Sheila Johnston PhD
Neuroscience Consultant
10 Queen’s Mews,
London, UK,
W2 4BZ
Please note this is a summary document drawing on the expertise of the many international expert authors quoted directly and indirectly. I am only the gatherer of their statements. I acknowledge them fully.
Please note that each Specific Research Study Design (Epidemiological, Human Volunteer, In Vivo, In Vitro) can be read independently, but I would advise for full understanding that you read the complete document.
INTERNATIONAL GUIDELINES FOR QUALITY EMF (RF or ELF) RESEARCH
IEEE ICES TC-95, SubCommittees 3 and 4
ICES EMF Literature Surveillance
IEEE ICES EMF Standard Setting
ICNIRP, IARC and WHO EMF Project Collaboration
ELF Reviews: IARC-2002, ICNIRP-2003, WHO EMF Project-2005
RF Reviews: IARC-2006, ICNIRP-2007, WHO EMF Project-2008
Revision of the ICNIRP Guidelines 0-300 GHz -1998
GUIDELINES FOR QUALITY EMF (RF / ELF) RESEARCH
Replication and EMF Standard Setting Criteria
General Experimental Design Criteria
SAR as a Measure of Temperature Increase
Traditional Evaluation of Research
New Evaluation of Research: Molecular Epidemiology
The Epidemiological Study Design
Case Control and Cohort Studies
Spatial Epidemiology (Quoted from Elliott and Wartenberg, 2004)
Human RF Exposure in the Near Field
Human RF Exposure in the Far Field
Data collection and quality assurance
For Example IEEE SC-4: In Vivo Triage: 16 Screens Are Summarized Below:
International expert evaluations of the published literature are carried out according to guidelines for quality EMF (0-300 GHz) research. As technology progresses, it is our duty as scientists and engineers to continually review and monitor new findings and to update and revise our safety standards and guidelines accordingly (Chou & D’Andrea, 2003; ICNIRP, 1998; Gajšek et al., 2002; ICNIRP, 1998).
A comprehensive and critical review of the extant scientific database of electromagnetic field (EMF) published literature is updated periodically by panels of current qualified experts, as recognized by the international scientific community.
An important task of the international expert panels is to assess the relevant extremely low frequency (ELF) and radiofrequency (RF) accumulating papers (2200+ papers) for standard setting for human exposure limits to protect the population against any adverse health effects.
While exposure to EMF may cause biological effects, without any known adverse consequences, the standards are based on established threshold levels for adverse health effects, i.e., levels of exposure above which adverse health effects have been established and below which adverse health effects have not been established.
There are currently 2 international expert panels that evaluate the ever-increasing EMF literature according to criteria for quality EMF (0-300 GHz) research to set the standards and guidelines.
1. The Institute of Electrical and Electronics Engineers Incorporated (IEEE)[1], International Committee on Electromagnetic Safety (ICES), Piscataway, New Jersey. ICES membership is open to all interested persons; membership of the central governing and the technical committees (TC-95 and TC-34) stands at more than 150 professionals representing 24 countries. [http://grouper.ieee.org/groups/scc28/]. ICES develops standards through an open consensus process that is transparent at every level. In addition to standards prescribing safety levels, ICES also develops standards and recommended practices for implementing these standards, e.g., safety programs, methods for exposure assessment.
2. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) Oberschleissheim, Germany (14 members from 13 countries, see board 2004-8). [http://www.icnirp.de/]. New members are appointed by the existing members.
Although IEEE ICES standards and ICNIRP guidelines are advisory (voluntary), and carry neither a mandate for compliance nor a mechanism for enforcement, these documents frequently serve as the bases for guidelines and regulations set forth by regulatory and other agencies in diverse countries that have issued their own standards, which, in some cases, may differ substantially from those of ICES and ICNIRP.
Because of the international expertise in EMF research of IEEE ICES and ICNIRP members, it is valuable to focus attention on their processes of evaluating the relevant literature for the purpose of establishing safety criteria.
