Cancer Registry. For
each case, two controls were selected at random from the cohort among people who had
lived in the power-line corridor for at least one year before the reference date and who
lived near the same power line as the case. The controls were matched to the case on age(within five years), gender, and parish of residence in the year of the diagnosis. A detailed
description of the exposure assessment method is given in section 4.3.1. Sixty-six cases ofglioma and 157 of glioblastoma were included in the analysis. There was no association
with any measure of exposure to ELF EMF. The authors noted the small number ofcases, which prevented further analyses by duration of exposure, and on the lack of
information on exposure from other sources, particularly occupational.
In a follow-up to this study, Feychting et al. (Feychting et al., 1997) obtained information
on occupation from the censuses performed by Statistics Sweden as described in detail in
section 4.2.2.2. No association was seen between the risk for tumors of the CNS andcalculated residential exposure to magnetic fields after excluding subjects who were notexposed residentially but were exposed to ³ 0.13 mT occupationally; and no association
was seen when the analyses were restricted to people who had only residential exposure(OR, 0.7; 95% CI, 0.3Ð1.7; seven exposed cases).
In a caseÐcontrol study described in detail in section 4.2.2.2, Li et al. (Li et al., 1997)
studied 705 histologically confirmed incident cases of brain tumor (ICD-O 191) innorthern Taiwan identified from the National Cancer Registry between 1987 and 1992.
Controls were chosen among people with cancer, excluding cancer types potentiallyrelated to exposure to magnetic fields. Nine caseÐcontrol pairs were excluded after
verification of hospital records and a further 241 because one of the members of the pairresided in one of the 14 districts for which maps were not available. No association wasseen with calculated exposure to magnetic fields in the year of diagnosis (OR, 0.9; 95%
CI, 0.5Ð1.7 for exposure to 0.1Ð0.2 mT; 1.1; 0.8Ð1.6 for exposure to > 0.2 mT, comparedwith < 0.1 mT). In analyses by tumor subtype, the odds ratios varied between 0.6 and2.8. [See comments in section 4.4.2 on the limitations of this study.]
In the study of Verkasalo et al. (Verkasalo et al., 1996) described in section 4.2.2.1, therisk for gliomas and meningiomas was also analyzed. Over the study period, 301 cases oftumors of the CNS were observed. The incidence was not different from that of theFinnish population, and no association with calculated cumulative exposure to magnetic
fields was observed. The SIRs with respect to the general population were 0.94 (95% CI,
0.8Ð1.1, 238 cases) for < 0.2 mT, 1.1 (0.77-1.5; 35 cases) for 0.2Ð0.39 mT, 0.64 (0.37Ð1.0,
16 cases) for 0.4Ð0.99 mT, 0.55 (0.18-1.3, five cases) for 1.00Ð1.99 mT, and 0.92 (0.37Ð
1.9, seven cases) for ³ 2.00 mT. Although separate analyses were carried out for gliomas
and meningiomas, and the authors reported only that the results were consistent with143

those for cancer of the nervous system as a whole. [See comments on the limitations of
this study in section 4.4.2.]
4.2.2.5 Summary
Leukemia
The risk for leukemia associated with use of electrical appliances was considered in twocaseÐcontrol studies in the USA. Because of limitations in design and exposure
assessment, neither study provides information for evaluation of an association.
Magnetic fields were calculated on the basis of distance from transmission lines, historicalloads, and line configuration in three caseÐcontrol studies, from Finland, Sweden, andTaiwan. No information on other sources of residential exposure was available in any ofthese studies. In the Swedish study, no association was observed between the risk for any
leukemia and exposure to magnetic fields, either for calculated fields closest to the time ofdiagnosis or for cumulative exposure over 15 years. A slight increase in risk for acute
myelogenous leukemia (AML) and chronic myelogenous leukemia (CML), but not forchronic lymphocytic leukemia (CLL), was seen with calculated fields. The increase for
AML disappeared when the analyses were restricted to subjects with no or very low
occupational exposure, based, however, on a very small number of cases. The risk ofpeople with both high residential and high occupational exposures was increased. In the
Finnish study, no association was seen between either all leukemias or specific subtypes
and highest annual or cumulative exposure to magnetic fields. A significant increase in therisk for CLL (but not for other leukemia subtypes) was seen in association withcumulative exposure to ³ 0.20 or ³ 0.40 mT-years for 10 years or more before diagnosis.
In the study in Taiwan, a small increase in risk for leukemia was seen in association with
exposure to 0.1Ð0.2 or > 0.2 mT of magnetic fields during the year of diagnosis.
In one study in the USA, in which wire coding was used to estimate exposure, noassociation was seen with the risk for leukemia.
Direct measures of magnetic fields in the homes of the study subjects were used in two
studies. In the US study, a small, nonsignificant increase was seen in association withmean exposure but not with weighted mean exposure; measurements were made,moreover, in only a fraction of homes. In the Swedish study, no association was seen
between spot measurements of exposure to EMF and the risk for leukemia.
Breast cancer
The association between use of electric blankets and the risk for breast cancer wasconsidered in a large study in the USA of pre- and postmenopausal women. A modest,
nonsignificant increase in risk was seen in both groups, which reached statistical144

significance when the two were combined; however, there was no evidence for an
association with duration of exposure.
Calculated fields were used in three studies, in Finland, Sweden, and Taiwan. In the
Finnish and Taiwanese studies, no association was seen between exposure to magnetic
fields and the risk for breast cancer. In the Swedish study, although no association wasseen overall, nonsignificant increases were observed in the highest cumulative exposure
category among young women, particularly those who were estrogen receptor-positive(based on very small numbers).
The Swedish study also considered the risk for male breast cancer. Although the numberof cases was extremely small, a two-fold, nonsignificant increase was observed.
Cancers of the central nervous system
The association between calculated exposure to extremely low frequency magnetic fields
and the risk for cancer of the brain was considered in one study in Taiwan, and theassociation with cancers of the central nervous system in general was assessed in one
study in Finland and one in Sweden. No association was seen in any of these studies.
Considerations
None of the associations between cancer and residential exposure to magnetic fields wasby itself convincingly positive; however, the quality of exposure assessment is a serious
limitation in all these studies. Omission from consideration of occupational exposure is
likely to lead to substantial misclassification. Studies that simultaneously address both
exposures are needed to address this limitation.
Evaluation
There is inadequate evidence that residential exposure to extremely low frequency
magnetic fields is carcinogenic to adults.
[This conclusion was supported by 24 Working Group members; there was one vote forÔlackÕ of evidence, 1 abstention, and 3 absent.]145

Table 4.10 Epidemiological studies of exposure to EMF and cancer at all sites
Reference; type ofstudy; country

Cohort description

Exposure classification

All cancers
No. ofcases

Comments

RR for casesa(95% CI)(Tynes et al., 1992);
cohort,Norway37945 male workers (age 20-70)
followed 1961-85 in the Cancer
Registry of Norway

12 electrical occupations3806

1.1 (1.0-1.1)

SIR
adjusted for age(Sahl et al., 1993);
cohort,California (USA)Southern California Edison Company
utility workers, mortality from 196088, 36221 workers in cohort

Electrical occupations in utility261

1.1 (0.92-1.3)

Internal cohort RR, adjusted forage(ThŽriault et al., 1994);
case-control,
Canada and France

Male utility workers in 3 large
companies: base population of
223292; 4151 cancer cases; 6106
controls. Cumulative exposure fromjob history and magnetic field JEM

Cumulative magnetic fields³ median ³ 3.1 mT - year
³ 90th percentile ³ 16 mT - year

2158
443

1.0 (0.91-1.1)
1.0 (0.86-1.2)(Savitz & Loomis, 1995);
cohort,USA

138905 men employed for > 6 months
in 5 electric utilities were followed
for mortality from 1950-86

Cumulative magnetic fields
highest category, > 4.3 mT-year
exposure response, RR/mT-year

505
4833

highest category > 0.7 mT-year
exposure response, RR/mT-year

746
4833

Total exposure:
1.2 (1.1-1.4)
1.0 (1.0-1.0)
Past 2-10 years:
1.1 (1.0-1.3)
1.1 (1.0-1.2)

Cumulative electric fields
highest category > 414 V/m-year

195

0.89 (0.74-1.1)

986

0.89 (0.75-1.0)(GuŽnel et al., 1996)
case-control,
FranceEDF cohort of (ThŽriault et al.,1994);
170000 men in cohort with 1915
cases of cancer matched to 7568
controls

exposure response, OR per
500 V/m-year

PCB, polychlorinated biphenylsa
All RRs are normalized to the null hypothesis = 1.0

146

OR, adjusted for social classfrom case-control analysis withmagnetic field JEM

Internal cohort RR, adjusted forage, year, race, class, work
status, PCBs, and solvent
exposuresOR, adjusted for social classTable 4.11 Epidemiological studies of leukemia with full-shift measurements of magnetic fields
Reference, typeof study,
country(Floderus et al.,1993)
case-control,
Sweden(Matanoski etal., 1993);
case-control,
USA(Sahl et al.,1993);
case-control,
California(USA)

Study population

Exposure assessment
methodMagnetic field exposures
category/magnitude/exposure
metriccategory

Risk estimates

No. ofcases

OR(95% CI)

Exposures from JEMs for
TWA and 3 other metrics
in job held the longest in
the 10 years before
diagnosis. JEMs for 169
job categories based on
1015 magnetic fieldmeasurements taken at
subjectÕs workplace andjob (or surrogate)

TWA
2nd quartile
0.16-0.19 mT
3rd quartile
0.20-0.28 mT
4th quartile³ 0.29 mT³ 90th percentile ³ 0.41 mT

AML
24
18
23
8

1.0 (0.5-1.8)
0.8 (0.4-1.6)
1.0 (0.6-1.9)
0.9 (0.4-2.1)

2nd quartile
0.16-0.19 mT
3rd quartile
0.20-0.28 mT
4th quartile³ 0.29 mT³ 90th percentile ³ 0.41 mT

CLL
17
33
41
22

1.1 (0.5-2.3)
2.2 (1.1-4.3)
3.0 (1.6-5.8)
3.7 (1.8-7.7)

Cohort of white males who
were employed by AT&T or
pensioned during 1975-80.
Cases were deaths fromleukemia (except CLL) whose
job histories were obtained.
For each case, 3 controls
without leukemia werematched on gender, date ofbirth, date of hire, work
status, and local telephonecompany

Cumulative exposures fromjob histories and JEMs for
TWA and peaks frommagnetic fieldmeasurements on 204
workers. Different
exposures noted for central
office technicians from oldrelay switches and newsolid-state switches

Cumulative exposure
TWA ³ median

36221 southern California
Edison Company utility
workers. Cancer mortality
determined for 1960-88. 10
controls per case matched ondate of birth, gender, and race

Exposure based on job
history and JEMs for TWA
and 4 other metrics from776 person-days ofmagnetic fieldmeasurements

All male workers in a large
region of mid-Sweden who
were 20-64 year old in 1980.
250 leukemia cases fromcancer registry, 1121 controls
matched on age from census
records

test for trend

Leukemias (except CLL)35
2.5 (0.7-8.6)
p = 0.21-0.35

Peak ³ median (w/ all switches)
test for trend35

1.6 (0.5-4.9)
p = 0.12-0.28

Peak ³ median (w/ oldswitches) test for trend35

2.6 (0.8-8.6)
p=0.04-0.06

Total cumulative exposure
TWA 25 mT-year
Median 3.5 mT-year

Leukemia13
1.1 (0.80-1.5)
10
1.0 (0.75-1.4)

2-12 years before deathMedian 3.5 mT-year

--

147

0.63 (0.32-1.2)

Comments

OR with highest EMF
exposure as high as 4.7(2.2-9.7) after adjusting forionizing radiation,benzene, and solvents. Nochange after adjusting forsmoking, or pesticides

3 tests for trend (onetailed) done over exposure
quartiles measured byquartile ordinals, means,
and log of means

OR increase per defined
exposure magnitude
calculated by conditional
logistic regression

Table 4.11 (continued)
Reference, typeof study,
country

Study population

Exposure assessment
methodMagnetic field exposures
category/magnitude/exposure
metriccategory

Risk estimates

No. ofcases(London et al.,1994);
case-control,
Los Angeles
County (USA)(ThŽriault et al.,1994);
case-control,
Canada andFrance(Savitz &Loomis, 1995);
case-control,USA

Men age 20-64 years withcancer diagnosis andoccupation in LA County
tumor registry. 2355
leukemia cases (121 among
electrical workers) comparedwith all other cancers withthe exception of CNS tumors

Cohorts of male utility
workers in 3 large companies:
base population of 223292;
4151 cancer cases determinedfrom cancer registries,
company records, etc. 6106
controls matched to cases byutility and date of birth

138,905 men employed for > 6
months in 5 electric utilities
followed for mortality in
1950-86

Exposure based on job
title reported on hospitalrecords and on JEM for the
TWA and 2 other metrics
derived from full-shift
magnetic fieldmeasurements on 278
electrical workers and 105
non-electrical workers.
Current measurements
adjusted based on
estimates of time spent on
tasks 15-20 years
previously
Cumulative exposure
based on job history plus
JEMs from 2066
workweek EMF
measurements (50/60 Hz
magnetic fields, electricfields and pulsed EMF).
JEMs for TWAs adjusted
for past practices
constructed for 260 job
titlesTWA
highest category ³ 0.81 m T
exposure-response OR/m T

Cumulative magnetic field
exposure estimated fromjob history plus JEM
based on 2842 magnetic
field measurements

Cumulative TWA exposure
highest category ³ 4.3 mT-year
exposure-response RR/mT-year

highest category ³ 0.81 m T
exposure-response OR per m T
highest category ³ 0.81 m T
exposure-response OR per m T
highest category ³ 0.81 m T
exposure-response OR/m T
Cumulative TWA exposure³ median³ 3.1 mT-year³ 90th percentile ³ 16 mT-year

OR for trend³ median³ 3.1 mT-year³ 90th percentile ³ 16 mT-year

OR for trend

highest category ³ 2.0 mT-year
exposure-response RR/mT-year

148

Comments

OR(95% CI)

Leukemia30
1.4 (1.0-2.0)2355
1.2 (1.0-1.5)
ANLL
10
1.3 (0.7-2.3)853
1.2 (0.8-1.6)
CLL4
0.8 (0.4-1.5)534
1.0 (0.6-1.5)
CML
10
2.3 (1.4-3.8)487
1.6 (1.2-2.0)

No confounding detectedwith chlorinatedhydrocarbon solvents,
ionizing radiation, benzene
or gasoline exhaust

AML
26
4
47
CLL
24
6
41

Trend calculated over 4
exposure groups. No
significant confounding
detected for benzene,
gasoline, paint, solvents, orionizing radiation

AML
5
49
CLL
5
34

3.2 (1.2-8.3)
2.7 (0.5-15)
1.5 (0.31-7.6)
1.5 (0.5-4.4)
1.7 (0.44-6.7)
1.4 (0.44-4.1)

1.6 (0.51-5.1)
1.0 (0.93-1.2)
0.55 (0.17-1.8)
0.96 (0.78-1.1)

Risks adjusted for PCB andsolvent exposures. Ionizing
radiation exposure
insignificant

Table 4.11 (continued)
Reference,
type of study,
country

Study population

Exposure assessment
methodMagnetic field exposures
category/magnitude/exposure metriccategory

Risk estimates

No. ofcases(Feychting etal., 1997);
case-control,
Sweden(Miller et al.,1996);
case-control,
Ontario(Canada)(Johansen &Olsen, 1998);
cohort,Denmark

Combined occupationaland residential exposure
assessment:
approximately 400000
subjects living within
300 m of transmission
lines; 325 leukemia
cases

Ontario Hydro cohort of(ThŽriault et al., 1994),
1484 cancer cases, 50
leukemia

Employees of 99 Danish
utility companies,
32 006 total

OR(95% CI)

Residential magnetic
field exposure from aphysical model of
distance fromtransmission line andhistorical reconstructionof power loads.
Occupational exposurefor job on census before
diagnosis was estimatedfrom JEM developed frommeasurements of Floderus(Floderus et al., 1993)

TWA
Occupational
0.13-0.19 mT
exposures only ³ 0.2 mTCumulative exposuresestimated from job
history in company
records combined with
JEMs for EMF derived
from Ontario Hydro
measurements taken by(ThŽriault et al., 1994).

Cumulative TWA exposure
magnetic fields 3.2-7 mT-years³ 7.1 mT-years
electric fields
172-344 V/m-years
magnetic fields 3.2-7 mT-years³ 7.1 mT-years
electric fields³ 345 V/m-years
magnetic fields 3.2-7 mT-years³ 7.1 mT-years

Leukemia
16
1.7 (0.58-4.8)
24
1.6 (0.47-5.2)

Magnetic field exposures
for subjectÕs first job
taken from a JEM basedon expert judgment and24-h measurements on
129 workers at 6
companies. JEM has 5
exposure categories(including backgroundand unknown) for 25 job
titles and 19 sites

TWA
low exposure
mediumhigh

Leukemia, men
16
1.0 (NS)16
0.9 (NS)
12
1.1(NS)

Occupational exposures ³ 0.2 m T
Residential< 0.2 mT
exposures³ 0.2 mT

AML
26
14

1.7 (0.9-3.2)
1.8 (0.9-3.8)
1.5 (0.6-3.6)
6.3 (1.5-26)

Occupational
0.13-0.19 mT
exposures only ³ 0.2 mT

11
3
CLL
37
28

Occupational exposures ³ 0.2 m T
Residential< 0.2 mT
exposures³ 0.2 mT

26
2

1.5 (0.8-2.7)
2.1 (0.4-10)

149

0.1-0.29 mT
0.3-0.99 mT³ 1.0 mT

Comments

CML risks also significant
with occupational +residential exposures³ 0.2 m T [OR 6.3, (1.5-27)].
Crude estimates ofconfounding from smoking
and chemical exposures did
not change results

1.2 (0.7-1.9)
1.7 (1.0-2.9)26

1.2 (0.10-15)
7.8 (1.1-58)

8
17

11 (1.5-84)
11 (1.3-97)

ORs adjusted for EMF
interactions, benzene,
herbicides, and ionizing
radiation. Without EMF
interaction, OR for highest
exposure is 3.5 (0.56-22)

Risks calculated as an SIR
adjusted for age, gender, anddate of diagnosis relative tobackgroundTable 4.11 (continued)
Reference,
type of study,
country

Study population

Exposure assessment
methodMagnetic field exposures
category/magnitude/exposure metriccategory

Risk estimates

No. ofcases(Kheifets etal., 1997a);
Meta-analysis

38 studies of leukemia
in EMF-exposed worker
populations

Indicators of EMF
exposure varied from asingle job (e.g. welding)to magnetic fieldmeasurements

Electrical occupations or high EMF
exposures (broadly defined)

OR(95% CI)AML
18 studies 1.4 (1.2-1.7)
CLL
12 studies 1.6 (1.1-2.2)

Magnetic field measurements
low exposure
50th-75th %medium75th-90th %high³ 90th %Comments

Significant heterogeneity (p< 0.05) among AML and
CLL studies with broad
definitions of EMF exposure

All leukemia (6 studies)1.2 (0.94-1.6)
1.4 (1.1-1.8)
1.3 (1.0-1.7)

OR, odds ratio; CI, confidence interval; TWA, time-weighted average; JEM, job-exposure matrix; AML, acute myelogenous leukemia; CLL, chronic lymphocytic leukemia; ANLL, acute non-lymphocytic leukemia;
PCB, polychlorinated biphenyls

150Table 4.12 Epidemiological studies of brain cancer with full-shift measurements of magnetic fields
Reference,
type ofstudy,
country

Study population

Exposure assessment
methodMagnetic field exposures
category/magnitude/ exposure
metriccategory

Risk estimates

No. ofcases

OR(95% CI)All male workers in alarge region of midSweden who were 2064 years old in 1980.
346 brain cancer cases
from cancer registry,
1121 controls matchedon age from census
records.

Exposures from JEMs for
TWA and 3 other metrics
in job held the longest in
the 10 years before
diagnosis. JEMs for 169
job categories based on
1015 magnetic fieldmeasurements taken at
subjectÕs workplace andjob (or surrogate).

TWA
2nd quartile 0.16-0.19 mT
3rd quartile 0.20-0.28 mT
4th quartile ³ 0.29 mT³ 90th percentile ³ 0.41 mT

All brain tumors59
1.0 (0.7-1.6)
72
1.5 (1.0-2.2)
74
1.4 (0.9-2.1)
24
1.2 (0.7-2.1)

2nd quartile 0.16-0.19 mT
3rd quartile 0.20-0.28 mT
4th quartile ³ 0.29 mT³ 90th percentile ³ 0.41 mT

Astrocytoma III-IV
48
1.3 (0.8-2.0)
57
1.7 (1.1-2.7)
52
5 (1.0-2.4)
14
1.1 (0.5-2.1)(Sahl et al.,1993);
casecontrol,
California(USA)36221 southern
California Edison
Company utility
workers. Cancer
mortality determinedfrom 1960-88. 10
controls per casematched on date ofbirth, gender, and racewith 32 brain cancer
cases

Exposure based on job
history and JEMs for TWA
and 4 other metrics from776 person-days ofmagnetic fieldmeasurements in thecurrent electric utility
working environment

Cumulative TWA exposure (total)
TWA 25 mT-year
Median 3.5 mT-year
2-12 years before deathMedian 3.5 mT-year

Brain cancer
40.81 (0.48-1.4)
7
0.95 (0.62-1.5)(ThŽriault
et al.,
1994)
casecontrol,
Canada andFranceCohorts of male utility
workers in 3 large
companies: base
population of 223292;
4151 cancer cases (250brain cancer)
determined from cancer
registries, company
records, etc. 6106
controls matched tocases by utility anddate of birth

Cumulative exposure basedon job history plus JEMs
from 2066 work-week EMF
measurements (50/60 Hz
magnetic fields, electricfields and pulsed EMF).
JEMs for TWAs adjusted
for past practices
constructed for 260 job
titlesCumulative TWA exposure

Malignant brain cancer
48
1.5 (0.85-2.8)
12
2.0 (0.76-5.0)
108
1.7 (0.68-4.1)(Floderus
et al.,
1993);
casecontrol,
Sweden³ median ³ 3.1 mT-year³ 90th percentile ³ 16 mT-year

OR for trend³ median ³ 3.1 mT-year³ 90th percentile ³ 15.7 mT-year

OR for trend³ median ³ 3.1 mT-year³ 90th percentile ³ 15.7 mT-year

151

Comments

With 90th percentile of themedian magnetic fields, risk
for all brain tumors is 1.6 (1.02.6). No change significant inrisks after adjustment forbenzene, ionizing radiation,or solvent exposures

OR increase per defined
exposure magnitude
calculated by conditional
logistic regression

1.1 (0.62-2.0)

Astrocytoma
120.97 (0.34-2.8)
5
12 (1.1-140)41
9.4 (1.1-83)
Benign brain cancer
19
2.3 (0.79-6.7)
4
1.6 (0.35-7.6)

Trend calculated over 4
exposure groups.
Astrocytoma OR in highexposure group much reduced
when calculated by exact
method for small sample.

Table 4.12 (continued)
Reference,
type ofstudy,
country

Study population

Exposure assessment
methodMagnetic field exposures
category/magnitude/ exposure
metriccategory

Risk estimates

No. ofcases

OR(95% CI)(Savitz &Loomis,
1995)
Historic
cohortstudy,
USA

138905 men employedfor > 6 months in 5
electric utilities
followed for mortality
1950-86,; 144 deaths
from brain and CNS
cancers

Cumulative magnetic field
exposure estimated fromjob history plus JEM
based on 2842 magnetic
field measurements. JEM
constructed for 28
occupational categories(120 location-specificcategories) collapsed into
5 exposure groups for
TWA

Cumulative TWA exposure(total)highest category ³ 4.3 mT-year
exposure-response RR per mT-year

Brain cancer
16
2.3 (1.6-4.6)
144
1.1 (1.0-1.1)

2-10 year window
highest category ³ 0.7 mT-year
exposure-response RR per mT-year43
144(Feychting
et al.,
1997);
casecontrol,
SwedenCombined
occupational andresidential exposure
assessment.:
approximately 400000
subjects living within
300 m of transmission
lines; 223 CNS tumor
cases.

Residential magnetic field
exposure from physicalmodel of historical fields
from transmission lines.
Occupational exposure
estimated from JEM
developed by (Floderus etal., 1993)

TWA
Occupational 0.13-0.19 mT
exposures only ³ 0.2 mT

CNS tumors
79
1.2 (0.8-1.7)
43
1.2 (0.8-1.9)

Occupational exposures ³ 0.2 m T
Residential < 0.2 mT
exposures ³ 0.2 mT

40
3(Harringto
n et al.,1997);
casecontrol,
UK84018 utility workers
at the Central
Electricity Generating
Board of England andWales. 112 deaths fromprimary brain cancers
matched to 654
controls by gender anddate of birth.

Magnetic field exposure
estimated fromcomputerized job histories
and a JEM based on limited
measurements on 127
workers. Many subjects
unclassifiable because ofgaps in job records or JEM.

Cumulative TWA exposure (total)
highest category ³ 6.0 mT-year
trend OR/m T-year
0-5 year before diagnosis
highest category ³ 6.0 mT-year
trend OR/m T-year

152

Risks adjusted for PCB andsolvent exposures. Ionizing
radiation exposure
insignificant.

2.6 (1.4-4.9)
1.9 (1.3-2.8)

1.2 (0.7-1.9)
1.3 (0.3-4.8)

Primary brain cancers
27
0.97 (0.53-1.8)
94
0.92 (0.68-1.2)
11
40

Comments

0.59 (0.25-1.4)
0.78 (0.51-1.2)

Unclassifiable cases andcontrols had an OR = 2.0(CI = 1.1-4.4).
No associations with 24
potential confounders

Table 4.12 (continued)
Reference,
type ofstudy,
country

Study population

Exposure assessment
methodMagnetic field exposures
category/magnitude/ exposure
metriccategory

Risk estimates

No. ofcases(Johansen& Olsen,1998);
Retrospecti
ve cohort,Denmark

Male and female
employees of 99
Danish utility
companies, 46284
total.

Magnetic field exposures
for subjectÕs first job takenfrom a JEM based on expert
judgment and 24-h
measurements on 129
workers at 6 companies.
JEM has 5 exposure
categories (including
background and unknown)TWA
low exposure 0.1-0.29 mT
medium 0.3-0.99 mThigh ³ 1.0 mT
low exposure 0.1-0.29 mT
medium 0.3-0.99 mThigh ³ 1.0 mT

CNS tumors, men
17
13
8
women
3
0
4

OR
(95% CI)
0.9 (NS)
0.7 (NS)
0.7 (NS)
3.3 (NS)-1.4 (NS)OR, odds ratio; CI, confidence interval; TWA, time-weighted average; JEM, job-exposure matrix; PCB, polychlorinated biphenyls; CNS, central nervous system

153

Comments

Risks calculated as SIR
relative to background. For
women employed³ 10 years, the risk for low
exposure is significant (SIR =9.2 for 2 cases)

Table 4.13 Cohort studies of breast cancer and occupational exposure to EMF
Reference,
country

Cohort description

Exposure classification

Males
No. ofcases

RR (95% CI)

FemalesNo. ofcases

RR (95% CI)(Tynes et al.,1992);
Norway37 945 male workers (aged 20-70)
followed 1961-85 in the Cancer
Registry of Norway

12 electrical occupations
Electric transport work
(ISCO codes 631-632,
641, 693)

170
42.1 (1.1-3.6)
4.0 (1.1-10)NA(GuŽnel et al.,1993);
Denmark

All actively employed Danes (aged20-64) in 1970 followed 1970-87 in
the cancer registry. 172 000 men and
83 000 women in jobs exposed tomagnetic fields were compared withreference workers in unexposed jobs

Jobs with intermittent
magnetic field exposure
Jobs with continuous
exposure23

1.2 (0.77-1.8)

1526

0.96 (0.91-1.0)

2

1.5 (0.16-4.9)

55

0.88 (0.68-1.2)(Floderus et al.,1994);
SwedenMale railway workers (aged 20-64)
in the 1960 census compared withall employed men (17 150 940
person-years in 1960-69). Cancers
for 1960-69 and 1970-79 obtained
from Cancer-Environment Registry.

Engine drivers
Conductors
Railway workers (andstation masters,
dispatchers & linemen)214

8.3 (2.0-34)
2.7 (0.4-20)
4.3 (1.6-12)

NA

SIR

RR, relative risks; CI, confidence interval; NA, not applicable; SIR, standardized incidence ratio; SMR, standardized mortality ratio; PIR, proportional incidence ratio

154

Comments

SIR relative toeconomically active
subjects

SIR adjusted for age.
All cases occurred in
1960-69 follow up
period (none in the
1970s)

Table 4.14 Case-control studies of male breast cancer and occupational exposure to EMF
Reference, country

Study population

Exposure classification

Risk estimates
No. of cases(Matanoski et al.,1991);New York State(USA)

Workers < 65 employed in one statewide
telephone company during 1976-80(Demers et al.,1991);
USA

Cases were 227 male workers in all
occupations diagnosed with breast cancer
1983-87. 300 controls matched by age fromrandom-digit dialing and Medicare records.
Exposure assignment based on longest-held
job reported at interview

Line jobs
Central office technician(personal monitoring of asample of workers indicates
central office technicians
exposed to mean magnetic
field of 0.25 m T)
All electrical occupations
electric utility trades
welders
All electrical occupations
electric utility trades
welders(Loomis, 1992);
USA - 24 states(Rosenbaum et al.,1994);New York State &8 western counties
(USA)

2

RR (95% CI)
6.5 (0.79-24)

All subjects
33
1.8 (1.0-3.7)
13
6.0 (1.7-21)
4
0.8 (0.2-3.1)
Exposed before age 30
and for > 30 years until diagnosis
22
3.3 (1.5-7.3)
11
7.4 (1.6-34)
3
4.3 (0.4-43)

Death registration data from 24 states. Cases
are men over age 19 who died of breast cancer
1985-88. Occupational data obtained fromdeath record

Age at death less than 65
years
All electrical occupations
Telephone workers

31

2.2 (0.6-7.8)
9 (0.9-89)

71 male breast cancer cases reported to acancer registry 1979-88; 256 controls who
participated in a free cancer screening but
were found to be disease free. Usual
occupation reported in questionnaire,
supplemented with city directory information

Job exposure to EMF

6

0.6 (0.2-1.6)

155

Comments

SIR
Denominator is state incidence.
Cases identified from New YorkState tumor registry

Risks not altered by adjustment for
education, Jewish ethnicity,history of head injuries, exposure
to diagnostic X-rays, or BMI

OR, controls randomly selectedwith other causes of death, matchedby year of deathOR, adjusted for age, county, andoccupational heat exposures
The risks from heat exposures weresignificant (OR = 2.5, CI = 1.0-6.0)

Table 4.14 (continued)
Reference, country

Study population

Exposure classification

Risk estimates
No. of cases(Stenlund &Floderus, 1997);
SwedenAll male workers aged 20-60 in 1980, 56
males diagnosed with breast cancer(adenocarcinoma) 1985-91

TWA magnetic fields
Quartile 2, 0.16-0.19 mT
Quartile 3, 0.20-0.28 mT
Quartile 4, > 0.29 mT
90th percentile > 0.41 mT
Quartile 2, 0.16-0.19 mT
Quartile 3, 0.20-0.28 mT
Quartile 4, > 0.29 mT
90th percentile, > 0.41 mTOR, odds ratio; CI, confidence interval; SIR, standardized incidence ratio; BMI, body mass index

156

All subjects
17
17
11
4
£ 60 years
9853Comments

RR (95% CI)
1.2 (0.6-2.7)
1.3 (0.6-2.8)
0.7 (0.3-1.9)
0.7 (0.2-2.3)
2.9 (0.7-11)
2.5 (0.6-9.5)
0.9 (0.2-4.5)
1.5 (0.3-8.3)

OR adjusted for age, education,and solvent exposure
EMF exposure estimate based on
job titles identified from the work
histories, plus the JEM from themagnetic field measurements in
Floderus (Floderus et al., 1993)

Table 4.15 Case-control studies of female breast cancer and occupational studies of EMF
Reference, country

Study population

Exposure classification

Risk estimates
No. of cases(Loomis et al.,1994b);
24 US states

Women who died of breast cancer 1985-89
compared with those who died of othercauses. 27 814 cases and 110 750 controls(Cantor et al.,1995a);
24 US states

Women who died of breast cancer 1984-89(same dataset used by (Loomis et al., 1994b)with an additional year of data). 29 397 white
and 4112 black woman who dies from breast
cancer(Coogan et al.,1996);
4 US states

All female workers in state registry records
with breast cancer, 6888 cases and 9529
controls

15 electrical occupations
other occupations
computer programmer
telephone operator
data entry keyer

RR (95% CI)

68

1.4 (1.0-1.8)

26
328
77

1.1 (0.70-1.7)
0.96 (0.84-1.1)
0.75 (0.42-1.3)

medium exposurehigh exposure

white women
1746
123
black women
273
20

All womenhigh exposure jobs
test for trend

6851
57

1.4 (0.99-2.1)
p = 0.11

Premenopausal women only
high exposure jobs
test for trend

1424
20

2.0 (1.0-3.8)
p = 0.49

Postmenopausal women only
high exposure jobs
test for trend

5163
35

1.3 (0.82-2.2)
p = 0.30

medium exposurehigh exposure

MOR, mortality odds ratio; CI, confidence interval; BMI, body mass index; OR, odds ratio

157

Comments

1.1 (1.0-1.2)
0.97 (0.8-1.2)
1.3 (1.1-1.5)
1.2 (0.7-2.1)

MOR, adjusted for age, race, andclass

MOR, adjusted for age and class(Cantor et al., 1995b) reported asignificant association with radio
frequency fields in the same
population
OR, adjusted for age, BMI, history ofbreast disease, age at menarche,
parity, age at first birth, education,
and alcohol consumption
Potential EMF exposure classified
by an industrial hygienist for themost representative occupationcollected at an interview

Table 4.16 Epidemiological studies of lung cancer with full-shift measurements of magnetic fields
Reference; type ofstudy, country

Study population

Exposure classification

Lung cancer risks
No. of cases

OR (95% CI)
OR, adjusted for social classMale utility workers in 3 large companies;
cohort of 223292 employees; 4151 cancer
cases;
6106 controls. Cumulative exposure fromjob history and JEM based on magnetic
field measurements of 2066 workers

Cumulative TWA magnetic
fields³ median ³ 3.1 mT-years

450

0.92 (0.70-1.2)³ 90th percentile93

1.0 (0.67-1.5)(Armstrong et al.,1994);
case-control,
Quebec (Canada)
and France

Male utility workers in 2 large companies:
base population of about 192 000 workers;
508 lung cancer cases and 508 controls.
Cumulative exposures from job histories
and JEM of PEMF measurements on 1295
workers.

Cumulative PEMF*
exposure³ median³ 90th percentile(³16 mT-years)(Savitz et al.,1997);
cohort,USA

Male utility workers in 5 large companies:
base population of 138 905 workers; 20
733 worker deaths. Cumulative exposuresfrom job histories and JEMs for magnetic
fields (Savitz & Loomis, 1995) and PEMF
(Armstrong et al., 1994)

60 Hz exposure:0.7-2.3 mT-year(2-10 year lag)
0.9-2.9 mT-year(10-20 year lag)2-14.6 mT-year(> 20 year lag)(ThŽriault et al.,1994);
case-control,
Canada and France

highest pulsed MF
exposures
5.4-11.9 mT-year
11.9-41.2 mT-year

Comments

OR, adjusted for social class308
84

1.3 (0.96-1.7)
3.1 (1.6-6.0)

302

1.3 (1.1-1.6)429

1.2 (1.0-1.4)

243

1.3 (1.0-1.5)

401
196

1.3 (1.1-1.6)
1.4 (1.1-1.7)

PEMF sensor found to be sensitive
to radio transmission as well as
shocks from electric lines.
SMR with US population as
reference, PMR with comparison
between exposure categories for morecommon cancers

RR, relative risk; CI, confidence interval; SIR, standardized incidence ratio; OR, odds ratio; TWA, time-weighted average; JEM, job-exposure matrix; PEMF, pulsed EMF; nominally 5-20 Mhz; SMR, standardizedmortality ratio; PMR, proportional incidence ratio

158

Table 4.17 Central nervous system tumors in offspring of EMF-exposed parents
Reference, type ofstudy, country

Study population

Exposure classification

Risk estimate
No. of cases(Spitz & Johnson,1985);
case-control study,
Texas (USA)(Nasca et al., 1988);
case-control,
New York State(USA)

Comments

OR (95% CI)

157 children who died ofneuroblastoma (1964-78) identified
from Texas State death certificate records
matched with 314 controls randomly
selected from birth records.

Broad definition of EMF
exposure
Narrow definition of EMF
exposure
Electronics workers only17

2.1 (1.1-4.4)

13

2.1 (0.95-4.8)

6

12 (1.4-99)

338 cases of primary CNS tumors
obtained from tumor registries. Twocontrols per patient selected from birthcertificates (676 controls total).
Parental occupation from phoneinterview.

Narrow definition of EMF
exposure(from Spitz, 1985)

15

1.7 (0.80-3.6)

Broad definition of EMF
exposure19

1.6 (0.83-3.1)

OR, controlled for gender, race andyear of birth. Controls with ionizing
radiation exposures excluded.
Diagnosis confirmed by histologic
examination of pathology slides

All electrical occupations

28

1.4 (0.88-2.4)

OR, controlled for gender, age, andyear of birth

Narrow definition of EMF
exposure(Spitz & Johnson, 1985)

Preconception
9
1.3 (0.4-4.1)
During pregnancy
3
0.3 (0.1-1.3)

Broad definition of EMF
exposure

Preconception
14
1.0 (0.4-2.3)
During pregnancy
7
0.6 (0.2-1.6)(Johnson & Spitz,1989);
case-control,
Texas (USA)499 cases of intracranial and spinalcord tumors obtained from deathcertificates. Birth certificates provided
parentÕs occupation plus 2 controls percase (998 controls total)(Bunin et al.,1990);
case-control,
Philadelphia, PA(USA)

181 children diagnosed withneuroblastoma identified in tumor
registries. Single control per caseidentified through random-digit
dialing. Parents of cases and controls
interviewed by phone to obtainoccupational history for each parent

159

OR, narrow definition limited toelectricians, electric and electronics
workers, linemen, utility workers, andwelders

OR, controlled for race, birth year, andtelephone exchange

Table 4.17 (continued)
Reference, type ofstudy, country

Study population

Exposure classification

Risk estimate
No. of cases(Wilkins &Hundley, 1990);
case-control,
Columbus, OH(USA)(Wilkins &Wellage, 1996);
case-control,
Columbus, OH(USA)(Tornqvist, 1998);
retrospective andprospective cohort
studies,
Sweden101 cases of neuroblastoma identified
through the Children's Hospital Tumor
Registry. Four controls per cases
selected from State birth certificate
roster. Paternal occupation andindustry obtained from birth certificates.

94 cases of CNS tumors identified
through hospital tumor registry. 166
cancer-free controls identified byrandom-digit dialing. Fathers
interviewed to obtain occupation before
conception, during pregnancy, and frombirth to diagnosis.

Retrospective study:
Fathers who had electrical occupationsin the power industry selected fromcensus over a 25-year span. Children
identified from Medical Birth Registry,
and cancers from the national tumor
registry.
Prospective study:
Cohort of first-employed powerindustry workers had health outcomes
followed over 10 years.

Electrical occupation
definitions:(Deapen & Henderson, 1986)(Lin et al., 1985):
definite exposure (A)probable exposure (B)possible exposure (C) A+B(similar to narrow in Spitz &Johnson, 1985) A+B+C(similar to broad in Spitz &Johnson, 1985)
Occupations with presumed
EMF exposure

Occupations
welding

involving

Retrospective study:
Electric jobs in year before
birthElectrical jobs at any time
Electric jobs in year before
birthElectrical jobs at any time
Prospective study:First employed powerindustry workers; same
occupations as retrospective
study

RR, relative risks; CI, confidence interval; OR, odds ratio; CNS, central nervous system; SIR, standardized incidence ratio160

OR (95% CI)

4

1.6 (0.3-9.1)

1
5
13
6

NR
1.2 (0.2-6.4)
0.5 (0.2-1.2)
1.9 (0.4-9.7)

190.7 (0.3-1.5)

Preconception
11
Pregnancy
9
Preconception
6
Pregnancy
5

1.3 (0.58-3.0)
1.0 (0.45-2.4)

OR, controlled for year of birth, race,
gender, and motherÕs county at timeof birth

OR, controlled for year of birth, race,and gender. Jobs involving welding
are defined more liberally than thestandardized occupational
categories.

3.8 (0.95-16)
2.5 (0.67-9.3)

All cancers
60.75 (0.24-2.3)

12

SIR = 2.1 (p = 0.02)

CNS tumors (estimates)
30.75 (0.14-4.1)
6

Comments

SIR = 5.4 (p = 0.002)

Prospective study:
No cancer cases identified[Risks were calculated by Working
Group from observed and expectedcancers (all types) reported in thepaper. Expected CNS cancers
estimated from US rates For RR, theexposed are fathers who held electricjobs in the year before the birth ofthe child with cancer, and theunexposed were electric workers at
some other time.
For SIR, the childhood cancer
outcome for the entire cohort ofelectrical workers compared with thegeneral population]

Table 4.18 Design of studies of leukemia and residential exposure to EMF
Study

Case selection

Control selection

Exposure metrics

Confirmed AML and CML cases
aged 20-69, resident in LA
county, alive at interview andEnglish speaking from cancer
registry (1979-85)
224 cases included in analyses

Neighborhood controls (1 percase) matched on sex, race andbirth year, resident in LA country,
alive at interview and English
speaking
224 controls included in analyses

Electric blanket use from questionnaire(ever/never, duration, year of first andlast regular use)

Sex
Race
Age
Diagnostic X-rays
Work as a welder
Life on a farm

Severson et al.
(1988)ANLL cases aged 20-79,
resident in Western
Washington State, from cancer
registry (1981-84)
114 cases included in analyses(91 AML)

Population-based controls fromrandom-digit dialing, matched on
geographical area and frequency
matched on age and sex
133 controls included in analyses

Wertheimer and Leeper wire-coding
Estimation of magnetic fields from maps
and wire coding -Ðmethod of Kaune(1987)
One-time measurements of 60 Hz
magnetic fields inside (kitchen,
bedroom, family room in HPC1 andLPC1) and outside house
24-hour measurements in sample ofhousesElectric appliance use fromquestionnaire

Age
Sex
Cigarette smoking
Family income
Race

Lovely et al.
(1994)

Same cases as Severson
67-70 cases included inanalyses:, depending on
appliance (missing data)

Same controls as Severson
66-69 controls included inanalyses:, depending on appliance

Use of electric razors, hair dryers andmassage units from questionnaire

Age
Sex
Smoking

Same as Lovely and Severson,
excluding proxy respondents
24 cases included in analyses

Same as Lovely and Severson

Same as Lovely

Sex

All incident cancer cases fromcancer registry( 19601985),from cohort of Swedish
population aged 16 or over,living on a property locatedwithin 300 meters of any 220 or
400 kV power lines
325 cases in analyses (72 AML,
57 CML, 14 ALL and 132 CLL)

Two controls per case from samecohortMatched on age, sex, parish andresidence near same power line
1 091 controls in analyses

Distance to power lines from residence
In-home magnetic field spotmeasurements under low and highpower use conditions
Calculations of the magnetic fields
generated by the power lines at thetime spot measurements were assessed(calculated contemporary fields) andfor the year closest in time to diagnosis(historical calculated fields)

Age
Sex
Year of diagnosis
Residing or not in the county of
Stockholm
Type of residence
SES

USA
PrestonMartin et al.
(1988)

Sussman &Kheifets(1996)
SwedenFeychting andAhlbom(1994)

161

Confounders analyzed

Table 4.18 (continued)
Study

Case selection

Exposure metrics

Confounders analyzed

Feychting etal. (1997)

Same as Feychting and Ahlbom(1994)

Same as above

Same as above for residential
Occupational exposure from jobexposure matrix developed fromworkday measurements made for a large
number of occupations outside theframework of this study andinformation on occupation held in theyear prior to the reference dateSame as above
Occupational exposures to motor
fuel/exhaust fumes, benzene, oil
products, solvents and welding
fumes

All primary leukemia cases
reported to the Finnish Cancer
Registry (1974-89) from cohortof Finnish population, aged 20
or older, living within 500 m ofoverhead power lines of 110-400
kV in building with a calculated
magnetic field of ³ 0.01 mT for
any period between the years
1970-89
203 cases identified

Cohort study: consisting of 383
700 persons (189 300 men) who
contributed 2.5 million person
years of follow-up after age 20

Average annual magnetic fields
Cumulative exposure
Estimates based on residential history,
distance between center of residentialbuildings and each power line in 500
m corridor and calculated averageannual magnetic fields for eachbuilding. Takes into account current,
typical locations of phase conductors
in power lines, and distanceSex
Age
Socioeconomic status

Same as Verkasalo et al (1996)
196 leukemia cases included (60AML, 12 ALL, 30 CML, 73
CLL, and 21 other or unknown
subtype)10 controls per case from cohort
Matched on sex, age at diagnosis
and alive in the year of diagnosisof the case

Cumulative exposure: total and within
0-4, 5-9, and 10 years or more ofdiagnosis
Annual average magnetic fields 1
through 20 years prior to diagnosis
Highest annual average magnetic field
ever and in time windows before
diagnosis
Age at first exposure to annual averagemagnetic field greater than a specified
level
Duration and time since exposure toannual averages above that level.

Sex
Age
Type of municipality
Type of housing
Occupational exposure(none/possible or probable)

Finland
Verkasalo et al.
(1996)

Verkasalo et al.
(1998)

Control selection

162

Table 4.18 (continued)
Study
TaiwanLi et al. (1997)

Case selection

Control selection

Exposure metrics

Pathologically confirmed
incident cases of leukemia from
northern Taiwan from cancer
registry (1987-92)
870 cases included in analyses

One control per case from cancer
registry, excluding leukemia,
brain and breast cancers, cancersof the haematopoietic andreticulo-endothelial system, skin,ovary, fallopian tube, and broad
ligament.
Matched on date of birth, sex, anddate of diagnosis
889 controls included in analyses

Distance from lines
Average and maximum magnetic fields
assessed using distance from the lines,
distance between wires, height ofwires above the ground, annual andmaximum loads along the lines from1987 to 1992, current phase, andgeographical resistivity of earth

Confounders analyzed
AgeSex
Index of urbanization

AML, acute myelogenous leukemia; CML, chronic myelogenous leukemia; LA, Los Angeles; ANLL, acute nonlymphocytic leukemia; HPC: high power configuration; LPC: low power configuration; ALL, acutelymphocyte leukemia; CLL, chronic lymphocytic leukemia

163

Table 4.19 Results of studies of leukemia and residential exposure to EMF
Study
Studies of electric appliance(Preston-Martin et al., 1988)(Lovely et al., 1994)

Main results: OR and 95% CI(unless otherwise specified)Electric blanket use:
Ever vs. never used:AML
CML

0.9 (0.5-1.6)
0.8 (0.4-1.6)

Ever vs. never use
Any appliance
RazorsHair dryers
Massage units

0.71 (0.41-1.2)
1.3 (0.80-2.2)
0.38 (0.22-0.66)
3.0 (1.4-6.3)

Study using wiring configuration(Severson et al., 1988)
Residence where lived longest
OLCC
0.60 (0.29-1.2)
OHCC
0.77 (0.35-1.7)
VHCC
0.79 (0.22-2.9)
Reference: end poleStudies using calculated magnetic fields(Severson et al., 1988)
Magnetic fields(Reference: 0-0.05 mT)
Residence where lived longest
0.051-0.199 mT
0.69 (0.37-1.3)³ 0.2 mT
0.75 (0.31-1.8)(Feychting & Ahlbom, 1994)

Magnetic fields closest to diagnosis(Reference £ 0.09 mT) Ð Matched analyses
All leukemia 0.1-0.19 mT
1.0 (0.5-1.8)³ 0.20 mT
1.1 (0.6-1.8)
AML
0.1-0.19 mT
1.5 (0.4-5.3)³ 0.20 mT
2.2 (0.7-6.8)
CML
0.1-0.19 mT
1.3 (0.3-5.1)³ 0.20 mT
3.2 (0.9-11)CLL
0.1-0.19 mT
0.9 (0.4-2.2)³ 0.2 mT
0.6 (0.3-1.6)
Cumulative exposure over 15 years(Reference £0. 99 mT -years) Ð Matched analyses
All leukemia 1.0-1.99 mT -year
1.1 (0.6-2.2)³ 2.0 mT -year
1.4 (0.8-2.3)
AML
1.0-1.99 mT -year
1.7 (0.4-6.6)³ 2.0 mT -year 3.5 (1.0-12)
CML
1.0-1.99 mT -year
2.1 (0.3-15)³ 2.0 mT -year
1.6 (0.6-4.8)
CLL
1.0-199 mT -year
1.0 (0.4-2.6)³ 2.0 mT -year
1.0 (0.4-2.2)

164

Additional notes

Many potential risk factors
analyzed
Information on electric blanket
use included after the fact inquestionnaire of on-going casecontrol studies
Information on response rate incontrols not given
Majority of cases deceased Ðmost of data from proxy
respondents
Small numbers of subjects

Refusal rate for measurements
much higher among controls(27%) than cases (4.9%)
One-time measurements made ina limited number of houses(56%) since many subjects had
moved recently
Refusal rate for measurements
much higher among controls(27%) than cases (4.9%)
One-time measurements made ina limited number of houses(56%) since many subjects had
moved recently
Same as above

Table 4.19 (continued)
Study

Main results: OR and 95% CI(unless otherwise specified)

Additional notes(Feychting et al., 1997)

Magnetic fields closest to diagnosis
Subjects with only residential exposure (i.e. withoccupational exposure < 0.13mT)(Reference £ 0.2 mT) Ð Unmatched analyses
All leukemia³ 0.2 mT
0.9 (0.4-1.8)
AML³ 0.2 mT
1.3 (0.4-5.0)
CML³ 0.2 mT
0.5 (0.1-3.9)
CLL³ 0.2 mT
0.8 (0.3-2.3)

Same as above(Verkasalo, 1996)

Magnetic fields Ð highest annual average
exposure(Reference < 0.1 mT)
All leukemia (No. of exposed cases)
0.10 - 0.19 mT (ND)
1.1 (0.60-2.0)
0.20 - 0.29 mT (ND)
1.2 (0.40-3.3)³ 0.30 mT (ND)
0.53 (0.16-1.7)
CLL
0.10 - 0.19 mT (5)1.0 (0.37-2.5)
0.20 - 0.29 mT (1)
1.4 (0.16-11)³ 0.30 mT (2)0.87 (0.20-3.8)

Cohort study, SIRs
No information on othersources of residential EMF
exposure
No direct information fromstudy subjects
Cumulative exposure nottreated as time dependent
variable in the analyses

Magnetic fields - cumulative exposure(Reference < 0.40 mT-years)
CLL
0.40 - 0.99 mT-years (8) 0.98 (0.45-2.2)
1.00 - 1.99 mT -years (3) 1.3 (0.37-4.4)³ 2.00 mT -years (3)1.7 (0.48-5.8)
Cumulative exposure
CLL³ 0.20 mT -years vs. < 0.20 mT -years< 5 years before
diagnosis (12)0.93 (0.48-1.8)
5 - 9 years (11)
1.5 (0.72-3.1)³ 10 years (9)2.8 (1.1-7.4)³ 0.40 mT -years vs. < 0.40
< 5 years (5)0.84 (0.32-2.2)
5 - 9 years (5)1.4 (0.52-4.0)³ 10 years (6)4.6 (1.4-15)
Duration of exposure to magnetic fields(Reference < 3 years)
3 - 5 years (1)0.54 (0.90-3.0)
6 - 8 years (1)0.55 (0.10-3.0)
9 - 11 years (1)0.81 (0.15-4.5)³ 12 years (3)4.8 (1.5-15)

165

Table 4.19 (continued)
Study

Main results: OR and 95% CI(unless otherwise specified)(Li et al., 1997)

Magnetic field exposure in year of diagnosis(Reference < 0.1 mT)
0.1-0.2 mT
1.3 (0.8-1.9)> 0.2 mT
1.4 (1.0-1.9)
Studies using direct residential measurements(Severson et al., 1988)
Mean exposure from one time measurements(Reference: 0-0.05 mT)
Low-power configuration
0.05-0.199 mT
1.2 (0.52-2.6)³ 0.2 mT
1.5 (0.48-4.7)
High-power configuration
0.05-0.199 mT0.55 (0.25-1.2)³ 0.2 mT
1.6 (0.49-5.0)
Weighted mean exposure (vs. 0-0.5 mT)
Low-power configuration
0.05-0.199 mT
1.2 (0.54-2.5)³ 0.2 mT
1.0 (0.33-3.2)
High-power configuration
0.05-0.199 mT
0.91 (0.42-2.0)³ 0.2 mT
1.3 (0.35-4.5)(Feychting & Ahlbom, 1994)

Spot measurements(Reference £ 0.09 mT) Ð Matched analyses
All leukemia
0.10-0.19 mT
1.1 (0.7-1.9)³ 0.20 mT
1.2 (0.8-1.9)
AML
0.10-0.19 mT
0.9 (0.3-2.3)³ 0.20 mT
1.1 (0.4-2.4)
CML
0.10-0.19 mT
0.6 (0.1-1.8)³ 0.20 mT
1.5 (0.7-3.2)
CLL
0.10-0.19 mT
1.3 (0.7-2.6)³ 0.20 mT
0.9 (0.5-1.8)

Additional notes
Limited information on
confounders because ofrestrictions on interview

Refusal rate for measurements
much higher among controls(27%) than cases (4.9%)
One-time measurements made ina limited number of houses(56%) since many subjects had
moved recently

Matched and unmatchedanalyses, adjusted or not forage and SES were carried out
No information on othersources of residential EMF
exposure

AML, acute myelogenous leukemia; CML, chronic myelogenous leukemia; OLCC, ordinary low current configuration; OHCC, ordinary highcurrent configuration; VHCC, very high current configuration; SES, socioeconomic status; CLL, chronic lymphocytic leukemia; ND, notdetermined; SIR, standardized incidence ratio

166

4.3 Epidemiological studies of carcinogenicity in children
Wertheimer and Leeper (Wertheimer & Leeper, 1979) were the first to generate thehypothesis that EMF from electrical power lines and substations are associated withchildhood cancer. Since their seminal paper, a number of epidemiological studies havebeen undertaken to investigate that hypothesis. Interpretation of epidemiological evidence
on the potential causal relationship between exposure to magnetic fields and childhood
cancer is difficult because of the low incidence of the diseases involved and the rarity ofhigh exposures. The results of several epidemiological studies have been combined toderive a single summary measure of association, and the consistency of the results acrossindividual studies have been examined in meta-analyses by several researchers.
The Working Group decided to exclude studies in which established epidemiologicalmethods were not used, for example those in which advertisements were used to identify
subjects or in which dwellings were analyzed rather than subjects. Studies in which themethods were too crude to assess exposure to magnetic fields were not considered; thus,
results based on distance alone were not included, nor were those of one study in which
0.1 mT was the highest exposure cut-point (Myers et al., 1990). One study in which
exposure was assessed for only 12% of the subjects was also not evaluated (Dockerty etal., 1998). The Working Group also decided not to consider studies that were re-analysesof primary data. As weight is given in the evaluation to individual studies with primarydata, formal meta-analyses are included but are only briefly discussed.
The characteristics of all of the studies are summarized in Table 4.20, while the results are
summarized in Tables 4.21Ð4.24, and the meta-analyses are summarized in Tables 4.25
and 4.26.

4.3.1 Effects of power lines
In the case-control study of Wertheimer and Leeper (Wertheimer & Leeper, 1979) cancer
mortality was examined from death certificates for residents of greater Denver, Colorado(USA), who died at less than 19 years of age during the years 1950Ð73. The population
was further restricted to subjects living in the greater Denver area and born 1949Ð73 in
Colorado. A total of 344 cases of childhood cancer were identified, and 344 population
controls were selected from Denver-area birth certificates matched on birth month andcounty. Exposure was assessed from the wire code configurations of the homes occupied
at the time of birth and the homes occupied at the time of death. Addresses at the time ofbirth were missing for 20% of cases and addresses at the time of death for 5%. The
equivalent information for controls was not available. Wire code configurations weredeveloped as a surrogate method of estimating long-term exposure to EMF frominformation on nearby distribution lines, transmission lines, and substations (see section
2.5). Two classes of wire-code configuration have been examined: high-current and low-167

current configurations. These measures were developed specifically for the Denver area,
considering such issues as location of transformers, placement of service drops, and age ofthe lines (pre-1956 or later). They noted that children who died of cancer were more
likely to have lived in homes classified as high-current configuration than in homes
classified as low-current configuration. The unadjusted relative risks for leukemias,
lymphomas, and nervous system tumors (exposure classification conducted at the death
address) were 3.0 (95% CI, 1.8Ð5.0), 2.1 (0.84Ð5.2), and 2.4 (1.2Ð5.0), respectively.
In this exploratory study, when wire codes were assigned, the case or control status of
the homes was known to the coder. Thus, exposure assessment was not conducted in ablinded fashion. This may have introduced bias, although the investigators conducted two
smaller studies to assess the possible effect of lack of blinding on the outcome(Wertheimer & Leeper, 1979). In part of that study, a separate investigator blindly coded
the homes of 70 cases and 70 controls and found a 91% agreement, with about half of thedisagreements favoring the association with higher wire codes and half countering theassociation. [This rate of agreement is similar to that observed in studies in which theprocess of wire coding was blinded] (Tarone et al., 1998). In a second, smaller study
including birth addresses in Colorado Springs and Pueblo, 32% of the cases and 18% of
the controls had lived in high-wire code homes, whereas in the larger study the numbers
were 37 and 20%, respectively. Furthermore, accounting for potential confounding factors
and effect modifiers (e.g. socioeconomic class, urbanÐsuburban differences, traffic density,and gender) did not change the results. None of the relative risks reported in this study
was adjusted for these factors. [Death certificate-based studies are subject to differential
survival bias. Children in families of higher socioeconomic class have greater access tohealth care and may thus have higher rates of survival from cancer. Consequently, there
may be a bias toward lower socioeconomic cases in this study. If children in families oflower socioeconomic class tended to be categorized in the high-current configuration
homes, such bias would inflate the risk estimates.]
Savitz et al. (Savitz et al., 1988) conducted a case-control study of residential exposure in
the same area as that of Wertheimer and Leeper (Wertheimer & Leeper, 1979). They
studied Denver residents under 15 years of age and assessed the exposure in the homes
occupied at the time of cancer diagnosis and two years before diagnosis. Cases wereobtained from population-based cancer registries and hospital records for the years 1976Ð
83. Controls were selected by random-digit telephone dialing after the close of the study
period and were further restricted to have been living in the study area at the time theirmatched cases (by age ± three years, gender, and telephone exchange at the time of cancer
diagnosis of the matched case) were diagnosed. A total of 356 childhood cancer cases were
eligible, and 278 population controls were identified. [It is unclear why there are fewer
controls than cases despite the matched selection of controls.] Exposure in the home
occupied at the time of diagnosis was assessed by the dichotomous wire coding scheme ofWertheimer and Leeper (Wertheimer & Leeper, 1979) and the five-level wire code of
Wertheimer and Leeper (Wertheimer & Leeper, 1982) for 90% of cases and 93% of
controls and by spot measurements of EMF taken 1Ð9 years after diagnosis, by the front
door, in the childÕs and parentsÕ bedrooms, and in all rooms occupied by the child for at168

least 1 h/d; 36% of cases and 75% of controls participated. Both the electric and magnetic
fields were measured with a model 111 or 113 Electric Field Meter. A weighted average ofmeasurements in all measured rooms was computed and used as a summary exposure
measure.
The relative risk for all cancers among children living in homes in the high-current
classification was 1.5 (95% CI, 1.0Ð2.3). A detailed categorization of wiringconfigurations (very low, which included buried wires, ordinary low, ordinary high, andvery high) was analyzed to elucidate a doseÐresponse relationship. The estimated relative
risks tend to increase in a linear fashion up to an almost tripling of risk in the highest
exposure category (2.8; 0.9Ð8.4), representing a statistically significant linear trend. This
association was not corroborated by spot field-strength measurements, regardless of low
or high power use conditions. For leukemias, a relative risk of 1.5 (0.9Ð 2.6) was reported
when comparisons were made between high- and low-current classifications; the relativerisk with spot measurements of ³ 0.2 mT was 1.9 (0.7Ð5.6) under low-power use
conditions and 1.4 (0.6Ð3.5) under high-power use conditions. For brain cancer, a relativerisk of 2.0 (1.1Ð3.8) was found for the high-current configuration exposure category. For
homes occupied at the time of diagnosis, the relative risk for brain cancer associated withaverage spot magnetic field-strengths > 0.2 mT was 1.0 (0.2Ð 4.8). No increase in the risk
for childhood lymphoma was found in a comparison of high-current and low-current
configurations. The relative risk for lymphoma with spot measurements ³ 0.2 mT was 2.2(0.5Ð10) under low and 1.8 (0.5Ð6.9) under high power use conditions. Approximately 20
other potential risk factors for childhood leukemia were considered, and those found to berelated to the risk for leukemia, e.g., socioeconomic status, traffic density, maternal age,and smoking during pregnancy, were controlled for in the analyses. Control for
confounding did not change the risk estimates.
[An important methodological issue is the selection of controls that represent a
residentially stable subset of the population in which the cases occurred after the study
period. Control selection bias may have been introduced if exposure was related tocharacteristics of residential stability. Jones et al. examined the effect of the differential
stability in a different population and concluded that the control selection bias would leadto an exaggerated estimate of risk. Wertheimer and Leeper, however, presented additional
analyses of the Savitz et al. study to show that the effect of the bias was to attenuaterisk. The very low participation rate for spot measurements among the cases limits thevalidity of the results based on these measurements. Control selection through randomdigit dialing is also a limitation. A strength of the study is the evaluation of a large numberof potential confounding factors, including socioeconomic status and traffic density.](Jones et al., 1993; Savitz et al., 1988; Wertheimer et al., 1994)
London et al. (London et al., 1991) conducted a caseÐcontrol study of 232 cases and 232
population controls, focusing strictly on the incidence of childhood leukemia, andassessed exposures in selected homes during an Ôetiologic periodÕ defined as the period
beginning at the estimated time of conception and ending on the date of diagnosis forchildren aged one year or less at diagnosis, six months before diagnosis for children aged

169

one to two years at diagnosis, and one year before diagnosis for children aged above twoyears at diagnosis. The population base in this study consisted of all children under 10
years of age living in Los Angeles County during the years 1980Ð87. The 331 eligible
cases were obtained from a population-based tumor registry. Controls were friends (65controls accrued during the period 1980Ð84) or obtained by random-digit telephonedialing (167 controls accrued during the period 1985Ð87) and were matched to the casesby age, gender, and ethnicity. [Whether friends of cases are representative of the entire
population from which the cases were identified is not clear. Issues previously discussedwith regard to random-digit telephone dialing are also applicable here.]
Exposure was assessed by three methods: five-level wire code configuration
classifications developed by Wertheimer and Leeper (Wertheimer & Leeper, 1982); spotmeasurements in the center of the childÕs bedroom of EMF, static magnetic fields, and theharmonic content of the magnetic field; and 24-h measurements of magnetic fields underthe bed in the childÕs bedroom. Spot measurements were made with a Deno Power
Frequency Meter 120; 24-h measurements were made with an IREQ meter in the earlyparts of the study and with an EMDEX-100 meter for most of the study. The
comparability of the data collected with the IREQ and EMDEX meters was ascertained.
Harmonic content was determined during the spot measurement period with the broadband mode of the Deno meter. The investigators also recorded the EarthÕs magnetic field
during the spot measurements with a fluxgate magnetometer (Bartington MAG-01). The
participation rates were 42% for both cases and controls for the spot measurements, 50%
for cases and 56% for controls for 24-h measurements, and 66% for cases and 81% forcontrols for wire codes. The measurements were made 1Ð10 years after diagnosis.
Comparisons across these various exposure metrics and between previous studies showedthat the 24-h average measurements were considerably higher than the spot measurementsin the same homes, and in contrast to the study of Savitz et al. (Savitz et al., 1988), morethan twice the number of control homes were classified in the high-current configuration
categories (45%), but spot-measured magnetic fields were lower within five-level wiringconfiguration code categories (the difference was especially pronounced in the highcurrent categories). London et al. (London et al., 1991) noted that this discrepancy may
have been due to the differences in the electrical distribution system in the Los Angeles
and Denver areas.
The relative risk for leukemia in relation to wire code configuration (high- versus lowcurrent classification) was 1.7 (95% CI, 1.1Ð2.5). With a more detailed categorization of
wiring configuration (very low, ordinary low, ordinary high, and very high), the estimatedrelative risks tended to increase in a linear fashion (statistically significant linear trend) up
to more than a doubling of risk in the highest exposure category (2.2; 1.1-4.3). No
associations were found with spot electric or magnetic field measurements or static
magnetic fields. The results with the 24-h magnetic field measurements indicated anincreased risk only for the highest cut-point used (> 0.27 mT) with a relative risk of 1.5(0.7Ð3.3). The authors noted that similar results were obtained for the ALL and ANLL
subtypes of leukemia, but they did not report them separately. Potential factors
associated with cancer risk that were controlled for and included were age, gender,170

ethnicity, paternal use of pesticides, use of cigarettes, drugs, and incense, traffic density,and socioeconomic status. [A limitation of this study is the uneven ascertainment of wirecode information between cases and controls: spot and 24-h measurements of magnetic
fields resulted in much lower percentages of ascertainment than wire codes.]Feychting and Ahlbom (Feychting & Ahlbom, 1993) conducted a population-based caseÐ
control study in Sweden to examine the association between exposure to magnetic fields
generated by high-voltage power lines and cancer incidence in children. The populationbase for this study consisted of all children who resided on a property located in a highvoltage power-line corridor, defined as a property located at least partially within 3 m ofany 220 or 400 kV power lines. The subjects were children under 16 years of age who
resided within a high-voltage power-line corridor during 1960Ð85. They were followedfrom the time they moved into the corridor through the end of the study period. The
Swedish Cancer Registry was used to identify the 142 cancer cases occurring within highvoltage corridors during the study period. Approximately four controls per case (total,
558) were selected randomly from the study base and were matched according to age,gender, parish residence during the year of diagnosis or the last year before the case
moved, and proximity to the same power line.
Exposure to magnetic fields was assessed by spot measurements, contemporary
calculated fields, and historical calculated fields (see section 2.4). The spot measurements
were made closely following the protocol implemented by Savitz et al. (Savitz et al.,1988) with a meter constructed for the purpose of the study. Spot measurements were
performed in the home within the power-line corridor in which the patients andcorresponding controls had lived closest to the time of diagnosis and were obtained for
62% of cases and controls. The measurements were made 5Ð31 years after diagnosis, witha median of 16 years (Feychting et al., 1995). Most of the dwellings in whichmeasurements were not made were located in Stockholm. Contemporary calculated fieldstrengths were estimated from information about the height of the towers, distance
between the towers, distance between phases, ordering of phases, and line load. The
contemporary line load was obtained during the visit to each dwelling. Both transmission
and distribution lines were considered; however, less than 20% of the homes were locatednear distribution lines. Historical annual average line load during the study period wasused in calculating historical field strengths for all but one case and four controls. In theiranalysis, Feychting and Ahlbom (Feychting & Ahlbom, 1993) emphasized the use ofhistorical fields calculated from exposure metrics, due to the presumed accuracy of using
historically calculated field strengths to estimate exposures several decades previously forsome subjects and the fact that averaged spot measurements are not a representative
measure of long-term exposure. Cut-points for the analyses of historical calculations
consisted of a three-level, ordinal scale with the following categories: < 0.1 mT , 0.1 mT, £0.2 mT , and ³ 0.2 mT; analyses were also made for exposures of ³ 0.3 mT. Feychting etal. (Feychting et al., 1995) examined exposures ³ 0.5 mT. With spot measurements, thehighest exposure examined was ³ 0.2 mT.

171

The results for historically estimated field strengths showed elevated risks for childhood
leukemia with increase in exposure (statistically significant linear trend), up to more thana tripling of risk in the exposure category ³ 0.3 mT (RR, 3.8; 95% CI, 1.4Ð9.3). When thedata on leukemia were further stratified by age and gender, a doseÐresponse trend wasobserved for single-family dwellings but not multiple-family dwellings. Controlling forpotential confounders (age, gender, county, dwelling type, year of diagnosis,
socioeconomic status, and levels of nitrogen dioxide as an estimate of exposure to motor
vehicle exhaust) did not alter this relationship. For exposure to 0.5 mT, the relative risk
was 4.6 (1.5Ð14). There was no evidence in this study of an association between
historically calculated exposure to magnetic fields and all cancers combined, lymphomas,
or central nervous system tumors. In analyses based on spot measurements, no increasein risk was observed for all cancers, leukemia, or central nervous system tumors.
In analyses to validate the various calculations and measurements of magnetic fields usedby Feychting and Ahlbom (Feychting & Ahlbom, 1993), spot measurements showedpoor agreement with calculated historical fields but good agreement with contemporary
calculations. This result was interpreted by the authors as an indication that spotmeasurements are poor predictors of exposure many years earlier. [A strength of thisstudy is the minimal potential for selection bias in the analyses of historical calculations.
Another strength is that the historical calculations are based on established laws ofphysics and conditions prevailing prior to diagnosis. A limitation is the small number of
exposed subjects.]
Olsen et al. (Olsen et al., 1993) conducted a population-based case-control study toinvestigate whether residence before and after birth near high voltage facilities was
associated with an increased risk for childhood cancer. They studied 1707 cases ofleukemia, malignant lymphoma, and central nervous system tumor in Danish children aged
< 15 reported to the Danish Cancer Registry during the years 1968Ð86. Two to fivecontrols, selected randomly from the Danish Central Population Register among cancerfree children, were matched to each case by gender and age (± one year), for a total of
4788 controls. They assessed exposure from calculated average magnetic field strengths.
Residences located outside the area of potential exposure to high-voltage facilities(generally > 300 m away from overhead lines or transformer substations) were assumed
to have an average calculated magnetic field of zero. Estimates of relative risk wereobtained for cut-points associated with low (0.1 mT), intermediate (0.25 mT), and highexposure (0.4 mT) and were adjusted for gender and age at diagnosis.
Comparisons made between exposure to ³ 0.4 mT and to < 0.1 mT resulted in crude
relative risks of 6.0 (95% CI, 0.8Ð44) for leukemia, 6.0 (0.7Ð44) for central nervous
system tumors, and 5.0 (0.3Ð 82) for malignant lymphoma. In analyses further adjusted
for the potential confounding effects of population density, socioeconomic class, andfamilyÕs mobility, no effect on the risk estimates was observed. [The current on thetransmission lines was not recorded, but was estimated on an annual average basis by anexpert group of utility planners. This process led to uncertainty in the calculated fields. In

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addition, the methods of calculation were not confirmed by measurements. Due to the low
prevalence of exposure, the risk estimates were unstable.]
Verkasalo et al. (Verkasalo et al., 1993) conducted a population-based cohort study of
134 800 Finnish children (68 300 boys and 66 500 girls) aged < 20 who lived within 500
m of 110Ð400 kV overhead power lines and to magnetic fields calculated to be ³ 0.01 mT
during the period 1970Ð89. The 140 cases of childhood cancer were obtained from the
Finnish Cancer Registry and included all primary tumors of the nervous system,
leukemia, lymphoma, and all other cancers grouped. Exposure to magnetic fields wasestimated from calculations of the annual average fields for all years between birth anddiagnosis, based on information about typical line configurations, historical load on thelines, and distance (obtained from computerized sources). The historical load for the last
third of the observation period was obtained from simulations, those for the middle thirdfrom existing records, and those for the first third from the last year with existing records.
Exposure was assessed by two calculated estimates: average magnetic field and cumulative
exposure. Cumulative exposure was defined as the average exposure per year multipliedby the number of years exposed (mT-years). The cut-points chosen for high exposure
were 0.2 mT for average exposure and 0.4 mT-years for cumulative exposure to magnetic
fields. These cut-points were selected a priori from the distribution of the number of
exposed children and taking into account the typical residential magnetic field of 0.01 mT(referent exposure). [The calculated fields were not validated by actual measurements.] A
cohort approach with personÐyears calculations was used to investigate the risk of cancer
in children living close to power lines. The expected number of cases was calculated from
Finnish national incidence rates.
Regardless of exposure metric, a four-fold increase in risk for nervous system tumors wasseen among boys (SIR, 4.2; 95% CI, 1.4Ð9.9) for cumulative exposure, but not for girls
for whom no cases were observed at high exposure. The increase in risk was largely
attributable to one boy who had three primary tumors of the nervous system. If theanalysis had been restricted to first primary cancers, the estimate would have beenslightly elevated, with a larger confidence interval overlapping the null. The SIRs forleukemias, lymphomas, and cancers at other sites were close to unity for both average andcumulative exposure. The results for cumulative exposure of ³ 1.0 mT-years has also beenreported (Verkasalo et al., 1994). The relative risk estimates were 2.3 (95% CI, 1.0Ð1.3)
for all cancers combined, 3.5 (0.7Ð1.0) for leukemia, and 2.8 (0.6Ð8.1) for nervous system
tumors. These risk estimates were not adjusted for potential confounding factors. In
particular, Verkasalo et al. (Verkasalo et al., 1993) reported that childhood cancer, otherthan leukemia, was commoner in urban than in rural settings. Thus, the crude risk
estimates reported (excepting leukemia) are slightly higher than they would have been had
the analysis been adjusted for this covariant. [Selection bias is not a concern in this study
since it is population-based. The study is limited by the small number of exposed
subjects. The calculated field strengths were not validated by measurements. The validityof including three brain tumors in one subject as three separate cases is questionable.]

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The United States West Coast Childhood Brain Tumor Study was a multicenter,
population-based caseÐcontrol interview study to evaluate potential environmental andnutritional risk factors for diagnosis of brain tumor (benign or malignant tumor of thebrain, cranial nerves, or cranial meninges) in children aged £ 19 in 1984Ð90. To be eligible
for participation in the study, each childÕs biological mother had to speak English, beavailable for interview, and have a telephone. Mothers of children with brain tumors wereasked questions about exposure and conditions thought likely to be related to risks forpediatric tumor (e.g. ionizing radiation, predisposing genetic syndromes, exposure tomagnetic fields during pregnancy). Subanalyses of this multicenter trial addressed the risk
for childhood brain tumor in relation to residential exposure to magnetic fields in Los
Angeles, California (Preston-Martin et al., 1996b), to residential power-line
configurations, electric heating sources, and electric appliances in Seattle, Washington(Gurney et al., 1996), and the use of electric blankets and water-bed heaters for the entire
study population (Preston-Martin et al., 1996a).
Preston-Martin et al. (Preston-Martin et al., 1996b) initiated a study of magnetic fields
two years after the beginning of the multicenter interview study. The parents of cases
were re-contacted by telephone in order to obtain measurements of magnetic fields at theirresidences. Of the 304 cases in the multicenter study, 298 cases were included in thesubstudy. A control group of 298 children within the same range of birth years and withthe same distribution by gender as the cases were identified by random-digit dialing, werematched to the cases by gender, birth date (± one year), and had to be the same age at thetime of interview as the case had been at the time of diagnosis. Cases and controls were
accrued concurrently during 1989 to the end of the study period; before 1989, thecontrols were accrued by random-digit dialing [but further details are not given]. Exposure
to magnetic fields was assessed from spot measurements taken outside the residence andfrom wire code configurations. Magnetic fields could be measured for 59% of the eligible
cases and 54% of the eligible controls. The exterior residential measures included the fields
over water meters and water pipes, static magnetic fields, front-door fields, and STARmagnetic field profiles (see section 2.3.1), including the front wall and perimeter of thedwelling. [The STAR meter does not measure magnetic fields at harmonic frequencies.]
For cases whose current residence was also the residence in which they lived at the timeof diagnosis (and for their matched controls), interior home measurements were taken,
consisting of 24-h EMDEX measurements in the childrenÕs bedrooms and in a second
room in which the children spent most of their time.
Wire codes were obtained for three types of residences: the residence occupied at the
beginning of the study (nine months before birth), the residence occupied for the longest
time, and the residence occupied at the date of diagnosis. Wire codes were obtained for
80% of cases for homes two years before diagnosis. The investigators found that too few
subjects were within category of the usual reference wire code, ÔundergroundÕ, to serve asa stable reference, and so they pooled the 114 cases and 102 controls in the Ôvery lowÕand Ôordinary lowÕ categories and used this as the reference category. [This categorizationof wire codes is unusual.]

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Preston-Martin et al. (Preston-Martin et al., 1996b) reported elevated risks for brain
cancer in several exposure categories but no statistically significant trend, e.g. for all
exposure metrics. When the analyses were restricted to very high exposure (> 0.3 mT ),the 24-h EMDEX measure revealed a relative risk of 1.7 (95% CI, 0.6Ð 5.0), and spotmeasurements and STAR profiles both led to a relative risk of 0.9 (95% CI, 0.3Ð 3.2 and
0.2Ð4.1, respectively). These estimates are highly unstable owing to the small numbers ofsubjects living in residences with magnetic field strengths > 0.3 mT, i.e. 12 or fewer cases
and 7 or fewer controls. [Limitations associated with random-digit dialing telephonemethods to select controls are applicable to this study. Notably, the participation rates
for all EMF measurements except wire codes were low. Stratified analyses based onwhether controls were concurrently accrued with cases yielded inconsistent risk estimateswith wire codes.]Gurney et al. (Gurney et al., 1996) initiated an epidemiological study to assess therelationship between childhood brain cancer and proximity to high-current power lines.
The study population was derived from the Seattle, Washington, component of themulticenter United States West Coast Childhood Brain Tumor Study and comprised
children < 20 years of age at diagnosis of a primary brain tumor in 1984Ð90, who wereidentified from a population-based cancer registry. Of the 179 eligible cases, 133participated in the study (a participation rate of 74%). A control group of children
stratified within the same range of birth years and county of residence as the cases was
identified by random-digit dialing, which resulted in the participation of 270 controls outof 343 eligible for inclusion (a participation rate of 79%). Exposure was assessed by the
five-level wire coding scheme developed by Wertheimer and Leeper (Wertheimer &Leeper, 1982).
Gurney et al. (Gurney et al., 1996) reported no association between the occurrence ofpediatric brain tumors and residential exposure to magnetic field sources, which included
analyses of five-level and two-level wire code configurations. The risk for brain tumor did
not increase with increasing exposure (relative to underground wiring) when the five-level
Wertheimer and Leeper wire code configuration was analyzed, the relative risks being 1.3(95% CI, 0.7Ð2.1) for very low current configuration, 0.7 (0.3Ð1.6) for low current
configuration, 1.1 (0.6Ð2.1) for high current configuration, and 0.5 (0.2Ð1.6) for very highcurrent configuration. When the wire codes were dichotomized (high vs. low), the relativerisk was approximately unity. After evaluating 13 potential risk factors, the authors
found no associations, and thus crude risk estimates were reported. [The limitations
associated with random-digit dialing to select controls are applicable to this study. A
strength is the large number of potential confounding factors evaluated.]Linet et al. (Linet et al., 1997) assessed the association between childhood ALL andresidential exposure to magnetic fields for children aged < 15 who resided in Illinois,
Indiana, Iowa, Michigan, Minnesota, New Jersey, Ohio, Pennsylvania, or Wisconsin andwere registered with the ChildrenÕs Cancer Group, in whom ALL was diagnosed during
the period 1989Ð94. A total of 767 cases were eligible for inclusion. Random-digit
telephone dialing was used to recruit the controls, who were individually matched to the175cases by the first eight digits of their telephone numbers (including area code), age, andrace, resulting in 725 controls who were eligible for inclusion. The authors reported aparticipation rate of 78% for cases and 63% for controls.
Magnetic fields were measured at all subjectsÕ residences with EMDEX-C meters. The
standardized measurement protocol followed included 24-h measurements in the childÕs
bedroom (with the meter placed under or adjacent to the bed), 30-s measurements in thecenter of the childÕs bedroom, the family room, the kitchen, and the room in which themother slept during the subjectÕs pregnancy, and a 30-s outdoor measurement madewithin 1 m of the front door of the residence. A single summary exposure metric for eachhome was calculated from a weighted average of the room measurements (see section
2.3.1). The weights were based on the typical amount of time spent in each room
according to the childÕs age (Kleinerman et al., 1997). For each child under the age of five,the investigators attempted to measure magnetic fields in all homes the subject had lived
in for at least six months and required that at least 70% of the childÕs life had been spentin the measured homes. For children over the age of five, the investigators measured amaximum of two homes lived in during a reference period of five years immediately
preceding diagnosis, and required that the child had lived for at least 70% of the reference
period in the measured houses. A weighted average of all homes was used as the summary
exposure metric. On the basis of the distribution of the measurements in the control
homes, the following exposure categories were chosen a priori for the summary
measurements of residential magnetic fields: 0.065 mT, 0.065Ð0.09 mT, 0.1Ð0.19 mT, and³ 0.2 mT . Higher exposures (up to 0.5 mT) were also measured. Wire code classifications(the five-level Wertheimer-Leeper classification and the modified three-level KauneÐ
Savitz scheme) were assigned to the subjectsÕ main residences for a subgroup of 408 caseÐ
control pairs in which both the case and the control had been residentially stable, i.e. lived
for at least 70% of the reference period in one home, and to those in which the family had
lived during the motherÕs pregnancy (230 matched caseÐcontrol pairs). [In most cases, thefields were measured within two years of diagnosis; thus, the measurements taken are
more representative of exposure during the relevant etiologic period than fields many
years and sometimes decades after diagnosis. There are apparent discrepancies in thereported participation rates of all eligible subjects: we calculate participation rates of 68%
for cases and 48% for controls. Another concern is that wire codes were assessed for only
43% of the eligible cases and 32% of the eligible controls. Limitations associated with theuse of random-digit dialing to select controls apply to this study.]
For TWA exposure to ³ 0.2 mT, the matched and unmatched analyses give relative risksof 1.5 (95% CI, 0.91Ð2.6) and 1.2 (0.86Ð1.8), respectively. For exposure to ³ 0.3 mT,matched analyses were not reported, but the unmatched analyses gave a relative risk of
1.7 (1.0Ð2.9). For the a priori measurement categories, when exposure was evaluated as acontinuous variable, the p value for trend was 0.09 for the matched analysis and 0.15 forthe unmatched analysis. When exposure was evaluated as a categorical variable, the pvalue for trend was 0.12 for the matched analysis and 0.22 for the unmatched analysis. In
the matched analyses based on wire code configurations, the risk for childhood ALL was
not associated with very high wire codes in the subjectÕs main residence: relative risk =176

0.88 (95% CI, 0.48Ð1.6) for the Wertheimer-Leeper wire code and 1.0 (0.65Ð1.7) for the
KauneÐSavitz wire code. The results reported for the 225 matched caseÐcontrol pairs forwhich wire codes were assessed for the mothersÕ residences during pregnancy showed atrend (p = 0.07) for the WertheimerÐLeeper wire code configuration.
All of the unmatched risk estimates reported by Linet et al. (Linet et al., 1997) were
adjusted for the age of the subject at the reference date, the subjectÕs gender, the motherÕs
educational level, and family income. These adjustments for potentially confounding
variables had little effect on the risk estimates. The authors note that a limitation of thisstudy is the use of random-digit dialing, which was believed to have resulted in higherfamily incomes of controls as compared with cases. The authors interpret their study as
providing little evidence for an association between exposure to magnetic fields andchildhood leukemia. [It is unclear why the criteria for matching controls to cases did notinclude gender, since males are at greater risk for leukemia than females.] (Robison et al.,1995) [The heterogeneity of wire codes as estimates of exposure to magnetic fields acrossgeographic areas (nine states) may also be of concern. The use of TWA measured fields inseveral different homes may have diluted the effect (e.g. high exposures for short times
averaged with low exposures for longer times). The results based on 24-h measured fields
strengthen the evidence for an association, especially in view of the pattern of trend in theestimates; however, the results for wire codes detract from this evidence.]
Tynes and Haldorsen (Tynes & Haldorsen, 1997) conducted a nested case-control studyof Norwegian children < 15 years of age who had lived in a census ward crossed by powerlines (voltages of 45 kV or more in urban areas and more than 100 kV in rural areas) during
at least one of the years 1960, 1970, 1980, 1985, 1987, or 1989. Cases were identified
from the Cancer Registry of Norway and consisted of children in whom cancer had been
diagnosed during the years 1965-89. For each case, five controls were selected from thecohort who had been alive at the time of diagnosis of the case and were matched bygender, year of birth, and municipality. Calculated historical magnetic fields were theprimary basis for classifying study subjects into different categories of exposure. All
power lines 11 kV or greater were considered in the calculations of exposure.
Underground cables were not taken into account because it was assumed that they were
not a significant source of magnetic fields. Categories for the analyses of exposure wereobtained for a three-level ordinal scale from average background levels in a typical
Norwegian residence (< 0.05 mT) and the median TWA exposure of the controls (0.14mT). [The calculated fields were not validated by actual measurements.]
The risk for cancers at all sites combined in relation to calculated TWA exposure tomagnetic fields from birth to diagnosis was estimated to be 1.9 (1.2Ð3.3) for the category
0.5 £ 0.14 mT and 0.9 (0.5Ð1.8) for exposure to ³ 0.14 T; the corresponding risks forleukemia were 1.8 (0.7Ð4.2) and 0.3 (0.0Ð2.1), respectively. Adjustment forsocioeconomic status and number of residences did not affect these results. [The results
are based on a low exposure category (0.14 mT, and few subjects were exposed tomagnetic field strengths of ³ 0.14 mT: approximately 2% (TWA exposure) and 4%(calculated exposure closest to time of diagnosis) of the study population.]

