2006 WHO Research Agenda for Static Fields
Introduction
In 1997, the WHO International EMF Project developed a Research Agenda in order tofacilitate and coordinate research worldwide on the possible adverse health effects ofelectromagnetic fields (EMF). In subsequent years, this agenda has undergone periodic
review and refinement.
In December 2004, WHO carried out a health risk assessment of static electric and magnetic
fields, which was published as a WHO Environmental Health Criteria monograph 1. One ofthe objectives of the review was to identify gaps in knowledge about possible health effects ofstatic field exposure. The Task Group conducting the review concluded the following.
-For static electric fields, there appears to be little benefit in continuing research into theirhealth effects. None of the studies conducted to date suggest any adverse health effects,
except for possible stress resulting from repeated exposure to microshocks. Thus, there
are no recommendations for further research concerning biological effects from exposure
to static electric fields. In addition, there is only limited opportunity for significant
exposure to these fields in the workplace or living environment and this therefore does
not warrant any epidemiological studies.

-For static magnetic fields, research carried out to date has not been systematic and hasoften been performed without appropriate methodology and exposure information.
Coordinated research programs are recommended as an aid to a more systematic approach.
There is a need to investigate the importance of physical parameters such as fieldintensity, exposure duration and field gradient on biological outcome. Research
recommendations from this review are given below.

Researchers are encouraged to use this Research Agenda as a guide to studies that have highvalue for health risk assessments. To maximize the effectiveness of research programs,government and industry funding agencies are encouraged to address the WHO Research
Agenda in a coordinated fashion. Such coordination will minimize unnecessary duplication ofeffort and will ensure the most timely completion of the studies identified as being of highpriority for health risk assessment.

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World Health Organization (2006) Static fields. Environmental Health Criteria 232. Geneva:
World Health Organization (see: www.who.int/emf)

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The Research Agenda defines as "high priority" research whose results would contributesignificantly to future health risk assessments of static field exposure. The document isordered in successive sections according to the weight each research activity carries in humanhealth risk assessment: epidemiology, laboratory studies in humans, animals, cellular systems,and mechanisms. It should be recognized that, while epidemiological and human laboratory
studies directly address endpoints related to human health, cellular and animal studies are ofvalue in assessing causality and biological plausibility. Dosimetry is considered separately,
but is important for all research.
Each research activity is given a priority as follows.
-High priority research needs: Studies to fill important gaps in knowledge focused onhealth risk assessment that are needed to significantly reduce the uncertainty in thecurrent scientific information.

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Other research needs: Studies to better assist the understanding of the impacts of static
field exposure on health and that would contribute useful information to health risk
assessment.

Epidemiology
Epidemiological studies are of primary importance in health risk assessment. When planningepidemiological studies, investigators should consider international coordination andcollaboration to maximize statistical power to estimate small risks and to evaluate the role ofexposure patterns in different countries. Particular attention should be paid to the use of
adequate estimates of exposure from all relevant sources.
High priority research needs:•Nested case-control study of chronic diseases in highly exposed occupational groups
Rationale: There are a number of categories of workers with elevated exposures to static
magnetic fields, including MRI technicians, workers at aluminium smelting plants, andcertain transportation workers (those on subways, MagLev trains, commuter trains, andlight rail). For rare chronic diseases, such as specific cancers, feasibility studies areneeded to identify the highly exposed occupational groups that could be considered for
epidemiological studies. Feasibility studies also need to determine which other exposures
are present in these occupations. If sufficient numbers of workers can be identified, then anested case-control approach is probably the most appropriate, since detailed information
about the exposure and important confounding variables, such as toxic fumes, needs to beobtained. International collaborative studies will probably be necessary to obtainsufficient numbers of exposed subjects.

•Cohort study of short-term effects in highly exposed occupational groups
Rationale: For other more common health outcomes with short latency periods, specifichighly exposed occupational groups (for example, workers in industries where MRI
systems are manufactured) can be identified and followed over time. Information about
different health outcomes may already be available from routinely performed healthexaminations of these workers, but this can only be used if similar information is alsoavailable for a comparable unexposed group. A health survey of surgeons, nurses andother workers using interventional MRI would provide useful information as to levels,durations and frequency of exposures of workers to static fields in these systems.