These expert panels are multidisciplinary and include, for example, epidemiologists, neurologists, biologists, toxicologists, oncologists, and psychologists who are appropriately specialized medical scientists, and physicists, engineers, and statisticians. Only peer reviewed scientific studies are included in the review. While anonymous peer review for publication adds confidence in the study results, additional review is necessary to evaluate the study design, conduct of the experiment and the statistical analyses, and to compare various aspects of the results with the results of other studies to reveal the consistency of the results. National expert reports that for the most part are not published in scientific journals may also be considered for review. But conference abstracts are of little value as they generally receive no peer review, contain sparse information, and cannot be considered as the final outcome of an experiment (Repacholi, 1998). The task of the expert panels is to assess the entire ELF and RF scientific database (2200+ papers) for standards setting for human exposure to avoid any established adverse health effects.
Subcommittee 3 and Subcommittee 4 (SC-3 and SC-4) of Technical Committee 95 (TC-95) develop standards for safety levels with respect to human exposure to electromagnetic fields. SC-3 covers the frequency range of 0 to 3 kHz; SC-4 covers the range of 3 kHz to 300 GHz. These subcommittees review the EMF literature continuously and periodically they may publish review papers in the scientific peer reviewed literature for the purpose of updating the standards (cf. BEMS Supplement). The revision process established by the ICES is a continuing rigorous and open scientific process that is transparent at all levels and includes the opportunity for input from all stakeholders.
The EMF literature surveillance covers health effects in two separate exposure frequency ranges, 0-3 kHz and 3 kHz - 300 GHz, because adverse biological effects (associated with exposures above the exposure limits) are manifested primarily as induced in situ electric field stimulation in the lower frequency range and as tissue heating in the upper range, respectively. There is some overlap of the effects associated with induced in situ electric field stimulation and with heating in the intermediate range 3 kHz to 100 kHz (or higher for pulsed fields).
The IEEE standards are living documents and in accordance with IEEE rules must be reaffirmed or revised every 5 years. The IEEE C95 standards are based on IEEE ICES members’ anonymous peer reviews of all the published scientific studies of health effects. They provide a wide margin of safety to workers and the public from adverse health effects from exposure to EMFs. The IEEE EMF safety limits are issued as two separate standards.[2] As indicated above, SC-3 and SC-4 have independent literature review panels who evaluate the papers in a parallel process for the ranges, 0-3 kHz and 3 kHz -300 GHz, respectively. Each subcommittee independently drafts and approves the standard that applies to its frequency range.
Each standard is first balloted by the subcommittee, which requires at least 75% of the ballots returned and at least 75% affirmative ballots following ballot resolution (during which time all negative ballots, comments and changes to the draft resulting from ballot resolution are circulated to the balloting group to allow members to comment, change or reaffirm their vote). This process is repeated at the ICES Committee level after which the draft standard is submitted to the IEEE Standards Association Standards Board (SASB) Review Committee (RevCom). The SASB RevCom has oversight to ensure that due process has been afforded to all, and that the rigid IEEE SASB Rules for standards development and balloting have been followed. When satisfied, the RevCom recommends to the SASB approval of the standard. The SASB procedures provide a mechanism for appeals based on violations of the IEEE balloting process; technical appeals are referred to the Committee and Subcommittees. Once approved by the SASB, the standards are published, usually within 2-3 months.
The ELF standard (C95.6) was approved in September 2002 and published in October 2002. When C95.6 was balloted by ICES, 93% of the ballots were returned with a 90% approval.
The current RF standard (C95.1) was approved in 1991, reaffirmed in 1997, an amendment was published in 1999 and a second amendment was published in 2004.
TC-95 SC-3 was responsible for the development of IEEE C95.6-2002. During development of this standard, SC-3 was chaired by Kent Jaffa (USA) and had about 75 voluntary ELF research members from 11 countries. The results of the SC-3 review are incorporated within IEEE Std C95.6-2002.
The SC-3 review of the literature continues with Thanh Dovan (AU) and Philip Chadwick (UK) as SC-3 co-chairs. In addition, SC-3 members have published review papers in Health Physics, 83:3, 2002, from an international conference in Brussels, 2000, entitled “The EMF exposure guidelines science workshop”.