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Michaelis et al. (Michaelis et al., 1998; Michaelis et al., 1997) performed a populationbased caseÐcontrol study to explore the association between childhood leukemia andexposure to EMF in Lower Saxony, Germany, and later used the same study design inBerlin; they then pooled the two sets of results. Cases were recruited from the GermanChildhood Cancer Registry. The eligibility criteria for the study in Lower Saxony were
newly diagnosed leukemia during the years 1988Ð93, date of birth after 1 July 1975, < 15years of age at diagnosis, and a resident of Lower Saxony at the date of diagnosis. For thecases in Berlin, the diagnosis had to have been made between January 1991 and
September 1994, and the children had to be residents of Berlin at the time of diagnosis. A
total of 283 cases were eligible. Controls (919) were selected from the respective local
government offices for registration of residents and were matched to the cases by gender,
date of birth, and district within the city. Questionnaires were distributed to patients andcontrols to ascertain their residential history and potential confounding factors, i.e.
socioeconomic status and degree of urbanization. The participation rates were 62% forcases and 45% for controls. [The age ranges and observation periods differed for the twocohorts, but these were controlled for in the analysis.]
Exposure was assessed by two methods: measurements of the magnetic field over a 24-h
period and indoor spot measurements with an EMDEX II meter. The 24-h measurements
were collected in the subjectÕs bedroom and in the living room of the residence where thechild had lived longest before the date of diagnosis. Measurements were made 1Ð7 years
after diagnosis. The median magnetic field strength during the 24-h period in the childÕs
bedroom was the primary measure used in the analyses. Median values were preferred tomean values since they are less likely to be influenced by outlying values. The relativerisk estimates were adjusted for gender, age, socioeconomic status, and degree ofurbanization.
The exposure was dichotomized at 0.2 mT, and the risk estimate was 2.3 (95% CI, 1.2Ð12). The risk was higher in Lower Saxony, 3.2 (0.7Ð15) than in Berlin, 1.3 (0.1Ð12). Whenthe analysis was restricted to the median magnetic field measured during the night, the risk
estimate for the 0.2 mT cut-point was 3.8 (1.2Ð12). No associations were reported
between the incidence of childhood leukemia and indoor spot measurements. [The main
limitations of this study are the low percentage of subjects exposed to magnetic fields atstrengths > 0.2 mT, the reduction in the study size due to inability to obtain permission
to measure residential magnetic fields, and the lower participation rate among controls
than among cases.]

4.3.2 Effects of appliances
Several epidemiological studies have been conducted to determine the association between
exposure to magnetic fields attributed to the use of various electrical appliances andchildhood cancer. Appliances that can result in substantial exposure were usually studied
and assessed on the basis of each subjectÕs recall of use. Electrical appliances may be apotentially important contributor to overall exposure to EMF.
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Savitz et al. (Savitz et al., 1990) examined the association between the incidence ofchildhood cancer and prolonged exposure to electrical appliances on the basis of
information from interviews conducted during their previous caseÐcontrol study (Savitz etal., 1988), described in the previous section. The appliances of primary interest in thisstudy were electric blankets, heated water-beds, electric heating pads, and bedside electric
clocks, and they studied both the motherÕs and the childÕs use, i.e. prenatal and postnatal
exposure, respectively. Exposure was first examined as ÔeverÕ or ÔneverÕ use, separately
for prenatal and postnatal exposures; more detailed information obtained included electricblanket and heated water-bed settings, duration of use, and timing of use. Complete
information on use of appliances was obtained for 233 mothers of patients (65% of thoseeligible) and 206 mothers of controls (74% of those eligible) and for 244 patients (69% of
those eligible) and 216 controls (78% of those eligible).
Use of none of the appliances considered in the study was associated with a notably
elevated relative risk (ever vs. never use) for cancers at all sites. The estimated, unadjusted
risks with prenatal exposure to electric blankets were 1.8 (95% CI, 0.9Ð4.0) for childhood
brain cancer, 1.3 (0.7Ð2.6) for leukemia, and 1.1 (0.4Ð3.6) for lymphoma. In analyses ofprenatal exposure stratified by electric blanket use during the first trimester, the estimatedrisks were 1.6 (0.8Ð3.2) for cancers at all sites, 4.0 (1.6Ð9.9) for brain cancer, and 2.3(1.0Ð5.8) for leukemia. For postnatal use of electric blankets, the crude risk estimates
were 1.5 (0.6Ð3.4) for cancers at all sites, 1.5 (0.5Ð5.1) for leukemias, 1.2 (0.3Ð5.7) for
brain cancer, and 1.0 (0.2Ð8.6) for lymphoma.
[The methodological limitations of this study include those with the control selection
process, described by Savitz et al. (Savitz, 1988) and the fact that the study size wasseverely limited for assessing the exposures of interest, especially in the postnatal
analyses, as very few children were exposed to electric blankets or electric water-bed
heaters. ParentsÕ recollection of appliance use was the only method used to assess
exposure, and their recall may be incomplete; furthermore, the parents of patients mightreport differently from those of controls, resulting in recall bias. The questionnaire was
not validated. Most of the statistical analyses in this study were based on Ôever/neverÕ
use of appliances. An underlying assumption is that the pattern of appliance use amongusers was similar for cases and controls; if the patterns of use were dissimilar, thesensitivity to detect an association would be diminished.]
London et al. (London et al., 1991) examined the association between the incidence ofchildhood cancer and prolonged exposure to electrical appliances on the basis of
information collected at interviews during their study of residential exposure. The
appliances of primary interest were those that could produce considerable magnetic fields.
ChildrenÕs exposure was estimated on the basis of regular use (at least once a week) of theappliance. The statistical analyses were based on regular vs. infrequent use (less than once
per week). MothersÕ exposure was based on use of the appliance at any time during
pregnancy. Complete information on use of 15 appliances by mothers and children was
obtained for 232 cases and 232 controls; the participation rates were 70% for cases and
90% for controls.

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The relative risks associated with use of 11 of the appliances were greater than the null.
The risks for leukemia among children who used black-and-white televisions and electric
hair-dryers at least once a week were 1.5 (95% CI, 1.0Ð2.2) and 2.8 (1.4Ð6.3),
respectively, as compared with nonusers and children who used these appliances lessthan once a week. The largest relative risks were associated with use of electric blankets
and curling irons, but these estimates were unstable because of the small number ofsubjects. The risks associated with use by the mothers of three of the five appliances thatwere evaluated were greater than the null. [The limitations of this study are similar to
those described for the study of Savitz et al.] (Savitz et al., 1990).
As part of the study of Preston-Martin et al. (Preston-Martin et al., 1996b), a
questionnaire was administered to mothers and fathers about exposures and conditions
thought likely to be related to the risk for pediatric brain tumors. Mothers were asked
about exposure to appliances during their pregnancy and about their childÕs daily
exposure to specific appliance-related sources of magnetic fields. The exposures were
examined as ÔeverÕ or ÔneverÕ used, separately for the motherÕs exposure during pregnancy
and the childÕs exposure. Complete information on appliance use by mothers and children
was obtained for 304 cases and 304 controls.
The risks associated with use by the mothers of six of the seven appliances that were
evaluated were greater than the null. An approximately two-fold increase in risk for brain
tumors was reported among children whose mothers had slept in electrically heatedwater-beds during pregnancy (2.1; 1.0Ð4.2). For the 12 appliances that were evaluated forchildren, the relative risks were greater than the null for six. As for the mothers, there wasa two-fold increase in risk among children who slept in electrically heated water-beds (2.0;0.6Ð6.8). [With such low percent use of these appliances, it is difficult to assess theirimpact with respect to cancer risk.]
Preston-Martin et al. (Preston-Martin et al., 1996a) evaluated the effects of use of electricblankets and water-bed heaters on the risk for pediatric brain tumors. Since there were notenough cases in Los Angeles to adequately address this hypothesis, cases were included
from two other regions that participated in the multicenter US West Coast Childhood
Brain Tumor Study: Seattle, Washington and San Francisco, California. The cancer
registry at each location was used to identify 813 cases, of which 540 children wereconsidered to be eligible on the basis of information in the registry and the study criteria
and were enlisted in the study as cases. Controls were identified and recruited from thesame geographic regions in which the cases arose by a two-step random-digit telephonedialing procedure. This resulted in a comparison group that was similar to the cases withregard to gender and age and at ratios of approximately two controls per case in Seattle
and San Francisco and one control per case in Los Angeles, for a total of 801 eligible
controls. Of those eligible to participate, 73% of cases and 74% of controls wereinterviewed for the study.
Maternal use of electric blankets during pregnancy with the patient, regardless oftrimester or use, was not associated with subsequent risk for brain tumor; thus, the180relative risk as compared with nonusers of these appliances was 0.9 (95% CI, 0.6-1.2).
Similar results were reported for prenatal use of water-beds with electric heaters, but therisk varied substantially with geographic area. The relative risk for pediatric brain tumor
associated with maternal use of heated water-beds during pregnancy was 2.1 (1.0Ð4.4) for
Los Angeles participants and 0.7 (0.4Ð1.0) for participants from San Francisco andSeattle. [This study includes information about use of electric blankets and heated waterbeds that was reported by Preston-Martin et al. and Gurney et al.] (Preston-Martin et al.,1996b) and (Gurney et al., 1996). [Although data from three study sites was pooled,exposure to electric blankets and heated water-beds was relatively uncommon, especiallyamong children. Furthermore, reported use of these appliances from the questionnaires
may not have been a sensitive enough measure to detect differences in brain cancer risk
due to prolonged exposure to magnetic fields.]
Gurney et al. (Gurney et al., 1996) assessed exposure to magnetic fields from electricblankets and heated water-beds on the basis of responses to a questionnaire administeredin person to 133 patients and 270 controls, with participation rates of 74% among cases
and 79% among controls. A mailed questionnaire was used subsequently to collectinformation on use of electric heating and electric appliances other than electric blankets
and water-beds. Questionnaires were returned for 98 cases and 208 controls. The analyses
of use of electric heaters (within three years before diagnosis of the cancer) and applianceswere based on whether the subject had ever used the appliance in question or never usedit.
MothersÕ use of seven appliances and heat sources was evaluated. The only increase inrelative risk was that associated with prenatal use of an electric water-bed. Of the relative
risks associated with use of 19 appliances and heat sources that were evaluated forchildren, eight were greater than the null. [The study size was severely limited forassessing the exposures of interest. Recall may have been incomplete, and it is unclear
whether the parents of the patients report differently from those of controls, resulting inrecall bias. Most of the statistical analyses in this study were based on Ôever/neverÕ use of
appliances. An underlying assumption is that the pattern of appliance use among users
was similar for cases and controls; if the patterns of use were dissimilar, the sensitivity todetect an association would be diminished.]
As part of a study of residential exposure to magnetic fields, Linet, et al. (Linet et al.,1997), Hatch, et al. (Hatch et al., 1998), evaluated the association between childhood ALL
and use of electrical appliances during pregnancy and childhood. The study population is
described in section 4.2.2. Personal interviews were conducted with 788 patients and 699
controls, corresponding to participation rates of 84% among cases and 54% among
controls. [The authors report participation rates of 88% and 64%, but the number of
eligible cases was 942 and that of eligible controls, 1232.] Of these participants, 640
matched pairs were used in the analysis. Questions were asked about the motherÕs use
during pregnancy and the childÕs use of electric blankets, mattress pads, heating pads,
water-beds, stereos or other sound systems, television, video machines in arcades,
computers, microwave ovens, sewing machines, hair-dryers, curling irons, humidifiers,

181

and electric clocks. Use of stereo systems without headsets, night lights, and ceiling fans
was considered unlikely to have resulted in substantial exposure to magnetic fields, butthey were included as Ôred herringÕ variables to evaluate the potential for recall bias. Theinterviewers asked for the childÕs age when starting and stopping use of a specificappliance and the frequency of use during the year before diagnosis. For three appliances
associated with potentially high exposure to magnetic fields (electric blankets, water-beds,
and hair-dryers), questions were asked about the frequency of use during the last year ofuse if the child had stopped using the appliance. The authors analyzed the use of each of
the appliances separately and did not create an overall estimate of exposure to magnetic
fields from appliances. Mattress pads and electric blankets were analyzed together.
Matched analyses were conducted with adjustment for income and maternal education.
Potential confounding from parental age, occupation, smoking, type of dwelling,urbanization, number of siblings, and breast feeding were evaluated. Age- and genderspecific analyses were done, and the motherÕs use was analyzed according to trimester.
The estimated risks were 1.6 (95% CI, 1.1Ð2.3) for motherÕs use of electric blankets or
mattress pads and 1.5 (1.0Ð2.1) for their use of heating pads and humidifiers, but with noconsistent doseÐresponse pattern. When frequency of use was evaluated, a reduced risk
was found for use of sewing machines (0.76; 0.59Ð0.98). The risk estimates for use ofother appliances were close to unity.
Elevated risks were found for childrenÕs use of electric blankets (2.8; 1.5Ð5.0), hair-dryers(1.6; 1.2Ð2.1), curling irons (1.7; 0.91Ð3.3), video arcade machines (1.7; 1.2Ð2.3), soundsystems with headset (1.3; 0.97Ð1.8), and video games connected to a television (1.9; 1.4Ð
2.7). Consistent doseÐresponse patterns were found for use of sound systems with aheadset, video arcade machines, and video games connected to a television, but not for useof electric blankets, hair-dryers, or curling irons. The risk estimates for other applianceswere close to unity, except for night-lights (0.81; 0.63Ð1.0). None of the Ôred herringÕ
variables was associated with an increased risk. Time spent watching television was
associated with disease, and the risk increased with increasing time. Watching television at
closer than 6 feet (2 m) was also associated with disease, but the highest risk was foundfor distances ³ 4 to £ 6 feet (³ 1.3 and £ 6 m; relative risk, 1.7; 1.2Ð2.4). For distances <4 feet (< 1.3 m), the relative risk was 1.6 (1.1Ð2.4).
When the time spent watching television and the distance from the television werecombined, inconsistent doseÐresponse patterns were seen. The authors emphasized thepotential for differential recall bias, especially when patterns of use changed after
diagnosis, as may be the case for television viewing patterns. They also mention thepossibility that mothers of children with ALL may be more prone to remember use of
appliances discussed in the media as potential risk factors for leukemia, such as electricblankets. Another source of error noted by the authors is potential selection bias due tothe use of random-digit dialing for control selection and the lower participation rate among
controls, both being associated with socioeconomic status. The authors also mention thepossibility of confounding from some factor related to the type of life-style associatedwith, for example, watching television for many hours per day. They found it unlikely
182

that the associations found reflect a causal association between exposure to magnetic
fields and childhood ALL. [The inconsistent doseÐresponse patterns may also be theresult of nondifferential exposure misclassification.] Selection bias is unlikely to explain
the findings for use of electric blankets. Differential recall bias may have affected theresults, but a comparison between answers from an earlier telephone interview and thoseobtained at the later personal interview about electric blanket use did not indicate
differences in the recall between cases and controls. [Questions on other appliances were
not validated. Another limitation is the considerable lower participation rate among
controls as compared to cases. Finally, the magnetic fields of the appliances were notmeasured.]

4.3.3 Meta-analyses of studies of effects of power lines
In reviewing the individual epidemiological studies, it is difficult to summarize and draw
overall conclusions about a possible association between exposure to ELF EMF and theincidence of childhood cancer. These difficulties arise due to differences in study design,case selection, identification of controls, exposure assessment methods, and accounting
for such factors as confounders and effect modifiers. Furthermore, a common feature ofmost of the studies was the lack of a large population of highly exposed children.
Meta-analysis provides a means for summarizing the results of individual studies into asingle measure of effect (Fleiss, 1993). The objectives of a meta-analyses often include
identification and review of all studies conducted on a specific topic; assessment of theconsistency and comparability of the results of each identified study; estimation of
average measures of effect, if studies are sufficiently similar; and assessment of reasonsfor heterogeneity (Blair et al., 1995).
Four meta-analyses have been conducted of studies of the possible association between
exposure to magnetic fields and the incidence of childhood cancers, in which summary
effect measures were stratified by exposure metric (wire codes, distance from electricalfacility, calculated magnetic fields, and measured magnetic fields) (NRPB, 1992); (Ahlbom
et al., 1993); (Miller et al., 1995); (Meinert & Michaelis, 1996). These are summarized inTables 4.25 and 4.26. In general, the summary risks for each of the metrics consideredwere elevated but less than 2.0 at all cut-points. [In general, as the number of studies
included in the meta-analysis increased, the confidence intervals narrowed, indicating
increasing statistical power; however, the effect estimates did not change substantially.
Use of different exposure metrics, such as 24-h measures vs. spot measures, or cutpoints, such as 0.2 mT vs. 0.3 mT, can result in quantitative but not qualitative
differences.]
Wartenberg and colleagues (Wartenberg et al., 1998) and National Academy of Sciences(NRC et al., 1997) conducted a more extensive meta-analysis of the studies of thepossible association between exposure to magnetic fields and the incidence of childhood

183

leukemia and brain tumors. In addition to calculating a summary effect measure, they
conducted a limited sensitivity analysis, assessed the heterogeneity among the studies,
evaluated possible doseÐresponse relationships, evaluated the likelihood of publicationbias, and assessed the robustness of results to inclusion of additional studies. They also
provided a more carefully considered rationale for grouping studies.
The reported summary effect measures are similar to those reported in previous metaanalyses: generally > 1.0 but < 2.0. The results were moderately robust to exclusion ofindividual studies. Substantial heterogeneity was reported for wire codes and proximity toelectrical facilities for both leukemia and brain tumors. Analyses to characterize the sourceof the heterogeneity gave equivocal results. The relative risk estimates for doseÐresponse
relationships for spot measures were weakly elevated, those for calculated fields wereslightly higher, and those for wires codes (converted to magnetic fields by using the midrange of the wire code category) were still slightly higher. There is little evidence forpublication bias. Calculations showed that inclusion of an extremely large study would be
required to substantially change the reported summary estimates of effect.
[This meta-analysis included several studies that this Working Group excluded fromconsideration in their deliberations.]

4.3.4 Summary
Cancers at all sites
The Working Group considered that an evaluation of cancers at all sites combined would
not be informative because it would be driven largely by the results for leukemia and brain
cancer.
Childhood leukemia
Four studies in which wire codes were used to assess exposure to EMF were considered
to be of sufficient quality to be used in the evaluation of an association between theincidence of childhood leukemia and exposure to magnetic fields. Three of the studies
found an increased risk (Wertheimer & Leeper, 1979); (Savitz et al., 1988); (London et al.,1991), and one study found no effect on the risk for childhood leukemia (Linet et al.,1997). A trend of increasing risk with increasing wire codes was found by both Savitz et
al. and London et al. Wertheimer and Leeper did not assess trend. The unblindedassessment of the wire codes in the latter study may have affected the results, but it isunlikely that this potential bias can fully explain the observed increase in risk.
Selection bias introduced by the control selection technique is unlikely in the Wertheimer
and Leeper study, because a birth registry was used as the population source. In the other184three studies, random-digit dialing was used to select controls, which may have introduced
some bias toward higher socioeconomic status among the controls. If higher
socioeconomic status is related to lower wire codes, use of random-digit dialing may have
led to an overestimation of the risk. As Savitz et al., London et al., and Linet et al. all used
random-digit dialing to select controls, it is unlikely that the associated bias would haveaffected only the risks found by Savitz et al. and London et al. The study of Savitz et al.
has a further limitation in the way in which controls were selected, requiring them to beresidentially stable; this may have introduced bias leading to an overestimation of the risk,
but it is unlikely that this could entirely explain the larger risk estimate. The observed
elevated risks and doseÐresponse patterns cannot be explained by selection bias.
Confounding from other risk factors for childhood leukemia must also be considered. The
etiology of this disease is largely unknown. The most frequently discussed factors that
may be related to both wire codes and childhood leukemia are traffic density andsocioeconomic status. Confounding from traffic density was evaluated in all three studies
that showed increased relative risks and was found not to explain the observed
association. It was not evaluated in the study of Linet et al. The potential impact ofsocioeconomic status was evaluated in all four studies: it did not explain the observed
results. Furthermore, Savitz et al. evaluated a substantial number of additional potential
risk factors, which were also shown to have little effect on the risk estimates.
The lack of an association with wire codes in the study by Linet et al. is difficult to
explain, given the associations observed in the other studies. The validity of using wire
codes in regions other than in Denver is not clear, but the potential shortcomings shouldhave applied to the studies of both Linet et al. and London et al. Linet et al. included
several regions in their study, however, and the validity of using the wire codes asestimates of exposure to magnetic fields may vary among the regions. The fact that the
proportion of subjects exposed to magnetic fields > 0.2 mT was considerably higher in the
study of Savitz et al. than in those of Linet et al. or London et al. may explain some of thedisparity in the results. Linet et al. included only cases of acute lymphoblastic leukemia,
while the other studies included all types of leukemia. The results of the studies, whentaken together, support the association between classification of exposure from wire
codes and the incidence of childhood leukemia. This is further supported by the results ofthe formal meta-analysis, which found, on average, a 40% excess risk for leukemia (OR =1.5; 95% CI, 1.0Ð2.2) (Wartenberg et al., 1998).
Among the studies in which calculated fields were used to assess exposure to magnetic
fields, four Nordic studies were considered to be of sufficient quality to be used in theevaluation. Three of the studies found increasing leukemia risk with increasing calculated
fields (Feychting & Ahlbom, 1993; Olsen et al., 1993; Verkasalo et al., 1993), and asmaller study found no effect (Tynes et al., 1992). All four studies were populationbased, with minimal potential for selection bias both in terms of control selection andparticipation rates. The exposure assessment method used in these studies is based on thelaws of physics and engineering design and provides estimates of the exposure for a
relevant etiologic period from historical information about line loads and configurations.

185

Thus, the exposure estimates may be less subject to misclassification than those in thestudies based on wire codes. The main limitations of all four of the studies are the small
number of cases and the low prevalence of exposure. Potential confounding from traffic
exhaust was controlled in the Swedish study and did not change the effect estimate.
Adjustment for socioeconomic status was made in all of the studies except that in
Finland, again with no effect on the observed risk estimates. The results of these studies,when taken together, support an association between exposure to calculated magnetic
fields and the incidence of childhood leukemia. This conclusion is further supported by
the results of the formal meta-analysis which found, on average, a 63% excess risk forleukemia (OR = 1.6; 95% CI, 0.8Ð3.0) (Wartenberg et al., 1998).
Of the studies in which spot measurements were used to assess exposure to magnetic
fields, three were considered to be of sufficient quality to be used in the evaluation(London et al., 1991; Michaelis et al., 1998; Savitz et al., 1988). The results of these threestudies are inconsistent, two being close to unity and the third (Savitz et al.) showing
increased risks. The very low participation rate among cases in the study of Savitz et al.
limits its validity. The study of Feychting and Ahlbom (Feychting & Ahlbom, 1993) is
not included in this assessment because the spot measurements were made too long after
the relevant etiologic period.
Neither selection bias nor confounding had a major impact on the reported results. The
study of Michaelis et al. is limited by the small number of exposed subjects. Exposure
misclassification is a potential limitation in all three studies. The usefulness of spotmeasurements for retrospective assessment of exposure to magnetic fields during the
etiologically relevant period has been questioned. These studies do not provide sufficient
information to evaluate the association between exposure to magnetic fields evaluated byspot measurements and the incidence of childhood leukemia. Furthermore, the formal
meta-analysis did not find an appreciable excess risk for leukemia (OR = 1.2; 95% CI,
0.7Ð2.1) (Wartenberg et al., 1998).
Three studies in which 24-h measured magnetic fields were used to assess exposure tomagnetic fields were considered to be of sufficient quality to be used in an evaluation of
the association between the incidence of childhood leukemia and exposure to magnetic
fields (Linet et al., 1997; London et al., 1991; Michaelis et al., 1998). The results of all
three studies showed an increased risk for children in higher exposure classes. The datareported by Linet et al. showed an exposureÐresponse relationship, which was not foundby London et al. and was not assessed by Michaelis et al.
The studies of both Linet et al. and London et al. had potential limitations due to use of
random-digit dialing to select controls. Control selection in the study of Michaelis et al. is
unlikely to be subject to selection bias. The low participation rates in all three studies
might have resulted in selection bias. Confounding due to socioeconomic status wascontrolled in all three studies. Confounding by traffic exhaust was addressed in previous
studies in which other exposure assessment methods were used, and was found unlikely
to affect the results. The study of Michaelis et al. is limited by the small number of186

exposed subjects, and there were few highly exposed subjects in all three studies. It is notclear how well a 24-h magnetic field measurement reflects exposure during the relevant
etiologic period, nor how representative it is of long-term exposure, given the weekly,
seasonal, and secular patterns. This method is, however, an improvement over spotmeasurements of magnetic fields. The study of Linet et al. is an improvement over theprevious studies because of the markedly shorter time between diagnosis and exposure
assessment.
The results of these studies provide some support for a possible association between
exposure based on 24-h measured magnetic fields and the incidence of childhood leukemia.
This conclusion is further supported by the results of the formal meta-analysis, whichshowed, on average, a 50% excess risk (OR = 1.5; 95% CI, 1.0Ð2.3).
Three studies of appliance use were considered to be of sufficient quality to be used in an
evaluation of the association between the incidence of childhood leukemia and exposure tomagnetic fields (Hatch et al., 1998; London et al., 1991; Savitz et al., 1990). The results
do not fit a coherent pattern, but elevated risks were reported for a variety of appliancesin different studies. Many increased risk estimates were found by Hatch et al.; however,
it is interesting to note that no associations were found for the three appliances that do
not to involve significant exposure to magnetic fields (i.e. those that were included in the
study to assess the possible role of recall bias). The possibility of recall and reporting
bias in the study of Hatch et al. and in any of the other studies cannot, however, be ruledout. Furthermore, chance cannot be ruled out as an explanation for the observations. In
addition, low participation rates and use of random-digit dialing in all three of the studies
may have influenced the results in any direction. These studies provide inadequate
evidence to assess an association of use of appliances and the incidence of childhood
leukemia.
Childhood nervous system tumors
Four studies were considered to be of sufficient quality to be used in an evaluation of theassociation between the incidence of childhood brain tumors and classification of exposure
based on wire codes. The two early studies found an increased risk (Savitz et al., 1988;
Wertheimer & Leeper, 1979), and the two later studies found no effect on the incidence ofchild brain tumors (Gurney et al., 1996; Preston-Martin et al., 1996b). Selection bias is anunlikely explanation for the observed increased risks in the earlier studies or the lack ofassociation in the later ones. A large number of potential confounding factors were
evaluated in three of the studies. The disparity of the results precludes the drawing of aninference. The formal meta-analysis bears this out, providing a relative risk estimate of 1.2
with an associated 95% confidence interval of 0.7Ð2.2 (Wartenberg et al., 1998).
Equally inconclusive results were observed in studies of the possible association between
childhood brain tumors and spot-measured magnetic fields, 24-h measured magnetic fields,
and use of appliances. The data from studies on childhood brain tumors and calculated187

magnetic fields provide some evidence that there is no association; however, these results
are based on a very small number of cases, and chance cannot be ruled out as an
explanation for the lack of association. The results of the meta-analysis results areinconclusive with regard to all exposure metrics.
Childhood lymphoma
The number of cases of lymphoma in each of the studies was too small for any reliable
inferences to be drawn.
Reasoning for the evaluation of degree of evidence from studies of childhood leukemia
The results of the studies of a possible association between exposure to magnetic fields
and the incidence of childhood leukemia present a complex picture. The most compelling
data come from the Nordic studies, in which calculated magnetic fields were used as themetric of exposure to magnetic fields, arguably the most accurate way of reconstructing
exposure during the relevant etiological periods, especially if they are very long. These
data are supported by the results of studies in which 24-h magnetic field measurements
and wire codes were used as the exposure metrics. The only exposure metric that did notappear to be associated with an increased leukemia risk with increased exposure was spotmeasurement, but this exposure metric has been criticized as being unrepresentative of
long-term exposure to magnetic fields because it fails to capture the daily, weekly,
seasonal, and long-term fluctuations in magnetic field strength. The studies of the possible
association of use of appliances and the incidence of childhood leukemia were not viewed
as contributing to this evaluation. Chance is an unlikely explanation for the observed
associations, and the doseÐresponse patterns observed strengthens this conclusion.
Confounding seems to be an unlikely explanation for the observed results. A confoundermust be associated with a sufficiently large relative risk to overcome that associated withmagnetic fields. Given the extensive search for possible confounders and the fact that nostrong candidates have been identified, the impact of confounding appears to be minimal.
Selection bias cannot be ruled out in several of the studies; however, increased risk
estimates and consistent doseÐresponse patterns were found also in the Nordic studies, inwhich selection bias is unlikely.
As research on EMF evolved, both exposure assessment and study designs have
improved. The results of studies would thus have been expected to become moreconsistent. In fact, this has not occurred, which raises questions about whether theÔimprovementsÕ in exposure assessment have more accurately captured the relevant EMF
exposure.
In sum, although the exposure metrics used as surrogates for exposure to magnetic fields
are of varying precision, it is difficult to find an explanation other than exposure to188

magnetic fields for the consistency of the reported excess risks for childhood leukemia instudies conducted in different countries under different conditions, with different study
designs. Overall, the Working Group gave preference to the Nordic studies in which bias
in the selection of study subjects can be ruled out and in which the most sophisticatedexposure assessment methods were used. The Working Group considers, with someminor reservations, that the strengths and consistency of these study results aresuggestive in spite of their limitations.
Evaluation
There is limited evidence that residential exposure to ELF magnetic fields is carcinogenic
to children.
[This conclusion was supported by 20 Working Group members; there were 6 votes forÔinadequateÕ evidence, 2 abstentions, and 1 absent.]
There is inadequate evidence with respect to childhood nervous system tumors.
[This conclusion was supported by 25 Working Group members; there were 2
abstentions and 2 absent.]
There is inadequate evidence with respect to childhood lymphoma.
[This conclusion was supported by 25 Working Group members; there were 2
abstentions and 2 absent.]

189

Table 4.20 Summary of epidemiological studies on childhood cancers
Study*

Case selection

Control selection

Exposure metrics

Wertheimer
and Leeper(1979)

Cancer mortality records(1950-1973) of persons lessthan 19 years of age, thatwere born in Colorado andresided in DenverLargest number of cases
used in the analysis: 328

Denver-area birthcertificatesTotal number of controls
enrolled: 344

2-level wire code
(HCC vs. LCC)
Non-blinded wire code
assessment

Cancer onset age
Urban/suburban
Socioeconomic status
Birth order
Maternal age
Traffic congestion
GenderCrude relative risk estimates cited
Potential confounders wereindividually analyzed

Savitz et al.
(1988)All cancer incidence cases
reported in Denver,
Colorado during the years
1976-1983 of persons lessthan 15 years of age
356 cases identified
320 cases had 5-level wire
codes assessed
252 cases were interviewed
128 cases had magnetic fieldmeasurement data

Controls selected via
random digit telephonedialing methods
Matched to cases by age,gender, and telephoneexchange area
278 controls identified
259 cases had 5-level
wire codes assessed
222 cases wereinterviewed
207 cases had magnetic
field measurement data

5-level wire code
In-home electric andmagnetic field spotmeasurements under low
and high power use
conditions

Gender, age
Type of housing
Socioeconomic status
Smoking during pregnancy
Traffic density
Parental age
Race and education
IncomeFamily cancer history,In utero exposure to Alcoholuse
X-rays, influenza, andmedications
Birth defects
Birth order
Birth weight
Illness
Residential stability
Medication x-rays

Control selection procedures
resulted in the controls being more
residentially stable than the cases
Matched analysis not performed
Adjusted relative risk estimates
were described but not presented
in a table and did not change theresults.

190

Confounders analyzed

Additional notes

Table 4.20 (continued)
Study*

Case selection

Control selection

Exposure metrics

Confounders analyzed

Additional notes

London etal. (1991)

All leukemia incidence
cases reported to the Los
Angeles County Cancer
Surveillance Program(1980-1987) of persons lessthan 10 years of age
331 cases identified and
232 interviewed
169 cases had 24-hourmagnetic field measurements
recorded
140 cases had spotmeasurements recorded
219 cases had 5-level wire
codes assessed

Controls were obtained
through friends of cases(1980-1984) and via
random digit telephonedialing methods (19801987)
Matched to cases by age,gender, and ethnicity
257 controls identified
and 232 interviewed
149 controls had 24-hourmagnetic fieldmeasurements recorded
109 controls had spotmeasurements recorded
207 controls had 5-level
wire codes assessed

5-level wire code
Outdoor and in-homeelectric and magnetic
field spot measurements
under low and normal
power use conditions
24-hour magnetic fieldmeasurements
underneath the bed in
the childÕs bedroom
Self-report of applianceuse

Various factors associated withcancer that were reported inprevious studies
Appliance use
Socioeconomic status

Exposures assessed in homes during
an Òetiologic periodÓ defined as theperiod beginning at the estimatedtime of conception and ending on thedate of diagnosis inset Òfor children
aged 1 year or less at time ofdiagnosis date minus 6 monthsÓ forchildren aged 1-2 years at diagnosis;
and one year prior to diagnosis forchildren diagnosed at ages greaterthan 2 years
Matched and unmatched analyses
were carried out since the mean 24hour magnetic field exposure waslower among matched controls ascompared to unmatched

Olsen et al.
(1993)All leukemia, tumor of thecentral nervous system, or
malignant lymphoma
incidence cases reported to
the Danish Cancer Registry(during the period from
April 1, 1968 to December
31, 1986) of persons lessthan 15 years of age
1707 cases identified

Two to five controls wereselected at random fromamong people who had
survived without cancer
until the date ofdiagnosis of the caseControls matched to thecase by gender and date ofbirth4788 eligible controls
identified

Distance fromtransformer substations,overhead lines, andunderground cables
Average calculated
magnetic field exposure
averaged over residence
periodCumulative calculated
magnetic field exposure= (number of months
exposed) multiplied by(average calculated levelof magnetic field at theresidence)

GenderAge at diagnosis
Socioeconomic status
Population density at place ofresidence
Number of changes of address

Analyses controlled for gender andage at diagnosis for each cancergrouping
At cut-point 0.4 mT and greater thenumbers of exposed cases andcontrols is too small to indicate
significant increases in cancer
incidence for individual cancer types.

191

Table 4.20 (continued)
Study*

Case selection

Control selection

Exposure metrics

Confounders analyzed

Additional notes

FeychtingandAhlbom(1993)All cancer incidence cases
reported to the Swedish
Cancer Registry of persons
under 16 years of age livingon a property locatedwithin 300 meters of any
220 or 400 kV power lines
in Sweden (1960-1985)
142 cases identified
141 cases had calculated
fields assessed
89 cases had spotmeasurements recorded

Controls per case wererandomly selected from all
persons under 16 years ofage living on a property
located within 300 metersof any 220 or 400 kV
power lines in Sweden(1960-1985)
Controls matched to cases
by birth year, gender,
residence in the sameparish during the year of
diagnosis or the last year
before the case moved,
lived near the same powerline as the case
558 controls identified
554 controls had
calculated fields assessed
344 controls had spotmeasurements recorded

Distance to power lines fromresidence
In-home magnetic field spotmeasurements under low andhigh power use conditions
Calculations of the magnetic
fields generated by the powerlines at the time spotmeasurements were assessed(calculated contemporary
fields) and for the year closest
in time to diagnosis(historical calculated fields)

Age
GenderYear of diagnosis
Whether or not the subject
lived in the county of
Stockholm
Type of residence (singlefamily home or apartment)
Nitrogen dioxide content as anindex of air pollution from roadtraffic
Socio-economic status

Matched analysis was conducted
Magnetic field spot measurements
taken 5-31 years after diagnosis.
Median 16 years

Verkasalo
et al.
(1993)All primary cancer cases
reported to the Finnish
Cancer Registry ( 19701989) of persons less than
20 years of age living
within 500 m of overhead
power lines of 110-400 kV
in magnetic fields calculated
to be 0.01 mT and greater
140 cases identified

Entire cohort consisted of
68,300 boys and 66,500
girls less than 20 years ofage living during 19701989 within 500 m ofoverhead power lines of110-400 kV in magnetic
fields calculated to be
0.01 mT and greater

Calculated magnetic field
exposure
average exposure
cumulative exposure

GenderAge

Analysis based upon cohort
approach (standardized incidence
ratios) with person years at risk
stratified by gender, age (groupedin 5-year age categories), andexposure category
Analysis included all primarycancers rather than first primarycancers, which resulted in
multiple cancers per person being
counted192

Table 4.20 (continued)
Study*

Case selection

Control selection

Exposure metrics

Confounders analyzed

Additional notes

PrestonMartin etal. (1996a)

Patients under 20 years ofage who were residents of
Los Angeles County andhad a benign or malignant
primary tumor of the brain,
cranial nerves, or cranial
meninges of any histologic
type diagnosed during theperiod January 1, 1984-June30, 1991
437 eligible cases wereobtained
304 cases had complete
interview data
292 cases had wiring maps
assessed for at least one
residence
255 cases had spotmeasurement data
236 cases had at least one
STAR magnetic field profile
110 cases had 24-hourmeasurements assessed in atleast one room

Controls were obtained
via random digit
telephone dialing
methods
Matched to cases by birthdate, age at time ofdiagnosis
433 eligible controls
were obtained
304 controls hadcomplete interview data
269 controls had wiringmaps assessed for at least
one residence
206 controls had spotmeasurement data
181 controls had at least
one STAR magnetic field
profile101 controls had 24-hourmeasurements assessed in
at least one room

Wire coding according to the5-level Wertheimer-Leeper
classification
Spot measurements insideand outside the residenceSTAR magnetic field profiles
24-hour magnetic fieldmeasurements taken in thechildÕs bedroom and otherrooms
Self-report of appliance use

Demographic variables
Parental occupation
Exposures during gestation
Building type
Appliance use
Maternal occupational
exposure to high magnetic
fields during pregnancy

Matched and unmatched analyses
performed
Compared to parents of cases, ahigher proportion of control
mothers and fathers were LatinoCompared to cases, a higher
proportion of controls were in thehighest social class

Gurney etal. (1996)

Patients under 20 years ofage who were diagnosed
with a benign or malignant
primary tumor of the brain,
cranial nerves, or cranial
meninges of any histologic
type diagnosed during theperiod 1984-1990
195 cases were eligible
Largest number of cases
used in the analysis: 120

Controls were obtained
via random digit
telephone dialing
methods
Approximately two cases
per control were stratified
by age, gender, and area ofresidence
270 eligible controls
were identified
Largest number ofcontrols used in theanalysis: 240

Wire coding according to the5-level and 2-level
Wertheimer-Leeper
classifications
Self-report of heating sources
and appliance use

Age, gender, race
County at reference date
Reference year
MotherÕs education
Family history of brain
tumorsPassive tobacco smoke
exposure in the home
Whether the child lived on a
farm
Whether or not the child had
a history of head injury,
x-ray to the head or neck,epilepsy, or fits from severe
fever

A small percentage of cases wereclassified in the very high current
classification (3%)

193

Table 4.20 (continued)
Study*

Case selection

Control selection

Exposure metrics

Confounders analyzed

Additional notes

Linet et al.
(1997)All acute lymphoblastic
leukemia incidence cases
registered with theChildrenÕs Cancer Group(1989-1994) of persons lessthan 15 years of age
942 cases were eligible forthe study
629 unmatched cases hadmagnetic field measurements
recorded (463 case-control
pairs included in theanalysis)408 matched cases had wire
codes assessed in their main
residence
225 matched cases had wire
codes assessed in theresidence of pregnancy

Controls were obtained
via random digit
telephone dialing
methods
Matched to cases by the
first eight digits of thetelephone number, age,and race
1292 controls were
eligible for the study
619 unmatched controls
had magnetic fieldmeasurements recorded(463 case-control pairs
included in the analysis)
408 matched controls had
wire codes assessed intheir main residence
225 matched controls had
wire codes assessed in
the residence ofpregnancy

24-h magnetic fields
measurements in the childÕs
bedroom
30-s measurements in thecenter of the childÕs bedroom,
family room, kitchen, theroom in which the motherslept during the index
pregnancy, and near the front
door of the residence
Wire coding according to the5-level Wertheimer-Leeper
classification and themodified 3-category KauneSavitz scheme 24-h
measurement 1-bedroom

Age
GenderRace
Socioeconomic status
Temporal factors
Urbanization
Type of residence Gender
Race
MathewÕs educational
level

Magnetic field measurements
generally measured within two
years of leukemia diagnosis
Single summary exposure formagnetic field measurements
was calculated based upon aweighted average of the roommeasurements with weights
based upon estimated time spentin each room according to thechildÕs age. Matched andunmatched analyses cited.
Measurements summarized as
time-weighted-average over five
years preceding diagnosis.

194

Table 4.20 (continued)
Study*

Case selection

Control selection

Exposure metrics

Tynes andHaldorsen(1997)All cancer incidence cases
reported to the Cancer
Registry of Norway (19651989) of persons less than
15 years of age who had
lived in a census ward
crossed by high-voltage
power lines (45 kV or morein urban areas and more than
100 kV in rural areas)
during at least one of theyears 1960, 1970, 1980,
1985, 1987, or 1989
532 cases identified
Largest number of cases
used in the analysis: 500

5 controls per case wereselected at random fromamong Norwegianchildren living in a
census ward crossed byhigh-voltage power lines(45 kV or more in urban
areas and more than 100
kV in rural areas) during
at least one of the years
1960, 1970, 1980, 1985,
1987, or 1989 that werealive at the time ofdiagnosis of the caseMatched to cases bygender, birth year, andmunicipality
2122 controls identified
Largest number ofcontrols used in theanalysis: 2004

Distance to power line fromresidenceCalculated magnetic field
exposure estimate
Time-weighted averagecalculated magnetic field
exposure
Time-weighted average
cumulative exposure
Average maximal exposure
MotherÕs exposure at the timeof conception
ChildÕs exposure in the year
closest in time to diagnosis
Average exposure during thefirst year of the childÕs life
Average exposure during thefirst 4 years of the childÕs life

Confounders analyzed
Socioeconomic status
Type of building
Number of dwellings

Gender24-h magnetic field
Controls were obtainedAgemeasurements in the childÕs
from the files of local
Age at diagnosis
bedroomgovernment offices forSocioeconomic status
24-h magnetic fieldregistration of residents
Urbanization
measurements in the living
Two controls per caseroom
were selected
Spot measurement at theone control from the same
residence where the childregistration office as the
lived the longest
case
Non-blinded magnetic field
one control selected fromassessmenta randomly chosen
registration office in
Lower Saxony
328 controls had 24-hmagnetic fieldmeasurements recorded* All studies are case-control with the exceptions of Verkasalo et al. (1993), Lin and Lee (1994), and Li et al. (1998), which are cohort studies
1
Analysis results based upon dwelling counts of cases and controls
Michaelis
et al.
(1997)All leukemia incidence
cases reported to theGerman Childhood Cancer
Registry (1988-1993) ofpersons less than 15 yearsof age and a resident ofLower Saxony at the date ofdiagnosis
219 cases were identified
129 cases had 24-hmagnetic field measurements
recorded

195

Additional notes
Few subjects were exposed to
calculated, magnetic fields
greater than 0.14 mT
The narrow distribution of
exposures resulted in limited
discrimination of the effects ofdifferent exposure indices

Matched analysis conducted
A prior cut-point of mT G waschosenLow percentage of subjects
exposed to measured magnetic
field strengths greater than 2 mT
(1.5% of the entire study
population)

Table 4.21 Childhood leukemia
Studies wire codes
Wertheimer & Leeper(1979)

Exposure classification
Birth address:
LCC
HCC
Death address:
LCC
HCC

Savitz et al.
(1988)

HCC/LCC
VHCC/Buried

London et al.
(1991)

UG+VL
OLCC
OHCC
VHCC

Linet et al(1997)UG+VLCC
OLCC
OHCC
VHCC

Calculated fields
Feychting & Ahlbom(1993)

Olsen et al.
(1993)

Unmatched analyses
(mT)
< 0.1
0.1-0.19³0.2³0.3
Matched analyses:(mT)0.1-0.19
³0.2
(mT)
< 0.1
0.1-0.24
³0.25
³0.40

Leukemia no. cases

RR (95% CI)

84
52

reference
2.28 (1.34-3.91)

92
63

reference
2.98 (1.78-4.98)

27 / 70
7 / 28

1.54
2.75

31
58
80
42

(0.90-2.63)(0.94-8.04)

Acute lymphoblastic
no. of cases

19 / 59
6 / 24

RR (95% CI)

1.28
2.75

(0.70-2.34)(0.90-8.44)

references
0.95 (0.53-1.69)
1.44 (0.81-2.56)
2.15 (1.08-4.26)
175
116
87
24

27
4
7
7

reference
2.1(0.6-6.1)
2.7(1.0-6.3)
3.8(1.4-9.3)
4.3
3.5

829
1
3
3

(1.0-8.9)(0.9-13.6)

reference
0.5(0.1-4.3)
1.5(0.3-6.7)
6.0(0.8-44)

196

references
1.07 (0.74-1.54)
0.99 (0.67-1.48)
0.88 (0.48-1.63)

Table 4.21 (continued)
Studies wire codes
Verkasalo et al. (1993,
1994)

Tynes & Huldersen (1997)

Spot measurements
Savitz et al.
(1988)

London et al(1991)

Exposure classification
Cumulative exposure (mT-years)
0.01-0.39³ 0.40³ 1.0
Average exposure (mT)0.01-0.19³ 0.2
Average exposure (mT)
< 0.050.05-0.13³ 0.14Closest to diagnosis (mT)
<0.05
0.05-0.13³ 0.14³ 0.2
Low Power conditions (mT)
< 0.2
³ 0.2
High power conditions (mT)
< 0.2
³ 0.2
Electric fields (mT)
< 12 V/m³ 12 V/m
Low power conditions (mT)
< 0.032
0.032-0.067
0.068-0.124³ 0.125

Leukemia no. cases

RR (95% CI)

Acute lymphoblastic
no. cases

RR (95% CI)

32
3
3

0.90
1.2
3.5

(0.62-1.3)(0.26-3.6)(0.7-10)

32
3

0.89
1.6

(0.61-1.3)(0.32-4.5)

139
8
1

reference
1.8(0.7-4.2)
0.3(0.0-2.1)

134
10
4
2

reference
1.5(0.7-3.3)
0.8(0.3-2.4)
0.5(0.1-2.2)31
5

reference
1.93 (0.67-5.56)

23
3

reference
1.56 (0.42-5.75)

30
7reference
1.41 (0.57-3.50)

23
4reference
1.05 (0.34-3.26)

31
6reference
0.75 (0.29-1.91)

23
4

reference
0.67 (0.22-2.04)

67
34
23
16

reference
1.01 (0.61-1.69)
1.37 (0.65-2.91)
1.22 (0.52-2.82)

197

Table 4.21 (continued)
Studies wire codes

Exposure classification

Leukemia no. cases

RR (95% CI)

Short-term measurement (mT)
< 0.2
³ 0.2

170
6

reference
0.7(0.3-1.8)

London, et al.
(1991)

24 hour measurements (mT)0-0.067
0.068-0.118
0.119-0.267³ 0.268

85
35
24
20

reference
0.68 (0.39-1.17)
0.89 (0.46-1.71)
1.48 (0.66-3.29)

Michaelis, et al. (1997a)

Median of measurements (mT)
< 0.2
³ 0.2

125
4

reference
3.2(0.7-14.9)

Mean of measurements (mT)
< 0.2
³ 0.2

125
4

reference
1.5(0.4-5.5)

Median during the night (mT)
< 0.2
³ 0.2

124
5

reference
3.9(0.9-16.9)

Median of measurements (mT)
< 0.2
³ 0.2

167
9

reference
2.3(0.8-6.7)

Median during the night (mT)
< 0.2
³ 0.2

167
9

reference
3.8(1.2-11.9)

Michaelis (1997b)

Michaelis et al. (1997b)

198

Acute lymphoblastic
no. cases

RR (95% CI)

Table 4.21 (continued)
Studies wire codes
Linet et al. (1997)

Exposure classification

Leukemia no. cases

Unmatch Analysis (mT)
< 0.065
0.065-0.099
0.1-0.199
0.2-0.299
0.3-0.399
0.4-0.499
³ 0.5
³ 0.2
³ 0.3
Matched Analysis (mT)
< 0.065
0.065-0.099
0.1-0.199
0.2-0.299
0.3-0.399
0.4-0.499
³ 0.5
³ 0.2

199

RR (95% CI)

Acute lymphoblastic
no. cases

RR (95% CI)

267
123
151
38
22
14
9
83
45

reference
1.1(0.81-1.50)
1.1(0.83-1.48)
0.92 (0.57-1.48)
1.39 (0.72-2.72)
3.28 (1.15-9.39)
1.41 (0.49-4.09)
1.24 (0.86-1.79)
1.7(1.0-2.9)

206
92
107
29
14
10
5
58

reference
0.96 (0.65-1.40)
1.15 (0.79-1.65)
1.31 (0.68-2.51)
1.46 (0.61-3.50)
6.41 (1.30-31.73)
1.01 (0.26-3.99)
1.53 (0.91-2.56)

Table 4.22 Results for childhood nervous system tumors
Studies
Wire codes
Wertheimer and Leeper(1979)

Exposure classification

No. of cases

RR (95% CI)

Birth address
HCC/LCC

22 / 35

2.36 (1.03-5.41)

Death address
HCC/LCC

30 / 36

2.40 (1.15-5.01)

HCC/LCC

20 / 392.04 (1.11-3.76)

VHCC/Buried

3 / 17

1.94 (0.47-7.95)

Preston-Martin et al.
(1996a)UG
VLCC/OLCC
OHCC
VHCC

39
114
97
31

2.3 (1.2-4.3)
reference
0.8 (0.6-1.2)
1.2 (0.6-2.2)

Gurney et al. (1996)

High/low

23 / 97

0.9 (0.5,1.5)

UG
VLCC
OLCC
OHCC
VHCC

47
39
11
19
4

reference
1.3 (0.7-2.1)
0.7 (0.3-1.6)
1.1 (0.6-2.1)
0.5 (0.2-1.6)

Unmatched analyses (mT)
< 0.1
0.1-0.19
³ 0.2
³ 0.3

29
2
2
2

reference
1.0 (0.2-3.8)
0.7 (0.1-2.7)
1.0 (0.2-3.9)

Savitz et al. (1988)

Calculated fields
Feychting & Ahlbom (1993)

Matched analyses
0.1-0.19³ 0.2

0.8 (0.1-4.9)
0.7 (0.1-3.2)

Olsen et al. (1993)< 0.1
0.1-0.24³ 0.25
³ 0.4

621
1
2
2

reference
1.0 (0.1-9.6)
1.0 (0.2-5.0)
6.0 (0.7-44)

Verkasalo et al. (1993)

Cumulative exposure (mT-years)
0.01-0.39³ 0.40
³ 1.0

32
7
3

(SIR)
0.82 (0.56-1.2)
2.3 (0.94,4.8)
2.8 (0.6-8.1)

Average exposure (mT)0.01-0.19
³ 0.2

34
5

0.85 (0.59-1.2)
2.3 (0.75-5.4)

Average exposure (mT)
< 0.050.05-0.13³ 0.14144
8
4reference
1.9 (0.8-4.6)
0.7 (0.2-2.1)

Closest to diagnosis (mT)
< 0.050.05-0.13³ 0.14142
59reference
0.9 (0.3-2.5)
1.1 (0.5-2.5)

Tynes & Haldorsen (1997)200

Table 4.22 (continued)
Studies
Measurements
Savitz et al. (1988)

Preston-Martin et al. (1996)

Exposure classification

No. of cases

Spot measurements
Low power conditions (mT)
< 0.2
³ 0.2

23
2

reference
1.04 (0.22-4.81)

High power conditions
< 0.2
³ 0.2

22
3

reference
0.82 (0.23-2.93)

Electric fields (V/m)
< 12
³12

22
3

reference
0.53 (0.15-1.81)

Spot measurements (mT)
> 0.2
> 0.25> 0.3
p for trend

13
11
7

0.7 (0.3-1.5)
0.9 (0.3-2.3)
0.9 (0.3-3.2)
0.29

24-h measurements (mT)
> 0.2
> 0.25> 0.3
p for trend

16
13
12

1.2 (0.5-2.8)
1.4 (0.5-3.8)
1.7 (0.6-5.0)
0.79STAR profiles (mT)
> 0.2
> 0.25> 0.3
p for trend

13
10
5

1.2 (0.5-3.3)
1.5 (0.5-5.1)
0.9 (0.2-4.1)
0.82

201

RR (95% CI)

Table 4.23 Results for childhood lymphoma
Studies
Wire codes
Wertheimer and Leeper (1979)

Savitz et al. (1988)
Calculated fields
Feychting & Ahlbom (1993)

Exposure classification

No. ofcases

RR (95% CI)

Birth address
HCC/LCC

10 / 21

2.48 (0.73-8.37)

Death address
HCC/LCC

18 / 26

2.08 (0.84-5.16)

HCC/LCC

50.80 (0.29-2.18)

VHCC/Buried

3

3.30 (0.80-13.65)

Unmatched analyses (mT)
< 0.1
0.1-0.19
³ 0.2
³ 0.3

16
1
2
1

reference
0.9 (0.0-5.2)
1.3 (0.2-5.1)
0.9 (0.0-5.4)

Matched analyses
0.1-0.19³ 0.2

0.8 (0.1-7.8)
0.9 (0.2-5.0)

Olsen et al. (1993)< 0.1
0.1-0.24³ 0.25
³ 0.4

247
2
1
1

reference
5.0 (0.7-36)
5.0 (0.3-82)
5.0 (0.3-82)

Verkasalo et al. (1993)

Cumulative exposure (mT-years)
0.01-0.39³ 0.4014
1(SIR)
0.88 (0.48-1.5)
0.64 (0.02-3.6)

Average exposure (mT)0.01-0.19
³ 0.2

15
0

0.91 (0.51-1.5)
0.0 (0.0-4.2)

Average exposure (mT)
< 0.050.05-0.13³ 0.1427
1
2

reference
1.0 (0.1-8.7)
2.5 (0.4-15.5)

Closest to diagnosis (mT)
< 0.050.05-0.13³ 0.1427
1
2

reference
0.8 (0.1-6.7)
1.2 (0.2-6.4)

Spot measurements
Low power conditions (mT)
< 0.2
³ 0.2

11
2

reference
2.17 (0.46-10.31)

High power conditions
< 0.2
³ 0.2

10
3

reference
1.81 (0.48-6.88)

Electric fields (V/m)
< 12
³ 12

11
2

reference
0.70 (0.15-3.27)

Tynes & Haldorsen (1997)

Measurements
Savitz et al. (1988)

202

Table 4.24 Summary of appliance studies
Studies

Appliances

Leukemias
Prenatal

Lymphoma
Postnatal

Savitz et al.
(1990)1

Electric blanket
Electric water bed
Bedside electric clock
Heating pad
Hair dryer

1.3 (0.7-2.6)
0.3 (0.1-1.2)
0.9 (0.5-1.6)
0.9 (0.4-2.2)-

1.5 (0.5-5.1)
0.7 (0.2-2.5)
1.4 (0.7-2.9)
0.5 (0.2-1.3)

London et al.
(1991)2

Bedroom. air
conditioner.
Electric blanket
Electric fanElectric space heater
Electric water bed
B&W television
Electric clock (all)Electric clock-dial
Electric clock-digital
Color television
Curling ironElectric clippers
Electric hair dryer
Microwave ovenVideo game

0.91 (0.51-1.66)

0.54 (0.21-1.25)

1.21 (0.66-2.29)
1.16 (0.77-1.75)
1.18 (0.62-2.32)
0.67 (0.34-1.28)-

7.0 (0.86-121.8)
1.20 (0.81-1.80)
1.45 (0.82-2.66)
1.00 (0.45-2.29)
1.49 (1.01-2.23)
1.33 (0.90-1.97)
1.86 (0.97-3.83)
1.10 (0.71-1.72)
1.06 (0.66-1.74)
6.0 (0.72-104.8)
1.0 (0.06-19.60)
2.82 (1.42-6.32)
0.81 (0.48-1.36)
1.57 (0.80-3.27)

Nervous system tumors

Prenatal

Postnatal

Prenatal

Postnatal

1.1 (0.4-3.6)
0.5 (0.2-1.2)
2.0 (0.7-5.9)-

1.0 (0.2-8.6)
1.5 (0.6-4.5)
0.7 (0.2-2.5)

1.8 (0.9-4.0)
0.5 (0.2-2.0)
0.8 (0.4-1.7)
0.9 (0.4-2.7)-

1.2 (0.3-5.7)
0.3 (0.1-2.7)
1.1 (0.5-2.8)
0.6 (0.3-1.7)

Preston-Martin etal. (1996a)1

Electric blanket
Electric water bed
Electric clock (all)Electric clock-dial
Electric heat
Electric heat-radiantMicrowave
Ham radio
Hair dryer
Curling iron
B&W television
Baby monitor

1.2 (0.6-2.2)
2.1 (1.0-4.2)
1.0 (0.8-1.3)
1.1 (0.7-1.8)
1.6 (0.8-3.0)
1.3 (0.2-8.3)
1.4 (0.9-2.3)-

1.2 (0.5-3.0)
2.0 (0.6-6.8)
0.7 (0.4-1.0)
0.6 (0.3-1.4)
1.3 (0.7-2.4)
1.4 (0.4-5.0)
1.0 (0.6-1.5)
2.1 (0.2-23.7)
1.2 (0.7-2.1)
1.0 (0.4-2.5)
0.7 (0.4-1.4)
0.6 (0.2-0.7)

Preston-Martin etal. (1996b)1

Electric blanket
Electric water bed

0.9 (0.6-1.2)
0.9 (0.6-1.3)

1.0 (0.6-1.7)
1.2 (0.7-2.0)

203

Table 4.24 (continued)
Studies

Hatch et al.
(1998)

Appliances

Electric blanket
Ever used
Electric water bed
Ever used
Hair dryerEver used
Curling ironEver used

Leukemias

Lymphoma

Prenatal

Postnatal

1.59 (1.11-2.29)

2.75 (1.52-4.98)

0.9 (0.67-1.21)

1.19 (0.87-1.62)

1.14 (0.8-1.61)

1.55 (1.18-2.05)

1.06 (0.83-1.36)

1.74 (0.91-3.31)

Reference: Neverused or not within
3 feetReference: Not usedduring reference year

Prenatal

Postnatal

Nervous system tumors
Prenatal

Electric clock
1.20 (0.83-1.76)
0.98 (0.73-1.31)
Digital display
1.69 (0.61-4.65)
0.81 (0.52-1.28)
Dial display
TV video game
1.91 (1.36-2.68)
Ever used1
Odds ratios (ever use versus never use)
2
Matched analysis. Odds ratios (prenatal use: anytime during pregnancy versus never use, postnatal use: at least once a week versus less than once a week)

204

Postnatal

Table 4.25 Summary of meta-analysis results
Metaanalyses

Studies included

All childhood cancers

Leukemias

Lymphomas

Central nervous
system tumors

Wertheimer and Leeper (1979)
Fulton et al. (1980)
Tomenius (1986)
Savitz et al. (1988)
Coleman et al. (1989)
Lin and Lu (1989)
Myers et al. (1990)
London et al. (1991)

Measured EMFs:
1.82 (1.09-3.04)

Measured EMFs:
1.16 (0.65-2.08)

Measured EMFs:
1.85 (0.91-3.77)

Distance from EMF
source:1.11 (0.71-1.73)

Distance from EMF source:
1.31 (0.72-2.21)

Distance from EMF
source:1.09 (0.50-2.37)

Ahlbom etal. (1993)

Feychting and Ahlbom (1993)
Olsen et al. (1993)
Verkasalo et al. (1993)

Calculated EMFs:
1.3 (0.9-2.1)

Washburn etal. (1994) 2,3

Wertheimer and Leeper (1979)
Fulton et al. (1980)
Tomenius (1986 )Savitz et al. (1988)
Coleman et al. (1989)
Myers et al. (1990)
London et al. (1991)
Lowenthal et al. (1991)
Fajardo-Gutierrez (1993)
Feychting and Ahlbom(1993)
Olsen et al. (1993)
Petridou et al. (1993)
Verkasalo et al. (1993)

NRPB(1992)1

Wire codes (HCC vs.
LCC):
1.53 (1.04-2.25)

Wire codes (HCC vs. LCC):
1.39 (1.08- 1.78)

Wire codes (HCC vsLCC):
2.04 (1.11-3.76)

Calculated EMFs:
2.1 (1.1-4.1)

Calculated EMFs:
1.0 (0.3- 3.7)

Calculated EMFs:
1.5 (0.7-3.2)

Distance from EMF source:
1.49 (1.11-2.00)

Distance from EMF source:
1.58 (0.91- 2.76)

Distance from EMF
source:1.89 (1.34-2.67)

205

Table 4.25 (continued)
Metaanalyses

Studies included

NAS
Report(1994)2,4

Wertheimer and Leeper (1979)
Fulton et al. (1980)
Tomenius (1986 )Savitz et al. (1988)
Coleman et al. (1989)
London et al. (1991)
Fajardo-Gutierrez (1993)
Feychting and Ahlbom(1993)
Olsen et al. (1993)
Petridou et al. (1993)
Verkasalo et al. (1993)

All childhood cancers

Leukemias

Lymphomas

Central nervous system
tumorsWire codes (HCC vs. LCC):
1.48 (1.18-1.85) - fixed
1.52 (1.08-2.14) - random
Wire codes and distances lessthan 100 m:
1.36 (1.13-1.63) - fixed
1.38 (1.08-1.76) - random
Spot measurements (2 mg
exposures and greater):
0.92 (0.57-1.49) - fixed
0.89 (0.51-1.57) - random

Feychtinget al.
(1995) 5

Feychting and Ahlbom (1993)
Olsen et al. (1993)

0.1 - 0.19 mT: 1.4 (0.6-2.9)³ 0.2: 1.5 (0.9-2.7)³ 0.5: 3.5 (1.7-7.3)

0.1 - 0.19 mT: 2.0 (0.7-5.3)³ 0.2: 2.0 (1.0-4.1)³ 0.5: 5.1 (2.1-12.6)

0.1 - 0.19 mT: 0.7 (0.1-5.6)³ 0.2: 2.1 (0.8-5.5)³ 0.5: 3.3 (0.7-15.0)

1.0 - 1.9 mT: 1.1 (0.3-3.6)³ .2: 0.8 (0.3-2.4)³ .5: 2.3 (0.6-8.0)

MeinertandMichaelis(1996)2,6

Wertheimer and Leeper (1979)
Fulton et al. (1980)
Tomenius (1986 )Savitz et al. (1988)
Coleman et al. (1989)
Myers et al. (1990)
London et al. (1991)
Fajardo-Gutierrez (1993)
Feychting and Ahlbom(1993)
Olsen et al. (1993)
Petridou et al. (1993)
Verkasalo et al. (1993)
Preston-Martin et al. (1994)

Wire code (HCC vs. LCC):
1.37 (0.94-2.00)

Wire code (HCC vs. LCC):
1.66 (1.11-2.49)

Wire code (HCC vs.
LCC):
1.32 (0.52-3.37)

Wire code (HCC vs.
LCC): 1.50 (0.69-3.26)

Distance:< 100 m: 1.09 (0.89-1.35)< 50 m: 1.10 (0.86-1.40)< 25 m: 1.42 (0.88-2.29)

Distance:< 100 m: 1.13 (0.79-1.62)< 50 m: 1.31 (0.92-1.87)< 25 m: 1.85 (0.98-3.49)

EMF measures:> 0.1 mT: 0.97 (0.82-1.15)> 0.2 mT: 1.23 (0.96-1.57)> 0.3 mT: 1.62 (1.10-2.39)

EMF measures:> 0.1 mT: 1.55 (0.88-2.73)> 0.2 mT: 1.89 (1.10-3.26)> 0.3 mT: 1.27 (0.28-5.76)

1

Distance:< 50 m: 1.53 (0.19-12.0)

EMF measures:> 0.1 mT: 2.18 (0.51-9.34)> 0.2 mT: 2.21 (0.72-6.80)> 0.3 mT: 1.69 (0.43-6.59)

Relative risk estimates do not incorporate the results from the Wertheimer and Leeper (1979) study
Relative risk estimates do incorporate the results from the Wertheimer and Leeper (1979) study
3
Relative risk estimates in relation to distances 50 meters and greater
4
Relative risk estimates based upon fixed and random effects statistical models
5
Relative risk estimates in relation to calculated historical magnetic field exposures less than 0.1 mT (1 mG, adjusted for age, gender, and country)
6
Relative risk estimates in relation to dichotomous cut-points
2

206

EMF measures:> 0.1 mT: 0.89
(0.39-2.05)> 0.2 mT: 1.30
(0.78-2.19)> 0.3 mT: 1.89
(0.80-4.43)

Table 4.26 Summary of NIEHS meta-analysis
Leukemia: metaanalysis

No. ofstudiesNo. of exposed
cases

Random effects odds
ratio (95% CI)

Fail-safe N

Sample size
neededP-Value forheterogeneity

Range of odds ratios fromsensitivity analysis

Calculated Fields
Measured Fields
Wire Codes
Proximity toelectrical facilities

5
6
5
11

20
125
336
375

1.6 (1.0-2.7)
1.3 (0.8-2.0)
1.4 (1.0-2.0)
1.4 (1.1-1.8)

¾
¾
13
31

3268
2454
1898
3433

0.4
0.1
0.03
0.06

1.3-1.8
1.1-1.4
1.3-1.6
1.3-1.5

Leukemia: doseresponse analysis

No. ofstudies

Random effects
relative risk (95% CI)
per 0.1 mT

Regression
slope

Spot measurements
Calculated fields
0.2 or 0.25 mT
0.3 or 0.4 mT
Wire codes
Scored by spotmeasurements
Scored by 24-hour
Bedroommeasurements

4

1.1 (0.9-1.3)

0.08

0.10

0.3

4
4

1.2 (0.9-1.5)
1.2 (1.0-1.5)

0.16
0.20

0.13
0.11

0.2
0.2

2

2.7 (0.8-8.7)

0.99

0.60

0.1

2

1.6 (0.5-4.6)

0.45

0.55

0.02

No. of exposed
cases

Random effects odds
ratio (95% CI)

Fail-safe N

Sample size
neededP-value forheterogeneity

Range of odds ratios fromsensitivity analysis

13
36
193
208

1.2 (0.6-2.4)
1.4 (0.8-2.4)
1.2 (0.7-2.2)
1.1 (0.7-1.7)

¾
¾
¾
¾

2699
612
1106
1790

0.2
0.4
0.01
0.03

0.8-1.5
1.1-1.6
1.0-1.5
0.9-1.3

Brain cancer: meta
analysis

No. ofstudies

Calculated fields
Measured fields
Wire codes
Proximity toelectrical facilities
Spot measurements
Calculated fields
0.2 or 0.25 mT
0.3 or 0.4 mT

4
4
4
6

Standard
error

P-Value forheterogeneitytest

3

1.1 (0.7-1.6)

0.05

0.20

4
4

1.1 (0.9-1.3)
1.1 (1.0-1.3)

0.08
0.10

0.08
0.07

207

Table 4.26 (continued)
Brain cancer: dose
response analysis
Wire codes
Scored by spotmeasurement
Flat modelLinear model

No. ofstudies

Random effects
relative risk (95% CI)
per 0.1 mT

Regression
slopeStandard
error

P-Value forheterogeneity
test

2
2

1.2 (0.8-2.0)
1.2 (0.7-2.0)

0.22
0.18

0.23
0.25

0.3
0.2

208

4.4

Non-cancer health effects in experimental animals

4.4.1 Immunological effects
Experimental evaluation of the response of the immune system to antigenic challenge isdifficult because the immune system is highly redundant. An extensive range of assay
systems has therefore been developed to measure the effects of adverse insults. These
assay systems are targeted at acquired (humoral or cellular) and innate immunity; they
include measurements to determine an animalÕs ability both in vivo and in vitro torespond to invaders including bacteria, intracellular parasites, viruses, and tumor cells(host resistance) and immunoassays that are correlated with activities associated withhumoral, cellular, and innate immunity.
In general, the experimental models used to study interactions with EMF have been
guided by methods and end-points developed to assess the effects of drugs, chemicals,
and ionizing radiation on the immune system. Specific assays have been developed tomeasure suppression and/or stimulation (immunopotentiation) of a specific immune organ(thymus, spleen, lymph nodes), cell (helper and suppresser T cells, antibody-producing
cells, natural killer cells, and macrophages), or function (antibody synthesis, cytokine
production, cytotoxic activity, host resistance to infectious and/or malignant disease)(Luster et al., 1990; Luster et al., 1992a; Luster et al., 1994; Luster et al., 1993; Luster etal., 1992b). Changes in the results of these assay have been correlated with hostresistance. Alterations in antibody-producing cells, NK cell activity, and delayed
hypersensitivity are significantly related to altered disease resistance (Luster et al., 1993).
Multiple end-points must be examined in order to clearly establish an interaction between
an outside influence and the multiple-faceted immune system.
The exposure, biological end-points, and responses observed in a number of studies are
summarized below and in Table 4.27.
4.4.1.1 Magnetic and electric fields
Exposure of adult male baboons in vivo to EMF has yielded contradictory information(Murthy et al., 1995). In a pilot study, a social group of six baboons was followed for six
weeks before exposure, for six weeks of exposure, and for six week after exposure. The
animals were exposed to a 6 kV/m electric field and a 50 mT magnetic field. Blood samples
were taken in the fifth week of each period, and the distribution of helper and suppressor
T cells, expression of interleukin-2 receptors, and NK cells were determined. Total
lymphocyte count (cells/mm3) and stimulation of isolated peripheral blood lymphocytes
by concanavalin A, phytohemagglutinin, and pokeweed mitogen were measured.
Comparison of results obtained before exposure indicated a significant decrease (p < 0.05)

209

in the numbers of lymphocytes, helper, and suppressor T cells, interleukin-2 receptors,
and response to phytohemagglutinin and pokeweed mitogen.
In a second study, eight baboons were field exposed (30 kV/m, 100 mT) and eight weresham exposed, and the responses in mitogen stimulation assays and the distribution ofcell types as identified by surface markers and interleukin-2 receptor activity werecompared. The decreases seen in the pilot study were not seen in this follow-up study.
4.4.1.2 Magnetic fields
Groups of nine female Sprague-Dawley rats (52Ð54 days old) were exposed continuously(24 h/d) on 7 d per week for 2, 4, 8, or 13 weeks to a 50 Hz, 100 mT magnetic field withconcurrent sham-exposed controls (Mevissen et al., 1998b). The biological end-points
were body weight, splenic cellularity, and immune parameters (stimulation of spleen cellsby concanavalin A and pokeweed mitogen and assessment of interleukin-1 production in
pokeweed mitogen-stimulated cells). At 2, 4, 8, and 13 weeks after the start of the study,
a significant reduction in viable lymphocytes from exposed rats was observed whencompared with sham-exposed controls (p < 0.05). Splenic T cells showed an increased (p< 0.05) proliferative response to concanavalin A at 2 and 4 weeks of exposure, followed
by a decrease (p < 0.05) at 13 weeks. No significant effects were observed on bodyweight, splenic T-cell response to pokeweed mitogen, or the production of interleukin-1
by pokeweed mitogen-stimulated cells. [Given the method by which the spleen cells werehandled and the 20Ð25% reduction in control spleen-cell viability between weeks 2 and 4,
the meaning of these results is unclear.]Two separate studies (Tremblay et al., 1996) were conducted in which Fischer 344/N
pregnant rats were exposed to 60 Hz, sinusoidal magnetic fields of 2, 20, 200, or 2000 mT
for six weeks with sham-exposed controls, beginning on gestational day 20. At weaning,pups were separated from their mothers and held under the same field intensity for theduration of exposure of six weeks. In both studies, a cage control was included. Duplicate
treatment groups of eight animals per group per study were included. The biological endpoints were innate immunity (NK cell and peritoneal macrophage activities) and T and B
cell counts in spleen based on specific surface markers (CD5+, CD4+, CD8+, and Ig+). The
distribution of CD5+ cells (all T cells) was reduced in rats exposed to 200 (p < 0.25) or
2000 mT (p < 0.05), and the numbers of CD4+ cells (T helper cells) and CD8+ cells (Tcytotoxic/suppressor cells) were decreased significantly in rats exposed to 2000 mT (p <0.005). A significant reduction in all B cells was observed in rats exposed to 20 or 200 mT(p < 0.05). An enhanced response of NK cells was observed in rats exposed to 2000 mT
when compared with cage controls (p < 0.05). Regression analysis of the data indicated asignificant positive relationship between NK activity and magnetic field intensity (p <0.05). The authors concluded that 60 Hz magnetic fields have significant effects on the
immune responses of exposed animals. [The significant effects were found in comparisonswith cage controls; no effects were seen when comparisons were made with shamexposed animals.]210

An extensive series of studies in mice and rats (House et al., 1996) was conducted tomeasure body and tissue weights, cellularity and lymphocyte subtypes in spleen, andfunctional activity, delayed hypersensitivity, and host resistance of the immune system
in vivo. Mice and rats received actual or sham exposure to 2, 200, or 1000 mT
continuously or 1000 mT intermittently and to a 60 Hz magnetic field. No significant
difference in the distribution of lymphocyte subsets in the spleens of exposed mice wasobserved when compared with controls.
NK cell activity was measured by 51Cr release in female mice exposed to 1000 mT
magnetic fields continuously or 1000 mT intermittently. A positive control was included
to validate the responsiveness and repeatability of the assay system. Significantly (p <0.05), consistently enhanced responses were seen in spleen-cell preparations from micefour weeks after exposure to 1000 mT magnetic fields continuously or intermittently, but
the response was suppressed after 13 weeks of exposure to 200 or 1000 mT continuously
or 1000 mT intermittently (p < 0.05). The studies were repeated three times for six weeks
of exposure; the results were inconsistent.
The authors also conducted a series of exposures in Fischer 344 rats exposed for six
weeks to sham, 2, 200, or 1000 mT continuous magnetic fields or an intermittent 1000 mT
intensity. No consistent differences were observed in comparison with sham-exposed
controls. Studies of cellular immunity (delayed hypersensitivity to oxazolone) in male andfemale mice exposed or sham-exposed for 4 or 13 weeks did not show a clear pattern or
trend. No significant differences in mortality or survival time were observed in exposed
mice administered Listeria monocytogenes when compared with appropriate shamexposed controls.
House et al. (House et al., 1996) concluded that continuous exposure of male and female
mice to linearly polarized, pure sinusoidal 60 Hz magnetic fields at field strengths up to
1000 mT for up to 90 days did not significantly affect a broad range of immune effector
functions. Moreover, this exposure regimen had no observable effect on the ability ofmice to resist infection to a bacterial infection. [The results provide little support for the
hypothesis that magnetic fields can alter immune responses.]
4.4.1.3 Magnetic fields and 7,12-dimethylbenz[a]anthracene
Female Sprague-Dawley rats, 52 days of age, received actual or sham exposure to 50 Hz,
50 mT magnetic fields for 13 weeks (Mevissen et al., 1996b). Half of the controls and halfof the exposed rats also received DMBA at 5 mg per week for four weeks by gavage. At
the end of the 13 weeks, the mitogenic response of spleen cells to concanavalin A andpokeweed mitogen and splenic cellularity were measured. In rats exposed to the fields andnot treated with DMBA, a significant reduction in concanavalin A stimulation wasobserved in spleen cells when compared with sham-exposed controls (p < 0.05). The
response of rats treated with DMBA and exposed to magnetic fields was not significantly
different from that of rats that were sham-exposed and DMBA-treated. The authors211

concluded that immunoprotection may be compromised by exposure to magnetic fields.
[Given the method by which the spleen cells were handled and the 20Ð25% reduction incontrol spleen-cell viability between weeks 2 and 4, the meaning of these results is
unclear.]
4.4.1.4 Summary
The effects of EMF on the immune system have been investigated in baboons, rats, andmice. The studies varied in quality. Because of experimental difficulties, the studies ofsplenocytes are inadequate; three of the five studies were adequate to determine function,
while two studies were inadequate.
There is no evidence in experimental animals for effects of ELF EMF on the immune
system.
[This conclusion was supported by 13 members of the Working Group; there were 6
votes for ÔweakÕ evidence, 1 abstention, and 9 absent.]212

Table 4.27 Summary of immunological studies of exposure to EMF in experimental animals
Reference

Animals

Magnetic fields(House etmiceal., 1996)
BALB/C,
B6C3F1

Age andField
gender characteristics

Male andfemaleB6C3F1, 3
confirmatory
studies(Tremblay
et al.,
1996)

ExposureTimeof dayLight/darkcycle

Comments

Immunological and biological endpoints

Body and organ
weights, < 0.1 mT
stray field to shampositive controls(p < 0.05)

Splenic subsets (flow) (CD-3, 4, 8, and B cells) noteffected by exposure.
Host resistance not affected by exposure
Cellularity of spleen not effected by exposuresaby (PFC/spleen) not effected by exposure.
Body, spleen and thymus weights - not effected byexposures
DTH - oxazolone - no consistent effect on contact
hypersensitivity
NK -spleen-males- no consistent pattern of effect (4 or 13
weeks)
NK -females- 10G/10G intermittent - enhanced response
at 4 weeks (p< 0.05) (200 mT, 10 mT,. and 10 mT,
intermittent), suppressed response 13 weeks. (p< 0.05)

No. ofDays

h/d

60 Hz, Sham,
0, 2, and 200
mT, 1 mT, 1 mT
intermittent

28 or
90 d

18.5
h/d 7
d/weekSham, 0, 2,
and 200 mT, 10
mT, 10 mT
intermittent

6 weekNK activity changes were observed but mixed:
study 1 - one assay ( ) value was decreased
study 2 - reduction of NK function (200 mT, 10 mT, and10 mT intermittent, p < 0.05)
study 3 - enhanced NK function (200 mT, 10 mT, and 10
mT intermittent, p < 0.05)
NK - spleen - varied effect with various target to effector
ratios exhibiting effect (p < 0.05) in males or females

F344 rats

Male andfemaleSham, 0, 2,
and 200 mT, 10
mT, 10 mT
intermittent

6 and
13
week

F344 rats
Studies
repeated
twice (8rats/groupn= 15-16
for endpoints

Rats/group; final n=15-16 forend
points60 Hz, sham(<0.02 mT), 2,
20, 200, 2000
mT

42 d

20

12:12

1300
to 900

2 separate
experiments - ratsborn/raised infield pregnant
females (d 20)
building = ~0.024
mT

213

Macrophage activity: H202 -no effect on spontaneous
production, PMA-stimulated enhanced at 20 and 2000mT;
TNF activity - no effect correlated with exposure
NO2 - no effect correlated with exposure
CD5, 4, 8 and B cells - decrease CD5 (200 & 2000 mT,
p< 0.05)

Table 4.27 (continued)
Reference

Animals

Age andField
gender characteristics

Exposure
No. ofDays(Mevissen
et al.,
1998b)

SpragueDawleyrats
9/group52-54 dFemaleMagnetic and electric fields(Murthy et Baboons
adult,
al., 1995)
male

6/groupTime ofday

Light/darkcycle

Comments

Immunological and biological endpoints

Pregnant females
placed in exposurefor 20 d

Decrease CD4 and 5 (2000mT, p < 0.05), decrease B
cells(20 and 200 mT, p< 0.05), regression analysis (MFintensities negative dose-response for CD5, CD4, CD8,p< 0.05)
NK activity = LU - 50 % increased NK (2000mT,
p< 0.05)
LU = number of cell for 20% lysis - linear regression of
MF vs. response (p< 0.05)

12 h/12 h red
light (approx.
1 lux)

Body weight
Randomized(weight)
Building = 0.03-.04
mT

Cellularity - viable lymphocytes reduced for 2, 4, 8, and13 weeks, p < 0.05
Con-A response enhanced at 2 and 4 weeks, p < 0.05
PWM - no change
No effect on IL-1 production after 13 weeks

12:12

CD 3, 4, 8 &NK(flow studies),
IL-2R, WBC
mitogen (PHA,
PWM), in vivo
exposure, ANOVA
Building £ 0.1 mT

h/d

50 Hz, 100 mT

91 d, 2 ,4, 8,
and 13weeks

24, 7
d/week60 Hz horizontal
magnetic fieldand verticalelectric field6
weeks.

12

Exp III - 6
kV/m and
50mT, onegroup

Pre-exp.
-5
week
Exp. - 6
week
Postexp. - 6
weekduringlight

214

Decrease of CD4 cells
IL2-R, p<0.05

Table 4.27 (continued)
Reference

Animals

Age andField
gender characteristics

Exposure
No. ofDays

8/group

Magnetic fields and DMBA
(Mevissen
Sprague52 d
et al.,
DawleyFemale1996b)
rats

Exp. IV - 30
kV/m and 100
mT,
experimental
and shamgroupsPre-exp.
-5
week
Exp. - 6
week,
Postexp. - 6
week

50 Hz, 500 mT

91, 13week

Time ofday

Light/darkcycle

Comments

Immunological and biological endpoints

h/d

24, 7
d/week12:12, off at 5PM, red light(approximately. 1 lux)

215

Building £ 0.2 mT

Essentially did not replicate Exp. III

Mitogen responses(spleen),cellularity, bodyweight, spleen andliver weights,
randomized(weight), building= 0.03-0.04 mT,
DMBA

Cellularity - spleen in DMBA-treated rats decreased(p< 0.04)
Spleen and liver weights not affected
Con-A response suppressed (no DMBA) in exposed
rats (p< 0.05)
Con-A response suppressed (with DMBA) in exposed
rats (not significant)
PWM - no change

4.4.2 Hematological effects
Hematological studies include measurement of the distribution of erythrocytic indices (redblood cells, hemoglobin concentration, packed red cell volume, mean corpuscular volume, mean
corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hematocrit, and numberof reticulocytes), platelets, total counts of nucleated leukocytes and red blood cells, and total
and differential leukocyte counts (lymphocytes, neutrophils, basophils, monocytes, andeosinophils). Assessments of bone-marrow cellularity and the impression of bone-marrowsmears complete the picture of the distribution of these cell types in peripheral blood.
4.4.2.1 Magnetic and electric fields
In a preliminary study (Picazo et al., 1994), six female OF1 mice were exposed to a 50 Hz 0.1
mT sinusoidal magnetic field for three months. Six control mice were available. The biologicalend-points were hematocrit, leukocyte count, and differential leukocyte count. No difference
was found in the hematocrit, and the red blood cells were similar in size in exposed mice andcage controls; however, there was a significant (p < 0.05) reduction in leukocyte count andchanges in the distribution of some differential counts (monocyte and lymphocyte size
subsets). [The groups were small, and there were no sham-exposed controls.]
In a follow-up study (Picazo et al., 1995b), OF1 mice were exposed for two generations to a 50
Hz 15 mT sinusoidal magnetic field. The first generation (mothers: 12 control and 12 exposed)
was exposed for 17 weeks, and the second generation (daughters: 30 control and 30 exposed)
was born and exposed for 14 weeks. Comparisons of hemological parameters in exposed andcontrol mice showed no statistically significant change. [This study involved only females.]Three groups of 18 mice were used to assess peripheral blood characteristics after exposure to a
20 mT magnetic field for 24 h/d for seven days (Lorimore et al., 1990). The leukocytes werecounted 0, 2, 4, 7, 10, and 18 days after exposure in three mice at each time. The authors statedthat there were no significant differences between the field-exposed and sham-exposed groups.
[The groups were extremely small.]Margonato et al. (Margonato et al., 1993) examined numerous hematological and serum
chemical parameters in groups of 20 adult male Sprague-Dawley albino rats sham-exposed or
field-exposed to 25 or 100 kV/m 50 Hz electric fields for 8 h/d for 280, 440, or 1240 h. No
statistically significant effects were observed.
Margonato et al. (Margonato et al., 1995) assigned 512 adult male Sprague-Dawley albino rats
to sham or field exposure to a 50 Hz, 5 mT magnetic field for 22 h/d for a total of 32 weeks.
Hematological and serum chemical variables were measured at weeks 0, 12, 24, and 32. No
statistically significant differences were detected.

216

Groups of 10 male and 10 female Fischer 344/N rats were sham-exposed or exposed to 60 Hz
magnetic fields at 20, 200, or 1000 mT continuously or 1000 mT intermittently for 18.5 h/d forseven days per week (Boorman et al., 1997). After eight weeks, the animals were anesthetizedwith CO2, and blood was collected. Hematological and clinical chemical parameters did not
differ between sham-exposed and field-exposed animals.
Zecca et al. (Zecca et al., 1998) used three groups of 64 adult male Sprague-Dawley rats; onegroup was sham exposed; a second group was exposed to a 50 Hz, 5 mT, 1 kV/m field; and athird group was exposed to a 100 mT, 5 kV/m field. Blood samples were collected before
exposure and after 12 weeks. No statistically significant difference was observed in numerous
hematological and serum variables.
[The seven studies reviewed provide no evidence that exposure to power-frequency EMF
affects the hematological or clinical chemical picture of rodents. These studies were generally
short and some included a limited number of animals.]
4.4.2.2 Summary
There is no evidence that exposure to power-line frequency EMF affects the hematologicalparameters of rodents.
[This conclusion was supported by 17 members of the Working Group; there was 1 abstention
and 11 absent.]