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Similarly, patient records may exist in some hospitals from which it might be possible toobtain data on people who were exposed, but whose condition was subsequently found tobe benign.
•Prospective study of pregnancy outcomes in relation to occupational exposure and
MRI examinationsRationale: A prospective study of pregnancy risks associated with static magnetic field
exposure is needed because of the increasing number of pregnant women in the workforce(chronic exposure), as well as follow-up studies of outcomes of pregnant women who
undergo MRI examinations (acute exposure).

•

Development of dosimeters for obtaining reliable estimates of static fields exposurein epidemiological studies
Rationale: Experience with other frequencies has shown that obtaining reliable estimatesof exposure to electromagnetic fields for use in epidemiological studies can be very
difficult, and surrogate measures of exposure, such as job title or distance from aparticular source, may not always provide sufficiently accurate assessments. The use ofspecific instruments is thus required to measure exposure. Relatively small personal
dosimeters have proved very useful in research on ELF fields. Personal dosimeters would
therefore greatly improve exposure assessment in epidemiological studies. Numerical andexperimental validation of the dosimeters should be performed. Magnetic field strength,
magnetic field gradients, exposure durations and, ideally, the rate of change of themagnetic field due to motion should be recorded.

Human volunteer studies
Human laboratory studies allow static field effects to be studied on humans with control ofexperimental parameters but are confined to investigations of acute transient effects.
High priority research needs:•Studies on vestibular function, head and eye coordination in a gradient field
Rationale: With a wider utilization of MRI studies where support staff are in close
proximity to patients within a magnet, such as in MRI interventional procedures, and areconsequently exposed to relatively high static magnetic fields, additional studies areneeded of head and eye coordination, cognitive performance and behaviour in a static
magnetic field. Further investigation of mechanisms and intensity of field-induced
vestibular dysfunction including vertigo is considered of special interest because of theincreasing likelihood that medical staff will be performing complicated tasks for extended
periods of time within a magnetic field.

Other research needs:•Cognitive and behavioural effects of static magnetic fields
Rationale: The cognitive and behavioural effects due to exposure to static magnetic fields
should be investigated further. However, the available data do not suggest particular risks
to specific aspects of cognition nor do they suggest which parameters should be tested in
the laboratory. In the absence of a clear direction, a possible approach would be toinvestigate the effects of exposure on the performance of a battery of cognitive tasks thatencompass standard tests of attention, reaction time and memory, if only to act as an
initial screen pending more focused work. The initial work could be done with volunteers
as part of experimental studies.

3•Cardiac function in the routine clinical environment
Rationale: Additional studies on cardiac function would be useful and could investigate
effects on the cardiovascular system. These studies should also be performed at higher
than 3 T to evaluate potential risks beyond those in the routine clinical environment.

Animal studies
Animal studies are used when it is unethical or impractical to perform studies on humans andhave the advantage that experimental conditions can be rigorously controlled, even forchronic exposures.
High priority research needs:•Long-term (including life-time) studies concentrating on cancer-related effects using
both normal and genetically-modified animals
Rationale: The effects of long-term exposure to static magnetic fields can be addressedusing animal models. In the absence of specific information regarding the carcinogenic
potential of static magnetic fields, long-term (including life-time) studies arerecommended. Both normal and genetically-modified animals could be used. For example,
if an amplification of free radicals was considered a possible route whereby cancer risk
may be increased, a mouse model with deletion of the superoxide dismutase gene could
be used. The susceptibility to tumours and other free radical related diseases is greatly
enhanced in this model. The use of microarray techniques allows the effects of manydifferent exposure parameters to be readily assessed and quantified on the genome andproteome.

•Developmental and neurobehavioural effects
Rationale: The possibility of increased risk of developmental abnormalities andteratological effects needs to be addressed in a systematic fashion. The developing brain
may be particularly susceptible to the effects of movement-induced currents sinceorientation effects are very important for guiding the normal growth of neuronal dendrites.
It is also possible that long lasting changes could be induced by relatively short exposures.
The study of neurobehavioural parameters can provide a rapid and sensitive assay toexplore the effects of exposure on developing brain function, and such studies arerecommended. Studies to chart the subtle morphological changes that occur during
development of specific regions of the brain, such as the cortex or hippocampus, are alsoof value. The use of appropriate transgenic models should be considered.

Other research needs:•Effects on cardiac functions under very high field intensity (10-20 T)
Rationale: Although there are data indicating that exposure of animals (and humans) tofields of around 2 T does not cause electrophysiological effects, it would be useful toknow the effects of higher fields. Thus the effects of exposure to high intensity fields (1020 T) could usefully be explored in animals.