The IEEE ICES sponsored a one-day ‘Short Tutorial Course on IEEE Standard C95.6’ in June and December 2004 in conjunction with their annual and semi-annual meetings. The same short-course was presented to the Canadian Electrical Association in March 2004 and in Dublin in June 2005. J. Patrick Reilly and Kent Jaffa, both of the USA, present this short course.
TC-95 is working toward harmonisation of the C95.6 standard with ICNIRP and to that purpose, within the ELF range, J.P. Reilly has published a paper in Health Physics, “An analysis of differences in the low-frequency electric and magnetic field exposure standards of ICES and ICNIRP,” (Reilly, 2005).
A complete revision of the RF standard (C95.1-1991) by SC-4 is now in progress. The revision is based on the peer reviewed literature identified by the Literature Surveillance Working Group chaired by Lou Heynick (USA, 1978-2005) who continuously identified the literature for review. This process has been taken over by Joseph Morrissey and new papers are now entered on the WHO EMF Project website
The membership of SC-4 stands at 122 members representing 24 countries and is co-chaired by C-K. Chou and J.A. D’Andrea (both USA). Chou and D’Andrea coordinated the literature evaluation and, along with the literature evaluation working group chairs and other designated experts published 12 RF and health, review papers in, the Bioelectromagnetics journal, Supplement 6, 2003 (Chou and D’Andrea, 2003).
They have also incorporated a thorough literature review within the draft revision of IEEE Std C95.1-1991/1999. This standard has undergone a complete revision, which was approved by SC-4 in March and is now (August 2005) undergoing Sponsor (ICES) ballot. The SC4 literature evaluation process is explained in detail in Appendix A 1.6 of the IEEE Std PC95.1-2005 Briefly adapted from IEEE Std PC95.1-2005:
Working groups (WGs) evaluate engineering, epidemiology, in vivo, and in vitro aspects of the research. Additionally, a WG on mechanisms assesses the role of mechanisms of interaction in standard setting. The Engineering WG is tasked with assessment of the exposure systems, field characteristics and measurements, dosimetry, specific absorption rates, induced currents and fields, and temperature/humidity measurements. The sufficiency of the information provided in each publication, to allow a full understanding of how the experiment was performed, is paramount. The chair of each WG is responsible for providing copies of each paper to two independent reviewers, together with specially designed and approved review forms called Triages. These ‘Triage’ forms (available in Appendix A, below) are in a computer format that requires numerical scoring by individual reviewers for entry into a computerized database. When a review is completed, the reviewer gives the paper an overall technical merit rating on a 5-point scale. The rating scale is: Very High = 5; Moderately High = 4; Acceptable = 3; Low = 2; and Very Low = 1. For ratings of 1 or 2, a request is made for justification in writing by the reviewer. This is not requested for ratings of 3 and above, which are considered acceptable. Strong discordance between the two reviews of a given paper requires a third independent review. Periodically, the chair of each WG submits a summary of the reviews completed to the Chair of the Risk Assessment WG (RAWG). All of the reviews are performed by volunteers who are randomly selected from within each working group. The identification of each reviewer will remain confidential.
The ICNIRP, IARC, and WHO EMF Project expert members work in phased collaboration with each other to evaluate the EMF literature.
1. The International Agency for Research on Cancer (IARC), with their secretariat in Lyon, France, is part of the WHO. (Classifications of carcinogens: ELF, 2001). [http://www.iarc.fr/]
2. The World Health Organisation (WHO) EMF Project have their secretariat in Geneva with members from 40+ countries. [http://www.who.int/peh-emf/en/]
The ICNIRP / IARC/ WHO EMF Project, EMF literature reviews cover health effects in the two separate exposure frequency ranges of 0-100 kHz and 100 kHz - 300 GHz.
The IEEE and WHO/ IARC/ICNIRP have not yet harmonized on the intermediate division between the two ranges but they may in the near future (Reilly, 2005).
On each of the two frequency ranges IARC evaluates the cancer literature, makes a classification and writes a Cancer Monograph.