4.4.3 Effects on the nervous system
4.4.3.1 Field detection(a) Electric fields
There is no doubt that animals can perceive electric fields, as previously reviewed by the
National Research Council (NRC et al., 1997). Briefly, Graves et al. (Graves et al., 1978),
Cooper et al. (Cooper et al., 1981), and Graves (Graves, 1981) used conditioned response
suppression techniques to assess perception. The data suggest that pigeons can detect 50 kV/mand chickens, 32 kV/m fields. Stern et al. (Stern et al., 1983) and Stern and Laties (Stern &Laties, 1985) reported electric field detection thresholds of 3Ð10 kV/m in psychophysicalexperiments with rats, but the authors tended to emphasize the best performance of theanimals. Sagan et al. (Sagan et al., 1987) observed mean thresholds of 8 and 13 kV/m, dependingon the psychophysical method used.
Stell et al. (Stell et al., 1993) reported that the mean electric field detection threshold in rats was
8 kV/m (Table 4.28). In a series of experiments with six baboons, Rogers et al. (Rogers et al.,217

1995c) demonstrated that electric fields of 22Ð64 kV/m can serve as a discriminative stimulus
and a secondary reinforcer, implying detection. Orr et al. (Orr et al., 1995) usedpsychophysical methods to measure electric field detection by six baboons: the mean threshold
was 12 kV/m; however, one animal with an estimated threshold of 5 kV/m was able to detect
electric fields of less than 4 kV/m, the lowest intensity achievable.
Weigel et al. (Weigel et al., 1987) recorded single-unit activity in the sensory nerves of a catÕs
forearm; exposure to 600 kV/m (60 Hz) increased the firing rate, and shaving and application ofmineral oil reduced it. Weigel and Lundstrom (Weigel & Lundstrom, 1987) showed that relative
humidity affected vibration of the whiskers of anesthetized rats in a 50 kV/m electric field,
suggesting that charges trapped on the hair led to vibration at 60 Hz. In dry air, there was lessvibration. Stell et al. (Stell et al., 1993) suggested, however, that hair vibration does not play a
critical role in the detection of electric fields (0Ð25 kV/m, 50 Hz) by rats, and Graves (Graves,
1981) argued that electric field (50 kV/m, 60 Hz) detection by pigeons did not involve vibrationof feathers. Hair vibration is thus probably sufficient but not necessary for detection of electricfields.
[Detection of electric fields is a well-established phenomenon, and the detection thresholds for
mammals appear to be similar. Differences within species appear to be about as large as
differences between species.](b) Magnetic fields
Smith et al. (Smith et al., 1994) reported that a very strong magnetic field could serve as a cue
for five Long-Evans female rats in a conditioned suppression paradigm (Table 4.29). Fivefrequency- and flux-dependent pairs of stimuli, ranging between 1900 mT at 7 Hz and 200 mT
at 65 Hz, were used. The effect did not vary with different magnetic field intensity or
frequency combinations. Stern (Stern & Justesen, 1995) suggested that the design of this study
was inadequate to support the conclusion reached; no sham-field tests were completed, andtemporal contingencies might have supported responses. [There is no experimental evidence
that mammals can perceive magnetic fields at an environmentally relevant flux density.]
4.4.3.2 Avoidance and aversion(a) Electric fields
It was reported in some early studies that exposure of rodents to electric fields was ÔstressfulÕ
(see section 4.4.3.4 for a discussion of the endocrine effects of exposure to electric fields).
Stimuli detectable at low intensities become aversive when present at high levels. The
microshocks that animals can receive when exposed to high-voltage electric fields could elicit
adverse behavioral or physiological responses. Thus, perception and/or aversion might be anÔindirectÕ causative mechanism in experiments using supra-threshold electric fields. Thesepossibilities were not carefully considered in the early studies of exposure to electric fields, inwhich very high electric field strengths were used in an effort to address the problem of scaling218between rodents and humans (see section 3.4 for a discussion of electric field scaling factors;
size, shape, and orientation are all important).
Hjeresen et al. (Hjeresen et al., 1980; Hjeresen et al., 1982) reported that exposure to electricfields (60 to 105 kVm, 60 Hz) induced avoidance of the exposure area (p < 0.05) during theinactive portion of the dayÐnight cycle: eight sham-exposed and 32 exposed rats showed
avoidance during the day, and 15 sham-exposed and seven exposed pigs (30 kVm, 60 Hz)
showed avoidance at night. Rosenberg et al. (Rosenberg et al., 1981) demonstrated that deer
mice (21Ð34 per group) responded to strong electric fields (100 kV/m) with a transitory
increase in activity. Rosenberg et al. (Rosenberg et al., 1983) indicated that the increase inactivity appeared at about 50 kV/m, and Blackwell and Reed (Blackwell & Reed, 1985)
reported that 20 sham-exposed and 20 mice exposed to 400 V/m (50 Hz) or less did not showchanges in activity. Easley et al. (Easley et al., 1991) demonstrated that social stress was
induced in baboons (eight per group) exposed to 60 kV/m (60 Hz) electric fields. These results,
in several species, implied that exposure to electric fields might be aversive; however, Creim(Creim et al., 1984) reported that exposure to as much as 133 kV/m electric fields did not
induce taste aversion in male rats (three per group), and Stern and Laties (Stern & Laties, 1989)
established that five male rats would not turn off a 100 kV/m (60 Hz) electric field but would
turn off a light. [These results suggest that exposure to electric fields up to 133 kV/m is nothighly aversive.]
Coelho et al. (Coelho et al., 1991) reported that exposure to electric fields at 30 kV/m (60 Hz)
increased the frequency of occurrence (p < 0.05) of three of ten categories of social behavior ofbaboons (eight per group) during a six-week exposure, in comparison with the equivalent rates
observed in six-week pre- and post-exposure periods (Table 4.29). The effects on passive
affinity, tension, and stereotypy were of the same magnitude with exposure to 30 or 60 kV/m
(Easley et al., 1991).
Easley et al. (Easley et al., 1992) reported a replication of the behavioral effect at 30 kV/m. The
means for the entire exposure period differed (p < 0.05) from those for the pre- and postexposure periods, which were equivalent; analyses of weekly means indicated that the effectoccurred almost exclusively during the first week of exposure (p < 0.05). The effect also
occurred during the first week in the experiments reported by Easley et al. (Easley et al., 1991)
and Coelho et al. (Coelho et al., 1991).
Rogers et al. (Rogers et al., 1995c) found that six male baboons would not turn off an electricfield above their detection thresholds, suggesting that exposure to electric fields is not aversive.
[This outcome is generally similar to those of several studies in rats.]
Rogers et al. (Rogers et al., 1995b) examined the effects of exposing two groups of six malebaboons to 30 kV/m (60 Hz) electric fields. The baboons had been trained, under signal control,
to respond on either FR30 (fixed ratio 30) or DRL 20 (differential reinforcement of low rate, 20s) schedules. They were assigned randomly to field-exposed and sham-exposed groups andentered into a six-week pre-exposure, exposure, and post-exposure schedule. On the first day

219

of exposure, the field-exposed baboons showed Ôwork stoppageÕ (p < 0.05) or did not respond.
Most began responding on the second day of exposure; once responding began, performance
was normal. In a cross-over experiment, the effect was examined a second time. When theformer controls received their first 30-kV/m exposure, they showed work stoppage. The
original experiment was repeated at 60 kV/m with a new set of baboons, and the same work
stoppage effect was observed (p < 0.05). Because exposure to a novel stimulus usuallyinterrupts operant response, the authors did not regard this as an adverse effect.
[Introduction of a perceptible electric field can change the behavior of mice, rats, and nonhumanprimates; however, the changes are transitory, appear to be secondary to detection of a novel
stimulus, and do not suggest acute adverse effects.](b) Magnetic fields
Smith and Justesen (Smith & Justesen, 1977) reported that exposure to magnetic fields (1.7
mT, 60 Hz) increased activity in mice. Rudolph et al. (Rudolph et al., 1985) reported that
exposure to 40 mT (50 Hz) increased activity in male Wistar rats (24 per group) but only at the
beginning of tests conducted in the presence of illumination. Lovely et al. (Lovely et al., 1992)
reported that a 60 Hz magnetic field of 3.03 mT did not induce place avoidance in adult malerats (eight sham- and 24 field-exposed). [Too few experiments are available to reach aconclusion on the effect of magnetic fields on avoidance and aversion reactions.](c) Electric and magnetic fields
Groups of eight field-exposed (6 kV/m, 50 mT, 60 Hz) and eight sham-exposed baboons were
tested by the approach described previously (Coelho et al., 1991). When the same animals were
subsequently exposed for six weeks to 30 kV/m, 100 mT, 30 kV/m electric fields did not elicit
the initial increases in the frequency of passive affinity, tension, and stereotype. The authors
speculated that the presence of the magnetic field might have blocked the response normallyelicited by strong exposure to electric fields.
Orr et al. (Orr et al., 1995) examined the effects of exposure to EMF in two groups of five malebaboons trained to perform a match-to-sample operant task. In the first experiment, initial
exposure to 6 kV/m and 50 mT did not induce work stoppage. When the same animals were
exposed to a perceptible 30 kV/m field accompanied by 100 mT, no work stoppage occurred. A
short cross-over experiment was completed in which the unexposed controls were exposed to
30 kV/m and 100 mT for the first time; once again, exposure to EMF did not induce work
stoppage. Inclusion of the 100 mT field prevented the occurrence of work stoppage seen with
30 kV/m alone.
[The available evidence, including that from the series of experiments conducted withnonhuman primates in a well-controlled exposure facility suggests that exposure to EMF is notaversive] (Rogers et al., 1995a; Rogers et al., 1995b). [This series of experiments also suggests

220that addition of a magnetic field can modulate the acute behavioral response of animals to
exposure to perceptible electric fields.]
4.4.3.3 Learning and performance(a) Electric fields
Several investigators have examined the ability of power-frequency, sinusoidal electric fields toaffect learning and/or performance. Gavalas et al. (Gavalas et al., 1970) and Gavalas-Medici and
Day-Magdelano (Gavalas-Medici & Day-Magdaleno, 1976) reported that exposure to very
weak electric fields (7-100 V/m) at 4Ð10 Hz (in the range of electroencephalogram (EEG)
frequencies) disrupted the ÔtimingÕ behaviors of macaques (3-5 animals) performing a DRL-like
operant schedule. Frey and Wesler (Frey & Wesler, 1984) reported that exposure to a relatively
weak electric field (3.5 kV/m) induced a reduction response in suppression (Table 4.30). [Thisbrief report is lacking many important details.]
Eight measures of the operant behavior of baboons on a FR30/DRL20 schedule were studied at
30 kV/m and at 60 kV/m (Rogers et al., 1995b) and analyzed by analysis of variance. Other
than the initial work stoppage, no effect on operant performance was seen. In a series of sevenexperiments with a set of six baboons, Rogers et al. (Rogers et al., 1995c) observed that
exposure to electric fields had no effect on response rate, number of errors, or extinction of asimple, appetitively motivated operant task.
[There is relatively little information on the possibility that exposure to power-frequency
electric fields can affect performance of learned behavior. The available evidence does notsuggest major, persistent effects.](b) Magnetic fields
As reviewed by the National Research Council (NRC et al., 1997), Davis et al. (Davis et al.,1984) reported that exposure to a 1.65 mT (60 Hz) magnetic field did not affect passive
avoidance learning by male mice. Thomas et al. (Thomas et al., 1986) reported that a 30-min
treatment with a combined horizontal 60 Hz magnetic field (26 mT) and static magnetic field
adversely affected performance of five male rats on a DRL schedule, increasing DRL response.
Fixed ratio performance was unaffected. The DC field was used to ÔcancelÕ the EarthÕs
geomagnetic field. The key behavioral observation was that fixed ratio response was unaffected
but DRL performance was adversely affected (p < 0.05), suggesting an effect on cognitive
function. The key physical concept is that the EarthÕs geomagnetic field can interact with apower-frequency magnetic field to produce an effect. The authors reported that neither DC
exposure nor sinusoidal exposure to magnetic fields alone produced the effect. Liboff et al.
(Liboff et al., 1989) reported further studies in the same animals, which showed a threshold at
27 mT. A step-function ÔthresholdÕ, rather than a monotonically increasing function over arange of values, was observed. [These reports by themselves are not convincing; they were221

based on data from only five rats and a few sessions conducted at the end of a series ofexperiments.]
Details of the following studies on learning and behavioral are presented in Table 4.30.
Trzeciak et al. (Trzeciak et al., 1993) reported that exposure to magnetic fields (50 Hz, 18 mT)
had no effect on locomotor activity or on open-field behavior of groups of 10Ð12 adult maleand female Wistar rats; however, ÔirritabilityÕ, defined as response to blowing air on the back,touching the whiskers and back with a glass rod, and holding the animal in the hand was
reduced. [The behavioral testing and scoring methods were not adequately explained.]
Sienkiewicz et al.(Sienkiewicz et al., 1994) exposed CD1 mice to 20 mT (50 Hz) fields nearlycontinuously throughout pregnancy; dams and pups were removed from the magnetic field lessthan 18 h after birth. Many behavioral indices were examined at multiple times in 168 shamexposed pups from 21 litters and 184 pups from 23 litters as the pups developed. Threesignificant effects (p < 0.05) were detected: exposed animals acquired the righting reflex earlier;exposed males (but not females) were lighter, only at 30 days of age; and exposed animals
performed less well on the rotorod, only at days 30 and 45 of age. The authors concluded thatno major effects occurred.
Kavaliers et al. (Kavaliers et al., 1996) reported that exposure of groups of five male and fivefemale deer mice to 100 mT, 60 Hz for 5 min during acquisition and retention of a learned task(Morris water maze task) improved performance and acquisition. Similar results were foundwith meadow voles (Kavaliers et al., 1993). Lai et al. (Lai & Singh, 1997b) presented datasuggesting that exposure to a magnetic field (1 mT, 60 Hz) for 1 h immediately before testing
adversely affected some aspects of the performance of male Sprague-Dawley rats in a Morris
water-maze (five cage controls, 10 sham-exposed, 9 field-exposed). The motor component of
this task was not affected by exposure; however, spatial reference memory was diminished.
The authors also noted that the deficit was related to a decrease in motivation rather than to a
deficit in learning ability.
Sienkiewicz et al. (Sienkiewicz et al., 1996b) field-exposed (5 mT, 50 Hz) or sham-exposed
CD-1 pregnant mice until just before parturition. The offspring were allowed to develop
without further exposure to magnetic fields. Beginning at 83 days of age, 10 males per groupbegan training on an eight-arm radial maze. No differences in performance were observed.
Sienkiewicz et al. (Sienkiewicz et al., 1996a) studied the effects of exposure to a 50 Hz
magnetic field at intensities of 5Ð5000 mT on acquisition of an eight-arm radial arm maze task
by adult male CD-1 mice (10 per group). Exposure occurred only while the animals were in themaze. The authors concluded that concurrent exposure to magnetic fields had no effect on
spatial learning.
Groups of 4Ð8 male Sprague-Dawley rats exposed for 45 min to a 0.75 mT 60 Hz magnetic
field immediately before training on a 12-arm radial maze made more errors than did the shamexposed controls (p < 0.05) (Lai, 1996). The running speeds of the two groups did not differ.

222

Pretreatment with the cholinergic agonist physostigmine blocked the effect but had no effect on
animals not exposed to magnetic fields.
Sienkiewicz et al. (Sienkiewicz et al., 1998) present data from four experiments showing that
exposure to 0.75 mT (60 Hz) for 45 min before training in an eight-arm radial maze slowed
acquisition of the task by male C57Bl/6J mice (six animals per group). The results of all four
experiments were similar. Inter-group differences were most apparent in sessions 2Ð4 and weregone by session 6 or 7. These results confirm the observation of Lai (Lai, 1996) that exposure
to magnetic fields just prior to training sessions slows acquisition but not final performance ofthe task.
[One interpretative difficulty with these studies is that changes in performance can be due to avariety of causes, including level of arousal. Thus, in the absence of additional experiments, theconclusion of an effect on spatial reference memory is only a testable hypothesis for additional
experiments.]
Stern et al. (Stern et al., 1996) conducted two experiments in an effort to replicate the findingsof Thomas et al. (Thomas et al., 1986) and Liboff et al. (Liboff et al., 1989), who suggested that
cyclotron resonance could affect the operant behavior of rats. None of the several exposure
conditions tested had an effect on the operant behavior of the 13 rats examined. [No obvious
reasons are apparent for the differing results of the two groups.][Ten experiments indicate that exposure to power-frequency magnetic fields can affectacquisition or performance of learned behavior. The effects are either adverse, beneficial, or
absent, depending on the task and the timing of exposure to magnetic fields.](c) Electric and magnetic fields
Few investigators have examined the effects of combined EMF. Wolpaw et al. (Wolpaw et al.,1989) exposed six macaques to electric fields of 3Ð30 kV/m in combination with magnetic fieldsof 10Ð90 mT for 18 h/d for three weeks. The performance of a simple food-motivated operanttask was not affected as compared with sham-exposed controls. Salzinger et al. (Salzinger et al.,1990) exposed rats to 60 Hz 30 kV/m and 100 mT. In a complex operant experiment withmultiple extinctions and testing at various times during the diurnal cycle, there was someevidence (p < 0.05) for a slower response at the mid-point of the light portion of the lightÐdark
cycle.
de Lorge and Grissett (de Lorge & Grisset, 1977) studied the effects of EMF on the operant
behavior of 10 male and female monkeys (Table 4.30) but detected no effects on match-tosample, fixed interval, or reaction time response. [This brief publication summarizes acomplicated series of experiments performed with various exposure paradigms and dependent
behavioral variables; the information provided is insufficient for detailed review of this work.]

223

Orr et al. (Orr et al., 1995) studied the effects of exposure to EMF on a match-to-sample
operant task with two groups of six male baboons. As in the studies of social behavior,
described previously (Coelho et al., 1995) imperceptible 6 kV/m 50 mT fields had no effect on
any aspect of operant performance. When the same animals were exposed to 30 kV/m and 100
mT, no effects on operant performance were observed.
[All of the experiments in which nonhuman primates were used to examine the effects ofcombined exposure to electric and magnetic fields did not detect effects on operant
performance. The single experiment in rats showed a subtle effect. Overall, no major adverse
effects on operant performance have been reported as a result of exposure to power-frequency
EMF.]
4.4.3.4 Neurophysiology(a) Endocrinology
Some of the early studies of the effects of exposure to electric fields on growth anddevelopment (Burack et al., 1984; Marino et al., 1977; Marino et al., 1976; Marino et al., 1980)
suggested that it was ÔstressfulÕ. Thus, investigators have sought endocrine changes that are thesine qua non of stress.
As reviewed by the National Research Council (NRC et al., 1997), Marino et al. (Marino et al.,1977) measured blood corticosterone concentrations in rats exposed to a 15 kV/m, 60 Hz
electric field for 10 months; they reported reductions in six of the ten experiments. Hackman
and Graves (Hackman & Graves, 1981) reported that adult mice (5Ð15 per group) exposed toelectric fields of up to 50 kV/m, 60 Hz showed reductions in plasma corticosterone
concentrations, but only at the onset (15 min) of exposure. Free et al. (Free et al., 1981) noincrease in corticosterone concentration was found at 30 or 120 days. Quinlan et al. (Quinlan etal., 1985) exposed four Long-Evans hooded rats to 100 kV/m (60 Hz) for 1 or 3 h. Plasma
corticosterone concentrations were not elevated in the four field-exposed rats relative to foursham-exposed controls. Portet and Cabanes (Portet & Cabanes, 1988) reported that rabbits(seven per group), but not rats (25 per group) exposed to 50 kV/m (50 Hz) showed reduced
adrenal gland cortisol content. Changes were not observed in blood corticosterone
concentrations.
Rommereim et al. (Rommereim et al., 1990) observed chromodacryorrhea in female rats (68 pergroup) exposed continuously to 130 kV/m (60 Hz) and interpreted this as a stress response.
Leung et al. (Leung et al., 1990) quantified the chromodacryorrhea effect, reporting that it wasincreased in incidence and severity at 65 and 130 kV/m; the group at 10 kV/m did not differ
from the sham-exposed control group.
Margonato et al. (Margonato et al., 1993) exposed groups of 20 rats to 50 Hz electric fields ofeither 25 or 100 kV/m for 8 h/d for 280, 440, or 1240 h. The plasma concentrations oflutenizing hormone, follicle-stimulating hormone, and testosterone differed widely among224

animals within groups, and no differences between field-exposed and sham-exposed groups
could be detected. No effects on testis were reported. (see Table 4.31)
In three experiments, Kato et al. (Kato et al., 1994a) measured plasma testosterone
concentrations in adult male Wistar king rats (10Ð12 per group) after 42 days of exposure to a
50 Hz circularly polarized magnetic field of 0.02, 0.1, 1, 5, or 50 mT. There was no effect.
Picazzo et al. (Picazo et al., 1995a) report that groups of 30 male mice continuously exposed toa 15 mT 50 Hz magnetic field had a 27% increase (p < 0.05) in serum testosterone
concentration, accompanied by a 7% increase (p < 0.05) in testis weight with a 12% increase in
the area of the interstitium.
de Bruyn and de Jager (de Bruyn & de Jager, 1994) suggested that continuous exposure of miceto electric fields (50 Hz, 10 kV/m) acts as a stressor (Table 4.31). Their conclusion is based on
two positive observations (out of a larger set) in the offspring of breeding pairs exposed to 10
kV/m, 22 h/d during gestation until either 35 days, 6 months, or 18 months of age. Mice of eachsex and three ages were examined in daytime or night-time for several different variables. In one
study, the serum corticosterone concentration was determined both day or night. In the
exposed adult males (5Ð13 per group), the mean daytime corticosterone concentration was
higher than in the controls (p < 0.02). Lipid staining of the adrenal cortex in the zona
glomerulosa but not in the zona fasiculata or zona reticularis was elevated (p < 0.05) only inadult males.
Picazo et al. (Picazo et al., 1996) report that the second generation of OF-1 mice (30 exposedand 30 controls) continuously exposed to a 15 mT 50 Hz magnetic field showed significant
changes (p < 0.05) indicative of adrenocortical effects: the normal diurnal rhythms in plasma
cortisol rhythms and adrenal cortex thickness were lost. The authors indicated that 15Ð20% of
the exposed animals showed changes associated with adrenocortical hyperplasia; however,extensive histopathological examination did not reveal statistically significant differences. [Thecontrols were not sham exposed, and the pathology assessments were not conducted in a blindfashion.]Thompson et al. (Thompson et al., 1995) exposed 10 sheep beneath a 500 kV (60 Hz)
transmission line; the 10 controls were housed away from the line. The average field strengths
were 6 kV/m and 4 mT. Blood samples were obtained at intervals of 0.5Ð3 h over a 48-h periods
on eight occasions over eight months. After the pre-exposure sampling, blood was sampled two
weeks after initiation of exposure. No change in plasma cortisol concentration was detected.
Burchard et al. (Burchard et al., 1996) studied numerous aspects of the physiology of 16
lactating, pregnant Holstein cows during periods with and without exposure to EMF. Cortisol
was sampled twice a week and showed no changes, while progesterone was measured weekly
and was increased by 11% (p < 0.05).
[Some of these studies present evidence that exposure to electric fields can be stressful, but theavailable evidence does not clearly establish that such an effect occurs.]

225

(b) Effects on opioid action
Ossenkopp and Kavaliers (Ossenkopp & Kavaliers, 1987b) examined the effects of 60 Hz
magnetic fields of 2, 100, and 150 mT intensity; 30-min exposure of groups of 10Ð16 CF-1 mice
produced a field intensity-dependent reduction (p < 0.05) in the analgesic effect of morphine.
Ossenkopp and Kavaliers (Ossenkopp & Kavaliers, 1987a) also described a field intensitydependent reduction (p < 0.05) in morphine analgesia in two experiments conducted at 50Ð150mT (Table 4.31). Morphine was given at the mid-point of a 60-min exposure and testing wasdone at the end of exposure to magnetic fields. In the hot-plate analgesia test, the latency toforepaw lick was 56% of the control time in mice at 50 mT, 45% at 100 mT, and 23% at 150
mT. [The latency cut-off of 150 s was excessive for studies of morphine analgesia and raises
concern about the method, especially with regard to determining a relationship with theendogenous opioid system. It limits interpretation of the effects on analgesia.]
Lai and Carino (Lai & Carino, 1998) exposed 6Ð10 male Sprague-Dawley rats to a 2 mT, 60 Hz
magnetic field for 1 h and repeated their earlier observation of decreased (p < 0.05) cholinergic
activity in the frontal cortex and hippocampus. They also showed that pretreatment of rats
with the m-opiate receptor agonist 3-funaltrexamine or the d-opiate receptor agonist naltrindole
through an intracerebroventricular cannula 24 h before exposure to magnetic fields blocks theinduced decrease in sodium-dependent, high-affinity choline uptake in the frontal cortex andhippocampus. Zecca et al. (Zecca et al., 1998) exposed groups of 64 male Sprague-Dawley rats
to 5 mT and 1 kV/m or 100 mT and 5 kV/m for eight months and measured m-opiod receptors in
the frontal and parietal cortex and hippocampus in subgroups of 10-21 rats; no change in mopiod receptor concentration was found in the hypothalamus, striatum, or cerebellum.
(c) Neurotransmitters
Vasquez et al. (Vasquez et al., 1988) measured monoamines in the hypothalamus and striatumof groups of six male Sprague-Dawley rats after exposure to 39 kV/m (60 Hz) for 20 h/d for 30
days; measurements were made every 4 h throughout the lightÐdark cycle. Changes in phase,rather than amplitude, were reported for norepinephrine, dopamine, and the serotonin
metabolite 5-hydroxindole acetic acid in the hypothalamus and for 3,4-dihydroxyphenyl acetic
acid in the striatum. Seegal et al. (Seegal et al., 1989) measured monoamine concentrations in the
cerebrospinal fluid of macaques after exposure to 60 Hz 10 mT, 3 kV/m or 30 mT, 10 kV/m or
90 mT, 30 kV/m for 20 days. The concentrations of the dopamine metabolite homovanillic acidand 5-hydroxindole acetic acid were reduced in field-exposed animals.
Zecca et al. (Zecca et al., 1991) measured norepinephrine, serotonin, 5-hydroxindole acetic acid,dopamine, and it metabolites homovanillic acid and 3-4-dihydroxyphenyl acetic acid in striatumof animals exposed to electric fields of 25 and 100 kV/m (50 Hz) for various times. The aminoacid neurotransmitters taurine, glutamine, aspartic acid, glutamic acid, glycine, alanine, and gaminobutyric acid were also measured. Numerous t tests were performed, and some small (10%or less) differences (p < 0.05) were observed (Table 4.31).

226

Lai et al. (Lai et al., 1993) examined the effects of 45 min exposures to a 60 Hz magnetic field of500, 750, and 1000 mT intensity on sodium-dependent, high-affinity choline uptake in thebrains of six male rats. Brains were collected immediately after exposure. Decreased (p < 0.05)
sodium-dependent high-affinity choline uptake was demonstrated; dose-dependent reductions
were observed in frontal cortex and hippocampus. The authors also showed that the opioid
antagonist naltrexone, administered just before exposure to magnetic fields, blocked theseeffects, but naloxone did not. [Concern was raised by the differential effects of these two
narcotic antagonists, since both inhibit central opioid receptors.]
Sakamoto et al. (Sakamoto et al., 1993) exposed Sprague-Dawley dams and sires to 60 Hz, 50
mT circularly polarized magnetic fields before mating and dams during gestation. Six to 12
embryos per group were harvested at days 12, 14, 16, 18, and 20 of gestation and cholinetransferase activity in brain was measured. In an additional experiment, groups of six animals
were exposed for three months before mating. The brains of offspring were analyzed 10 days
after birth. In both studies, normal age-related changes were found but no effects of exposure.
Margonato et al. (Margonato et al., 1995) measured the brain neurotransmitter concentrationsin 256 male Sprague-Dawley rats (groups of 15) after 5000 h of exposure to a 50 Hz, 5 mT fieldfor 20 h/d. Striatum, hypothalamus, hippocampus, and cerebellum were analyzed for
norepinephrine, dopamine, 3,4-dihydroxyphenyl acetic acid, homovanillic acid, serotonin, and5-hydroxindole acetic acid. No group differences were detected. Zecca et al. (Zecca et al., 1998)
determined norepinephrine, dopamine, 3,4-dihydroxyphenyl acetic acid, homovanillic acid,serotonin, and 5-hydroxindole acetic acid in the frontal cortex, parietal cortex, striatum,
hypothalamus, and cerebellum; D2 receptor concentrations were measured in striatum andfrontal cortex. No effects of an eight-month exposure to 5 mT and 1 kV/m or to 100 mT and 5
kV/m were found. [In both experiments, neurotransmitter concentrations were assessed at theend of long-term exposure, and any acute temporal trends would not have been determined.][Although a few studies have shown effects of magnetic fields on neurotransmitters, the results
are mixed and the effects noted are relatively small. The design of many of these studies
included terminal sampling at the end of long-term exposure, and limited end-points were
evaluated to assess the functioning of the neurotransmitter system. The inherent difficulty inassociating changes in regional neurotransmitter concentrations with functional or behavioral
alterations makes interpretation of the biological significance of these findings difficult.]
4.4.3.5 Electrophysiology(a) Electric fields
Jaffe et al. (Jaffe et al., 1983) indicated that exposure of groups of 2-9 rats exposed in vivo toelectric fields (60 Hz, 65 kV/m) increased the synaptic excitability, measured ex vitro, of theexcised superior cervical ganglion. Jaffe et al. (Jaffe et al., 1981) reported that exposure toelectric fields (65 kV/m, multiple frequencies) increased the fatiguability at the rat
neuromuscular junction (13-22 animals per group). Jaffe et al. (Jaffe et al., 1980) measured

227

visual evoked potentials repeatedly in developing rats exposed to 60 kV/m; exposure to electricfields had no effect. Blackwell (Blackwell, 1986) measured the firing rates of 51 single units in
rat cortex. Electric fields of 100 V/m had no effect on the overall firing rate; at 15 or 30 Hz,
some synchrony with the applied waveform was observed, but the effect was not observed at
50 Hz.
Gavalas et al. (Gavalas et al., 1970) and Gavalas-Medici and Day-Magdelano (Gavalas-Medici& Day-Magdaleno, 1976) suggested that exposure of macaques to electric fields within therange of normal EEG frequencies, typically 30 Hz or less, affected neuronal activity. ELFmodulated VHF fields appear to be a particularly effective stimulus for such effects (Bawin etal., 1973).
(b) Magnetic fields
As reported by the National Research Council (NRC et al., 1997) Ossenkopp and Cain
(Ossenkopp & Cain, 1988) found that groups of 17 adult male rats field-exposed or shamexposed to a 100 mT magnetic field at 60 Hz showed attenuation of seizure discharges in akindling model. Ossenkopp and Cain (Ossenkopp & Cain, 1991) presented data from six
experiments with group sizes of 11Ð20 rats in which a 60 Hz magnetic field of 50Ð185 mT wasapplied for 1 h before induction of seizures with pentylenetetrazol (Table 4.32). In only two of
six studies was seizure duration decreased (p < 0.05), and fewer seizures (p < 0.05) wereobserved in only one experiment. Mortality due to seizures was diminished by exposure but
not in relation to field intensity. [Overall, exposure to 60 Hz magnetic fields does not aggravate
seizures; however, this paper does not convincingly demonstrate that exposure to electric fields
diminishes their number.]
Lyskov et al. (Lyskov et al., 1993a) exposed 12 female Sprague-Dawley rats to magnetic fieldsof 126 mT or 1.26 mT for 24 h (multiple frequencies) and then recorded an EEG. An average
response (based on measurements taken immediately and 15 and 30 min after exposure) of four
statistically significant effects was observed after sham exposure. The observation of 4-fold(1.26 mT) and 8.5-fold (126 mT) increases in the number of statistically significant (p <0.05)
changes in EEF variables was taken by the authors as evidence of an effect of exposure tomagnetic fields on the EEG. Numerous other comparisons led the authors to the generalizations
that power in the delta (1Ð4 Hz) and theta (4Ð8 Hz) bands was decreased and power in the beta
(12Ð20 Hz) and high frequency (30Ð60 Hz) bands was increased. [They analyzed 31 EEGparameters for four electrode combinations and three times, so that many statisticalcomparisons were made, and the probability that one or more of the results would besignificant by chance alone (Type I errors) was high. The study is statistically invalid and hasother methodological short comings. Use of pre-implanted metallic screws as EEG electrodes
might be an issue.]228

(c) Electric and magnetic fields
Dowman et al. (Dowman et al., 1989) measured auditory, visual, and somatosensory evoked
potentials twice a week during three-week exposures in six adult macaques exposed to EMF
combinations of 3 kV/m and 10 mT, 10 kV/m and 20 mT, and 30 kV/m and 30 mT; there werefour sham-exposed controls. Evoked potentials were measured during the daily 6-h periods
without exposure to EMF. There were some signs that the amplitudes of the later components
of somatosensory evoked potentials were reduced in the two groups exposed to higher field
intensities.
[A few papers indicate that exposure to power-frequency electric and/or magnetic fields canchange the characteristics of EEGs or evoked potential activity in animals. The effects on the
EEG are more prominent at frequencies less than 30 Hz, where the imposed field is in the same
frequency range as endogenous neural activity; however, none of the results suggests that such
effects are hazardous. The available data suggest that exposure to magnetic fields inhibits, rather
than stimulates, epileptic activity.]
4.4.3.6 Summary
There is strong evidence that electric fields can be perceived.
[This conclusion was supported by 18 members of the Working Group; there were 2
abstentions and 9 absent.]
There is weak evidence for the neurobehavioral, neuropharmacological, neurophysiological, andneurochemical effects of electromagnetic fields.
[This conclusion was supported by 9 members of the Working Group; there were 8 votes forÔmoderateÕ evidence, 3 abstentions, and 9 absent.]229

Table 4.28 Perception in experimental animals exposed to EMF
Reference

Animals

GroupsExposure conditions

OutcomeSpragueDawley
rats, six
adult maleWithinsubject design
standard inpsychophysics

Vertical, 60 Hz, 0 Ð 25 kV/m;brief daily exposures during
training trials

Moving air did not changemean detection thresholdof 7.5 kV/m, implies
detection not mediated byhair movement(Rogers et al., 1995c)

Baboon,Papio c.,six young
adult maleWithinsubject designcommon inoperant
experiments

Vertical, 60 Hz, 22-65 kV/m;brief daily exposures during
training trials in sevenexperiments distributed overa 1 year

Stimuli can serve as
discriminative stimulus
and as a secondary
reinforcer on a simple
operant task, implying
detection(Orr et al., 1995)

Baboon,Papio c.,six young
adult maleWithinsubject design
standard inpsychophysics

Vertical, 60 Hz from 4 to 41
kV/m; brief daily exposuresduring training trials over 16
weeks

Average detection
threshold 12 kV/m; effectnot mediated by sound andunder stimulus control

LongEvans rat,
five young
adult
femaleWithinsubject design
standard inpsychophysics

200 Ð 1900 mT at 7, 16, 30,
60 and 65 Hz; 1 h/d for 5 d
per week for 5 weeks

MF presence served as cue
for conditioned
suppression of operant
responding

Electric fields(Stell et al., 1993)

Magnetic fields(Smith et al., 1994)

230

Table 4.29 Summary of experiments assessing aversion in experimental animals fields
Reference

Animals

GroupsExposure conditions

OutcomeBaboon, Papioc., young adultmale

8 field-exposed
and 8 shamexposed

30 kV/m, 60 Hz, vertical; 12h/d, 7 d/week for 6-week preexposure, exposure, and postexposure periods

Rates of occurrence of Passive
Affinity, Tension and Stereotypy
were increased in Exposurecompared to Pre- and Postexposure(Easley et al.,1991)

Baboon, Papioc., young adultmale

8 field-exposed
and 8 shamexposed

60 kV/m, 60 Hz, vertical; 12h/d, 7 d/ week for 6-week preexposure, exposure, and postexposure periods

Rates of occurrence of passive
affinity, tension and stereotypy
were increased in exposurecompared to pre- and postexposure periods(Easley et al.,
1992)

Replication of
Easley et al.,
1991

8 field-exposed
and 8 shamexposed; crossover fromprevious
experiment

30 kV/m, 60 Hz, vertical; 12h/d, 7 d/week for 3-week preexposure, and exposure
periods

Rates of occurrence of passive
affinity, tension and stereotypy
were increased only in first weekof exposure; true for two
previous experiments as well

(Rogers et al.,1995c)

Baboon, Papioc., six young
adult maleWithin-subject
design,common inoperant
experiments

Vertical, 60 Hz, 0-65 kV/m;brief daily exposures during
training trials conducted over
1 year period

Subjects would not turn off
electric fields, indicating
exposure was not aversive;
subjects responded readily forfood rewards(Rogers et al.,
1995b)

Baboon, Papioc., young adultmales

Six field- andsix shamexposed

Vertical, 60 Hz, 30 kV/m; 12h/d, during 6-week preexposure, exposure and postexposure periods

Initial day of exposure produced
work stoppage on FR30/DRL20
operant task

Electric fields(Coelho et al.,1991)

6 field and 6
sham-exposed,cross-overdesignVertical, 60 Hz, 60 kV/m; 12h/d, during 6-week preexposure and exposure periods

Electric and magnetic fields(Coelho et al.,Baboon, Papio
1995)
c., young adultmale

8 field-exposed
and 8 shamexposed

60 Hz ,vertical electric field (6kV/m) and horizontal magnetic
field (50 mT); 12 h/d during 6week pre-exposure, exposure
and post-exposure periods

Based on 12 kV/m detection
threshold, observed absence ofchanges in social behavior at
onset of 6 kV/m ÒexpectedÓ andat onset of 30 kV/m exposureÒunexpectedÓ; magnetic fieldinteraction?

(Orr et al.,
1995)

5 field- and 5
sham-exposed

60 Hz ,vertical electric field (6kV/m) and horizontal magnetic
field (50 mT); 12 h/d during 6week pre-exposure, exposure
and post-exposure periods

Based on 12 kV/m detection
threshold, observed absence ofchanges in operant behavior at
onset of 6 kV/m ÒexpectedÓ andat onset of 30 kV/m exposureÒunexpectedÓ; MF interaction?

Baboon, Papioc., young adult
male

231

Table 4.30 Learning and performance in experimental animals exposed to EMF
Reference

AnimalGroupsExposure conditions

OutcomeSprague
Dawley rat,
adult maleTwo groups ofseven, fieldexposed andsham-exposed

3.5 kV/m, 60 Hz, 22 h/d; testing
continued for 8 dExposed rats made twice as many
responses during conditioned
emotional response testing(Rogers et al.,1995c)

Baboon,Papio c.,six young
adult maleWithin-subject
design, common
in operant
experiments

Vertical, 60 Hz, 22-65 kV/m;brief daily exposures during
training trials in 7 experiments
distributed over a 1 year

Exposure had no effect on
response rate or extinction ofoperant responding on a simple
appetitive task

(Rogers et al.,
1995b)

Baboon,Papio c.,young
adult male

Six field- and six
sham-exposed

Vertical, 60 Hz, 30 kV/m; 12 h/dfor 6-week pre-exposure,
exposure, and post-exposure
periods

No effect on performance on
FR30/DRL20 operant task

Meadowvole,
Microtusp., adult

Male and female,
MF on and MF
off; 8 - 12 pergroup

60 Hz, linear, 0.1 mT for c. 5
minutes per day (during testing)for 10 days

Exposure improved acquisition
and retention of Morris water mazetask, especially in females(Trzeciak et al.,
1993)

Wistar rat,
adult maleand female(pregnantand nonpregnant)Three groups of
10 Ð 12 animals

50 Hz, 18 mT; 2 hours per day
for 20 days; test at days 0, 4, 10
and 17

Decrease in irritability score; no
effects on open field behavior or
locomotion(Sienkiewicz et al.,
1994)

CD1
mouse,
pregnant

Field-exposed(184) or shamexposed (168)

50 Hz, 20 mT for duration ofgestation; dams removed fromMF shortly before parturition;
offspring were tested at days 7,
14, 21, 30, 60 and 90, without
further MF exposure

Numerous variables from abehavioral teratology test battery
were measured; three effects weredetected, none regarded asimportant(Kavaliers et al.,
1996)

Deer mice,
Peromyscus m.,
adult

Field-exposedand shamexposed, male andfemale, fivesubjects per cell

100 T, 50 Hz, brief exposure (< 5minutes) during 10 daily
training sessions

Males perform better in Morris
water maze than females, MF
exposure improves performance offemales(Lai, 1996)

Sprague
Dawley rat,
young
adult male2 groups of 8
field-exposed andsham-exposed

45 minutes of exposure to 0.75
mT immediately before each of ten
daily training sessions

Increase in errors in 12-arm radial
maze acquisition, final
performance matches controls

Electric fields(Frey & Wesler,
1984)

Magnetic fields(Kavaliers et al.,
1993)

Exposure increased errors inacquisition of 12-arm radial maze,but pre-treatment withphysostigmine prevented theincrease in errors

4 groups of 4 or 5
field-exposed andsham-exposed,
drug-treated andnon-treated(Stern et al., 1996)

LongEvans rat,
adult maleGroups of 5, 2
experiments by 3
conditions

Horizontal, 60 Hz, 50-72 mT
magnetic fields plus DC field to
reduce geomagnetic field; brief
daily exposures during training
trials232

No effects on performance on
FR30/DRL20 scheduleTable 4.30 (continued)
Reference

AnimalGroupsExposure conditions

Outcome(Sienkiewicz et al.,1996a)

CD1 mouse,
adult maleField-exposed andsham-exposedgroups of 10, 4
experiments

Vertical, 50 Hz at 5, 50, 500 or
5,000 mT; exposure during ten
daily test sessions

Acquisition of radial arm
maze performance notaffected by exposure during
testing

Field- and shamexposed groups of
10

Vertical, 50 Hz; experimentalgroups exposed to 5 mT only inutero

Acquisition of radial arm
maze performance as adultnot affected by in utero
exposure(Sienkiewicz et al.,1998)

C57BL/
6J mouse, adultmale

4 experiments, fieldexposed and shamexposed groups of 6

Vertical, 50 Hz, magnetic fields at
0.75 mT for 45 min immediately
before testing

Acquisition of radial arm
maze performance slowed,
but final performance was
equal to that of controls(Lai et al., 1998)

Sprague
Dawley rat,
adult male

Cage controls (5),sham-exposed (10),and field-exposed(9)

60 Hz, 1 mT, 1 h; test immediately
after exposure

Exposed rats swam more
slowly in Morris water
maze but performed as wellas controls during
training; in a probe trail,
exposed rats performed lesswell

10 adult (males andfemales) animals
used in multiple
experiments,
within-subject
comparisons

14 experiments with 7-60 Hz, 129 V/m and 0.3 or 1.0 mT;
exposures were 1 - 24 h/d for 5 Ð1008 hNo effects on match-tosample, fixed interval orreaction time responding

5 field-exposed and5 sham-exposed

60 Hz; vertical electrical fields
and horizontal magnetic fields; 6
kV/m with 50 mT, 12 h/d during
6-week pre-exposure, exposure
and post-exposure periods

No effects on match-tosample performance, normal
time-delay accuracy curves

5 field-exposed and5 sham-exposed

60 Hz; vertical electric fields andhorizontal magnetic fields; 30
kV/m with 100 mT; 12 h/d during
6-week pre-exposure, exposure
and post-exposure periods

No effects on match-tosample performance, normal
time-delay accuracy curves

5 field-exposed and5 sham-exposed,cross-over design

60 Hz; vertical electric fields andhorizontal magnetic fields; 30
kV/m with 100 mT; 12h/d during
1 week pre-exposure andexposure periods

No effects on match-tosample performance, normal
time-delay accuracy curves

Combined electric and magnetic fields(de Lorge & Grisset,
Squirrel1977)
monkey,Saimiri s. (6),and rhesus
monkey,Macaca m.
(Orr et al., 1995)

Baboon, Papioc., young adult233

Table 4.31 Neurophysiological effects of EMF in experimental animals
References

Animals

Effects on the endocrine system(Margonato et al.,Sprague Dawley
1993)
rat, young adultmaleGroupsExposure conditions

Outcome

280 subjects, ingroups of 20

50 Hz vertical EF for 8 h/d for
280, 440 or 1240 h at 25 kV/mor 100 kV/m

No significant changes in
LH, FSH or testosterone(Kato et al., 1994a)

Wistar-King rat,
adult male

5 groups of 20 - 24
animals

0.02, 0.1, 1, 5 and 50 mT for 6
weeks (near continuous);
circularly polarizedNo effects on plasma
testosterone
concentrations(de Bruyn & de Jager,
1994)

Balb/c mouse,males andfemales, 6 and18 months

Exposed andcontrols (non-sham
exposed), day andnight, 5 Ð 13 pergroup

10 kV/m, vertical, 50 Hz; 22 h/dfrom conception to death, for up
to 6 generations

Median daytime serum
corticosterone elevated
2.5-fold for adult males
only; no other differences

Balb/c mouse,males andfemales; 1, 6 and18 months

Exposed andcontrols (non-sham
exposed); 12 - 21 pergroup

10 kV/m, 50 Hz; 22 h/d fromconception to sampling

Lipid content of one zoneof adrenal cortex reduced
by one third, only in 6month-old males(Picazo et al., 1995a)

OF1 mouse,
male; second
exposedgeneration;
exposed inutero and to 10
weeks of age

Litters from 24
females; 30 exposedand 30 controls used
for testes studies

15 mT at 50 Hz, horizontal,
near-continuous exposure;dams exposed for 14 weeks
prior to mating, exposure
continued until offspring were
10 weeks of age

Increases in serum
testosterone and testis
weight occurred in
exposed animals(Thompson et al.,1995)

Suffolk lamb,female, prepubertal

Field-exposed andsham-exposed

6 kV/m and 4 mT at 60 Hz,
exposed from 2 to 10 months ofage

Diurnal pattern ofcortisol secretion was
unaffected(Burchard et al.,
1996)

Holstein cow,
multiparous

One group of 16
studied in 28-d
periods with orwithout exposure

30 mT horizontal and 10 kV/mvertical; presumably 60 Hz,
apparently 23 h/dProgesterone waselevated 11% duringexposure, cortisol was
unchanged

OF1 mouse,male and female,secondgeneration, 10
weeks of age
Effects on analgesic and opioid action(Ossenkopp &CF-1 mouse,
Kavaliers, 1987b)
adult male

30 control and 30
exposed, divided
into day and nightgroupsHorizontal, 15 mT, 50 Hz;
continuous exposure

Exposed rats did notshow normal diurnal
differences in cortisol
concentration andadrenal cortex thickness

Cage control, fieldexposed and shamexposed, groups of
10-16 animals

Linear, 60 Hz
50, 100 or 150 mT for 1 h

Analgesia was reduced ina dose-dependent manner

Field-exposed andsham-exposed; setsof 6 Ð 8 subjects

2 mT, 60 Hz, 1 h

MF exposure reduced
high affinity choline
uptake in frontal cortex
and hippocampus

Field-exposed andsham-exposed,
vehicle or one of two
drugs, groups of 6 Ð
8

2 mT, 60 Hz, 1 hour

Administration of opiate
antagonists blocked theeffect(Picazo et al., 1996)(Lai & Carino, 1998)

Sprague Dawley
rat, adult male234

Table 4.31(continued)
References

Animals

GroupsExposure conditions

Outcome(Zecca et al., 1998)

Sprague Dawley
rat, adult male3 groups of 64, 1
sham-exposed and 2
field-exposed

Horizontal magnetic fields andvertical electric fields, 5 mT and
1 kV/m or
100 mT and 5 kV/m,
22 h/d for 8 months

Decreased opiod
receptors in frontal andparietal cortex and inhippocampus

4 experiments, fieldor sham-exposed;
numbers not given,
but standard errors
very small

Vertical, 50 Hz, 25 and 100
kV/m; 8 Ð 22 h/d for 5-7 d per
week, 320-1408 hours total

Short exposures reduced
most of the amino acids;
moderate duration
exposures reduced only
tau, and long exposuresagain reduced most ofthem; temporal effects notdepending on electricfield strength

Effects on neurotransmitters(Zecca et al., 1991)
SpragueDawley rat,
adult male(Lai et al., 1993)

SpragueDawley rat,
adult male

10 groups of 6-10,
sham- and fieldexposed, saline and 2
drugs

Horizontal, 60 Hz; 0.5, 0.75 or
1 mT; 45 min

High affinity choline
uptake reduced at 0.75
and 1 mT, effect blockedby central cholinergic
antagonist but not by
peripheral antagonist(Sakamoto et al.,
1993)

SpragueDawley rat

Field-exposed andsham-exposedneonates examined atdays 5 and 10

60 Hz, circular, 50 mT;
apparently continuously
exposed in utero and to time ofanalysis

No effects on brain
choline transferase
activity, normal
developmental changes

11 groups of 6 Ð 12
embryos measured atdays 12, 14, 16, 18
and 2060 Hz circular, 50 mT apparently
continuous; exposed in utero
and to time of analysis

No effects on brain
choline transferase
activity, normal
developmental changes(Margonato et al.,
1995)

SpragueDawley rat,
young adultmale

A total of 30
subjects, field- andsham-exposed, two
replicate experiments

5 mT, 50 Hz, horizontal; 22hours per day for 32 weeks

No changes in six
neurotransmitters or
metabolites in four brain
regions(Zecca et al., 1998)

SpragueDawley rat,
adult male3 groups of 10, 1
sham-exposed and 2
field-exposed

Horizontal magnetic field andvertical electric field; 5 mT and 1
kV/m or 100 mT and 5 kV/m; 22
h/d for 8 months

At 100 T and 5 kV/m,increased pineal gland
norepinephrine content;
no changes in serotoninor 5-HIAA*

LH, luteinizing hormone; FSH, follicle-stimulating hormone; 5-HIAA, 5-hydroxindole acetic acid235

Table 4.32 Electrophysiological effects of EMF in experimental animals
References

AnimalEffects on electrophysiology(Ossenkopp & Cain,
Long-Evans rat,
1991)
adult maleGroupsExposure conditions

Outcome18 groups of 11 Ð
20; sham- or fieldexposed

60 Hz, horizontal magnetic field of
up 50 to 185 mT for 1 h; drug
injected after exposure

Exposure modestly
decreased seizure
mortality(Lyskov et al.,1993a)

Wistar rat, adultfemaleOne group, measured
in baseline and 0, 15
and 30 min after
exposure

45 Hz, vertical; 126 mT and 1.26
mT; 2 24-h exposures (24 h apart);
1 s on and 1 s off

4 ÒhitsÓ after sham, 34
after 126 mT and 16
after 1.26 mT(Ossenkopp &Kavaliers, 1987b)

CF-1 mouse,
adult male

Cage control, fieldexposed and shamexposed, groups of
10 Ð 16

Linear, 60 Hz, 50, 100 or 150 mT
for 1 hAnalgesia was reduced
in a dose-dependent
manner236

4.4.4 Reproductive and developmental effects
Assessments of the effects of magnetic fields on reproduction and development haveincluded a wide spectrum of biological end-points, including gametogenesis, fertilization,
implantation, embryogenesis, and pre- and postnatal development. A series of reviews(Brent et al., 1993; Chernoff et al., 1992; Huuskonen et al., 1998; Juutilainen, 1991;
Juutilainen & Lang, 1997) have been published on the reproductive and developmental
toxicity of EMF. This section addresses studies of the effects of magnetic fields on
reproduction and development in avian and mammalian systems; these are summarized inTable 4.33. Studies of avian systems involving pulsed magnetic fields are not consideredin this section.
4.4.4.1 Birds
Juutilainen and Saali (Juutilainen & Saali, 1986a) exposed 10 chicken embryos during thefirst 48 h of development to 50 Hz magnetic fields at field strengths of 0.1Ð10 mT; there
were 10 controls. The embryos were scored for developmental stage and categorized as
normal or abnormal. No change in developmental stage due to exposure was observed.
The number of abnormal embryos was increased (p < 0.05) at 10 and 100 A/m.
Pafkova et al. (Pafkova et al., 1994) reported the effects of 50 Hz magnetic fields at field
intensities of 6 mT or 10 mT on avian embryonic development at 2, 6, 16, 20, and 40 h.
No effects were observed on mortality or structural malformations evaluated on the ninth
day.
In a related study, Pafkova and Jerabek (Pafkova & Jerabek, 1994) combined magnetic
fields with ionizing radiation (X-ray). Chick embryos were pre-exposed to a 50 Hz, 10
mT magnetic field from the second to fortieth hour of incubation and exposed to X-rays(4 or 5 Gy) on the third or fourth day of embryonic age. In a second series, chicks were
exposed to magnetic fields before or after X-ray treatment on day 3 or 4. The authors
found a statistically significant reduction in teratogenic development in embryos exposed
to magnetic fields before ionizing radiation (p < 0.003) when the results of all studies werecombined. Exposing the embryos to magnetic fields after ionizing radiation resulted in a
potentiation of adverse developmental effects (p < 0.02).
Pafkova et al. (Pafkova et al., 1996) conducted a series of studies in which chick embryos
were pre-exposed to magnetic fields (50 Hz, 10 mT) for eight 2-h sessions for the first 48
h of incubation. After two or three days of incubation, the eggs were injected through awindow in the shell with 10 ml of insulin (0.00Ð0.05 mg) or tetracycline (10Ð30 mg).
Controls were injected with 10 ml of water. Exposure of eggs to magnetic fields before
treatment with insulin reduced the embryotoxic effects (p < 0.01). Exposure to magnetic
fields and tetracycline conclusion inconsistent with paper.

237

The effects of an intermittent horizontal sinusoidal 50 Hz magnetic field was reported by
Veicsteinas et al. (Veicsteinas et al., 1996). In these studies, eggs were exposed to anintermittent (2 h on/ 22 h off) magnetic field of 200 mT. The eggs were exposed or shamexposed for 48 h to magnetic fields and incubation was continued in an artificial brooder.
The embryos were examined for developmental anomalies and maturity at the end of the
48 h. Other end-points included extracellular membrane components on day 7 andhistological malformations in the brain, liver, and heart on days 2, 7, 12 and 18 of
incubation. Egg fertility and weight was examined on days 2, 7, 12, and 18. Additionally,
eggs from each treatment group were allowed to hatch and the chicks were followed, being
weighed at intervals, for 90 days, when the organs were examined histologically. No
effects were seen on any of the end-points of embryo development, body weight, ororgans.
Farrell et al. (Farrell et al., 1997) reported the effects of 60 Hz, 4 mT sinusoidal magnetic
fields on 545 developing chick embryos. A significant increase (p < 0.01) in morphologicalabnormalities was observed in eggs exposed to the sinusoidal magnetic field.
[Development abnormalities were observed in three of five studies in which chickembryos were exposed to sinusoidal 50 or 60 Hz magnetic fields, but the relevance of
these results to mammalian growth and development is unclear.]
4.4.4.2 Mice
Juutilainen et al. (Juutilainen et al., 1997) reported their investigations of resorptions ingroups of 30Ð50 CBA/Ca mice exposed to low-frequency magnetic fields. Mice from 34Ð
56 litters per group were exposed on days 0Ð18 of pregnancy for 24 h/d to a 50 Hz
sinusoidal magnetic field of 13 or 130 mT. No differences were observed in resorption
rates between exposed and sham-exposed mice.
In studies with CD-1 mice, Kowalczuk et al. (Kowalczuk et al., 1994) exposed or shamexposed pregnant mice on days 0Ð17 of gestation to a 50 Hz sinusoidal magnetic field at
20 mT. Pre- and postimplantation survival was recorded, and fetuses were examined forthe presence of gross external, internal, and skeletal abnormalities. There were 90 exposed
and 86 sham-exposed mice, and 2167 fetuses were examined. The study was conducted
over a two-year period. No association was found between exposure to magnetic fields
and these end-points, but an association was found between exposure and longer, heavier
fetuses at term.
Spermatogenesis was evaluated in groups of five male hybrid (C57Bl/Cne x C3H/Cne) F1
mice (de Vita et al., 1995), 8Ð10 weeks of age, which were exposed to 50 Hz magnetic
fields (1.7 mT) for 2 or 4 h and analyzed 7, 14, 21, 28, 35, and 42 days after exposure.
Flow cytometric DNA histograms were prepared on testicular cell suspensions todetermine the relative frequencies of the various spermatogenetic cell subpopulations. In

238groups exposed for 2 h, no effects were observed at any time. In the groups exposed for 4h, a statistically significant effect (p < 0.001) was observed only on day 28.
[Exposure to EMF at power frequencies has not been found to have teratogenic effects inmice.]
4.4.4.3 Rats
Huuskonen et al. (Huuskonen et al., 1993) exposed groups of 72 pregnant Han:Wistar
rats to 50 Hz sinusoidal magnetic fields (12.6 mT) on days 0Ð20 of pregnancy for 24 h/d.
Minor skeletal malformations were observed in the offspring of the exposed group. The
mean numbers of implantations and living fetuses were statistically significantly
increased. The incidence of major malformations or resorption was not increased underthe exposure conditions used in this study.
Mevissen et al. (Mevissen et al., 1994) exposed female Wistar rats on days 1Ð20 of
gestation to a 50 Hz sinusoidal magnetic field (30 mT). Three sets of exposures wereconducted in which 12 rats per group were exposed or sham-exposed. On gestational day
20, the dams were sacrificed for reproductive and teratological assessment. No major
malformations were seen in any groups but a number of fetuses had minor skeletal
malformations.
In a study by Rommereim et al. (Rommereim et al., 1996), pregnant Sprague-Dawley rats
were weighed and randomly assigned to field- or sham-exposed groups. The rats were
exposed to a 1 or 0.61 mT 60 Hz horizontal magnetic field, on days 1Ð20 of gestation, 20h/d, 7 d per week. The studies were conducted as two replicate, with 96 rats pertreatment group. On day 20 of gestation, the dams were sacrificed for assessment ofreproductive and teratogenic end-points. The litters were evaluated for the numbers of
implantations, fetal deaths, and resorptions and for gross external, visceral, and skeletal
malformations and fetal weights. A total of 7903 fetuses from 519 litters were examined.
In the first replicate study, the number of fetuses per litter was decreased in the group
exposed to 1 mT (p < 0.05). This decrease was not observed in the replicate study. No
major malformations were correlated with exposure to magnetic fields.
Ryan et al. (Ryan et al., 1996) exposed groups of 46-55 timed-pregnant Sprague-Dawley
rats to linearly polarized, 60 Hz magnetic fields on gestational days 6Ð19. The fieldstrengths were 2 mT, 200 mT, and 1 mT with concurrent sham-exposed controls. A
positive control group of 15 rats treated with ethylenethiourea was included. The animals
were exposed or sham-exposed for 18.5 h/d, 7 d per week. On gestation day 20, the dams
were sacrificed for reproductive and tertalogical assessments. No evidence of maternal
toxicity was observed as a result of exposure. A battery of fetal examinations did notdemonstrate any significant difference in the incidence of fetal malformations or anomalies
between field-exposed and sham-exposed rats. The positive control caused malformations

239

and body-weight reductions in 100% of treated animals. [No malformations were seen inrats exposed to 50 or 60 Hz magnetic fields.]
In a study of similar design, Ryan et al. (Ryan et al., 1998) failed to show any effect of
exposure to magnetic fields in multigeneration studies of reproductive toxicity in groupsof 40 male and female Sprague-Dawley rats.
4.4.4.4 Hamsters
Niehaus et al. (Niehaus et al., 1997) exposed or sham-exposed groups of 45 Djungarian
hamsters to a sinusoidal 50 Hz magnetic field (450 mT) for 56 days. Flow cytometric
DNA histograms were prepared on testicular-cell suspensions to determine the relative
frequencies of the various spermatogenetic cell subpopulations on the basis of their DNA
contents. Significant differences (p at least < 0.05) in spermatogenetic cell populations
were observed.
4.4.4.5 Summary
A few laboratories have reported alterations in the development of chick embryos
exposed to sinusoidal magnetic fields. The results of studies of teratogenic andreproductive effects in mammalian systems have generally been negative; no studies wereavailable on other developmental end-points.
There is no evidence for the reproductive or developmental effects of exposure tosinusoidal magnetic fields.
[This conclusion was supported by 17 Working Group members; there were 3 votes forÔweakÕ evidence, 8 abstentions, and 1 absent.]240

Table 4.33 Studies on EMF exposures and reproductive and developmental effects of EMF in experimental animals and birds
ReferenceSpecies

Exposure

Reproductive effects analyzed

Comments

Time

Waveform

Frequency

Intensity

Sinusoidal

1 Hz - 100
kHz

13-125.7 mT

Malformations at 48 h (pc)

Effects observed: increase in abnormal
embryos(Juutilainen& Saali,
1986a)

Chick embryos
Total embryos =800

0-52 h pc(Pafkova etal., 1994)

Chick embryos

0-40 h pc

50 Hz

6 mT or 10 mT

Malformations at day 9 (pc)

No effects observed on mortality or
structural malformations(Pafkova &Jerabek,
1994)

Chick embryos

0-48 h pc

50 Hz

10 mT
X-rays 4 or 5 Gy

Malformations at day 9 (pc)

Combination of exposure (magnetic
fields and X-rays)
No effects beyond effect observed for Xrays(Pafkova etal., 1996)

Chick embryos

0-52 h pc

50 Hz

6 mT or 10 mT

Malformations at day 9 (pc)

Combination of exposures (magnetic
fields and X-rays or chemicals)
Pre-exposure reduces some effects ofinsulin or tetracycline and radiation(Veicsteinas
et al., 1996)

Chick embryos
Total embryos =420

0-48 h pc

Sinusoidal

50 Hz

200 mT

Anomalies
Staging, fertilityGroup followed for 90 days posthatchingNo effects(Farrell etal., 1997)

Chick embryos
Total embryos =2500

0-48 h pc

Rectangular
0.5 ms pulse
Sinusoidal

100 Hz
60 Hz

1 mT
4 mT

Structural abnormalities
Development

Effects on abnormality rates (p < 0.01 to
0.001)
No effect in 60 Hz study

Mice(Juutilainen
et al., 1997)

CBA/S
CBA/Ca0-18 dG

Sawtooth
45 ms rise and5 ms fall time
Sinusoidal

20 kHz50 Hz

15 mT
12.6 mT

Gestational day 19
Total implantations
Viability of fetuses

Non-significant increase in resorption
in sawtooth(Kowalczuk
et al., 1994)

C3H
Total fetuses = 2167

0-17 dG

Sinusoidal

50 Hz

20 mT (rms)

Gestational day 17
Total implantations
Viability of fetuses
Fetal weight
Malformations

No effects

241

Table 4.33 (continued)
ReferenceSpecies

Exposure
Time

Waveform

Frequency

Reproductive effects analyzed

Comments

Intensity(de Vita etal., 1995)

F1 hybrids
8-10 weeks

2 or 4 hSinusoidal

50 Hz

1.7 mT (rms)

Relative frequency of spermatogenic
cell subpopulations
Testicular cell suspensions analyzed
at 7, 14, 21, 28, 35, and 42 days after
exposureEffects seen at 28 days after 4 h exposureof male mice (p <0.001)

Rats(Huuskonen
et al., 1993)

Han:Wistar
72 females

0-20 dG

Sawtooth
5 ms rise and45 ms fall
times
Sinusoidal

20-k pulses
per s (pps)
50 Hz

15 mT
12.6 mT

Gestational day 20
Total implantations
Viability of fetuses
Fetal weight
Malformations

Increase in implants and living
fetuses/litter at 50 Hz group
Increase in minor skeletal anomalies at
20 k-pps(Mevissen etal., 1994)

Wistar72 dams

0-20 dG

StaticSinusoidal

50 Hz

30 mT

Gestational day 19
Total implantations
Viability of fetuses
Malformations

No major malformation seen in any
group
Minor skeletal ossification found inboth exposures
Decrease in living fetuses/litter (p<0.05)
Enhanced postnatal growth anddevelopment(Rommereim
et al., 1996)

Sprague-Dawley
7903 fetuses
519 litters
Study conducted as
two replicates

0-20 dG

Sinusoidal

60 Hz

0.61, 1 mT

Gestational day 20
Total implantation
Viability of fetuses
Fetal weight
Malformations

Decrease in number of fetuses/litter(replicate 1, p < 0.05)
Effect not seen in replicate 2(Ryan et al.,
1996)

Sprague-Dawley
55 dams/treatment
group
Study included
positive control,
n=15 dams treatedwith
ethylenethiourea

0-19 dG

Sinusoidal

60 Hz

0, 2, and 200 mT,
and 1 mT, or 1 mT
intermittent (1 hon/ 1 h off)

Gestational day 19
Total implantations
Viability of fetuses
Fetal weight
Malformations

No biologically significant difference
observed in exposed groups
Positive control: 100% demonstrated
malformations

242

Table 4.33 (continued)
Reference(Ryan et al.,
1998)
Hamsters
Niehaus etal., 1995

Species

Exposure

Reproductive effects analyzed

Comments

Time

Waveform

Frequency

Intensity

40 male and female
Sprague-Dawley rats
F1, F2 generations

18.5
h/d

Linearlypolarized

60 Hz

0, 2, 200 mT, 10
mT and 10 mT
intermittent (1 hon/ 1 h off)

Reproductive performance
Fetal viability
Body weightNo effects on reproductive performance ordevelopmental toxicity

Djungarian hamsters
n=45/group

56 dSinusoidal
Rectangular

50 Hz

450 mT
360 mT

Testicular cell suspensions analyzed
at 7, 14, 21, 28, 35, and 42 d after
exposure
Relative frequency of spermatogenic
cell subpopulations

Testicular cell numbers increased at 28 dafter 4 h exposure of male hamsters (p<0.001)

pc, post-gestational; dG, days gestation

2434.4.5 Effects on melatonin
The hypothesis that modification of melatonin production and release is a possible
mechanism for some of the effects of exposure to EMF has been proposed and discussed
by many authors (Baldwin & Barrett, 1998; Stevens, 1987). A useful introduction topineal melatonin production can be found in the report of the National Academy of
Sciences (NRC et al., 1997, pp. 95Ð96). Since then, a number of studies have been done toelucidate the role of melatonin and the mechanism of its physiological activity. Reviewsof these studies are available (Dubocovich, 1995; Reiter, 1997).
The studies discussed in this section are summarized in Table 4.34. Laboratory
experiments on suppression of nocturnal melatonin in human volunteers are described in
section 4.6.4.1.
4.4.5.1 Electric fields
Groups of five adult male Sprague-Dawley rats, eight weeks old, with long day cycles (14h light, 10 h dark) were sham-exposed or exposed to 1.7Ð1.9 kV/m linearly polarized 60
Hz electric fields continuously for 30 days (Wilson et al., 1981; Wilson et al., 1986).
Exposure was given with a parallel-plate system, in which the rats were in electricalcontact with the reference ground electrode. Sham-exposed rats were housed identically
except for the electric field. [The fields were not verified independently.] At the end of
exposure, pineal melatonin, 5-methoxytryptophol, and serotonin-N-acetyltransferase
activity were measured at 08:00 and 14:00 (light phase) and 22:00 and 02:00 h (darkphase). Significant decreases in nocturnal pineal melatonin (p < 0.05, t test) and Nacetyltransferase activity (p < 0.002) were found.
Groups of 20 adult male Sprague-Dawley rats, eight weeks old, with long day cycles (14h light, 10 h dark) were sham-exposed or exposed to 39 kV/m linearly polarized 60 Hz
electric fields continuously for four weeks (Wilson et al., 1986), as described above. Aftereach week of exposure, 10 field-exposed and 10 sham-exposed rats were sacrificed
immediately after field termination (dark phase), and pineal melatonin and Nacetyltransferase activity were measured. Additional sacrifices and measurements weremade three and 14 days after exposure. Significant decreases in nocturnal pineal melatonin
and N-acetyltransferase activity were found after three or four weeks of exposure [no pvalue given]. The levels returned to normal within 3 d after exposure.
Groups of six to eight pregnant rats with long day cycles (14 h light, 10 h dark) were
exposed throughout gestation, and their pups were exposed from birth to day 23 to 0, 10,65, or 130 kV/m linearly polarized 60 Hz electric fields for 19 h/d (Reiter et al., 1988) by
a parallel-plate system, with the rats in electrical contact with the reference groundelectrode. Sham-exposed rats were housed identically except for the electric field. At theend of exposure, male pups from six to eight litters per time were sacrificed at 22:00,

244

02:00 (2 h after lights off), 04:00, 06:00, and 10:00 (lights on), and their pineal melatoninlevels were measured. Significant decreases in pineal melatonin were found at 02:00 (p <0.001), when the concentration of melatonin would be expected to be highest.
Groups of 7Ð16 eight-week-old male Sprague-Dawley rats with long day cycles (14 hlight, 10 h dark) were sham-exposed or exposed to 65 kV/m linearly polarized 60 Hz
electric fields for 20 h/d for 30 d (Grota et al., 1994). The exposure apparatus consisted ofthree parallel plates: a top electrified plate and grounded intermediate and bottom plates.
The animals between the top two plates were exposed to a 60 Hz electric field, and theanimals between the bottom two grounded plates were sham exposed. Harmonics were
not detected, and the spillover to the sham condition between the lower plates was 1% or
less. The effective field strength was estimated to be 82% in clean cages, which was
reduced to 43% in cages in which rats had lived for more than four days. Clean cages were
provided twice a week, and husbandry was done during the daily field-off period.
Immediately after exposure, at 04:00 (light) or 16:00 (dark), groups of field-exposed andsham-exposed rats were sacrificed, and the plasma and pineal melatonin concentrations
and pineal N-acetyltransferase and hydroxyindole-O-methyltransferase activities were
measured. Significant decreases were found in nocturnal plasma melatonin (p < 0.05) but
not in pineal melatonin or in N-acetyltransferase or hydroxyindole-O-methyltransferase
activity.
[In all of these studies except that of Grota et al. exposure to electric fields had astatistically significant effect on at least one observation of pineal melatoninconcentration. They speculated that the difference in the results of their study and others
may be due to the sensitivity of the measurements to time. In particular, they consideredthat the dark phase was not the most sensitive for measurements of pineal function. In
some experiments, the pineal and blood melatonin concentrations decreased in rats
exposed to linearly polarized 60 Hz electric fields.]
4.4.5.2 Exposure to magnetic fields for < 1 h
Adult male and female Djungarian hamsters with long day cycles (16 h light, 8 h dark)
were exposed to a 100 mT 60 Hz linearly polarized magnetic field for 15 min starting 2 h
before lights off (Yellon, 1994). The exposure system consisted of two Merritt coils
modified to produce highly uniform fields across two perpendicular axes. The fieldstrength was monitored and was found to be uniform to within ± 10%. Sham-exposed
controls were placed in an adjacent exposure system in which no current was applied; thefield was found to be 0.04 mT. Groups of four to six animals were sacrificed at 0.5Ð2-hintervals from 1 h before lights off to 1 h after lights on, and their sera were harvested andpineal glands obtained for radioimmunoassay for melatonin. In controls, the pineal
melatonin concentration increased significantly from an average daytime baseline of lessthan 0.3 ng per gland to 3 ng per gland by 3 h after lights off (p < 0.05). This increase wassustained for the duration of the night and returned to baseline within 1 h after lights on.
A similar melatonin rhythm was found in plasma; the concentrations ranged from 30 to 50
pg/ml at night and returned to a baseline of 12 pg/ml or less by 1 h before lights on. The
245

single exposure to magnetic fields reduced the duration and blunted the rise in thenocturnal melatonin rhythm (p < 0.05). When the study was repeated in its entirety six
months later, the same exposure did not significantly suppress the pineal melatonin
content 5 h after lights off or reduce the plasma melatonin concentrations 3 or 5 h after
the onset of dark in comparison with sham-exposed controls.
Adult Djungarian hamsters with long day cycles (16 h light, 8 h dark) were exposed once
to a 10 or 100 mT linearly polarized 60 Hz magnetic field for 15 min beginning 4 h before
or 4 h after lights off (Truong & Yellon, 1997). Other hamsters were exposed to a 100 mT
linearly polarized 60 Hz intermittent (1 min on, 1 min off) magnetic field for 15 or 60 min
between 1 and 2 h before lights off. The exposure system consisted of two Merritt coils
modified to produce highly uniform fields across two perpendicular axes. Six hamsters pertime per group were sacrificed 1, 1.75, 2.5, 3, and 4 h after lights off, and their sera were
harvested and pineal glands obtained for radioimmunoassay of melatonin. In shamexposed controls, i.e. hamsters placed in an adjacent coil system but without current (<0.6 mT), the pineal and plasma melatonin concentrations increased from a low baseline (1h after lights off) to concentrations that were typical of the night-time peak by 3 h after
darkness. Exposure to the continuous magnetic field for 15 min either 4 h before or 4 hafter lights off did not disrupt the nocturnal rise in pineal or plasma melatoninconcentration. Similarly, the onset of the melatonin rhythm was not suppressed incomparison with that in sham controls by intermittent exposure to magnetic fields. Thus,
several paradigms of exposure to magnetic fields failed to alter the rising phase of themelatonin rhythm in pineal gland content or in the circulation. The authors conclude thatthe biological clock mechanism that mediates photoperiodic time measurement in thisseasonally breeding rodent is resistant to a variety of continuous or intermittent
exposures to magnetic fields.
Adult Siberian hamsters in constant darkness were exposed to a 100 mT linearly polarized
60 Hz magnetic field for 15 min (Yellon & Truong, 1998). Sham-exposed hamsters were
simultaneously placed in an adjacent coil system but without current (< 0.6 mT). Groupsof five to seven animals per group were sacrified 0, 0.75, 1.5, 2.25, and 3 h after lights off,
and their sera were harvested and pineal glands obtained for radioimmunoassay of
melatonin. The increase in the pineal and the circulatory content of melatonin during
subjective night was not affected by exposure to magnetic fields; regression of the testes
occurred in both sham-exposed controls and in hamsters in constant darkness exposed
daily to magnetic fields. The authors concluded that magnetic fields are unlikely to serve
as a zeitgeber for the circadian changes in the melatonin rhythm; rather, the photoperiod isa predominant cue for the rising phase of melatonin production in the pineal gland andconcentration in circulation.
In juvenile hamsters exposed to a 100 mT magnetic field for 15 min daily for nine days,
statistically significant reductions in nocturnal melatonin concentrations were observed atsome times, but pubertal development was normal. A replicate study showed no
reduction in nocturnal melatonin (Truong et al., 1996).

246

Adult Djungarian hamsters were exposed to a 100 mT 60 Hz magnetic field for 15 min 2 hbefore dark daily for three or six weeks. The night-time rise in melatonin concentration
was delayed, and the duration was reduced in the animals exposed for six weeks but not in
those exposed for three weeks (Yellon, 1996).
Groups of male Siberian hamsters, four to six months of age, were exposed to a 100 mT
60 Hz linear magnetic field. Exposure depressed the pineal melatonin concentration at 4 h
but not 2 h after the onset of darkness in male but not female hamsters. The hamsters
with a short photoperiod were more sensitive to the magnetic field-induced response thanthose with a long photoperiod. The depression in melatonin was not seen after 42 days of
exposure to magnetic fields (Wilson et al., 1998).
[The apparent contradiction between the effects seen in the YellonÕs 1994 study and thelack of effects in the 1997 and 1998 studies from his laboratory may be due to diurnal
cycling (long days in 1994 and 1997, constant darkness in 1998), time of exposure (2 hbefore darkness in 1994, 4 h before or after darkness in 1997), or continuity of exposure(continuous in 1994 and 1998, continuous or intermittent in 1997). The effect of amagnetic field may be influenced by the length of the day of the exposed animals. Truong
et al. found that the 1994 exposure schedule resulted in changes in melatonin but not tothe expected downstream effects in reproductive development. Additionally, Yellon was
unable to reproduce the effects that he obtained in 1994. A single continuous exposure toa 100 mT linearly polarized 60 Hz magnetic field does not reproducibly shorten or bluntnight-time plasma melatonin concentrations in Djungarian hamsters.]
4.4.5.3 Exposure to magnetic fields for 1Ð24 hGroups of six nine-week-old male Wistar rats with standard day cycles (12 h light, 12 hdark) were exposed through rectangular coils to 1, 10, or 100 mT linearly polarized 50 Hz
magnetic fields for 12 h (Selmaoui & Touitou, 1995). Sham-exposed animals were kept ina similar environment. The animals were sacrificed under dim red light at the end of
exposure, during the dark phase. Decreased nocturnal plasma melatonin concentration (by30%; p < 0.05) and pineal N-acetyltransferase activity (23%; p < 0.05) were seen but
only at the highest intensity (100 mT). No significant differences from control were seenat the other intensities or in hydroxyindole-O-methyltransferase activity.
Groups of eight male Sprague-Dawley rats, 12 weeks old, with standard day cycles (12 hlight, 12 h dim red light) were exposed through Helmholz coils to 1 mT intermittent (1min on, 1 min off cycles) linearly polarized 60 Hz magnetic fields for 1 h, starting 2 h
before darkness (John et al., 1998). Sham-exposed rats were simultaneously placed in an
adjacent coil system but without current (< 0.17 mT). Urine was collected at 2-h intervals.
The circadian profile of urinary 6-sulfatoxymelatonin was examined before, during, andafter exposure; no significant effect on excretion was observed.

247

Groups of 10 male and 10 female adult Wistar rats with short day cycles (9 h light, 15 hdark) were exposed to either 5 or 500 mT linearly polarized 50 Hz magnetic fields througha pair of double-wound coils embedded in epoxy resin for 24 h (Bakos et al., 1995).
Sham-exposed rats were simultaneously placed outside the coil system (5 mT strayfields). The fields were homogeneous to within 1%. The animals were all housed inmetabolic cages. The urine of the animals was collected twice per day for five consecutive
days, and the concentration of 6-sulfatoxymelatonin was measured by 125Iradioimmunoassay. The urinary excretion of 6-sulfatoxymelatonin did not change
significantly from baseline during or after exposure.
Groups of five adult male Wistar rats with short day cycles (9 h light, 15 h dark) were
exposed to either 1 or 100 mT linearly polarized 50 Hz magnetic fields for 24 h (Bakos etal., 1997). Sham-exposed rats were simultaneously placed outside the coil system (1 mTstray fields). The animals were all housed in metabolic cages. The urinary excretion of 6sulfatoxymelatonin was not statistically significantly decreased during or after exposure
to either flux density. Excretion of rats at 100 mT was significantly increased the day after
exposure (p < 0.02) in comparison with the value during exposure, but was not
significantly different from the baseline value before exposure.
[These studies neither directly support nor contradict each other because of confounding
effects of strain (Wistar vs. Sprague-Dawley), field characteristics (50 Hz continuously
vs. 60 Hz intermittently), and effects measured (plasma melatonin, pineal Nacetyltransferase activity, or urinary 6-sulfatoxymelatonin excretion). The difference
between the two studies by Bakos, one indicating a potential for increased 6sulfatoxymelatonin excretion, is confusing. The results of Selmaoui remain suggestive,
although the study suffers from the lack of a well-characterized exposure system. The
biological significance of small changes in melatonin concentrations is not clear.]
4.4.5.4 Exposure to magnetic fields for > 24 hGroups of 6Ð28 adult (11Ð18-week old) male Wistar-King rats with standard day cycles(12 h light, 12 h dark) were exposed to 0.02, 0.1, 1, 5, 50, or 250 mT circularly polarized
50 Hz magnetic fields continuously for six weeks from a modified Helmholtz coil (Kato etal., 1993). The uniformity of the system and stray fields were fully characterized(Shigemitsu et al., 1993). Sham-exposed control rats were placed inside an unactivated coilsystem with stray fields that were 1/50th of those of the exposure fields. The room wasconstantly illuminated by four small, dim-red lights (< 0.07 lux in dark period). The
animals were sacrificed at the end of exposure, and the concentrations of plasma andpineal gland melatonin were determined by radioimmunoassay. Significant decreases were
found in plasma melatonin concentration during light (08:00, 12:00 h, p < 0.05) and dark
(20:00, 24:00 h, p < 0.05) with an intensity of 5 mT and during light (08:00, 12:00 h, p <0.05; 16:00, p < 0.01) and dark (24:00 h, p < 0.01) with an intensity of 250 mT; in pineal
melatonin concentration during dark (24:00 h, p < 0.05) at an intensity of 5 mT and during
light (12:00, p < 0.05; 16:00, p < 0.01) and dark (24:00 h, p < 0.01) at 250 mT; in daytime
plasma melatonin concentrations at intensities of 0.1 (p < 0.01), 1 (p < 0.05), 5 (p < 0.05),
248

and 50 mT (p < 0.01) and in night-time concentrations (p < 0.01) at intensities of 1, 5, and
50 mT; in night-time pineal melatonin concentrations at intensities of 1 (p < 0.01), 5 (p <0.05), and 50 mT (p < 0.01); and in day-time pineal melatonin concentrations (p < 0.01) at
intensities of 1, 5, and 50 mT. The authors concluded that plasma and pineal melatoninconcentrations at night (24:00 h) are statistically significantly decreased after continuous
exposure for six weeks to 50 Hz rotating magnetic fields stronger than 1 mT.
In a study with similar exposure, groups of 22Ð30 adult (11Ð18 weeks old) male,pigmented Long-Evans rats with standard day cycles were exposed to 0.02 or 1 mT
circularly polarized 50 Hz magnetic fields continuously for six weeks (Kato et al., 1994a).
Significant decreases in plasma melatonin concentration (> 20%, p < 0.01) were found at
the mid-points of the dark and light phases at both 0.02 and 1 mT. Significant decreases inpineal melatonin concentration (p < 0.01) were found during the light phase at bothintensities and during the dark phase at 1 mT.
In a further study, groups of eight adult (13Ð21 weeks old) male Wistar-King rats withstandard day cycles were exposed to either 0.02 or 1 mT circularly polarized 50 Hz
magnetic fields continuously for six weeks (Kato et al., 1994b). Animals were sacrificed at
the end of exposure, and the plasma melatonin concentrations were determined at thattime and one and four weeks after cessation of exposure. The nocturnal melatoninconcentration was reduced by 25% (p < 0.05), but the concentration one week after theend of exposure was normal, and no further change was observed four weeks later.
In yet another study, groups of 23Ð30 adult (11Ð20 weeks old) male Wistar-King rats
were exposed to 0.02 or 1 mT linearly polarized 50 Hz magnetic fields continuously for
six weeks (Kato et al., 1994c). No significant change in plasma melatonin or pineal
melatonin concentration was found.
Groups of 36 six-week-old female Sprague-Dawley rats with standard day cycles were
either sham-exposed or exposed to a gradient of 0.3Ð1 mT linearly polarized 50 Hz
magnetic field continuously through six cylindrical coils for 91 days beginning eight tonine weeks after intragastric administration of 20 mg (5 mg/week) DMBA (Lšscher et al.,1994). Sham-exposed rats were housed in the same room and experienced stray fields of
0.02Ð0.04 mT. The animals were sacrificed at the end of exposure, and the concentrationsof plasma and pineal gland melatonin were determined by radioimmunoassay. The
nocturnal melatonin levels were reduced by 20% (p < 0.05) at all intensities.
Groups of 99 six-week old female Sprague-Dawley rats with standard day cycles were
either sham exposed or exposed to a 50 mT linearly polarized 50 Hz magnetic fieldcontinuously for 91 days after intragastric administration of 20 mg (5 mg/week) DMBA
(Mevissen et al., 1996b). The sham-exposed rats were housed in the same room andexperienced stray fields of 0.05 mT. The animals were sacrificed at the end of exposure,and the concentrations of plasma and pineal gland melatonin were determined byradioimmunoassay. Determination of nocturnal plasma melatonin after 9 and 12 weeks of249

exposure to 50 mT showed no significant difference between field-exposed and shamexposed rats. In another study with the same experimental design but with exposures to
10 mT, a significant decrease was observed in serum but not in pineal melatoninconcentration (Mevissen et al., 1996a).
Groups of 12 male five-week-old Wistar rats with standard day cycles were exposed toeither 1, 10, or 100 mT linearly polarized 50 Hz magnetic fields from rectangular coils for
18 h/d for 30 days (Selmaoui & Touitou, 1995). Sham-exposed animals were kept in asimilar environment. The animals were sacrificed under dim-red light at the end of
exposure during their dark phase. The nocturnal plasma melatonin concentration andpineal N-acetyltransferase activity were depressed at both 10 (27%, p < 0.05) and 100 mT(42%, p < 0.05). No effect was seen on hydroxyindole-O-methyltransferase activity.
Groups of 45 male Djungarian hamsters with long days (16 h light, 8 h dark) were
exposed to a 300 mT linearly polarized 50 Hz magnetic field from Helmholz coils
continuously for 56 days (Niehaus et al., 1997). Sham-exposed rats were simultaneously
placed outside the coil system and experienced < 3 mT stray fields. No effects onnighttime plasma or pineal melatonin concentrations were found as determined byradioimmunoassay.
Groups of eight adult male Sprague-Dawley rats with standard day cycles were exposed
to a 1 mT linearly polarized 60 Hz magnetic field for 20 h/d for 10 d or six weeks or to 1
mT intermittently (1 min on, 1 min off) of a linearly polarized 60 Hz magnetic field for 20
h/d beginning 1 h before darkness for two days (John et al., 1998). Sham-exposed rats
were simultaneously placed in an adjacent coil system but without current (< 0.17 mT).
Urine was collected at 2-h intervals. The circadian profile of urinary 6-sulfatoxymelatonin
was examined before, during, and after exposure. No significant effect on excretion wasobserved during exposure.
Groups of 10 seven-week-old female Sprague-Dawley rats with standard day cycles were
either sham-exposed or exposed to 100 or 500 mT linearly polarized 50 Hz magnetic
fields or to a 100 mT linearly polarized 60 Hz magnetic field for 18.5 h/d for 4, 8, or 12
weeks, with intragastric administration of 8, 10, or 20 mg DMBA (NTP, 1998a). Control
rats were housed in a separate room. The animals were sacrificed at the end of exposure,and the concentrations of plasma and pineal gland melatonin were determined by liquid
chromatography and tandem mass spectrometry. No significant differences were foundbetween field-exposed and sham-exposed rats. [The data varied considerably.][As in the studies of short-term exposure, confounding variables such as species (hamstervs. rat), strain (Wistar vs. Sprague-Dawley), sex, co-exposure (DMBA), fieldcharacteristics (polarization, intermittence), and measured outcome (plasma melatonin,
pineal melatonin, pineal N-acetyltransferase activity, urinary 6-sulfatoxymelatonin)
complicate interpretation of the database. Long-term exposure to circularly polarized 50
Hz magnetic fields may decrease dark-phase melatonin concentrations in rats, and long-250

term exposure to 10 or 100 mT linearly polarized 50 Hz magnetic fields decreases plasmaand pineal melatonin concentrations in male Wistar rats.]
4.4.5.5 Exposure to electric and magnetic fields
Groups of 10 female Suffolk lambs, eight weeks old and housed outdoors, were exposed
to mean fields of either 4 mT and 6 kV/m or 3.77 mT and 6.3 kV/m from the electricalenvironment of a 500 kV transmission line and < 3 mT and < 0.01 kV/m or 0.02 mT and <0.01 kV/m from a nearby pen (Lee et al., 1995; Lee et al., 1993). The sheep remained inthese pens for eight months, and the fields were monitored continuously. Plasma samples
were collected at 0.5Ð3 h intervals over eight 48-h periods from the same animals
throughout the study. The melatonin concentrations in the plasma were determined byradioimmunoassay. The characteristic pattern of melatonin secretion during night-time(amplitude, phase, and duration) did not differ between control and treated groups.
Groups of three male baboons, aged seven to eight years, with long day cycles (15.5 hlight, 8.5 h dark) were exposed to either 50 mT, 6 kV/m or 100 mT, 30 kV/m linearlypolarized 60 Hz EMF without transients for three blocks of 4 h (08:30Ð12:30, 13:00Ð
17:00, 17:30Ð21:30) each day for six weeks (Rogers et al., 1995d). Homogeneous verticalelectric fields were generated between a bus-suspended at 2.5 m and a large, nonferrous
metal gate. Homogeneous magnetic fields were generated by a series of conductors
beneath the grate. The field strengths were logged at 15-min intervals. Plasma melatoninconcentrations were determined at 2-h intervals from the same animals throughout the day
on days before, during, and after the six weeks of exposure period. No changes in plasma
melatonin concentration were observed.
In a similar study, groups of two adult male baboons with long day cycles were exposedfrom the same sources to a complex schedule of 50 mT, 6 kV/m or 100 mT, 30 kV/mlinearly polarized 60 Hz electric and magnetic fields for 0Ð24 h/d for 30 d (Rogers et al.,
1995e). Transients were purposely not avoided, and 300 Hz transients were observed.
The night-time plasma melatonin concentrations during exposure were decreased by morethan 80% from pre-exposure levels.
[The studies of mixed exposure, unlike the others summarized here, were all done on nonrodent species. Changes in plasma melatonin concentrations were found only by Rogers etal.; however, only two animals were used.]
4.4.5.6 Summary
The studies on melatonin in animals exposed to electric fields have both strengths andweaknesses; the latter are primarily in exposure characterization, statistical methods, anddifferences within studies. The evidence is lacking in both quantity and consistency, but
the weight of the evidence leads to the conclusion that long-term exposure to electric251

fields slightly decreases the concentrations of melatonin in rats. The biological significanceof this apparent effect is not understood.
It was reported that long-term exposure to magnetic fields (100-1000 mT) can reduce thenocturnal pineal or blood concentrations of melatonin in rodents, but other laboratories
did not find similar results.
Field orientation and linear or circular polarization may be important. Reductions inmelatonin levels were not found in sheep or baboons. Similarly, studies of the effects ofacute exposure to magnetic fields in hamsters showed reductions in melatonin;
nonsignificant results were obtained more frequently than significant ones, but all thosethat were significant showed suppression. The intensities used were relatively high, evenwhen humanÐrodent scaling issues are considered. The biological significance of melatonin
reduction is not clear.
There is weak evidence that exposure to electric and magnetic fields alters the levels of
melatonin in rodents.
[This conclusion was supported by 14 members of the Working Group; there were 9
votes for ÔmoderateÕ support; 4 abstentions, and 2 absent.]
There is no evidence that exposure to electric and magnetic fields alters the levels of
melatonin in sheep or baboons.
[This conclusion was supported by 14 members of the Working Group; there were 13
abstentions and 2 absent.]