•Animal study to cover different endpoints
Rationale: A variety of other endpoints have been investigated in animals that have so far
provided only limited information. While a series of single studies for each of those4

endpoints might not be cost-effective, a broad animal study to cover different endpoints
might be worthwhile.

Cellular studies and mechanisms
Studies in tissues, living cells and cell-free systems play a supporting role in health risk
assessments. Static magnetic fields may interact with biological systems in a number of ways,
although the most likely means of causing health effects are via field-induced effects on
charged molecules and alterations in the rate of biochemical reactions.
High priority research needs:•Mutagenicity and transformation in primary human cells
Rationale: Reports of a co-mutagenic effect in various cells are of particular interest
concerning the carcinogenic potential of static magnetic fields. This type of study shouldbe performed using human primary cells and extended to include transformation andgenetically-modified systems.

Other research needs:•Interaction mechanisms on radical pair reactions and enzymatic activity
Rationale: Further studies are needed on possible mechanisms and targets for biologicaleffects of static magnetic fields. It is recommended to investigate the effects of static
magnetic fields of 0.01 - 10 T on interaction of ions (e.g. Ca2+ or Mg2+) with enzymes andradical pair formation. Although it is considered difficult to do, there is merit in searchingfor more enzymatic reactions that proceed through radical pair mechanisms in model
systems that are relevant for human health. Another suggestion is to concentrate on toxic
radical species, such as the superoxide, which are known to be damaging and are
produced by free radical mechanisms.

•Gene expression in primary human cells
Rationale: Static magnetic fields might affect gene expression and relevant functions inhuman and mammalian cells under specific conditions of exposure, but there is only little
information available on this. Studies with techniques such as proteomics and genomics
should be performed with primary human cells to search for possible molecular markers
for effects of static magnetic fields relevant to human health issues.

Dosimetry
Expert dosimetric support for experimental studies of all types is critical to their proper design
and interpretation. Computational dosimetry provides the link between an external static
magnetic field and the internal electric fields and induced currents caused by movement ofliving tissues in the field. Such theoretical techniques allow the fields to be characterised in
specific tissues and organs.

5High priority research needs:•

Development of a very fine resolution head-and-shoulder phantom
Rationale: A very fine resolution head-and-shoulder phantom should be developed andused to investigate the electric fields and currents associated with visual phosphenes andvertigo. This model could also be used to investigate the fields and currents generated byhead and eye movements in a static magnetic field. The latter is considered of particular
relevance to interventional MRI procedures where reduced head movements of surgeons
and other clinical staff may necessitate increased movement of the eyes. Whole-bodymovement by staff around the interventional system should also be simulated.

•A detailed model of induced current in the heart
Rationale: Computations using a detailed model of the heart and modelling of common
cardiac pathologies are considered important. This model should include the microarchitecture of the heart as well as the smaller blood vessels within the heart that might
produce fields and currents that could have some influence on pacemaker rhythm
generation and the propagation of depolarisation. In addition, calculations are necessary
to estimate the magnitude and spatial distribution of currents that are induced in the heart
as a consequence of field and field gradient exposure. Multiple orientations to the fieldshould be studied. These would allow comparison with the currents that have been
calculated to induce cardiac effects. Supportive experimental and laboratory studies arerecommended.

•Dosimetric studies on the fetus under high field MRI
Rationale: Although there is a reluctance to use high field MRI on pregnant women at themoment, it is acknowledged that this situation may change. It would therefore beadvisable to carry out modelling studies investigating the currents induced in a fetus bymaternal or intrinsic fetal movement in a high field. These calculations (and similar
studies with gradient and radiofrequency fields) would allow an estimate to be made ofthe likelihood of possible effects on the fetus.

Other research needs:•Dosimetric studies with male/female/pregnant voxel phantoms.
Rationale: There are four fine resolution, anatomically realistic, voxel phantoms of adultmen available, and these have been widely used in studies with time-varying
electromagnetic fields. However, very little work has been done with static fields, andfurther work is considered necessary using these models. In particular, the use of different
sized phantoms, and the use of female phantoms, is considered important, as is the use ofpregnant phantoms with fetuses of differing ages. Similar studies could be performed withphantoms of pregnant animals to aid interpretation of the results of developmental studies
with these models.

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