On each of the two frequency ranges the ICNIRP panel reviews the biological literature and publishes its review as a Blue Book.
Consequently the WHO EMF Project panel prepares a review on each of the two frequency ranges and writes an Environmental Health Criteria (EHC) Monograph.
Finally once they have fully reviewed and evaluated the literature on both the 0-100 kHz and the 100 kHz-300 GHz ranges, the ICNIRP panel will revise the EMF guidelines for limiting human exposure over the entire EMF range, 0-300 GHz, as a paper published in Health Physics (1998; 2008?).
Presently IARC has evaluated the cancer literature on ELFs and published an IARC Monograph ‘Non-ionizing Radiation, Part 1: Static and Extremely Low Frequency Electric and Magnetic Fields’ (Vol. 80, 2002) and has made a cancer classification 2B for ELFs (19-26 June 2001). The IARC Panel (19-26 June 2001) consisted of 21 members from 11 countries and 4 observers (chosen by the secretariat) and the IARC secretariat.
Following this, the ICNIRP panel 2000-2004 (12 members, the Chair A. McKinlay, vice chair and chairman emeritus), along with invited consultants have written a review of the biological scientific literature concerning exposure to static and low frequency EMFs 0-100 kHz (2003) including dosimetry (2 members, 5 consultants), experimental investigations of EMF biological effects (of cellular, animal and human experiments)(7 members, 7 consultants), and epidemiology (2 members, 4 consultants). Their report is published as the ICNIRP Blue Book entitled Exposure to Static and Low Frequency Electromagnetic Fields, Biological Effects and Health Consequences (0 - 100kHz), (2003).
The WHO EMF Project panel are completing their update of the previous Environmental Health Criteria (EHC) Monograph 35 on ELF Fields, (1992) including comprehensive risk assessment and policy recommendations, expected in late 2005.
After IARC completes the meta analyses of results of the 13 country Interphone Study (2000-2005) a similar progression of literature evaluations by the panels of IARC, ICNIRP and the WHO EMF Project will be initiated for RF exposures in the range 100 kHz to 300 GHz.
IARC will evaluate the cancer-related literature of the RF bands and make a classification of RF possibly in 2006 and publish an RF IARC Monograph.
Then ICNIRP will evaluate the biological science and publish an RF Blue book.
And WHO EMF Project will write an EHC Monograph on RF to update the previous EHC monograph 137.
Following the completed cycles of IARC/ ICNIRP/ WHOEMF Project evaluations of both the ELF and RF published literature, ICNIRP will update the ‘ICNIRP guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields up to 300 GHz’ (Health Physics 1998), possibly in 2008. Thus we may have about a 10-year cycle to update the ICNIRP EMF guidelines for limiting human exposure according to the current literature evaluation process.
The fifth international RF literature review group is the European Cooperation in the Field of Scientific and Technical Research- Telecommunication Information Science and Technology, (COST 281), with their secretariat in Bonn, Germany. The COST 281 science members are drawn from the 25 signatory European countries. http://www.cost281.org.
The COST 244 (1996-2000) continued on as COST 281 from 2001. The COST (281) members continuously review the scientific literature on radio telecommunications and health and report to the European Commission.
Previously, COST 244 members wrote two comprehensive reviews of the RF literature [Possible Health Effects Related to the Use of Radiotelephones: Proposals for a research programme by a European Commission Expert Group, 1996 (McKinlay); McKinlay, 1997; 1999 (Veyret)].
COST 281 members are not directly involved in setting standards; however they do advise the EC on RF health effects literature for the purpose of policy and evaluating proposals for further research funding.
The first hurdle to demonstrate quality in research is publication; papers considered for health risk assessment must be published in a peer reviewed journal.