252

Table 4.34 Studies of the effect of exposure to EMF on melatonin in experimental animalsnIntensity

Long term exposure to electric fields(Wilson et
60 Hz linear
5
al., 1981)

AuthorWaveform

Animal

MeasureEffect

1.7 - 1.9 kV/m
24 h for 30 days

Male Sprague-Dawley
rat

Plasma MT, pineal MT,
NAT, 5-MTOL

Pineal MT down at night(Wilson etal., 1986)

60 Hz linear

20

39 kV/m
24 h for 30 days

Male Sprague-Dawley
rat

Pineal MT, NAT

Pineal MT, NAT down
after 3, 4 weeks returned 3days after exposure end(Reiter etal., 1988)

60 Hz linear

6-8

10, 65, 130 kV/m
19 h /d GD 0 to PND 23

Sprague-Dawley rat
pups

Pineal MT

Pineal MT down at night

65 kV/m
20 h for 30 days

Male Sprague-Dawley
rat

Plasma MT, pineal MT,
HIOMT, NAT

Plasma MT down at night

100 mT
15 minDjungarian hamster

Plasma and pineal MT

Plasma and pineal MT
down at night, notreplicated10, 100 mT
15 minDjungarian hamster

Plasma and pineal MT

None(Yellon &60 Hz linear
5-7
Truong,
1998)
Short-term exposure to magnetic fields(Selmaoui
50 Hz linear
6& Touitou,
1995)(John et al.,60 Hz linear
8
1998)

100 mT
15 minSiberian hamster

Plasma and pineal MT

None

1, 100, 1000 mG for 12 hMale Wistar rat

Plasma MT, pineal NAT,
HIOMT

MT, NAT down at 1000mG at night

1 mT intermittent 1 h

Sprague-Dawley rat

6-OHMS in urine

None(Bakos etal., 1995)

50 Hz linear

5

5, 500 mT
24 h

Wistar rat

6-OHMS in urine

None(Bakos etal., 1997)

50 Hz linear5

1, 100 mT
24 hMale Wistar rat

6-OHMS in urine

Increased night after
exposure(Grota et
60 Hz linear
7-16
al., 1994)
Single exposure to magnetic fields(Yellon,
60 Hz linear
4-6
1994)
(Truong &Yellon,1997)

60 Hz linear

6253

Table 4.34 (continued)
AuthorWaveformnIntensity

Animal

MeasureEffectLong-term exposure to magnetic fields(Kato et al.,50 Hz circular
6-28
1993)

0.02, 0.1, 1, 5, 50, 250 mT
22 h for 6 weeks

Male Wistar rat

Plasma and pineal MT

Plasma MT down at 0.1 mT
day and night
pineal MT up at 0.1 mT day(Kato et al.,1994a)

50 Hz circular

22-30

0.02, 1 mT
22 h for 6 weeks

Male Long-Evans rat

Plasma and pineal MT

Plasma MT down day andnightpineal MT down at 0.1 mT
day, 1 mT night(Kato et al.,1994b)

50 Hz circular

80.02, 1 mT
22 h for 6 weeks

Male Wistar rat

Plasma MT at night

Plasma MT down after
exposure returns to normal
1 week later(Kato et al.,1994c)

50 Hz linear

23-30

0.02, 1 mT
22 h for 6 weeks

Male Wistar rat

Plasma and pineal MT

None(Lšscher etal., 1994)

50 Hz linear36

0.3 - 1 mT gradient24 h for 91 days

Female Sprague-Dawley
rat

Plasma MT at night

Plasma MT down

(Mevissen
et al.,
1996b)

50 Hz linear

99

50 mT
24 h for 9, 12 weeks

Female Sprague-Dawley
rat + DMBA

Plasma MT at night

None(Selmaoui& Touitou,
1995)

50 Hz linear12

1, 10, 100 mT
18 h for 30 days

Male Wistar rat

Plasma MT, pineal NAT,
HIOMT

MT, NAT down at 100,
1000 mG(Niehaus etal., 1997)

50 Hz linear45

300 mT
24 h for 56 days

Male Djungarian
hamsters

Plasma and pineal MT

None(John et al.,1998)

60 Hz linear

81000 mT (continuous orintermittent)
20 h (10 or 42 days)
1 h (2 days)

Male Sprague-Dawley
rat

6-OHMS in urine

None

(NTP,
1998a)

60 Hz linear

10

10, 500 mT
24 h for 4, 8, 12 weeks

Female Sprague-Dawley
rat + DMBA

Plasma and pineal MT at
night

None

254

Table 4.34 (continued)
WaveformnAnimal

MeasureEffect(NTP,
60 Hz linear
1998a)
Mixed E/MF exposures(Lee et al.,
60 Hz
1993)
powerline

Author101000 mG
24 h for 9, 12 weeks

Intensity

Female Sprague-Dawley
rat + DMBA

Plasma and pineal MT at
night

None

10

4 mT, 6 kV/m
24 h for 8 months

Female Suffolk lambs

Plasma MT

None(Lee et al.,
1995)

60 Hz
powerline

15

3.8 mT, 6.3 kV/m
24 h for 8 months

Female Suffolk lambs

Plasma MT

None(Rogers etal., 1995d)

60 Hz linear

2-4

50 mT, 6 kV/m or
100 mT, 30 kV/m
12 h for 6 weeks

Baboons

Plasma MT

None(Rogers etal., 1995e)

60 Hz linearwithtransients

2

50 mT, 6 kV/m or
100 mT, 30 kV/mirregular for 30 days

Baboons (self controls)

Plasma MT

Plasma MT down

MT, Melatonin; NAT, N-acetyltransferase; 5-MTOL, 5-methoxytryptophol; H10MT, hydroxyindole-O-methytransferase; GD, gestation day; PND, postnatal day; 6-OHMS, 6-OHMS,
6hydroxymelatonin sulfate; DMBA, 7, 12,-dimethylbenz [a] anthracene

2554.4.6 Bone and tissue repair and adaptation
4.4.6.1 Clinical bone healing with pulsed electromagnetic fields
The clinical use of non-invasive exposure to EMF for the promotion of bone healing ischaracterized by three assumptions: its presumed physiological basis, the nature of the
waveforms used, and the understanding that such exposure can be highly beneficial. While
much of the concern about the hazards of exposure to EMF is related to thecharacteristics of the magnetic field, in the realm of bone healing it is the induced electricfield that is considered to be the exclusive active agent of stimulation. The pioneeringstudies of Fukada and Yasuda (Fukada & Yasuda, 1957) and Becker (Becker, 1961)
showed that substantial electric fields are endogenous to the skeleton, and these were
presumed to form the basis of WolffÕs law or the observation that bone architectureappears to adapt to mechanical loading imposed on the skeleton. Their application to thepromotion of fracture healing was therefore obvious, and in early studies direct electrodecoupling was used to permit exogenous electrical stimulation. The electrodes, however,necessitated surgical implantation and removal, produced electrochemical by-products,
and limited the region that could be treated. For these reasons, alternative methods of
inducing electrical currents in bone tissue have been developed, the most successful being
based on magnetic induction (Bassett et al., 1977).
The transition to reliance on magnetic induction required identification of a dynamic flux
pattern to induce the appropriate electrical currents. Unlike the studies of hazard, which
are based largely on sinusoidal fields, the development of clinical devices has focused
almost exclusively on use of pulsed fields. This approach was primarily pragmatic, as
high rates of change could easily be implemented for relatively low flux densities,
permitting the induction of currents similar in magnitude to those observed during
development or the mechanical deformation of bone structures (i.e. 0.1Ð1 V/m). The
clinical PEMF signals typically consist of peak flux densities in the range of 0.1Ð5 mTwith rise times on the order of hundreds of microseconds. This results in a typical dB/dt
in the range of 1Ð50 T/s and corresponding peak induced electric fields of 0.1Ð1 V/m. Theenergy distribution in such complex fields is centered near the pulse repetition rate andthe harmonics of this rate. The pulse repetition rates range from 15 Hz up to several
kilohertz; however, many of the clinical signals involve a pulse burst pattern, in which ashort burst of pulses is repeated at a low-duty cycle. Burst repetition rates are always in
the ELF range, which can be as low as 1 Hz and rarely extend beyond several tens ofhertz. Such pulse-burst signals have extremely complex energy distribution spectra which
cover the frequency range starting at the burst repetition rate and extending to higherorder harmonics associated with the pulse width (McLeod & Rubin, 1990).
EMF-induced healing differs in two main ways from the most studies of the hazards of
EMF. While the major emphasis in the development of these devices has been on induced
electric fields, the preferred technique is to center the induction coils over the injury. The
effect of this strategy is to minimize the magnitude of the induced electric field at the256focus of the injury while maximizing the induced field in the periphery. The maximum
reported induced electric fields in the central region of healing are therefore far below thereported peak induced electric fields, perhaps by an order of magnitude or more. This
exposures is, however, spatially far more consistent than those experienced in any studyof whole-body exposure, in that the induction coils are generally strapped to the body,ensuring a fixed orientation of the flux to the body part and, correspondingly, a fixed
electric field distribution. This spatial coherence may be a critical aspect of field-induced
healing.
Pulsed electromagnetic field therapy for tibial fractures
PEMF have been used to promote bone healing under conditions of non-union, delayed
union, osteotomy, and bone fusion. By far the majority of the published studies are
retrospective analyses of patient populations. Representative of these reports is themulticenter review of cases of tibial non-union compiled shortly after the Food and Drug
Administration approved PEMF devices as a safe and effective for the treatment of nonunions and failed fusions (Bassett et al., 1981). In this report, the cases of 125 adultpatients who had undergone PEMF therapy for delayed union (no evidence of union fourto nine months after fracture) or non-union (no union nine months after fracture) werereviewed; true pseudoarthroses were specifically excluded from the study. The treatment
consisted of cast immobilization and treatment of the fracture site for at least 10 h/d byexposure to a 15 Hz pulse-burst signal. A peak flux of 1.5 mT, decaying in 25 ms, wasused, with pulses repeated at a 4-kHz rate over the burst duration of 5 ms. This resulted
in an induced electric field pulse in the bone tissue estimated to be on the order of 0.1Ð0.2
V/m. The reported overall success rate in this study was 87%, requiring an average
duration of treatment of 5.2 months (range, 2Ð22 months). Failure to promote healing was
attributed by the authors to absence of rigid immobilization, fracture gaps greater than 1
cm, use of the stimulus for less than 10 h/d, or off-center or skewed placement of theinduction coils.
In 1984, the first of a series of double-blind, randomized, placebo-controlled trials of
pulsed magnetic field therapy was published (Barker et al., 1984), in which 16 patientswith tibial fractures that had been un-united for at least 52 weeks were enrolled,
immobilized in casts, and randomly assigned to treatment with either an active or placebo(no coil current) device. Patients were excluded if the fracture gap was greater than 0.5 cm,
internal or external fixation was present at the fracture site, sepsis was present, or thepatient was undergoing steroid treatment. Patients were instructed to use the device for12Ð16 h/d with a minimum of 1 h/d. Satisfactory compliance was considered to be anaverage of 10 h/d, with less than 6 h/d use on no more than 7 d in each six-week period.
The patients were monitored every six weeks. At 24 weeks, the fractures of five of theseven patients with placebo devices had healed as compared with five of nine patientswith active devices. While the group with active devices was significantly older than theplacebo group (38 years vs. 29 years), the authors concluded that conservative
management of true tibial non-unions is as effective as magnetic field therapy.

257

At the same time, a randomized double-blind trial on delayed unions was undertaken(Sharrard, 1990), in which adult patients with tibial fractures that had not united at 16
weeks but had occurred less than 32 weeks previously and who had not undergone
surgical treatment were enrolled. After the fractured limbs had been immobilized in longleg plaster casts, those with apposition over less than 50% of the fracture surface or witha fracture gap greater than 0.5 cm were excluded. Over a period of six years, 51 patientswere identified who met the study criteria. Patients were instructed to undergo therapy
each day for a total of 12 h/d; treatment continued for 12 weeks, with the same exposuresystem as described by Barker et al. (Barker et al., 1984). The study protocol wascompleted by 45 patients. Despite randomization, the age distribution was found to besignificantly different in the two study populations, the mean age of patients in the active
group being 35 years (median, 28), while that of the control group was 45 (median, 45).
Radiographic assessment showed that five of the actively treated fractures had healed
within 10 weeks, with progress in five and no progress in 10. Conversely, in the placebogroup, one fracture had healed, progress was seen in one patient, and no progress wasobserved in 23 patients. The results were interpreted as demonstrating a significant effectof magnetic field therapy (p < 0.002). [The extended duration required to recruit thiscohort and the significant age difference between the two groups raise serious concern
about the actual efficacy of magnetic field therapy for this condition.]
Pulsed electromagnetic field therapy for osteotomies
Osteotomies are a distinctly different type of fracture from others. Normally, fractures
progress through the process of secondary bone formation or endochondral ossification;that is, in a normally displaced fracture, healing is a sequential process starting when thehematoma is replaced by a fibrous fracture callus, which is replaced by cartilage, which
subsequently calcifies. In a minimally displaced fracture (e.g. a hairline fracture), however,hematoma and callus do not form, and healing occurs by primary bone formation or the
direct bridging of the fracture site by new bone. This primary healing process also occurs
after osteotomies, the surgical procedure of transecting a bone in order to realign anarticulating surface.
Promotion of osteotomy healing by magnetic field therapy has been investigated in two
randomized, placebo-controlled clinical trials. In the first of these (Borsalino et al., 1988),
32 patients treated by intertrochanteric osteotomy for degenerative arthritis of the hip
were randomly assigned into treatment and placebo groups. Treatment consisted of
exposure to a 75 Hz repetitive pulse signal consisting of a 1.8 mT flux with a rise time of
1.3 ms. The peak induced electric field intensities can be estimated to have been about 50
mV/m. Induction coils were not energized in the placebo devices. Exposure was for 8 h/dfor 90 d. Healing was evaluated radiographically at days 40 and 90 in the 31 patients whocompleted the treatment protocol. Trabecular bridging was found to be significantly
increased in the active treatment group at both 40 days (p < 0.02) and 90 days (p <0.001).

258

Subsequently, a study of tibial osteotomy was undertaken (Mammi et al., 1993), in which
40 consecutive patients treated with vagus tibial osteotomy for degenerative arthrosis of
the knee were randomly assigned to placebo or treatment by order of admission. The
distributions of sex and age were similar in the two groups. Exposure was given from adevice similar to that used by Borsalino et al. (Borsalino et al., 1988), consisting of a 75
Hz pulsed signal of 1.8 mT with a 1.3 ms pulse width, with instructions to use it for 8
h/d; the output current was shorted in the placebo devices. Healing was assessedradiographically by four independent orthopedic surgeons on a four-point scale. A totalof 37 patients completed the protocol. At 60 days, the average score for the actively
treated population was 3 vs. 2.1 for the placebo-treated group, reflecting a significant
enhancement in healing rate (p < 0.006 by Fisher exact test).
Pulsed electromagnetic field therapy for lumbar spinal fusion
While lumbar spinal fusion is a common surgical procedure, the intervertebral space
represents a wide vascular region, making it difficult to ensure revascularization of thebone graft. As lumbar fusions are therefore slow to achieve union, the potential for PEMF
therapy to accelerate fusion has also been investigated. Mooney (Mooney, 1990) studied
the efficacy of this therapy to stimulate fusion in a randomized double-blind trial
involving 195 patients with autogenous, cadaverous, or combination grafts and patientswith and without internal fixation hardware. Exposure was given from a 15 Hz pulseburst signal, 1.5 mT in magnitude, with a 25 ms rise time and 4 kHz pulse repetition rate
for bursts of 5 ms. Patients in both the active and placebo groups were fitted with a bracethat they were instructed to wear for 8 h/d. Radiographic analysis by the orthopaedic
surgeon was used to determine time to fusion, with confirmation by an independentradiologist. The overall fusion rate was 92% in the 65 patients in the active group and
65% in the 98 patients on placebo. The spines of the 34 patients who used the treatment
device sporadically (< 4 h/d) fused with the same success rate as those on placebo. The
author interpreted the results to represent a significant increase in success rate with
PEMF therapy (p < 0.005).
The most recent of the double-blind clinical trials addressing the clinical efficacy of PEMF
on bone healing involved administration of pulse-field therapy during limb lengthening
procedures (Eyres et al., 1996). In this orthopedic procedure, an osteotomy is performed
and external fixation hardware is inserted to obtain progressive distraction of the proximaland distal bone ends. Bone then regenerates in the distraction gap. After distraction iscomplete, the gap undergoes consolidation, similar to that seen in fracture healing. In thisstudy, patients were randomly assigned to active treatment or placebo, with instructions
to use the induction devices for 4 h/d. The characteristics of the field exposure weresimilar to those described above: 15 Hz pulse-burst field, 1.5 mT pulses with a 25 ms risetime, repeated 4 kHz pulse rate in a 5 ms burst. The effectiveness of the treatment wasquantified by dual energy X-ray analysis, which provides bone density measurements at
the mid-point of the distraction gap and proximal and distal to the osteotomy site.
Densities were normalized to those of the contralateral, non-operated limb. The patientswere followed for 12 months. No significant difference was observed in limb-lengthening259

rate or in distraction gap bone density due to PEMF; however, large differences wereobserved in the proximal and distal segments of the bone. In the proximal segment, asignificant (p < 0.0001) increase in bone mineral density was observed as compared withplacebo controls, an effect which began after three months of stimulation and resulted in
20% greater bone mineral density than in controls at 12 months. On the distal side, thecontrol bone mineral density dropped by 46% (such bone loss due to disuse is expectedin this procedure), whereas the field-exposed population had a loss of less than 15% (p <0.0001).
4.4.6.2 Experimental studies
The primary objective of most studies of the effects of induced fields on bone, nerve, andskin in vivo has been clinical applications. The studies reviewed here are the direct
outcome of research in the 1950s and early 1960s to demonstrate the existence ofendogenous electrical currents in the body, which arise not only from diffusive Ôinjury
currentsÕ but also as a result of the mechanical deformation of tissues which create
currents through both piezoelectric and electrokinetic mechanisms. In the earliest studiesof the efficacy of fields to affect tissue healing, the stated objective was commonly toimitate the endogenous fields in the absence of normal mechanical loading. Subsequently,
the emphasis of studies in this area underwent a shift toward identifying those fieldcharacteristics that are most effective in stimulating a tissue response, the secondary goal
being the tying of these observations to the underlying physiology.
Initial attempts to develop non-invasive electric field therapy involved capacitive
coupling, although the effectiveness of this technique in the ELF regime was limited andelectromagnetic coupling rapidly supplanted this simpler technique.
Exogenously induced field effects on bone tissue
After the demonstration of the piezoelectric properties of bone (Fukada & Yasuda, 1957),
numerous investigators pursued measurements of electrical potentials in bone during
deformation in order to determine whether the distribution of currents or charge might
account for the adaptive responses of bone tissue. In 1968, McElhaney and Stalnakerhypothesized the converse, that application of electric fields results in a reverse
piezoelectric effect, leading to deformation of the tissue sufficient to inhibit bone loss due
to disuse. In their study, the right legs of 48 male Sprague-Dawley rats weighing about
100 g were immobilized in casts after 3/4 x 1/2 x 1/16-inch [19 x 12.7 x 1.6-mm] insulated
and waterproofed copper electrodes had been fastened to the medial and lateral surfaces.
The animals were assigned to four groups: sham exposure (no voltage applied to plates),
DC control (100 V DC applied to plates), 3 Hz stimulus at 200 V, or 30 Hz stimulus at
200 V. [The induced electric field due to the time-varying electric field can be estimated tobe 0.1Ð1 V/m. The DC field would induce no field in the tissue.] All animals were treatedfor 1 h every 12 h for 28 d. The bone cross-sectional area, hardness, and compressive
strength were measured, and chemical and histomorphometric analyses were performed260

on the left and right femurs of the 24 animals that survived the protocol. On the basis of
this broad array of measures, the authors concluded that the most robust exposure, ascompared with sham exposure, was the 30 Hz stimulus, the 3 Hz stimulus appearing lesseffective in maintaining the bone normally lost due to disuse; the DC exposure was theleast effective. Eight apparent bone tumors or prolific new bone formation were seen in
the 18 electrically treated animals. Five of these tumors occurred in the group exposed to
30 Hz, two in those at 3 Hz, and one in those exposed to DC. No tumors were found in
the sham-exposed group.
In a study to specifically address the incidence of bone tumors reported by McElhaney etal. (McElhaney et al., 1968) undertook a similar study of disuse osteoporosis in 50 maleSprague-Dawley rats weighing 150 g with limbs immobilized in casts. Four study groups
were used: a control group with no implanted electrodes, a sham-exposed group withimplanted electrodes (19 x 13 x 1.6 mm copper with epoxy insulation) but no excitation, agroup exposed to a 30 Hz stimulus at 200 V peakÐpeak applied to the plates for 1 hevery 12 h, and a group exposed to the same stimulus but for 8 h per weekday and 1 h/d
on weekends. At 28 days, the animals were sacrificed, and the cortical area, mass, density,and percent ash of the femurs were determined. A much smaller effect on disuse was seen
than in the previous study. [The greater size (and therefore age) of the animals may
account for much of this difference.] A strong effect of exposure to 30 Hz was again
observed, with a duration dependence, as the group exposed for 8 h/d had a greater
increase in cross-sectional area than those exposed for 2 h. No evidence of tumors or
hypertrophic growth was found in any of the animals examined. [Of concern in this trialis the asymmetric loss of animals in the various groups, prohibiting comparison of thegroups exposed for 2 and 8 h with regard to three of the four properties assayed.]
Cruess et al. (Cruess et al., 1983) revisited the question of osteoporosis, using PEMF totreat disuse osteoporosis in a rat model. Two groups of 250 g male rats underwent
surgical removal of the gastrocnemius and soleus muscles bilaterally and were then placedin plaster casts. One of the groups was treated continuously by whole-body exposure toa repetitive 65Ð72 Hz pulse of 325 ms in width, sufficient to induce an electric field of
150 mV/m at the tibia; the second group remained untreated. A third group of freeroaming normal rats was included in the study. After 14 days of exposure, the tibias were
removed and morphological and biochemical assays performed. While the surgicalprocedure resulted in significant loss of body mass over the two-week period ascompared with the free roaming controls, no significant difference in wet weight or inpercent ash weight was observed between treated and untreated animals. Biochemical
assays showed significantly (p < 0.05) higher collagen synthesis rates, lower collagenase
activity, and higher mineral uptake in the treated group than in the operated group withno field exposure.
Enzler et al. (Enzler et al., 1984) completed a study in a canine ulna non-union model
system to test the efficacy of PEMF to accelerate fracture healing. Twelve female beagle
dogs aged four to six years underwent bilateral surgical procedures for osteotomy of theulna. The right limbs of six animals and the left limbs of the remaining six were exposed to261

PEMF for 24 h/d, the contralateral limb being used as control. The pulse waveform was
similar to that used in clinical studies: a 2-ms burst comprised of 10 pulses, with the burst
repeated at a 10 Hz rate. [The magnitude of the peak flux density was not reported,
although it can be expected to have been 1Ð2 mT, consistent with the other experimental
devices produced by ElectroBiology, Inc. During the 1970s and 80s, this company was in
the forefront of development of PEMF therapy and provided exposure systems to a large
number of research groups. Two systems were commonly used: a 70Ð75 Hz repetitive
pulse signal and a 1.5Ð15 Hz pulse-burst signal waveform, both with a peak flux range of
1Ð2 mT. In these studies, induced electric field intensity is estimated as the product of thepeak time-rated change of the flux and a characteristic dimension of the exposed tissue. In
this specific study, the approximate 30 ms rise time would be consistent with a dB/dt on
the order of 50 T/sec, corresponding to peak induced electric fields in the range of 1 V/m.]
After sacrifice 22Ð30 days after the start of exposure, the fractures were tested for
torsional stiffness and examined histologically. None of the osteotomies healed during theexperimental period, no histological changes were evident, and no statistical differences inthe torsional stiffness of the fracture calluses were observed between the treated anduntreated limbs.
Bone tissue healing can be classified as comprising three distinct processes: fracture
healing, appositional growth, and epiphyseal plate growth (lengthening) by endochondral
ossification. While most early studies of the effects of EMF on bone healing emphasized
the first two of these processes, Smith and Nagel (Smith & Nagel, 1983) investigated theeffect of PEMF on bone elongation in the hind limbs of rabbits. In order to study the timeof growth-plate closure, female rabbits aged 12 weeks at the beginning of the protocol
were exposed for 18 weeks. To study bone elongation, the animals were exposed for eightweeks starting at the age of six weeks. Exposure was for 24 h/d to a 72 Hz repetitive
pulse signal generated by hardware supplied by Electrobiology, Inc. [The peak flux
densities were not reported but are presumed to be in the range of 1Ð2 mT.] Induction
coils were attached to the left and right sides of the animals by a coil support, which
permitted some movement. In addition to limb length and growth-plate closing time,
blood flow was evaluated by technetium scanning, and glycosaminoglycan distribution
was analyzed in extracted articular cartilage. No effect of exposure on the pattern of
epiphyseal plate closure was observed, either with a 12-h on/off cycle of exposure orwith continuous exposure (n = 6). Similarly, no effect on morphological measures of thetibia or on blood flow patterns was evident; however, the growth rate of the femurs of theanimals experiencing continuous exposure was slightly inhibited (n = 18; p < 0.06), andthe glycosaminoglycan content was significantly elevated (22%, p < 0.003). The authorsinterpreted their results as indicating that PEMF inhibits cartilage maturation.
It is not uncommon in orthopedic surgery for segmental, autogenous cortical bone grafting
operations to fail due to graftÐhost non-union. Given the extensive anecdotal reports ofhealing of traumatic non-unions following PEMF therapy, Miller et al. (Miller et al.,1984) studied the potential use of this therapy to promote healing in autogenous grafts.
Twenty adult mongrel dogs underwent bilateral surgery to remove 4 cm long fibular
segments, which were then inverted and replaced in the graft bed with no internal fixation.

262

One week post-operatively, one leg of the animal was exposed to a pulsed magnetic fieldfrom an orthosis incorporating a Helmholtz coil pair producing a 5 ms burst of 22 30 ms
wide pulses repeated at a 15 Hz rate. The estimated peak induced electric field wasreported to be 1.5 V/m. All of the animals were exposed for 20 h/d, with 10 animals
treated for two months and 10 for six months. All animals were sacrificed six months
post-operatively and histological and biomechanical analyses performed. No statisticallysignificant differences were seen in biochemical or biomechanical measures or in terms oftime to union.
Aaron et al. (Aaron et al., 1989) also studied the effect exposure to EMF on endochondral
ossification, but in a model system based on subcutaneous implantation of decalcified
bone matrix. In an early report, the effect of field exposure on collagen synthesis andmatrix calcification was studied. Decalcified bone matrix (25 mg) obtained from the tibia
and femur of mature male CD rats was implanted along the thoracic musculature in
immature male CD rats. The animals were randomly assigned to one of three groups: freeroaming controls, sham-exposed, and treated groups. Sham- and field-exposed groups
were confined in restraining boxes for 8 h/d during the animalÕs normal sleep cycle. The
treated group was given a whole-body exposure to a pulse-burst magnetic stimulus
consisting of a 4.5-ms burst containing 20 20 ms pulses of 2.0 mT. The burst was
repeated at a rate of 15 Hz. This waveform therefore produced a peak dB/dt of 100 T/s,
corresponding to an estimated peak induced electric field on the order of 1 V/m. The
animals were sacrificed at 2-d intervals over two weeks, and the ossicles were evaluatedbiochemically, histologically, and histomorphometrically. Exposure had no significant
effect on the total volume of calcified tissue in the ossicles at any time. A transient
increases in sulfate incorporation and in the volume of cartilage were observed inassociation with field exposure, peaking at day 8, and the calcium content of thedeveloping ossicles was consistently higher than that in restrained control animals (p <0.05). [A confounding aspect of this study is that the restrained controls had asignificantly inhibited ossicle development pattern as compared with the free-roaming
controls, such that the effect of field exposure was essentially to return the development
process to normal.]
In a study of the ability of magnetic fields to promote appositional bone growth, McLeod
and Rubin (McLeod & Rubin, 1992) coupled observations made with pulse fields tothose based on exposure to sinusoidal ELF fields. Bone resorption and formation werestudied in an avian model of disuse osteopenia. Bone loss due to disuse was initiated byproximal and distal osteotomies on the left ulna of adult male turkeys, and Delrin caps
were installed over the bone ends to prevent re-union. Exposure to magnetic fields was
accomplished from a Helmholtz-like coil pair strapped to the wing of the bird. Exposure
was for 1 h/d, five days per week. Six experimental groups were used, representing disuse,sham exposure (unenergized coils), exposure to a 75 Hz pulsed field (0.2 mT peak withrise time of 380 ms), and exposure to three sinusoidal fields at 75 and 150 Hz(representing the fundamental and second harmonics of the pulsed waveform) and 15 Hz.
The flux densities of the sinusoidal fields were established to provide the same dB/dt as in
the fundamental component of the 75 Hz pulsed stimulus. The electric fields induced in263

the preparation were estimated to be on the order of 10Ð20 mV/m with the pulsed field
and less than 1 mV/m with the sinusoidal fields. Morphological assessment after eightweeks showed a clear frequency dependence of the bone remodeling response, 150 Hz
being less effective than 75 Hz, which was significantly (p < 0.05) less effective than 15
Hz. The 15 Hz stimulus was found to be more effective than the pulsed field exposure ininitiating new bone formation, despite the similar peak flux density used (0.24 mT) andthe much lower peak induced electric field. [As the peak dB/dt was kept constant for thesinusoidal fields, the current flow into the coils would have had to increase by 10-foldbetween the 150 Hz and 15 Hz stimuli. In the absence of an active sham-exposed control,
this dose dependence may, to some degree, simply reflect a difference in heating of theinduction coils.]
Takano-Yamamoto et al. (Takano-Yamamoto et al., 1992) investigated the ability ofmagnetic fields to promote bone formation in a bone defect model. A 2 mm non-healingbone defect was surgically prepared in the premaxilla of 180 g male Wistar rats, and they
were either treated with 7 mg demineralized bone matrix or not, with or without field
exposure, yielding a total of five groups with the sham-operated group, with 4Ð10 animals
per group. Animals were exposed in a 25 x 20 x 60 cm plastic container which was placedin a solenoid 30 cm in diameter and 60 cm in length. Exposure was for 12 h/d to a pulseburst waveform composed of a 10 ms burst of 100 ms pulses, with a burst repetition rateof 15 Hz. The peak flux densities were 0.15Ð0.18 mT. After sacrifice of the animals atdays 0, 21, and 35, the defect sites were examined for histological alterations, alkaline
phosphatase activity, and Ca45 incorporation. Defects treated with demineralized bonematrix graft and PEMF had significantly greater alkaline phosphatase activity andcalcium incorporation (p < 0.05) than those with any of the four alternative treatment
protocols. In addition, histological examination showed almost complete osseous bridging
of the defect by day 35.
In a another test of the efficacy of PEMF to promote bone growth, Buch et al. (Buch etal., 1993) studied in-growth into a titanium bone harvest chamber. The titanium chamber(6 x 10 mm) was surgically implanted into the proximal tibia metaphyses of six male andfemale rabbits and became anchored within four weeks. Bone tissue was then harvested atthree-week intervals with the implant in situ, providing a repeated measure of in-growth.
Bone tissue was harvested once before field exposure, six times during the exposure
period, and then twice after field exposure was terminated. The animals were restrained
and underwent whole-body exposure 2 h/d from a Helmholtz-like coil pair. The waveformconsisted of a 72 Hz repetitive pulse pattern with a peak flux density of 3 mT. [Becauseof the geometry and the presence of a metal chamber, the induced electric field cannot beeasily calculated.] The mass of bone harvested from the bone chamber declined
significantly after the first three-week harvest (p < 0.003 by repeated measures analysis).
[While this result may well be due to the inability of the tissue to sustain a high level ofbone in-growth, the decline coincides with the period of field exposure, resulting in an
apparent inhibitory effect.] After termination of the field exposure at the time of the sixth
harvest, bone in-growth into the chamber declined further (p < 0.004). The authorsinterpreted these results to indicate that field exposure sustains a level of in-growth that264

would have continued to decline in the absence of stimulation. [Without concurrent shamexposed controls, this conclusion is difficult to support.]
Pienkowski et al. (Pienkowski et al., 1994) attempted to optimize PEMF therapy in a
rabbit fibular osteotomy model. This study is unique in that it was fully blinded, withplacebo devices for the controls. Fibular osteotomies were performed on the right limbs of
399 immature (2.8Ð3.2 kg) male rabbits, which underwent 20 experimental conditions.
Field exposure was accomplished from a saddle-shaped induction coil placed around theright leg and centered over the osteotomy site. A pulse-burst waveform pattern was used
in a 5-ms burst with a burst repetition rate of 15 Hz. The peak flux density and pulse
width were varied in an attempt to identify optimal exposure conditions. The peak flux
densities were 0.028Ð1.1 mT and the pulse widths were 0.5Ð10 ms. All of the animals
were sacrificed on day 16 after the operation, and the efficacy of treatment was evaluatedby a three-point bending test of the mechanical stiffness of the fibula. While certain
combinations of pulse width and amplitude appeared to result in a significantly stiffer (p< 0.05) callus, replication experiments did not confirm this observation. No clear patternof doseÐ or durationÐresponse was evident in this partially factorial experiment,suggesting that no consistent improvement in fracture healing resulted from field
exposure.
In an extension of their studies on the acceleration of endochondral ossification by
exposure to magnetic fields, Aaron and Ciombor (Aaron & Ciombor, 1996) investigatedthe effect of phased exposure. Immature (80 g) male rats received demineralized bonematrix pellets in the thoracic musculature and were exposed to a magnetic field stimulus
for only a fraction of the 20-d experimental protocol. There were four exposure groups:
on days 1Ð3, corresponding to the mesenchymal phase of ossicle development; on days
4Ð8, corresponding to the chondrogenic phase; on days 9Ð19, corresponding to thecalcification phase; and for the full 20 days. Exposure was accomplished as describedabove, with a pulse-burst waveform of 5 ms bursts repeated at a 15 Hz rate, and a peak
flux of 2 mT. Animals underwent whole-body exposure while confined in exposure
containers. All of them were sacrificed on day 20, and glycosaminoglycan synthesis andCa45 uptake were measured. While all of the exposed animals showed significantly
increased calcium uptake and glycosaminoglycan synthesis rates as compared with
unexposed controls, stimulation for just the first three days (mesenchymal phase) was
found to be as effective in promoting ossicle development as exposure for the full 20
days.
McLeod and Rubin (McLeod & Rubin, 1998) also continued their studies on the responseof the disuse avian ulna model to exposure to magnetic fields in an attempt to identify thefrequency and doseÐresponse characteristics of bone tissue. They continued to use
proximal and distal osteotomies of the left ulnas of adult male turkeys to create a bone
disuse situation; however, in this study the bone ends were capped with stainless-steel(non-magnetic) caps to prevent re-union, and external fixation hardware was used toprevent any inadvertent mechanical loading of the bone. In addition, a solenoid induction
coil was used to impose the magnetic field along the long axis of the bone. The induced265electrical currents therefore had an essentially uniform two-dimensional distribution,
permitting more accurate calculation of the induced current and field intensities. Groupsof three to four treated ulnas were exposed for 1 h/d under one of 10 exposure conditions,which spanned the frequency range of 5Ð150 Hz (all at a constant dB/dt of 0.025 T/s) anda flux density ranging up to 2.5 mT at a frequency of 15 Hz. The bone cross-sectional
area at the ulna mid-diaphysis was assayed after sacrifice of the birds eight weeks after
operation. A distinct frequency response was observed, with sensitivity peaking at 15
Hz. The investigators noted that the very low sensitivity observed at 5 Hz removes
concern about a possible heating effect, although no sham-exposed control was used. A
dose-dependent response was observed for flux densities up to 250 mT, with a significant
effect (p < 0.05) as compared with no field treatment for flux densities as low as 2.5 mT at
15 Hz. The authors considered that the lack of an increased response at 2.5 mT over thatobserved at 250 mT confirms the non-thermal origin of the effect. The distributions of theinduced electric fields, determined by two-dimensional impedance network techniques,indicate that the peak-induced 15 Hz electric field in the bone tissue at 250 mT would beapproximately 0.3 mV/m.
Effects of exogenous induced fields on nerve and skin healing
In principle, the same electrokinetic processes that give rise to electrical currents in bone
tissue will also produce electrical currents in soft connective tissues. In fact, the normal(i.e. non-destructive) mechanical deformations of soft tissues during typical physiologicalactivities far exceed that seen in bone tissue; however, with the exception of cartilage, thecharge density in these tissues is far lower than that of bone. In addition, soft connective
tissues lack the highly organized collagen structure that can permit a large piezoelectriccoefficient. Thus, the predominant electrical currents in skin, tendon, and ligament
probably arise through the extracellular currents generated during muscle contraction. The
approval and extensive use of pulsed magnetic fields in the clinical setting for bone healing
naturally led to investigations on the efficacy of pulsed fields to affect soft connective
tissue healing, particularly over the last 10 years.
Following the report of several studies demonstrating effects of ELF fields on fibroblasts
in vitro (Liboff et al., 1984; McLeod et al., 1987c; Ottani et al., 1988) undertook a study
to determine whether pulsed magnetic fields could affect skin wound healing in vivo. In
this study, a 3 x 3-cm square of skin (with the cutaneous muscle) was surgically removed
from the dorsal thoracolumbar region of four-month-old male Wistar rats (weighing 350Ð
370 g). The animals were then exposed or sham-exposed, and eight animals from eachgroup were sacrificed at days 6, 12, 21, and 42 for histological and ultrastructural analysisof the wounds. Field exposure was implemented in a 40 cm diameter solenoid driven by a
50 Hz triangular wave to a peak flux of 8 mT, providing a dB/dt of 0.8 T/s, sufficient to
induce electric field intensities on the order of 10Ð20 mV/m. The animals were exposed for
30 min every 12 h. Rats undergoing sham exposure spent the same time in the exposure
apparatus with no excitation. The rate of healing, as assayed by area of wound vs. time,
was found to be significantly higher (p < 0.001 by linear regression) in exposed animals,
reflecting an approximate halving of the healing time. The investigators noted the266appearance of a network of blood vessels in the wound as early as six days postoperatively. [The investigators also referred to unreported data collected at a variety ofother exposure frequencies (e.g. 60 and 400 Hz) with which similar results were obtained
and suggested that the waveform is probably not critical to ensure a physiological effect.]
Lin et al. (Lin et al., 1993) reported similar studies using a ligament defect model in
rabbits. In their investigation, 80 male rabbits underwent square resections (4 x 4 mm) of
both the left and the right patellar ligaments. They were then assigned to one of fourgroups representing exposure to a 0.2, 1, or 5 mT peak or control. A pulse magnetic field
was generated by a device of undescribed design, but which induced a 10 Hz electric field
pulse of 25 ms in width, consistent with a maximum dB/dt of 200 T/s, sufficient to induce
electric field intensities in the range of 10Ð100 V/m. The animals were exposed for 6 h/d,
and five animals from each group were sacrificed each week for four weeks. Blood flow,
collagen synthesis, collagen typing, and histological assays were performed. Significant (p< 0.05) increases in the collagen content of the wounds were observed in all treatedgroups as compared with controls, and significant (p < 0.05) increases in blood flow andcross-sectional area were observed within two weeks in the group exposed to 5 mT, aneffect sustained throughout the four-week experimental protocol. No differences incollagen type distribution were observed between the exposed and control groups. The
authors noted that these results are consistent with those of their earlier studies.
Patino et al. (Patino et al., 1996) reported the results of a study in which flux densities of
20 mT were used. A circular lesion was made on the backs of 22 male Wistar rats
weighing 250Ð360 g, and the animals were then used as controls, treated withnitrofurazone, or treated with PEMF (35 min twice a day to a 20 mT, 50 Hz flux from a
23-cm diameter solenoid 50 cm in length). Planimetry of the wounds was obtained every
7 d over one month. Both the area and the perimeter of the wounds of the field-treatedanimals were significantly reduced as compared with sham-exposed controls (p < 0.01).
Field treatment resulted in significantly smaller wounds on day 21 as compared with thenitrofurazone-treated group (p < 0.01).
Effects of induced fields on nerve tissue
As for bone and soft connective tissue healing, early investigations on the potential use ofelectric fields to promote nerve healing began with studies of DC fields in the 1970s.
Investigations on the use of pulsed magnetic fields to promote nerve healing date from the
1980s, although these studies have been pursued by a relatively small group ofinvestigators. OÕBrien et al. (O'Brien et al., 1984) made one of the earliest efforts todetermine the efficacy of magnetic field therapy to enhance regeneration in the peripheral
nervous system. The peroneal nerves of 12 cats were exposed, and compound action
potentials were recorded to provide a baseline measure. The nerve was then transected
and repaired by microsurgery. Five days post-operatively, the animals were assigned to
one of four groups, representing untreated controls, sham-treated controls, magnetic fieldtreated with a pulse-burst waveform (15 Hz burst repetition rate), or treated with a 72
Hz repetitive pulse waveform. All treated animals were exposed for 10 h/d, 6 d per week,267

for 12 weeks. The peak flux density is not reported, but the exposure hardware wasprovided by Electrobiology, Inc. [The peak flux was probably in the range of 1Ð2 mT.]Electrophysiological and histological assays were performed at 12 weeks. Both the area ofthe compound action potential and the retrograde transmission of horseradish peroxidase
to the anterior horn of the spinal cord were significantly greater (p < 0.01 by ANOVA) inanimals receiving the pulse-burst field than in the other three groups at 12 weeks. [This isa remarkable outcome, given that only three animals were available in each group.] The
authors noted that no functional assays were incorporated to ensure successful
regeneration.
A more thoroughly described study on nerve regeneration was later reported by Sisken etal. (Sisken et al., 1989), in which a crush lesion was used rather than nerve transection.
Male Sprague-Dawley rats weighing 300 g underwent a surgical procedure to produce acrush lesion in the right sciatic nerve. At days 3, 4, and 6, a pinch test (pinching theexposed nerve to produce muscle twitches) was performed under anesthesia to assay theextent of regeneration. Field exposure was accomplished with a 30 cm diameter Helmholtz
coil pair, the rats being either restrained or free-roaming in plastic cages. A 2 Hz squarewave drive was applied to the coils, creating a peak flux of 0.3 mT with a rise time of
approximately 1 ms, thereby producing a peak induced electric field proportional to 0.3
T/s or on the order of 10 mV/m. The animals were exposed for 4 h/d; sham-exposed
animals were placed in the exposure chamber without current excitation. No significant
effect of restraint as compared with free roaming was observed in the control or the fieldexposed group; however, field exposure was found to result in a significant (20%; p <0.001) increase in regeneration rate. In collateral studies, no effect of magnetic fieldorientation (horizontal vs. vertical) or exposure duration (1 vs. 4 vs. 10 h/d) was
observed, all variations resulting in significantly enhanced nerve regeneration rates.
Similarly, exposure of the animals to fields for 4 d before creating the crush lesion also
resulted in an increased regeneration rate post-operatively.
The frequency dependence of enhanced nerve regeneration capability was subsequently
reported by Rusovan et al. (Rusovan et al., 1992). A crush lesion of the sciatic nerve was
induced in female Sprague-Dawley rats weighing 200 g. The animals were randomly
assigned to one of eight groups corresponding to controls or exposure to one of seven 0.1
mT sinusoidal fields at a frequency of 50, 100, 250, 500, 1000, 1500, or 2000 Hz. The
induced fields were estimated by the authors by assuming an average radius of 5 cm perrat, suggesting an induced electric field intensity of 15 mV/m at 1 kHz. The regeneration
distance was evaluated by the pinch test at days 3, 4 and 6. While exposure to 50 or 100
Hz had no effect on regeneration, exposure to 250, 500, or 1000 Hz resulted insignificantly enhanced regeneration rates (p < 0.001). The maximal effect was a 24%
increase at 1 kHz, while the responses at 1.5 and 2 kHz were similar to that at 100 Hz.
The authors noted that the increase in response as a function of frequency is consistent
with an effect of the induced electric field, as the magnetic flux was held constant;however, they also note that similar decreases in sensitivity at higher field frequencies
have been observed in numerous in-vitro systems.

268

This group of investigators continued their studies on the effects of magnetic fields onnerve regeneration, pursuing their observations of pretreatment effects (Kanje et al.,1993). Female Sprague-Dawley rats weighing 200 g underwent a variety of pretreatment
exposures, ranging from 15 min/d for 2 d to 4 h/d for 4 d. The sciatic nerves of the animals
were then submitted to a crush injury, and the regeneration distance was assayed on days
1, 2, 3, 4, 7, and 14. Field exposure was accomplished with the apparatus described by
Sisken et al. (Sisken et al., 1989), consisting of a 30 cm diameter Helmholtz coil paircreating a vertical flux. Two peak flux densities, 60 and 300 mT, were used with a 2 Hz
pulsed signal and a rise time of 0.8 ms, corresponding to peak induced electric fields on
the order of 10 mV/m. The animals were allowed to roam freely throughout exposure.
While the 60 mT pretreatment had no effect on subsequent regeneration rates, all 300 mT
pretreatments, including treatments as short as 15 min/d for 2 d were found to
significantly enhance the regeneration rates. Animals pretreated for 4 h/d for 2 d had anincreased regeneration rate for at least 10 d.
4.4.6.3 Summary
Human clinical studies
If retrospective reports of the efficacy of PEMF in promoting the healing of fractures are
ignored, there is little clinical evidence of a real effect of exposure to fields in accelerating
or improving the probability of successful fracture healing. Two prospective, blinded
trials of the treatment of non- and delayed unions were undertaken, but both have serious
design flaws and furthermore show no or only a weak effect. The trial on limb lengthening
appears to be both well designed and definitive in showing a lack of effect on bone
fracture callus formation or on the process of secondary bone healing. In clinical use of
PEMF devices, however, it has been the rule to center the induction coil over the fracturesite. This technique may well have ensured a low success rate by minimizing the induced
electric field intensity at the distraction or fracture gap.
Conversely, there appears to be substantial, accumulating evidence that complex clinicalexposures to PEMF have a significant effect on primary bone healing processes. The
studies of both osteotomy and spinal fusion show a robust effect. While quantification
and analysis were weak in these two studies, they are prospective, randomized, doubleblind trials, a rarity in the field of orthopedics. Perhaps the most convincing trial is that of
the response of bone tissue during limb lengthening. While no effect on secondary bonehealing was observed, there was significant inhibition of bone resorption and evidence of
new bone formation. Unlike secondary bone healing, primary bone healing, new boneformation, and inhibition of bone resorption depend mainly on the state of vascularizationof the tissue. The results of the two studies therefore indicate that the predominant effectof exposure to PEMF is on the vascular supply or on cells capable of stimulating
revascularization, rather than a direct effect on the bone cell population. Of course, theissue of coil placement cannot be ignored in the study of limb lengthening, in which theproximal and distal segments of the bone would, in fact, experience the maximum induced269

electric field intensities. The responses observed in these two regions may therefore
simply reflect much higher field intensities.
In capacitive coupling, with application of a 3 Hz field, the distribution of the induced
electrical currents is readily determined by the placement of the external plates, and the
maximal field intensity can be expected to occur in the central region between the coupling
plates. In electromagnetic coupling, however, the issue is more complicated, as theinduced electric field will actually reach a maximum at the periphery of the magnetically
exposed area. In clinical trials in which local exposure is desired, the investigators havetypically centered the exposure coils over the site of interest, essentially ensuring that theinduced electric fields in the region will not be maximal.
Studies in experimental animals
Although early trials suggested that non-union tissue responds to EMF, and despiteextensive clinical use of magnetic field therapy for treatment of this condition, studies inanimals in vivo indicate only limited efficacy. Magnetic field therapy appears incapable ofenhancing the healing of osteotomies, in-growth of bone into a defect, bone elongation, or
graft healing and, in at least one case (in-growth), may inhibit the normal process. The
results obtained in a model of endochondral ossification after exposure of whole animals
suggest, however, that magnetic field therapy can be effective. This raises two
possibilities. One is that neither magnetic fields nor induced electric fields have any direct
effect on the endochondral ossification process but have an effect at the systemic level
manifested by accelerated growth processes. Alternatively, the ossification model differs
critically from bone healing in situ in that the induced electric fields are distributed in boththe healing tissue and the surrounding tissue. Exposure to local fluxes can result inminimal induced electric field intensities at the healing site. As the distribution of induced
fields is quite complex, however, the effect of this variable may be beyond interpretation.
Conversely, magnetic fields appear to have a strong, reproducible effect on the process ofappositional (surface) bone growth and on inhibition of bone resorption. Moreover, thefact that exposure to pure electric fields and time-varying magnetic fields can inhibit boneloss suggests that this effect is mediated by the induced electric field. In the studies
reviewed here, the frequency range within which maximal bone tissue responses areobserved is consistent, induced fields in the range of 15Ð75 Hz appearing to be optimal in
all of the studies. The effect of field intensity is much less clear; however, in a study thatspecifically addressed this factor (McLeod & Rubin, 1998), a threshold intensity of < 0.1
mV/m was established for exposure at 15 Hz.
Consistent effects on the healing of soft connective tissue have been reported bynumerous groups. Perhaps the most notable feature is that remarkably high flux densities(5Ð20 mT) are required to ensure an enhanced healing rate. Because no active shamexposure device was used in any of these studies, there is clearly potential concern about270

warming of the animals. In addition, the fact that whole-animal exposure was used inthese studies suggests the possibility of neuroendocrine stimulation.
Consistent responses were also seen in the studies of nerve regeneration, although theyusually represented only about a 20% enhancement in growth rate. These studies confirm
the results of the studies of soft and hard connective tissue healing, particularly withregard to the sensitivity of the nerve healing process to frequency. In addition, attention
was drawn to the angiogenic properties of stimulation of nerve regeneration by magnetic
fields, as has been observed repeatedly in studies of both skin and bone healing. Thisobservation may be critical with regard to the role of magnetic fields in the promotion oftumor growth, which is known to depend on angiogenesis.
As in the clinical studies, the nature of the exposure of the target tissue is not precisely
defined. Whole-body exposure has commonly been used in studies of small animals,
which can result, for sites of interest near the periphery of the body, in maximal induced
electric field intensity. This type of exposure may also affect many other sites in thebody, producing systemic responses that could influence tissue healing. For example,
calcitonin, a growth hormone which has strong effects on bone growth in young animals,
is produced by the C cells of the thyroid. The location of the thyroid at the periphery of
the body ensures maximal exposure to electric fields under the conditions of either verticalor horizontal exposure to magnetic fields. Stimulation of the thyroid could therefore resultin enhanced bone growth or healing, independent of any local effect on the bone or
surrounding tissue. This Working Group did not address the possible adverse side-effects
of exposure to electromagnetic fields on bone and tissue repair and adaptation.
There is strong evidence that exposure to electric and magnetic fields affects bone repair
and adaptation.
[This conclusion was supported by 14 Working Group members; there were 5 votes forÔmoderateÕ evidence, 8 abstentions, and 2 absent.]
The Working Group could not reach a conclusion about whether exposure to electric andmagnetic fields affect nervous and non-bone connective tissue repair and adaptation invertebrates.
[This conclusion was supported by 12 Working Group members; there were 10 votes forÔmoderateÕ evidence, 6 votes for ÔweakÕ evidence, and 1 absent.]

271

4.5

Epidemiological studies of non-cancer health effects in humans

4.5.1 Occupational exposureThis review includes only the studies that are the strongest methodologically, on the basisof exposure assessment, on occupational exposure to EMF and neurodegenerative andpsychological diseases, reproductive disorders, and cardiovascular disease (see Table
4.35).
Table 4.35. Minimal exposure assessment required for a study to be included in this review
DiseaseExposure assessment

Spontaneous abortions after maternal exposure to VDTs
Other reproductive abnormalities due to maternal exposure
Reproductive abnormalities due to paternal exposure
Alzheimer disease (or dementia)
Amyotrophic lateral sclerosis
SuicideDepression
Cardiovascular disease

Measurements on VDTs
Questions about VDT usea
Job titles
Job titles of electrical workersa,bJob titles of electrical workersa,bJob titles of electrical workersa
Full-shift monitoring
Job titles of electrical workers

VDT, visual display terminalaIncludes one or more studies with full-shift measurementsbIncludes studies with expert judgments of magnetic field exposures

4.5.1.1 Reproductive effects(a) Adverse birth outcomes and maternal exposure to electromagnetic fields
Possible reproductive effects of womenÕs exposure to EMF from video display terminals(VDTs) were examined in four studies (Table 4.36). VDTs emit EMF with saw tooth
waveforms in both ELFs (3Ð3000 Hz) and VLFs (3000Ð30 000 Hz). VDT fields havemarkedly different characteristics from the sinusoidal ELF fields that are the primary
component of environmental EMF. The magnitudes of the magnetic fields around a VDTvary widely with the model (Juutilainen & Saali, 1986b; Moss & Booher, 1995;
Schiffman et al., 1998), and that information has been used to categorize such exposures
for studies of reproductive effects.
Schnorr et al. (Schnorr et al., 1991) conducted a retrospective study of spontaneousabortions in women employed as telephone operators by two large telephone companies
in 1983Ð86. The study base consisted of 4246 married women aged 18Ð33 who wereidentified from company records and agreed to an interview about their reproductive,
medical, and occupational histories (76.6% of the 5544 woman identified). The 136 cases
were pregnancies resulting in spontaneous abortions while the respondent worked as atelephone operator. The 737 controls were pregnancies among operators who had live272

births. Exposure to EMF was assessed by job title and validated by field measurements.
Women considered to be exposed were directory assistance operators who had always
used conventional VDTs with cathode ray tubes during the study period. Thoseconsidered to be unexposed were general telephone operators who had worked atmonitors with light-emitting diode or neon glow tube displays up to 1986; these monitors
emitted no VLF fields and lower ELF magnetic fields than the VDTs (Bracken, 1991;
NIOSH, 1990). The EMF fields from the VDTs had rough saw tooth waveforms withprincipal frequencies of 45 Hz for one model and 60 Hz for another; the non-VDT
monitors had 60 Hz sinusoidal waveforms. The exposure of the operators to EMF at thelevel of their abdomen varied considerably with the workerÕs location and the type ofmonitor. In measurements taken at a sample of work sites with Holiday Industries model
HI 3600-01 and 3600-02 meters, the geometric mean operator exposure to ELF magnetic
fields was 0.078 mT for one model and 0.073 mT for the other. The exposure from VDTs
was the same as from the light-emitting diode monitors (geometric mean = 0.078 mT) andhigher on average than that from the neon glow tube monitors (0.041 mT). In comparison
with those in other office environments, this ELF exposure of the telephone operators is
not elevated, although VLF fields were rare before the introduction of computers.
The spontaneous abortion rate was similar for the VDT-exposed and the generaltelephone operators (14.8 and 15.9%, respectively). No associations were found with
VDT use at any period of pregnancy, either when the analyses were unadjusted or when
they were adjusted for such risk factors as smoking, thyroid disorders, alcohol
consumption, and spontaneous abortions before the study period. [As the comparison of
VDTs with non-VDT monitors produced a clear differential in exposure to VLF (but not
ELF) EMF, this study does not allow any conclusions about the risks for spontaneousabortion from exposure to ELF magnetic fields. Derivation of information on spontaneousabortions from questionnaires has limitations.]
Grajewski et al. (Grajewski et al., 1997) examined the risk for preterm births and reduced
birthweights among VDT operators from the study population of Schnorr et al. (Schnorr
et al., 1991). They evaluated 304 singleton pregnancies in 284 women who had worked as
VDT telephone operators during the first 28 weeks of pregnancy and 403 among 363
unexposed operators. Birthweight, gestational age, birth defects, and the reproductive risk
factors studied by Schnorr et al. were determined during interviews. The self-reported
data were validated from birth certificates and medical records and found to be within ±100 g for birth weight and ± two weeks for gestational age for more than 80% of thesubjects. The number of hours that the subject had been exposed to VDTs was estimatedfrom the time she had spent working as a directory assistance operator in the telephonecompanyÕs payroll records, which also reported the number of hours of work per day,leave, and vacations. The following potential confounders were included in the analysis:
diabetes, maternal weight gain during pregnancy, thyroid conditions, hypertension
medications, pre-eclampsia, toxemia, interpregnancy interval, and adverse pregnancy
outcomes (including previous reduced-weight or preterm births) before the study period.

273

No association was found between length of work with VDTs at any period of thepregnancy and either reduced birth weight (< 2800 g) or preterm birth (21Ð37 weeks
gestation). Seven cases of major birth defects (2.3%) were reported by the VDT-exposed
operators and four (1.0%) by the unexposed; however, only three of the 11 self-reported
birth defects could be confirmed from medical records. [See summary of Schnorr et al. forcomments on limitations of the study. Some validation of outcome was possible frommedical records.]
Lindbohm et al. (Lindbohm et al., 1992) performed a retrospective study of spontaneousabortions among women using VDTs. The study base consisted of women employed asbank clerks and clerical workers by three large companies during the years 1975Ð85. The
368 cases of spontaneous abortion among study base members aged 20Ð35 identified fromthe Finnish pregnancy registry had to be confirmed by questionnaire for the subject to be
included in the analysis (8.5% of miscarriages unconfirmed). The 1069 controls were
woman who had given birth to liveborn infants in the registry. Job histories, VDT use,
reproductive risk factors, and ergonomic factors were requested on the questionnaires,
which were returned by 191 cases (52%) and 394 controls (36%). Exposure to VDTfields was assessed from the questionnaires, company records on the VDT models usedby different work groups, and laboratory measurements of VLF and ELF magnetic fields
at a fixed location (approximating the fetusÕ position) near the various VDT models.
Exposure to magnetic fields was expressed as the time derivative (dB/dt) for VLF fields
and the peak-to-peak magnitude for ELF fields. [In order to compare peak-to-peak values
in this study with the root-square-squared (rms) magnitudes used in other studies, a rangeof conversion factors (0.266Ð0.010) was derived empirically from the Finnish VDTmeasurements reported by Jokela et al. Because these are saw tooth waveforms, theempirical conversion factor is less than the better-known value: 1/2Ö2 = 0.354 derived forsinusoidal waves.] (Jokela et al., 1989)
An increased risk was reported in association with exposure to ELF magnetic fields from
VDTs, expressed both as rms magnitude ³ 0.24 mT and cumulative exposure per week;
the increase was significant for the highest exposure category (see Table 4.36). [Thereappeared to be exposureÐresponse relationships, although they were not tested
statistically]. The relative risk for high exposure was markedly greater for latespontaneous abortions, ³ 12 weeks into the pregnancy (8 cases; OR = 9.5; 95% CI = 1.8Ð52). No association was seen with VLF VDT fields, but a significant association was seen
with the time-weighted average exposure per week (which incorporated time spent at
VDTs, calculated from company records) in the group with high exposure (2.7; 1.2Ð6.1).
The relative risks were adjusted for self-reported work load, exposure to solvents, numberof previous births, use of intrauterine devices, and frequency of breakdowns in automatic
data processing machines. [The response rate was very poor, particularly among controls,
and subjects for whom all VDT models could not be identified were excluded. The
magnetic fields were measured in the laboratory, with high background ELF fields, rather
than in workplaces.]274Bracken et al. (Bracken et al., 1995a) performed a prospective cohort study of fetal
growth and exposure to EMF (see section 4.5.2.1 for a full description of the study).
Although the focus was residential sources of EMF, such as electrically heated beds andwire codes, occupational exposures were also assessed by seven-day monitoring ofmagnetic fields and questions about VDT use. The study population consisted of womenwith a uterine pregnancy and no diabetes who had received prenatal care in the New
Haven, Connecticut, area over a four-year period. The participating subjects (83% of
eligible women) were interviewed before 16 weeks of estimated gestational age and took
part in a program of EMF measurements that included the AMEX-2 wrist monitor. The
monitoring encompassed much occupational exposure, because 81.3% of the subjects
worked outside the home. The outcomes were low birthweight (< 2500 g) and intrauterine
growth retardation (< 10th percentile of weight for gestational age). Neither outcome wasassociated with VDT use or TWA exposure to magnetic fields. [The AMEX-2 has amagnetic field sensor in only one direction and therefore provides very inaccurate
measures in comparison with three-axis monitors. See Section 4.5.2.1 for comments on
the limitations of this study.](b) Adverse reproductive effects from paternal exposure to EMF
Concern about the effects on children of paternal EMF exposure first arose from crosssectional studies of workers in high-voltage substations in the former USSR (Asanova &Rakov, 1966). At that time, ELF electric fields were the exposure considered most likely
to be responsible for adverse health effects. The average exposure in the substations was
98 V/m, compared with 5Ð10 V/m in offices and homes (Bracken et al., 1995a). It is onlyin two recent studies that broader assessments of exposure to EMF have been considered.
Two studies were focused on the male:female ratio of offspring (Mubarak & Mubarak,1996); (Irgens et al., 1997) [but the exposure assessments were inadequate].
Tornqvist (Tornqvist, 1998) studied reproductive effects among electric workers in theutility industry, in a large retrospective study and a small prospective study of perinatal
survival, multiple births, low birthweight, sex ratio, congenital malformations, andchildhood cancers (also discussed in section 4.2.1). In the retrospective study, Swedish
census data were used to establish a cohort of 2077 male electrical workers and to obtain
information on their work histories and spouses or cohabitants for a 25-year period.
Information on 3350 children born to these couples was obtained from the Medical BirthRegistry, and any cancers that the children incurred were ascertained from the National
Cancer Registry. For each child, the fatherÕs exposure to EMF was determined from job
titles reported in the five-year censuses before and after the year of the birth. The father
was considered to have been exposed if he had held electrical occupations at bothcensuses spanning the prenatal year; otherwise, he was considered to be unexposed. Since
the unexposed fathers held electrical occupations either before or after the child wasconceived, they are assumed to belong to a socioeconomic class similar to that of the
exposed fathers. Relative risks were calculated for the various reproductive outcomes
relative to those in the total population of births, adjusted for maternal age, parity, and275

year of birth. Relative risks were also calculated for the exposed vs. the unexposed
fathers.
In the prospective study, the health of a cohort of 460 young electrical workers whose
first job was in the power industry was followed. Questionnaires covering job histories
and reproductive issues were part of the health examinations administered every three
years. Over a 10-year period, these men fathered 364 children. Exposure to EMF during
the prenatal year were derived from the job histories and a JEM based on measurements
taken in the Swedish power industries (Lindh et al., 1997). Workers considered to behighly exposed were those with exposure to both TWA magnetic fields > 0.5 mT andelectric fields > 30 V/m for at least 10 min per shift; low exposure was defined as
exposure to both electric and magnetic fields below these thresholds.
Neither study showed any significant association with multiple births, low birth weight,
sex ratio, or congenital malformations. The proportion of malformations was slightly
increased among the offspring of highly exposed fathers in both the retrospective study(OR = 1.1; 95% CI, 0.82Ð1.5) and the prospective study (1.6; 0.43Ð14.8). [The paper
gives 1.48 as the upper confidence limit, which must be a typographical error.] The
author noted that the retrospective study involved large numbers and crude information
on exposure, while the prospective study involved small numbers but good information
on exposure.
4.5.1.2 Neurodegenerative diseases
Alzheimer disease is a progressive, irreversible degenerative disease of the brain that
presents as dementia, usually in people over the age of 65. The diagnosis includes
symptoms of dementia (e.g. loss of memory and mental and cognitive functions) andexcludes other causes such as Parkinson disease, head trauma, alcoholism, and stroke(vascular dementia). Alzheimer disease is biologically distinct from other dementias, but
its characteristic form of brain degeneration is seen only at autopsy. Alzheimer disease is
the commonest form of dementia: e.g. of the 77 cases of dementia studied by Feychting etal. (Feychting et al., 1998), 71.4% were diagnosed as Alzheimer disease, 15.6% asvascular dementia, 10.4% as other forms, and 2.6% as unspecified dementia. Twohypotheses have been advanced with regard to the effect of EMF on dementia. Sobel and
Davanipour (Sobel & Davanipour, 1996) proposed that EMF contributes to theneurodegenerative processes behind Alzheimer disease, while Feychting et al. (Feychting
et al., 1998) hypothesized that the brain damage caused by EMF could increase the risks
for all forms of dementia. EMF as a risk factor for Alzheimer disease or all dementias has
been the subject of six studies (Table 4.37).
Sobel et al. (Sobel et al., 1995) used three case-control sets to study ÔsporadicÕ Alzheimer
disease, i.e., patients who had no first-degree relatives with the disease. The cases werediagnosed at hospitals and university clinics in Finland (53 in 1982-85 and 198 in 197778) and southern California (136 in 1982-83). For the older Finnish series, the diagnostic

276

criteria were different than those used in California and for the other Finnish series (thoseof the National Institute of Neurologic and Communicative Disorders and StorkeAlzheimerÕs Disease and Related Disorders Association; NINCDS-ADRDA), and theagreement between the clinical diagnosis and autopsy results in a sample of cases was
only 82%, in comparison with 90-98% in the other series. In the first Finnish series andthe California series cases with familial disease were eliminated by questioning next-of-kin
about Alzheimer disease among relatives. The controls were patients with sporadic
vascular dementia in the first Finnish series, hospital patients with not neurologicaldisease in the second series, and neighborhood volunteers who were neurologically normal
in the California series. In formation on the primary lifetime occupation was obtained byinterviewing a proxy respondent for demented subjects and by direct interview for
healthy controls. High, medium, or low exposure to ELF magnetic fields was attributed
to each job by an industrial hygienist. Since the commonest occupation with medium-tohigh exposure in this population were seamstresses and tailors, magnetic fields were
measured around a sample of industrial and home sewing machines; the average spotmeasurement was 1.93 mT. [To judge the quality of these exposure assessment, theoccupation judged to involve medium-to-high exposure was compared in Table 2.4 withmeasured TWAs; 87% are above the 540th percentile for men, excluding occupations forwhich these were no measurements.]
A significant association was found in women with exposure to medium-to-high magnetic
fields (OR = 3.9; 95% CI, 1.7-8.9) and for the men and women combined (2.9; 1.6-5.4).
Despite the different composition of the three case-control series, elevated risks were
found consistently, except among men in the series in which people with vasculardementia were used as controls (0.7; 0.1-8.9) with one exposed case). [The limitations of
the study are use of different control groups in the three series, particularly patients with
vascular dementia who may in fact have had Alzheimer disease; obtaining job histories byquestionnaires; lack of validation of exposure of the study population; dependence on
proxy respondents for job histories for cases but not for some of the control; and failure
to take into account potential confounding by heredity. These limitations makeinterpretation of the results problematic.]
Sobel et al. (Sobel et al., 1996) used a similar study design for a new case-control series
drawn from an Alzheimer disease clinic in California. The cases were dementia orprobably Alzheimer disease diagnoses in 86 men and 240 women at the clinic [period
unspecified] by the criteria of the NINCDS-ADRDA. The controls were 76 male and 76
female patients at the clinic in whom other dementias (excluding vascular dementia andmixed diagnoses) were diagnosed. In a departure from the method of Sobel et al. (Sobel etal., 1995), subjects under the age of 65 were excluded from the analysis, but thosereporting a family history of Alzheimer disease were included because the reports could
not be verified. Information on primary occupation and education was available fromclinical records. Work with sewing machines was again prevalent among cases. High,medium, or low exposure to ELF magnetic fields were attributed to each of these jobs
following the classification used in the previous study. The high and medium exposure
categories were combined into a single category for the analyses. Odds ratios were277

adjusted for education (an apparent risk factor), gender, and age of onset (possible
confounders) by logistic regression. An association with magnetic fields was noted, which
was significant in men, but not in women: the odds ratios were, respectively, 4.9 (1.3-7.9)
and 3.4 (0.76-16) for men and women. [The odds ratios in this study were higher for men
than for women, contrary to what had been observed in the previous study. The
limitations of this study were that the cases included 24 patients with unclear diagnoses;
the controls were not matched by age or gender to the cases and were from the same
clinic, which specialized in Alzheimer disease; job histories were obtained byquestionnaire; and the exposure of the study population was not validated. The different
designs used in this study and in the three other studies of Sobel et al. lead to a diverse
collection of relative risks and potential biases that make interpretation of these resultsvery difficult.]
Feychting et al. (Feychting et al., 1998) examined exposure to magnetic fields in the
population of a study of dementia in Swedish twins (Gatz et al., 1997) in which twins in
the Swedish registry were screened for dementia by a complete clinical work-up including
neurological and neuropsychological assessments and neuro-imaging (81% response rate);the diagnoses followed the criteria of the NINCDS-ADRDA but were not confirmed by
autopsy. All 77 cases in this study were dementia, and 71% (55) were Alzheimer disease.
When both twins were demented, one of them was selected randomly to be a case in the
study. Controls were twins found to be free of dementia at clinical examination. To obtainenough older controls, 14% of the control population was recruited from a twin registry
population different than that from which the cases were derived. Two independent
control groups of 228 and 238 subjects, respectively, were formed so that sibling twins
could be assigned to different groups, eliminating double representation of the same genes
among the controls. Complete histories of jobs and exposure in the workplace wereobtained by structured interviews with controls and people who knew the case patients.
For the job held the longest and the job held last, TWA magnetic field magnitudes wereassigned from a JEM based on full-shift TWA magnetic field magnitudes were assigned
from a JEM based on full-shift measurements (Floderus et al., 1994). Risk estimates
were adjusted for age at onset, education, and birth date.
A significant association was found between all dementias and exposure to TWA
magnetic fields > 0.2 mT in the job held last (OR, 1.6; 95% CI, 0.6Ð4.0 for TWA 0.12Ð
0.19 mT and 3.3; 1.3Ð8.6 for > 0.20 mT, compared with < 0.12 mT). The association was
smaller and not significant when the primary occupation was considered. The association
between Alzheimer disease and exposure to TWA magnetic fields > 0.2 mT in the job held
last was also increased but not significantly so (2.4; 0.8Ð6.9). When the disease wasdiagnosed in the patient before the age of 75, significant relative risks were found between
exposure to TWA magnetic fields > 0.2 mT and all forms of dementia combined (5.8; 1.4Ð24) and with Alzheimer disease alone (5.0; 1.1Ð21). The risks reportedly increased further
when fewer than 10 years had elapsed between the last job and disease onset. The relative
risks for a small number of non-Alzheimer dementia cases are also elevated. [Thelimitations are the small number of cases, particularly of Alzheimer disease; possible
selection bias due to twins who refused to be examined; potential information biases in278

the job histories, which were obtained for cases from proxy respondents; lack of autopsy
confirmation of the diagnosis of Alzheimer disease; and failure to evaluate potential
confounding by heredity.]
Johansen and Olsen conducted a cohort mortality study of neurological disorders among
electrical utility workers, using a JEM based on expert judgments from magnetic fieldmeasurements (Johansen, 1998). The study design is similar to that of their cancer cohort
study, reviewed in section 4.2.1.1 (Johansen & Olsen, 1998). Only four deaths due tosenile dementia were found, and the SMRs were not elevated at any level of exposure tomagnetic fields. [The major limitations of this study are the use of death certificates toassess dementia, which is often not the immediate cause of death; failure to take into
account potential confounding by heredity; and the very small number of cases.]
Savitz et al. also studied mortality from neurodegenerative disease and exposure tomagnetic fields in the cohort of men working at five US electric utilities (described in
section 4.2.1.1) (Savitz et al., 1998a). The cohort was followed from mortality in 195088. These were 24 cases of Alzheimer disease, 45 of Parkinson disease, and 28 of
amyotrophic lateral sclerosis (ALS) listed on death certificates as either the underlying or
secondary cause of death. The magnitudes of cumulative exposures to TWA magnetic
fields were calculated for five durations (total career, ³ 2, 2-10, 10-20, and ³ 20 years)
from job histories and a JEM based on full-shift measurements taken for the previous
study. Mortality rate ratios relative to the cohort were computed of the five exposure
categories by Poisson regression with adjustment for age, decade of death, race, social
class, retirement status, and exposure to solvents.
For Alzheimer disease, a non-significant association with career exposure was noted, withrelative risks of 1.4 (0.4Ð5.3) for 0.54Ð1.13 mT-years, 1.8 (0.5Ð6.7) for 1.13Ð2.06 mTyears, and 2.0 (0.6Ð7.0) for 2.06Ð4.75 mT-years. The risk was highest for the highest
exposure category (2.7; 0.8Ð8.9) for exposures received ³ 20 years previously. No
increase in risk or exposureÐresponse relationship was apparent for Parkinson disease.
[The major limitations of this study are the use of death certificate to assess outcome,particularly since Alzheimer disease is difficult to diagnose and is often underreported ondeath certificates; the failure to take into account potential confounding by heredity; andthe very small number of cases.]
Savitz et al. considered mortality rates from neurodegenerative disease among working-age
men in 25 states in the USA, using death certificates from National Center for Health
Statistics (Savitz et al., 1998b). Over the period 1985-91, 1,768,411 death certificates met
the inclusion criteria. The underlying cause of death was Alzheimer disease for 256
subjects, Parkinson disease for 168, and ALS for 114. For each case, three controls who
had diet of other causes were selected by frequency matching on casesÕ age and year ofdeath. A subject was considered to have been exposed if the job on his death certificate
was one of 14 electrical occupations. [As shown in Table 2.4, 71% of these electricaloccupations involve exposure to TWA magnetic fields above the 50th percentile for maleworkers.] Internally standardized mortality odds ratios for the electrical occupations were279

calculated by logistic regression with adjustment for age, year of death, social class, andrace.
The relative risk for Alzheimer disease for men in all electrical occupations was weak but
significantly elevated (1.2; 1.0-1.4), mainly due to an excess of deaths in men over 65 (1.2;.1-1.4). No association between electrical occupations and Parkinson disease wasobserved (1.1; 0.9-1.2). [As in the two previous studies, the use of death certificates fordiagnosis of Alzheimer disease is a limitation as is failure to take into account confoundingby heredity and the absence of validation of exposure in the study population; see also
section 4.2.1.1 for comments on limitations of this study.](b) Amyotrophic lateral sclerosis and other motor neuron diseases.
Motor neuron diseases are progressive degenerative diseases that are invariably fatal. The
most common form is ALS; others are progressive bulbar palsy and progressive muscularatrophy, which differ in the location of the symptoms. ALS and motor neuron diseases asa whole in relation to occupational exposure to EMF have been studied epidemiologically(Table 4.38).
Deapen and Henderson (Deapen & Henderson, 1986) conducted a caseÐcontrol study of
ALS with an a priori hypothesis that the cause is electrical shocks. Their 678 cases had
voluntarily registered with the Amyotrophic Lateral Sclerosis Society in 1977Ð79 and had
filled out a mailed questionnaire. The names of the 518 controls of the same gender andage were solicited from the patients [no criteria given]. All 518 caseÐcontrol pairs
completed questionnaires about job histories, genetic factors, electric shocks resulting in
unconsciousness, and other exposure. Nineteen cases and five controls reported electricaloccupations. Odds ratios were determined by a matched analysis for all risk factors,
including a group of 19 electrically related occupationÐindustry combinations. [Asindicated in Table 2.4, 71% of the electrical occupations in this paper involve exposure to
TWA magnetic fields above the 50th percentile for male workers.] The relative risks weresignificant for both electrical occupations (3.8; 1.4Ð13) and shocks (2.8; 1.0Ð9.9), but the
number of exposed cases was small. [Limitations of this study are that exposure to EMF
was assessed from job titles based on responses to the questionnaire, failure to report thecriteria for control selection, and the potential recall bias inherent in using occupational
histories and reports of electric shock.]
Davanipour et al. (Davanipour et al., 1997) conducted a case-control study involving 28
patients at an ALS clinic. The cases were diagnosed ALS with no history of polio or ALS
apparent in the family. The controls were one blood relative and one non-blood relative(except spouses), if they existed and were willing to participate, matched on age andgender when possible. In total, 28 controls were recruited, but eight cases had no control.
Occupational histories were obtained by interviewing the subjects. For each job, exposure
to magnetic fields was judged to be high, medium, or low by an industrial hygienist withexperience in measuring EMF but blinded to the disease status of the person. [As shown280

in table 2.4, 75% of the occupations judged to involved medium-to-high exposure were
those in which the TWA magnetic fields were above the 50th percentile for maleworkers.] Scores for cumulative exposure to magnetic fields were calculated for eachsubjectÕs working life. In the highest exposure category, the odds ratios adjusted forgender were 2.5 (0.80-6.6) for all subjects and 7.5 (1.4-38) for subjects with ³ 20 yearsÕ
work experience. Logistic regression analysis revealed a statistically significant exposureresponse relationship for workers with ³ 20 yearsÕ experience (p < 0.02) but not for all
subjects. [The study is limited by the small sample size and potential control selection
bias.]
Johansen and Olsen (Johansen & Olsen, 1998) conducted a cohort study of mortality
among electrical utility workers, using a JEM based on expert judgment from magnetic
field measurements. Details of the study design are described in section 4.2.1.2. There
were 14 deaths from ALS. The risks for this condition appeared to increase acrossexposure categories (SMR = 2.8 for TWA magnetic fields > 1.0 mT) but are too imprecise
to be significant. The authors attributed the association between ALS and exposure tomagnetic fields to confounding by non-lethal electric shocks. Although they had no dataon exposure to shocks to test their hypothesis of confounding, they noted that deaths
from electrical accidents correlate with exposure to magnetic fields (SMR = 0 for
background vs. SMR = 31 for fields > 1.0 mT; p < 0.05). [The very small number of ALS
cases and the absence of confidence intervals make these results difficult to interpret;diagnosis of ALS from death certificates has a 5Ð10% error rate; and family histories of
ALS were not assessed.]
Savitz et al. included ALS in their cohort study of mortality from neurodegenerative
disease and exposure to magnetic fields (see above) (Savitz et al., 1998a). No association
was seen between total career exposure and mention of ALS as a cause of death (28cases), but a non-significant increase was seen for exposure in the highest category for ³
20 years (RR = 2.4; 95% CI, 0.7Ð8.0). [Limitations of this study are the modest numberof ALS cases, diagnosis from death certificates, and the absence of data on electric shocks
or the familyÕs disease history.]
Savitz et al. examined ALS in their study of mortality from neurodegenerative diseases in
US working-age men (see above) (Savitz et al., 1998b). There were 114 deaths from ALS.
The mortality odds ratio for this disease category was slightly elevated for electricaloccupations (1.3; 1.1Ð1.6). [The diagnosis of ALS from death certificates in this study
was based on ICD9, which groups ALS with other motor neuron diseases. Other
limitations of this study include the fact that only one occupation was taken from deathcertificates and the absence of data on important confounders, such as familial
neurodegenerative disease or exposure to electric shocks.]281

4.5.1.3 Suicide and depression
As depression is a proven risk factor for suicide, the sparse literature on these twooutcomes and occupational exposure to EMF are reviewed together (Table 4.39). In thebest papers, exposure was assessed on the basis of job titles for depression and JEMs for
suicide. A study of suicide based on job titles (Baris & Armstrong, 1990) was notreviewed. Wilson (Wilson et al., 1998) hypothesized that EMF could contribute todepression by an effect on melatonin, but this mechanism has no corollary for
epidemiological studies.
Savitz et al. studied depression and exposure to EMF in a cohort of US Army veterans
who had been examined in the Vietnam Experience Study (Savitz et al., 1994). In thisstudy, a sample of male veterans whose service had started in 1965Ð71 and lasted for asingle term underwent medical and psychological examinations (52% participation rate).
The population of the study of EMF was 4044 men who were employed at the time ofthe examination. They were asked in an interview about the job held currently, the job
held the longest and its duration, demographic information, and data on potential
confounders. At the time of the examination, the 183 exposed subjects had a job belonging
to a group of 15 electrical occupations (Table 2.4). Depression was assessed on the basisof the Diagnostic Interview Schedule and the Minnesota Multiphasic Personality
Inventory. For this study, the results of the former were used to test for three diagnoses
of depression and eight symptoms; and the latter gave eight indicators of depression andfive symptoms. The risk ratios for these outcomes were adjusted for race, marital status,
education, alcohol use, and duration of employment.
Subjects who had held their most recent job for less than 10 years were generally more
likely to be depressed. Some non-significant associations were found between electric
work and markers of depression (see Table 4.39). Neither electricians nor electrical
workers had an increased frequency in thoughts of death (OR = 0.8; 95% CI, 0.3Ð1.8).
[Some of the elevated risks could be due to chance, given the many outcomes analyzed.
Other problems are the very small number of exposed cases, exposure assessment basedon job title, and the difficulty in generalizing results for Army veterans, especially withthe low participation rate.]
Baris et al .(Baris et al., 1996a) examined suicide in a caseÐcohort study of the HydroQuŽbec workers who had been studied by ThŽriault et al. Deaths in the cohort weretracked over 18 years through company records for current employees, pension records
for retirees, and QuŽbec death certificates for former employees. Forty-nine suicides were
found on the death certificates. The reference group was a 1% sample of the entire cohort(n = 217). Exposures were assessed from JEMs for electric fields, magnetic fields, andPEMF as described above (Armstrong et al., 1994; ThŽriault et al., 1994). The TWA andthe GM over the shift were used as exposure metrics for EMF, while the TWA was the
only metric for PEMF. For each employee, both cumulative and current exposures were
calculated from the companyÕs job records and JEMs for these five metrics. The
companyÕs records from periods before employment of the subject and annual medical282

examinations was examined for information on alcohol consumption and changes inmarital status. The cohortÕs sick-leave records were scanned for any diagnoses of mental
illness, which was a strong risk factor for suicide in this population (RR = 15; 95% CI,
6.8Ð34).
The results showed no significant association with cumulative or current TWA exposure
to magnetic fields (OR = 1.6; 0.69Ð3.8 for TWA ³ 0.37 mT). Of the 10 types of exposure
analyzed, only cumulative GM electric fields in the intermediate category were associatedwith a significant suicide rate (3.1; 1.9Ð8.2), but the risks declined with greater exposure,making a causal relationship less likely. In addition, the association with intermediate
electric fields decreased somewhat after adjustment for previous mental disorders (2.8;0.93Ð8.1). According to the authors, mental illness could be either an intermediatevariable, if depression were caused by EMF, or a confounder, if psychological disorders
predispose workers toward jobs with high or low exposure to EMF. The hypothesis thatmental illness is an intermediate variable receives some support from the finding of adecrease in suicide risk after adjustment for mental disorders. Support for the hypothesisthat it is a confounder is provided by the finding that 70.2% of the 20 cohort memberswith absences for mental illness had had geometric mean exposure to electric fields above
the 50th percentile. The authors noted that their study did not have the complex designneeded to distinguish a confounding from an intermediate variable.[For former employeesof Hydro QuŽbec, minor errors may have been introduced owing to lack of information on
suicides occurring outside the Province. Data on confounders of suicide, such as alcoholuse, are difficult to obtain accurately from company records. Moreover, the analysis of 10
exposure measures may have generated associations by chance.].
Johansen and Olsen (Johansen & Olsen, 1998) also examined suicides and exposure tomagnetic fields in the cohort study described in section 4.2.1.2. A slight nonsignificant
increase in the relative risk for suicide (OR = 1.4) was reported for exposure to TWA
magnetic fields estimated to be > 1.0 mT.
4.5.1.4 Cardiovascular disease
For a cohort of Hydro QuŽbec workers included by ThŽriault et al. (see section 4.2.1.1)(ThŽriault et al., 1994), Baris et al. (Baris et al., 1996b) reported a significant decrease in
the SMR for death reported on death certificates as due to Ôcirculatory diseasesÕ among
workers exposed to > 1.6 mT when compared with workers with lower exposure (basedon 217 deaths). [The grouping Ôcirculatory diseaseÕ might be too broad, and the 1.6 mT
cut-point might not include groups with sufficiently high exposure.]
Savitz et al. (Savitz et al., 1998c) reported the results of an analysis of mortality from
specific types of cardiovascular disease in their study of five utilities (Savitz & Loomis,
1995) (described in section 4.2.1.1) in relation to exposure to magnetic fields. The
investigation was motivated by clinical findings that suggested a decrease in heart ratevariability in people exposed to 20 mT 60 Hz magnetic fields. Various categories of causes283

of death from heart disease, based on the International Classification of Diseases, werecombined into four groupings: arrhythmia-related ( 212 deaths), acute myocardial infarct(4238 deaths), atherosclerosis (142 deaths), and chronic coronary heart disease (2210
deaths). These causes accounted for 88% of all cardiovascular deaths identified in thecohort. The groupings were chosen a priori because the underlying pathological lesions of
the first two potentially involve disruption of autonomic nervous system control ofcardiac function, whereas loss of autonomic nervous system control is not believed to be
critical for the second pair. The exposure of a random sample of workers in 28
occupational categories was measured over 2842 full shifts with an AMEX 3D meter. In
all of the analyses, adjustment was made for age, calendar year, race, social class, andwork status (active versus inactive).
As predicted, no association was found between total exposure to magnetic fields and therisk for atherosclerosis or chronic coronary heart disease (see Table 4.40). The relative
risks for myocardial infarct were consistently and statistically significantly increased ineach category of total exposure: 1.1 (1.0Ð1.3) for cumulative exposure of 0.4£ 1.2 mTyears, 1.2 (1.1Ð1.3) for 1.2£ 2.0 mT-years, 1.4 (1.2Ð1.5) for 2.0 £ 4.3 mT-years, and 1.6(1.5Ð1.8) for 3 4.3 mT-years. Significant increases were also seen for each category of
exposure more than 5, 10, and 20 years previously, while significant decreases were seenfor people in the highest exposure categories during the previous five years. In addition,
the increased relative risks showed a statistically significant doseÐresponse trend.
Arrhythmia-related diseases were related similarly but less consistently to cumulative
exposure. Although no direct information on known risk factors was available, the authors
argued that it is unlikely that smoking and other lifestyle factors were important
confounders, since no association was seen between exposure to magnetic fields and deathfrom atherosclerosis or coronary heart disease. [The analysis of death from cardiovasculardisease was an addition to the existing cohort study of cancer, and death certificates wereused for the diagnosis of cardiovascular disease. See section 4.1.1.1 for comments on thelimitations of the study. It is unclear why significant decreases in risk were observed for
myocardial infarct and arrhythmia-related diseases after exposure during the five-year
period prior to death, while significant increases were consistently found for exposure at
the other times considered.]
4.5.1.5 Summary
Adverse reproductive effects from mother's exposure to EMF
The relationship between spontaneous abortion and exposure to ELF EMF was
considered in two studies. In the first (Schnorr et al., 1991), no association with VDT use
was observed; however, ÔexposedÕ and ÔunexposedÕ subjects had similar levels of
exposure to ELF fields but different levels of exposure to VLF fields. In the second study,
a significant association was seen with exposure to high magnetic and VLF fields;
however, the response rate was very poor, particularly among controls.