When evaluating submitted papers for journal publication anonymous reviewers and editors may use the following criteria to comment on the technical content of the papers: Does the TITLE accurately and briefly portray the content? Does the ABSTRACT clearly convey the problem(s), findings, and conclusion(s)? Does the INTRODUCTION clearly and concisely define the problem or issue? Is the METHODOLOGY clear, complete, and adequate for the biology and dosimetry? Are the RESULTS clearly and concisely presented, making proper use of tables? Is the DATA ANALYSIS complete and valid, using appropriate statistical methods and tests, and error analysis? Is the DISCUSSION valid, relevant, and concise? Are the CONCLUSIONS drawn fully, valid and stated concisely? Are any key citations missing in the REFERENCES? Does the list include all the references used in text? (Chou, 2003)
Since the paper will have already met the publication criteria, the panel members review the paper to see if it can meet replication criteria and, if replicated, can meet the EMF standard setting criteria. Review panels approach the literature in a structured way. Panels have a chairman and section heads with their committee members representing expertise in epidemiology, in vivo (animal and human laboratory studies) and in vitro research (tissue cultures) as well as engineering/dosimetry, statistics and biophysical mechanisms of interaction. The section heads summarise their areas of review for the chairman. We base guidelines on scientific data related to adverse health effects meeting the literature evaluation criteria and we require information to be consistent from multiple studies and disciplines.
Overall criteria for general experimental design, general research priorities as well as criteria for the specific areas of research (epidemiology, human acute, in vivo and in vitro) are listed below. The review criteria are derived from numerous published papers, books and standards and guidelines and the five ICES SC-4 Triages. Some key references are listed directly below:
Papers: Hill, 1965; Blundell, 1996; Rothman et al., 1996; Cardis and Rice, 1997; Repacholi and Cardis, 1997; Repacholi, 1998; Rothman and Greenland, 1998; Repacholi and Greenebaum, 1999; Lin, 2002; Adair, 2003; Brodsky et al., 2003; Chou, 2003; Gajsek et al., 2003; Habash, 2003; Habash et al., 2003; Rushton and Elliott, 2003; Kheifets et al., 2003; Ahlbom et al., 2004; Elliott and Wartenberg, 2004; Foster and Repacholi, 2004; Feychting et al., 2005; Greenland, 2005; Johnston and Scherb, 2005.
Books: EPRI, 1994; NIEHS, 1998; IARC Vol 80, 2002; ICNIRP, 2003; Stravoulakis (Ed), 2003 (Johnston chapter, 2003); Ahrens and Pigeot, (Eds) 2005.
Standards and Guidelines: ICNIRP, 1998; IEEE Std C95.6-2002; IEEE Std C95.1-1991/1999; IEEE Std 1528-2003; Draft IEEE Std PC95.1- 2005.
Five Triages: Developed by ICES members for consistent literature review in SC-4 [listed in full in Appendix A].
Good Laboratory Practice (GLP) should be used throughout the design and conduct of any study where possible and practical, but especially with large and long-term studies (see, e.g., FDA, 1993, NTP 1992[3]).
Quality assurance (QA) procedures should be included in the protocol, including traceable dosimetry and monitoring of the programme by both a team from within the experimental staff and an independent group, as required by GLP [Repacholi et al., 1998; Repacholi and Greenebaum, 1999; Schönborn et al., 2000, 2004; ICNIRP, 2003; IEEE Std C95.6-2002; IEEE Std C95.1, 1991/1999; IEEE Std 1528-2003; Draft IEEE Std PC95.1-2005].
· It is essential for high quality research that accurate assessment of RF and ELF exposure is an integral part of all studies and that each research team include scientists and engineers skilled in traceable EMF dosimetry, in sufficient detail for replication (Triages).
· Computational dosimetry provides the quantitative link between internal dose quantities for direct effects and external fields that can be measured. (Quoted from NRPB, 2004).
· A comprehensive uncertainty[4], variability and artifact dosimetric analysis is required to achieve consistent interpretation of the results (quoted from Kuster et al., 2004; IEEE Std 1528-2003).
· In relation to dosimetry of ELF local exposures, most internal cellular effects associated with low-level ELF exposure are linked with the induced electric field stimulation and therefore the internal induced electric field should be determined in ELF research where possible [IEEE Std C95.6-2002; ICNIRP, 2003; Reilly, 2005].
· Human exposure to (external ELF) magnetic fields is measured in flux density (B) in milliTesla (mT) and magnetic field strength (H) in amps per meter (A/m) respectively (IEEE Std C95.6-2002).
Scientists are required to take responsibility for:
[Quoted from Rushton and Elliott, 2003; see also Conrads et al., 2004; Dorman, 2005; Espina et al., 2005; Gilham et al., 2005; Greenland, 2005; LaPorte, 2005]
Review of the new research proposals should give a high priority to studies with ELF and RF levels, frequencies, modulation and pulse characteristics relevant to human exposures from new technologies with endpoints relevant to human health. [Repacholi, 1998; Foster and Repacholi, 2004; Andersen, Foster, presentations, COST 281, Zurich, February 2005]
· SAR remains the major RF dosimetric quantity; modulation should not be added to a study unless adequate statistical power can be maintained [ICNIRP, 1998; ICNIRP, 2003; Foster and Repacholi, 2004; COST 281, Zurich, February 2005; DRAFT IEEE Std PC95.1-2005].
· Some research, not necessarily a full set of studies, would be warranted for new RF technologies that employ new modulation schemes (changes in peak relative to average signal level and changes in frequency content of a signal) if the potential for public exposure is high. This includes UMTS now being rolled out [Foster and Repacholi, 2004; Andersen, Foster, presentations, COST 281, Zurich, February 2005].
· In the low frequency range the standard is based on electrostimulation which is defined as induction of a propagating action potential in excitable tissue by an applied electrical stimulus; electrical polarization of presynaptic processes leading to a change in post synaptic cell activity [Quoted from IEEE Std C95.6-2002].
· In most biological experiments of low-frequency field (ELF) effects the induced electric fields are poorly known. It is necessary to improve macroscopic dosimetry and, particularly in the case of in vitro studies, also to examine the microscopic distribution of the induced electric field [Quoted from ICNIRP, 2003; see also IEEE Std C95.6-2002; Reilly, 2005].
· There is a lack of well-replicated studies that reveal the existence of biological effects or adverse health effects from low-level RF or ELF exposure below, at, and above public and occupational guideline limits [ICNIRP, 2003; COST 281, Zurich, February 2005].
· Similarly there is a lack of well-replicated studies that reveal the existence of biological effects or adverse health effects from low-level RF or ELF exposure at various durations of exposures similar to real life durations of exposure conditions including intermittent exposures [Ivancsits et al., 2005; Diem et al., 2005].
· We need to establish the human threshold SAR values where RF exposure has a biological and an adverse effect [COST 281, Zurich, February 2005; IEEE, ICES, COST 281: 2004/09 Thermal Physiology Workshop, Paris].
· We need to establish more precisely the ELF thresholds for human electrostimulation values where ELF exposure has a biological and an adverse effect in various tissues [IEEE Std, C95.6-2002; ICNIRP, 2003; Reilly, 2005].
· A future goal is to develop appropriate techniques and thermal models for accurately predicting the thermo physiological responses of human beings who are exposed to RF fields at specific frequencies, field strengths, and field characteristics and to validate some predictions with existing human exposure data [Stolwijk and Hardy, 1977; Adair and Berglund, 1986, 1992; Adair et al., 1998, 1999, 2001, 2003, 2005; Kheifets et al., 2003; Foster and Adair, 2004; IEEE, ICES, COST 281: 2004/09 Thermal Physiology Workshop, Paris]. Much data exists that describes the regulatory response changes in the human body as a function of environmental variables, work, exercise, age, fitness, clothing insulation, and other characteristics of each individual. [WHO Geneva Workshop, 2002: Adverse Temperature Levels in the Human, International Journal of Hyperthermia, Vol 19(3), 2003]. Much of this material is amenable to comparison with data derived from RF-exposed humans and animals. [IEEE, ICES, COST 281: 2004/09 Thermal Physiology Workshop, Paris].