284

The association with low birthweight was assessed in two studies (Bracken et al., 1995a;
Grajewski et al., 1997), which found no association with either use of VDTs or exposure
to magnetic fields.
Intrauterine growth retardation was considered by Bracken et al., who found noassociation with either use of VDTs or exposure to magnetic fields.
One study addressed the association between preterm birth and use of VDTs (Grajewski
et al., 1997). No association was found.
Adverse reproductive effects from the father's exposure to EMF
The effect of paternal exposures to EMF on the frequency of congenital anomalies wasconsidered in one study (Tornqvist, 1998). No increase was seen among the offspring of
exposed male workers.
Alzheimer disease
The association between exposure to EMF and Alzheimer disease was considered in fivestudies. Two of these (Savitz et al., 1998a; Savitz et al., 1998b) are given little weight in
the evaluation as they are based on diagnoses from death certificates. In one (Savitz et al.,1998b), no increase in risk was seen for all electrical workers. In the other four studies,risk was considered by intensity of exposure to magnetic fields. Significant associations
with intermediate and high intensity magnetic fields were seen in both studies of Sobel etal. (Sobel & Davanipour, 1996; Sobel et al., 1995) in specific groups of subjects. The
limitations of these studies include the fact that different groups of cases and controls
were used, some of the control groups including persons with other types of dementia;
and proxy information was used to define the exposure of cases. Feychting et al.
(Feychting et al., 1998) found a nonsignificantly increased risk for occupational exposure
to TWA magnetic fields > 0.2 mT. This study, which was based on data for twins, also
suffered from a number of limitations. A nonsignificant increase was seen with exposure
throughout a working career in the study of Savitz et al. (Savitz et al., 1998a), which was
based on diagnoses reported on death certificates.
Feychting et al. (Feychting et al., 1998) also considered a possible association with alldementia, including Alzheimer disease, and found a significant association with exposure
to TWA magnetic fields > 0.2 mT. As mentioned above, this study has limitations and theresults are therefore difficult to interpret.
Amyotrophic lateral sclerosis
The association between exposure to magnetic fields and amyotrophic lateral sclerosis(ALS) was assessed in three studies. Adequate adjustment could not be made for285

confounding by exposure to electric shocks or a family history of ALS. The study ofDavanipour et al. (Davanipour et al., 1997) showed an increased risk for workers with thehighest exposure, which was significant for those with 20 yearsÕ or more experience. The
study had a limited sample size and potential control selection bias. A nonsignificant
increase in the mortality rate from ALS was also seen by Johansen and Olsen (Johansen,
1998), based on a very small number of exposed cases. In the mortality study of Savitz etal. (Savitz et al., 1998a), no increase in risk was seen with career exposure, while anonsignificant increase in risk was seen with exposure 20 years previously. The study
was based on diagnoses from death certificates and did not account for potential
confounders.
Suicide and depression
One study addressed the risk for depression among electrical workers in a cohort of Viet
Nam veterans. A nonsignificantly increased risk was observed for only one of the 24
measures of depression used. Given the small number of cases and the many outcomesanalyzed in the study, the finding may be due to chance.
The risk for suicide was considered in two studies. No significant association with
exposure to EMF was seen by Johansen and Olsen (Johansen, 1998), while an increased
risk was seen with only one of 10 measures of exposure by Baris et al. (Baris et al.,1996a).
Cardiovascular disease
Two studies have assessed possible adverse cardiovascular outcomes that may result
from exposure to magnetic fields. In the first study (Baris et al., 1996a), a significant
decrease in risk in a broadly defined cardiovascular grouping was observed; however, thestudy had severe limitations.
Savitz et al. (Savitz et al., 1998c) examined data from their study of five utilities,
motivated a priori by a biological hypothesis based on clinical data and the results ofhuman studies in vivo, which predicted increased numbers of deaths due to arrhythmia
and acute myocardial infarct but no increase in risk for arteriosclerosis and chronic
coronary heart disease. Significant, exposure-dependent associations were reported.
Although no direct information on potential confounder was available, the authors
provided indirect justification that smoking and life-style factors are unlikely to strongly
confound the observed association.
Evaluation
There is inadequate evidence that maternal occupational exposure to ELF EMF causes
adverse birth outcomes.

286

[This conclusion was supported by 22 Working Group members; there were 2 votes forÔlackÕ of evidence, 1 abstention, and 4 absent.]
There is inadequate evidence that paternal occupational exposure to ELF EMF causes
reproductive effects.
[This conclusion was supported by 20 Working Group members; there were 3 votes forÔlackÕ of evidence, 2 abstentions, and 4 absent.]
There is inadequate evidence that occupational exposure to ELF EMF causes Alzheimer
disease.
[This conclusion was supported by 23 Working Group members; there was 1 vote forÔlackÕ of evidence, 1 abstention, and 4 absent.]
There is inadequate evidence that occupational exposure to ELF EMF causes
amyotrophic lateral sclerosis.
[This conclusion was supported by 24 Working Group members; there was 1 abstention
and 4 absent.]
There is inadequate evidence that occupational exposure to ELF EMF causes suicide or
depression.
[This conclusion was supported by 17 Working Group members; there were 6 votes forÔlackÕ of evidence, 2 abstentions, and 4 absent.]
There is inadequate evidence that occupational exposure to ELF EMF causes
cardiovascular disease.
[This conclusion was supported by 24 Working Group members; there was 1 abstention
and 4 absent.]

4.5.2 Environmental exposure
4.5.2.1 Pregnancy outcome
Wertheimer and Leeper (Wertheimer & Leeper, 1986) investigated the relationshipbetween use of electrically heated water-beds and electric blankets and pregnancy
outcomeÑspecifically, length of gestation, birth weight, congenital abnormalities, andfetal lossÑ in Colorado, USA. The study population consisted of the 1806 (out of 4271)

287

families in which a birth had occurred in two Denver-area hospitals in 1982, for which abirth announcement had been published. Of these, 1318 (73%) could be reached by
telephone for an interview on their use of electrically heated water-beds and electricblankets in the previous eight years. Information was successfully obtained on 1256
births (95% response rate). The Colorado birth records were consulted to obtain moredetailed information on these births and on 528 of the 692 other births that had occurred
to the same parents from 1976 onwards. The data available from these records included
parentsÕ age and education, birth weight, mothersÕ last menstrual period, parity, reported
abnormalities of pregnancy, labor, or fetal development, and date of most recent fetal loss,
if any (this included both spontaneous and induced abortions).
Seasonal patterns of occurrence of slow fetal development were observed among users ofelectric waterbeds and blankets, suggesting that use of these appliances at the time ofconception might have had an adverse effect. The proportion of above-median gestational
periods was significantly greater for conceptions in SeptemberÐJune than for those inJulyÐAugust (56% vs. 38%, p < 0.0005) and was shown to follow a marked seasonalpattern among users, being high for babies conceived in winter and low in summer; theproportion was approximately constant at about 58% in the period OctoberÐApril anddecreased regularly down to around 40% during MayÐSeptember [data presented only ingraphical form]. No seasonal pattern was observed among non-users of electric blankets
and water-beds. The prevalence of birth weight < 2500 g was similar in users and nonusers (4.5 and 4.1%, respectively). Owing to a tendency not to announce the births ofbabies with congenital malformations, these were analyzed only among the 528 siblingbirths. One of 335 births among non-users (0.3%) and five of 193 among users (2.6%) hadcongenital defects. The frequency of abortions during the year preceding conception of alive infant was significantly higher (p < 0.05) among electric blanket users (7.8%; 24
cases)Ñbut not among water-bed users (6.3%; 28 cases)Ñthan among those who had
used neither electric blankets nor water-beds (4.2%; 50 cases). A significant excess ofabortions in SeptemberÐJanuary was noted among users of electric blankets and waterbeds. [The ascertainment of pregnancy outcome may have been biased by the fact that the
study population was defined on the basis of publication of birth announcements (only
42% of all births at the hospital) and that the sample was further restricted to those who
could be located by telephone, who were presumably of higher socioeconomic status than
the general population. Further, although efforts were made to exclude induced abortions
by studying fetal loss in the year before conception of a live infant, some induced
abortions were probably still included; the frequency of these is likely to have varied withsocioeconomic status, as does the frequency of use of electric blankets and water-beds. It
is also unclear whether the ascertainment of spontaneous fetal loss is complete from birth
records. Finally, only recognized fetal losses followed by a live birth are included.]
A population-based caseÐcontrol study of congenital malformations among children bornin the 57 counties in upstate New York and registered in the New York State Congenital
Malformation Registry was carried out by Dlugosz et al. (Dlugosz et al., 1992). The
cases were 224 neural tube defects and oral cleft defects (121 cleft palates and 197 cleftlips) diagnosed among children in 1983Ð84 and 224 neural tube defects diagnosed in288

1983Ð86. Three controls were randomly selected from birth registration records for eachcase and individually matched by maternal race, age, home county, month of motherÕs last
menstrual period, and childÕs gender. Maternal exposure to heated water-beds or electricalblankets one month before to three months after conception was assessed from responses
to a questionnaire mailed or administered by telephone. Information on maternal
education, prenatal vitamin intake, parity, smoking, high fever during pregnancy, andoccupation was also requested. The response rates were 83% for the cases and 77%
among controls. No association was found, with or without adjustment for other risk
factors, for various measures of exposure to EMF. For use of electric blankets at any time
during pregnancy, the adjusted odds ratios were 0.69 (95% CI, 0.25Ð1.9) for cleft palate,
0.70 (0.36Ð1.4) for cleft lip, and 0.77 (0.40Ð1.5) for neural tube defects. For use ofwaterbeds at any time during pregnancy, the corresponding odds ratios were 0.66 (0.23Ð
1.9), 0.63 (0.33Ð1.2), and 1.1 (0.59Ð1.9). No association was seen when different levels of
exposures were considered, such as duration of use and heat-control setting. No seasonalpattern of time of conception was observed. [No information was available on patterns ofuse, such as continual use throughout the night, and other sources of exposure were notcollected.]
The association between loss in early pregnancy and domestic exposure to ELF EMF wasinvestigated in a caseÐcontrol study in Finland (Juutilainen et al., 1993). The study wasnested within a cohort study of work and fertility in 443 healthy volunteer women who
were trying to become pregnant over the period 1984Ð86. Each woman in the cohort was
followed-up for six months or until she became pregnant. Pregnancy and loss in earlypregnancy (defined as pregnancies that ended before they became clinically apparent)
were detected by measuring serum human chorionic gonadotropin on the first day of
menstruation. All 107 women in this cohort whose first pregnancy resulted in an earlyloss were sought for inclusion in the study, with a random sample of 122 women withnormal pregnancies from the cohort. After exclusion of cases and controls for whom
information on exposure to EMF could not be obtained (refusals, address not found or
incomplete), 89 cases and 102 controls remained for analysis. Magnetic field intensity
was measured in the residences of the women at the time they participated in the study ofwork and fertility. Measurements were made at the front door of each residence and, for
48% of case and 57% of control residences, in the living-room, the kitchen, and theparentsÕ bedroom, with a self-constructed magnetic field meter with a small ferrite-coremeasuring coil similar to that used by Juutilainen and Saali (Juutilainen & Saali, 1986b).
Occupational exposure to EMF was assessed on the basis of job classification and somemeasurements. Odds ratios were calculated by the Mantel-Haenszel procedure, withadjustment for motherÕs smoking, age, and type of dwelling; separate analyses werecarried out for front-door measurements, average magnetic field in the home, andmaximum field. When the analyses were based on exposure in three categories, elevatedodds ratios were observed for the highest group versus the lowest: front door, > 0.126 mTvs. < 0.63 mT (OR = 5.1; 95% CI, 1.0Ð26); average field strength, ³ 0.252 mT vs. < 0.63mT A/m (4.6; 0.9Ð25); maximum field, ³ 0.63 mT vs. < 0.126 mT (2.7; 0.6Ð12), butintermediate groups did not have a higher risk than baseline. For dichotomous exposure
classification, only average magnetic field strengths was associated with loss in earlypregnancy (5.4; 1.1Ð28 for ³ 0.252 vs. < 0.252 mT) The authors concluded that their289

results suggest a causal association, possibly with a non-linear doseÐresponse
relationship. [Measurements inside houses were available for only a small proportion ofsubjects.]
Bracken et al. (Bracken et al., 1995a) carried out a prospective study of pregnancy
outcome in 3591 pregnant women living in the New Haven, Connecticut, area andreceiving prenatal care from 11 private obstetrical practices and two health maintenanceorganizations in the period 1988Ð91. The outcomes considered were intrauterine growth
retardation (being in the lowest tenth percentile of birth weight for each week ofgestational age), low birth-weight prevalence, birth weight, and gestational age.
Information on pregnancy outcome was obtained from the records of the health facilities.
Women were asked in a questionnaire interview to provide information on their frequency
and duration of use of electric blankets and water-beds and also on the type andtemperature setting. Electric-blanket field strength was estimated in temperaturecontrolled chambers on the basis of data about several blankets at selected chamber
temperatures and blanket settings. Other information collected during the interview
included age, race, marital status, education, religion, medical history, contraceptive use,smoking, job title, drug use, alcohol and caffeine consumption, and exercise. The
participation rate was 82.6%: thus, information was available on 2967 women.
A nested study design was used to monitor exposure at various stages of pregnancy byboth direct and indirect methods. Women who reported use of electrically heated beds anda random sample of non-users were placed in an intensively monitored group for
subsequent monitoring at approximately 20 (446 women), 28 (431 women), or 36 (427
women) weeks of gestation. The entire monitoring protocol was completed by 307, 281,
and 261 women, respectively (compliance was higher among electric bed users thanamong non-users: 70.8 vs. 62.7%). The monitoring program included seven-day personal
exposure assessment with AMEX-2 personal monitors; 24-h measurements of EMF in
the center of a room [not otherwise specified] with EMDEX meters; duty cycle
measurements of water-beds (i.e. proportion of time the bedÕs heating elements were
switched on); and wire coding of residences (up to four for women with more than one
residence). The wire coding was evaluated by the approach of Wertheimer and Leeper;
however, as the thickness of the wires could not be assessed because of insulation, electricutility company circuit maps were consulted to determine actual wire gauges.
None of the measures of exposure was significantly associated with any of the adverse
outcomes considered. There was no suggestion of an effect of use or heat setting ofelectrically heated beds at the time of conception or during the first four or the last threemonths of pregnancy on birth weight, low birth-weight rate (< 2500 g), or intrauterine
growth retardation. The results were similar with use of wire codes and of directly
measured exposures in the monitored sub-sample.
Belanger et al. (Belanger et al., 1998) reported on the 135 spontaneous abortions that
occurred in the same cohort between 7 and 25 weeks. No significant association was
found between the incidence of spontaneous abortion and any measure of exposure to290

EMF. For blanket use at the time of conception, the odds ratio, adjusted for ethnicity,
gestational age at interview, maternal age, and caffeine consumption, was 1.7 (95% CI,
0.96Ð3.2); no association, however, was seen for daily rather than less frequent use.
Logistic regression analyses for duration of exposure (hours of use per day) and intensityof exposure showed a slight increase in the risk for spontaneous abortion with increasing
duration and intensity of use. The small numbers of exposed cases, however, precluded aconclusive interpretation of these results. The odds ratio for water-bed use was 0.59
(95% CI, 0.33-1.1); no association was found with frequency, duration, or intensity ofuse. Although strong associations were observed with several other risk factors such as
intrauterine growth retardation and marital status, ethnicity, education, reproductive
history, and smoking, these did not have a confounding effect. [Assertainment of loss inearly pregnancy was not complete, as only 14% of the cohort was interviewed before 10
weeks of gestation. Spontaneous abortion was assessed by interview.]
Li et al. (Li et al., 1995) studied electric blanket use during pregnancy in relation to therisk for congenital urinary tract anomalies in a caseÐcontrol study in Washington State,USA. The cases were identified from the Washington State Birth Defects Registry overthe period 1990Ð91, and 118 cases with no chromosomal abnormalities and 369 controls,consisting of births randomly selected from all single live infants delivered in fivehospitals of King County in the study period, were included. Questionnaire interviews
were completed with 62.6% of the case mothers and 67.6% of control mothers.
Information was collected on history of reproduction, contraceptive use, smoking, alcohol
consumption, and other substances [not specified]. The hypothesis was that any effecton fetal development of exposure to EMF during pregnancy might be more pronounced insusceptible subpopulations, such as women with a history of subfertility.
No association was observed between the incidence of congenital urinary tract anomalies
and use of water-beds or blankets during the entire pregnancy or the first trimester.
Elevated risks associated with electric blanket use were found among subfertile women,
although this finding was based on few exposed cases (OR = 4.4; 95% CI, 0.9Ð22; 5 cases
during the entire pregnancy; OR = 10; 95% CI, 1.2Ð85; 3 cases during the first trimester).
The risk also appeared to increase with increasing duration of use of electric blankets. No
association was found with use of water-beds or VDTs during the entire pregnancy or the
first trimester. Recall bias might have influenced the results owing to media attention, but
the association was observed only in subfertile women. No information on other sourcesof exposure to EMF was available. The authors hypothesized that hormonal disturbances
caused by EMF (estrogen and progestogen production is affected by melatonin) could
explain the findings. [The definition of subfertility as no pregnancy after unprotectedintercourse for a year is inadequate, and applied to 23% of the study population. The
finding in ÔsubfertileÕ women is hypothesis generating.]291

4.5.2.2 Neurodegenerative diseases and neurobiological disorders
No studies have addressed residential exposure to EMF and the risk for neurodegenerative
diseases. In two studies Ôelectric shockÕ was mentioned as a risk factor for ALS (Gallagher& Sanders, 1987; Savettieri et al., 1991).
4.5.2.3 Summary
Pregnancy outcome
The risk for congenital anomalies in relation to use of heated water-beds and electricblankets by the mother around the time of conception was evaluated in one study in theUSA, in which no association was observed.
Pregnancy loss was investigated in two cohort studies. Early pregnancy loss was studied
in one study in Finland, in which an increased risk was observed in the highest but not theintermediate category of exposure to magnetic fields. Pregnancy loss toward the end of
the first trimester or later was studied in the USA; an elevated risk was found amongusers of electric blankets but not among users of water-beds.
In the same study in the USA, intrauterine growth retardation was assessed in a cohort ofpregnant women. No association with residential exposure to EMF was found on thebasis of a variety of measures, including use of electric blankets or water-beds and wire
coding.
Depression
Two studies have addressed depression in relation to exposure to EMF from transmission
lines. In the study in the USA, depressive symptoms were not related to measures ofmagnetic fields taken at the door of the subjectÕs residence. In the Finnish study, an
increased risk for severe depression was observed among subjects with higher calculated
exposures. This observation was based, however, on only four cases with unconfirmed
diagnoses and relatively low exposures (³ 0.17 mT).
There is inadequate evidence that environmental exposure to ELF EMF has adverse
effects on pregnancy outcome or is associated with depression.
[This conclusion was support by 23 Working Group members; there was 1 vote for Ôno
evidenceÕ, 1 abstention, and 4 absent.]292

Table 4.36 Adverse pregnancy outcomes and maternal exposure to EMF
Reference;
country

Study population(Schnorr etal., 1991);
USA

From a cohort of telephone
operators, 2705 directory
assistance operators using
VDTs were compared with
2839 general operators using
light-emitting diode or neonglow tube units.

VDT use > 25 h/week
in first trimester
in first 28 weeks

Spontaneous abortion169
1.0 (0.6-1.6)
179
0.9 (0.6-1.5)

OR adjusted for smoking, thyroid disorders, alcohol
consumption, and previous spontaneous abortions.
EMF measured on a sample of VDTs and othermonitors.

(Lindbohm etal., 1992);
Finland

Cohort of women 20-35
weeks of age in various
Finnish companies, mainlybanking and clerical work.
Pregnancy information fromnationwide database. 191
spontaneous abortions
treated in hospitals. 394
controls were mothers ofnormal children matched foryear of conception.

ELF magnetic field from VDT
0.11-0.24 mT rmsa
> 0.24 mT rms
Cumulative ELF fields per
week medium
high
VLF magnetic field from VDT5-30 mT/s> 30 mT/s
Cumulative VLF fields per
week medium
highSpontaneous abortion
19
1.9 (0.9-3.9)
20
3.4 (1.4-8.6)

OR adjusted for h/week of VDT use, work load,
solvent exposure, number of previous births,
previous spontaneous abortions, IUD use, andfrequency of ADP equipment breakdowns.

Women receiving care at 13
New Haven area obstetrics
practices and HMOs. About
2550 women in the study (notall women completed allquestions) and 1304 weremonitored for EMF exposure.

VDT use< 20 h³ 20 h
TWA magnetic field per week
0.1-0.19 mT³ 0.2 mTLow birth weight835
0.5 (0.3-0.8)424
0.6 (0.3-1.1)(Bracken etal., 1995a);
Connecticut(USA)

Exposure classification

No. OR (95% CI)

Comments

of cases

VDT use< 20 h³ 20 h
TWA magnetic field per week
0.1-0.19 mT³ 0.2 mT

293

17
22

1.7 (0.8-3.6)
3.8 (1.6-8.8)

725

0.8 (0.3-2.4)
1.6 (0.8-3.4)

29
21

1.2 (0.6-2.4)
2.7 (1.2-6.1)

122
0.7 (0.2-2.9)
58
1.4 (0.3-6.1)
Intrauterine growth
retardation
835
0.9 (0.6-1.3)424
1.2 (0.8-1.8)
122
58

0.4 (0.1-1.2)
1.2 (0.4-3.1)

Magnetic field exposure measured in lab on VDTmodels reportedly used by subjects.
To convert the peak-to-peak magnitudes for ELF
fields to root-mean-square (rms) magnitudes, aconversion factor = 0.266 was derived from VDTmeasurements reported by Jokela et al. (Jokela et al.,1989).
OR adjusted for maternal religion, race, height,
gravidity, age work in pregnancy, third trimester
smoking, and caffeine consumption. Primary interest
was in exposure to electric bed heaters, but VDT use
determined by questionnaire. Women who reported
using electric bed heaters monitored with personal
AMEX meters.

Table 4.36 (continued)
Reference;
country

Study population(Grajewski etal., 1997);
Southeastern
US

Cohort of 284 marriedpregnant telephone operators
using VDTs and 363
unexposed operators serving
as controls (same as Schnorr
et. al., 1991)

Exposure classification

No. OR (95% CI)

Comments

of cases
Preterm births
240.7 (0.4-1.1)
Reduced birthweight303
0.9 (0.5-1.7)
116
0.4 (0.1-1.0)120
1.4 (0.7-3.1)

Any VDT exposure
VDT exposure
1-25 h/week³ 25 h/weeka

OR adjusted for race, parity, gravidity, alcohol,
smoking, gestational age, previous problem
pregnancies, diabetes, thyroid conditions, diuretics,
pre-eclampsia, toxemia, and intra-pregnancy interval.

OR, odds ratio; CI, confidence interval; VDT, visual display terminal; ELF, extremely low frequency; IUD, intrauterine device; ADP, automatic data processing; VLF, very low frequency; HMO,
health maintenance organization

294

Table 4.37 Alzheimer disease and dementia in association with exposure to EMF
Reference;
type of study;
country

Study population(Sobel et al.,1995);
case-control;
Finland andCalifornia(USA)

Two case series with sporadic
Alzheimer disease, i.e. nocases in family (n=53 and136), and one series withboth sporadic and familial
forms of the disease (n=198).
Controls had vasculardementia for one sporadic
disease series (n=70) or werenormal neighborhood
subjects for the other(n=299); the series with bothforms of Alzheimer disease
had hospital controls withno neurological symptoms(n=106).

Exposure classification

No. of RR (95% CI)
cases

Comments

Medium / high magnetic
fieldsSporadic Alzheimer
diseaseControls with vasculardementia
1
0.7 (0.1-8.9)
5
10.2 (1.1-95.3)
normal neighborhood
controls
5
1.7 (0.3-10.3)6
3.7 (0.4-33.6)
All Alzheimer disease
Hospital controls
without dementia
7
2.7 (0.7-9.8)
12
3.5 (1.3-9.6)
All risks combined36
2.9 (1.6-5.4)

OR adjusted for age at onset, education, and social
class. Exposures estimated by industrial hygienist
for the reported primary occupation.

All Alzheimer disease
controls with nonvascular dementia
15
4.9 (1.3-7.9)
24
3.4 (0.8-16.0)39
3.9 (1.5-10.6)

OR adjusted for age of onset, education, and gender.
Exposure estimated by expert judgment fromoccupational history.

Dementia
control group 1
16
1.1 (0.4-2.6)
14
1.5 (0.6-4.0)

OR adjusted for age of onset, education. and birthdate. Exposure based on JEM constructed fromoccupational magnetic field measurements made1988-92.

16
1.6 (0.6-4.0)
19
3.3 (1.3-8.6)
AlzheimerÕs disease9
1.0 (0.4-2.9)
12
2.4 (0.8-6.9)

Results for control group 2 are similar, e.g. dementia
OR = 3.8 (1.4-10.2) for last jobÕs TWA > 0.2 mT.

Males
Females
Males
Females

Males
Females
Both sexes(Sobel et al.,1996);
Case-control;
California(USA)

326 clinic-based Alzheimer
disease patients. 152
controls were cognitively
impaired patients at the same
clinic (excluding vasculardementia).

Medium / high magnetic
fields(Feychting etal., 1998);
Case-control;
Sweden77 dementia cases (including
55 with Alzheimer disease)
identified in Swedish twin
study. Controls use twins
without dementia. 2 control
groups (228 and 238
subjects) formed to keep only
one member of a twin pair ineach group

TWA magnetic fields
Primary occupation
0.12-0.19 mT> 0.2 mT
Last occupation
0.12-0.19 mT> 0.2 mT
Last occupation
0.12-0.19 mT> 0.2 mT

Males
Females
Both sexes

295First series had 90% agreement between clinicaland autopsy diagnosis, and the second series had
98% agreement. The third series involved an older
diagnosis scheme and had 82% agreement.

Table 4.37 (continued)
Reference;
type of study;
country

Study population

Exposure classification

No. of RR (95% CI)
cases(Johansen &Olsen, 1998);
Cohort study;
Denmark

Cohort of male employees of
99 Danish utility companies,
21236 total, 3540 deaths

TWA magnetic fields
low exposure
0.1-0.25 mT
medium0.3-9.99 mT
high> 1.0 mT

Senile dementia
1
0.4 (NS)2
0.8 (NS)1
0.6 (NS)

SMR adjusted for age, education, and birth date.
Magnetic fields in subjectÕs first job from a JEM
based on expert judgment and 24-h measurements.

(Savitz et al.,1998a);
Cohort;USA

138905 men employed in 5
electric utilities followed for
mortality 1950-86. 20068
deaths; 24 deaths for which
Alzheimer disease wasmentioned as an underlying
cause of death and 56 forwhich it was mentioned as
cause of death.

Alzheimer disease
Underlying cause ofdeath
9
2.0 (0.6-7.0)

SMR adjusted for age, decade of death, race, class,retirement status, and solvent exposure. Magnetic
field exposure based on company job records and
JEM from full-shift measurements (Savitz et al.
1995).

(Savitz et al.,1998b);
Cohort;USA

National Center for Health
Statistics database of 25
states; 1931379 male deaths;
256 Alzheimer disease deaths.
Schulte et al. (1996) analyzed
AlzheimerÕs disease risks byoccupation with the same
database.

Cumulative magnetic fields
Total career exposure
Highest category(2-4.7 mT-year)
Exposure-response(RR / mT-year)
Exposure ³ 20+ year in pasthighest category(2.3-14.5 mT-year)
Exposure-response(RR / mT-year)
Electrical workers
All< 65 years³ 65 years

24

1.1 (0.9-1.2)

8

2.7 (0.8-8.9)

24

1.1 (0.9-1.3)

Alzheimer disease256
1.2 (1.0-1.4)
10
0.9 (0.5-1.7)
246
1.2 (1.1-1.4)

Comments

MOR adjusted for age, year of death, social class,and race. Exposure is work in an electricaloccupation as reported on death certificate.

NS, non-significant; RR, relative risk; CI, confidence interval; OR, odds ratio; TWA, time-weighted average; JEM, job-exposure matrix; SMR, standardized mortality ratio; MOR, mortality odds
ratio

296

Table 4.38 Amyotrophic lateral sclerosis in association with exposure to EMF
Reference;
type of study;
country

Study population(Deapen &Henderson,1986);
case-control;USA

678 cases of ALS, selfselected by responding toquestionnaire. Cases asked tonominate candidate controlsof same gender and age. 518
controls selected.

(Davanipour etal., 1997);
case-control;
California(USA)

28 clinic-based ALS patients.
32 controls were genetic
relatives (17) and non-blood
relatives (15) of cases, of samegender and similar age as
case.

Exposure classification

No. of RR (95% CI)
cases

Comments

Univariate analyses
19
3.8 (1.4-13.0)
142.8 (1.0-9.9)

OR
Exposure category based on self-reported work
experience

Electrical occupations
Electric shock

Bivariate re-analysis
3.5(1.3-9.5)
2.4(0.9-6.8)

Bivariate re-analysis based on report that 3 cases
and 0 controls were exposed to both factors

Cumulative magnetic fields> 75th percentile
OR per unit exposure

All subjects
NR
2.5 (0.9-8.1)
28
1.0 (1.0-1.0)

OR calculated by logistic regression, Exposure
scores calculated from occupational history andmagnetic fields estimated by industrial hygienist.

> 75th percentile
OR per unit exposure

Subjects with ³ 20 years
workNR
7.5 (1.4-38.1)20
1.0 (1.0-1.0)4
54
9Electrical occupations
Electric shock resulting in
unconsciousness(Johansen &Olsen, 1998);
Cohort;Denmark

Male employees of 99 Danish
utility companies, 21236
total, 3540 deaths

TWA magnetic fields
Low exposure, 0.1-0.25 mT
Medium , 0.3-9.99 mT
High, > 1.0 mT
High + medium > 0.3 mT(Savitz et al.,1998a);
cohort;USA

138 905 men employed for > 6
mo. in 5 electric utilities
followed for mortality from
1950-86. 20068 deaths, 33
deaths in which ALS was
mentioned as cause of death.

Cumulative magnetic fields
Total career exposure
Highest category(1.1-15.4 mT-year)
Exposure-response(RR / mT-year)
Exposures ³ 20 year
previously
Highest category(2.0-14.5 mT-year)
Exposure-response(RR / mT-year)297

1.9 (NS)
2.3 (NS)
2.8 (NS)
2.5 (1.1-4.8)

Mentioned cause of death16

1.2 (0.5-3.0)

33

1.0 (0.9-1.2)

5

2.4 (0.7-8.0)

33

1.1 (0.9-1.3)

SMR adjusted for age, education, and birth date.
Magnetic field exposures from a JEM based on
expert judgment and 24-h measurements. SMR forelectrical accidents = 31 (p < 0.05) for fields > 1.0 m
T.
SMR adjusted for age, decade of death, race, social
class, retirement status, and solvent exposure.
Cumulative magnetic field exposure based on job
history in company records and JEM from 2842 fullshift measurements (Savitz et al. 1995).

Table 4.38 (continued)
Reference;
type of study;
country

Study population(Savitz et al.,1998b);
cohort;USA

National Center for Health
Statistics database of 25
states; 1931379 male deaths;
114 ALS deaths

Exposure classification

Electrical workers
All ages< 65 year old³ 65 year

No. of RR (95% CI)
cases

114
56
58

1.3 (1.1-1.6)
1.4 (1.0-1.9)
1.2 (0.9-1.6)

Comments

MOR adjusted for age, year of death, social class,and race. Work in electrical occupation as reported
on death certificate.

RR, relative risk; CI, confidence interval; ALS, amyotrophic lateral sclerosis; OR, odds ratio; NR, not reported; TWA, time-weighted average; NC, not significant; SMR, standardized mortality
ratio; JEM, job-exposure matrix; MOR, mortality odds ratio

298

Table 4.39 Suicide and depression in association with exposure to EMF
Reference;
type of study;
country

Study Population(Savitz et al.,1994);
cohort;USA

In the Vietnam Experience
Study, a cohort of 4044 male
US Army veterans was givena personal health exam,including the diagnostic
interview survey and theMinnesota multiphasic
personality inventory fromwhich depression was
diagnosed and its symptoms
were determined.

(Baris et al.,1996a);
Case-cohort;
Quebec(Canada)Cohort of 21744 maleelectrical utility workers at
Hydro Quebec from ThŽriault
et al. (1994). Deaths weretraced through records of thecompany, its pension fund,and death certificates.

Exposure Classification

Electrical occupations
Electricians
Electrical occupations
Electricians
Electrical occupations
Electricians
Cumulative exposures
ELF electric fields (GM)
23.1-40.3 V/m ×per year
> 40.3 V/m ×per year
ELF magnetic fields (GM)
1.25-2.08 mT-×years>2.08 mT-×years
High-frequency pulsed EMF
1.1-6.4 man-weeks and> 100 ppb
> 6.4 man-weeks and> 100 ppb

(Johansen &Olsen, 1998);
cohort;Denmark

Male employees of 99 Danish
utility companies, 21236
total.

TWA magnetic fields
Low exposure, 0.1-0.25 mT
Medium, 0.3-9.99 mT
High, > 1.0 mT

No. of RR (95% CI)
cases

Comments

Diagnosis of depression (lastmonth)
5
1.7 (0.7-4.3)
3
2.5 (0.8-7.5)
Thoughts of death6
0.8 (0.3-1.8)
3
1.1 (0.4-3.4)
Obvious depression20
1.2 (0.8-2.0)
11
1.9 (1.1-3.3)

OR adjusted for race, marital status, education,
duration of employment, and alcohol use.
Exposure determined from current job at time ofpsychological testing. Most indicators ofdepression were not elevated.

SuicideRR adjusted for socioeconomic status, alcoholuse, and marital status. Cumulative exposure
based on job history plus JEMs from 2066
work-week EMF measurements. TWA(arithmetic mean) electric and magnetic fields
were the a priori metrics, but only the GM
electric fields were significant.

20
13

3.1 (1.2-8.2)
2.2 (0.6-7.8)

14
11

1.3 (0.5-3.1)
1.9 (0.3-2.5)

10

1.1 (0.2-5.8)

19

1.2 (0.3-5.7)

Suicide37
0.8 (NS)41
0.9 (NS)36
1.4 (NS)

SMR adjusted for age, education, and birth date.
Magnetic field exposures for subjectÕs first job
taken from a JEM based on expert judgment and
24-hr measurements.

RR, relative risk; CI, confidence interval; OR, odds ratio; ELF, extremely low frequency; GM, geometric mean; JEM, job-exposure matrix; TWQ, time-weighted average; NS, not significant; SMR,
standardized mortality ratio299

Table 4.40 Mortality from cardiovascular disease in relation to exposure to magnetic fields (Savitz et al., 1998c)
Arrhythmia-related
Exposure level(percentiles)

No. ofcases

RR

95% CI0 £ 0.6
0.6 £ 1.2
1.2 £ 2.0
2.0 < 4.3
4.3+
RR per mT-year

47
49
42
40
34
212

1.0
1.6
1.3
1.2
2.4
1.1

1.0-2.4
0.8-2.0
0.8-2.0
1.5-3.9
1.0-1.1

Acute myocardial infarct
No. ofcases

RR

95% CI

1031
852
899
946
510
4238

1.0
1.1
1.2
1.4
1.6
1.0

1.0-1.3
1.1-1.3
1.2-1.5
1.5-1.8
1.0-1.1

300

Atherosclerosis
No. ofcases

RR

95% CI

43
34
27
26
12
142

1.0
1.1
0.8
0.7
0.7
1.0

0.7-1.8
0.5-1.3
0.4-1.2
0.4-1.3
0.9-1.0

Chronic coronary heart disease
No. of
cases
664
422
452
441
241
2210

RR 95% CI
1.0
0.9
0.9
0.9
1.0
1.0

0.8-1.0
0.8-1.0
0.8-1.0
0.9-1.8
1.0-1.0

4.6

Laboratory studies of non-cancer health effects in humans
Health risks, particularly those associated with environmental factors, are often the resultof biological effects that accumulate over time and depend on dose. Thus, detailed
knowledge of effects is important in understanding risks. Biological effects and, to alimited extent, health effectsÑthose physiological changes that exceed normal ranges forbrief periodsÑcan be studied safely and effectively in the laboratory with humanvolunteers, although there are obvious limitations to the duration of exposure and thetypes of tests that can be performed. The focus in human studies is usually on effects
that occur within a time-frame of minutes, hours, days, or perhaps weeks; longer-term
studies in which exposure is adequately controlled are difficult, if not impossible, to carryout with human volunteers in a laboratory setting. The selection of physiologicalmechanisms to be studied is also limited to those that can be measured by non-invasive or
minimally invasive procedures.
Laboratory studies on humans have certain advantages. They focus directly on thespecies of main public interest, thus avoiding the problems of extrapolation from dataobtained in other species; furthermore, even negative results can be of immediate use inaddressing public concern. Such studies can also be used to directly evaluate the effects of
exposure on higher-order cognitive functions important in daily life, such as memory,
attention, and information processing, as well as their underlying electrophysiological andneurochemical substrates. Controlled laboratory testing with human volunteers can help
to define dose metrics and response categories for epidemiological studies, and can guideanimal research to areas in which more invasive mechanistic investigations might bevaluable. Like animal studies, human laboratory studies allow separate testing of theeffects of electric, magnetic, and combined fields to determine whether any effects found
are related to specific characteristics of the exposure situation or to their interactions.
The effects of experimental human exposure to EMF are derived from three major
research initiatives and from efforts in individual laboratories. These include a long seriesof studies of utility workers begun in the 1960s in the former USSR (Asanova & Rakov,
1966), the human laboratory research conducted in the 1970s in Germany (Hauf &Wiesinger, 1973; Silny, 1986), and the human laboratory research program started in 1982
at the Midwest Research Institute in the USA (Graham et al., 1990). Dedicated facilities
for human exposure testing have been designed and constructed in Australia (Wood et al.,1997), Canada (Blondin et al., 1996), England (Stollery, 1986), France (Selmaoui et al.,1996b), Germany (Hauf & Wiesinger, 1973), New Zealand (Podd et al., 1995), theRussian Federation (Lyskov et al., 1993b), and the USA (Cohen et al., 1992; Doynov etal., 1998). Research with human volunteers is currently under way in many of thesefacilities.

3014.6.1 Sensation and perception
The ability of humans to perceive EMF is of interest for several reasons. If such exposure
is considered to be a low-level environmental stressor (Bell et al., 1991), the reported
effects may be by-products of stress. Individual differences in field perception may also
be related to individual differences in sensitivity to other possible health-related effects of
exposure. Investigation of the biological mechanisms that subserve human perception canlead to a better understanding of how these fields affect the human organism.
4.6.1.1 Field perception
Humans can perceive power frequency, time-varying (AC), and static (DC) electric fields,
depending on field characteristics and other factors noted below. In contrast, there is little
evidence for human perception of power-frequency magnetic fields, until field intensities
well above ambient are encountered. Perception of AC electric fields can result from thealternating electric charge induced on the surface of body hairs; the charge causes the hairs
to vibrate, and the subjective sensation is usually one of itching or tingling. For otherpossible mechanisms, see section 4.4.3. Delaplace and Reilly (Delaplace & Reilly, 1978)
placed 122 men subjects directly under overhead transmission lines in various
environmental conditions; 90% of them could perceive a 20 kV/m 60 Hz electric field, andperception reached a self reported ÔannoyanceÕ threshold for 10%. A small percentage
reported perception at field strengths below 5 kV/m.
Graham and Cohen (Graham & Cohen, 1985) performed a laboratory-based study of theperception of 60 Hz electric fields (0Ð15 kV/m) and of magnetic fields (0Ð40 mT) by 10
men and 10 women aged 21Ð35. The men and women had similar sensitivity. The
threshold of 90% of the group was ³ 9 kV/m. Perception improved when the field onset
was abrupt and when the volunteer changed body position in the field. Perception of
initial field onset ceased after about 20 min of continuous exposure but was immediately
re-established by body movements within the field. No evidence was found forperception of magnetic field £ 40 mT, and the presence or absence of the magnetic field
did not influence perception of the electric field. These results replicate two earlier, wellcontrolled laboratory studies of perception of magnetic fields by human volunteers:
Schmitt and Tucker (Schmitt & Tucker, 1978) and Tucker and Schmitt (Tucker &Schmitt, 1978) tested the ability of 200 volunteers to perceive 60 Hz magnetic fields over
the range 0.7Ð1.5 mT and reported little evidence for perception.
4.6.1.2 Visual effects
Phosphenes are flickering visual sensations caused by non-photic stimulation such aspressure on the eyes and mechanical shocks. They are generated in the retina, not in the
optic nerve or the visual cortex (Lovsund et al., 1979). Volunteers can reliably experience
these sensations, now referred to as magnetophosphenes, during exposure to AC ELF

302

magnetic fields (Silny, 1986). Phosphenes can also be induced by direct application of
weak electric currents to the head. This is one of the few known and accepted
physiological effects of exposure to magnetic field in humans. The alternating magnetic
field induces electric fields which stimulate the visual receptors in the retina. The
threshold current density in the retina for induction of magnetophosphenes is estimatedto be about 10 mA/m2 at 20 Hz, a level well above typical endogenous current densities inelectrically excitable tissues.
The magnetophosphene phenomenon is also of interest in connection with the Ômelatonin
hypothesisÕ. Exposure to light at night is known to reduce circulating concentrations of
the pineal hormone melatonin. Wood et al. (Wood et al., 1997) suggested that magnetic
field-induced phosphenes may play a role similar to light at night and thus represent a
possible biological mechanism to account for the reported reduction in melatonin duringnocturnal exposure to magnetic fields. [The authors did not evaluate this possibility, andit does not seem to be a particularly promising avenue of research.] Induction ofmagnetophosphenes in humans is sharply frequency dependent and requires magnetic flux
densities more than 10 000 times higher than those usually encountered in residential
settings. Maximum sensitivity occurs between 20 and 30 Hz; higher thresholds have been
observed for both lower and higher frequencies (Lovsund et al., 1979). The minimum flux
density required to induce detectable magnetophosphenes is > 3Ð5 mT at 20 Hz (Silny,1986). At 60 Hz, the threshold at the retina for perception of magnetophosphenes is atleast an order of magnitude greater than at 20 Hz.

4.6.2 Central nervous system
The central nervous system is a potential site of interaction between biological systems
and electric and magnetic fields because of the electrical sensitivity of the tissues. In theearly studies of occupational exposure to EMF reported by Asanova and Rakov(Asanova & Rakov, 1966) and Sazonova (Sazonova, 1967), switchyard workers werereported to suffer from an abnormally high incidence of neurophysiological complaints.
Clinical EEG measurements were reported to show desynchronization of the alpharhythm (the dominant frequency range in the human brain, 8Ð12 Hz) and otherabnormalities in EEG activity. Although later studies of EEG results from periodic healthexaminations failed to confirm these initial observations, the topic has continued to be ofinterest . Table 4.41 summarizes the results of 10 recent studies designed to evaluate theeffects of occupational and laboratory-generated EMF on the basic bioelectricalcharacteristics of EEG activity in human volunteers.
4.6.2.1 Electroencephalographic spectral analysis
In the four studies summarized in the first half of Table 4.41, EEG activity from multiple
standardized scalp locations was tested in paradigms that allowed comparison of fieldexposed and unexposed conditions. The raw data were submitted to fast Fourier

303

transform spectral analysis to obtain information about possible field-induced alterationsin the absolute and relative power of the dominant brain frequency, the total amount ofenergy being generated, and the distribution of energy in different frequency bands andover various regions of the head. Gamberale et al. (Gamberale et al., 1989), for example,
performed standard clinical EEG examinations on experienced utility company linemen
before and after performance of their usual duties under typical exposure conditions on
one day and under simulated conditions on a second day. They found that acute exposure
over one day to fields associated with a 400 kV transmission line had no negative effects
on the nervous system in this group of healthy men.
Lyskov et al. (Lyskov et al., 1993a; Lyskov et al., 1993b) performed two double-blindlaboratory-based studies of the effects of continuous and intermittent (1 s on, 1 s off)
exposure to magnetic fields on EEG activity in 17 male and 17 female volunteers. A
Helmholtz-type coil device was used to produce a horizontal magnetic field (45 Hz, 1.26
mT, 25% uniformity) around the head of each volunteer, for 60 min in study 1 and for 15
min in study 2. EEG activity measured immediately before and after exposure and shamexposure periods indicated that effects were predominantly associated with intermittent
exposure. The 60-min exposure was associated with decreases in absolute and relative
power in the lower EEG frequency bands (delta, 1Ð4 Hz; theta, 4Ð7 Hz) and increases in
power in the higher frequency bands (alpha, 8Ð12 Hz; beta, 13Ð20 Hz). Field exposure
had significantly (p < 0.05) different effects from sham exposure in 14 of 36 measures.
This result was much greater than the two significant differences to be expected purely bychance alone. Intermittent exposure for 15 min under the same test conditions also
resulted in significant (p < 0.05) effects on EEG activity. The most prominent change wasan increase in both absolute and relative power in the alpha band; absolute power in thebeta band also showed a non-significant increase. Short-duration exposure, however, had
no effect on the lower frequency bands. The authors suggested that this pattern of EEGchanges is indicative of the combined effects of relaxation and activation caused by themagnetic field on different structural and functional systems of the brain.
Since 1991, Bell and Marino and their coworkers have examined the effects of magnetic
fields on human EEG activity. The study of Bell et al. (Bell et al., 1992) summarized inTable 4.41 is representative of the approach taken by these investigators. A Helmholtztype coil device is used to repeatedly expose the head and chest of neurological patientsor volunteers from the general population to DC fields or to AC magnetic fields ofvarying frequency (£ 60 Hz) and intensity (£ 100 mT), either alone or in combination, in atest series of second-duration exposure epochs interspersed with no-exposure epochs.
EEG activity during exposure epochs is compared with that in the preceding no-exposure
epochs by non-traditional analytical techniques, in which the EEG spectrum is divided
into 0.05 Hz bands and a field effect is defined as a change, either positive or negative, inthe power coefficients in one or more bands. [The findings across these studies areambiguous and not informative with regard to doseÐresponse relationships. A number ofpotential sources of error and artifact are associated with this type of test and analysis,
including fatigue, lapses of attention, body movements, visual-induced artifacts, and304

transients. The mixed use of neurological patients and normal volunteers in the same
experiment creates additional ambiguity.]
4.6.2.2 Event-related potential
Presentation of a stimulus evokes a transient electrophysiological response in the human
EEG, commonly referred to as an event-related potential (ERP). Computer averaging ofsuch responses results in a complex waveform with distinct electrically positive andnegative components. ERP components are usually identified by their electrical sign(negative, N; positive, P) and by the sequence in which they appear in the waveform (e.g.
N100 represents a negative peak that appears in the waveform about 100 ms after the
stimulus; P300, a positive peak that appears about 300 ms after the stimulus. Shortlatency ERPs (< 50 ms) are used clinically to evaluate hearing and vision in the newborn,
brain function during coma, and as one criterion of brain death. Longer-latency ERP
components (100Ð500 ms after stimulus) are also well documented and have been linked
to specific human information processing activities, such as attentional gating, stimulus
evaluation and discrimination, decision making, memory updating, and motor response.
The amplitude of ERP components is significantly affected by the value or attentiongetting properties associated with a stimulus (meaning, signal value, rarity). In
neurotoxicological studies, ERPs have been used to assess changes in neural function in
response to such toxicants as ethanol, carbon monoxide, xylene, methylene chloride, andtrichloroethylene (Arezzo et al., 1985; Dick & Johnson, 1986).
The lower half of Table 4.41 summarizes the results of six recent laboratory studies
designed to evaluate the effects of magnetic fields on ERP components. Graham et al.
(Graham et al., 1995) measured short-latency (< 50 ms) ERP components to visual,auditory, and somatosensory stimuli in a double-blind study of exposure to a 60 Hz 10
mT, 20 mT field of 36 healthy young men and women. ERP measures of neural conduction
time during exposure and under sham-exposure conditions were not statisticallysignificantly different in any of the three sensory modalities. In a study with similar
measures, described in section 4.4.3, Dowman et al. (Dowman et al., 1989) obtained
similar results in monkeys. [These results suggest that exposure to combined EMF or tomagnetic fields alone at levels higher than those found in most residences has no effect onneural conduction time in peripheral or central sensory afferent pathways.]
Four double-blind cross-over studies (Table 4.41) (Cook et al., 1992; Graham et al., 1987;
Graham et al., 1990; Graham et al., 1994) showed that exposure of human volunteers for
up to 6 h to combined EMF at intensities as high as 12 kV/m and 20 mT per axis had noeffect on longer-latency components of the visual ERP. These results replicate those of an
earlier report by (Silny, 1986) who used 50 Hz magnetic fields up to 5 mT. In contrast,
replicable effects of whole-body exposure to combined electric and circularly polarized 60
Hz magnetic fields on the auditory ERP have been reported in three laboratory studies(Cook et al., 1992; Graham et al., 1987; Graham et al., 1994). The field levels in thesestudies ranged from 6 kV/m and 10 mT to 9 kV/m and 20 mT. [All of the studies
conducted in this laboratory involved circularly polarized magnetic fields, and flux is305

reported as per axis (e.g. a 20 mT per axis circularly polarized field gives a resultant fieldof 28.3 mT).] Auditory ERP measures were obtained while volunteers performed a widelyused neurophysiological target detection task, the Ôoddball taskÕ (Donchin, 1984; Harbin,
1985; Otto et al., 1985). In comparison with sham exposure, field exposure wasassociated with a significant (p < 0.05) increase in the amplitude of P300, the primarycognitive component of the auditory ERP waveform. In the context of the oddball task,
increases in amplitude indicate possible interference in the normal physiological processes
involved in distinguishing relevant from irrelevant stimuli (i.e. increased susceptibility to
distraction). [These studies of auditory ERP activity represent within-laboratory
replications.] Lyskov et al. (Lyskov et al., 1993a) reported somewhat contradictory
results: the P300 component of the auditory ERP when measured in response to thepresentation of simple tone stimuli was not affected by 15 min of cephalic exposure to a
50 Hz 1.26-mT horizontal magnetic field.
[The studies of the effects of exposure to EMF on human EEG activity differ in a numberof important respects, e.g. exposure duration, strength, orientation, polarity, whole-bodyvs. cephalic exposure, physiological recording parameters, and analytical techniques.
Taken as a whole, however, they suggest that EEG measures are affected by exposure toelectric and/or magnetic fields; however, the reported effects do not appear to result fromalterations in neural conduction time in major sensory modalities and may well be related
to shifts in physiological arousal and attention during testing. The biological magnitude (<10 %) of the changes observed is well within normal ranges for the EEG parametersassessed. The data are insufficient to suggest a health effect.]
4.6.2.3 Sleep electrophysiology
Sleep is a complex biological process controlled by the central nervous system and which
is necessary for proper cognitive, metabolic, and immune function. Asanova and Rakov(Asanova & Rakov, 1966) were the first to suggest that occupational exposure to powerfrequency EMF might have a detrimental effect on night sleep. The switchyard workers
they evaluated made numerous complaints of exposure-related decrements in both thequantity and quality of sleep. Individuals who consider themselves hypersensitive to
EMF most commonly report disturbances of night sleep and feelings of tiredness andfatigue on awakening (Arnetz, 1997; Berg et al., 1992). Few studies have obtained
objective EEG measures of night sleep from human volunteers exposed to known field
conditions in a controlled laboratory environment.
Two recent reports (see Table 4.42) suggest that exposure to magnetic fields in the ELF
range also disrupt objective EEG measures of night sleep in human volunteers. Akerstedt
et al.(Akerstedt et al., 1997a; Akerstedt et al., 1997b) performed a double-blindlaboratory study to evaluate the effects of all-night exposure to a 50 Hz, 1 mT horizontal
magnetic field on EEG sleep parameters and endocrine or hormonal measures in 18 men
and women, 24Ð49 years old. Each subject slept in the exposure facility for two nights.
The first night was considered an adaptation session in which the subjects became used tosleeping in the laboratory while wearing physiological recording sensors. On the second
306night, half of the subjects at random were sham exposed, and half were continuously
exposed to the magnetic field. Sleep EEGs were recorded throughout the test nights, andblood samples were obtained six times per night from an indwelling catheter. In
comparison with sham-exposure conditions, field exposure was associated with asignificant (p < 0.01) reduction in the duration of slow-wave sleep (sleep stages III andIV), which is often considered to be the restorative portion of night sleep. The nights offield exposure nights were also associated with reduced total sleep time, reduced sleep
efficiency, and reduced rapid-eye-movement (REM) sleep; these effects did not reachstatistical significance.
Graham and Cook (Graham & Cook, 1998) performed a double-blind, laboratory-based
study to evaluate the effects of exposure to magnetic fields on EEG measures of nocturnal
sleep patterns in 24 healthy men aged 18Ð35. Each man slept in the exposure facility from23:00 to 07:00 h for three nights. The first two nights were adaptation sessions during
which the subjects became used to sleeping in the laboratory. On the third night, eight
men were sham exposed; seven men were continuously exposed to a 60 Hz, 20 mT per
axis (resultant, 28.3 mT) circularly polarized magnetic field; and nine men were exposedintermittently (1 h on, 1 h off) to the same field. The sleep EEG was recorded throughout
the night. Physiological data collection, sleep scoring, and statistical analyses were all
performed in a blinded fashion. The results seen with continuous exposure did not differ
from those in sham-exposed controls for any measure, while intermittent exposure
resulted in a significant distortion of nocturnal sleep in six of the 10 measures evaluated.
Intermittent exposure was associated with less total sleep time (p = 0.003), reduced sleep
efficiency (p = 0.003), increased time in stage 2 sleep (p = 0.009), decreased REM sleep(p = 0.001), and increased REM latency (p = 0.04). Subjects exposed intermittently to thefield also reported sleeping less well (p = 0.001) and feeling less rested in the morning (p =0.03) than subjects in the other two groups.
[The exposure and test procedures were quite different in these two studies, and thedifferent results obtained may be due to those differences. The findings of Akerstedt et al.
(1997a) are relevant to levels of residential exposure. However, the possible confounding
effect of serial blood sampling on EEG measures of nocturnal sleep should be examinedfurther. The exposure in the study of Graham and Cook are more relevant to occupational
exposure in the utility industry than to residential exposures, but they observed little
slow-wave sleep, suggesting that the volunteers were not completely adapted to thelaboratory environment. It will be important to determine whether the findings of thesepreliminary studies are replicable, to extend them to women and to older individuals, andto ascertain whether daytime exposure also alters sleep architecture. The available data on
the effects of ELF fields on sleep are insufficient to suggest a health risk; however, poor
sleep quality can have a detrimental effect on worker safety and performance, andmodification of REM sleep has been associated with decrements in memory function andlearning processes.]307

4.6.2.4 Cognition and performance
The ability to perceive the world around us, to process information quickly andaccurately, and to maintain appropriate levels of attention and arousal are all significant
human functions. Even subtle changes in such functions can have importantconsequences. Performance depends on intact, functioning physiological systems, andchanges in performance in toxicological or exposure studies can provide important
information about underlying neuronal dysfunction. The most frequently usedperformance measures in research on EMF with human volunteers are reaction time,
vigilance or sustained attention, memory function, and tasks involving time perception
and information processing. Many earlier studies were reviewed by Carstensen(Carstensen, 1987).
Table 4.43 summarizes the results of 10 recent studies. Even a cursory review of theTable indicates that the results for performance have been very mixed. For example, twostudies found improvements in a reaction-time task, two found decrements in reaction
time, and five found no effect. A similar lack of consistency is evident in the results ofstudies of more complex performance, partly because different investigators seldom use
the same task and the range of exposure conditions is limited. The mixed results may also
be due to differences in protocol between laboratories and to variations in volunteer
motivation. More standardization in this area of research is needed.
[Human performance of many types of task appears to be unaffected by exposure to
relatively high electric and/or magnetic fields. When effects are observed, however, themagnitude of the alteration is generally in the order of 10% or less, and little reliable
evidence exists for a consistent doseÐresponse relationship. Thus, there is insufficientevidence at this time to indicate that daytime exposure to ELF EMF at occupational
levels presents a health risk. The extent to which performance is disrupted by fields of
low intensity similar to those found in offices and residences, however, has not been wellevaluated. Similarly, it is not known if nocturnal field exposure has detrimental effects on
daytime performance.]

4.6.3 Cardiovascular system
4.6.3.1 Heart rate
Sazonova (Sazonova, 1967) examined groups of switchyard workers in the former USSR,
who differed in the duration and intensity of their exposure to 50 Hz fields. The pulse
rates of people in the group with an average exposure for > 5 h/d to 12Ð16 kV/m werelower by 2Ð5 beats/min at the end of the day, although they had been equivalent at thestart of the day, and this difference was found even after exercise (p < 0.05). Early studies
of effects on the heart rate in human volunteers were reviewed by Carstensen

308

(Carstensen, 1987) and Cook (Cook et al., 1992). A number of the earlier studies were
published as meeting abstracts or in non-English-language journals.
Table 4.44 presents the results of six recent studies of this phenomenon. Replicable fieldrelated slowing of the heart rate was reported in four laboratory-based studies withdouble-blind cross-over experimental designs (Cook et al., 1992; Graham et al., 1987;
Graham et al., 1990; Graham et al., 1994). Negative results have also been found,however. The biological mechanism underlying the phenomenon is unknown, and themagnitude of the observed effects across studies is small (< 10 % change from the mean).
Korpinen et al. (Korpinen et al., 1993) see table 4.44 used ambulatory recording
techniques to perform an extensive series of studies of the effects of occupational
exposure to EMF on heart rate. No field-related changes in mean heart rate were found as
a result of exposure to the 50 Hz fields directly under power transmission lines ranging in
intensity from 110 to 400 kV. [There are insufficient data to suggest a health risk.]
4.6.3.2 Heart-rate variability
Heart-rate variability (HRV) results from the action of neuronal and cardiovascularreflexes, including those involved in the control of temperature, blood pressure, andrespiration. Quantitative spectral analyses of alterations in HRV with digital Fouriertransform provide useful indicators of beat-to-beat variations in sympathetic andparasympathetic nerve activity in vivo. This type of variability is not consciously
perceived, and it should not be confused with heart-rate reactivity, which is the slowing
or speeding of the heart rate in direct response to perceived situational or personal stimuli(e.g. exercise, anxiety, and relaxation). Certain alterations in HRV have recognized
prognostic value for coronary artery disease (Hayano et al., 1990; Liao et al., 1997), postinfarction risk (Bigger et al., 1993; Kleiger et al., 1987), diabetic autonomic neuropathy(Bernardi et al., 1992), and systemic hypertension (Huikuri et al., 1996; Liao et al., 1996).
Data from large longitudinal human studies in the USA and other countries have indicatedthat quantitative spectral assessment of HRV in healthy and diseased populations offers
prognostic information for the risk of sudden cardiovascular death and death from allcauses, beyond that provided by the evaluation of traditional risk factors. In the
Framingham Study (Tsuji et al., 1996; Tsuji et al., 1994), HRV was examined in a middleaged and elderly cohort after exclusion of subjects with cardiovascular disease or
medications that could affect HRV. Reduced HRV was significantly associated withsubsequent sudden cardiovascular death, even after all previous risk factors (e.g. bloodpressure and cholesterol concentrations) had been taken into account. Similar results wereobtained in a 25-year prospective study of a middle-aged and elderly cohort (Dekker etal., 1997); these results complement more recent concordant findings (Liao et al., 1997).
Sastre et al. (Sastre et al., 1998); see Table 4.44, described three recent double-blind studies
in which sufficient data were collected to examine HRV in detail in 77 volunteers as theyslept through the night (23:00Ð07:00 h) in the laboratory while being exposed to309

intermittent (1 h on, 1 h off) or continuous 60 Hz magnetic fields at intensities of 1 or 20
mT. In study 1, intermittent exposure to 20 mT reduced HRV in the spectral bandassociated with the neural control of thermoregulation and blood pressure (known as theÔlow bandÕ) in comparisons with sham-exposure conditions and field exposure to 1 mT (p= 0.03). In study 2, each of the 23 volunteers served as his own control. They were sham
exposed in one session and exposed to the 20 mT field in a second session. In comparison
with sham-exposure conditions, intermittent field exposure was again associated with areduction in low-band power (p = 0.02) and also with a significant (p = 0.008) increase in
the power in the spectral band associated with natural respiration-induced alterations inheart rate (known as the Ôhigh bandÕ). In a third study performed to determine the effectsof continuous rather than intermittent exposure, no significant effects on HRV were found.
[Taken together, these findings are consistent with the hypothesis that intermittency of
exposure to magnetic fields is an important parameter in the human cardiac responses that
result from those exposures.]In the studies of Sastre et al., low-band power was reduced by approximately 17% bynocturnal exposure to an intermittent magnetic field of 20 mT, whereas the biologicalmagnitude of the reduction in low-band power typically seen in clinical studies is 20Ð
40%. In the studies of Sastre et al., none of the volunteers reported any cardiovasculardifficulties associated with the night-time exposures; secondly, the changes seen to date asa function of intermittent exposure are similar but not identical to those reported as
predictive of cardiovascular morbidity and mortality. In the clinical studies, a higher
cardiovascular risk was associated with a reduction in low-band power coupled withmodest reductions or no change in high-band power (Barron & Lesh, 1996; Bernardi et al.,
1992; Bigger et al., 1993; Hayano et al., 1990; Huikuri et al., 1996; Kleiger et al., 1987).
The pattern seen with field exposure is a reduction in low-band power with an increase inhigh-band power. This pattern has, to our knowledge, been reported only for changes in
HRV associated with stage 2 sleep (Vaughn et al., 1995).
Extrapolation of the laboratory data described by Sastre et al. (Sastre et al., 1998) in
combination with the results of clinical studies of HRV lead to the biological hypothesisthat chronic occupational exposure to intermittent power-frequency magnetic fields may
affect specific types of cardiovascular disease by altering cardiac autonomic control.
Under this hypothesis, such exposures would be linked to increased risks for arrhythmiarelated deaths and deaths due to acute myocardial infarct. No increase in risk would be
predicted for deaths due to cardiovascular events that are the end-product of processes
that develop independently form autonomic nervous input over extended periods of time(i.e. atherosclerosis and chronic coronary heart disease). Savitz et al. (Savitz et al., 1998c)
recently reported results that support both the positive and the negative predictions
derived from this hypothesis, in a cohort analysis of 139 903 male electric utility
workers. The study is described in detail in section 4.5.1.
[Primarily because of the small number of studies reported at this time, there isinsufficient evidence of a health risk.]

310

4.6.4 Other effects
4.6.4.1 Melatonin
Stevens et al. (Stevens et al., 1997) proposed that exposure-related suppression of
nocturnal melatonin might provide a plausible biological mechanism to account for someof the epidemiological reports linking occupational or residential exposure to EMF withincreased cancer risks. Much of the evidence for the melatonin hypothesis, however, isbased on data for rodents (see section 4.4.5). A crucial link for this hypothesis is todetermine whether melatonin is suppressed when humans are exposed to magnetic fields
at night.
Humans and rodents differ in regard to melatonin. Rodents are nocturnally active, andtheir nocturnal melatonin concentrations are more easily suppressed by light. Differencesin the geometry of the skull and the anatomical location of the pineal gland may cause
stronger eddy currents in field-exposed rodents. People show large individual variation in
their melatonin patterns, while inbred laboratory strains of rodents do not. Among
healthy young men, for example, the peak melatonin concentrations at night can range
from 10 pg/ml to over 100 pg/ml (Graham et al., 1998). Human melatonin concentrations
also vary as a function of age: in general, they are highest at the age of 1Ð3, decrease
sharply until adolescence, remain fairly stable through adulthood, and finally begin afurther decline after about the age of 50 (Waldhauser et al., 1993). Little is known about
the basic biology of melatonin in humans and how differences in the concentrations andpatterns of this hormone affect individual health and well-being.
The effects of exposure to electric and/or magnetic fields on blood concentrations ofmelatonin and its major urinary metabolite 6-hydroxymelatonin sulfate (6-OHMS) in
humans have been examined in 12 studies (Table 4.45), six with exposure in thelaboratory and six observational studies of occupational and residential exposure. The
results of five of the six laboratory studies were negative. All-night exposure of humanvolunteers to magnetic fields under controlled exposure and lighting conditions in thelaboratory had no apparent effect on nocturnal blood concentrations of melatonin whencompared with equivalent sham-exposure conditions. The exposure parameters evaluatedincluded field frequency (50 or 60 Hz), field polarity (linear or circular), field type(continuous or intermittent), and field intensity (1Ð20 mT). The studies were performed
under double-blind control, and four had a cross-over experimental design in which eachvolunteer served as his own control to further reduce error variance. When suppression ofmelatonin has been observed in experimental animals, it was typically a 25Ð30%
reduction (Portier et al., 1998). Two of the three studies reported by Graham et al.
(Graham et al., 1997; Graham et al., 1996) had statistical power greater than 0.80 todetect a similar degree of suppression of melatonin in humans at the p < 0.05 level ofsignificance.

311

The laboratory study of Wood et al. (Wood et al., 1997) is the single one with notcompletely negative results. They first determined the nocturnal melatonin curve for eachindividual in their study and then timed presentation of the magnetic field to occur before,
during, or after the time of the peak concentration of melatonin in the circulation.
Exposure during the rising portion of the nocturnal melatonin curve significantly (p <0.01) delayed peak onset in one individual, with possible trends for similar effects inseveral other individuals. The authors note that, while the results are suggestive, the study
should be considered only preliminary and the results interpreted with caution. [Owing
to the exploratory nature of this study, a number of concerns could be raised in regard to
the experimental design, statistical analysis, and interpretation of the findings.]
All six of the studies of occupational and residential exposure listed in Table 4.45 provide
at least some evidence of field-related suppression of 6-OHMS, the major urinary
metabolite of melatonin. [As would be expected, there is wide variation in exposure
conditions, the duration, precision, and type of measures obtained, the presence ofpossible confounders (e.g. light at night, shift work), and the general characteristics andhealth status of the individuals studied. Nevertheless, these studies are directly relevant to
the effects of magnetic fields under present-day environmental conditions. The study of
Burch et al. (1998) is perhaps the most relevant for occupational exposure in the utility
environment, and that of Kaune et al. (1997) for assessing the effects of residential
exposure.] Burch et al. reported that TWA magnetic field intensity, intermittency, or
cumulative exposure had little influence on morning concentrations of 6-OHMS in theworkplace. At home, morning concentrations of 6-OHMS were significantly (p < 0.05)
associated with 24-h measures of magnetic fields if the exposure remained temporally
stable over at least 3Ð5 min. Additional analyses suggested that morning 6-OHMS
concentrations were most likely to be reduced in individuals who were exposed totemporally stable magnetic fields both at home and in the workplace.
Using 72-h measurements of magnetic fields in bedrooms made with EMDEX-2 monitors,
Kaune et al. (Kaune et al., 1997) reported a significant (p < 0.05) decrease in the log 6OHMS concentration in morning urine samples as the log mean magnetic field intensity
increased (range, 0Ð1.5 mT). For example, a twofold increase in average magnetic field
resulted in a 6Ð8% decrease in urinary metabolite concentration. This effect was strongest
in summer and was limited to women who used medications known to reduce melatonin(e.g. beta blockers). A similar relationship was observed as a function of the proportion ofnight-time bedroom measurements > 0.2 mT. Additional analyses indicated that 6-OHMS
concentrations were not altered as a function of wire code, short-term variation in
bedroom or personal dosimetry measurements, or the proportion of light-at-nightmeasurements > 10 lux. No relationship was observed between 6-OHMS concentrationsin urine and menopausal status, current smoking, or use of an electric blanket within theprevious month.
[The data are inadequate to suggest an effect of EMF on melatonin concentrations;however, additional research is needed to better understand the differences found in thelaboratory and in observational studies. Obvious factors to consider include single versus

312

long-term exposure, the type and complexity of the exposure parameters assessed, andthe characteristics of the individuals studied. More needs to be known about the effects of
exposure at different times of day. Inclusion of morning urine samples to assess thecontribution of melatonin in studies of occupational or residential exposure might beuseful.]4.6.4.2 Neuroendocrinology
Five double-blind, laboratory-based studies have been conducted to evaluate the effects of
exposure to power-frequency electric and/or magnetic fields on a variety of biochemicalmeasures in humans. The volunteers in these studies were unable to detect a difference
between field and sham exposure. Selmaoui et al. (Selmaoui et al., 1997) described theresults of additional analyses performed on the data collected by Selmaoui et al. (Selmaoui
et al., 1996b) to evaluate pituitary, thyroid, and adrenocortical hormones. No significant
differences were observed between sham- and field-exposure (50 Hz, 10 mT, 8 h) in theconcentrations of thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing
hormone, triiodothyronine, thyroxine, free triiodothyronine, thyroxine-binding globulin,
cortisol, or 17-hydroxycorticosteroids. Gamberale et al. (Gamberale et al., 1989) also
failed to find any field-related change in the concentrations of testosterone, thyroidstimulating hormone, luteinizing hormone, follicle-stimulating hormone, cortisol, or
prolactin in his study of the exposure of 26 linesmen working on a 400 kV transmission
line. Maresh et al.(Maresh et al., 1988) reported no effect of exposure to a 9 kV/m, 20 mT
field on the concentrations of cortisol, growth hormone, testosterone, and plasma lactic
acid or on the hematocrit or hemoglobin content in comparison with sham-exposure
conditions. Graham et al.(Graham et al., 1990) also reported no effects of multiple 6-hsessions of exposure to combined EMF (9 kV/m, 20 mT) on the concentrations of
dopamine, cortisol, epinephrine, norepinephrine, 5-hydroxyindoleacetic acid,homovanillic acid, or vanillylmandelic acid, which include the traditional measures ofstress (cortisol, epinephrine, norepinephrine, and dopamine).
[These studies provide no evidence for detrimental effects of exposure to ELF EMF for atleast 8 h on human hypothalamic, pituitary, thyroid, or adrenal hormonal systems or on
traditional biochemical measures of the human stress response; however, very little is
known about the response of women to EMF or about possible effects on female
reproductive hormones.]
4.6.4.3 Immune system
Few laboratory studies have examined the effects of exposure to EMF on immune
function in human volunteers. In perhaps the most comprehensive report to date,
Selmaoui et al. (Selmaoui et al., 1996a) described the results of additional analyses of thedata they collected in 1996 to evaluate hematological and immune system measures. No
significant differences were observed between sham- and magnetic field-exposed (50 Hz,
10 mT, 8 h) men in hemoglobin concentration, hematocrit, or erythrocyte, platelet, total

313

leukocyte, monocyte, lymphocyte, eosinophil, or neutrophil counts. The results of flow
cytometric analysis of immunological variables (CD3, CD4, CD8, natural killer cells, andB cells) before and after exposure and control sessions were also unchanged. Earlier,(Hauf, 1982) and Graham et al. (Graham et al., 1990) also reported no reliable field-relatedchanges in blood chemistry, leukocyte or lymphocyte counts, blood gases, lactate
concentration, or circulating stress hormones.
[All of the results of laboratory studies obtained to date are based on short-term exposureof healthy young men; no published reports have addressed possible differential effects asa function of age or gender, although the observational studies of suppression of themelatonin metabolite suggest that such studies might be appropriate. The data areinadequate to suggest a health risk.]

4.6.5 Mood disturbances
Various authors have suggested that environmental exposure to electric and/or magnetic
fields acts as a low-level stressor or is associated with an increased frequency of a varietyof negative mood states, including clinical depression, suicidal tendencies, feelings ofirritability, and loss of libido (Bell et al., 1991; Poole et al., 1993; Reichmanis et al., 1979;
Wilson, 1988). In this context, it would be important to determine whether field exposure
under controlled laboratory conditions has a negative effect on traditional self-reported
measures of mood and personality or on objective biochemical indicators of the humanstress response. [The use of double-blind control procedures is essential in this type ofevaluation, since the primary purpose of such procedures is to allow a distinction
between any effects due to field exposure per se and any effects associated with thesubjective expectation about being exposed.]
Eight double-blind studies have addressed this issue (Akerstedt et al., 1997a; Akerstedt etal., 1997b; Cook et al., 1992; Graham et al., 1987; Graham et al., 1990; Graham et al.,
1994; Maresh et al., 1988; Selmaoui et al., 1997; Stollery, 1986; Stollery, 1987), withoverwhelmingly negative results. The range of exposure parameters assessed in thesestudies included field frequency (50 and 60 Hz), magnetic field flux density (1Ð30 mT),electric field strength (0Ð12 kV/m; and injection of electric current equivalent to 36 kV/m),and exposure duration (2Ð8 h). [Short-term exposure of healthy young volunteers to EMF
has no apparent health consequences for stress levels or mood.]

4.6.6 Electromagnetic hypersensitivity
Reports of individuals who claim to be sensitive to electricity first began to appear in thelate 1970s with the introduction of VDTs into the modern office environment (Pearce,1984). Thousands of employees, primarily in Sweden, have reported they are sensitive to
EMF (for recent reviews, see (Bergqvist & Vogel, 1997; Liden, 1996)). Although there is314substantial variation among individuals, the reported subjective symptoms andphysiological reactions include sleep disturbances, general fatigue, headache, difficulty inconcentrating, dizziness, eye strain, facial skin problems (e.g. dry skin, rosacea,
seborrhetic eczema, and sensations of itching, burning, or stinging). Typically, thesymptoms appear only intermittently at first, subsiding when the individual is away fromthe VDT. Over time, however, the symptoms may become more pronounced andpersistent and begin to interfere with the ability to work or to stay in the general work
environment (Bergqvist & Wahlberg, 1994; Sandstršm et al., 1997). Other electromagnetic
devices and appliances (e.g. office equipment, fluorescent lights, household appliances,
televisions, and mobile telephones) have also been reported to trigger these adverse
reactions in afflicted individuals.
A number of ÔprovocationÕ studies have been carried out to evaluate individual sensitivity
to DC fields, electrostatic fields, AC 50 Hz and 60 Hz EMF, low-MHz radio-frequency
fields, and EMF of the type described by Kavet and Tell (Kavet & Tell, 1991) asassociated with both plasma and cathode ray tube VDTs (Andersson et al., 1996; Arnetz,
1997; Arnetz et al., 1997; Sandstršm et al., 1997; Swanbeck & Bleeker, 1989). Thesestudies have been performed in a controlled laboratory environment with double-blind
control procedures. Healthy controls and volunteers suffering from electrical sensitivity
were asked to detect when they were being exposed in a series of standardized test trials.
The measures included detection accuracy, self-reported measures of stress and arousal,
blood samples for analysis of stress biochemistry, and histological samples from facial
skin.
In general, patients and volunteers in these studies were not able to reliably distinguish
exposed from unexposed conditions, and neither subjective symptoms nor biochemicalmeasures were significantly related to the actual exposure conditions. Patients did,
however, report accentuated symptoms when they believed they were being exposed,
regardless of the actual conditions (Andersson et al., 1996). Berg et al. (Berg et al., 1990)
performed a histopathological study of 134 individuals with skin complaints. Analysis ofobjective biopsy data revealed no significant difference between 83 persons highly
exposed to VDTs and 51 persons with low exposure to VDTs. No doseÐresponse effectwas observed between the amount of VDT exposure and objective skin signs.
Some positive results have, however, been reported. Rea (Rea et al., 1991) found that 16
patients out of 100 had symptoms and signs in response to blind exposure. This finding
could not be replicated in a subsequent study (Wang et al., ). Similarly, Johansson et al.
(Johansson et al., 1994) performed an uncontrolled provocation study in which twopatients sat in front of a television set. Analysis of skin biopsy samples revealed total
disappearance of somatostatin-positive cells after 3 h of exposure. [Few procedural or
exposure details were given, and the study has not been replicated.]
Sandstršm et al. (Sandstršm et al., 1995) performed a caseÐcontrol study of 163 VDTexposed workers with skin rashes and found an increased odds ratio (3.0; 95% CI, 1.2Ð7.2) for symptoms in people who worked in rooms with a 50 Hz background electric field315

> 31 V/m in comparison with workers in rooms with background electric fields < 10 V/m.
After adjustment for possible confounding factors (e.g. work duration, psychosocial
climate, and job stress), the odds ratio increased to 4.0 (1.2Ð13). Further work (Sandstršm
et al., 1997) indicated that the odds ratio was even higher when only females wereconsidered in the analysis (6.6; 1.7Ð26). [To date, this is the only well-controlled study
showing an association between exposure to ambient fields and skin rashes. It is notknown, however, whether this association implies a causal relationship between exposureand the symptoms.]
Various alternative hypotheses have been advanced to account for this phenomenon.
These include an imbalance in the autonomic nervous system (Portier et al., 1998),
enhanced neurophysiological sensitivity to flicker from fluorescent lights (Sandstršm etal., 1997), general hypersensitivity to environmental stimuli (Lyskov et al., 1998)
occupational stress resulting from increased work load and lack of personal autonomy andsocial support (Berg et al., 1992; Eriksson et al., 1997), and variations in the physical andchemical quality of the indoor environment (Arnetz et al., 1997; Nielsen & Schneider,
1998; Stenberg et al., 1995). Others have noted a similarity in the symptoms ofindividuals with electrical hypersenstivity and individuals suffering from Ômultiple
chemical hypersensitivityÕ, Ôenvironmental somatization syndromeÕ, Ôenvironmental
illnessÕ, and Ôtwentieth century diseaseÕ (Black et al., 1990; Liden, 1996).
[Some individuals have subjective symptoms apparently related to VDT use in the officeenvironment. The evidence is inadequate to relate such symptoms to the EMF associatedwith that use. Some individuals appear to show positive responses to EMF challenges,
but no high-quality double-blinded challenge studies have been conducted whichconclusively establish the existence of sensitivity to EMF. There is also no establishedmechanism for electrical hypersensitivity.]

4.6.7 Summary
There is weak evidence that short term human exposure to ELF EMF causes changes inheart-rate variability, sleep disturbance, or suppression of melatonin.
[The conclusion for effects on heart-rate variability was supported by 13 Working Group
members; there was 1 vote for ÔmoderateÕ evidence, 2 votes for ÔnoÕ evidence, 8abstentions, and 5 absent.][The conclusion for effects on sleep disturbances was supported by 15 Working Group
members; there were 9 abstentions and 5 absent.][The conclusion for effects on melatonin was supported by 16 Working Group members;
there was 1 vote for ÔmoderateÕ evidence, 2 votes for ÔnoÕ evidence, 5 abstentions, and 5
absent.]316

There is no evidence that such exposure has other effects on the biological end-points
studied in the laboratory.
[This conclusion was supported by 12 Working Group members; there were 2 votes forÔweakÕ evidence, 11 abstentions, and 5 absent. The tie vote was broken by the Chair.]317

Table 4.41 Effects on exposure to EMF on measures of electrical activity in human brain
Reference

Subjects

Exposure parameters

End-points

Major results

26 experienced
utility linesmen
aged 25-52 years

Men inspected insulators on 50 Hz, 400
kV transmission line, line active on one of
the two test days (0700-1700 h; personal
dosimeter: average exposure 2.8 kV/m,
23.3 mTStandard 21-leadclinical EEG exam given
at start and end of eachtest dayNo evidence of EEG abnormalities, no evidenceof changes in the stability or amplitude of the
EEG alpha (8-12 Hz) rhythm(Lyskov et al.,1993b)

9 male and 11
female volunteers

1-h no-exposure sham control condition.
1-h exposure of the head to a 45 Hz,
1.26 mT horizontal (ear-to-ear) magnetic
field, either continuously orintermittently (1s on, 1 s off).

Spectral analysis (FFT)of the EEG recorded
from 7 scalp sites before
and after exposure andcontrol conditions

Effects seen primarily with intermittent
exposure. Absolute and relative power
decreased in low frequency EEG bands (1-7Hz)*, and increased in higher frequency EEG
bands (8-20 Hz)*

(Lyskov et al.,1993a)

8 male and 6
female volunteers

15-min no-exposure sham control
condition. 15-min intermittent (1 s on, 1 soff) exposure of the head to abovemagnetic field condition.

Same as above.

Absolute and relative power increased inhigher frequency EEG bands (8-20 Hz)*, but
15-min exposure had no effect on lower
frequency bands.

(Bell et al., 1992)

10 volunteers and
10 neurologicalpatients

The head of each subject was exposed in aseries of 2 s on, 5 s off trials under four
test conditions: no-exposure control;
78 mT, AC magnetic field; 78 mT, DC
magnetic field; and combined 78 mT AC
and DC magnetic field conditions

EEG recorded frommultiple sites. Effectdefined as change (±) in
any 0.5 Hz EEG spectral
band compared withprevious control period.

No EEG effects found in control. Overall, ACmagnetic field associated with EEG changes in
19 of 20 subjects* (30% responded to DC field,
70-80% responded to AC field). Combined
AC/DC exposure not different from AC exposurealone

18 men18 women
18-35 years

12 in sham-exposed control group
12 in 60 Hz, 10 mT exposure group
12 in 60 Hz, 20 mT exposure group

Short-latency (< 50msec) neural conduction
components of auditory,visual andsomatosensory ERPs
recorded during
magnetic field andcontrol conditions

Main ERP neural conduction time measures not
influenced by magnetic field in any sensory
modality. One exception: amplitude decreased
for somatosensory ERP mid-latencycomponents**, an effect similar to that seen inmonkeys by Dowman et al., 1989

12 men18-35 years

All subjects participated in four, 6-h test
sessions; half sham, half involving
exposure to a 60 Hz 9 kV/m, 20 mT
combined field.

Long-latency (> 100msec) ERPs recorded instandard ÒoddballÓ
target-detection
paradigm before and after
test sessions.

No effects on visual ERP. Exposure associatedwith increased amplitude of P300 component of
the auditory ERP*

Spectral analysis(Gamberale et al., 1989)

Event-related-potential(Graham & Cohen,
1985)(Graham et al., 1987)

318

Table 4.41 (continued)
Exposure parameters

End-points

Major results(Cook et al., 1992)

Reference

30 men21-35 years

Subjects

18 men exposed and sham-exposed equally
over four, 6-h sessions to a continuous 9
kV/m, 20 mT combined field. 12 men
exposed to combined field in all sessions.

Long-latency ERPs
recorded in ÒoddballÓ
task before, during, andafter test sessions

No effects on visual ERP. Exposure associatedwith increased amplitude of the P300 component of
the auditory ERP* . Effects on ERP components
greatest soon after field activated, and again at endof day when field switched off.

(Graham et al., 1994)

54 men18-35 years

All subjects sham exposed in one 6-hsession.
In a similar session:
18 exposed to a 60 Hz, 6 kV/m, 10 mT field
18 exposed to a 60 Hz, 9 kV/m, 20 mT field
18 exposed to a 60 Hz, 12 kV/m, 30 mT
field

Same as above

Exposure to low and intermediate-strength groups
associated with a timing delay (latency) in theappearance of P300 component in ERP
waveform**. Effect did not occur in the high EMF
group. Amplitude of the N200/P300 component
complex increased in all field-exposed groups
compared with sham control*.

(Graham et al., 1990)

28 men18-35 years

14 subjects in sham control 6-h test
session.
In a similar session, 14 subjects exposed
to a continuous 60 Hz, 12 kV/m, 30 mT
field

Same as above

No effects found for visual ERP. Equipment
problems resulted in ambiguous effects on latency
and amplitude measures of the P300 component of
the auditory ERP.

EEG, electroencephalogram; AC, alternating current; DC, direct current; ERP, event-related potential* p < 0.05** p < 0.01

319

Table 4.42 Laboratory studies of the effects of magnetic fields on electroencephalographic measures of human sleep
Reference

Subject

Magnetic field parameters

Endpoints

Major results(Graham et al.,1998)

24 men18-35 years

60 Hz, circular polarization
8 No-exposure sham controls
7 Continuous exposure(20 mT/per axis, 2300-0700 h)
9 Intermittent exposure, 1 hr on, 1 h off(20 mT/per axis, 2300-0700 h)

10 objective EEG
sleep measures, sleep
quality report measures

Continuous exposure not different from sham on
any EEG measure. Intermittent exposure different
from sham on 6 of 10 EEG measures** (e.g., lesstotal sleep time, reduced sleep efficiency, increased
time in stage 2 sleep, and decreased REM sleep).
Sleep quality data reflected EEG disturbances*.

(Akerstedt et al.,1997a)

18 men& women24-49 years

50 Hz, Linear polarization
9 No-exposure sham control
9 Continuous exposure
1 mT, (2300-0700 h)
In dwelling catheter for serial blood draws

Objective EEG
measures, self-reportmeasures, melatonin,
Cortisol, GH, ACTH,
Prolactin

Exposure associated with a significant* reduction
in slow wave sleep (stages 3 and 4). Exposed
subjects also had less total sleep time and reduced
sleep efficiency. No effect on hormones.

EEG, electroencephalogram; REM, rapid eye movement; GH, growth hormone; ACTH, adrenocorticotrophic hormone* = p < 0.05** = p < 0.01

320

Table 4.43 EMF effects of exposure to EMF on human cognition and performance
Exposure parameters

Endpoints

Major results(Cook et al., 1992)

Reference

30 men21-35 years

Subjects

18 men exposed and sham exposed equally
over four, 6-hr sessions to a continuous 9
KV/m, 20 mT combined field. 12 men exposed
to combined field in all sessions.

Pre- and post- session
multi-task test battery(e.g., RT, math,vigilance, time
estimation, memory).

EMF exposure effects on performance different
from sham-exposed on only one task in the test
battery (exposed subjects made fewer errors
when performing the choice RT task *).

(Gamberale et al.,1989)

26 linesmen
25-52 years

Men inspected insulators on 50 Hz, 400 KV
transmission line. Line active on one of thetwo test days (0700-1700 h; personal
dosimeter: average exposure 2.8 kV/m, 23 mT)

RT, vigilance, memory,and perceptual speed
tests before and after
exposure and control
days.

Performance on exposure days did not differ fromperformance on control days.

(Graham et al.,1987)

12 menFour 6-hr test sessions; half sham, half
involving cont. exposure to a 60 Hz 9 kV/m,
20 mT field.

Pre- and post- session
multi-task test battery.
(RT, math, vigilance,time estimation,
memory).

EMF exposure effects on performance weredifferent from sham -exposed on only one of thebattery tasks (exposed subjects made less errors
when performing the choice reaction time task *).

(Graham et al.,1990)

28 men18-35 years

14 men in sham control 6-h test session.
In a similar session, 14 men exposed tocontinuous 60 Hz, 12 kV/m, 30 mT field.

4 administrations ofmulti-task battery (RT,math, vigilance,
memory, time
estimation).

Performance on exposure days did not differ
from performance on control days.

(Graham et al.,1994)

54 men18-35 years

All men sham exposed in one 6-h session.
In a similar session:
18 men: 60 Hz, 6 kV/m, 10 mT field
18 men: 60 Hz, 9 kV/m, 20 mT field
18 men: 60 Hz, 12 kV/m, 30 mT field

RT, attention, and timeperception tests given
before, after, and 2 times
during exposure andcontrol sessions.

Only exposure at the lowest level was
associated performance changes, compared withsham-exposed conditions. RT was slower (12%)
and accuracy decreased (13%) on the timeperception task*.

(Lyskov et al.,1993b)

9 men
11 women

1 h no exposure control condition

RT to auditory stimuli

Performance on exposure days did not differ fromperformance on control days

(Lyskov et al.,1993a)

8 men
6 womenSame as above, except exposure duration in
all conditions was 15 min

RT to auditory stimuli

Performance on exposure days did not differ fromperformance on control days.

(Stollery, 1986)

76 men18-65 years

All men sham exposed in one session.
In 2nd session, 50 Hz, 50 mAmp current
injected from 10:30-16:00 h into each of 10
electrodes on body. (Equivalent to 36 kV/m)Memory, attention,
vigilance, andreasoning tasks given 4
times a day

No EMF effects on vigilance, sustained
concentration, or verbal reasoning wereobserved.

321

Table 4.43 (continued)
Exposure parameters

Endpoints

Major results(Podd et al., 1995)

Reference

6 men
18 women
19-55 years

Subjects

5-min exposure of head to a 0.1 mT, 0.2 Hz or
43 Hz magnetic field, or to a sham-exposed
condition

RT to visual stimuli

Performance on exposure days did not differ fromperformance on control days.

(Teresiak & Szuba,
1989)

64 men22-63 years

Study 1: 50 Hz ambient electric field (0, 4.4,
10.9, and 13 kV/m). Study 2: 50 Hz current
injected into men (0, 50, 135, and 160
mamps). Equivalent to Study 1.

RT to the presentationof visual and auditory
signals

Significant slowing of RT found in the presence ofthe 13 kV/m field*, and with current injection of
160 mA*.

RT, reaction time
* = p < 0.05** = p < 0.01

322

Table 4.44. Effects of exposure to EMF on heart rate and heart rate variability in human volunteers
Exposure Parameters

Endpoints(Graham et al., 1987)

Reference

12 men21-35 years

Subjects

All men participated in four, 6-h test sessions;half sham, half involving continuous exposure toa 60 Hz 9 kV/m, 20 mT field.

Electrocardiogram(R-R interval)

HR slowing was greater after EMF
exposure than in sham exposure*.

(Maresh et al., 1988)

11 men21-29 years

Sham exposure (2 h)
EMF exposure (2 h, 60 Hz, 9 kV/m, 20 mT)
Each preceded by 45 min of rest or exercise

Electrocardiogram(R-R interval)

HR slowing was greater during EMF
exposure than in sham exposure*.

(Cook et al., 1992)

30 men21-35 years

18 men exposed and sham exposed equally overfour, 6-hr sessions to a continuous 9 kV/m, 20 mT
combined field. 12 men exposed to combined fieldin all sessions.

Electrocardiogram(R-R interval)(Graham et al., 1994)

54 men18-35 years

All men sham-exposed in one 6-hr session.
In a similar session:
18 men: 60 Hz, 6 kV/m, 10 mT field
18 men: 60 Hz, 9 kV/m, 20 mT field
18 men: 60 Hz, 12 kV/m, 30 mT field

Electrocardiogram(R-R interval)

HR slowing was greater during EMF
exposure than in sham exposure** Also
lower in subjects who were field
exposed in all sessions, but the effectwas not significant.
HR slowing greater after EMF exposure
at 9 kV/m, 20 mT*, but not at lower orhigher exposure conditions.

(Graham et al., 1990)

28 men18-35 years

14 men in sham-exposed 6-hr test session.
In a similar session, 14 men exposed to acontinuous 60 Hz, 12 kV/m, 30 mT field.

Electrocardiogram(R-R interval)

HR was not slower at higher EMF
exposure than in sham exposure.

(Korpinen et al.,1993)

41 men21-48 yrs

26 men sat for 1-h under a 400 KV line (3-4 kV/m,
1.4 mT), and at 200 m from the line. 15 men also
tested in sham conditions (0.01 kV/m, 0.01 mT).

Ambulatory
monitoringof electrocardiogram

No effect on heart rate at field strengths< 6 kV/m and 10 mT.

(Sastre et al., 1998)

Study 1: 29 men
18-35 yrs

11 men in sham-exposed group. Two intermittent
Exposure groups of 9 men each (60 Hz, 1 mT and
20 mT).

HRV analyses basedon electrocardiogram
R- R intervals.

Intermittent exposure at 20 mT reducedÒlow bandÓ power compared with sham
exposure or 1 mT*.

Study 2: 22 men
18-35 yrs

Each man was his own control. 2 sessions: shamand intermittent exposure to 60 Hz, 20 mT.

Same as above.
Same as above.

Study 3: 26 men
18-35 yrs

Each man was his own control. 2 sessions: shamand continuous exposure to 60 Hz, 20mT.

HR, heart rate; HRV, heart rate variability* = p < 0.05** = p < 0.01

323

Major Results

Intermittent exposure reduced ÒlowbandÓ power*, and increased Òhigh
bandÓ power**, compared with sham
exposureContinuous exposure at 20 mT had noeffect on heart rate variability.

Table 4.45 Effects of exposure to EMF on melatonin and its metabolite in humans
Reference
Laboratory studies(Graham et al., 1996)(2 studies)

Subjects

Magnetic field parameters

End-points

Major results

Study 1:33 men18-35 years

60 Hz, circular polarization
11 men: no-exposure, sham control group
11 men: 60 Hz 1 mT intermittent exposure
11 men: 60 Hz 20 mT intermittent exposure(Exposure duration 23:00-07:00 h)

Hourly melatonin(2300-0700)

No overall effect; Men with low basal
melatonin had greater suppression in a response tolight* and magnetic fields*.

Study 2:40 men18-35 years

60 Hz, circular polarization (23:00-07:00 h)
All men sham exposed in one session.
All men intermittently exposed to 20 mT in 2nd
session. (Each man his own control).

Hourly melatonin(23:00-07:00)

Effects of exposure no different from sham exposure.
No effect in men with low basal melatonin.

(Graham et al., 1997)

40 men18-35 years

60 Hz, circular polarization, (23:00-07:00 hrs)
All men sham exposed in one session
All men continuously exposed to 20 mT in 2nd
session. (Each man his own control).

Hourly melatonin(23:00-07:00)

Effects of exposure not different from sham exposure.
No effect in men with low basal melatonin.

(Selmaoui et al.,1996b)

32 men20-30 years

50 Hz; 10 mT; continuous and intermittent
exposure linear and circular polarization; (23:0008:00)
Each subject was his own control

Hourly melatonin,
6-OHMS

Effects of exposure not different from sham exposure.

(Akerstedt et al.,1997b)

18 men andwomen
24-49 years

50 Hz, 1 mT, continuous exposure,linear polarization, (23:00-07:00)

Hourly melatonin

Effects of exposure not different from sham exposure(Wood et al., 1997)

30 men18-49 years

50 Hz, 20 mT, circularly polarized, sinusoidal andsquare wave fields,
1.5 - 4.0 h exposures

Periodic melatonin(1800-0700 hrs)

No effect when sinusoidal or square wave exposure
examined separately; no effect when exposure occurredat MLT peak time or later at night; early night
exposure delayed MLT onset in 1 subject exposedover 5 sessions**.

32 women
10 mentested at home

Home use of standard (conventional) versus
modified AC or DC CPW electric blankets for 8
weeks (0.2 - 0.6 mT exposure range).

Morning and evening 6OHMS levels (notcreatinine corrected)

No overall effect. 7 of 28 CPW users had decreased 6OHMS in the last 3-week test period* and showed arebound effect*.

108 maleelectric
railway
workers

42 controls (50 Hz, 1 mT); 66 locomotiveengineers (16.7 Hz, 20 mT)
Continuous sampling of magnetic field (30 min - 4h)Urinary 6-OHMS
samples collected inmorning and evening(creatinine corrected)

Evening 6-OHMS decreased on work days, but not on
leisure days*. No effect on morning 6-OHMS levels.
No evidence for dose-response curve.

Environmental studies(Wilson et al., 1990)(Pfluger & Minder,
1996)

324

Table 4.45 (continued)
Reference

Subjects

Magnetic field parameters

End-points

Major results(Burch et al., 1998)

142 maleutilityworkers
20-60 years

57 controls (60 Hz, 0.1 mT)
29 field generation workers (60 Hz, 0.2 mT) 56
field distribution workers (60 Hz, 0.1 mT)
72 h EMDEX magnetic field level and lightintensity measurements taken.

1 home baseline and 3
workday morning 6OHMS samples(creatinine corrected)

Workplace: No effects on 6-OHMS of magnetic field
intensity, intermittency, or cumulative exposure. At
home: Temporally stable magnetic field exposure
associated with reduced 6-OHMS*(Arnetz & Berg,
1996)

47 VDT
workers who
participatedin a 1988
study

Compared 1 day working versus not working infront of VDT. No magnetic field measures taken.

Assay of a.m. and p.m.
melatonin samples
obtained in earlier study(not creatinine
corrected)

Melatonin decreased on work day compared with
control day*.

(Kaune et al., 1997)

203 women(controlgroup inbreast cancer
study)
20-74 yrs

72-h EMDEX measurement of bedroom magnetic
field levels (range 0 - 1.5 mT) and light intensity.
Personal exposure monitoring.

Morning 6-OHMS
levels measured on 3
consecutive days, 3 or 6months apart(creatinine corrected)

As log mean bedroom magnetic field increased, log 6OHMS levels decreased*. Effect is strongest insummer and in women taking medications which
reduce melatonin. No effect on 6-OHMS of wire code,
intermittency, personal dosimetry, or light-at-night.

6-OHMS, 6-hydroxymelatonin sulfate; CPW, continuous polymer wire; VDT, visual display terminal* = p< 0.05** = p< 0.01

325

4.7

In vitro and mechanistic studies
Since a very large number of cellular components, cellular processes, and cellular systems
can conceivably be affected by EMF, mechanistic studies are essential to interpret andhelp guide the experimental work. Because evidence from previous theoretical andexperimental studies suggested that EMF are unlikely to induce DNA damage directly,
most studies have been conducted to examine its effect on the cellular membrane, generaland specific gene expression, and signal transduction pathways. More recently, studies
specifically addressing the genotoxic effect of exposure to magnetic fields have been
pursued.
While some studies were conducted with samples from animals exposed to EMF in vivo,
most results have come from studies of cultured cells exposed in vitro. The great
advantage of in-vitro exposure is its precision, since the geometry and physical propertiesof the system can be well controlled.
While a major concern of the possible effects of EMF on public health is cancer, only asmall number of in-vitro studies were designed to address particular hypotheses generated
from previous studies of carcinogenesis. Thus, while EMF have been tested in a numberof established assays for genetic toxicity, the effects primarily studied have been nongenotoxic mechanisms of carcinogenesis, including induction of cell proliferation,
inhibition of intercellular communication, modulation of cell differentiation, and aberrant
control of proto-oncogene expression. These cellular effects and subcellular effects suchas active oxygen production and modulation of protein kinase C signal transduction are
well-documented activities of non-genotoxic carcinogens such as the phorbol esters.
In this section, the in vitro effects of exposure to EMF are documented, including
theoretical and physical considerations of mechanisms by which EMF can induce
biological effects. The in vitro responses considered are mainly genotoxicity, regulation ofgene expression, cell signaling and proliferation, and cell differentiation.

4.7.1 Genotoxicity and regulation of gene expression
The interest in assessing the effects of EMF at the cellular level in order to understand themechanism(s) by which exposure may be harmful and/or beneficial to human health has
temporally coincided with a rapid increase in knowledge about regulation of gene
expression and the role that specific gene products play in cell replication, proliferation,differentiation, and pathological processes.

326

4.7.1.1 Genotoxicity
The genotoxic effects of EMF have been extensively reviewed by McCann et al.
(McCann et al., 1998; McCann et al., 1993).
DNA damage and chromosomal effects
It is generally accepted that ELF EMF do not transfer energy to cells in sufficientamounts to directly damage DNA; however, it is possible that certain cellular processes
altered by exposure to ELF EMF, such as free radicals, indirectly affect the structure ofDNA. Most investigators have looked for strand breaks and other chromosomal
aberrations, including sister chromatid exchange, formation of micronuclei, and/or effects
on DNA repair.
Cultured human peripheral blood lymphocytes from volunteers were used to assess theeffects of power-frequency sine wave or pulsed magnetic fields on cytogenetic events.
Magnetic fields of 1Ð7.5 mT and exposure durations of 48Ð72 h produced no significant
chromosomal effects (Paile et al., 1995; Rosenthal & Obe, 1989; Scarfi et al., 1994).
Simultaneous exposure to an electric field (60 Hz, 30 mA/cm2) and a magnetic field (0.1 or
0.2 mT) did not cause sister chromatid exchange or chromosomal breaks (Cohen et al.,1986a; Cohen et al., 1986b) In one study (Khalil & Qassem, 1991), however, EMF were
found to induce chromosomal aberrations in human lymphocytes. In this study, exposureof human lymphocytes to a pulsed field with a peak magnetic flux density of 1.05 mT for
24Ð72 h induced a statistically significant, twofold increase in the frequency ofchromosomal aberrations and a simultaneous lowering of the mitotic index. In human
lymphocytes exposed to a 4.4 kHz pulsed field with a 14 Hz repetition rate, no effect onsister chromatid exchange rate was seen (Garcia-Sagredo et al., 1990). [With only one
exception Rosenthal & Obe (1989), positive controls were not used in these studies.]
In another model, human amniotic fluid cells were exposed to a 50 Hz sine-wave field (30mT rms) for 72 h. They showed a modest but consistent increase in the frequency of total
chromosomal aberrations when compared with controls (Nordenson et al., 1992). Whilehigher flux densities (300 mT) did not affect the cells in this manner, intermittent exposure(15 s onÐoff for 72 h) to the 30 mT field was as effective as continuous exposure inincreasing aberration frequencies (Nordenson et al., 1994). In a study to replicate thesefindings, Galt et al. (Galt et al., 1995) reported a nonsignificant decrease in the number ofcells with chromosomal aberrations after exposure to 30 mT. [A striking difference
between these two investigations was the level of aberrations in the control cells, which
was fourfold higher in the study of Galt et al; the authors did not comment on this point.
Furthermore, the ambient DC field differed substantially between the two laboratories.]
In established cell lines, however, exposure to EMF does not appear to induce
chromosomal aberrations (Fairbairn & O'Neill, 1994; Fiorani et al., 1992; Livingston et al.,
1991; Reese et al., 1988; Takahashi et al., 1987).

327

The ÔCometÕ assay (DNA microelectrophoresis) has been used to detect DNA
fragmentation in single cells (Lai & Singh, 1997a; Lai & Singh, 1997c; Singh & Lai, 1998).
Increases in both single- and double-strand breaks were reported in brain cells of rats
exposed in vivo to a 60 Hz field at 0.1Ð0.5 mT. Radical scavengers like melatonin and Ntertbutylphenynitrone counteracted the effects of exposure, suggesting that magnetic
fields can affect the levels or lifetimes of certain free radical species (Lai & Singh, 1997c).
The authors further suggested that exposure to ELF magnetic fields (60 Hz, 0.5 mT, 2 h)can cross-link DNA and also DNA and proteins, in a manner similar to mitomycin C(Singh & Lai, 1998). [The authors used mitomycin C as a positive control only in human
lymphocytes; in addition, the report does not mention ambient DC fields.]
Scarfi et al. (Scarfi et al., 1991; Scarfi et al., 1993; Scarfi et al., 1994) were consistently
unable to detect an increase in micronuclei in normal cultured human lymphocytes
exposed to a 50 Hz pulsed magnetic field or a sinusoidal E field; however, cells frompatients with TurnerÕs syndrome showed an 80Ð100% increase in micronuclei after
similar exposure (Scarfi et al., 1997b). After exposure to a 100 Hz magnetic field, thenumber of micronuclei increased in cultured human lymphocytes (Scarfi et al., 1997a).
Tofani et al. (Tofani et al., 1995) found that the DC field is important, since exposure of
peripheral lymphocytes to 32 or 50 Hz (75 or 100 mT) with no DC component wasineffective in inducing micronuclei, whereas cells exposed to the 32 Hz field had a higher
incidence of micronuclei when a DC component (42 mT) was introduced parallel to theAC field. In Chinese hamster V79 cells, however, exposure to pulsed magnetic fields (10or 100 Hz, 20 or 80 mT) for 24 h increased 3H-thymidine incorporation, while exposure
to 0.4 mT decreased incorporation (Takahashi et al., 1986). Cadossi et al. (Cadossi et al.,1992) using the same assay conditions, reported that lymphocytes from aged donors andfrom patients with B-cell chronic lymphocytic leukemia responded better to the pulsed
magnetic field (2.5 mT, 2 mV PEMF with a 50 Hz repetition rate, 24 or 48 h) thanlymphocytes from young healthy donors. Exposure of human T-cell leukemia Jurkat cells
to a magnetic field (1.8 mT) bone healing signal reduced 3H-thymidine incorporation by
50%, whereas a 60 Hz sine wave (0.1 or 0.4 mT) applied for 20 min reduced
incorporation by 20Ð25 % (Nindl et al., 1997). Simko et al. (Simko et al., 1998) foundincreased micronucleus formation in a human squamous-cell carcinoma cell line (SCL II),but not in human amniotic fluid cells, exposed to a 50 Hz magnetic field (0.1Ð1.0 mT) for
24, 48, or 72 h. The results of most other studies on micronucleus formation have been
negative (Lagroye & Poncy, 1997; Livingston et al., 1991), although the latter authors
showed micronuclei formation in rat tracheal epithelial cells treated with ionizing radiation(6 Gy) prior to a 50 Hz, 100 mT field for 24 h, the magnetic field alone had no effect.
Very strong static fields (4.7 T) were shown to decrease micronuclei frequency inmitomycin-treated Chinese hamster lung/IU cells (Okonogi et al., 1996).
Several authors have studied the ability of ELF EMF to alter the repair of strand breaks
induced by hydrogen peroxide or by radiation. No effects were seen with exposure toeither B or E fields (Bersani et al., 1989; Cantoni et al., 1995; Frazier et al., 1990; Whitson
et al., 1986).

328

Mutational changes
Relatively few studies have been reported of the effects of EMF on gene mutation(McCann et al., 1998). As is often the case, the exposure protocols differ widely, and noconsistent picture has evolved on possible effects. Exposure to electric and/or magnetic
fields at various frequencies did not induce mutation in Salmonella typhimurium (Morandi
et al., 1996; Nafziger et al., 1993). Similarly, Ager and Radul (Ager & Radul, 1992) foundthat exposure of yeast cells to a magnetic field (1 mT) alone or in combination withultraviolet irradiation (2Ð50 J/m2) had no effect on mutations; and Pakhomova et al.
(Pakhomova et al., 1998) saw no mutations in Saccharomyces cerevisiae after exposure to
an ultra-wide bandwidth pulsed field (101Ð104 kV/m, impulses repeated at 16 or 600
Hz). In contrast, Koana et al.(Koana et al., 1997) reported that a strong static field (5 T,
24-h exposure) increased the frequency of somatic recombinations in third-instar larvae ofDrosophila melanogaster, which was blocked by vitamin E treatment, suggesting
involvement of oxygen radicals.
Prior and concurrent treatment of a rat embryo fibroblast cell line carrying the Escherichia
coli lacI gene with N-methyl-N-nitrosurea (MNU) or menedione and exposure to a 60 Hz
magnetic field (3 mT) for 120 h did not increase the mutation frequency (Suri et al., 1996).
The hprt gene mutation was induced in human MeWo cells exposed to 50 Hz, 400 mT for
2 h (Miyakoshi et al., 1996). Subsequently, these authors also reported (Miyakoshi et al.,1998) enhanced mutagenicity in a human osteosarcoma cell line, Saos-LP-12, exposed to a
50 Hz, 400 mT magnetic field. When this cell line, which does not carry the p53 gene, wastransfected with an inducible wild-type p53 gene, the enhanced mutagenicity associatedwith exposure to EMF was suppressed, suggesting a role for the wild-type p53 gene inguarding the genome from DNA damage. No marked differences in the mutation spectrum
in the hprt gene was observed in those cells with or without the p53 gene after exposure
to magnetic fields (Miyakoshi et al., 1998). Nafziger et al. (Nafziger et al., 1993),
however, did not observe induction of hprt mutations in Chinese hamster V79 cells after
exposure to a 50 Hz magnetic field at lower field strengths (1 or 10 mT). An effect of
EMF on hprt gene mutations was reported in Chinese hamster ovary cells after exposure
to ionizing radiation in two laboratories. Exposure to EMF alone did not induce mutations
in either study. A dose-related increase in mutation frequency induced by EMF (60 Hz,
0.47Ð0.7 mT) was reported after pre-exposure to g-irradiation (2 Gy) (Walleczek et al.,1998). A small increase in mutation rate was also observed when Chinese hamster ovary
cells were exposed to EMF (60 Hz, 5 mT) after pre-exposure to X-rays (3 Gy)(Miyakashi et al., 1998). Similarly, EMF (60 Hz, 400 mT) increased the mutation rate in
MeWo cells after prior exposure to X-ray (3 Gy) (Miyakoshi et al., 1996). [A clear effectof magnetic fields on mutation has so far been seen only at field strengths well above
those that occur in the environment.]329

4.7.1.2 Transcription
Effects on gene expression
Several studies have addressed the general question of whether ELF EMF can affect RNA
synthesis, with both positive and negative outcomes. This subject has been reviewed(Lacy-Hulbert et al., 1998).
Effects on gene expression, particularly at the transcriptional level, after exposure to ELF
EMF was first investigated by Goodman and coworkers. The main focus of their research
was the effect of EMF on c-myc mRNA levels in human HL60 cells, although in earlier
papers (Goodman et al., 1992; Goodman et al., 1989) they reported increased expressionof several specific transcripts (including b-actin, b-tubulin, histone H2B, c-myc, and csrc) as deduced by dotÐblot analysis. Goodman et al. (Goodman et al., 1989) found thatseveral types of fields (sinusoidal 60 or 72 Hz; pulsed fields at 1.5, 15, or 72 Hz) at fieldstrengths of 0.38Ð3.5 mT could increase mRNA levels by two- to threefold after 20 min
exposure, as measured by dotÐblot analysis. The strongest response was to 60 Hz
sinusoidal fields with a 1.5 mT peak B value. In contrast, this group reported later(Goodman et al., 1992) that the most prominent effects appeared after 20 min exposure
to a 60 Hz, 5.7 mT field. Stronger fields or longer exposure times tended to diminish theobserved effects. The paper included a report of northern blot analysis to confirm theidentity of the investigated transcripts [The group used dotÐblot analysis without internal
controls for quantification of mRNA levels]. Rao and Henderson (Rao & Henderson,
1996)] transfected HL60 cells with a c-fos promoter construct upstream of the bacterial
CAT gene to obtain a reporter gene assay system. The positive control, TPA, increased
CAT activity by 10Ð40% above control levels, while a 20-min exposure to a 60 Hz, 6 mT(rms) field increased the activity by 5Ð20 % above the control level. [The induction ofpromotor activity by TPA was rather small.] Increased expression of the large T antigen
mRNA and protein in SV40-transformed fibroblasts exposed to a 60 Hz, 8 mT field for 20
min (the only exposure conditions employed) was reported (Gold et al., 1994).
EMF (pulsed 72 Hz field, 3.5 mT peak value) stimulated 3H-uridine incorporation,
mRNA synthesis, and protein synthesis but not DNA synthesis in the human leukemia
cell line CCRF-CEM (Phillips & McChesney, 1991). While exposure for 30 min to 4 h
was effective, longer exposure diminished the response. The same cells were used insubsequent studies of transcription of c-myc, c-fos, jun, and PKC-b mRNA; nuclear runoff assays showed two- to threefold increases in mRNA transcription after exposure to a
60 Hz, 100 mT magnetic field for 15, 30, 60, or 120 min. The effects were dependent ontime cell density (Phillips et al., 1992). Exposure of CCRF-CEM cells to a pulsed
magnetic field (72 Hz, 3.5 mT) induced a modest decrease in p21Ðras mRNA and protein
levels (Phillips et al., 1993).
Possible effects of EMF on the expression of specific genes have been studied by othergroups. Lagroye and Poncy (Lagroye & Poncy, 1998) reported that exposure to a 50 Hz,

330

100 mT magnetic field for 5 h up-regulated c-jun expression in primary and immortalized
rat tracheal cells, while expression of c-fos increased in the immortalized cells anddecreased in the primary culture. Down-regulation of the multi-drug resistance gene
MDR1 mRNA was found after E-field stimulation (10Ð3000 mV/cm, 60 Hz, 16 h) (Walter
et al., 1997). Strong static fields (0.18Ð0.2 T) were shown to induce c-fos transcription in
HeLa cells (Hiraoka et al., 1992). In several studies on the effects of 60 Hz fields,
however, no effects on transcripts have been seen, including those of c-myc, c-fos, and cjun, in HL60 cells (Balcer-Kubiczek et al., 1996; Greene et al., 1993), HeLa cells, MCF7
breast cancer cells (Dees et al., 1996; Harrison et al., 1997), and several other human androdent cell lines (Parker & Winters, 1992). [These studies were performed under more
stringent conditions than earlier ones; they included better control conditions and stricter
exposure metrics.] In a study on HeLa cells stably transfected with an HIV-LTR-CAT
construct (Libertin et al., 1994), combined AC and DC fields (10 Hz to 1.6 kHz; 35Ð70mT; plus a 0.17 mT DC field) did not induce reporter gene expression. A 50 Hz (200 or
400 mT) sine-wave field induced expression of a reporter gene containing the human VIP
promoter in front of a b-galactosidase gene only when cells were simultaneously treatedwith forskolin, which activates adenylyl cyclase. These effects were blocked by the PKC
inhibitor calphostin C and also by nifedipine and dentrolen, suggesting that the effect ismediated by calcium (Ohtsu et al., 1995).
The effect of EMF on the general transcriptional level has been studied in the yeast S.
cerevisiae and in cultured human cells (Binninger & Ungvichian, 1997; Woloschak et al.,1998). After exposure of the yeast cells for 15 generations (24 h) to a 60 Hz sinusoidal
field at 20 mT, Binninger and Ungvichian (Binninger & Ungvichian, 1997) found that mostof the mRNA (44Ð67% in four separate experiments) was not affected by exposure,although 26Ð38% of the investigated mRNA species were increased twofold or more by
exposure; 7Ð18% seemed to be down-regulated by at least 50%. The relatively large
variations between experiments are possibly due to the unusually long exposure (several
generations), thus reflecting changes in properties that biological materials undergo withtime. Another genome-wide approach was adopted by Woloschak et al. (Woloschak et al.,1998), who used the so-called differential display reverse transcriptionÐpolymerase chain
reaction protocol. This procedure allows comparisons of material from two experimental
conditions and identification of virtually any change in mRNA pattern. The authors
exposed human HeLa cells for 24 h to a 60 Hz, 0.10 mT magnetic field. After analysis ofroughly 10% of all transcripts, they found two genes that were specifically induced byexposure. Their identity is unknown. The authors deduced that no more than 20 genes
would be affected by their specific exposure regimen.
Effects on c-myc expression
Although a fourfold increase in c-myc mRNA was initially found in HL60 cells exposed tovarious EMF, as measured by dotÐblot analysis (Goodman et al., 1989), the magnitude of
the increase has since been reported to be only 15% above control levels when analyzed
by northern blots and including proper controls after a 20 min, 8 mT, 60 Hz exposure(Karabakhtsian et al., 1994). In transfected HeLa cells, both endogenous c-myc mRNA
331

and the activity of the reporter gene were increased after exposure to a 60 Hz, 80 mT
magnetic field for 20 min (Lin et al., 1994). An additional group (Liburdy et al., 1993a)
has reported a three-fold increase in c-myc mRNA levels after exposure of rat thymocytes
to 60 Hz (22 mT).
Recently, several groups have tried to reproduce or replicate the findings of Goodman andco-workers on c-myc induction by power-frequency magnetic field in HL60 cells.
Exposure to 50 Hz sinusoidal fields (10 mT or 1 mT; 20 min to 72 h) was used by
Desjobert et al. (Desjobert et al., 1995) and a 60 Hz sine wave (0.57 mT to 10 mT, 20Ð60min exposure by Lacy-Hulbert et al. (Lacy-Hulbert et al., 1995), Saffer and Thurston(Saffer & Thurston, 1995), Owen et al. (Owen, 1998), and Miyakoshi et al. (Miyakoshi
et al., 1996). The latter group used only a 5 mT 60 Hz field for 30, 60, or 180 min. Noneof these studies showed an effect on c-myc levels, b-actin level (Lacy-Hulbert et al.,1995), or on any other transcripts as evaluated by the mRNA differential display method(Saffer & Thurston, 1995). In a follow-up study, Goodman and co-workers (Jin et al.,1997), demonstrated that different strains of the HL60 cell line have different responses
to the 60 Hz field. Only cells obtained from Columbia University showed increased c-myc
after exposure, whereas cells from the ATCC were unresponsive. Neither Lacy-Hulbert etal. nor Saffer and Thurston used the Columbia University cells; however, Owen et al.
(Owen, 1998) performed a similar comparison of these cell line variants. They founddifferences in several characteristics, as did Goodman and colleagues, but could not
replicate the finding of changes in c-myc after exposure in any of the strains. Owen et al.
also analyzed the cells in GoodmanÕs laboratory and found no effect of magnetic fields,
irrespective of the exposure location.
Stress protein gene transcription
It has been suggested that cells might respond to EMF with changes in transcription andtranslation of heat-shock proteins, as they do to some other environmental stresses(Goodman et al., 1994a; Lin et al., 1997; Weisbrot et al., 1993). In support of thissuggestion, exposure to a magnetic field (60 Hz sine wave, 8 mT peak B field, 11 mV /minduced field, 20 min) increased hsp70 mRNA in cultured human cells (Goodman et al.,1994b). Exposure to EMF (60 Hz sine wave; 0.8, 8, and 80 mT with an induced E electricfield of 1.1 mV/m, 11 mV /m, and 110 mV/m, respectively) had a similar effect on SSA1mRNA, corresponding to hsp70 in S. cerevisiae (Weisbrot et al., 1993). Additionally,
HL60 cells exposed to 60 Hz, 8 mT (peak-to-peak) for 20 min showed activation of heatshock transcription factor (hsf1) and subsequent DNA binding (Lin et al., 1997);
however, exposure of cultured mouse and human cells to rotating 60 Hz fields (0.1 mT for
24, 48, or 72 h) did not induce hsp70 mRNA synthesis (Parker & Winters, 1992).
4.7.1.3 Translation and protein synthesis
The effect of EMF on protein synthesis both in general and more specifically has beenstudied in several laboratories. Increases in protein synthesis were reported in332

prokaryotes and eukaryotes after exposure to EMF (Lacy-Hulbert et al., 1998). Only afew studies of the effects of EMF on the synthesis of specific proteins are available.
Increased synthesis of some proteins such as IGF II was reported (Fitzsimmons et al.,1992).
4.7.1.4 Summary
Despite the large number of studies of molecular effects in cells exposed to EMF, noconsistent picture emerges. The studies differ substantially in their biological approachand the techniques used; even within the same laboratory, some studies could not
subsequently be reproduced.
DNA damage and chromosomal effects
The results of studies of primary cultures of peripheral blood cells from volunteers
indicate that even quite strong fields, in the millitesla range, do not generally cause
chromosomal aberrations; positive results were reported in only one study.
As no consistency was seen in the exposure parameters required for such effects, theobserved findings have little predictive value.
Mutations
Mutation is an area of molecular research in which consistency among results appears tobe developing. In numerous studies, 48-h exposure to flux densities below approximately
0.1Ð1 mT have consistently shown no effect on mutagenesis in Salmonella typhymurium.
As discussed elsewhere, there is little evidence that EMF below 0.1 mT damage DNA or
induce cytogenetic damage; these effects are usually associated with mutation. Fields of
400 mT have, however, been reported to enhance mutagenicity at the HPRT gene locus ina human cell line after pre-exposure to ionizing radiation. In addition, a 2-h exposure to a
400 mT field enhanced mutagenesis in the absence of ionizing radiation in this same cellline and in a human osteosarcoma cell line. Expression of a regulated p53 transgene in theosteosarcoma cell line suppressed the effect of EMF on mutation. At lower field
intensities (0.23Ð5 mT), exposure was reported by two laboratories to enhancemutagenicity in Chinese hamster ovary cells after exposure to ionizing radiation, and in
one laboratory the mutation response was found to depend on the intensity of the field.
Finally, in a single study, a static field of 5 T was shown to increase the frequency ofsomatic recombination in Drosophila in a protocol that implicates the involvement ofoxygen radicals.

333Effects on gene expression and stress response
A few research groups have contributed most of the scientific literature on EMF-related
effects on transcription and gene expression. Overall, the results are conflicting, especiallywith regard to the effects of power-frequency fields. Attempts to replicate the findings ofother laboratories have met with little success, although reproducibility has been reported
within a single laboratory.
The steady-state mRNA levels of several genes, including proto-oncogenes such as c-myc,c-fos, and c-jun, were reported by a single laboratory to be increased after exposure to
EMF. The reports indicated that very low field strengths are effective and that specifictime-windows are needed to induce effects. The effect has been seen for several years.
Specific studies of replication regarding c-myc expression in other laboratories have notbeen able to confirm this finding. As the reported response was lowÑa 10Ð20%
increaseÑreplication will be difficult, if this effect is real. It is furthermore unclear
whether such small effects on c-myc are biologically important for downstream events.
The group that reported induction of proto-oncogene expression also tried to follow thespecific sequence of events that leads to induction of hsp70 transcription and translation.
Their findings indicate that the primary effect is a stress response to the field, but this isdifficult to reconcile with an increase in RNA synthesis and mRNA transcription in
general.

4.7.2 Signal transduction and proliferation
Signal transduction occurs in molecular systems at the cell membrane and inside the cell,in which signals from the environment and from other cells are received. These signals
regulate intracellular processes, such as metabolic activity, gene expression,differentiation, and cell proliferation. Signal transduction processes are important
pathways by which EMF may affect cell function. Membrane signal transduction
processes have been an area of particular attention, mainly because the cell membranepresents a substantial barrier to electric fields, especially in the range of field strengths
and frequencies present in the environment. Electric fields are attenuated between theexternal plasma membrane surface of mammalian cells and the interior of the cell by an
estimated factor of 103Ð105 (Polk, 1992b; Polk, 1992c) No significant penetration of
information-containing electric signals across the cell membrane can be postulated for the
60 Hz ambient fields encountered in ordinary domestic situations.
Membrane-mediated signal transduction by hormones and other signaling agents involves
transmission across the plasma membrane that does not require penetration of themembrane. Signals associated with a conformational change in a membrane protein arepropagated across the cell membrane by three well-understood mechanisms: opening andclosing of ion channels and resultant current flow; changes in an intrinsic enzymatic334

activity of the receptor; and changes in the affinities of the receptor for intracellular
proteins, which might have enzymatic activity.
In nearly all cases, the mechanism of signal transduction distal to the receptor involves
effects on intracellular pathways due to changes in the ionic composition of the cytosol(e.g. changes in intracellular calcium) or changes in phosphorylation of intracellular
proteins (e.g. enzyme activity, enzyme regulators, and factors transcriptional regulatory).
Cellular responses to signals are either short-term, with little or no persistence of theeffect after removal of the signal, or long-term, involving persistent changes in thefunction of cells, such as increased or decreased proliferation, changes in gene expression
or differentiation, and, in some cases, apoptosis (programmed cell death). The short-termchanges are generally mediated by modification of enzyme activity in the cytosol ormembrane of the cell. The long-term changes invariably involve alteration of nuclear
function, such as transcription, cell division, and cell-cycle regulation.
4.7.2.1 Calcium homeostasis and flux
Numerous experimental investigations have addressed the interaction between EMF andcalcium fluxes, because calcium is a principal regulator of processes such as muscle
contraction, bone formation, cell attachment, hormone release, nerve impulse
transmission, synaptic communication, membrane potential regulation, and cellproliferation. Calcium ions are strictly regulated in all cell types and serve as messengers
or effectors of many biological processes (Rasmussen & Barrett, 1984). They also serve
as second messengers in excitable and non-excitable cells, where the cytosolic
concentration of calcium regulates the activities of a series of molecules, including kinases,
phosphatases, phosphodiesterases, cytoskeletal components, and ion channels.
Walleczek and Liburdy (Walleczek & Liburdy, 1990) observed that 60 Hz magnetic fields
increased 45Ca influx during concanavalin A-induced signal transduction in lymphocytes.
Rat thymocytes were exposed to a 22 mT magnetic field (induced electric field, 1.0
mV/cm) for 60 min at 37 °C in the presence or absence of concanavalin A. In the absenceof the mitogen, the cells were unresponsive to the magnetic field: the 45Ca influx was notaltered. In its presence, the magnetic field increased the 45Ca influx by 50Ð200%.
Even though the ion cyclotron resonance mechanism (Liboff et al., 1990) is no longer
accepted as a plausible biophysical explanation, a number of experiments were performed
under exposure conditions corresponding to the calculated ion cyclotron resonancefrequency for calcium, with variable results. For example, some investigators (Liburdy,
1992; Walleczek & Budinger, 1992; Yost & Liburdy, 1992) found alterations when these
exposure conditions were combined with stimuli such as mitogens. Parkinson and Hanks(Parkinson & Hanks, 1989), however, saw no changes in cytosolic calcium concentrations
with resonant and nonresonant EMF in Balb/c#3T3, L929, V79, or ROS cells.

335

Lindstrom et al. (Lindstrom et al., 1993) showed that application of a 50 Hz 100 mT
magnetic field increased intracellular Ca++ signaling in the Jurkat T-cell line, and the effectwas similar to that obtained with an anti-CD3 monoclonal antibody, used as a positive
control. Additional work by this laboratory showed that exposure to this EMF resulted
in a significant increase in inositol 1,4,5-trisphosphate concentration (Korzh-Sleptsova etal., 1995). As chelation of intracellular Ca++ did not block the increase, magnetic fields
may affect signal transduction events upstream of inositol 1,4,5-triphosphate. Lyle et al.
(Lyle et al., 1997) failed to replicate these studies on calcium signaling. [Differences in thestrain of Jurkat cells may have affected the response.]
It is well established that intracellular calcium concentrations can oscillate in response to
an external stimulus (Fewtrell, 1993; Meyer & Stryer, 1991), the period of theoscillations typically being between 1 s and several min. A model based on nonlinear
dynamics and the theory of self-sustained (limit cycle) oscillators was developed whichshows how a small change in the signal pathway at an early stage can lead to large changes
in calcium metabolism in the cell (Eichwald & Kaiser, 1993); however, experimental
verification of this model is lacking.
More recent experimental work has taken advantage of technical advances in the study ofcell calcium metabolism, including the development of intracellular calcium probes,
sensitive imaging procedures, and calcium-selective microelectrodes (Borle, 1990;
McLeod, 1992). These studies also involve improved techniques for estimating exposure
to EMF.
Walleczek et al. (Walleczek, 1995) developed a dual-chamber real-time fluorescence
spectroscopy system that allows sham exposure to study the effects of low-level ELF
fields. Exposure to a 60 Hz 2 mT magnetic field inducing an electric field of 1.8 mV/m had
no effect on calcium influx in cells with a high initial calcium influx rate (n = 65), but incells with a low pre-exposure flux rate, field exposure resulted in a significant increase(3.5%, n = 88; p < 0.001) in comparison with sham-exposed samples after a single 2-min
exposure. The authors concluded that the cellular response to field exposure is strictly
dependent on the cell state.
McLeod (McLeod, 1992) studied changes in calcium transient activity in a transformed
bone cell line (ROS17/2.8) using a pure electric field exposure system. Aqueorin-loaded
cells growing in a monolayer on glass or polystyrene substrates were exposed to 60 Hz
electric fields (0.1Ð10 mV/m). Exposure resulted in a significant, dose-dependent decrease
frequency of Ca2+ pulses or amplitude. activity that was different for the two substrates.
The lowest threshold for a detectable field effect was estimated by the investigators by
extrapolation to be approximately 0.4 mV/m for the cells growing on polystyrene. Sisken
et al. (Sisken, 1998), using a similar approach for measuring calcium but a significantly
different exposure system based on magnetic induction, were unable to replicate theseeffects.

336

Sontag (Sontag, 1998) used HL-60 cells differentiated into granulocytes to study theeffect on cytosolic free calcium of sinusoidal electric fields at selected frequencies between
0 and 100 Hz with the calcium indicator fluo-3. Field strengths of 1-2000 Vpp/m (external
field) or 0.1-1000 Vpp/m (in medium) had no significant effect. [As the highest of these
intensities would depolarize the cells by more than 10 mV, the sensitivity of this assay todetect intracellular calcium changes is questionable.]
4.7.2.2 Receptor-mediated signaling pathways
Although many early studies on bone cell cultures were performed with complex
waveforms, it has since been demonstrated that sine-wave fields can have similar effects.
The cellular mechanism of bone stimulation by sine-wave fields appears to be similar tothat of pulsed fields. Exposure to a 0.1 mT, 60 Hz sinusoidal magnetic field (Luben, 1993;
Luben, 1994) significantly inhibited cAMP accumulation in osteoblasts in response to 1
nM parathyroid hormone. This inhibitory activity was decreased at higher doses ofparathyroid hormone, with no significant inhibition at 100 nM or 0.1 mM -7 mol/L.
Frequency spectrum analysis of the Electro-Biology TM pulsed fields indicated that themost widely used clinical device has a significant component of magnetic field strength in
the vicinity of 60 Hz (Polk, 1995). Subsequent experiments with the same 0.1 mT 60 Hz
exposure field (Luben, 1994) also showed that exposure for 30 min to 24 h caused
translocation of protein kinase C (PKC) to the membrane fraction of bone cells, followed
by a progressive down-regulation of PKC activity. Down-regulation of PKC is often seen
after treatment of cells with agents such as hormones and phorbol esters which activate it(Kikkawa et al., 1989). It has been known for some time that agents that regulate
parathyroid hormone receptor responses in osteoblasts also induce PKC translocationand down-regulation (Abou-Samra et al. 1989; Fujimori et al., 1992).
PKC is believed to be the receptor for tumor-promoting phorbol esters (Kikkawa et al.,1989), and several investigators have examined the effects of magnetic fields on PKC.
Monti et al. (Monti et al., 1991) showed that HL-60 lymphocytes exposed to a 50 Hz, 8mT magnetic field have increased binding of the PKC-specific phorbol ester PDBu,
suggesting that these relatively strong magnetic fields may modify the cellular response totumor promoters. Similar results were obtained by Holian et al. (Holian et al., 1996), whoshowed that PKC activity in the cytosol of HL-60 human leukemia cells is regulated byexposure to 60 Hz electric fields at 100Ð1000 mV/cm. The effects of EMF treatment wereadditive with those of 2mM TPA.
Miller et al. (Miller & Moulder, 1998) used the human promonocytic leukemia cell line
U937 to evaluate the hypothesis that exposure to a 60 Hz EMF amplifies the PKCdependent signal transduction pathway that mediates the activation of NF-kB or AP-1dependent reporter gene expression. In comparison with well-understood chemical andbiological agents, EMF of 80, 100, or 1300 mT for 0.5-24 h had no effect on the NF-kB or
AP-1 signaling pathway. This finding raises the possibility that the membrane receptor-

337

linked protein tyrosine kinase signaling pathway operating in B-lineage leukemia cells
may be important for the effects of EMF.
Uckun et al. (Uckun et al., 1995) also reported that PKC activity is increased in humanpre-B leukemia cells exposed to a 60 Hz 100mT magnetic field. Moreover, activation of
PKC was dependent on the activation of lyn kinase, a tyrosine protein kinase of the src
family which is known to be involved in proliferation of leukemia cell clones. In recent
studies, the same group used the DT-40 chicken lymphoma B-cell model to demonstratethat lyn kinase is essential for phospholipase c-g2 activation and inositol 1,4,5triphosphate turnover stimulated by exposure to 60 Hz, 100mT EMF (Dibirdik et al.,1998). In a third paper, this group reported that phospholipase c-g2 activation in EMFstimulated cells in the DT-40 model system is mediated by stimulation of BrutonÕs
tyrosine kinase (Kristupaitis et al., 1998). These three studies provide evidence that adelicate balance of growth regulation in B-lineage lymphoid cells might be altered by
EMF.
[The findings of UckunÕs group are of interest as they show that EMF affect a wellunderstood, important signal transduction pathway involved in signaling through the Bcell receptor. Simultaneous, blinded, real and sham exposure was not carried out in the
recent studies of Dibirdik et al. and Kristupaitis et al. since both reports indicate that theunexposed cells were placed in a Ôcontrol incubatorÕ with a measured field of 0.8 mT. Thisis a critical procedure for quality control. Their observation of apparently robust effects
occurring within 15 s of exposure to a 100mT 60 Hz field, coupled with the uncertain roleof the biological and exposure conditions required for a robust effect, indicate that
replication in other laboratories is essential.]
Miller and Furniss (Miller & Furniss, 1998) attempted to replicate the effect of a 100mT,
60 Hz EMF on inositol 1,4,5-trisphosphate shown by Dibirdik et al. and Kristupaitis etal., using the DT40 genetic model obtained directly from the Uckun group and with anexperimental design shared between the two laboratories. A rigorous experiment, withblinded sham and field exposure and B-cell receptor-induced signaling as a positive
control, showed no effect. [The failure to replicate the findings may be due to a number ofreasons. MillerÕs group presented a detailed protocol for exposure in a well-characterized
system and showed no causal effect, whereas UckunÕs group showed an apparently
robust effect and presented multiple types of evidence for an EMF-induced signaling
pathway but without sham exposure.]
4.7.2.3 Cell proliferation
Cell proliferation is a complex process which is under the control of cellular signaltransduction pathways. Altered proliferation of cells in vitro has been observed in a
number of studies, but in none were sham controls used and none have been
independently replicated. For example, Rosenthal and Obe (Rosenthal & Obe, 1989)
showed a 10Ð15% increase in cell-cycle progression of human lymphocytes exposed to a338

5 mT, 50 Hz field. West et al. (West et al., 1994) demonstrated increased colony growth
in anchorage-independent JB6 cells after 10Ð14 daysÕ exposure to a 1.1 mT 60 Hz
magnetic field. No effect of the induced electric field was reported. Antonopoulos et al.
(Antonopoulos et al., 1995) independently confirmed the effects of a 5 mT 50 Hz fieldreported by Rosenthal and Obe (Rosenthal & Obe, 1989). Using two exposure systems
with temperature control, they showed significant acceleration of the cycle of humanperipheral lymphocytes. Schimmelpfeng and Dertinger (Schimmelpfeng & Dertinger,1993)) reported a reduction in cell number after exposure of SV40-3T3 cells to a 2 mT, 50
Hz field. In a subsequent study of proliferation, Schimmelpfeng and Dertinger(Schimmelpfeng & Dertinger, 1997) used organ culture dishes with an inner and outercompartment and flow cytometry to demonstrate that the reduction in cell number after a
1h exposure to a 2 mT, 50 Hz field was due to the induced electric field. The peak
induced electric field was calculated to be 8Ð12 mV/m.
In the most recently reported study on proliferation, Katsir et al. (Katsir et al., 1998)
demonstrated an increase in cell proliferation with exposure over the frequency range of
50Ð100 Hz and intensity range of 0.1Ð0.7 mT, as assayed by cell counts, 3H-thymidine
incorporation, and MTT. Both frequency- and intensity-dependent responses wereobserved, with a maximum enhancement of proliferation of 70% seen with exposure to
100 Hz at 0.7 mT (p < 0.05). At 50 and 60 Hz, cell proliferation was enhanced by 13%
and 26%, respectively. A blinded experimental design was used which included shamÐ
sham studies, although active sham exposure (double-wound coils) was not included.
A potential correlation between cell proliferation and exposure to magnetic fields was
described by Liburdy et al. (Liburdy et al., 1993b) in human estrogen-responsive breast
cancer cells (MCF-7 cell line). These cells grow rapidly in the presence of normal
concentrations of estrogens, but their growth rate decreased in the presence of melatonin,a hormone produced by the pineal gland. It has been proposed that disruptions of thenormal daily cycle of melatonin synthesis are risk factors for human breast cancer(Stevens, 1987). Melatonin synthesis in whole animals has been shown to be altered byexposure to ELF EMF (Wilson et al., 1990). Liburdy et al. confirmed previous studies by
Blask (Blask, 1993) that melatonin at a normal physiological concentration (10-9 mol/L)
can decrease the growth rate of a specific strain of MCF-7 cells; however, application of a
1.2 mT sinusoidal magnetic field at 60 Hz prevented this action of melatonin. A field of
0.2 mT had no significant effect, suggesting that a threshold might exist between 0.2 and1.2 mT. In more recent work, LiburdyÕs group extended these findings to demonstrate inexperiments similar to those carried out using melatonin that the antiproliferative action oftamoxifen (an anti-cancer drug) is blocked by a 1.2 mT field (Harland & Liburdy, 1997).
They also showed that the effect was due to the magnetic field and not due to the induced
electric field.
Two other laboratories replicated the effects of 1.2 mT fields on inhibition of MCF-7 cell
growth by both melatonin and tamoxifen (Blackman et al., 1998; Liburdy & Levine,
1998). LiburdyÕs group reported similar effects of 1.2 mT on inhibition by tamoxifen of asecond human breast cancer cell line, T47B (Harland et al., 1998) and a human glioma cell339

line, SF-757 (Afzal & Liburdy, 1998). [While these results have been replicated, theextremely small effects observed (10Ð20% growth over 7 d) and the nature of theexperimental design raise serious concerns about the robustness of this effect.]
4.7.2.4 Enzyme synthesis and activity
BlankÕs group has reported effects of VLF electric fields on the Na/K ATPase ion pumpin membranes (Blank, 1992; Blank & Soo, 1992b). Electric fields of 30Ð300 Hz wereapplied for 15 min to membrane preparations at a current density of 55 mA/cm2 (1.1mV/cm); the response was complex, with either increases or decreases in enzyme activity,
depending on the concentrations of sodium and potassium ions in the medium. ATPase
activity was inhibited by fields when the enzyme was in a medium containing optimal
concentrations of activating cations and stimulated when the enzyme activity was reducedby ouabain or by lowering the temperature. Blank estimated that the threshold for effects
was an electric field strength of approximately 5 mV/cm across the membrane, and thisthreshold was associated with a current density of 8 mA/cm2. This threshold value,
although low by comparison with ambient electric fields in air near power lines, is muchhigher than those believed to be induced by environmental exposures to electric fields.
The results can be interpreted as indicating that electric fields induce changes in thebinding of substrate ions (Na+ and K+) to the ion pump at high and low concentrations of
the ligands, as in the studies of Liburdy and Luben described above.
Ornithine decarboxylase (ODC) activity is modulated by membrane-mediated signaling
events, and its activation during carcinogenesis is associated with the activity of mitogens
and tumor-promoting agents of various types. Byus et al. (Byus et al., 1987) reported
that ODC activity in three cell linesÑhuman lymphoma cells (CEM), mouse myeloma
cells (P3), and rat hepatoma (Reuber H35) cellsÑwas increased by up to 500% when
they were exposed to a sinusoidal 60 Hz electric field at 10 mV/cm. Increased ODC
activity in Reuber H35 cells was detected at fields as low as 0.1 mV/cm. In comparison,phorbol ester at doses associated with tumor promotion activated ODC by more than
1000%. The investigators concluded that electric fields act on the cell membrane, resulting
in an effect of signal transduction on ODC activation by mechanisms that were notdirectly investigated in these or subsequent studies. These findings have been used as abasis for the hypothesis that low electric fields act as a co-promoter with tumorpromoting agents, resulting in more activation of ODC and more growth promotion ofcarcinogen-induced cells than in the absence of electric fields. Litovitz et al. (Litovitz etal., 1991) also reported enhancement of ODC activity in mouse L929 cells by exposure toa 60 Hz magnetic field for 8 h at a strength of 1, 10, or 100 mT. Maximal enhancement ofapproximately 100% above the control level was produced by 4 h of exposure to amagnetic field at 10 mT.
Effects of EMF on ODC activity have also been reported by other laboratories, although
the conditions and signaling agents varied. Mevissen et al. (Mevissen et al., 1995) showedthat exposure of rats in vivo to a 50Hz, 50 mT field for six weeks doubled the ODC
activity in mammary tissue. Valtersson et al. (Valtersson et al., 1997) found that both340

ODC activity and polyamine levels were increased in the Jurkat human leukemia cell line,
but not in the non-leukemic CEM lymphocyte line, after exposure to a 50 Hz, 0.1 mT
magnetic field. Little effort was made in these studies to isolate the specific change inmembrane receptor mechanisms that resulted in the observed change in ODC activity.
Litovitz et al. (Litovitz et al., 1994) and Farrell et al. (Farrell et al., 1998) extended theirearlier observation of increased ODC activity in mouse L929 cells at 60 Hz, 10 mT, byshowing that an incoherent noise field could block the effect of the coherent 60 Hz field at
equal flux density. In contrast, Azadniv et al. (Azadniv et al., 1995) showed that a 4h
exposure of L929 cells to a 60 Hz 10 mT magnetic field had no statistically significant
effect on ODC activity. Moreover, Cress et al. (Cress et al., 1995) failed to show aneffect when using the cells, methods, and exposure system of LitovitzÕ group. [Thefunction generator and power amplifier used in this study were not, however, those usedby LitovitzÕ group.]
4.7.2.5 Apoptosis
Scarfi et al. (Scarfi et al., 1991) showed that micronucleus formation in human
lymphocytes was not affected by exposure to a pulsed magnetic field of 2.5 mT (peakpulse) at 50 Hz. This field also had no effect on mitomycin C-induced micronucleus
formation. This finding was consistent with that of a previous study from the samelaboratory (Cossarizza et al., 1989), in which the same pulsed magnetic field produced nochange in cell survival or unscheduled DNA synthesis in human lymphocytes with orwithout treatment with ionizing radiation.
Tofani (Tofani et al., 1995) reported a synergistic effect on micronucleus formation inhuman peripheral lymphocytes after concurrent exposure to mitomycin C and EMF at aCa++ resonance condition consisting of a 32 Hz 75 mT AC field with a 42 mT static field.
In these studies, neither a 75 mT nor a 150 mT AC field affected micronucleus formationin the absence of mitomycin C or an applied static magnetic field.
Lagroye and Poncy (Lagroye & Poncy, 1997) observed no change in micronucleus
formation in a spontaneously transformed tracheal epithelial cell line exposed to EMF
alone (50 Hz, 100 mT, sinusoidal), but when the cells were exposed to EMF plus 6 Gy ofionizing (gamma) radiation, the number of binucleated cells with micronuclei increased byapproximately 10% (p < 0.05).
Simko et al. (Simko et al., 1998) examined micronucleus formation and other apoptotic
morphological changes in two human cell lines exposed to 0.1Ð1.0 mT 50 Hz AC
magnetic fields. In the SCLII transformed squamous-cell line, a dose-dependent increase in
micronucleus and apoptosis was seen after 48 and 72 h continuous exposure to 50 Hz(0.8 and 1.0 mT). In contrast, in a non-transformed amniotic fluid cell line, no significant
changes were noted, suggesting that different cell lines react differently to the same field.
In a brief communication, Ismael et al. (Ismael et al., 1998) reported use of a specific341assay system for apoptotic cells (TUNEL assay) to observe in increase in apoptosis ofmouse thymocytes treated with dexamethasone. The increase was observed only inthymocytes and not in splenic T-cells from animals exposed to a 0.4Ð1.0 mT 60 Hz
magnetic field. The levels of apoptosis in thymocytes and spleen cells from mice exposed
to an 8Ð20 mT DC magnetic field were similar to those in controls.
[None of these recent studies of apoptosis has been replicated. The wide variety ofeffects, cell lines, and exposure conditions and the relatively qualitative techniques used
(e.g. micronucleus counting) cast doubt on any robust effect. Use of more accurate
techniques such as the TUNEL and other quantitative assays may result in moredefinitive answers in the future.]
4.7.2.6 Summary
The body of work on signal transduction suggests that power-frequency EMF, withmagnetic fields ³ 100 mT and electric fields ³ 1 mV/m, are likely to have some effect on anumber of signal transduction-related pathways in mammalian cells. Most of the studies,even those that appear to have been performed carefully, were reported from single
laboratories, and the results cannot be considered conclusive. Blocking of antiproliferative
effects has been replicated at 1.2 mT, but its physiological significance is unknown.

4.7.3 Induction of cytological markers
Cells undergoing embryogenesis, somatic differentiation, and some pathways in
carcinogenesis show changes in cytological markers that indicate the expression of lineagespecific genes. These markers include changes in the kinetics of embryonic staging,changes in matrix protein synthesis, changes in cell surface characteristics, changes in cellmorphology, and gap-junctional communication.
Changes in the kinetics of staging in embryogenesis are a well-accepted measure ofcoordinated development and can be readily measured in a number species in vitro. A
drawback to this assay is that there is little evidence that changes in the onset of thesestages result in aberrant development.
Changes in matrix protein synthesis, including both extracellular matrix molecules and celladhesion molecules, are also well-accepted measures of changes in a cell populationÕs
differentiated state. Not only does the matrix modulate cell differentiation, but many cell
types, particularly those of mesenchymal lineage, can significantly modify thecharacteristics of the matrix by synthesizing extracellular matrix molecules or matrix
metalloproteases. In addition, by changing integrin expression, cells incapable of altering
the substrate characteristics can modulate the degree and nature of their attachment to that
substrate (Shumaker et al., 1994) Differential adhesion can affect cell associative342

preferences in heterogeneous aggregates and is therefore considered to play an importantrole in malignant invasion (Steinberg & Foty, 1997).
Closely related to the process of cell adhesion and alterations in the extracellular matrix
are alterations in cell surface characteristics. The glycocalyx serves as the interface
between the cell and its environment, and changes in the charge density, enzyme content,or activity of this layer and the distribution of the various glycosaminoglycans are
accepted markers of differentiation.
There is accumulating evidence that cell shape is a major determinant of differentiation(Folkman & Moscona, 1978) and is a distinct marker of differentiation in many cell
types. Alterations in cell morphology, size, and orientation can reflect the cellularresponse to the extracellular matrix environment but also influence the way in which thecell affects its environment; examples are the orientation of forces in wound contraction
and the polarity of a tissue. Mobility is also closely related to orientation and is acommonly used end-point of differentiation.
Intercellular communication has been postulated as a necessary condition for cells toprogress through normal differentiation. Gap-junctional communication is considered toplay a key role in tissue homeostasis, and its disturbance has been associated with various
health problems.
4.7.3.1 Embryonic staging
Many studies have been undertaken to assess the developmental effects associated withembryonic exposure to PEMF. The most rigorously designed of these was aninternational collaboration involving six laboratories in four countries (Berman et al.,1990). Each laboratory used two identical egg incubators equipped to produce a 500-ms
pulse of 1 mT with a 2-ms rise-and-fall time. The pulse was repeated at a frequency of
100 Hz. [The induced electric field within the egg can be estimated to have been about 10
mV/m.] Eggs were sham exposed by incubation without energizing the magnetic field coil.
Incubated eggs were exposed for 48 h at 37.6Ð38 °C prior to evaluation for fertility, stageof development, and presence of abnormalities. The evaluations were performed blindly.
The principal observation from the combined results of these studies was a 6% increase in
the number of abnormal embryos (control, 19%; exposed, 25%; p < 0.001); however,significant inter-laboratory differences were observed. No significant effect on embryonicstaging was observed. [This study suffers from a small dynamic range of response andinadequate control, given the small flux densities used.]
Zimmerman et al. (Zimmerman et al., 1990) investigated the effect of a 60 Hz magnetic
flux on the development of sea-urchins. The exposure system consisted of two identicalchambers equipped with two pairs of Helmholtz coils 1.5 m in diameter in an orthogonal
orientation. The two coil pairs were driven 90o out of phase to obtain rms flux densities
up to 500 mT. The geomagnetic field was measured at 43.8 mT; for sham exposure, the343

two pairs of coils were not energized in one system. Fertilized eggs were maintained in 20
ml of seawater at 18 °C in 250-ml beakers [suggesting that the maximum induced rms
electric field intensities were approximately 5 mV/m]. The developmental progress of theembryos was assessed by counting the number of cells in the embryo at 10, 16, and 22 hafter fertilization. A significant delay (p < 0.001) in development was observed, whichshowed a dose-dependent correlation with flux density. The investigators concluded thatthe field had caused a temporary delay at the morula stage of development.
Using a similar exposure system, Cameron et al. (Cameron, 1993) investigated the effectof a 60 Hz field on mouse embryogenesis. Two-cell-stage mouse embryos were cultured
for 36 h after fertilization and then exposed to either a 10 or a 50 mT flux for 48Ð68 h at
37 °C. [As the size of the exposure chambers was not reported, the induced electric field
intensity cannot be estimated.] The developmental stage was assayed by counting thenumber of cells in 9Ð10 embryos under a phase-contrast microscope. Exposure at 10 mT
or 50 mT significantly delayed development (p < 0.025 and 0.01, respectively by binomial
test).
Levin and Ernst (Levin & Ernst, 1995) also investigated the effect of exposure to ELF
magnetic fields on early development of sea-urchins in a study which spanned thefrequency range of DC to 600 kHz. The exposure apparatus consisted of a 10 cm
vertically orientated solenoid, 7 cm in diameter, sufficient to permit insertion of a 250 ml
beaker, and exposure was to 60 Hz over the rms flux density range of 1.7Ð8.8 mT[corresponding to a maximum induced rms electric field intensity of 50 mV/m]. The
control and exposed samples were held in the same incubator at 12 °C, and the embryos
were stirred continuously with thermally isolated stirring motors. By analyzing 200
control and exposed embryos every 15 min, a significant advance in the time of both thefirst and second cell divisions was observed. Moreover, the degree of advance appeared tobe linear with flux density and duration of exposure but to have a complex relationshipwith the frequency of exposure. A monotonic decrease in efficacy was observed overfrequencies ranging from DC to 600 kHz, with a maximum response at DC, suggesting athermal effect.
In an investigation of chick embryo development, sinusoidal field exposure was used
(Veicsteinas et al., 1996). Groups of 210 exposed and sham-exposed (no coil excitation)
eggs were incubated for up to 18 d with 2 h on, 22 h off intermittent exposure to a 200
mT, 50 Hz field [consistent with an induced electric field intensity of about 1 mV/m]. The
embryos were examined for developmental stage after 48 h. Immunocytochemical analysisof extracellular components was performed on day 7, and histological examinations ondays 7, 12, and 18 of incubation. No difference in developmental progression, extracellularcomponents, or malformations in tissues was observed. In addition, follow-up 90 d after
hatching showed no difference between the exposed and unexposed chick populations.
In a recent replication of the chick embryo studies, both pulsed and sinusoidal fields wereused (Farrell et al., 1997). A total of 2500 chick embryos were examined in fiveexperimental series spanning five years. The pulsed field exposure comprised a 500-ms
344

pulse, 100 pulses per second, reaching a maximum flux of 1 mT in 2 ms. The sinusoidal
exposure was at 60 Hz, with a peak flux density of 4 mT. [This gives an estimated peak
induced electric field intensity of 10 mV/m. No sham exposure appears to have beenused.] In four of the five series, a significant increase (p < 0.01) in the number ofabnormally formed embryos was seen in a blinded fashion after 48 h of continuous
exposure. The investigators note, however, that there was also a nearly 10-fold variationin the rate of apparent abnormality in the control samples in the five experimental series,
suggesting that there would be no effect by analysis of variance.
4.7.3.2 Matrix synthesis and extracellular interactions
In association with a longstanding interest in the promotion of wound and fracture
healing, numerous investigators have addressed the ability of low-frequency magnetic
fields to alter extracellular matrix protein synthesis. In two related studies, Murray and
Farndale (Farndale & Murray, 1985; Murray & Farndale, 1985) investigated the effect ofpulsed-field exposure on collagen production in primary and cultured fibroblasts. Primarychick tendon fibroblasts were exposed in 30-mm culture dishes to a Helmholtz coil pairarrangement producing a 2.2 mT flux at 4 kHz lasting 4.8 ms, with the pulse burst
repeated at a 15 Hz rate. [The peak induced fields in the dishes were calculated to be 2.3
V/m. Sham exposure was not incorporated in the experimental design.] Total protein,collagen synthesis, and collagenolytic activity were assayed by radioisotope
incorporation after 6 d of exposure (6 h on, 6 h off). Exposure was found to increase
collagen production relative to total protein and to induce a significant, two-fold reduction
in collagen turnover. The effect of exposure was observed only after the cultures had
reached confluency. Similar results were obtained when cultured fibroblasts from rabbitbone-marrow stroma were used. Thermal effects were specifically addressed anddismissed as a confounding factor.
Fitzsimmons et al. (Fitzsimmons et al., 1986) reported the results of studies with acapacitively coupled exposure system to stimulate bone matrix formation in tissue
culture. Samples maintained in tissue culture were placed within a pair of capacitor plates
separated by 2 cm. Tritiated hydroxyproline incorporation in mouse calvaria and tibia
was assayed over the last 24 h of a 3 d exposure. Exposure to a 16 Hz electric field at a
calculated electric field intensity of 10 mV/m resulted in a twofold increase inincorporation in the calvaria but no significant change in the tibial preparation.
McLeod et al. (McLeod et al., 1987c) also investigated the effect of exposure to electricfields on matrix protein synthesis. Primary bovine fibroblasts were incorporated into
three-dimensional collagen gels which, when contracted, permitted transfer to an
apparatus in which a controlled current density could be applied through agar bridges.
Field intensities of 1 mV/m to 3 V/m were used over a frequency range of 0.1 Hz to 1
Khz. Sham exposure consisted of exposing the cell system in an identical system with nocurrent excitation. Tritiated proline incorporation into extracellular protein was assayed incultures sustained in serum-free medium and exposed for 12 h. Peak sensitivity of the cellsystem was found near 10 Hz, with significant inhibition of proline incorporation at 6.5345

mV/m rms (p < 0.02). Enhanced sensitivity (two-fold increase) of the cell system wasseen when the cells were orientated in the direction of the applied electric field.
MacGinitie et al. (MacGinitie et al., 1994) investigated field-stimulated matrix synthesis
in a cartilage explant model. In this system, 9.5-mm disks of cartilage from thefemuropatellar groove of one- to two-week-old calves were maintained in culture for 5Ð8
d and then exposed to 10Ð30 mA/cm2 at frequencies of 1 Hz to 10 kHz. The explants
were maintained in 0.1% defined serum-supplemented medium during exposure. After 12h of exposure, radiolabelled methionine (a measure of glycosaminoglycan synthesis) was
assayed. Peak sensitivity was observed at 100 Hz, with enhanced incorporation at 24 and30 mA/cm2 (p < 0.05). No significant increase was observed at 10 mA/cm2, a current
density associated with an induced electric field intensity on the order of 100 V/m.
The sensitivity of cartilage explants to fields was also evaluated by Liu et al. (Liu et al.,1996), who exposed 16-d-old chick embryo sternal cartilage explants to 30-ms pulse
bursts (pulse rate, 4 kHz) repeated at 1.5 Hz for 3 h/d for 2 d. Exposure was given from a
Helmholtz coil pair (14 cm in diameter), permitting a peak flux density of 100 mT with arise time of 230 ms and fall time of 30 ms. For sham exposure, the coils in a similar systemwere not energized. Glycosaminoglycan production was assayed by 35S incorporation.
The exposed explants showed a 21% increase in glycosaminoglycan content (p < 0.05)
and, correspondingly, a 30% decrease in glycosaminoglycan released into the medium (p <0.02). Exposure was also found to significantly decrease the amount of newly
synthesized glycosaminoglycan (76%, p < 0.001), leading the investigators to conclude
that the exposure also significantly suppressed pre-existing glycosaminoglycan
degradation in the explants.
Rodemann et al. (Rodemann et al., 1989) reported dramatic increases in protean synthesis
in fibroblasts in response to exposure to a 6 mT, 20 Hz magnetic field. Normal humanfibroblast cell lines (HH-8 and WI38) and virally transformed fibroblasts (WI385V40)
were exposed twice a day for 6 h in a water-cooled solenoid exposure system. Control
cultures were maintained in a separate incubator. S35-Methionine incorporation, 3Hproline incorporation, total protein, and the mitotic index were assayed. After 21 d of
exposure, a 5- to 13-fold increase in total protein synthesis was observed, accompanied
by a significant (p < 0.05) increase in collagen synthesis and a shift in the mitotic index.
The authors concluded that field exposure induced differentiation in these cell lines. [Thelack of a sham-exposed group in a system that required water cooling to maintain the
incubation temperature raises concerns about the reproducibility of these studies.]
4.7.3.3 Cell surface markers
Interest in the effects of pulsed magnetic fields has led to numerous studies of phenotypicchanges in exposed cell populations. Most cell types have a distinct coat (glycocalyx)
which presents a highly negatively charged surface to the environment. Smith et al. (Smithet al., 1991a) investigated the effect of exposure to PEMF on this cell coat by exposing a346

monocyte-like, non-adherent, mammalian cell line (U937) to a 25 Hz pulse-burst fieldfrom a Helmholtz coil pair (7.5 cm radius). A peak flux density of 0.63 mT were used,with a rise time of 200 ms and a fall time of 20 ms. [The induced electric field intensity at
the periphery of the culture vessel was estimated at 160 mV/m.] For sham exposure, theHelmholtz coils were not energized. Surface charge density was assayed by partition
chromatography. Cells exposed for 48 h had a significantly higher partition coefficientthan control cells (p < 0.03), consistent with an increase in the negative surface charge
density on the cells. In the context of previous experiments undertaken by this group, theinvestigators concluded that the observed effect was due to the induced electric field.
Differentiation of bone cells is commonly characterized by an abrupt rise in the activityof alkaline phosphatase, an ectoenzyme believed to be associated with the mineralization
process. McLeod et al. (McLeod & Guilak, 1993) investigated the effect of field
exposure, from three identical solenoid systems installed in a single incubator, on alkaline
phosphatase activity in a rat osteosarcoma cell line (ROS-17/2.8). Bifilar winding of thesolenoids permitted excitation of the sham-exposed samples, and a third unexcited coilsystem was used as the control. The tissue culture dishes were exposed for 72 h to a rms
flux density of 1.8 mT at 30 Hz [sufficient to induce a maximum electric field of 600
mV/m]. Cells were maintained in a normal growth medium with 10% serum, and enzyme
activity was assayed from the conversion of para-nitrophenylphosphate to paranitrophenol, which was quantified spectrophotometrically. While no effect on enzyme
activity was found in exposed cell populations plated sparsely, a doubling of activity (p <0.001) was observed for cells plated densely (3000, or use 3x104 cells/cm2) as comparedwith sham-exposed samples. As these results were associated with a significant
depression in cell numbers in the exposed population, the investigators concluded that thenormal differentiation response of these cells accelerates as they attain confluency.
Neural cell adhesion molecules are associated with neuronal differentiation. Horton et al.
(Horton, 1993) investigated the ability of a sinusoidal flux to affect the onset of
expression of these molecules in rat pheochromocytoma cells (PC12, ATCC), a wellinvestigated neuronal differentiation model. Field exposure was accomplished from a
Helmholtz coil pair (30 cm diameter) to produce a vertical field with a peakÐpeak flux
density of 40 mT at 16 Hz. A DC magnetic flux was imposed at 20 mT, colinear with theapplied AC flux. [The estimated induced electric field intensity would be 50 mV/m. Sham
exposure conditions were not reported.] Cells were exposed to the field for up to 72 h
while maintained in a low serum (1%) medium in T-75 flasks treated with polylysine orpolyornithine. Neural cell adhesion molecule expression was assayed by monoclonal
antibody labeling and immunoprecipitation. A transient effect of field exposure wasobserved, as neural cell adhesion molecule expression was found to be significantly
elevated at 24 h but not at 72 h. Moreover, the effect was observed only in cultures
exposed for 30 min/d and not in those exposed continuously.
Kula and Drozdz (Kula, 1996) investigated alterations in the character of the cell coat offibroblasts caused by field exposure. Balb/c mouse fibroblasts maintained in 5% heatinactivated serum in 43-cm3 flasks were exposed to a 50 Hz, 20 mT flux from a solenoid347

coil; for sham exposure, a similar apparatus was used which was not energized. [Theestimated induced electric field intensity would be 100 mV/m.] The length of exposure
ranged from 2 to 64 min/d from day 5 to day 8 of culture. Glycosaminoglycan distribution
was assayed in the cells, the medium, and cell coats by 35S incorporation. Rapid changes
in the distribution of glycosaminoglycans in the cell coat were observed. 35S incorporation
into heparin sulfate was found to decrease by two-thirds after exposure for only 16
min/d, although longer exposure had little additional effect. Conversely, 35S incorporation
into chondroitin sulfate nearly doubled with similar lengths of exposure. Control exposure
with static magnetic fields of up to 0.5 T showed no effect.
McLeod et al. (McLeod, 1998) used the upregulation of alkaline phosphatase activity indifferentiating bone cells to determine the doseÐresponse characteristics of cells to an ELF(30 Hz) sinusoidal field. A non-transformed bone-cell line which undergoes terminal
differentiation (MC-3T3-E1) was plated into confluent culture and maintained for 4 d in anormal growth medium with 10% serum. These cultures were then exposed to fields froma solenoidal apparatus, which provides an active sham exposure for comparison.
Exposure at 2.5 mT resulted in a non-uniform electric field distribution at the cellmonolayer surface, varying from approximately 100 to 6000 mV/m peak. Alkaline
phosphatase activity was then assayed in situ at periods of 4Ð64 h with an opticalscanning technique which allows spatial mapping of the overall cell response. Alkaline
phosphatase distribution was changed in comparison with that in the sham-exposed
samples within 16 h, reflecting suppression of activity correlated to the intensity of theinduced electric field. By 64 h of exposure, a uniform 25% suppression of alkaline
phosphatase activity was observed across the culture dish. These investigators concluded
that the cellular response depends on the magnitude of the induced electric field with athreshold intensity in the range of 100 mV/m.
4.7.3.4 Matrix interactions: Adhesion, morphology, and motility
In a series of investigations, Blackman et al. (Blackman et al., 1993a; Blackman et al.,1993b; Blackman et al., 1994; Blackman et al., 1998) studied the effect of ELF EMF on
neurite outgrowth in a well-developed model of neuronal differentiation. PC-12 cells wereprimed for growth by plating them on collagen-coated dishes and were maintained on
growth medium with 15% serum for one week; they were then replated, and nerve growth
factor (5 ng/ml) was added to initiate differentiation. The cells were exposed in a
Helmholtz coil pair to produce either a uniform flux of 0Ð30 mT or a non-uniform flux of
0-50 mT, in order to obtain data for determining a doseÐresponse relationship in a single
experiment. Sham exposure was not undertaken, but concurrent control samples wereplaced in an adjacent magnetically shielded enclosure. The percentage of cells undergoing
differentiation was assayed by counting all cells in randomly selected areas in which
neurite growth was greater than the cell body length. Blackman et al. (Blackman et al.,1993b) observed suppression of neurite outgrowth (normally about 60% of the cells),
with maximal inhibition of approximately 20% after 22 h of exposure to a 50 Hz magnetic
field. A threshold-like response in neurite outgrowth was observed, with a transition in
the range of 5Ð10 mT; higher flux densities induced no additional inhibition. In additional348

experiments, uniform suppression was observed in cells in dishes of different sizes
resulting in induced electric field intensities of 3.7Ð45 mV/m, for an applied flux density of
7.9 mT, suggesting that the observed effects were strictly dependent on the magnetic field.
In a subsequent experiment with identical exposure conditions but using the PC-12D cellline, Blackman et al. (Blackman et al., 1993a) showed that exposure to a 50 Hz magnetic
field enhanced neurite outgrowth by more than two-fold (maximum, 55%) in the absenceof nerve growth factor. This effect was also found to be dependent on the magnetic flux
density and not on the induced electric field intensity, 1Ð10 mV/m. Blackman (Blackman,
1994) then investigated the response of the PC-12 cell line to flux densities as high as 50
mT with a nerve growth factor concentration of 50 ng/ml to achieve 100% neurite
outgrowth in the absence of fields. Exposure of the cells at 45 Hz had no effect up to flux
densities of 5 mT, but outgrowth was inhibited at flux densities of 5-30 mT, with amaximum inhibition of up to 60%. With flux densities greater than 30 mT, the efficacy of
the field to inhibit neurite outgrowth appeared to be diminished. Blackman et al.
(Blackman et al., 1998) recently replicated these effects in a blinded fashion [althoughsham exposure was not incorporated in the experimental design].
A trial to replicate the findings of Blackman et al. was undertaken at the Oak Ridge
National Laboratory (Griffin et al., 1998). Populations of PC-12 cells previously primed
by treatment with nerve growth factor were treated with graded doses of this factor alone(2.5 mg/ml) or combined with EMF (2.38 mT at 45 Hz plus 3.66 mT DC). Appropriate
sham controls were included. No significant difference in neurite outgrowth was observed.
Different nerve growth factor-primed populations showed differential response tochallenge with the factor.
Greenebaum et al. (Greenebaum et al., 1996) reported the effects of exposure to pulsed
fields on neurite outgrowth. Chick dorsal root ganglia were isolated from 6 d-l d chickembryos and placed in 60-mm Primeria culture dishes. Neurite outgrowth was initiated bytreatment with 50Ð100 ng/ml nerve growth factor, and the cells were exposed to fields
from a Helmholtz coil pair, which produced a 4.0 mT flux pulse with a 200ms rise timeand a 20ms fall time. [The peak induced electric field intensity at the edge of the culture
dish was estimated to be 3 V/m.] A series of 22 pulses in 4.8 ms were repeated at a rate of
15 or 25 Hz. Exposure lasted 18 h, and the cells were then left undisturbed for an
additional 6 h before fixation and assessment. Controls samples were held in a similar
incubator with unenergized coils. Neurite outgrowth was determined by the length of thegrowth process from the dorsal root ganglion body. In addition, the positions of theganglia within the dish and the angular orientation of the growth processes were recorded.
In their study of 808 ganglia, the authors reported a high level of inter-experimentvariation but were able to identify a significant increase in neurite growth in the fieldexposed population that was independent of nerve growth factor concentration.
Moreover, field exposure led to greater directional growth. No dependence on induced
electric field intensity or frequency was identified.

349

Spadinger et al. (Spadinger et al., 1995) investigated motility and morphological changes incells during field exposure, using an automated tracking system to measure and record thefield-induced changes. NIH-3T3 fibroblasts were maintained in normal growth medium
with 10% serum and exposed in 6-cm petri dishes. They were exposed to verticalmagnetic fields in the frequency range of 10Ð1000 Hz, at rms flux densities of 10Ð800 mT,
from a short solenoid coil encased in plastic. [No sham exposure was performed.] No DC
field was applied, but the geomagnetic field was 29 mT. [The induced electric field
intensity at 60 Hz for a 100 mT flux was calculated to be 0.4 mV/m.] Motility was
assayed as cell speed, direction, and persistence, and the morphological measurements
included cell area and circularity. These assays were performed during 3Ð4-h field
exposures interspersed with periods of no exposure. The investigators found no evidenceof significant changes in motility or morphology that could be attributed to the appliedmagneticfield.
Osteoclast formation is a multistep process involving extensive cellÐmatrix and cellÐcell
interactions, in that cell migration, aggregation, and fusion are required. Rubin et al. (Rubinet al., 1996) investigated the effect of exposure to ELF fields on osteoclast formation in amixed murine marrow culture system. Marrow cells were obtained from the femurs andtibias of 4Ð8-week-old male C57Bl/6 mice and plated on chamber slides with medium andvitamin D to promote osteoclast recruitment. Exposure was begun immediately with thesolenoid exposure system described by McLeod et al. (McLeod & Guilak, 1993), which
provides matched field and sham exposure. The cultures were exposed for 8 d to 30- and
60 Hz fluxes of 1.8 mT [corresponding to an induced rms electric field intensity of 600
mV/m at 30 Hz]. Osteoclast recruitment was assayed by counting all multinucleated,
tartrate-resistant, acid phosphatase-positive cells in each 0.9-cm2 culture well. The counts
were performed in a blinded fashion. A 22% reduction (p < 0.0001) in osteoclast number
was found with exposure to 60 Hz and a 28% reduction with 30 Hz. The investigatorsconcluded that the fields may affect the pool of proliferating precursor cells.
Lee and McLeod (Lee & McLeod, 1998) reported the results of a study of themorphological adaptation of osteoblast-like cells (MC-3T3-E1) to a 60 Hz field. Cells
maintained in culture medium with 10% serum were exposed for 24 h to fields from asolenoid exposure system (McLeod & Guilak, 1993), with a 0.7 mT rms flux density,
sufficient to induce a 0.5-mV/m electric field intensity in the culture wells. Cell length,
width, area, perimeter, circularity, and angular orientation were calculated from digitizedphase-contrast images of the cells with commercial image-analysis software. As reportedby Spadinger et al. (Spadinger et al., 1995), no significant effect of exposure could be
identified when the cell measurements were pooled. When the morphologicalmeasurements were analyzed with respect to the orientation of the cells (angularorientation with respect to the induced electric field vector), however, the cells orientatedparallel to the induced electric field were found to be significantly longer, with larger areasand perimeters, and more spindle shaped (p < 0.001). The investigators concluded thatthese effects were due to the induced electric field rather than the magnetic field.