· We need to note the modulation of RF and ELF signals exactly. Different modulations could have the same average value. Presently there is no convincing evidence that there is a difference between continuous and modulated RF signals in their effects. But we need to get more clear evidence of the different modulations. Are there separate classifications according to biological effects? Is lower or higher SAR more significant at producing effects? [COST 281, Zurich, February 2005]
· Experimental EMFs should be fully characterized and re-measured periodically. Waveform, pulse shape and timing, frequency spectrum, harmonics and transients from both continuous sources and from switching exposure systems on and off should all be measured where appropriate (Kuster, 1996; Schönborn et al., 2000; Nikoloski et al., 2005).
· Background fields, such as ambient, equipment-derived, and crossover fields from other exposure systems, are also important and need to be characterized. Time-varying and static components should be measured, as well as the polarization and directions of the fields.
· Field modulation introduced by experimental factors such as motion of sample shakers should be noted and measured whenever possible. Positioning of cultures or animals within exposure systems should be noted and randomized where appropriate (Repacholi, 1998).
· The position of humans in exposure systems should be noted and stereotaxically (3-D) defined for replication. (Excell et al., 1996, 1998; Vaul & Excell, 1999).
· Reports of SAR increases due to the presence of nonmagnetic electrodes during RF exposure of up to a factor of 16 have been reported (Angelone et al., 2004). During RF exposure while recording EEG, better modelling of the human head SAR is required (Huber et al., 2003). For instance you cannot use a plastic shell head phantom the same as for mobile phone compliance when measuring the effect of metal leads (for EEG recording) on SAR because of the insulating plastic phantom shell since there would be no electrical connection between the leads and the fluid inside the phantom. (CK Chou personal communication; for SAR modelling methodology see Angelone et al., 2004).
· Further modelling of SAR of children is required using realistic head and body phantoms for both near and far field exposures [ICNIRP, 2003; NRPB, 2004; Draft IEEE Std PC95.1-2005].
· Meta studies are required on RF effects of UMTS and 4G signals on direct and established measures of human brain function and the possible mechanisms involved, using well validated measurements [Haarala et al., 2004; HCN, 2004; Angelone et al., 2004; Kuster et al., 2004].
· In vitro meta studies investigating DNA breaks, genomics, proteomics and molecular signalling pathways during ELF and RF exposures are a priority because of remaining positive studies in the cytogenetic literature (Vijayalaxmi and Obe, 2004; Moulder et al., 2005; Obe and Vijayalaxmi, 2005. reviews).
· Possible long-term biological effects (up to 30 years; IARC, 2002; ICNIRP, 2003; Ahlbom et al., 2004; Feychting et al., 2005) from mobile phone exposure of the public require investigation and should be given priority. Cohort studies including children are recommended. (Stewart et al., 2000; ICNIRP, 2003; Ahlbom et al., 2004; Feychting et al., 2005; Moulder et al., 2005).
· The incorporation of molecular epidemiological methods to aid the investigation of mechanistic pathways and gene-environment interactions should be included. [Rushton and Elliott, 2003; see also Conrads et al., 2004; Dorman, 2005; Espina et al., 2005].
Evaluation of research literature on the effects of ELF or RF exposure is reached in a complex confirmatory interplay of human epidemiological studies, human acute studies, in vivo bioassays (animal lifetime studies), animal acute studies and in vitro tissue culture studies. Traditionally, investigations in human beings of associations between exposure levels and adverse health effects can utilize either human acute or epidemiological studies. And it was biologically plausible and prudent to regard EMF exposure studies in animals, as evidence of lack of risk or risk in humans. This was and is dependent on whether there is evidence for extrapolation of the science from animals to man, based on known functional and structural homologies [i.e. Spatial memory: Kandel et al., 2000; Kandel, 2001; Cell division: Lee and Nurse, 1987]. Traditionally, cellular research was considered as the possible source of a plausible mechanism for any biological effect due to exposure to RF or ELF signals [Repacholi and Cardis, 1997; Repacholi, 1998].
Great advances in cellular research have given us a new understanding of the interplay of cellular research of genes, proteins and cell signalling in single living cells, and the functioning of the whole human body.
For instance molecular profiling for the treatment of individual patient's tumours is currently being evaluated in clinical trials at the National Institutes of Health, National Cancer Institute (Espina et al., 2005).