350

4.7.3.5 CellÐcell communication and gap junctions
Alterations in gap-junctional coupling provide two distinct views of the interactions of
EMF with cells and tissues. First, gap junctionally coupled cells theoretically interact
differently from isolated cells with induced electric currents. Second, gap-junctional
competence can serve as an assay of cellÐcell communication, a factor considered to be
essential in the normal development and function of tissue.
Ubeda et al. (Ubeda et al., 1995) investigated changes in gap-junctional competence indye-coupling experiments. C3H 10T1/2 cells were plated sparsely onto tissue culture
dishes [size not reported] and allowed to proliferate for 18 d until reaching confluence.
Melatonin was then added to the medium at a concentration of 0.1mM, and the cells wereallowed to incubate for another 27 h. At the end of this incubation period, they were
exposed for 30 min to a magnetic field of 50 Hz at 1.6 mT from a Helmholtz coil pair.
Controls were sham exposed by not energizing the coils. A subset of the cells in each dishwas then loaded with Lucifer yellow dye by a single scrape across the culture dish, andtransfer of the dye to adjacent cells was determined by counting fluorescently labeledcells. Exposure to the field blocked the up-regulation of coupling caused by the melatonintreatment.
Conversely, Schimmelpfeng et al. (Schimmelpfeng et al., 1995) showed in dye
microinjection studies with NIH 3T3 cells that a 50 Hz field could up-regulateintercellular coupling. NIH 3T3 fibroblasts which had obtained a monolayer density of 1Ð
3 x 105 cells/cm2 and aggregates of cells 200Ð400 mm in diameter were exposed in 60-mm
culture dishes to a sinusoidal 50 Hz field at 2 mT by placing the dishes within the air gapof an iron core electromagnet. [The maximum induced electric field intensity can becalculated to be approximately 10 mV/m.] Control cultures were placed in the same
incubator at a sufficient distance from the electromagnet that the flux densities were lessthan 2Ð3 mT. After exposure, three to nine cells were assayed for gap-junctional couplingby microinjection with Lucifer yellow. The dye that had spread into neighboring cells wasevaluated by counting fluorescent cells 2 min after the injection. Exposure to the field for
5 min was reported to cause a 1.6-fold increase in the average number of coupled cells in
the monolayer configuration. Coupling of cells in aggregates was not readily quantified.
[Four independent experiments with three to nine cells per experiment provides aquestionable statistical basis for comparison.]
Vander Molen (Vander Molen, 1997) reported a series of experiments designed to test thealtered sensitivity of a cell population to EMF in the absence of gap-junctional coupling.
An osteosarcoma cell line (ROS 17/2.8) was transfected with anti-sense connexin-43 toyield a cell line that was intercellular communication-deficient. Communication-competentand -incompetent cells at similar confluent densities were then exposed to a 1.8 mT rms
flux at 30 Hz [sufficient to induce a 600mV/m electric field intensity in the culture wells]
for up to 72 h from the exposure system of McLeod et al. (McLeod & Guilak, 1993). Cell
proliferation and alkaline phosphatase activity were assayed. The communicationcompetent and -incompetent cell lines had similar sensitivity to EMF exposure. These351

results were confirmed by exposing sparsely plated cell populations (precluding
significant numbers of gap-junctional couplings). The investigators conclude that gapjunctional coupling does not enhance cell sensitivity to EMF.
Griffin et al. (Griffin et al., 1998) examined the effects of EMF on the inhibition of gapjunctional communication by chloral hydrate. Clone 9 rat liver cells were treated with 1.5mmol/L of chloral hydrate for 24 h; they were then left for 30 min for CO2 andtemperature to reach equilibrium and then treated with EMF for 30 min. After exposure
to a combined field of 2.38 mT at 45 Hz and 3.66 mT DC, cell monolayers were assayedfor dye transfer by monolayer assay techniques. Mezerein was used as a positive control,and sham-exposed controls were available. No significant effects of EMF on dye transfer
were observed.
4.7.3.6 Summary
Patterns in cytological responses
The results of the studies described in this section do not show a clear pattern of effects
of EMF on cytological markers. Two of the studies on development showed no effect of
exposure to fields, and two had questionable protocols; the two remaining studies show asignificant effect of exposure, with a delay in the kinetics of progression ofembryogenesis. The delays were achieved, however, only after extended exposure (10Ð70h) to 50Ð500 mT, inducing electric field intensities of 0.5Ð5 mV/m. In none of thesestudies was an active sham-exposure system used, as is now standard in research on EMF
sponsored by the NIEHS.
The results of studies on alterations in extracellular matrix synthesis are interesting, forthree reasons. First, they include two investigations of only electric fields, which
established remarkably low-intensity thresholds (10 mV/m and 6 mV/m). Second, areasonable level of correlation is seen between dose and the differentiated state of thecells. The lowest reported threshold (10 mV/m) was observed for differentiating calvaria,
while the highest (100 V/m) was seen for fully differentiated articular cartilage. Cultures atintermediate stages of differentiation (primary cells, cell lines, and embryonic sternal
cartilage) had intermediate sensitivity to exposure to fields. Each of these experiments
involved long durations of exposure, ranging from a minimum of 12 h to 21 d. Third, itshould be noted that none of the exposure systems incorporated an active sham design.
Several important observations can be made on the basis of the results of the studies ofcell surface markers. In this series, an active sham-exposure system, calibrated according
to NIEHS guidelines, was used, and significant cellular responses were observed incomparison with cells exposed to the active sham. In addition, while high flux densities
that give rise to high-intensity induced electric fields were reported to alter cellular
activity, two investigations with significantly different flux densities (40 mT and 2.5 mT)
but inducing similar electric field intensities (50 mV/m and 100 mV/m) showed cellular352

effects. Perhaps of equal interest, the field frequencies used (16 and 30 Hz) and exposure
durations required (30 and 240 min) were similar in these two studies. Moreover, bothcell systems (PC-12 and MC-3T3-E1) were exposed during well-established stages ofdifferentiation. A critical observation in two of the studies was that the induced electricfield was the active agent.
Similar observations were made in studies of cell morphology. In a terminallydifferentiating osteoclast model, with active sham exposure, an 8-d exposure to a 1.8 mT,
30 Hz magnetic flux, inducing a 0.6-mV/m electric field, resulted in a significant delay.
Consistent with this observation were the morphological changes observed after a 24-h
exposure to a 60 Hz, 0.7 mT flux (inducing a 0.5-mV/m electric field), whereas no
significant morphological changes were observed with a 60 Hz, 0.1 mT flux applied for 3
h. Flux magnitudes and induced electric field intensities smaller than these induced
differential responses, while values well above these consistently produced robust
responses.
Few studies have been reported of the effect of EMF on gap-junctional communication,
and, of those studies that have been completed, fewer have been reported fully. The twostudies reported here provide little or no support for a role of gap junctions in cellularresponses to EMF.
Threshold field intensities and required exposure times
Exposure to EMF can be expressed either as induced electric field intensity or imposedmagnetic flux density. Studies of pure electric fields showed that only ELF fields canaffect cytological responses, with a required threshold intensity in the range of 0.1 mV/mplus or minus one order of magnitude. This threshold is consistent with those found inseveral experiments on magnetic induction. Moreover, no response has been found with
exposure shorter than 30 min, and most reported cellular responses require exposure oftens of hours. Finally, the threshold field intensity with exposure to 10Ð100 Hz appears
to be lower than that for broader-spectrum or higher-frequency exposure.
The patterns associated with magnetic fluxes are more difficult to identify. Flux densities
ranging from 1 mT to 2 mT have been reported as threshold values, although the lowest
are associated with stimuli with a higher frequency content. Assuming an electric field
threshold near 0.1 mV/m, it is difficult to separate the effects of magnetic flux from thoseof electric fields when the induced electric fields exceed this level. Only a few studies
reported cytological responses to induced electric fields below 0.01 mV/m, and theseobservations have not been replicated.

353

4.7.4 Summary
In-vitro experiments permit the testing of potentially toxic exposure under controlled
conditions, typically at doses well above those encountered in the environment. Studiesof the genotoxic effect of such exposure and effects on cell proliferation, alteration of
signal transduction pathways, and modification of differentiation processes can serve to
identify agents with potential carcinogenic effects or effects on other health end-points.
This toxicological approach may be applied to EMF, although careful consideration mustbe given to the range over which the ÔdoseÕ or intensity of EMF is varied; unlike many
chemical agents, EMF may have different mechanisms of fieldÐcell coupling over different
ranges of field intensity.
The generally accepted theoretical limits for effects of EMF are one to two orders ofmagnitude lower than they were a decade ago. The reasons for this change are that new
mechanisms have been considered that were not studied in detail previously and thatslightly more realistic biological models have been constructed. There is no controversy
about the theoretical basis and experimental evidence for biological effects at magnetic flux
densities greater than 0.1 mT or internal electric field strengths greater than approximately
1 mV/m. Similarly, there is general agreement about the lack of theoretical models andexperimental evidence for effects at magnetic flux densities of less than 0.1 mT, andtheoretical models for effects at densities less than 0.1 mT, and particularly less than 5
mT, are controversial. It is important to note that most of the theoretical results reported
to date are based on single-cell models. Realistic modeling of temporal and spatial
averaging across functional groups of cells (e.g. synchronized neurons) is a newly
developing area of research, which may serve to expand the range of physical mechanisms
of interaction. Existing models and theoretical thresholds are only as good as the biological
data used to construct them; advances in biology and biochemistry can therefore be
expected to serve as a basis for advances in our understanding of the mechanisms ofinteractions with EMF.
Three critical factors were considered in evaluating the contribution that in-vitro research
can make to our understanding of the potential effect of EMF on human health: whether
an observed (positive or negative) response has been independently validated, whether
there is a demonstrated physical mechanism for the response at the field intensities used,
and whether the end-points evaluated are widely considered to be predictive of potential
health effects.
A series of recent (1996Ð98) studies demonstrated the effects of fields on gene mutations.
Studies of ELF exposure at flux densities below 0.1 mT have consistently shown noeffect on mutation rates; however, exposure to 0.2Ð400 mT reproducibly and significantly
enhanced the mutation rate after X-ray or gamma-ray initiation. Moreover, exposure to
400 mT increased the number of mutations in the absence of ionizing radiation in two
human cell lines. Thus, multiple, self-consistent reports demonstrate a dose-dependent
effect on a process or end-point commonly considered to be associated with354

carcinogenesis. Importantly, the flux densities used in all of these studies (³ 0.1 mT) arewithin the range of a single physical transduction mechanism, specifically magnetochemical transduction. The potential for magneto-chemical effects at flux densities greaterthan 0.1 mT has been firmly established in both theoretical analyses and biochemical
investigations.
In addition to these reports on genotoxicity, numerous well-programmed studies haveshown strong effects on other end-points commonly associated with carcinogenic agents.
These include significantly increased cell proliferation, disruption of signal transduction
pathways, and inhibition of differentiation, all of these effects being seen at field levels³0.1 mT. These investigations were also performed at sufficiently high intensities thatmagneto-chemical transduction is a plausible mechanism of fieldÐcell transduction,although this does not preclude other mechanisms of interaction. Indeed, several wellcontrolled studies of physical transduction have clearly demonstrated that the induced
electric field can alter cell behavior. In addition to these studies, a large number of wellperformed studies have also shown biological effects of EMF that are not associated withcancer end-points, suggesting that exposure may affect other disease end-points.
A limited number of well-performed studies provide moderate evidence formechanistically plausible effects of EMF greater than 0.1mT in vitro at end-points
generally regarded as reflecting the action of toxic agents.
[This conclusion was supported by 27 Working Group members; there were 2
abstentions.]
There is weak evidence for an effect of fields lower than approximately 0.1mT.
[This conclusion was supported by 26 Working Group members; there were 3
abstentions.]
The potential role of magneto-chemical processes in the coupling of ELF fields tobiological systems suggests that extension of both theoretical and experimental studies ofintensity regimes below 0.1 mT should be conducted.

4.8

Biophysics of interactions of ELF EMF with biological systems
The fundamentals of the interactions of EMF with matter were elucidated over a century
ago and succinctly stated as the well-known Maxwell equations. Years of successful
application of these principles for practical advances has left little doubt about our ability
to understand and predict electromagnetic phenomena when the details of the system andfields are completely described. Application of these principles to biological systems,
however, is very difficult because of the extreme complexity, dynamic nature, and355

multiple levels of organization in living organisms. In addition to their structural andbiochemical complexity, biological systems are also electrically very complex and havewidely ranging conductivities and dielectric properties.
The difficulties encountered in applying electromagnetic theory to the enormous numberof potential interaction sites has slowed progress in understanding the possible biologicaland health effects of EMF. Knowledge of the mechanisms and sites of interaction could
be used to identify appropriate dose metrics, to predict doseÐresponse characteristics, todesign better experiments, and to assist in determining whether harmful effects are likely
at specific levels of exposure. The impetus for developing such an understanding is clear.
Several physical interaction mechanisms have been proposed to explain the possible
biological effects of EMF. Most are based on the well-known electromagnetic interactions
with inanimate materials that can be observed experimentally in the laboratory at
sufficiently high electric or magnetic field strengths. The controversy surrounding theapplication of these mechanisms to explain the biological effects of environmental
exposure to EMF arises for two reasons. First, the field strengths and resulting forces
associated with these exposures are very small. Second, the weak signals produced byfield exposure must compete with the noisy background of endogenous electric fields andnormal thermal fluctuations.
An additional complication in evaluating interaction mechanisms is the complex cascade of
information processing that is involved in normal cell physiology. Physical theory
focuses mainly on the first step in the detection of fields: conversion of energy from thefield into physical or biochemical changes. Measurable biological effects may well occur
far downstream from such interactions, thereby obscuring characteristics such as doseÐ
response that are important for identifying the physical basis of the initial interaction.
The research discussed in this section is useful for addressing four essential questions:
1. What are the mechanisms by which EMF interact with biological systems?
2. At what levels of exposure are effects due to these mechanisms plausible?
3. What experimental evidence exists in support of these mechanisms?
4. Do these mechanisms have implications for the interpretation of in-vivo andepidemiologicalresults?
It is important that a given study clearly state which of the above questions is being
addressed. Studies that address only theoretical signal-to-noise, for example, can be used
to answer question 2 but not the other questions. Because of the complexity of biologicalstructure and function, it can be argued that the presently available theoretical models are356

insufficient to predict or exclude the possibility of biological effects at specific levels of
exposure. The rationale for this argument is that detailed knowledge of local noise
environments, amplification, and specificity arising from spatial coherence of the field,
dynamic processes (e.g. frequency encoding of biological signals), and other factors is notavailable. Only when every potential interaction site has been evaluated can thepossibility of such effects be logically excluded.
Nevertheless, the reasonableness of a health concern is one of the first criteria for deciding
how much attention should be given to it. The results of epidemiological studies, forexample, are often evaluated in terms of HillÕs criteria, one of which is the plausibility of asuggested causal relationship. Epidemiological studies form a large fraction of the basis forconcern about exposure to EMF, and interpretation of their results requires a decision
about whether there is a plausible underlying mechanism of interaction with EMF that
could be responsible for the reported results. The current accumulated body of theoreticalwork provides more detailed guidance for experimentalists about the plausibility ofeffects than was available a few years ago. Although differences in findings persist, there
is general agreement about the plausibility of effects at some levels of exposure, agreement
about the lack of explanatory theoretical bases at other levels of exposure, andcontroversy about the explanations for effects at intermediate levels.
The need for a theoretical mechanism would be reduced if identical or similar experimental
results in vitro or in vivo were available from many laboratories. The lack of such
experimental support increases the role of theory in addressing questions of plausibility.
Thus, purely theoretical investigations of interaction mechanisms are perhaps more
relevant in evaluating the biological effects of EMF than they would be in disciplines inwhich robust experimental results are abundant. One problem in research on EMF is thecomplexity of the exposure environment, as described in section 2. Unless biologically
relevant exposure parameters are identified, biologists must search a massive range of
exposure parameters with few guiding principles.
Few experimental studies are available of the biological effects of EMF at the fieldstrengths commonly associated with residential exposure (< 0.5 mT). The increased risks
suggested by most epidemiological studies of EMF at these strengths are far too small tobe observed in vivo. It is uncertain that the biological changes associated with the small
increased risks (e.g. one additional case of childhood leukemia per 10Ê000 exposedchildren) could be observed as measurable changes in vitro.
Some attempts have been made to test the proposed mechanisms of EMF interactions
experimentally. The papers that are considered in this section directly address questions 1
and 3 above. Although in-vitro results do not provide definitive evidence for human healtheffects, they can provide critical information on important exposure metrics and on
intermediate end-points that may guide the search for health effects.

357

4.8.1 Biologically important interactions at the molecular level
Early attempts to explain the biological effects of EMF focused on simple application ofelectromagnetic theory to calculate the forces on biological molecules and the energies
transferred to them by weak EMF. The extremely small magnitude of these interactions
led many investigators to conclude that they would not occur at normally encounteredfield strengths. More recent theoretical analyses have demonstrated that spatial andtemporal averaging processes (e.g. arrays of ion channels, synchronized cell populations,multiple receptors, and charged species on cell membranes) substantially reduce thepredicted detection thresholds.
4.8.1.1 Forces and torques on ions and molecules
When the original ion (or electron) velocity is due to an electric field E0 (which could beendogenous), it can be expressed in terms of the electrical mobility me as v = me E0. The
transverse force resulting from application of a magnetic field would then be ET = (F/q) =v x B and the ratioET= me BE0

Eq. 4.1

Since the mobility of ions in biological fluids (Pethig, 1979) is on the order of 10Ð7 m2/V s,
this ratio would be £ 10Ð11 for B £ 10Ð4 T. The value of me for electrons inside DNA(Arkin et al., 1996; Meade & Kayyem, 1995; Murphy et al., 1993; Stemp et al., 1995) or
inside mitochondrial membranes (Nicholls, 1982) is not yet known.
When an electric field is alternating, the dipole moments p of molecules due todisplacement of counter-ions are not lined up with the applied electric field (owing tofinite surface conductivity and resulting time delays), and consequently a torque is
produced that gives rise to continuous rotation (Fuhr et al., 1986; Pohl, 1983). The
electric fields necessary to sustain this rotation, even in water (where the opposing
viscosity is only h = 10Ð3 N s/m2), however, is several kilovolts per meter inside the fluid.
This viscous torque opposing the rotation is given by StokesÕ law for a sphere of radius aby
T = 8ph a3 qÇ

Eq. 4.2

where qÇ is the angular velocity. On individual protein molecules after folding, the quasipermanent electric charge distribution is nearly symmetrical. Most protein molecules havetherefore a relatively small net dipole moment, considering their large size (Takashima,1989). Typical values of p are in the range of 500 Debye units (500 x 1.6 x 10Ð29 = 8 x 10Ð
27C m), but can be larger for very large molecules. The torque exerted on such a protein

358

molecule by the 2.5 V/m electric field inside the membrane of a 20 mm cell, which is
produced by a 10Ð3 V/m electric field in the fluid outside the cell, would then be 2 x 10Ð26
N m. By comparison, the value of the endogenous torque measured on the ÔgÕ subunit of
the mitochondrial F1 ATPase, which receives energy from ATP hydrolysis, is 4.5 x 10Ð20
N m (Noji et al., 1997). Relatively large torques can be exerted even by magnetic fields
less than 10Ð4 T on particles, including some of endogenous origin, with high magnetic
permeability (Adair, 1993; Frankel, 1986; Kirschvink, 1992a; Polk & Wu, 1994). Thismechanism is discussed below.
4.8.1.2 Perturbation of chemical reactions
The energy of the weakest, transitory, but nevertheless biologically very importantchemical bondÑthat due to Van der WaalsÕ forcesÑis about 1 kcal/mol (corresponding,on a per particle basis, to 1.62 kBt, where kB is BoltzmannÕs constant and t = 310 °K)(Stryer, 1989). The energies We and Wm shown on Figure 4.2 are given per unit volume.
The volume of an enzyme molecule with a molecular mass of 106 (Price & Stevens, 1989)
and a density of 1.7 x 103 kg/m3 (Stryer, 1989) is 10Ð24 m3. Over this volume, the electricenergy in a medium with relative dielectric constant er ~ 10 (as inside a cell membrane)
would be about 3 x 10Ð34 J £ 10Ð13 kBt for a 2.5 V/m electric field. Such a field would be
produced inside the 6 nm thick cell membrane of a 20 mm diameter cell by a 10Ð3 V/mexternal field. The magnetic energy over the same volume due to a 10Ð4 T magnetic field ina material with the magnetic permeability of free space would be 4 x 10Ð27 J ~ 10Ð6 kBt.
The assumption that the electric field within very complex biological structures is uniform
is, of course, highly unrealistic. Furthermore, the maximum potential energy pE of theelectric dipole with volume v in a field E is considerably larger than the available electricenergy obtained by the product Wev. The fixed charge distribution of the dipolar moleculewould modify the electric field in its vicinity by inducing charges on the interface of thesurrounding dielectric (Coelho, 1979), the resulting energy Wr depending very much on
the shape of the molecule and the electrical characteristics of the surrounding (probably
inhomogeneous and anisotropic) structure. The enzyme molecule considered here (ofmolecular mass 106) might have a dipole moment of 2000 Debye units (3.2 x 10Ð26 C m),giving a maximum value for the alignment energy pE of 8 x 10Ð26 J ~ 1.9 x 10Ð5 kBt. Thus,
the potential energy due to an applied 10Ð3 V/m field (leading to 2.5 V/m in the membrane)
can be specified only as 10Ð13 kBt £ W £ 10Ð5 kBt in the absence of detailed knowledge of
its environment and assuming that the electric field in the membrane is uniform.
All of the general considerations and numerical examples given above strongly suggest thatthe small electric and magnetic fields of interest here cannot be expected to supply, bythemselves, the energies necessary for chemical changes (Valberg et al., 1997). Even verysmall fields, however, might act as control signals to modify processes that depend on
metabolically supplied energy, analogous to the extremely weak radio signals, such as
those transmitted over thousands of miles, that control locally supplied energy which359

powers a loud-speaker or large-screen television set. The exact nature of biological signal
processing systems and their susceptibility to control by time-varying EMF is thus ofparticular interest.
4.8.1.3 Temporal averaging and time-dependent processes
Life processes depend, of course, on the quantities of chemical substances that areprocessed; they also depend on reaction velocities and the periods over which those
processes are completed. Many biological systems contain complex feedback loops andsequences, in which very small changes at one point can ultimately lead to very largechanges further along the communication chain. Prime candidates for the investigation ofsensitivity to EMF are the signal processing structures: receptors on cell surfaces andinter- and intracellular messenger processes. Probably equally important are the biologicalÔamplifier control elementsÕ, e.g. enzymes, particularly when they also are part of signal
processing systems, as in some cell surface receptors. Unfortunately, there is incomplete
knowledge about the intracellular events that transform receptor-mediated signals into cell
behavioral responses (Lauffenburger & Linderman, 1993); more information is available
about very early signal generation, which occurs immediately after receptor or ligand
binding. These early signals are more closely associated with short time-scale responses,
such as secretion and the release of certain cell products such as cyclic AMP, histamine,
and antibodies than long time-scale behavior, for example cell migration and proliferation.
For EMF fields, however, which may be active continuously over long periods, long-term
biological signaling is likely to be even more important than short-term behavior.
Surface receptors fall into three classes (Lauffenburger & Linderman, 1993): those that act
as ion channels, those that interact with G proteins to produce second-messenger
molecules, and those that act as enzymes. Some experimental evidence indicates thesecond group (Luben, 1993) and the third group (Blank, 1992) are of particular interestfor the effects of electric fields. Since the receptors of these two groups are quite different
from ordinary ion channels, caution must be exercised in generalizing information about
the electrical behavior of receptors obtained by analysis of ion channels.
Time scales that are susceptible to intervention from alternating signals are listed in Table
4.46 (Stryer, 1989), which shows the maximum turnover of some enzymes. ÒTheturnover number of an enzyme is the number of substrate molecules converted into
product by an enzyme molecule in a unit time when the enzyme is fully saturated with
substrateÓ. It is obvious that the turnover rates of some enzymes are well within thefrequency range of interest in the present context, which is < 100 Hz.
Finally, in considering the possible nature of biological signals, it is essential to recognizethat both frequency modulation and amplitude modulation or pulse code modulation may
be involved. Oscillations in electrical potential (Jagadeesh et al., 1992)) and in thequantities of calcium and other ions have been observed in many biological systems(Berridge & Galione, 1988), as illustrated in Table 4.47 (Berridge, 1989; Lauffenburger &360

Linderman, 1993). Berridge (Berridge, 1989) suggested that some physiological processes
are under frequency-dependent rather than amplitude-dependent control. After reviewing
reports on this subject and applicable mathematical models (Goldbeter et al., 1990;
Meyer & Stryer, 1991), Lauffenburger and Linderman (Lauffenburger & Linderman,
1993) concluded Òthat oscillations in receptor-generated second messenger systems may
indeed be capable of regulating cell behavioral response in a frequency-dependent
mannerÓ. It is also worth noting that the amplitude of the observed Ca++ oscillations is
not significantly affected by ligand concentration; furthermore, the observed oscillations(ÔspikingÕ) are clearly a non-linear phenomenon which requires models of non-linear
processes for its analysis and for possible effects of even small fields (Eichwald & Kaiser,1993).

4.8.2 Comparison of changes induced by EMF and competing physicalprocesses
The general approach for determining the minimum fields theoretically capable of causing
biological effects is a comparison of changes induced by the fields and by other naturally
occurring energies and forces.
4.8.2.1 Comparison with the geomagnetic fieldA representative value of the EarthÕs magnetic field over continental USA is 0.45 x 10Ð4T.
Bennett (Bennett, 1994) stated that this value is Òabout 200 times that from typical
distribution lines...sudden fluctuations often exceeding 100 mG [10Ð5 T] are correlatedwith unusual solar activityÓ. The second part of the statement is incorrect, since evenpeak variations in very large geomagnetic storms at mid-latitudes rarely exceed 5 x 10Ð7 T(Garland, 1971). In addition, changes of that magnitude take several hours, so that induced
electric fields are very much smaller than that produced by a power-frequency field,
which varies 60 times per second over the same amplitude. The first part of the statement
refers to a static field, which does not induce any electric field or current, although it canmodify the effects of alternating magnetic or electric fields, as suggested by equations (a)and (c) in Figure 4.2 or by its influence on electron spin. Uniform linear motion of a bodythrough a constant static magnetic field also does not induce an electric current, since thetotal magnetic flux through any closed contour does not change. Only tumbling motion,such as by somersaults, or rapid bending (changing the angle between a cross-sectional
area and the direction of the magnetic field vector) would change the total induced voltage
ò E × dl and produce current flow.
4.8.2.2 Comparison with endogenous electric fields
It has been suggested that an induced 10Ð3 V/m 60 Hz electric field is unlikely to affecthuman biology, because naturally occurring electric fields from electroencephalographic,361

electrocardiographic, and other bioelectric sources are about 106 times stronger andimprecisely the same frequency range (Foster, 1992). Electric fields and current densities
due to heart electrical activity (ÔelectrocardiographicÕ) have been calculated using ananatomical model based on magnetic resonance imaging with a volume resolution (1.974 x
1.974 x 3.0 mm) that is reasonably adequate for predicting fields at various body points(Hart & Gandhi, 1997). The results (Table 4.48) show that above 40 Hz the resulting
average endogenous fields are well below 10Ð3 V/m, except in the vicinity of the heart.
Recent measurements of the spectrum of endogenous fields confirm these results (Miller& Creim, 1997).
4.8.2.3 Comparison with thermal noise
Thermal noise, present in all physical systems, is an important factor in limiting thedetection of weak signals. To the extent that the transmembrane channels of a cell are in2
thermal equilibrium with their environment, the mean square thermal noise Vn in suchchannels, considered as a simple resistor, would be the ÔJohnsonÕ noise given by
Vn2 = 4 k tRdf
B

Eq. 4.3

where R is the channel resistance and df its bandwidth for electrical signal transmission.
As a first approximation, Vn could be considered the Ôtransmembrane potentialÕ, which
would have to be measured far enough into the conducting fluid that surrounds the cellthat its entire surface could be considered as at the same potential. If this is done, theresistance R in equation 4.3 is the mean membrane resistance of a membrane that isassumed to be homogeneous, and df becomes the bandwidth of a circuit in which theentire cell membrane is considered to be a single resistor in parallel with the membrane
capacitance C. Subject to these assumptions, by which the cell membrane becomes a lowpass filter,
1
4 RC

Eq. 4.4

Vn2 =

kBt
C

Eq. 4.5RC =e 0e rs

Eq. 4.6

df =

and

Since

where er is the relative dielectric constant of membrane » 6 according to Takashima(Takashima, 1989) and Pethig (Pethig, 1979).

362

df =

1
s
=
4 RC 4e 0e r

Eq. 4.7

The values given by Pethig (Pethig, 1979) and Barnes (Barnes, 1986; Barnes, 1996) forcell membrane conductivity vary between 10Ð5 and 10Ð9 S/m, leading to the estimate
4.5 Hz £ df £ 45 kHz

Eq. 4.8

The actual bandwidth for both noise and signal depends, however, on the source
resistance Rs (e.g. the resistance to current flow in the extracellular medium andcytoplasm) in series with the hypothetical RC parallel combination. With Rs ® 0, df ® ¥and [V(f)/V(f=0)] = 1 for any f; while with Rs >> R, [V(f)/V(f=0)] = 0.53 at f = 1/(4 RC).
When Rs » R, this ratio is 0.78. A more reasonable circuit model, in view of the Ôaccess
resistanceÕ of ion channels, is discussed further on in this section. Weaver and Astumian(1990) evaluated the thermal noise limit on the response of living cells, mainly on thebasis of the assumptions leading to equation 4.5. For a spherical cell with a radius of 10mm, they obtained n n = 2.8 x 10Ð5 V. [Since they used er » 2 rather than the probably
more appropriate er » 6, a better value might be 1.6 x 10Ð5 V, but the assumptions leading
to equation 4.5 are so radical that the value of Vn can be considered only a rough estimate.]
Relating the transmembrane voltage V on a spherical cell of radius r to the applied field E(Foster & Schwan, 1986),
V = 1.5 E r

Eq. 4.9

they obtain a value for the minimum detectable electric field E » 2 V/m for the prototype
cell with r = 10 mm. They then considered elongated cylindrical cells (radius r, length L)and found
Emin =

2 2A
1

3

r 2L 2

Eq. 4.10

where A, obtained from equation 4.3, including effects of signal frequency and membrane
conductivity. In evaluating Vn they used 10Ð7 £ s < 10Ð5 S/m and rather arbitrarily selectedvalues of df » 10 Hz or 100 Hz for the noise bandwidth. They then pointed out that Ôif acellular mechanism for signal averaging existsÕ, the signal-to-noise ratio would improve by
the square root of the number N of signal cycles during an exposure time T, or by fT(since the signal would be added in proportion to N = fT while the incoherent noise would
be added as N ). With time averaging over 4.3 x 104 s = 12 h, and a Df = 10 Hz, theyobtained a theoretical limit for bovine fibroblasts (L = 150 mm) of only 4 x 10Ð5 V/m at
100 Hz. Using a bandwidth of 10 Hz, they concluded that their estimates indicated that363

Òconcerns related to possible biological effects due to very weak environmental electricfields cannot be dismissed on the grounds of being swamped by thermal fluctuationsÓ.
Applying similar thermal noise considerations to molecules in solution, they came to theimportant conclusion that Òmembrane constituents should be much better detectors of an
applied (electric) field than isolated molecules in solutionÓ.
Gailey (Gailey, 1996) pointed out that current flowing through a channel must also passthrough cytoplasm on one side and the glycocalyx at the cell surface. In this Òaccess
resistance of the channelÓ (Hille, 1992), RH enters as resistances (RA, RB) between adjacentchannels in the circuit representation of multiple channels illustrated by Figure 4.1(Gailey, 1996). Gailey (Gailey, 1996) showed that a reasonable approximation of the net
resistance between the mouths of any two channels is given by twice RH as defined byHille (Hille, 1992),
RH =

1
4 as

Eq. 4.11

where a » radius of channel mouth and s is the conductivity of cytoplasm. From Figure
4.1, it is clear that the noise voltage V1 across the first channel depends not only on its
own noise voltage VG1 but also on the noise voltages in all the other resistances. Since RG1
is not directly in parallel with the other resistors, however, it cannot be assumed that thenoise in the different resistors is correlated. Gailey (Gailey, 1996) evaluated a general
expression for the normalized correlation or coherence, g(Vj,Vk), between the thermal noisein any two open ion channels, which depends on the total number of channels. The
results of this calculation are given in Figure 4.2, which indicates that g for typical channel
parameters can be as low as 0.002 when the number of channels reaches 7 x 104. The
noise voltages for this result were obtained from equation 4.3 using d¦ = 100 Hz, a valueof 6.5 x 109 W for channel resistance, and 3.3 x 109 W for access resistance. If voltage froman external coherent source is applied to the combination of N ion channels, the voltages
across all channels due to that source will remain coherent. This result is significant,however, only for open channels when RG is not very much larger than the access
resistances RA and RB. For closed channels, i.e. when RG >> RA,B, the correlation
coefficient g approaches 1, even for a large number of channels.
If a voltage from an external coherent source is applied to a cell with N1 open ion channels
and N2 closed channels, the applied voltages will be coherent across all channels, while thenoise voltages will be coherent only across the N2 closed channels and virtually incoherent
across the N1 open channels. Individual channels open and close randomly. The closing
and opening rate constants, a and b, for exponential probability functions for thesojourns in these states have been determined experimentally. The reciprocals are themean open time (1/a) and mean closed time (1/b). The dependence of these constants on
applied voltage Vm is generally non-linear; however, for small values of Vm the364

dependence can be characterized by slopes Ma and Mb. If ao and bo are the rate constants
before the perturbing signal, one can write (Gailey, 1996)
a (Vm) = ao + Ma Vm

Eq. 4.12b (Vm) = bo + Mb Vm

Eq. 4.13

Since the mean number of open channels N0 is related to the total number of channels by
N0 =

b
N
a +b

Eq. 4.14

it is possible to compute N0 as a function of the perturbing potential Vm from equations
4.12Ð4.14. Thermal noise voltages are practically incoherent across the open channels, as
N0 , while the applied voltage adds as N .
illustrated in Figure 4.2, and therefore add as
0This differential effect is not the case for closed channels. It can then be shown (Gailey,
1996) that the signal-to-noise ratio will improve by a factor ofSdæ ö =
è Nø

Mba 0 - Ma b 0
b M
Mba 0 - Ma b 0g - 0 a
N0

Eq. 4.15

where the signs of the slopes Ma and Mb are generally opposite. Also, for N0 » 104 orlarger, the denominator of equation 4.15 reduces to Mb ao. This improvement factor isshown in Figure 4.3 for a0 = bo. When the slopes Ma and Mb are equal in magnitude but
have opposite signs, the improvement factor due to noise incoherence is only about 2;
however, when Ma >> Mb (with g®0 and N®¥), the value of d(S/N) can approach 100.
4.8.2.4 Comparison with shot and 1/f noise
Biological processes experience not only thermal noise but also Ôshot noiseÕ and 1/f noise.
Shot noise is the fluctuation of a variable, such as ion current, due to its discreteness (e.g.
individual charges that make up the ion current) or ÔgranularityÕ. While the inevitablegraininess of the environment (through collisions) appears through kBt, the graininess ofthe variable itself shows up as a separate source of noise and appears only when a system
is not in thermal equilibrium with its environment and significant energy is passing into orfrom the system (MacDonald, 1962). Shot noise can generally be described by the
Poisson probability distribution, where the standard deviation, s , is proportional tothe mean value of the variable (e.g. current through a membrane channel).

365

1/f noise is noise that, when described according its spectrum, increases with decreasing
frequency as 1/f a . This noise, which appears in a great variety of macroscopic andmicroscopic systems, was thought to arise at cell membranes by flow of ion current
through an orifice (Verveen & DeFelice, 1974); however, recent analytical work andanalysis of available data indicate that 1/f noise in biological membranes is not an inherent
property of ion transport but is produced by random switching of channels between theirdifferent states (Bezrukov, 1996).
The voltage noise spectra of a frog node of Ranvier shown in Figure 4.4 indicate that totalnoise depends strongly on the value of the (quasi-static) membrane potential and that 1/f
noise must be a major component of total membrane noise. Verveen and Derksen(Verveen & DeFelice, 1968) concluded that 1/f is the largest source of noise at the cell
membrane below 160 Hz. Barnes (Barnes, 1986) estimated that 1/f noise and shot noise ina bandwidth of 1 Hz at 1 Hz in the frog node of Ranvier is 103 times greater than thermal
noise; this would translate to a ratio of about 16.7 at 60 Hz.
Astumian et al. (Astumian et al., 1995) and Weaver et al. (Weaver et al., 1998) considereda situation in which the Ònoise drift across a cell membrane is equal to the square root of
the number of molecules passing through the membrane plus the number absorbedÓ, i.e.
the typical Poisson process of shot noise. For membrane channels, calculation gives atime of about 1 h to reach (S/N) = 1 when the electric field E0 in the medium surrounding acell with 100 mm radius is 0.1 V/m. The principle limitation of this analysis is theassumption that only deviations in the total quantity of accumulated substance greaterthan noise in that parameter can be detected. No role is assigned to recognition by any
part of the complex cell signaling system of changes in the velocity of substanceaccumulation or regular periodic changes in that velocity.
Minimum detection limits for ensembles of voltage-gated ion channels were analyzed
theoretically by Gailey (Gailey, 1996)) with a two-state model for channel gating. The
stochastic gating of ion channels is a form of shot noise. Gailey compared the net change
in charge transferred over some period of time due to a small perturbing membranepotential to the expected fluctuations in charge transferred due to stochastic channel
activity. The model predicts that a 1 mV induced membrane potential can be detected aftera few milliseconds by an ensemble of 108 ion channels. Because most cell types havefewer than this number of channels, the model suggests that single cells are unlikely todetect signals of this magnitude; however, groups of synchronized cells, such as thosethat occur in the central nervous system, may be able to detect such signals.
4.8.2.5 Magnitude of competing thermal effects
Weaver et al. (Weaver et al., 1997) suggested that molecular changes due to temperature
variations within biological systems are larger than those expected from weak exposure to
EMF. This statement was based on their evaluation of the temperature dependence of thechemical rate constants, k, given by ArrheniusÕ equation366

k = Ae-Uk Bt

Eq. 4.16

and, apparently, the assumption that electric or magnetic fields could affect a chemical
reaction (or Ômolecular flowÕ) only by changing the activation energy U.
Before discussing either the pertinent numerical results or the assumptions that wereapparently made, equation 4.16 must be discussed in some detail. The energy U
represents the barrier between reactants and product. In deriving equation 4.16, it isassumed that reactions proceed slowly enough that thermal equilibrium between reactants
and the transition state is maintained at all times at the level of the energy barrier. Since
the equation is derived from thermodynamics, it describes only the average properties of asystem and not individual molecular changes. The constant A is given approximately by
Wojciechowski (Wojciechowski, 1975) and Price and Dwek (Price & Dwek, 1984) as
A=

kBt
s
h

Eq. 4.17

where h is PlanckÕs constant and s is a stearic factor, which can be derived from statisticalmechanics and has values between 1 (atom-to-atom reaction) and 10Ð5 (two non-linear
molecules) (Wojciechowski, 1975). At the physiological temperature t = 310 °K, thevalue of the ratio (kBt)/h is 6.5 x 1012/s.
The rate constant k is related to the time rate of change of product formation fromreactants [C] and [D] (where the square brackets indicate concentration) byd[ P]= k[C]c [ D]ddt

Eq. 4.18

where the order of the reaction is indicated by the exponents c and d. The total order of areaction is indicated by the sum of c and d; a reaction that is of Ôsecond orderÕ withrespect to the reactant C will obviously proceed much faster than a reaction that is of firstorder (c = 1). The exponents c and d are experimental quantities, which can be zero or
have either integral or non-integral values. In a single-step reaction (called an Ôelementary
reactionÕ), the order of the reaction is equal to its ÔmolecularityÕ, i.e. the number ofmolecules that must collide for the reaction to take place. When the exponents in anexperimental rate law are not equal to the coefficients of the chemical balance equation(e.g. 2C === D + E), the total reaction must generally occur in a sequence of steps. Ifthey are equal, the reaction may occur in a single step, but this is not necessarily the case(Freifelder, 1985). In complex biological systems, the order of a reaction can change during
its course (Johnson et al., 1974).

367

It will become apparent from the discussions in the next section that electric or magnetic
fields could affect both the stearic factor in equation 4.17 and the effective concentrationof reactants which can interact. Thus, any calculation that shows that the effect on
product formation (equation 4.18) due to a small voltage which modifies U in equation
4.16 is smaller than that caused by a temperature change Dt in equation 4.16 cannot be
generalized, as Weaver et al. (Weaver et al., 1997), to assume that molecular changes due
to temperature variations within biological systems are larger than those expected fromweak exposure to EMF.
It should also be noted that the important chemical reactions in mammals that involve
enzymes have overall rate constants that encompass the rate constants of several
intermediate reactions, so that the overall reaction rate cannot necessarily be described byequation 4.16 (Price & Stevens, 1989).

4.8.3 Proposed physical mechanisms
4.8.3.1 Effects of electric fields on cell surface structures and cell attachment(a) Polarization forces
Polarization forces have been proposed as a possible physical mechanism of theinteractions between fields and cells. It has been suggested that the pronounced
sensitivity of cells to low frequencies is related to the very large increase in dielectric
permittivity with decreasing frequency of living tissue (Foster & Schwan, 1986). Theinterface of the cell with its environment is a highly charged coat, or glycocalyx, and in thepresence of VLF electric fields an ion diffusion cloud develops within the glycocalyx tocompensate for depletion of the co-ion species in this region (Chew, 1984). ELF
excitation of this cloud is also likely to affect adjacent cells (Polk, 1992a). While themicroscopic relative dielectric permittivity of the glycocalyx region remains small (< 100),
the large dielectric enhancement at the macroscopic level produces a substantial force on
the macroscopic collection of fixed charges on the cell surface and in the glycocalyx(McLeod et al., 1993b). The large dielectric enhancement at the macroscopic level is thelarge polarization per unit volume of the bulk tissue, which is due to counter-ion
displacement on cell surfaces when an electric field is applied (Pethig, 1979). Thus, thegradient (Ñe) of the dielectric constant in the glycocalyx region is due to the cellÕs location
within a dielectric environment created by other, adjacent cells.
The Kelvin polarization force density Fv can be derived from equation (E) on Figure 2.3.
Thus, in a material with N dipoles per unit volume, each having a dipole moment p, thepolarization or dipole moment per unit volume P = Np and Fv = P ·ÑE (Haus & Melcher,1989). For non-uniform fields and non-uniform dielectrics, this can be generalized bystress tensor formalism (Stratton, 1941) to368

Fv = (Ð1/2) E2 Ñe

Eq. 4.19

This expression is the starting point for an explanation of at least some of the electricalforces that must be acting at the cellular level. McLeod et al. (McLeod et al., 1993b),
using, apparently, the vector identityÑ(P × E) = (P × Ñ)E + (E × Ñ)P + P ´ (Ñ ´ E) + E ´ (Ñ ´ P)

Eq. 4.20

considered only the purely electrostatic case, when Ñ x E = 0 and Ñ x P = 0, rather thanÑ x E = -(¶B/¶t), and then estimatedFv =ex - em
e 0 Et2 Nm -3
D

Eq. 4.21

where D is the thickness of the boundary layer and em its relative dielectric permittivity,
while ex is the relative dielectric permittivity of the external medium; Et is the tangential
electric field. The pressure, FA, at the boundary layer of area A will then be (Fv A D)/A or
FA » (ex - em) e0 Et 2 N mÐ2

Eq. 4.22

If one uses for ELF (Foster & Schwan, 1986) ex e0 » 10Ð4 F/m and em e0 » 10Ð9 F/m, one
obtains FA = 10Ð6 N/m2 if the applied electric field is as large as 0.1 V/m. This is only
slightly lower than the sound pressure at the threshold of hearing, of about 2 x 10Ð6 N/m2
(Beranek, 1954), which might suggest that the effect is physiologically significant at thisfield intensity.
Since the effect is proportional to the square of the applied field, a sinusoidally timevarying field would give a time average of E02/2, where E0 is the peak value of thesinusoidal field. Therefore, the resulting pressure would act continuously while the field isapplied. McLeod et al. (McLeod et al., 1993b) suggested that this temporal integration
might be responsible for the effects of low-intensity fields. They also pointed out that thepressure variation at constant frequency could excite or enhance the natural mechanicalvibration frequencies of some cellular structures. Furthermore, the same small pressure
applied simultaneously at the boundaries of many cells could have effects on organs ororgan cultures in vitro.
Support for the importance of boundary layer pressure is provided by the findings thatmodulation of bone-cell function by electric fields is dependent on the density (McLeod etal., 1993a) and that the effects of fields below 100 Hz reach a peak near 30 Hz (McLeod
et al., 1987c). Many of the effects seen in vitro in cells that involve neither electric nor
magnetic fields are, however, also dependent on cell density.

369

(b) Coulombic forces
Otter et al. (Otter et al., 1998) suggested that the component of the electric field
perpendicular to the cell in the glycocalyx is sufficiently large to affect cytoskeletal
polymerization by the mechanism known as the Brownian ratchet (Peskin et al., 1993).
The Brownian ratchet has been proposed as a means by which the cell rectifies thethermal motion of its membrane to permit it to extend cytoplasmic processes. It has also
been shown that addition of a weak, homogeneous force F in combination with squarewave modulation can cause particles of slightly different size to move in opposite
directions. The synergetic change in velocity caused by F can be much greater than thedrift velocity that would be caused by F alone (Tarlie & Astumian, 1998).
Otter et al. (Otter et al., 1998) suggested that small imposed oscillations of the membrane
add to the local thermal motion and enhance the ability of actin monomers to diffuse into
the space between the actin microfilament ends and the cell membrane. Atomic force
microscopy has been used to show that 1.2 nm oscillatory deflections of the cell
membrane can result in 1000-nm deformations of the cell surface (20Ð25% of the original
cell height) over 90 s when the frequency of oscillation is 15 Hz. Oscillation at lower (1.5
Hz) or higher (150 Hz) frequencies produces smaller deformations, indicating a strong
frequency dependence of this rectification mechanism.
The force imposed by the atomic force microscopy cantilever in these experiments is
estimated to be on the order of 0.1 pN. The surface charge density of the cell surface coat(glycocalyx) has been estimated to be between 0.001 and 0.2 C mÐ2 (Bongrad, 1988;
Lakshminarayanaiah, 1984; Pethig, 1979). With the largest of these values, an electric fieldof 10Ð3 V/m would exert a force per unit area of rE = 10Ð4 N/m2. Thus, the force on themembrane of a cell 10 mm wide by 100 mm long would be roughly 0.1 pN, similar to theforce shown to cause dramatic cell distortion by atomic force microscopy perturbation of
the cell surface (Otter et al., 1998).
To obtain a similar pressure from polarization forces, a much larger electric field, 0.1 V/m,
was required. Provided that the estimate of unbalanced charge density at the cell surface iscorrect, the force due to the perpendicular component of the electric field appears to havea greater effect on receptors than the combination of dielectric gradient and tangential
field. It is difficult, however, to believe that electric fields much smaller than 10Ð4 V/maffect cells through pressure effects at the boundary layer, unless the charged protein
molecules are particularly sensitive to stimuli at a particular frequency. Simultaneous,coherent pressure on many receptors and alternating pressure continued for a long time
could also increase very small pressure effects above the ÔnoiseÕ produced by random
motion of adjacent cells.

370

(c) Effects of induced charge on cells
Possibly as significant as the ÔpushÐpullÕ (i.e. alternating positive and negative) pressure
due to the interaction of a sinusoidally time-varying electric field with the permanent
surface charge on a cell is the interaction with the time-varying component, rÕ, of thatcharge density, which itself depends on the applied field. rÕ can be expressed in terms ofthe component of the applied electric field, E^, that is perpendicular to the cell surface.
For a long cylindrical cell of radius r, it is (Polk, 1990; Polk, 1992c).

r© =e 2 n0 r
E^
k t (1 + jw / fr )Eq. 4.23

At frequencies (w/2p) well below the relaxation frequency fr, the term jw/ fr is negligible. If
e is the elementary charge 1.6 x 10Ð19 C, n0 = 2 x 1017/m2 as before, r = 10Ð5 m, and kBt =4.28 x 10Ð21 J at 37 °C, one obtains rÕ = 1.2 x 10Ð5 E^ C/m2. If E^ = E0 cos wt, thepressure rÕ E^ will be proportional to E02 cos2wt, and its unidirectional time average willbe FÕA = 6 x 10Ð6 E02 N/m2. For E0 =10Ð4 V/m, one obtains FÕA = 6 x 10Ð13 N/m2.
(d) Induced surface charge on cell matrix or substrate
In addition to inducing charge at the cell surface, an electric field within a tissue induces asurface charge on the extracellular matrix or other growth substrate. This induced charge
can have a robust effect on processes such as protein absorption and cell adhesion, as cellmatrices and substrates typically have a low fixed charge density. Recent work has shownthat induced charge densities on growth substrates on the order of 0.1Ð1.0 mC/m2 cansignificantly affect cell growth and morphology through this induced surface charge
mechanism (McLeod, 1998).
4.8.3.2 Cyclotron resonance and ion parametric resonance
As a consequence of LorentzÕ force F = q(v x B), equation (a) on Figure 4.2, a charge q of
mass m which moves at velocity v in a constant (static) magnetic flux density Bs will
follow, in a vacuum, a circular path of radius Rc
Rc =

vm
qBs

The angular velocity wc and cyclotron frequency fc will be given by371

Eq. 4.24

w c = 2pfc =qBs
m

Eq. 4.25

If an electric field is applied as in a cyclotron (Sears et al., 1976) or induced by analternating magnetic field, B = B0 cos wct, that has the same direction as Bs, the tangential
velocity v of the charge will increase, as will correspondingly its orbital radius Rc. It has
been noted that the cyclotron frequencies, fc = wc/2p, of many physiologically importantions fall below 100 Hz in the geomagnetic field ( » 50 mT depending on latitude). For
example, fc = 38.4 Hz for the 40Ca++ ion at 50 mT. Chiabrera et al. (Chiabrera et al., 1985)
and Liboff et al. (Liboff, 1985) therefore proposed various mechanisms which require
cyclotron motion of ions along circular or helical paths, either in transmembrane channels
or at receptors on the cell surface. It has been pointed out (Durney et al., 1988; Halle,
1988; Sandweiss, 1990), however, that such motion is impossible in the dense, collisiondominated fluids of biological materials. Furthermore, ions in biological fluids are normally
hydrated, and the frequency given by equation 4.25 would depend on the number ofwater molecules (and their total mass) in the hydration sheath of each ion (Koryta, 1982).
Despite the apparent implausibility of cyclotron resonance as a mechanism forinteractions between magnetic fields and biological systems, many experiments haveshown a response to combinations of static and alternating magnetic fields, which reaches,in different systems, either a maximum or minimum at the frequency fc given by equation
4.25 for various physiologically important ions. Some attempts to replicate the results
independently in different laboratories have failed while others have been successful(Table 4.5).
(a) Lednev model
A refinement of the cyclotron resonance model is provided by a theory proposed byLednev (Lednev, 1991; Lednev, 1993; Lednev, 1994), which pertains to effects thatwould affect transport through ion channels only indirectly. It is based on the idea that an
ion weakly bound within a protein, notably Ca++ within calmodulin, can be modeled as acharged oscillator. The oscillations are metabolically excited and are at infrared
frequencies. An ambient, steady (DC) magnetic field, BS, such as that of the Earth, would
cause Zeeman splitting (Haken & Wolf, 1984) of each vibrational level into two levels, wA
and wB, separated by the ion cyclotron frequency. Thus, wc = wA Ð wB. When an
alternating field, B1, is then applied in parallel with BS, the resulting frequency modulationof levels wA and wB will change the probability of ion transition, P, from an excited levelto some ground state of frequency w0. Applying earlier work (Podgoretskii & Khrustalev,
1963), Lednev then predicted that the time average of P will bePÄ = K1 + ( -1)n K2 Jn ( x )cos d372

Eq. 4.26

where K1 and K2 depend on the amplitudes of infrared radiation corresponding totransitions from wA and wB to w0, d is the difference in phase of the radiation from two
sublevels, and the argument of the Bessel function Jn(x) is
x=

nB1
BS

Eq. 4.27

The Bessel function Jn(x) in equation 4.26 leads to maxima and minima when thefrequency of the applied sinusoidal magnetic field is
f =

wc
f
= c
2pn n

Eq. 4.28

where n is an integer. LednevÕs model thus not only predicts ÔresonancesÕ at the cyclotron
frequency and its subharmonics but also prescribes the relative amplitudes of B1 and BS
for which the ÔresonanceÕ effects should be maximized. These are given by the values of
the argument x that corresponds to extreme values of Jn(x). For example, J1(x) has its firstmaximum at x = 1.84. The model furthermore predicts, at a fixed BS and resonancefrequency fc, a variation of system response as the amplitude of B1 is varied, changing themagnitude of Jn(x).
One apparent advantage of this particular theoretical model was that it could be tested byapplying appropriate fields BS and B1 to proteins in chemical reactions without thepresence of complicated cells or tissue. Experiments to study the effect of parallel
directed BS and B1 fields on the phosphorylation of myosin in the presence of calmodulin
and troponinÑperformed, however, over only a very narrow frequency rangeÑseemed at
first to confirm the theoretical predictions (Shuvalova et al., 1991). A similar experimentalso showed that phosphorylation of myosin can respond to purely static magnetic fields
between 0 and 200 mT in the absence of an alternating field (Markov et al., 1993). An
investigation of calcium binding to metallochromic dyes involving an indirect measurementof Ca++ binding to calmodulin in the presence of combined AC (50 and 120 Hz) and DC(0 to 299 mT) magnetic fields, however, failed to show any effect of the magnetic field(Bruckner-Lea et al., 1992).
The principal difficulty of the theory is that the width of the infrared spectral lines, due
to vibration of Ca++ in the calmodulin molecule, must be extremely narrow (< fc) if
splitting into two frequencies, separated by fc, is to be significant. Lednev suggested thatshielding of the Ca++ ion within the structure of the calmodulin molecule would prevent atleast Doppler broadening. Furthermore, an ion inside a molecule is largely protected fromcollision with atoms or molecules in the external environment.
Calmodulin is ubiquitous in living organisms and is essential to normal cell function(Cheung, 1982). It interacts with many Ca++-dependent enzymes and regulates their373

activity (Stryer, 1989). Since the location of Ca++ ions at four possible binding sites
within calmodulin and the strength of binding at each site (Rainteau et al., 1989)
profoundly influence the interaction of calmodulin with various enzymes, any effect ofmagnetic fields on Ca++ binding with calmodulin would affect a wide range ofphysiological processes.
(b) Ion parametric resonanceBlackman et al. (Blackman et al., 1994; Blackman et al., 1995) subjected PC-12 cells
stimulated by nerve growth factor to combinations of AC/DC magnetic fields and foundthat the number of cultured cells with neurite outgrowths decreased in comparison with
unexposed cells as a function of AC/DC amplitude. That behavior was, however,restricted to narrow frequency bands determined by the amplitude of the applied DC
magnetic field, suggesting a ÔresonanceÕ behavior. They were able to fit their data to a
Bessel function by assuming a dependencePÄ = K1 + K2 ( -1)n Jn (2 nB1 / B0 )Eq. 4.29

in which the factor of (2) in the argument of the Bessel function accounts for adependence on the B1/B0 ratio that differs substantially from that predicted by LednevÕs
equations 4.26 and 4.27. Using fairly elaborate curve fitting, they suggested that the data
for PC-12 cells indicate ÔresonancesÕ corresponding to ions of vanadium, magnesium,
manganese, and hydrogen. The original experiments were later replicated under doubleblind conditions in the same laboratory [Blackman, In Press #1788]. Blackman et al.
(Blackman et al., 1996) also demonstrated that their experimental results are not related tothe amplitude of the magnetically induced electric field (Blackman et al., 1993a) and thatmutually perpendicular, rather than parallel oriented, AC and DC magnetic fields evoke
different biological responses.
The results obtained by Blackman et al. (Blackman et al., 1994; Blackman et al., 1995;
Blackman et al., 1998; Trillo et al., 1996) for neurite outgrowth of PC-12 cells appear to
confirm the Blanchard and Blackman (Blanchard & Blackman, 1994; Blanchard et al.,1995) version of the ion parametric resonance theory (equation 4.29). The results ofexperiments with living land snails (Prato et al., 1996), however, agree better withLednevÕs original proposal (equations 4.26Ð4.28).
Despite these experimental results, questions remain about the validity of the ion
parametric resonance theory. Adair (Adair, 1992) pointed out that it requires the radiating
ion to be shielded from collision-like interactions with the surrounding material. Even if
the de-excitation time of the above-ground state oscillation were as long as 0.1 s, thewidth of that state would be only 10 Hz, and a 16 Hz cyclotron resonance would be ill
defined. Furthermore, presumably any substantial transient change in the ion-excited state
would interrupt the mechanism, which depends on a specific energy difference between

374

the split states (at frequencies wA and wB). Adair (Adair, 1992) suggested that largetransient electric fields from far-off collisions would destroy the fine tuning required by
the mechanism; however, such transients would most likely shift the vibrational sublevels
at frequencies wA and wB equally, so that the important difference wC would be preserved.
He pointed out that an ion as heavy as Ca++ would not radiate strongly and noted that themechanism also requires perfect three-dimensional symmetry of the vibration before theperturbing alternating field is applied, e.g. equal Ôspring constantsÕ in different directions.
In addition, a large set of ions would have to be excited and modulated coherently by theexternal field for a noticeable effect to occur.
Lednev (Lednev, 1994) responded that the model applies primarily to the effects ofexternal fields on vibration of Ca++ or Mg++ in calcium-binding proteins and that theatomic structure of Ca++ binding sites is known from X-ray diffraction studies in a
number of calcium-binding proteins, including calmodulin (Babu et al., 1988). These
results indicate that the symmetry condition is satisfied. As an example, Lednev referredto the radial distribution of protein oxygens around the Ca++ at two calcium-binding sites
in parvalbumin, which show sharp peaks at the identical ultraviolet wavelength (Ahlstrom
et al., 1987).
Concerning the requirement that the excited vibrational mode have a ÔlongÕ lifetime (i.e.
long de-excitation time) in order for the ELF field (periods, 10Ð50 ms) to be effective,
Lednev cited Ritov (Ritov, 1976), Martin et al. (Martin et al., 1985), and Cox (Cox, 1988)
to confirm that the lifetime of Ca++ and Mg++ chelated in the calmodulinÐkinase complex
is about 1 s.
In a detailed analysis of the ion parametric resonance mechanism, applying quantum
mechanics, Engstrom (Engstrom, 1996) concluded that the model makes many predictions
for biological systems that are sensitive to differences in excited states of biochemicals,
and that these predictions can be tested experimentally. Another interesting direction ofresearch is investigation of the effects of fields at angles other than parallel andperpendicular orientations. In the context of a search for mechanisms that can explain the
biological effects of weak magnetic fields, a particularly important feature of the ion
parametric resonance model is that it assumes no energy input from the applied magnetic
field into the affected biological system. It postulates only that the energy already in thesystem will be redistributed. Lednev (Lednev, 1994) suggested that, for this reason, it is
not applicable to a system in equilibrium such as the solution containing calmodulin and
CaCl2 that was used in the experiments of Bruckner-Lea et al. (Bruckner-Lea et al., 1992)
mentioned earlier in this section.
4.8.3.3 Biological electron transfer
Long-range intermolecular and intramolecular electron transfer plays an important role inconferring the specificity and directionality of numerous biological processes (Gray &Winkler, 1996). These include the classical enzyme reactions that have been suggested as375

a medium for field interactions (Grundler et al., 1992). Specific examples may becytochrome C oxidation by the enzyme cytochrome oxidase and effects of EMF on Na/K
ATPase function (Blank, 1992; Blank & Soo, 1992a; Blank et al., 1995). It has also beenshown that a non-equilibrium chemical reaction catalyzed by a membrane enzyme can act
as an active element in an external electric circuit and provide the energy for driving
electrical oscillations (Derenyi & Astumian, 1998).
One difficulty in accepting biological electron transfer as a likely initial site for detectionof weak externally applied electric or magnetic fields is that the endogenous energies
involved in electron binding are many orders of magnitude larger than those contained in
the weak fields of interest here. Electron affinity values for organic molecules generally
fall within the range 0.5Ð2.0 eV (19Ð75 kBt) (Pethig, 1979). Free or diffusing electrons
might, however, be affected by even weak electric or magnetic fields. As mentioned
earlier, the electric mobility me of ions in biological fluids is of the order of 10Ð7 m2/V s.
The interaction of a magnetic field with any charged particle by LorentzÕ force depends
on the velocity of that particle [equation (a) on Figure 4.3]. Since that velocity v is related
to the electric mobility by v = me E0, the magnitude of effects on charged particle motion
by a magnetic field B can be estimated by considering the ratio of the transverse electricfield ET (transverse force/charge q) to the electric field E0 (probably of endogenous origin)that was responsible for the original linear motion at velocity v. That ratio is meB. While
the mobility of electrons over long distances along protein strands is probably also small,it could be sufficiently large in some locations for electron motion to be affected by arelatively weak magnetic field.
It has been shown that electron mobility along the p bonds in the central core of DNA
strands can be surprisingly large (Arkin et al., 1996; Meade & Kayyem, 1995; Murphy etal., 1993; Stemp et al., 1995); however, it is not known whether it is large enough to maketransverse deflection of electron currents due to applied magnetic fields plausible. Direct
effects on DNA of externally applied EMF have been suggested (Blank & Goodman,1997).
Another important site for consideration of possible effects on electron transfer byapplied magnetic fields is the mitochondrial membrane (Nicholls, 1982), where proton andelectron transfer are involved in energy conversion mediated by ATPases (Polk, 1997).
4.8.3.4 Effects on biogenic magnetite
Magnetite biomineralization occurs in the human brain (Kirschvink et al., 1992), and oneline of human leukemic leukocytes was nearly 100 times more magnetic than brain tissues,
giving cellular magnetic moments of ~ 10Ð12 A m2 (Kirschvink & Kobayashi-Kirschvink,1993). Kirschvink (Kirschvink, 1992a) suggested that the interaction energy of even weak
ELF magnetic fields with magnetic particles of magnetic domain size would be larger than
the thermal energy of (1/2) kBt per degree of freedom within a system in thermal
equilibrium. Using a model of magnetic particles floating in a fluid medium, Adair (Adair,376

1993) proposed that a 60 Hz magnetic field weaker than 5 mT could not generatesignificant biological effects in the cell by acting on magnetic elements. That conclusion
appears to be premature, however, because not enough is known about the relationship ofthe magnetite particles to other components of the cell interior or of the cell membrane toformulate a mathematical model that is adequate for precise numerical predictions.
A description of the dynamics of any kind of anchoring of the ÔmagnetosomesÕ to the cellstructure would require a non-linear differential equation; even a linearized equation would
have no constant coefficients unless the applied alternating magnetic field is exactly
perpendicular to the geomagnetic field and the magnetosome deflection is very small. In
addition, the effective viscosity of the fluid within the cell in the vicinity of themagnetosomes, which is a critical parameter in the Adair model, cannot be well specified.
Even if this clearly oversimplified model is used but combined action by multiple
magnetosomes within the cell is allowed, a signal-to-noise ratio well above 1 might bepossible with a 60 Hz magnetic field of 2 mT (Polk, 1994). Neither estimate can beconsidered adequate at the present time; however, it is likely that any effect of multiple
magnetosomes within a cell would make use of their coherent motion, and thus there
would be no significant thermal noise limitation if the energy supplied by an applied field
to a single magnetosome were much smaller than kBt. For single domain particles of Fe304,
the magnetic moment is given by (Frankel, 1986):
m = volume x 4.8 x 105 A m2

Eq. 4.30

and the energy supplying torque to a spherical particle of 60-nm diameter in a 2 mT fieldwould already be 0.1 kBt at 37 °C. Therefore, it is important to perform further
experimental work on the behavior of such particles within cells or of similar particles
that might be present in cell culture media (Dobson & Grassi, 1996; Kobayashi et al.,1995). Vaughan and Weaver (Vaughan & Weaver, 1996; Vaughan & Weaver, 1998)
suggested that endogenous or contaminating magnetic particles could create pores in cell
membranes when magnetic field pulses are applied; however, they indicated that for
simple biologically synthesized magnetosomes (radius = 10Ð7 m; magnetic moment = 2 x
10Ð17 A m2) and typical cell membranes, the estimated pulse magnitude must exceed B0 »1Ð7 x 10Ð2 T, and the optimal pulse duration is in the range 10Ð5 s < tpulse < 10Ð1 s. For
larger contaminating particles with larger net magnetic moments, the pulse magnitudes
could only be somewhat smaller, and the optimal durations are about the same.
4.8.3.5 Magnetochemistry: Effects of magnetic fields on free-radical reactions
Free radicals are important in many biological processes (Freifelder, 1985). For example,
they are formed as intermediate products when light is incident upon the visual pigment
rhodopsin. It has been known for some time that chemical reactions that involve free
radicals are strongly influenced by static magnetic fields (Blankenship et al., 1977; Hoff etal., 1977; Werner et al., 1978), but more recent work (Cozens & Scaiano, 1993; Hamilton
et al., 1988; McLauchlan, 1989) suggested that DC fields as low as 1Ð10 Gauss may
377

affect such chemical processes. By implication, as is shown below, alternating fields ofthe same order of magnitude, acting in concert with steady fields should also affectreaction yields. The effects of even smaller alternating fields have been predicted byanalytical work (Adair, 1997; Brocklehurst & McLauchlan, 1996; Canfield et al., 1994)
and are discussed further on.
Observations in this area are based on PauliÕs exclusion principle, which states that theelectronic states of an atom can only be occupied in such a way that no two electrons
have exactly the same set of quantum numbers. Thus, if there are, for example, twovalence electrons in the same orbital, characterized by the same set of orbital quantum
numbers, their individual spin quantum numbers must be +1/2 and Ð1/2; i.e. their spinsmust be in opposite directions. If two electrons in a chemical bond are paired in thismanner and if this bond is broken, for example by incident light, resulting in two free
radicals, subsequent recombination is possible only if the two electrons preserve this
oppositely directed spin. Interaction with the local magnetic fieldÑdue to nuclear
magnetic moments or other nearby spinning and orbiting electronsÑcan, depending on theparticular molecular structure, either favor or destroy opposite spins. In the latter case, of
now equally orientated spins, recombination of the radicals becomes impossible.
Conversely, if the radical pair was formed from excited atomic states with the unpaired
electrons coming from different atomic shells, they may already have equal spin,
preventing chemical combination of intermediate products.
As long as the electrons have opposite spin, the products have a ÔsingletÕ character, i.e.
the total quantum number J, which characterizes the electron states, is equal to the orbital
quantum number L, since the spin quantum number S = (1/2) Ð (1/2) = 0 and J = S + L.
As the products diffuse, however, some fraction will acquire a ÔtripletÕ character; i.e. theelectron spins may become parallel, and S = ± (1/2 + 1/2) = ñ1 and J can have threevalues, L + 1, L Ð 1, and L, in view of the quantum rules for combination of angularmomenta. If the products were initially in the triplet state, diffusion will have theopposite effect, i.e. partial conversion from a triplet to a singlet character.
The singlet and triplet states have, in general, different energies, as indicated at B = 0 on
Figure 4.5. Any magnetic field, including that of nearby magnetic nuclei, will cause triplet
states T + 1 and T Ð 1, which have electron spin in the direction of the field, to gain orlose energy. Therefore, the energy levels of these states will separate with increasing B, as
indicated on Figure 4.5. Interconversion between the singlet and triplet states can occur
either by external energy input or between T0 and S through a distance-dependentÔelectron exchange interactionÕ at any level of B. At some critical level of B = Bc,
interconversion between T Ð 1 and S is also possible without external energy input. It has
been shown experimentally that this level is approximately 1 mT in a pyreneÐ
dimethylaniline system (Hamilton et al., 1988).
Since interconversion between singlet and triplet states in the direction of greater singlet
product will make chemical combination possible, application of the correct value of Bc
will obviously affect the rate of chemical reaction. It is also possible that an ambient flux378

density (from external and internal sources) may have a value B1, which is either slightly
larger or smaller than the required Bc. In that case, addition of an alternating field BA cos
wt will periodically establish optimum conditions for conversion (the period 2p/w of ELF
fields is much longer than the nanoseconds required for the T Ð 1 ® S transition). It
appears therefore to be at least possible that small AC magnetic fields in the presence ofthe geomagnetic field could affect chemical reactions in biological systems that involve
free radicals as intermediate products. Many authors, e.g. Walleczek (Walleczek, 1995),
have pointed out that the spin of valence electrons in free radicals is not coupled strongly
to the thermal environment and is therefore not subject to a kBt thermal noise limit.
With regard to the basic free-radical effect of magnetic fields, the frequency of an ELF
field would not be recognized, since the diffusion time of the free radical is much shorter
than the period of an applied ELF field. The latter would therefore be indistinguishable
from a static field. It has been shown (Eichwald & Walleczek, 1997), however, thatsensitivity to ELF fields results if the radical pair process is integrated into a scheme
involvingdynamicsignaling.
Time-dependent perturbation theory with iterative solution of SchroedingerÕs equation
has been applied to the problem of singlet-to-triplet yields in radical-pair reactions
subjected to oscillating magnetic fields (Canfield et al., 1994). Considering frequencies of
the alternating magnetic field between 0.5 and 3.0 MHz, which include the precession
frequency of an electron (1.4 MHz) in the EarthÕs magnetic field (50 mT), they showed
effects on triplet yield at a surprisingly low amplitude of 0.7 mT when the static field was
50 mT. They emphasized that the radical-pair mechanism is inherently non-linear and thatthe effects on the singlet-to-triplet yields did not always increase as the oscillating fieldstrength was increased. Thus, if this mechanism does indeed account for some of thebiological effects of magnetic fields, simple doseÐresponse should not be expected. They
also pointed out that the singlet-to-triplet yield versus frequency spectrum could bealtered dramatically by simply changing the orientation of the oscillating field and that theeffects of two simultaneously applied oscillating fields are not simply additive but
interact in a nonlinear fashion. They concluded that such nonlinear interactions (due tosecond-order and higher perturbation expansion terms) of experimentally applied fields,
which become more apparent at higher oscillating field strengths, with uncontrolledenvironmental fields may account for some of the conflicts in the literature on the
biological effects of magnetic fields.
In another theoretical treatment of radical-pair re-formation by very weak magnetic fields,
thus far reported only in an abstract (Adair, 1997), the author reported that, using exact
calculations on an appropriately general model system, small but significant modificationsof the recombination rate by a 50 mT field could be expected only under a narrow range ofcircumstances. The radical-pair containment time must be exceptionally long, 50 ns or
longer; the hyperfine field of neither radical must be appreciably greater than that which
generates a precession period greater than the cage containment time; and thecharacteristic recombination time of the radical pair in the singlet state must be about379

equal to the containment time. Fields as small as 5 mT produced no significant change inthe recombination rate. He concluded that environmental magnetic fields much weaker
than the EarthÕs field have no significant biological effect by modifying the recombination
probabilities of radical pairs. The figure included in the abstract, however, shows anapproximately two-to-one change of the difference in the escape probability of the radical
when a 5 mT field was added to a 50 mT (» geomagnetic) field, see Figure 4.6. For a ÔcageÕ
confinement of the radical lasting 100 ns, this is a change from 0.01 to 0.02. One mightquestion whether such a small change in escape probability could ultimately have a large
effect under some circumstances. One possibility might be the existence of magnetic fielddependent radical-pair chain reactions. Analysis of such reactions (Grissom, 1995)
indicated that even a small field-induced change in the concentration of radical propagators
would have a large effect on the reaction rate of the process, because each radical cancause multiple chain events. A numerical simulation (Eichwald & Walleczek, 1996b)
showed that an amplification factor can be derived in some enzyme reactions from thespecific relationships between rate constants. As a consequence, although the magnetic
field-induced change in radical-pair recombination probability is very small, the effect on
the enzyme reaction rate is much larger, for example by a factor of 1Ð100.
The effects of magnetic fields on radical-pair chemical reactions are firmly established,both theoretically and experimentally. Some experiments have shown that effects canoccur at applied static field levels as low as 100 mT (Batova et al., 1993; Nossol et al.,1993). The effects of low-intensity ELF fields on free-radical reactions in biologicalsystems have been studied experimentally in very few systems (Harkins & Grissom,
1994). Since studies in this area may explain many presently poorly understood
experimental results (Sciano et al., 1994), it deserves substantial effort in the future.
4.8.3.6 Non-linear dynamics and application of stochastic resonance
It has been recognized for about 30 years that non-linear, non-equilibrium phenomena
play a very important role in biological systems (Adey, 1975; Adey, 1981; Adey, 1983;
Frohlich, 1968). Such systems are characterized by sensitivity to initial conditions, suchthat slight changes in one or more parameters can significantly alter the state of thesystem after some time. Some non-linear, non-equilibrium processes were considered inpreceding sections (e.g. magnetochemistry).
The effects of electric fields on chemical oscillations have been established experimentally(Barnes, 1996; Eichwald & Kaiser, 1993; Eichwald & Kaiser, 1995; Eichwald &Walleczek, 1996a; Eichwald & Walleczek, 1996b; Kaiser, 1994; Sevcikova et al., 1992;
Wachtel, 1979). Such studies have shown that biological and functional status is offundamental importance for an effective interaction. For example, in studies of theregulation of calcium uptake by cells of the immune system, particularly T lymphocytes,
either stimulatory, inhibitory, or no effects are observed for identical field parameters,
depending on the degree of cellular activation. Eichwald and Walleczek (Eichwald &Walleczek, 1996a) presented a theoretical approach to account qualitatively for effects of380

exposure to EMF that depend on the degree of cellular activation and that show abiphasic response (stimulation and inhibition). In this model, biochemical stimulation of
the cell resulted in activation of specific signaling pathways that regulate calcium
dynamics in the cell (release from intracellular stores and capacitative entry). They
assumed that a specific EMF-sensitive enzyme system which is controlled by thesepathways becomes activated. The activated enzyme, in turn, would exert feedback control
on the signal processes, thus leading to modulation of calcium entry which may affectother cellular processes that are calcium-dependent such as DNA synthesis.
One phenomenon, that is characteristic of some non-linear systems is the possible
occurrence of stochastic resonance (McNamara & Wiesenfeld, 1989; Moss & Wiesenfeld,
1995), in which the output signal-to-noise ratio improves, at first with increasing input
noise before it decreases as the noise increases further. The importance of thisphenomenon for the detection of weak biological signals has been suggested by several
authors (Grundler et al., 1992; Kaiser, 1994) and is confirmed by some experimental
results (Collins et al., 1996; Douglass et al., 1993; Gluckman et al., 1996). Most
applications of this theory have been based on threshold triggered systems in which aweak, below-threshold signal is raised above the threshold by the presence of noise(Moss & Wiesenfeld, 1995; Wiesenfeld et al., 1994). A mathematical model developed by
Bezrukov and Vodyanoy (Bezrukov, 1996; Bezrukov & Vodyanoy, 1997b) shows thatstochastic resonance can also occur in Ôthreshold-free systemsÕ, i.e. systems that can
respond to signals of arbitrarily small amplitude. They considered time-dependent
Poisson processes, such as the opening and closing of voltage-dependent ion channels,
where the system output can be described as a random train of identical pulses with theprobability of pulse generation exponentially dependent on the input signal. In particular,
they assume that the pulse generation rate is given byr[V(t)] = r(0) exp[V(t)]Eq. 4.31

where r(0) is the equilibrium rate of pulse generation and V(t) is a dimensionless voltage.
After publication of the paper by Bezrukov and Vodyanoy (Bezrukov & Vodyanoy,
1997b), Astumian et al. (Astumian et al., 1997) described computations made with themodel that showed that the mechanism could not explain the reported finding that fieldsof < 0.1 V/m caused effects on cells. In their response, Bezrukov and Vodyanoy(Bezrukov & Vodyanoy, 1997a) stated that selection of more realistic cell parameters andparticularly long biological integration times would give effects at lower strengths.
Galvanovskis and Sandblom (Galvanoskis & Sandblom, 1997) considered the effect of a
weak sinusoidal signal on opening and closing rates of ion channels and consequent
modulation of ion currents. They applied the original theory of McNamara andWiesenfeld (McNamara & Wiesenfeld, 1989) but extended it from a single device to N ion
channels subjected simultaneously to the same sinusoidal signal. A very interesting result
was obtained when the underlying transition rate was assumed to be asymmetrical withthe channel open time, at 10 times the closed time (but still in the order of microseconds).
In that case the ÔoutputÕ (i.e. the periodic component of the ion current across the381membrane) contained not only the applied frequency but also several harmonics (Figure 4
in their paper). For N = 1000, a signal frequency of 50 Hz, and a ÔcylindricalÕ human of
only 10 cm in radius, the authors concluded that, under optimum conditions, even very
weak low-frequency electromagnetic signals (< 100 Hz and 100 mT) could be detected in acellular system with a large number of ion channels. They also noted that the capacity ofa cell to detect periodic changes in ionic influx is essential for the effect of an external
sinusoidal signal to be biologically important,. The cytosolic Ca++ oscillator, a complex
system of biochemical reactions that allows a cell to create sophisticated spatiotemporal
patterns of Ca++ intracellular concentrations, may function as a detector of the small
component of Ca influx.

4.8.4 Summary
Examination of the forces and energies involved in biochemical processes indicates thatthey are far stronger than those corresponding to power-frequency electric fields inside
cultured tissues or cells (£ 10Ð3 V/m) or, equivalently, induced in humans by 60 Hz
magnetic fields (< 3 x 10Ð5 T). Biological tissues and cells are, however, extremely
inhomogeneous, and when the average electric field is £ 10-3 V/m the actual field atselected locations (e.g. cell membranes) may be orders of magnitude larger. Since themagnetic permeability of tissue is usually very close to that of free space, noenhancement of the internal over the external magnetic field is to be expected, except forbiogenicmagnetite.
Living systems contain many structures that can sum inputs over both time and space.
Thus, several thousand receptors of a particular type on a single cell may send the samemessage to the cell interior, where they may be added; likewise, repetitions of the samemessage sent over a finite period may be cumulative. In contrast, the ÔnoiseÕ or random
fluctuations may differ at different receptors and partially cancel. The averaging of noiseover time or number of receptors can substantially improve a systemÕs ability to detect
small signals.
Most life processes, although in steady state, are far from thermal equilibrium and dependon continuous energy input. Therefore, analyses based on equilibrium thermodynamics
can lead to erroneous results. Furthermore, while the Ôquantity of molecular changeÕ iscertainly important, the rate at which change is accomplished is equally important: life as
we know it would be impossible without the acceleration of biochemical reactions
accomplished by the presence of enzymes. Furthermore, biological signal processing may
not depend onlyÑand possibly in some cases not at allÑon the amplitude of a signal but
also on the rate at which it is repeated (e.g. the frequency and duration of Ca++oscillations).
Many biochemical and biomechanical processes (e.g. Ca++ oscillations and the motion ofmagnetizable particles attached to tissue) can be accurately described only by nonlinear382differential equations. The solutions of such equations are subject to very small changes inboundary conditions and also give rise to the phenomenon of Ôstochastic resonanceÕ, i.e.
enhancement of the output signal-to-noise ratio by the presence (up to a certain level) of
noise rather than its absence. The application of non-linear dynamics to biology is still in
its infancy.
The stochastic nature and ultimate discreteness (ÔgraininessÕ) of electrochemical life
processes is likely to enhance rather than obviate the sensing of weak electric andmagnetic fields. It has been suggested that time-varying pericellular electric fields of 10Ð4
to 10Ð3 V/m can affect biological signals and that the electrical in homogeneity of living
tissue can raise field intensities to this level at some points, although the field averages,
calculated over a large volume, may be much lower. At 60 Hz, a 3 mT magnetic field cangenerate a 10Ð4 V/m electric field in the human body. While ion channels cannot be
excluded as locations for initial detection of fields at this level, receptors and enzymes are
possibly more likely sites.
The necessary non-linearity in the mathematical description of biochemical processes at
the molecular level leads to time and amplitude ÔwindowsÕ and guarantees that ÔmoreÕ (i.e.
a larger signal) is not necessarily ÔbetterÕ, or (depending on the point of view) ÔworseÕ.
Direct effects of time-varying magnetic fields, e.g. effects that do not occur primarily as aconsequence of magnetically induced electric fields, are very likely at amplitudes above
100 mT, and there is experimental evidence to support these predictions, but their
existence at lower intensities cannot be excluded. The spatial and temporal coherence of
externally applied EMF and their application for extended times must play an importantrole in the biological detection of low-intensity fields. The entire area of biological signaltransmission by frequency and/or pulse code modulation needs much further research.
All of the theories of the biological effects of small-amplitude EMFÑboth those thatdeny the possibility and those that address experimental observationsÑare speculative
and unproved. They suffer from a lack of detailed, quantitative knowledge about theprocesses to be modeled, such as the Ôsecond messengerÕ signal cascade, the modus
operandi of many receptors, the precise origin of Ca++ oscillations and their biological
function, the timing of the making and breaking of chemical bonds, chemical transition
states, the dependence of magnetic fields on specific free-radical processes, and even theeffective viscosity inside particular cells. Nevertheless, theoretical models are useful, evenin the absence of critical data, because they can indicate which data are needed, suggest
previously uncontemplated experiments, or elicit modifications to routinely performed
investigations and thus generate ÔsolidÕ new information.
In the area of low-intensity, low-frequency bioelectromagnetics, experiments that would
contribute to the construction and verification of theoretical models might address:·

the duration of exposure to fields that is necessary to produce effects over several
different exposure periods;

383

·

different frequencies of exposure, even when the ultimate interest is in the effects of
60 Hz fields;·

different field intensities (preferably those suggested by theoretical models), notnecessarily to establish ÔthresholdsÕ but to determine how results depend on field
intensity;·changes in observed biological effects in response to deliberate addition of different
types of electric and/or magnetic ÔnoiseÕ;·the physical basis for the sensory perception of electric and magnetic fields byanimals;·

temperature variations during exposure to fields and, when an effect can be mimickedby chemical exposure, the temperature-dependence of the effects due to exposure to
fields and chemicals;·

whether an effect is produced by a magnetically induced electric field, by themagnetic field alone, or by a combination of the two;·measurement of static magnetic fields and their orientation relative to the alternating
magneticfield;·

the possibility of ÔcontaminatingÕ magnetic particles in all experiments in vitro; and·the presence of high-intensity EMF transients in epidemiological studies in theworkplace and their characterization with regard to amplitude, rate of rise, duration,and frequency of occurrence for use in in-vitro studies.

The fundamental laws of electricity and magnetism are well understood, but they clearly
allow a great variety of possible interactions with extremely complex, inhomogeneous,often anisotropic, and continuously varying living organisms. In the inanimate world,
EMF have very different effects in electric motors, Xerox machines, radios, andcomputers. Only 50 years ago, understanding of the interaction of EMF withsemiconductors was in its infancy, and new devices incorporating field effects are still
being invented. There is no reason to believe that only one type of field coupling exists inthe vastly complex, still poorly understood living systems. Different types of interaction
are likely to be important at various field intensities in different organisms. Thus, several
theoretical models may be appropriate for different intensities and in different biologicalenvironments. Valid quantitative models for the action of fields at the molecular level
require quantitative understanding of biological processes, such as enzyme catalysis andbiological signal processing.

384

Figure 4.1 Equivalent circuit for an array of N membrane channels with conductive media on eachside of the membrane (A discrete resistance value is associated with each channel (RG) and witheach of the access resistances (RA and RB) near the channel mouths. All resistors in the circuit
produce voltage noise, and these sources (VGi, VAi, and VBi) are completely independent anduncorrelated. When circuit analysis techniques with the proper methods are used for summing
incoherent signals, the net noise voltage across an arbitrary channel (V1 in this figure) can becalculated. Note that the noise voltage of interest (V1) is that occurring across the channel, andnot across the series combination of the channel and access resistances. The model assumes thatany voltage gating mechanism is inside the channel or at the channel mouth. From Gailey(Gailey, 1996).

385

Figure 4.2 Normalized correlation coefficients for thermal electrical noise occurring across an ion
channel as a function of the number of channels in the membrane (Electrical parameters used inthis calculation apply to gap-junction channels with a channel resistance of 6.5 GW and an access
resistance of 0.33 GW.). The coherence or correlation between noise signals occurring in different
channels decreases by a factor of 10 per decade with increasing number of channels. From Gailey(Gailey, 1996).

386

Figure 4.3. Improvement in signal-to-(thermal) voltage noise ratio due to lack of correlation
between noise signals occurring in different open channels in the membrane (The x axis is theabsolute value of the slope of the closing rate constant divided by the slope of the opening rate
constant. The solid line was generated from equation 4.15 with equal opening and closing rate
constants and assuming no effect of thermal voltage noise on the closing rate constants (g = 0,No ®ì.)). When the slight correlation between voltage noise in the open channels and the effectof the uncorrelated noise in these channels is included, the dashed line is obtained for a membranewith 50,000 open channels. From Gailey (Gailey, 1996).

387

Figure 4.4. Voltage noise spectra of a frog node of Ranvier at various membrane potentials.
From Verveen and DeFelice (Verveen & DeFelice, 1974); reproduced by Barnes (Barnes, 1986).

388

Figure 4.5. Effect of magnetic fields on radical-pair energy levels (Electron spins in the three sublevels of the triplet state: T+1 spins parallel in the direction of the magnetic field, T-1 spins
parallel in the direction opposite to the magnetic field, T0 spins antiparallel but in phase in thefield direction.). S, singlet state From Polk (Polk, 1992a).

389

Figure 4.6. Maximum change in escape probability and maximum relative change are shown as afunction of cage retainment time for an increment of 5 mT to an external field of 50 mT (Therecombination probability for electrons in a relative singlet state is taken as twice the escapeprobability and the internal field magnitudes and directions are selected from Monte Carloprocedures, as is the direction of the external field. The variation of escape probability with cagetime of radicals with fields chosen so as to maximize the escape at a cage time of 10 ns, is also
shown.) From Adair (Adair, 1997).

390

Table 4.46 Maximum numbers of turnovers of some enzymes
EnzymeTurnover number (per second)

Carbonic anhydrase
3-Ketosteroid isomerase
Acetylcholinesterase
Penicillinase
Lactate dehydrogenase
Chymotrypsin
DNA polymerase I
Tryptophan synthetase
Lysozyme

600,000
280,000
25,000
2,000
1,000
100
15
2
0.5

From Stryer (Stryer, 1989)

Table 4.47 Cells showing Ca++ oscillations
Cell
Rat myocyte
Rat hepatocyte
Macrophage
Smooth muscle
REF52 fibroblasts
Endothelial cells
B lymphocytes
Mouse oocyte

Stimulus

Period (s)Caffeine
Vasopressin
Cell spreading
Phenylephrine or histamine
Gramicidin + vasopressin
Histamine
AntigenFertilization

0.3-3
18-24019-69
30-48
35-10040-12550-75
600-1800

From Lauffenberger and Linderman (Lauffenburger & Linderman, 1993)

Table 4.48 Average endogenous fields due to heart activity induced field (Hz)Induced field (Hz)Tissue0 - 4040 - 70

70 - 100

Brain
Cerebrospinal fluid
Pineal gland
Pituitary gland
Eye humor
Lung
Heart
Liver
StomachPancreas
Intestine
KidneyBladder
Prostate
Testis

0.30
0.26
0.18
0.46
0.16
38.1
160
18.5
33.8
15.1
4.85
4.42
1.19
0.91
0.35

0.04
0.03
0.02
0.06
0.02
5.73
25.4
2.15
3.75
1.64
0.52
0.54
0.13
0.10
0.04

0.01
0.009
0.006
0.02
0.005
2.39
12.4
0.78
2.06
0.61
0.19
0.18
0.05
0.04
0.01

From Hart and Gandhi (Hart & Gandhi, 1997)

391

Table 4.49 Experimental papers reporting resonance depending on the static magnetic fields (BDC)
Reference

Frequencyof
exposure(Hz)

BAC (mT)

BDC(mT)

fR (mT)

Ion

Cells
organism

Exposure
duration

Ca2+

Effect

Notes

Attenuation of oploidIncluded analgesia byapproximately 20%
Inhibits Ca Influx triggeredby ConA

BAC/and BDC variable

Micronuclel formation
frequency incresed 97 to
100% 6 subjects (marker ofchromosomal damage)No effect

Genotoxic effectSubharmonics, BAC/BD
dependence
Off resonance (effectdepends on NGF
concentration)
Effect at main resonan(n=1)(Prato etal., 1996)

60

299 peak

78 ± 160

40

Snails15 min(Yost &
Liburdy,
1992)

16

42.1

23.4

16

45

Mitogenactivatedlymphocyte

60 min(Tofani etal., 1995)

32

150 rms
75 rms

42

ND

40

Human
Lymphocytes

72 h

50
32

150 rms.
75, 150
rms
7.7-46.8
7.8-18.1
0.79-2.1

0

ND

36.6
20.3
2.0

45
25

Mg, V,Mn
Li, H

PC-12 Neuite
Outgrowth

23 hReduction of % cells withneuite outgrowthNo effect0.29-4.11
rms
0.79-2.05
rms

2.96

45

H+

PC-12

23 h

1.97

30

Reduction of % cells withneurite outgrowth according
to IPR, except near (Bac/Bdc)=0.85
No effect0.79-2.05

1.97

60

10 peak

78.4

60

40

60

10 peak

51.13

60

K+

60

20 peak

78.4,
39.2,
26.1,
153.3
76.6,
51.1,
47.5,
9.5

60

40

(Blackman
et al., 1994)

45
25
45

(Trillo etal., 1996)

45
30

Ca2+

Ca2+

45
(Jenrow etal., 1995)(Smith etal., 1987)

Ca2+

Ca2+
K+
Mg2+

392

No effect: DC only A
only

Off resonance (no DC)

Off resonance

Planaria

300 h

Delay of cephalic regeneraton
by 48 hNo effect

Controls: BDC =18.2
mT, or BAC=0

Radish seeds

21 d

Ca turning slowed
germination, stimulates
growthK tuning speeded
germination, inhibits growth.
Mg tuning did not affectgermination, stimulates
growth.

Also AC unexposed
controls

Table 4.49 (continued)
Reference

Frequencyof
exposure(Hz)

BAC (mT)

BDC(mT)

fR (mT)

Ion?

Cells
organism

Exposure
duration(Bowman etal., 1995)

60

>0.3

38 ±
4.5
50.6
±
4.5

29
39.5

40

Children

1-11 years

Increase in childhood
leukemia risk.

Resonant DC fields
B=fR / n for n = 2 & 3/
are derivd from Caefflux studies(Fitzsimmo
ns et al.,
1994)

13.5-18

20 peak

20

16.3

45

TE-85
Sa OS-2

10 min.
40 min.

Increase of 45Ca uptake intobone cells

2 Hz, 50% band width(Fitzsimmo
ns et al.,
1995)

15.3

20 peak

20 ±
2

15.3

40

Ca2+

TE-85

10 minoptimum

Increase of IGF-II release(human osteoscarcoma)

DNA synt. incr. durin
24 h post exposure
Maximum e = 1.6x10-5
V/m(Davies,
1996)

60

14.4

78.3

Ca2+

Seeds
(Replication ofSmith et al.)(Liboff etal., 1995)

45, 25

7.7-46.8
7.8-18.1

36.6
20.3

Mg2+

PC-12
(Discussionof Blackman
et al.)(Blanchard
et al.,
1995)

45, 25
Several(Response to
above)(Blackman
et al.,
1996)(Blackman
et al.,
1993a)

45

12-35
perp.

36.6
16.6

Several

PC-12

50

< 10

44.7

(Blackman
et al.,
1995)

45

23.3141.6

36.6

Ca2+

Ca2+

PC-12

Mg2+, Mn

393

PC-12

EffectNotes

Table 4.49 (continued)
Reference

Frequencyof
exposure(Hz)

BAC (mT)

BDC(mT)(Blackman
et al.,
1998)

45

23.8

(Liboff etal., 1987)

10-30(McLeod etal., 1987b)fR (mT)

Ion?

Cells
organism

36.6

ND

PC-12

50-150

21

Ca2+

Human
lymphocytes

5-32

0-14.6

20.9

Ca2+

Diatoms(Smith etal., 1987)

16, 32, 48,
64

20.9

20.9

Ca2+

Diatoms(Reese etal., 1991)

16

20.9

20.9

Ca2+

Diatoms(Prasad etal., 1991)

10-30

50-15021

No Ca2+Humanlymphocytes(McLeod etal., 1987a)

8-64

15

Ca2+ , K+

Diatoms(Smith etal., 1991b)

16, 80

14.14

110.4
5,
20.9
12.740.9

Ca2+,
Mg2+

Chick femurs

ND, not determined

394

Exposure
duration

EffectNotes

5Final Summary and Evaluation
As mentioned in the Introduction, the final evaluation of the carcinogenicity of extremely
low frequency electric and magnetic fields (ELF EMF) was made following the working
procedures and evaluation method of the International Agency for Research on Cancer(IARC), as modified in Appendix A. The final evaluations for non-cancer end-points weremade by a similar procedure, with consideration of other data relevant to the evaluation ofcarcinogenicity and its mechanisms (Section 12 (b) in Appendix A). A brief discussion of
the levels of evidence as defined by the IARC is warranted.
The predominant evaluations of the various health end-points covered in this report areÔlimitedÕ and ÔinadequateÕ evidence. ÔLimited evidenceÕ is not an unusual finding for
epidemiological data in the IARC Monographs on the Evaluation of Carcinogenic Risks to
Humans. This degree of evidence is generally provided by studies for which there iscredible evidence of an association and for which a causal linkage cannot be establishedwith a high degree of certainty. This does not mean the effect is weak, nor does it mean
there is clearly an effect, although these issues enter into the evaluation. In most cases,
this degree of evidence is associated with one or more of the following problems:
questionable identification of the exposure factor(s) associated with the disease outcome(either a dose surrogate was used or individuals were missclassified as to their exposure
category), bias may have played a small role in the finding, confounders were not ruledout to the satisfaction of the original investigator and/or the Working Group, the observed
effect was small, making clear detection of an effect difficult, and/or there is little
information on doseÐresponse in the available report. The careful reader is directed to thesections on human epidemiological findings for a clear description of each study. For
experimental animal bioassays, Ôlimited evidenceÕ for an effect is generally driven by clear
findings in only a single study for a single end-point or minor problems with a set of data
which otherwise would have been positive; confounding, bias, and exposure
missclassification generally should not exist in laboratory studies.
ÔInadequate evidenceÕ can imply one of four possibilities: (1) there are insufficient data
for making a judgment of any kind (e.g. poor study design, making interpretation
impossible); (2) the data suggest a positive effect but, due to limitations in design or very
weak findings, cannot be interpreted as suggesting a causal linkage; (3) the data suggest anegative effect but, due to limitations in design or very few findings, cannot be interpreted
as suggesting no effect; and (4) the data are contradictory and no clear pattern isdiscernible. For case (1), given a solid hypothesis, it may be beneficial to continue tostudy an inadequate finding using a better design in the same experimental system. For
case (2), if the effect seen is of public health consequence, it should be studied further butwith a clear hypothesis and perhaps in conjunction with other studies such as those
providing mechanistic interpretation. In case (3), unless there is a clear scientific reason
for further study, again involving a defined hypothesis, there is little need to continue tostudy the observed effect. Finally, for case (4), the effect might be further studied if thescientific issues are compelling or if health concerns are raised, but it is unlikely that395

another study of similar design would be performed. Additional studies might not beneeded. Again, a careful reader searching for scientific hypotheses for further study
should read the more detailed descriptions of the findings presented in the three preceding
chapters.
The final evaluations and a brief description of the evidence supporting these evaluations
are given below.

5.1

Carcinogenicity in humans
The Working Group concluded that ELF EMF are possibly carcinogenic to humans(Group 2B, Appendix B). This evaluation was supported by 19 members of the Working
Group; 8 members considered that the evidence fell into Group 3 (ÔELF EMF are notclassifiable as to their carcinogenicity to humansÕ), 1 member considered that the evidence
fell into Group 4 (ÔELF EMF are probably not carcinogenic to humansÕ), 1 member
abstained from the vote, and 0 members were absent and did not vote. 2 members of theWorking Group who were absent for the final vote left clear instructions as to what theirvote would be, and these are recorded in the counts given above.

5.1.1 Evidence from epidemiological studies to support the evaluation
The majority (20 out of 26) of the Working Group members who voted concluded there islimited evidence that residential exposure to ELF magnetic fields is carcinogenic tochildren on the basis of the results of studies of childhood leukemia; the remaining 6
voting members concluded that there was inadequate evidence. Three lines of evidence
supported the overall finding: the association between exposure to calculated magnetic
fields and risk for childhood leukemia, the association between exposure to measured 24-hmagnetic fields and risk for childhood leukemia, and continued concern about theassociation between wire codes and risk for childhood leukemia. There was inadequate
evidence from spot measurements of magnetic fields in homes to support this finding.
The majority (14 out of 25) of the Working Group members who voted considered that
there is limited evidence that occupational exposure to ELF magnetic fields is carcinogenic
to humans on the basis of results of studies of chronic lymphocytic leukemia (CLL); theremaining 11 voting members concluded that there is inadequate evidence. The association
between exposure to magnetic fields and risk for CLL was considered in three studies of
its incidence (two in Sweden and one in Canada and France) and in one study of mortality
from this disease (in the USA). No association was found in the US study, which was
based on diagnoses derived from death certificates. In the CanadaÐFrance study, anonsignificantly increased risk was seen overall and in two of the three cohorts.
Differences in definition and in follow-up of the three cohorts, however, limit theinterpretation of these results. A significant increase in risk was seen in both of the396Swedish studies (Feychting et al., 1997; Floderus et al., 1993). Although the study of
Feychting et al. provides unique information on the potential importance of combined
occupational and residential exposure in adults, it suffers from small numbers andweakness in exposure assessment, particularly for women. In the study of Floderus et al.,the risk increased with increasing exposure; it was particularly strong for the highest
exposure category and increased somewhat when adjusted for exposure to potential
confounders. The refusal rate in that study, however, could have introduced a bias in the
results.
The majority (22 out of 25) of the Working Group members who voted concluded that
there is inadequate evidence for an association between occupational exposure to ELF
EMF and the risk for other cancers; 2 voting members concluded that there is limited
evidence and one that there is evidence for lack of an effect. The cancers considered were
acute myelogenous leukemia (4 studies), brain cancer (5 studies), male breast cancer (10studies), and female breast cancer (4 studies). Overall, the inadequacy of the findings isdue to limitations in study design, inconsistency in findings across studies, and/or a lackof association.
The majority (24 out of 25) of the Working Group members who voted concluded that
there is inadequate evidence that residential exposure to ELF magnetic fields is
carcinogenic to adults; the other voting member concluded there is evidence suggestinglack of effect. The cancers considered in this evaluation included leukemias (2 studies ofuse of appliances, 3 studies of distance from power lines, 2 studies of measured fields,
and one study of calculated fields), breast cancer (4 studies), and cancers of the nervous
system (3 studies). Overall, the inadequacy of the findings is due to limitations in study
design, inconsistency in findings across studies, and/or a lack of association. In general,none of the associations between residential exposure to magnetic fields and the risk forcancer was by itself convincingly positive; however, the quality of the exposure
assessment is a serious limitation in all of these studies.
There is inadequate evidence with respect to childhood nervous system tumors. Thisconclusion was supported by 25 Working Group members; there were 2 abstentions and2 absent.
There is inadequate evidence with respect to childhood lymphoma. This conclusion was
supported by 25 Working Group members; there were 2 abstentions and 2 absent.

5.1.2 Evidence from studies of carcinogenicity in experimental animals invivo to support the evaluation
The majority (19 out of 27) of the Working Group members who voted concluded that
there is inadequate evidence in experimental animals for the carcinogenicity of exposure to
ELF EMF; the other 8 members concluded that there was evidence for a lack of effect.

397

The overall conclusion of the Working Group was that most of the studies suggest a lackof carcinogenicity, and the few that gave results of borderline positivity are inadequate toconclude that exposure to magnetic fields at the magnitude and configurations at which
they were investigated increases the incidence of cancer in rodents. Two long-termbioassays showed no carcinogenic response, but one showed an equivocal response at one
tumor site in animals of one sex of one species. Within the limits of the experimental
model of multistage mammary carcinogenesis, the results of the ensemble of experiments
did not provide convincing evidence for a promoting effect of EMF on chemically induced
mammary cancer. In another commonly investigated model, skin carcinogenesis, exposure
to magnetic fields had no effect. EMF did not induce leukemia or lymphoma in mice orrats in several studies.

5.1.3 Mechanistic and in vitro evidence to support the evaluation
When mechanistic data are available to support reported toxicological results, the IARC
guidelines allow that support to be categorized as ÔweakÕ, ÔmoderateÕ, or ÔstrongÕ. All (27)of the Working Group members who voted concluded that a limited number of wellperformed studies provide moderate evidence for mechanistically plausible effects of ELF
EMF in vitro at intensities greater than 100 mT on end-points generally regarded asreflecting the action of toxic agents. All (26) of the Working Group members who voted
concluded that the in-vitro evidence and information on physical mechanisms provide
weak support for an effect of fields of intensities below approximately 100 mT.
A series of recent (1996Ð98) studies has shown that field exposure induces genemutations. ELF fields at flux densities below 100 mT have consistently been shown tohave no effect on mutation rates, but fields of 200Ð400 000 mT reproducibly andsignificantly enhance mutation rates after initiation with either X-rays or gamma-rays.
Moreover, exposure to 400 000 mT has been shown to increase the number of mutationsin the absence of ionizing radiation in two human cell lines. Thus, multiple, self-consistentreports demonstrate a dose-dependent effect on a process or end-point commonly
considered to be associated with carcinogenesis. Importantly, the flux densities used in allof these studies (³ 100 mT) are within the range of a single physical transduction
mechanism, specifically magneto-chemical transduction. The potential for magnetochemical effects at flux densities above 100 mT has been firmly established in boththeoretical analyses and biochemical investigations.
Numerous well-performed studies have also shown strong effects on other end-points
commonly associated with carcinogenesis, including significantly increased cellproliferation, disruption of signal transduction pathways, and inhibition of differentiation,
all of these effects occurring at field intensities greater than 100 mT. Like the studies ofgene mutations, these investigations were performed at sufficiently high intensities thatmagneto-chemical transduction is a plausible mechanism of fieldÐcell transduction,although this does not preclude other mechanisms of interaction.

398

5.1.4 Discussion
There is little doubt that the evidence in support of the decision to classify ELF EMF
into Group 2B is driven by the results of studies on childhood leukemia in residential
environments and on CLL in adults in occupational settings. The fact that limited
evidence was seen for CLL in adults should not be construed as providing support for thefinding with regard to leukemia in children, however: childhood leukemia and adult CLL
are very different diseases with different etiologies. Also, the inadequacy of the evidence
for an effect on the risk for CLL in adults in the studies of residential exposure neither
supports nor refutes the findings in the studies of occupational exposure. The in-vitro andmechanistic data provide, at best, marginal support for the conclusion that ELF EMF are
possibly carcinogenic to humans. While ELF magnetic fields at intensities greater than 100
mT provide moderate support for effects in vitro, there was little evidence of effects at
intensities below this limit, which cover most of the range of exposure in the studies ofresidential childhood exposure and adult occupational exposure. Relatively few of thestudies of occupational exposure addressed exposure to electric fields. Finally, theinadequate evidence from long-term bioassays for carcinogenicity in rodents is driven
more by lingering concerns about single findings in two separate studies than by an overall
concern that something has been missed in these studies or that there is a trend toward a
positive effect in poorly conducted studies.

5.2

Non-cancer health effects

5.2.1 Non-cancer adverse health effects
None of the evidence for adverse health effects seen after exposure to ELF EMF achieveda degree of evidence exceeding ÔinadequateÕ (for humans) or ÔweakÕ (for experimental
animals). The end-points evaluated in humans were adverse birth outcomes after maternal
exposure, adverse reproductive effects after paternal exposure, Alzheimer disease,amyotrophic lateral sclerosis and other motor neuron diseases, suicide and depression,and cardiovascular disease.
There is inadequate evidence that maternal occupational exposure to ELF EMF causes
adverse birth outcomes. This conclusion was supported by 22 Working Group members;
there were 2 votes for ÔlackÕ of evidence, 1 abstention, and 4 absent.
There is inadequate evidence that paternal occupational exposure to ELF EMF causes
reproductive effects. This conclusion was supported by 20 Working Group members;
there were 3 votes for ÔlackÕ of evidence, 2 abstentions, and 4 absent.

399

There is inadequate evidence that occupational exposure to ELF EMF causes Alzheimer
disease. This conclusion was supported by 23 Working Group members; there was 1 votefor ÔlackÕ of evidence, 1 abstention, and 4 absent.
There is inadequate evidence that occupational exposure to ELF EMF causes
amyotrophic lateral sclerosis. This conclusion was supported by 24 Working Group
members; there was 1 abstention and 4 absent.
There is inadequate evidence that occupational exposure to ELF EMF causes suicide or
depression. This conclusion was supported by 17 Working Group members; there were 6
votes for ÔlackÕ of evidence, 2 abstentions, and 4 absent.
There is inadequate evidence that occupational exposure to ELF EMF causes
cardiovascular disease. This conclusion was supported by 24 Working Group members;
there was 1 abstention and 4 absent.
There is inadequate evidence that environmental exposure to ELF EMF has adverse
effects on pregnancy outcome or is associated with depression. This conclusion was
support by 23 Working Group members; there was one vote for ÔnoÕ evidence, 1abstention, and 4 absent.
There is no evidence in experimental animals for effects of ELF EMF on the immune
system. This conclusion was supported by 13 members of the Working Group; there
were six votes for ÔweakÕ evidence, one abstention, and nine absent.
There is no evidence that exposure to power-line frequency EMF affects thehemotological parameters of rodents. This conclusion was supported by 17 members of
the Working Group; there was 1 abstention and 11 absent.
There is weak evidence for the neurobehavioral, neuropharmacological,
neurophysiological, and neurochemical effects of electromagnetic fields in experimental
animals. This conclusion was supported by 9 members of the Working Group; there
were 8 votes for ÔmoderateÕ evidence, 3 abstentions, and 9 absent.
There is no evidence for the reproductive or developmental effects of exposure tosinusoidal magnetic fields in experimental animals. This conclusion was supported by 17
Working Group members; there were 3 votes for ÔweakÕ evidence, 8 abstentions, 1 absent.
Because of the complexity of the electromagnetic environment, the review of
epidemiological and other biological studies did not allow precise determination of thespecific, critical conditions of exposure to ELF EMF associated with the disease endpoints studied.

400

5.2.2 Other biological effects
There was one biological effect which the majority (14 out of 19) of the Working Group
found to have strong evidence; exposure to electric and magnetic fields affects bone repair
and adaptation. The remaining 5 votes were for moderate evidence. There appears to be
substantial, accumulating evidence that complex clinical exposures to PEMF have asignificant effect on the primary bone healing processes. The studies of both osteotomy
and spinal fusion show a robust effect. While quantification and analysis were weak inthese two studies, they are prospective, randomized, double-blind trials, a rarity in thefield of orthopedics. Perhaps the most convincing trial is that of the response of bone
tissue during limb lengthening. While no effect on secondary bone healing was observed,
there was significant inhibition of bone resorption and evidence of new bone formation.
Studies in animals in vivo indicate only limited efficacy. Magnetic therapy appears
incapable of enhancing the healing of osteotomies, ingrowth of bone into a defect, boneelongation, or graft healing and, in at least one case (ingrowth), may inhibit the normal
process. The results obtained in a model of endochondral ossification after exposure ofwhole animals suggest, however, that magnetic field therapy can be effective. Conversely,
magnetic fields in animals appear to have a strong, reproducible effect on the process ofappositional (surface) bone growth and on inhibition of bone resorption.
The Working Group could not reach a conclusion about whether exposure to electric andmagnetic fields affect nervous and non-bone connective tissue repair and adaptation invertebrates. This conclusion was supported 12 Working Group members abstaining;
there were 10 votes for ÔmoderateÕ evidence, 6 votes for ÔweakÕ evidence, and 1 absent.
There is weak evidence that short term human exposure to ELF EMF causes changes inheart-rate variability. This conclusion was supported by 13 Working Group members;
there was 1 vote for ÔmoderateÕ evidence, 2 votes for ÔnoÕ evidence, 8 abstentions, and 5
absent.
There is weak evidence that short term human exposure to ELF EMF causes changes insleep disturbance. This conclusion was supported by 15 Working Group members; there
were 9 abstentions and 5 absent.
There is weak evidence that short term human exposure to ELF EMF causes suppressionof melatonin. The conclusion for effects on melatonin was supported by 16 Working
Group members; there was 1 vote for ÔmoderateÕ evidence, 2 votes for ÔnoÕ evidence, 5abstentions, and 5 absent.
There is no evidence that such exposure has other effects on the biological end-points
studied in the laboratory. This conclusion was supported by 12 Working Group
members; there were 2 votes for ÔweakÕ evidence, 11 abstentions, and 5 absent. The tie
vote was broken by the Chair.

401

There is weak evidence that exposure to electric and magnetic fields alters the levels of
melatonin in rodents. This conclusion is supported by 14 members of the Working
Group; there were 9 votes for moderate support; 4 abstentions; 2 absent.
There is no evidence that exposure to electric and magnetic fields alters the levels of
melatonin in sheep or baboons. This conclusion is supported by 14 members of theWorking Group; there were 13 abstentions; 2 absent.
There is no evidence in experimental animals for effects of ELF EMF on hematologicalsystem from exposure to ELF electromagnetic fields. This conclusion was supported by
17 members of the Working Group; there was 17 abstention and 11 absent.
There is strong evidence that electric fields can be perceived. This conclusion was
supported by 18 members of the Working Group; 2 abstentions; 9 absent.

5.3

Overall evaluation
A majority of the Working Group concluded that classification of ELF EMF as possibly
carcinogenic (Group 2B) is a conservative, public-health decision based on limited
evidence of an increased risk for childhood leukemias with residential exposure and anincreased occurrence of CLL associated with occupational exposure. For these particularcancers, the results of in vivo, in vitro, and mechanistic studies do not confirm or refutethe findings of the epidemiological studies. The overall body of evidence has, however,laid a foundation for furthering our understanding of the biological effects, mechanisms,
and exposure circumstances that may be related to the possible carcinogenicity and otheradverse human health effects of exposure to ELF EMF.

402

6

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7

Abbreviations•

angstrom

AC

alternating current

ALL

acute lymphocytic leukemia

ALS

amyotrophic lateral sclerosis

AML

acute myelogenous leukemia

ANLL

acute nonlymphocytic leukemia

ANOVA

analysis of varianceBflux density

bw

body weightCI

confidence interval

CLL

chronic lymphocytic leukemia

CML

chronic myelogenous leukemia

CNS

central nervous systemDCdirect current

DG

days gestation

DMBA

7,12-dimethylbenz[a]anthracene

DOE

Department of Energy

EDFElŽctricitŽ de France

EEGelectroencephalogram

ELF

extremely low frequency

EMF

electric and magnetic fields

EMFRAPID

Electric and Magnetic Fields Research and Public Information
Dissemination

ENU

ethyl-N-nitrosourea

EPRI

Electric Power Research Institute

ERP

event-related potential

FSH

follicle - stimulating hormone

G

gauss

GH

growth hormone

GLP

good laboratory practice

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GM

geometricmean

GSD

geometric standard deviationH

magnetic field strength

HCC

high current configuration

HF

high frequency

HRVheart-rate variability

IARC

International Agency for Research on Cancer

IRR

incidence rate ratio

JEMjobÐexposure matrix

LCC

low current configuration

LH

luteinizing hormone

MNU

methyl-N-nitrosourea

MTmelatoninNA

not applicable

ND

not determined

NIEHS

National Institute of Environmental Health Sciences

NINCDS-ADRDA

National Institute of Neurologic and Communicative Disorders andStroke-AlzheimerÕs Disease and Related Disorders Association

NIOSH

National Institute of Occupational Safety and HealthNS

not significant

NTP

National Toxicology Program

ODC

ornithine decarboxylase

OHCC

ordinary hi current configuration

6-OHMS

6-hydroxymelatonin sulfate

OLCC

ordinary low current configuration

OR

odds ratio

PEMF

pulsed electromagnetic fields

PKC

protein kinase C

PIR

proportional incidence ratio

RCMS

standardized rate of change metric

REM

rapid eye movementrms

root mean square

RR

relative risk
468

RT

relative timeSD

standard deviation

SIR

standardized incidence ratio

SMR

standardized mortality ratio

TPA

12-O-tetradecanoylphorbol 13-acetate

TWA

time-weightedaverage

UG

undergroundwiring

VDT

video display terminal

VHCC

very high current configuration

VLCC

very low current configuration

VLF

very low frequency

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8

glossary

AC magnetic field

A magnetic field originating from AC electricity. Commonlyused as an antonym for DC magnetic field, regardless of thesource.

Average-sensing rms response

Time response of a meter that gives the average of the rectified
signal, calibrated to give the root-mean-square (RMS) of asinusoidal power frequency input. If the field has harmonics,
an average-sensing rms meter will have some errors

Axial ratio

The ratio of the rms magnitudes of the semi-minor and semimajor axes for a single frequency. Ranges from zero for linear
polarization to one for circular polarization.

Characteristics

Detailed physical properties of electric or magnetic fields, suchas the magnitude, frequency spectrum, polarization, etc.

DC magnetic field

Magnetic fields originating from DC electricity. Commonlyused term for all static magnetic fields, including geomagnetic
fields and those originating from permanent magnets.

Data processing

A summary table heading which describes the calculation of an
exposure metric from an instrumentÕs digital output, whether
performed on a calculator, a personal computer, or aprogrammed microprocessor within the instrument.

Data-logger

An digital memory device which automatically records one ormore measurements along with the measurement time.

Dose

A toxicological term for the amount of a chemical or physicalagent delivered to a target organ. Since neither the target organ
nor the mechanism of delivery are well understood for most
biological effects of ELF fields, an EMF dose can seldom bedefined, and the concept of exposure metric is used instead.

Dosimeter

An instrument that can be worn on a person for measuringexposures over time. Since the dose cannot usually be
determined for ELF fields, ÒdosimeterÓ is a misnomer, and aterm like personal monitor or "exposure meter" is preferred.

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Duration

The total time over which an instrument is regularly taking
samples. (See Sample and Sampling time.)

Dynamic range

The range between an instrument's overload input and its
minimum acceptable input (as determined by noise, resolution,
distortion, etc.).

Electric field

A vector field E measured in volts / meter.

Electromagneticfields

The combination of electric and magnetic fields in theenvironment. This term is easily confused withÒelectromagnetic radiationÓ, and can therefore be misleadingwhen used with extremely low frequencies whose radiation isbarely detectable. Therefore Òelectric and magnetic fieldsÓ isthe preferred term.

ELF (extremely low frequency) The frequency range from 3 - 3000 Hz.
EMF

Electric and magnetic fields.

Exposure

The amount of a chemical or physical agent in the environmentthat a person comes in contact with over a some period of time.

Exposure assessment

The evaluation of a person's exposure by measurements,
modeling, information about sources, or other means.

Exposure metric

A single number which summarizes an electric and/or magnetic
field exposure. An exposure metric is usually determined by a
combination of the instrument's signal processing and the data
analysis performed after the measurement. Also called anÒeffects functionÓ and an "exposure summary."

FilterElectronic components of an instrument which modify its
frequency response to an analog or digital signal. ELF magnetic
field meters generally have bandpass filters whose response is
set equal to one at the power frequency. These ELF bandpass
filters have been classified in various ways: flat, linear,broadband, narrowband, fundamental, and harmonic

Free-body sensor

An electric field sensor that is supported in space without
conductive contact to any object.

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Frequency response

An instrument's output as a function of frequency relative tothe magnitude of the input signal. Specification of an
instrument's frequency response includes the type of filter andits bandwidth.

Frequency spectrum

An EMF characteristic as a function of frequency, which canbe plotted as a bar graph. Usually means the frequency
components of the rms vector magnitude calculated by a fast
Fourier transform (FFT). However, the rms component
magnitudes, the component's phases, and axial ratios also havefrequency spectra.

Fundamental (filter)

A narrowband filter that responds to the power frequency (50or 60 Hz) but not to any harmonics.

Fundamental (frequency)

The lowest frequency component of the Fourier series of aperiodic waveform.

Geomagnetic fields

Magnetic fields originating from the earth (including theatmosphere). Predominantly a static magnetic field, but includes
some oscillating components and transients.

Ground reference sensor

An electric field sensor that measures the induced current or
charge oscillating between an isolated electrode and a grounded
conductor.

Harmonic (filter)

A broadband filter in the EMDEX-II meter that responds to themagnetic field's harmonics but not the 60 Hz power frequency.

Harmonic (frequency)

Frequencies that are integral multiples of the power frequency
or some other reference frequency.

Hazard surveillance

Assessing exposures to chemical or physical agents in a large
sample of workplaces for purposes of evaluating the extent of ahealth hazards and planning efforts for its evaluation andcontrol.

Health hazard evaluation

A short-term study for the assessment of a potential healthhazard in a workplace.

Intermittent fields

Fields whose rms vector magnitude changes rapidly. In
contrast to transients, intermittent fields may have high levels
for longer times and are generally in the ELF frequency range.

473

LF (low frequencies)

The frequency range from 30-300 kHz.

Magnetic field strength

A vector field H with units of ampere/meter.

Magnetic field

Both the H and B fields. In health studies, these two fields are
essentially interchangeable since their vectors are parallel in air,the human body, and other non-ferromagnetic materials. In
studies at extremely low frequencies, Òmagnetic fieldÓ isgenerally used for the magnetic flux density (B field). When the
topic is radio frequencies and microwaves, the term usuallymeans the magnetic field strength (H field).

Magnetic flux density

A vector field B with units of tesla (SI) or gauss (CGS).

Magnitude

See Vector magnitude.

Maximum field

The greatest rms magnitude of an electric or magnetic fieldmeasured by rotating a single-axis sensor in all directions

MethodA complete set of instructions for the measurement of EMF
exposures in an environment.

MetricSee Exposure metric.

MonitorAn instrument for measuring exposures over time. As a verb,
to measure over time.

Output

The final numbers which an instrument routinely producesfrom measurements, either as its read-out or a digital datalogger file which can be transferred to a computer.

Personal monitor

An instrument that can be worn on a person for measuringexposure over time.

Polarization

The shape traced by the tip of an EMF vector over a single
cycle. For fields with a single frequency, the polarization iseither linear, elliptical or circular. For fields with multiple
frequencies, the polarization can be a complex shape, and isbetter expressed as a spectrum of the axial ratio at different
frequencies.

474

Power frequency

The frequency at which AC electricity is generated. For electricutilities, the power frequency is 60 Hz in North America,
Brazil, and parts of Japan. Electric power is 50 Hz in much of
the rest of the world. Isolated AC electrical systems may haveother power frequencies, e.g. 440 Hz in commercial airliners.

Principal harmonic

See Power frequency and Fundamental.

Resultant

The mathematical function used to calculate the vector
magnitude B from the vector components Bx, By, Bz with the
Pythagorean theorem: If Bx, By, and Bz are the rms components
of a field, the resultant equals the rms vector magnitude. (SeeRoot-mean-square.) In ELF measurements, "resultant" iscommonly used to mean "rms vector magnitude" of themagnetic or electric field. However, the resultant function canalso be used to obtain the instantaneous vector magnitude B(t)and the magnitude Bo of the static (DC) field.

Root-mean-square (rms)

The most versatile mathematical function for averaging themagnitude of time-varying electric and magnetic fields.. Metersthat measure the rms of a signal can have true rms or averagesensing rms circuitry.

SampleA continuous measurement covering a fraction of the duration
over which the exposure is monitored.

Sampling rate

The frequency with which samples are taken, expressed as thetime between the beginning of each sample.

Sampling strategy

A strategy for determining the sites, subjects, timing, duration,and methods for measuring exposures.

Sample time

The length of a sample, i.e. the time over which an instrument
is continuously taking measurements, (as opposed to theduration which is the total time the monitor is taking samples)

Semi-majoraxis

The longest axis of the trace of an elliptically polarized field.

Semi-minoraxis

The shortest axis of the trace of an elliptically polarized field.

Spot measurement

An instantaneous measurements at a designated location.

475

Static field

A field vector that does not vary with time. In mostenvironments, electric and magnetic fields change with time, but
their frequency spectra has a component at 0 Hz.. ThisÒquasi-staticÓ component of the field is measured by an
instrument with a low-pass filter set at a small frequency (e.g. 3Hz) or by averaging the oscillating signal over the sample time.

Sub-harmonics

Frequencies in the spectrum that are lower than the power
frequency.

Three-axis (3D) sensor

A sensor with three axial probes aligned orthogonally in order
to measure the field's three spatial components simultaneously.

Time response

The methods by which an instrument responds to the signal's
variations over time, such as A/D conversion, the capture ofdigitized waveforms, and a true rms response.

Time-weighted average (TWA)

A weighted average of exposure measurements taken over a
period of time with the weighting factor equal to the timeinterval between measurements. When the measurements aretaken with a monitor with a fixed sampling rate, the TWA
equals the arithmetic mean of the measurements.

Trace

The three-dimensional pattern made by the tip of an electric or
magnetic field vector over one or more periods of oscillation.

Transients

Brief bursts of high frequency fields, usually resulting frommechanical switching of AC electricity. (Not to be confusedwith Intermittent fields.)

True rms response

The time response of a meter that gives the root-mean-square(RMS) of the input signal accurately.

ULF (ultra low frequency)

The frequency range below 3 Hz.

Vector components

The length of a vector when it is projected onto threeorthogonal axes.

Vector magnitude

The length of an EMF vector.

VLF (very low frequency)

The frequency range from 3 - 30 kHz.

476

Walkthrough survey

An exposure assessment conducted by walking through aworkplace or other environment while carrying a monitor.
Exposures in the workplace are summarized from different
exposure metrics calculated from the measurements madeduring the walkthrough.

Waveform

A single component of the field measured as a function of timeby an instrument with a response time much faster than thefield's frequency of oscillation. The term also means the shapeof the wave as displayed on a graph or oscilloscope trace.

Waveform capture

Measuring waveforms with an oscilloscope or other instrument
which can display the waveform and/or digitize the data forfurther calculations.

Table 8.1 Units
Quantity

SymbolUnits
International System (SI)Electric field
Magnetic flux density

E
B

Magnetic field strength

H

Volts / meter (V/m)
Tesla (T)
1 mT = 10 G
Ampere / meter (A/m)
B = wo H
where
wo = 4"x10-7 T-m / A

Magnetic field conversion in vacuum
and non-ferromagnetic media.

477

CGS
Volts / cm
Gauss (G)Gaussor Oersted
B=H

478

Appendix A
IARC MONOGRAPHS PROGRAMME ON THE EVALUATION OF
CARCINOGENIC RISKS TO HUMAN
PREAMBLE
1.

BACKGROUND
In 1969, the International Agency for Research on Cancer (IARC) initiated a programme
to evaluate the carcinogenic risk of chemicals to humans and to produce monographs on
individual chemicals. The Monographs programme has since been expanded to include
consideration of exposures to complex mixtures of chemicals (which occur, for example, insome occupations and as a result of human habits) and of exposures to other agents, suchas radiation and viruses. With Supplement 6 (IARC, 1987a), the title of the series was
modified IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans to IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, inorder to reflect the widened scope of the programme.
The criteria established in 1971 to evaluate carcinogenic risk to humans were adopted by
the working groups whose deliberations resulted in the first 16 volumes of the IARC
Monographs series. Those criteria were subsequently updated by further ad-hoc working
groups (IARC, 1977, 1978, 1979, 1982, 1983, 1987b, 1988, 1991a; Vainio et al., 1992).

2.

OBJECTIVE AND SCOPE
The objective of the programme is to prepare, with the help of international working
groups of experts, and to publish in the form of monographs, critical reviews andevaluations of evidence on the carcinogenicity of a wide range of human exposures. The
Monographs may also indicate where additional research efforts are needed.
The Monographs represent the first step in carcinogenic risk assessment, which involves
examination of all relevant information in order to assess the strength of the available
evidence that certain exposures could alter the incidence of cancer in humans. The second
step is quantitative risk estimation. Detailed, quantitative evaluations of epidemiological
data may be made in the Monographs, but without extrapolation beyond the range of the479

data available. Quantitative extrapolation from experimental data to the human situation is
not undertaken.
The term ÔcarcinogenÕ is used in these monographs to denote an exposure that is capableof increasing the incidence of malignant neoplasms; the induction of benign neoplasms
may in some circumstances contribute to the judgment that the exposure is carcinogenic.
The terms ÔneoplasmÕ and ÔtumourÕ are used interchangeably.
Some epidemiological and experimental studies indicate that different agents may act atdifferent stages in the carcinogenic process, and several different mechanisms may be
involved. The aim of the Monographs has been, from their inception, to evaluate evidenceof carcinogenicity at any stage in the carcinogenesis process, independently of theunderlying mechanisms. Information on mechanisms may, however, be used in making theoverall evaluation (IARC, 1991a; Vainio et al., 1992).
The Monographs may assist national and international authorities in making risk
assessments and in formulating decisions concerning any necessary preventive measures.
The evaluations of IARC working groups are scientific, qualitative judgments about theevidence for or against carcinogenicity provided by the available data. These evaluations
represent only one part of the body of information on which regulatory measures may bebased. Other components of regulatory decisions may vary from one situation to anotherand from country to country, responding to different socioeconomic and national
priorities. Therefore, no recommendation is given with regard to regulation orlegislation, which are the responsibility of individual governments and/or otherinternational organizations.
The IARC Monographs are recognized as an authoritative source of information on the
carcinogenicity of a wide range of human exposures. A survey of users, made in 1988
indicated that the Monographs are consulted by various agencies in 57 countries. About
4000 copies of each volume are printed, for distribution to governments, regulatory
bodies and interested scientists. The Monographs are also available from the International
Agency for Research on Cancer in London and via the Distribution and Sales Service ofthe World Health Organization.

3.

SELECTION OF TOPICS FOR MONOGRAPHS
Topics are selected on the basis of two main criteria: (a) there is evidence of human
exposure, and (b) there is some evidence or suspicion of carcinogenicity. The term ÔagentÕ
is used to include individual chemical compounds, groups of related chemical compounds
physical agents (such as radiation) and biological factors (such as viruses). Exposures to
mixtures of agents may occur in occupational exposures and as a result of personal andcultural habits (like smoking and dietary practices). Chemical analogues and compoundswith biological or physical characteristics similar to those of suspected carcinogens may

480

also be considered, even in the absence of data on a possible carcinogenic effect in humans
or experimental animals.
The scientific literature is surveyed for published data relevant to an assessment ofcarcinogenicity. The IARC surveys of chemicals being tested for carcinogenicity (IARC,
1973-1992) and directories of ongoing research in cancer epidemiology (IARC, 19761994) often indicate those exposures that may be scheduled for future meetings. Ad-hoc
working groups convened by IARC in 1984, 1989, 1991 and 1993 gave recommendations
as to which agents should be evaluated in the IARC Monographs series (IARC, 1984,
1989, 1991b, 1993).
As significant new data on subjects on which monographs have already been preparedbecome available, re-evaluations are made at subsequent meetings, and revised
monographs are published.

4.

DATA FOR MONOGRAPHSThe Monographs do not necessarily cite all the literature concerning the subject of anevaluation. Only those data considered by the Working Group to be relevant to making
the evaluation are included.
With regard to biological and epidemiological data, only reports that have been publishedor accepted for publication in the openly available scientific literature are reviewed by theworking groupsi. In certain instances, government agency reports that have undergone
peer review and are widely available are considered. Exceptions may be made on an adhoc basis to include unpublished reports that are in their final form and publicly available,
if their inclusion is considered pertinent to making a final evaluation (see pp. A.17 etseq.). In the sections on chemical and physical properties, on analysis, on production anduse and on occurrence, unpublished sources of information may be used.

5.

THEWORKINGGROUP
Reviews and evaluations are formulated by a working group of experts. The tasks of thegroup are: (i) to ascertain that all appropriate data have been collected; (ii) to select thedata relevant for the evaluation on the basis of scientific merit; (iii) to prepare accurate
summaries of the data to enable the reader to follow the reasoning of the Working Group;(iv) to evaluate the results of epidemiological and experimental studies on cancer; (v) toi

The EMF-RAPID Working Group elected to include non-published literature under the conditions that a) it passed
peer review of the Working Group members, b) the author(s) of the document agreed to allow inclusion and releaseof the document following completion of the monograph and c) the manuscript made a substantive contribution tothe overall document.

481

evaluate data relevant to the understanding of mechanism of action; and (vi) to make anoverall evaluation of the carcinogenicity of the exposure to humans.
Working Group participantsii who contributed to the considerations and evaluations
within a particular volume are listed, with their addresses, at the beginning of eachpublication. Each participant who is a member of a working group serves as an individual
scientist and not as a representative of any organization, government or industry. In
addition, nominees of national and international agencies and industrial associations may
be invited as observers.

6.

WORKINGPROCEDURESiii
Approximately one year in advance of a meeting of a working group, the topics of themonographs are announced and participants are selected by IARC staff in consultation
with other experts. Subsequently, relevant biological and epidemiological data arecollected by IARC from recognized sources of information on carcinogenesis, including
data storage and retrieval systems such as BIOSIS, Chemical Abstracts, CANCERLIT,
MEDLINE and TOXLINEÑincluding EMIC and ETIC for data on genetic and related
effects and reproductive and developmental effects, respectively.
For chemicals and some complex mixtures, the major collection of data and the
preparation of first drafts of the sections on chemical and physical properties, on
analysis, on production and use and on occurrence are carried out under a separate
contract funded by the US National Cancer Instituteiv. Representatives from industrial
associations may assist in the preparation of sections on production and use. Information
on production and trade is obtained from governmental and trade publications and, insome cases, by direct contact with industries. Separate production data on some agents
may not be available because their publication could disclose confidential information.
Information on uses may be obtained from published sources but is often complemented
by direct contact with manufacturers. Efforts are made to supplement this information
with data from other national and international sources.
Six months before the meeting, the material obtained is sent to meeting participants, or isused by IARC staff to prepare sections for the first drafts of monographs. The firstii

Virtually all members of the NIEHS Working Group were chosen through a process of nomination and review
involving NIEHS senior staff and two external advisory committees (the National EMF Advisory Committee andthe EMF-RAPID Interagency Comittee). Last minute substitutes replacing cancellations (3 scientists) wereappointed by the NIEHS without external review. Every attempt was made to include these advisory groups indecisions concerning the format, structure and voting procedures of the Working Group.
iii
The selection of areas for review and associated literature were done by NIEHS staff, two permanent advisorygroups and three ad-hoc advisory groups formed for three symposia held prior to the Working Group meeting (seeIntroduction).
iv
separate contracts with scientists knowledgeable about ELF-EMF health effects were funded by the NIEHS toprovide first drafts. These individuals are listed at the beginning of this publication.

482

drafts are compiled by IARC staff and sent, prior to the meeting, to all participants of theWorking Group for reviewv.
The Working Group meets in Lyon for seven to eight daysvi to discuss and finalize thetexts of the monographs and to formulate the evaluations. After the meeting, the mastercopy of each monograph is verified by consulting the original literature, edited andprepared for publication. The aim is to publish monographs within six months of theWorking Group meeting.
The available studies are summarized by the Working Group, with particular regard to thequalitative aspects discussed below. In general, numerical findings are indicated as they
appear in the original report; units are converted when necessary for easier comparisonvii.
The Working Group may conduct additional analyses of the published data and use themin their assessment of the evidence; the results of such supplementary analyses are given
in square brackets. When an important aspect of a study, directly impinging on its
interpretation, should be brought to the attention of the reader, a comment is given insquare brackets.

7.

EXPOSUREDATA
Sections that indicate the extent of past and present human exposure, the sources of
exposure, the people most likely to be exposed and the factors that contribute to the
exposure are included at the beginning of each monograph.
Most monographs on individual chemicals, groups of chemicals or complex mixtures
include sections on chemical and physical data, on analysis, on production and use and on
occurrence. In monographs on, for example, physical agents. occupational exposures andcultural habits, other sections may be included, such as: historical perspectives,
description of an industry or habit, chemistry of the complex mixture or taxonomy.
Monographs on biological agents have sections on structure and biology, methods ofdetection, epidemiology of infection and clinical disease other than cancer.
For chemical exposures, the Chemical Abstracts Services Registry Number, the latest
Chemical Abstracts Primary Name and the IUPAC Systematic Name are recorded- othersynonyms are given, but the list is not necessarily comprehensive. For biological agents,
taxonomy and structure are described, and the degree of variability is given, whenapplicable.

v

Most drafts were circulated two months prior to the Working Group meeting.
The NIEHS Working Group met in Brooklyn Park, Minnesota for nine days.
vii
In general, SI units were used in this publication and conversions are discussed in Chapter 2.
vi

483

Information on chemical and physical properties and, in particular, data relevant to
identification, occurrence and biological activity are included. For biological agents, modeof replication, life cycle, target cells, persistence and latency and host response are given.
A description of technical products of chemicals includes trade names, relevant
specifications and available information on composition and impurities. Some of the trade
names given may be those of mixtures in which the agent being evaluated is only one of
the ingredients.
The purpose of the section on analysis or detection is to give the reader an overview ofcurrent methods, with emphasis on those widely used for regulatory purposes. Methods
for monitoring human exposure are also given, when available. No critical evaluation or
recommendation of any of the methods is meant or implied. The IARC publishes a seriesof volumes, Environmental Carcinogens: Methods of Analysis and Exposure
Measurement (IARC, 1978-93), that describe validated methods for analyzing a wide
variety of chemicals and mixtures. For biological agents, methods of detection andexposure assessment are described, including their sensitivity, specificity andreproducibility.
The dates of first synthesis and of first commercial production of a chemical or mixture
are provided: for agents which do not occur naturally, this information may allow areasonable estimate to be made of the date before which no human exposure to the agent
could have occurred. The dates of first reported occurrence of an exposure are also
provided. In addition, methods of synthesis used in past and present commercial
production and different methods of production which may give rise to different
impurities are described.
Data on production, international trade and uses are obtained for representative regions,which usually include Europe, Japan and the United States of America. It should not,however, be inferred that those areas or nations are necessarily the sole or major sources
or users of the agent. Some identified uses may not be current or major applications, andthe coverage is not necessarily comprehensive. In the case of drugs, mention of their
therapeutic uses does not necessarily represent current practice nor does it imply
judgment as to their therapeutic efficacy.
Information on the occurrence of an agent or mixture in the environment is obtained fromdata derived from the monitoring and surveillance of levels in occupational environments,
air, water, soil, foods and animal and human tissues. When available, data on thegeneration, persistence and bioaccumulation of the agent are also included. In the case of
mixtures, industries, occupations or processes, information is given about all agents
present. For processes, industries and occupations, a historical description is also given,noting variations in chemical composition, physical properties and levels of occupational
exposure with time and place. For biological agents, the epidemiology of infection is
described.

484

Statements concerning regulations and guidelines (e.g., pesticide registrations, maximal
levels permitted in foods, occupational exposure limits) are included for some countries as
indications of potential exposures, but they may not reflect the most recent situation,
since such limits are continuously reviewed and modified. The absence of information on
regulatory status for a country should not be taken to imply that country does not haveregulations with regard to the exposure. For biological agents, legislation and control,
including vaccines and therapy, are described.

8.

STUDIES OF CANCER IN HUMANS(a) Types of studies considered
Three types of epidemiological studies of cancer contribute to the assessment ofcarcinogenicity in humansÑcohort studies, case-control studies and correlation (orecological) studies. Rarely, results from randomized trials may be available. Case series
and case reports of cancer in humans may also be reviewed.
Cohort and case-control studies relate individual exposures under study to the occurrenceof cancer in individuals and provide an estimate of relative risk (ratio of incidence ormortality in those exposed to incidence or mortality in those not exposed) as the main
measure of association.
In correlation studies, the units of investigation are usually whole populations (e.g., inparticular geographical areas or at particular times), and cancer frequency is related to asummary measure of the exposure of the population to the agent, mixture or exposure
circumstance under study. Because individual exposure is not documented, however, acausal relationship is less easy to infer from correlation studies than from cohort and casecontrol studies. Case reports generally arise from a suspicion, based on clinical experience,that the concurrence of two eventsÑthat is, a particular exposure and occurrence of acancerÑhas happened rather more frequently than would be expected by chance. Case
reports usually lack complete ascertainment of cases in any population, definition or
enumeration of the population at risk and estimation of the expected number of cases in
the absence of exposure. The uncertainties surrounding interpretation of case reports andcorrelation studies make them inadequate, except in rare instances, to form the sole basis
for inferring a causal relationship. When taken together with case-control and cohort
studies, however, relevant case reports or correlation studies may add materially to the
judgment that a causal relationship is present.
Epidemiological studies of benign neoplasm, presumed preneoplastic lesions and otherend-points thought to be relevant to cancer are also reviewed by working groups. Theymay, in some instances, strengthen inferences drawn from studies of cancer itself.

485

(b) Quality of studies considered
The Monographs are not intended to summarize all published studies. Those that are
judged to be inadequate or irrelevant to the evaluation are generally omitted. They may bementioned briefly, particularly when the information is considered to be a usefulsupplement to that in other reports or when they provide the only data available. Their
inclusion does not imply acceptance of the adequacy of the study design or of theanalysis and interpretation of the results, and limitations are clearly outlined in square
brackets at the end of the study description.
It is necessary to take into account the possible roles of bias, confounding and chance in
the interpretation of epidemiological studies. By ÔbiasÕ is meant the operation of factors
in study design or execution that lead erroneously to a stronger or weaker association thanin fact exists between disease and an agent, mixture or exposure circumstance. ByÔconfoundingÕ is meant a situation in which the relationship with disease is made toappear stronger or to appear weaker than it truly is as a result of an association between
the apparent causal factor and another factor that is associated with either an increase or
decrease in the incidence of the disease. In evaluating the extent to which these factors
have been minimized in an individual study, working groups consider a number of aspects
of design and analysis as described in the report of the study. Most of these
considerations apply equally to case-control, cohort and correlation studies. Lack ofclarity of any of these aspects in the reporting of a study can decrease its credibility andthe weight given to it in the final evaluation of the exposure.
Firstly, the study population, disease (or diseases) and exposure should have been welldefined by the authors. Cases of disease in the study population should have been
identified in a way that was independent of the exposure of interest, and exposure shouldhave been assessed in a way that was not related to disease status.
Secondly, the authors should have taken account in the study design and analysis of othervariables that can influence the risk of disease and may have been related to the exposureof interest. Potential confounding by such variables should have been dealt with either inthe design of the study, such as by matching. or in the analysis, by statistical adjustment.
In cohort studies, comparisons with local rates of disease may be more appropriate thanthose with national rates. Internal comparisons of disease frequency among individuals at
different levels of exposure should also have been made in the study
Thirdly, the authors should have reported the basic data on which the conclusions arefounded, even if sophisticated statistical analyses were employed. At the very least, theyshould have given the numbers of exposed and unexposed cases and controls in a casecontrol study and the numbers of cases observed and expected in a cohort study Further
tabulations by time since exposure began and other temporal factors are also important. Ina cohort study, data on all cancer sites and all causes of death should have been given, to486

reveal the possibility of reporting bias. In a case-control study. the effects of investigatedfactors other than the exposure of interest should have been reported.
Finally, the statistical methods used to obtain estimates of relative risk, absolute rates ofcancer, confidence intervals and significance tests, and to adjust for confounding shouldhave been clearly stated by the authors. The methods used should preferably have been
the generally accepted techniques that have been refined since the mid-1970s. Thesemethods have been reviewed for case-control studies (Breslow & Day, 1980) and forcohort studies (Breslow & Day, 1987).
(c) Inferences about mechanism of action
Detailed analyses of both relative and absolute risks in relation to temporal variables, suchas age at first exposure, time since first exposure, duration of exposure, cumulative
exposure and time since exposure ceased, are reviewed and summarized when available.
The analysis of temporal relationships can be useful in formulating models ofcarcinogenesis. In particular, such analyses may suggest whether a carcinogen acts early orlate in the process of carcinogenesis, although at best they allow only indirect inferences
about the mechanism of action. Special attention is given to measurements of biologicalmarkers of carcinogen exposure or action, such as DNA or protein adducts, as well as
markers of early steps in the carcinogenic process, such as proto-oncogene mutation,
when these are incorporated into epidemiological studies focused on cancer incidence ormortality. Such measurements may allow inferences to be made about putative
mechanisms of action (IARC, 1991a; Vainio et al., 1992).
(d) Criteria for causality
After the quality of individual epidemiological studies of cancer has been summarized andassessed, a judgement is made concerning the strength of the evidence that the agent,
mixture or exposure circumstance in question is carcinogenic for humans. In making their
judgment, the Working Group considers several criteria for causality. A strong association(a large relative risk) is more likely to indicate causality than a weak association although
it is recognized that relative risks of small magnitude do not imply lack of causality andmay be important if the disease is common. Associations that are replicated in several
studies of the same design or using different epidemiological approaches or under different
circumstances of exposure are more likely to represent a causal relationship than isolated
observations from single studies. If there are inconsistent results among investigations,
possible reasons are sought (such as differences in amount of exposure), and results ofstudies judged to be of high quality are given more weight than those from studies judged
to be methodologically less sound. When suspicion of carcinogenicity arises largely from asingle study, these data are not combined with those from later studies in any subsequent
reassessment of the strength of the evidence.

487

If the risk of the disease in question increases with the amount of exposure, this isconsidered to be a strong indication of causality, although absence of a graded response is
not necessarily evidence against a causal relationship. Demonstration of a decline in risk
after cessation of or reduction in exposure in individuals or in whole populations also
supports a causal interpretation of the findings.
Although a carcinogen may act upon more than one target, the specificity of an
association (an increased occurrence of cancer at one anatomical site or of one
morphological type) adds plausibility to a causal relationship, particularly when excess
cancer occurrence is limited to one morphological type within the same organ.
Although rarely available, results from randomized trials showing different rates among
exposed and unexposed individuals provide particularly strong evidence for causality.
When several epidemiological studies show little or no indication of an association
between an exposure and cancer, the judgment may be made that, in the aggregate, theyshow evidence of lack of carcinogenicity. Such a judgment requires first of all that thestudies giving rise to it meet, to a sufficient degree, the standards of design and analysis
described above. Specifically, the possibility that bias, confounding or misclassification of
exposure or outcome could explain the observed results should be considered and excluded
with reasonable certainty. In addition, all studies that are judged to be methodologicallysound should be consistent with a relative risk of unity for any observed level of exposure
and, when considered together, should provide a pooled estimate of relative risk which isat or near unity and has a narrow confidence interval, due to sufficient population size.
Moreover no individual study nor the pooled results of all the studies should show any
consistent tendency for relative risk of cancer to increase with increasing level of
exposure. It is important to note that evidence of lack of carcinogenicity obtained in thisway from several epidemiological studies can apply only to the type(s) of cancer studied
and to dose levels and intervals between first exposure and observation of disease that are
the same as or less than those observed in all the studies. Experience with human cancer
indicates that, in some cases, the period from first exposure to the development of clinicalcancer is seldom less than 20 years; latent periods substantially shorter than 30 years
cannot provide evidence for lack of carcinogenicity.

9.

STUDIES OF CANCER IN EXPERIMENTAL ANIMALSAll known human carcinogens that have been studied adequately in experimental animals
have produced positive results in one or more animal species (Wilbourn et al., 1986
Tomatis et al., 1989). For several agents (aflatoxins, 4-aminobiphenyl, azathioprine, betel
quid with tobacco, BCME and CMME (technical grade), chlorambucil, chlornaphazine,
ciclosporin, coal-tar pitches, coal-tars, combined oral contraceptives, cyclophosphamide,
diethylstilboestrols melphalan, 8-methoxypsoralen plus UVA, mustard gas, myleran, 2naphthylamines nonsteroidal oestrogens, oestrogen replacement therapy/steroidal

488

oestrogens, solar radiation, thiotepa and vinyl chloride), carcinogenicity in experimental
animals was established or highly suspected before epidemiological studies confirmed the
carcinogenicity in humans (Vainio et al, 1995). Although this association cannot establishthat all agents and mixtures that cause cancer in experimental animals also cause cancer inhumans. nevertheless, in the absence of adequate data on humans, it is biologicallyplausible and prudent to regard agents and mixtures for which there is sufficientevidence of carcinogenicity in experimental animals as if they presented a
carcinogenic risk to humans. The possibility that a given agent may cause cancer
through a species-specific mechanism which does not operate in humans should also betaken into consideration.
The nature and extent of impurities or contaminants present in the chemical or mixture
being evaluated are given when available. Animal strain, sex, numbers per group, age atstart of treatment and survival are reported.
Other types of studies summarized include: experiments in which the agent or mixture
was administered in conjunction with known carcinogens or factors that modify
carcinogenic effects; studies in which the end-point was not cancer but a defined
precancerous lesion; and experiments on the carcinogenicity of known metabolites andderivatives.
For experimental studies of mixtures, consideration is given to the possibility of changes
in the physicochemical properties of the test substance during collection, storage,
extraction, concentration and delivery. Chemical and toxicological interactions of thecomponents of mixtures may result in nonlinear dose-response relationships.
An assessment is made as to the relevance to human exposure of samples tested inexperimental animals, which may involve consideration of: (i) physical and chemical
characteristics, (ii) constituent substances that indicate the presence of a class of
substances, (iii) the results of tests for genetic and related effects, including genetic
activity profiles, DNA adduct profiles, proto-oncogene mutation and expression andsuppressor gene inactivation. The relevance of results obtained, for example, with animalviruses analogous to the virus being evaluated in the monograph must also be considered.
They may provide biological and mechanistic information relevant to the understanding of
the process of carcinogenesis in humans and may strengthen the plausibility of aconclusion that the biological agent that being evaluated is carcinogenic in humans.
(a) Qualitative aspects
An assessment of carcinogenicity involves several considerations of qualitative
importance, including (i) the experimental conditions under which the test was performed,
including route and schedule of exposure, species, strain, sex, age, duration of follow-up;(ii) the consistency of the results, for example, across species and target organ(s): (iii) the489

spectrum of neoplastic response, from preneoplastic lesions and benign tumours tomalignant neoplasma; and (iv) the possible role of modifying factors.
As mentioned earlier the Monographs are not intended to summarize all publishedstudies. Those studies in experimental animals that are inadequate (e.g., too short aduration, too few animals, poor survival; see below) or are judged irrelevant to theevaluation are generally omitted. Guidelines for conducting adequate long-term
carcinogenicity experiments have been outlined (e.g., Montesano et al., 1986).
Considerations of importance to the Working Group in the interpretation and evaluationof a particular study include: (i) how clearly the agent was defined and, in the case of
mixtures, how adequately the sample characterization was reported; (ii) whether the dose
was adequately monitored, particularly in inhalation experiments; (iii) whether the doses
and duration of treatment were appropriate and whether the survival of treated animals
was similar to that of controls; (iv) whether there were adequate numbers of animals pergroup; (v) whether animals of both sexes were used; (vi) whether animals were allocatedrandomly to groups; (vii) whether the duration of observation was adequate; and (viii)
whether the data were adequately reported. If available, recent data on the incidence ofspecific tumours in historical controls, as well as in concurrent controls, should be taken
into account in the evaluation of tumour response.
When benign tumours occur together with an originate from the same cell type in an organor tissue as malignant tumours in a particular study appear to represent a stage in the
progression to malignancy, it may be valid to combine them in assessing tumour
incidence (Huff et al., 1989). The occurrence of lesions presumed to be preneoplastic
may in certain instances aid in assessing the biological plausibility of any neoplastic
response observed. If an agent or mixture induces only benign neoplasms that appear to
be end-points that do not readily undergo transition to malignancy, it should neverthelessbe suspected of being a carcinogen and requires further investigation.
(b) Quantitative aspects
The probability that tumours will occur may depend on the species, sex, strain, and age ofthe animal, the dose of the carcinogen, and the route and length of exposure. Evidence ofan increased incidence of neoplasms with increased level of exposure strengthens theinference of a causal association between the exposure and the development of neoplasms.
The form of the dose-response relationship can vary widely, depending on the particular
agent under study and the target organ. Both DNA damage and increased cell division areimportant aspects of carcinogenesis, and cell proliferation is a strong determinant of doseresponse relationships for some carcinogens (Cohen & Ellwein, 1990). Since many
chemicals require metabolic activation before being converted into their reactive
intermediates, both metabolic and pharmacokinetic aspects are important in determining
the dose-response pattern. Saturation of steps such as absorption, activation,490

inactivation, and elimination may produce nonlinearity in the dose-response relationship,
as could saturation of processes such as DNA repair (Hoel et al., 1983; Gart et al., 1986).
(c) Statistical analysis of long-term experiments in animals
Factors considered by the Working Group include the adequacy of the information given
for each treatment group: (i) the number of animals studied and the number examinedhistologically, (ii) the number of animals with a given tumour type and (iii) length ofsurvival. The statistical methods used should be clearly stated and should be thegenerally accepted techniques refined for this purpose (Peto et al., 1980; Gart et al.,1986). When there is no difference in survival between control and treatment groups, theWorking Group usually compares the proportions of animals developing each tumour
type in each of the groups. Otherwise, consideration is given as to whether or not
appropriate adjustments have been made for differences in survival. These adjustments
can include: comparisons of the proportions of tumour-bearing animals among theeffective number of animals (alive at the time the first tumour is discovered), in the casewhere most differences in survival occur before tumours appear; life-table methods, when
tumours are visible or when they may be considered ÔfatalÕ because mortality rapidly
follows tumour development; and the Mantel-Haenszel test or logistic regression, whenoccult tumours do not affect the animalsÕ risk of dying but are ÔincidentalÕ findings at
autopsy.
In practice, classifying tumours as fatal or incidental may be difficult. Several survivaladjusted methods have been developed that do not require this distinction (Gart et al,1986), although they have not been fully evaluated.

10.

OTHER DATA RELEVANT TO AN EVALUATION OF
CARCINOGENICITYANDITSMECHANISMS
In coming to an overall evaluation of carcinogenicity in humans, the Working Group also
considers related data. The nature of the information selected for the summary depends
on the agent being considered.
For chemicals and complex mixtures of chemicals such as those in some occupationalsituations and involving cultural habits (e.g., tobacco smoking), the other data considered
to be relevant are divided into those on absorption, distribution, metabolism andexcretion; those on toxic effects; reproductive and developmental effects: and genetic andrelated effects.
Concise information is given on absorption, distribution (including placental transfer) andexcretion in both humans and experimental animals. Kinetic factors that may affect thedose-response relationship, such as saturation of uptake, protein binding, metabolic
activation, detoxification and DNA repair processes, are mentioned. Studies that indicate
491

the metabolic fate of the agent in humans and in experimental animals are summarized
briefly, and comparisons of data from humans and animals are made when possible.
Comparative information on the relationship between exposure and the dose that reaches
the target site may be of particular importance for extrapolation between species. Data are
given on acute and chronic toxic effects (other than cancer), such as organ toxicity,
increased cell proliferation, immunotoxicity and endocrine effects. The presence andtoxicological significance of cellular receptors is described. Effects on reproduction,
teratogenicity, fetotoxicity and embryotoxicity are also summarized briefly.
Tests of genetic and related effects are described in view of the relevance of gene mutationand chromosomal damage to carcinogenesis (Vainio et al ., 1992). The adequacy of thereporting of sample characterization is considered and, where necessary, commented uponwith regard to complex mixtures, such comments are similar to those described for animal
carcinogenicity tests. The available data are interpreted critically by phylogenetic groupaccording to the end-points detected, which may include DNA damage, gene mutation,
sister chromatid exchange, micronucleus formation, chromosomal aberrations, aneuploidy
and cell transformation. The concentrations employed are given, and mention is made ofwhether use of an exogenous metabolic system in vitro affected the test result. These data
are given as listings of test systems, data and references; bar graphs (activity profiles) andcorresponding summary tables with detailed information on the preparation of the
profiles (Waters et al., 1987) are given in appendices.
Positive results in tests using prokaryotes, lower eukaryotes, plants, insects and cultured
mammalian cells suggest that genetic and related effects could occur in mammals. Resultsfrom such tests may also give information about the types of genetic effect produced andabout the involvement of metabolic activation. Some end-points described are clearly
genetic in nature (e.g., gene mutations and chromosomal aberrations), while others are to
greater or lesser degree associated with genetic effects (e.g., unscheduled DNA synthesis).
In-vitro tests for tumour-promoting activity and for cell transformation may be sensitive
to changes that are not necessarily the result of genetic alterations but that may havespecific relevance to the process of carcinogenesis. A critical appraisal of these tests has
been published (Montesano et al, 1986).
Genetic or other activity manifest in experimental mammals and humans is regarded as
being of greater relevance than that in other organisms. The demonstration that an agent or
mixture can induce gene and chromosomal mutations in whole mammals indicates that it
may have carcinogenic activity, although this activity may not be detectably expressed inany or all species. Relative potency in tests for mutagenicity and related effects is not areliable indicator of carcinogenic potency. Negative results in tests for mutagenicity inselected tissues from animals treated in vivo provide less weight, partly because they do
not exclude the possibility of an effect in tissues other than those examined. Moreover,negative results in short-term tests with genetic end-points cannot be considered toprovide evidence to rule out carcinogenicity of agents or mixtures that act through othermechanisms (e.g., receptor-mediated effects, cellular toxicity with regenerative
proliferation, peroxisome proliferation) (Vainio et al., 1992). Factors that may lead to492

misleading results in short-term tests have been discussed in detail elsewhere (Montesano
et al., 1986).
When available, data relevant to mechanisms of carcinogenesis that do not involve
structural changes at the level of the gene are also described.
The adequacy of epidemiological studies of reproductive outcome and genetic and related
effects in humans is evaluated by the same criteria as are applied to epidemiologicalstudies of cancer.
Structure-activity relationships that may be relevant to an evaluation of the carcinogenicity of an agent are also described.
For biological agentsÑviruses, bacteria and parasitesÑother data relevant to carcinogenicity include descriptions of the pathology of infection,. molecular biology (integrationand expression of viruses, and any genetic alterations seen in human tumours) and otherobservations, which might include cellular and tissue responses to infection, immune
response and the presence of tumour markers.

11.

SUMMARY OF DATA REPORTED
In this section, the relevant epidemiological and experimental data are summarized. Only
reports other than in abstract form, that meet the criteria outlined are considered forevaluating carcinogenicity. Inadequate studies are generally not summarized: such studies
are usually identified by a square-bracketed comment in the preceding text.
(a) Exposures
Human exposure to chemicals and complex mixtures is summarized on the basis ofelements such as production, use, occurrence in the environment and determinations inhuman tissues and body fluids. Quantitative data are given when available. Exposure tobiological agents is described in terms of transmission, and prevalence of infection.
(b) Carcinogenicity in humans
Results of epidemiological studies that are considered to be pertinent to an assessment of
human carcinogenicity are summarized. When relevant, case reports and correlation
studies are also summarized.

493

(c) Carcinogenicity in experimental animals
Data relevant to an evaluation of carcinogenicity in animals are summarized. For eachanimal species and route of administration, it is stated whether an increased incidence ofpreneoplastic lesions was observed, and the tumour sites are indicated. If the agent or
mixture produced tumours after prenatal exposure or in single-dose experiments, that is
also indicated. Negative findings are also summarized. Dose-response and otherquantitative data may be given when available.
(d) Other data relevant to an evaluation of carcinogenicity and its mechanisms
Data on biological effects in humans that are of particular relevance are summarized.
These may include toxicological, kinetic and metabolic considerations and evidence ofDNA binding, persistence of DNA lesions or genetic damage in exposed humans.
Toxicological information, such as that on cytotoxicity and regeneration, receptor binding
and hormonal and immunological effects, and data on kinetics and metabolism inexperimental animals are given when considered relevant to the possible mechanism of the
carcinogenic action of the agent. The results of tests for genetic and related effects are
summarized for whole mammals, cultured mammalian cells and nonmammalian systems.
When available, comparisons of such data for humans and for animals, and particularly
animals that have developed cancer, are described.
Structure-activity relationships are mentioned when relevant.
For the agent, mixture or exposure circumstance being evaluated, the available data on endpoints or other phenomena relevant to mechanisms of carcinogenesis from studies inhumans, experimental animals and tissue and cell test systems are summarized within one
or more of the following descriptive dimensions:(i) Evidence of genotoxicity (structural changes at the level of the gene): for example,
structure-activity considerations, adduct formation, mutagenicity (effect on specificgenes), chromosomal mutation/aneuploidy(ii) Evidence of effects on the expression of relevant genes (functional changes at the
intracellular level): for example, alterations to the structure or quantity of the product of a
proto-oncogene or tumour suppressor gene, alterations to metabolic
activation/inactivation/DNA repair(iii) Evidence of relevant effects on cell behaviour (morphological or behavioural changes
at the cellular or tissue level): for example, induction of mitogenesis, compensatory cellproliferation, preneoplasia and hyperplasia, survival of premalignant or malignant cells(immortalization, immunosuppression), effects on metastatic potential494

(iv) Evidence from dose and time relationships of carcinogenic effects and interactions
between agents: for example, early/late stage, as inferred from epidemiological studies;
initiation/promotion/progression/malignant conversion, as defined in animal
carcinogenicity experiments; toxicokinetics
These dimensions are not mutually exclusive, and an agent may fall within more than oneof them. Thus, for example, the action of an agent on the expression of relevant genes
could be summarized under both the first and second dimension, even if it were knownwith reasonable certainty that those effects resulted from genotoxicity.

12.

EVALUATION
Evaluations of the strength of the evidence for carcinogenicity arising from human andexperimental animal data are made, using standard terms.
It is recognized that the criteria for these evaluations, described below, cannot encompass
all of the factors that may be relevant to an evaluation of carcinogenicity. In considering
all of the relevant data, the Working Group may assign the agent, mixture or exposure
circumstance to a higher or lower category than a strict interpretation of these criteria
would indicate.
(a) Degrees of evidence for carcinogenicity in humans and in experimental animals andsupporting evidence
These categories refer only to the strength of the evidence that an exposure is carcinogenic
and not to the extent of its carcinogenic activity (potency) nor to the mechanisms
involved. A classification may change as new information becomes available.
An evaluation of degree of evidence, whether for a single agent or a mixture, is limited tothe materials tested, as defined physically, chemically or biologically. When the agents
evaluated are considered by the Working Group to be sufficiently closely related, they
may be grouped together for the purpose of a single evaluation of degree of evidence.
(i) Carcinogenicity in humans
The applicability of an evaluation of the carcinogenicity of a mixture, process, occupation
or industry on the basis of evidence from epidemiological studies depends on thevariability over time and place of the mixtures, processes, occupations and industries. The
Working Group seeks to identify the specific exposure, process or activity which isconsidered most likely to be responsible for any excess risk. The evaluation is focused as
narrowly as the available data on exposure and other aspects permit.

495

The evidence relevant to carcinogenicity from studies in humans is classified into one of
the following categories:
Sufficient evidence of carcinogenicity: The Working Group considers that a causal
relationship has been established between exposure to the agent, mixture or exposure
circumstance and human cancer. That is, a positive relationship has been observed
between the exposure and cancer in studies in which chance, bias and confounding could
be ruled out with reasonable confidence.
Limited evidence of carcinogenicity: A positive association has been observed between
exposure to the agent, mixture or exposure circumstance and cancer for which a causal
interpretation is considered by the Working Group to be credible, but chance, bias orconfounding could not be ruled out with reasonable confidence.
Inadequate evidence of carcinogenicity: The available studies are of insufficient quality,
consistency or statistical power to permit a conclusion regarding the presence or absenceof a causal association, or no data on cancer in humans are available.
Evidence suggesting lack of carcinogenicity: There are several adequate studies covering
the full range of levels of exposure that human beings are known to encounter, which aremutually consistent in not showing a positive association between exposure to the agent,
mixture or exposure circumstance and any studied cancer at any observed level of
exposure. A conclusion of Ôevidence suggesting lack of carcinogenicityÕ is inevitably
limited to the cancer sites, conditions and levels of exposure and length of observation
covered by the available studies. In addition, the possibility of a very small risk at thelevels of exposure studied can never be excluded.
In some instances, the above categories may be used to classify the degree of evidence
related to carcinogenicity in specific organs or tissues(ii) Carcinogenicity in experimental animals
The evidence relevant to carcinogenicity in experimental animals is classified into one of
the following categories:
Sufficient evidence of carcinogenicity: The Working Group considers that a causal
relationship has been established between the agent or mixture and an increased incidenceof malignant neoplasms or of an appropriate combination of benign and malignant
neoplasms in (a) two or more species of animals or (b) in two or more independentstudies in one species carried out at different times or in different laboratories or under
different protocols.

496

Exceptionally, a single study in one species might be considered to provide sufficientevidence of carcinogenicity when malignant neoplasms occur to an unusual degree withregard to incidence, site, type of tumour or age at onset.
Limited evidence of carcinogenicity: The data suggest a carcinogenic effect but are limited
for making a definitive evaluation because, e.g., (a) the evidence of carcinogenicity is
restricted to a single experiment; or (b) there are unresolved questions regarding theadequacy of the design, conduct or interpretation of the study; or (c) the agent or mixture
increases the incidence only of benign neoplasms or lesions of uncertain neoplastic
potential, or of certain neoplasms which may occur spontaneously in high incidences incertain strains.
Inadequate evidence of carcinogenicity: The studies cannot be interpreted as showing
either the presence or absence of a carcinogenic effect because of major qualitative or
quantitative limitations, or no data on cancer in experimental animals are available.
Evidence suggesting lack of carcinogenicity: Adequate studies involving at least two
species are available which show that, within the limits of the tests used, the agent or
mixture is not carcinogenic A conclusion of evidence suggesting lack of carcinogenicity isinevitably limited to the species, tumour sites and levels of exposure studied.
(b) Other data relevant to the evaluation of carcinogenicity and its mechanisms
Other evidence judged to be relevant to an evaluation of carcinogenicity and of sufficientimportance to affect the overall evaluation is then described. This may include data on
preneoplastic lesions, tumour pathology, genetic and related effects, structure-activity
relationships, metabolism and pharrnacokinetics, physicochemical parameters andanalogousbiologicalagents.
Data relevant to mechanisms of the carcinogenic action are also evaluated. The strength ofthe evidence that any carcinogenic effect observed is due to a particular mechanism isassessed, using terms such as weak, moderate or strong. Then, the Working Groupassesses if that particular mechanism is likely to be operative in humans. The strongest
indications that a particular mechanism operates in humans come from data on humans or
biological specimens obtained from exposed humans. The data may be considered to be
especially relevant if they show that the agent in question has caused changes in exposed
humans that are on the causal pathway to carcinogenesis. Such data may, however, never
become available, because it is at least conceivable that certain compounds may be kept
from human use solely on the basis of evidence of their toxicity and/or carcinogenicity inexperimental systems.
For complex exposures, including occupational and industrial exposures, chemicalcomposition and the potential contribution of carcinogens known to be present areconsidered by the Working Group in its overall evaluation of human carcinogenicity. The

497

Working Group also determines the extent to which the materials tested in experimental
systems are related to those to which humans are exposed.
(c) Overall evaluation
Finally, the body of evidence is considered as a whole, in order to reach an overall
evaluation of the carcinogenicity to humans of an agent, mixture or circumstance of
exposure.
An evaluation may be made for a group of chemical compounds that have been evaluatedby the Working Group. In addition, when supporting data indicate that other, related
compounds for which there is no direct evidence of capacity to induce cancer in humans
or in animals may also be carcinogenic, a statement describing the rationale for thisconclusion is added to the evaluation narrative; an additional evaluation may be made forthis broader group of compounds if the strength of the evidence warrants it.
The agent, mixture or exposure circumstance is described according to the wording of oneof the following categories, and the designated group is given. The categorization of anagent, mixture or exposure circumstance is a matter of scientific judgment, reflecting thestrength of the evidence derived from studies in humans and in experimental animals andrelative or from other relevant data.
Group 1ÑThe agent (mixture) is carcinogenic to humans
This exposure circumstance entails exposures that are carcinogenic to humans.
This category is used when there is sufficient evidence of carcinogenicity in humans.
Exceptionally an agent (mixture) may be placed in this category when evidence in humans
is less than sufficient but there is sufficient evidence of carcinogenicity in experimental
animals and strong evidence in exposed humans that the agent (mixture) acts through a
relevant mechanism of carcinogenicity.
Group 2ÑThis category includes agents, mixtures and exposure circumstances for which,at one extreme, the degree of evidence of carcinogenicity in humans is almost sufficient, as
well as those for which, at the other extreme, there are no human data but for which thereis evidence of carcinogenicity in experimental animals. Agents, mixtures and exposure
circumstances are assigned to either group 2A (probably carcinogenic to humans) or group
2B (possibly carcinogenic to humans) on the basis of epidemiological and experimental
evidence of carcinogenicity and other relevant data.
Group 2AÑThe agent (mixture) is probably carcinogenic to humans.
The exposure circumstance entails exposures that are probably carcinogenic to humans.

498

This category is used when there is limited evidence of carcinogenicity in humans andsufficient evidence of carcinogenicity in experimental animals. In some cases, an agent(mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals andstrong evidence that the carcinogenesis is mediated by a mechanism that also operates inhumans. Exceptionally, an agent, mixture or exposure circumstance may be classified inthis category solely on the basis of limited evidence of carcinogenicity in humans.
Group 2BÑThe agent (mixture) is possibly carcinogenic to humans.
The exposure circumstance entails exposures that are possibly carcinogenic to humans.
This category is used for agents, mixtures and exposure circumstances for which there islimited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of
carcinogenicity in humans but there is sufficient evidence of carcinogenicity inexperimental animals. In some instances, an agent, mixture or exposure circumstance forwhich there is inadequate evidence of carcinogenicity in humans but limited evidence of
carcinogenicity in experimental animals together with supporting evidence from otherrelevant data may be placed in this group.
Group 3ÑThe agent (mixture or exposure circumstance) is not classifiable as to its
carcinogenicity to humans.
This category is used most commonly for agents, mixtures and exposure circumstances
for which the evidence of carcinogenicity is inadequate in humans and inadequate or
limited in experimental animals.
Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate inhumans but sufficient in experimental animals may be placed in this category when there
is strong evidence that the mechanism of carcinogenicity in experimental animals does notoperate in humans.
Agents, mixtures and exposure circumstances that do not fall into any other group are also
placed in this category.
Group 4ÑThe agent (mixture) is probably not carcinogenic to humans.
This category is used for agents or mixtures for which there is evidence suggesting lack ofcarcinogenicity in humans and in experimental animals. In some instances, agents or
mixtures for which there is inadequate evidence of carcinogenicity in humans but evidence
suggesting lack of carcinogenicity in experimental animals, consistently and strongly
supported by a broad range of other relevant data, may be classified in this group.

499

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APPENDIX B
Minority Statement on Animal Carcinogenicity
1.

Introduction
The vote on the animal carcinogenicity data on EMF, which suggests that they provide
evidence for an effect on cancer is not consistent with the recommendation of thesubgroup on studies of animals in vivo and is not justified by the data in the report.
This disagreement seems to focus on four points:

2.

(1)

the weight given to data from the Lšscher laboratory on the interaction between
DMBA and EMF in inducing mammary cancer in the Sprague-Dawley rat;(2)

the interpretation of induction of C-cell tumors in the thyroid in animals of one
strain, one exposure group and one sex in a single long-term bioassay;(3)

the focus on only adverse effects of EMF exposure and the lack of
acknowledgment of the observations of the effect of EMF to decrease several
tumor types for single-dose points in the long-term bioassay; and(4)weight given to the negative results of high-quality long-term bioassays.

Mammary carcinogenicity in the Sprague-Dawley rat
The Sprague-Dawley rat is hypersensitive to chemicals that induce mammary cancer.
This hypersensitivity proceeds from an oversecretion of prolactin, which acts toÒpromote initiating events.Ó For instance, Welsh et al. (Welsh et al., 1997) showed thattamoxifen, which prevents prolactin-induced proliferation of mammary epithelial cells,
dramatically inhibits radiation-induced cancer. Tamoxifen also reduced mammary cancer
incidence in women at increased risk for this cancer.
This hypersensitivity to initiating events was exploited in order to distinguish between
the carcinogenic effects of neutrons and photons in the classical study of Shellabarger etal. (1980) which demonstrated unequivocally that histopathological examination isessential to discriminate between fibroadenomas and adenocarcinomas, the former benign
tumor being a confounder that can obscure the induction of overt cancer. Further, this and505other studies, showed the importance of measuring the number of tumors per animal. The
hypersensitivity of Sprague-Dawley rats to initiating events limits their use as a model
for initiation-promotion studies. The dose of the initiating agent sets the dynamic rangeof possible response to the promoter; if it is too potent, it obscures interpretation of theÒpromotingÓ agent.
LšscherÕs data fail on all three points. They do not observe increases in the number oftumors per animal; the study does not consistently report an increase in tumor size or
demonstrate an association between tumors palpated early and histological verification inearly stages (i.e. determination of tumor latency conducted by population only); and theinitiating doses are too high.

3.

C-Cell thyroid tumors
The relevance of induction of this cancer, is compromised in four ways:

4.

(1)

It is not induced by any known animal or human carcinogen.

(2)

It is a microscopic tumor susceptible to sampling artifacts.

(3)

The historical rates (4-36%), are highly variable.

(4)

It is not found in females.

(5)Pre-neoplastic hyperplasia is most prevalent in controls and least prevalent in
exposed animals.

Protective effects of EMF against cancer:
NTP study:(1)mononuclear-cell leukemia in male mice (B6C3F1) exposed to 1000 mT (p =0.045);(2)

alveolar/bronchial adenoma in male mice exposed to 2 or 200 mT (p < 0.001) and infemale mice exposed to 200 mT (p = 0.002);(3)

combined adenoma and carcinoma in male and female mice exposed to 200 mT (p =0.041 and 0.015);

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5.

(4)

malignant lymphoma in female mice exposed to 1000 mT (p = 0.045). (Mandeville,
1997);(5)

incidence of pituitary adenoma was reduced at 2 mT (p = 0.01) and at 2000 mT(p = 0.02).

Long-term bioassays are the most predictive of all laboratorymodels for human response.
The strong predictive power of the long-term bioassay in rodents has been demonstrated
in hundreds of such studies with known human carcinogens. While studies with a single
species of rodents may have limited predictive value, the use of one mouse and one rat
strain increases the predictive power. Most of the inconsistencies between the responses
of different animal species to chemical carcinogens have been shown to result from thedifferent pharmacokinetics and metabolism of the species, a confounder that is not likely
to affect EMF.
The four long-term bioassays performed with exposure to EMF include studies in species
demonstrated to be sensitive to mammary carcinogens and to leukemogenesis. Indeed, theFischer 344 rat is particularly susceptible to leukemia, as the Sprague-Dawley rat is
hypersensitive to mammary cancer. The results of all of the studies are completely
negative. Furthermore, as described above, significant decreases in the incidences of
specific tumors were seen in animals of one sex and one species at some doses. Thesefindings are probably the result of random variation in the large number of response
categories.

6.

In summary:(1)

The study of Lšscher is fundamentally flawed by its lack of consistency in effectand absence of critical histological data.

(2)

Although the incidence of thyroid C-cell tumor was elevated in a single study, thistumor has never been considered been relevant in assessing the carcinogenic
potential of any agent. The natural history of the tumor makes it difficult tomeasure with precision.

(3)

In five cases, reduced induction of specific types of cancer was seen after
exposure to EMF in well-executed bioassays.

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(4)

In well-executed long-term bioassays conducted in animal models known to besusceptible to the induction of lymphoma/leukemia and mammary cancer as wellas other forms of cancer, there is no suggestion of an increased incidence of cancer.
The single exception is C-cell thyroid tumor, the incidence of which was elevatedin only one bioassay, however, this observation has no predictive value for humanor animal carcinogens, as noted above.

References
Mandeville, R., Franco, E., Sidrac-Ghali, S., Paris-Nadon, L., Rocheleau, N., Mercier, G., Desy,
M. & Gaboury, L. (1997). Evaluation of the potential carcinogenicity of 60 Hz linear
sinusoidal continuous-wave magnetic fields in Fisher F344 rats. FASEB Journal, 11, 1127 1136.
Shellabarger, C.J., Chmelevsky, D. & Kellerer, A.M. (1980). Induction of mammary neoplasmsin the Sprague-Dawley rat by 430 keB neutrons and X-rays. Journal of the National Cancer
Institute, 64, 821-833.
Welsh, J. (1997). Vitamin D compounds as potential therapeutics for estrogen-independent
breast cancer. Nutrition, 13, 915-917.

Members of the Working Group supporting this minority statement:
Jerry Williams
Fred M. Dietrich
Walter R. Rogers
James Felton
Paul L. Zweiacker

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