And high-resolution serum proteomic features are being implemented for various kinds of cancer detection (Conrads et al., 2004).
These molecular advances have an impact on EMF research priorities. Molecular profiling may become essential at all levels of research namely in epidemiology, human acute studies, animals studies and tissue cultures.
Molecular epidemiology is based on general epidemiology and utilizes the same designs (i.e., case control and cohort studies) as those employed by general epidemiology. However, molecular epidemiology utilizes molecular biology to define the distribution of disease in a population (i.e., descriptive epidemiology) and identify its potential etiologic determinants (i.e., analytical epidemiology) [Quoted from Dorman JS, Director, Collaborating Center for WHO Multinational Project for Childhood Diabetes (DiaMond), U of Pittsburgh; see also LaPorte RE, Director, Molecular Epidemiology and DNA Technology Transfer http://www.pitt.edu/~rlaporte/who.html]
The following sections are on specific research designs in epidemiology, human acute studies, in vivo and in vitro research designs respectively.
Epidemiologic investigations of possible associations of EMF exposure with risk of chronic disease pose unique and substantial difficulties. Among them are difficulties specific to an outcome studied, assessment of exposure, and interpretation of findings and long latency periods required to detect any cancer risk (up to 30 years), (IARC, Vol 80, 2002).
· The hypothesis must be explicitly and clearly stated before the onset of the research.
· Subjects and controls must have given informed consent.
· The method of ascertaining cases of adverse health must be stated.
· Case identification must be independent of exposure. Definition of cases should be objectively, and histologically confirmed.
· Controls should be appropriate to the specific aim and design.
· Controls must be matched (to cases) individually, on age and sex, within study region, and on the basis of frequency, and be population based –i.e. ‘representative’
· Minimization of non-response or non-participation is required to achieve the necessary sample size and minimize bias through selective non-response.
· Total number of original subjects and controls must be stated as well as those removed from the study due to non-response or death.
· An adequate population sample size must be used based on previous calculation of the statistical power. Expected number of cases must be adequate in the study populations to show a relatively small effect of exposure to EMF emissions, if there is one, for instance, from electrical power devices, or mobile phones.
· Study populations must be well defined before the onset of the research.
· Study designs should recognize that the exposure metric for possible effects of weak ELF and weak RF fields is uncertain and usually proxy. Subjects' exposures, particularly historical exposures that are often determined via surrogates, should be validated from specific measurements where possible. Data should include as much information relevant to alternate metrics as possible to aid future research. [Beaglehole et al., 1993; Bracken et al., 1993; Ahlbom, (ICNIRP), 1996; ICNIRP, 1998; IEEE Std C95.6-2002; ICNIRP, 2003; Ahlbom et al., (ICNIRP) 2004; Feychting et al., 2005; IARC, Vol 80, 2002; Draft IEEE Std PC95.1-2005; Neubauer et al., 2005; Reilly, 2005].
· The results must be calculated to evaluate the original hypothesis. It is on the basis of the stated original hypothesis that the power of the study is calculated and the size of the sample is set.
· The authors should report the basic data on which the conclusions are drawn (IARC, Vol 80, 2002).
· Post hoc comparisons on subsets of the data may be hypothesis generating only. Appropriate corrections for multiple comparisons must be applied (Keppel, 1982; Steenland et al., 2000; Johnston and Scherb, 2005).
· Meta analyses should take into consideration prior distributions for the unidentified bias parameters used in the original sensitivity-analysis model. Accounting for uncontrolled confounding and response bias under a reasonable prior (distribution) can substantially alter inferences about the existence of an electromagnetic field effect. Analyses with informative priors (distributions) for unidentified bias parameters can help avoid misinterpretation of conventional results and ordinary sensitivity analyses [Quoted from Greenland, 2003; 2005; see also Blettner & Schlattmann, 2005].
· Studies should include collection of blood samples to create a bio-bank for molecular biological studies on brain tumours and other diseases.
· In new studies, improvement of the exposure assessment is crucial. (Feychting et al., 2005). Personal monitoring systems are being developed for base site exposures.