Thursday, April 16, 2015

Scientific evidence contradicts findings and assumptions of Canadian Safety Panel 6: microwaves act through voltage-gated calcium channel activation to induce biological impacts at non-thermal levels, supporting a paradigm shift for microwave/lower frequency electromagnetic field action

Scientific evidence contradicts findings and assumptions of Canadian Safety Panel 6: microwaves act through voltage-gated calcium channel activation to induce biological impacts at non-thermal levels, supporting a paradigm shift for microwave/lower frequency electromagnetic field action

Pall ML. Scientific evidence contradicts findings and assumptions of Canadian Safety Panel 6: microwaves act through voltage-gated calcium channel activation to induce biological impacts at non-thermal levels, supporting a paradigm shift for microwave/lower frequency electromagnetic field action. Rev Environ Health. 2015 Apr 16. pii: /j/reveh.ahead-of-print/reveh-2015-0001/reveh-2015-0001.xml. doi: 10.1515/reveh-2015-0001. [Epub ahead of print]


This review considers a paradigm shift on microwave electromagnetic field (EMF) action from only thermal effects to action via voltage-gated calcium channel (VGCC) activation. Microwave/lower frequency EMFs were shown in two dozen studies to act via VGCC activation because all effects studied were blocked by calcium channel blockers. This mode of action was further supported by hundreds of studies showing microwave changes in calcium fluxes and intracellular calcium [Ca2+]i signaling. The biophysical properties of VGCCs/similar channels make them particularly sensitive to low intensity, non-thermal EMF exposures. Non-thermal studies have shown that in most cases pulsed fields are more active than are non-pulsed fields and that exposures within certain intensity windows have much large biological effects than do either lower or higher intensity exposures; these are both consistent with a VGCC role but inconsistent with only a heating/thermal role. Downstream effects of VGCC activation include calcium signaling, elevated nitric oxide (NO), NO signaling, peroxynitrite, free radical formation, and oxidative stress. Downstream effects explain repeatedly reported biological responses to non-thermal exposures: oxidative stress; single and double strand breaks in cellular DNA; cancer; male and female infertility; lowered melatonin/sleep disruption; cardiac changes including tachycardia, arrhythmia, and sudden cardiac death; diverse neuropsychiatric effects including depression; and therapeutic effects. Non-VGCC non-thermal mechanisms may occur, but none have been shown to have effects in mammals. Biologically relevant safety standards can be developed through studies of cell lines/cell cultures with high levels of different VGCCs, measuring their responses to different EMF exposures.

The 2014 Canadian Report by a panel of experts only recognizes thermal effects regarding safety standards for non-ionizing radiation exposures. Its position is therefore contradicted by each of the observations above. The Report is assessed here in several ways including through Karl Popper's assessment of strength of evidence. Popper argues that the strongest type of evidence is evidence that falsifies a theory; second strongest is a test of "risky prediction"; the weakest confirms a prediction that the theory could be correct but in no way rules out alternative theories.

All of the evidence supporting the Report's conclusion that only thermal effects need be considered are of the weakest type, confirming prediction but not ruling out alternatives. In contrast, there are thousands of studies apparently falsifying their position. The Report argues that there are no biophysically viable mechanisms for non-thermal effects (shown to be false, see above). It claims that there are many "inconsistencies" in the literature causing them to throw out large numbers of studies; however, the one area where it apparently documents this claim, that of genotoxicity, shows no inconsistencies; rather it shows that various cell types, fields and end points produce different responses, as should be expected. The Report claims that cataract formation is produced by thermal effects but ignores studies falsifying this claim and also studies showing [Ca2+]i and VGCC roles. It is time for a paradigm shift away from only thermal effects toward VGCC activation and consequent downstream effects.
There has been a literature reporting various non-thermal effects of microwave/radiofrequency radiation exposures starting with the Soviet literature in the 1950s. Subsequently, there have been thousands of international published studies reporting non-thermal or what are sometimes called micro-thermal effects producing therapeutic responses, changes in calcium fluxes and signaling, increased oxidative stress, and a wide variety other health-related responses in humans and animal models.
Nevertheless, there has been a series of medical reports, arguing that only thermal effects need be considered when setting guidelines or safety standards for microwave electromagnetic field (EMF) exposures. These have been based mainly on two types of arguments:
  1. That there cannot be any biophysically viable mechanism for any such non-thermal effects and therefore that reports of such effects should be viewed with great skepticism.
  2. That there are many “conflicts” or “inconsistencies” in the literature which according to these reports, justify rejection of the various thousands of publications showing apparent non-thermal effects.
The focus of this review is to consider whether it is time for a “paradigm shift” away from strictly thermal effects toward non-thermal effects. Specifically, it is focused on the recent finding that most, possibly all non-thermal effects can be produced by microwave activation of voltage-gated calcium channels (VGCCs). It is also focused on the 2014 Report of the Canadian Panel of Experts on Safety Code 6 as the most recent and therefore up-to-date summary of the evidence supporting the strictly thermal point of view ...
Brief Overview
Havas’ recent review (80) discusses 14 different documents prepared by international scientists (dated 2002 through 2012) expressing deep concern about various non-thermal effects of microwave radiation exposures and other studies have expressed similar views. W.R. Adey’s papers (6, 21) reviewed much of the then current evidence for many non-thermal effects of microwave radiation. But his prescience is most clearly shown by his statement that “Collective evidence points to cell membrane receptors as the probable site of first tissue interactions with both extremely low frequency and microwave fields for many neurotransmitters, hormones, growth-regulating enzyme expression, and cancer-promoting chemicals. In none of these studies does tissue heating appear to be involved causally in the responses” [italics added, from a talk at the Royal Society of Physicians, London May 16–17, 2002, quoted in ref. (81)]. The recent Herbert and Sage review (81) discusses “the emergence of ever larger bodies of evidence supporting a large array of non-thermal but profound pathophysiological impacts of EMF/RFR in transforming our understanding of the nature of EMF/RFR impacts on the organism.” In a second paper (82), Herbert and Sage state that “Our EMF/RFR standards are also based on an outdated assumption that it is only heating (thermal injury) which can do harm. These thermal safety limits do not address low-intensity (non-thermal) effects. The evidence is now overwhelming that limiting exposure to those causing thermal injury alone does not address the much broader array of risks and harm now clearly evident with chronic exposure to low-intensity (non-thermal) effects.” The Khurana et al. review (83) states: “The authors reviewed more than 2000 scientific studies and reviews, and have concluded that: (1) the existing public safety limits are inadequate to protect public health; (2) from a public health policy standpoint, new public safety limits on further deployment of risky technologies are warranted based on the total weight of evidence. A precautionary limit of 1 mW/m2 was suggested ….” The Scientific Panel on Electromagnetic Field Health Risks listed four well-documented central conclusions at the beginning of their publication (77):
  1. Low-intensity (non-thermal) bioeffects and adverse health effects are demonstrated at levels significantly below existing exposure standards.
  2. ICNIRP and IEEE/FCC public safety limits are inadequate and obsolete with respect to prolonged, low-intensity exposures.
  3. New biologically-based public exposure standards are urgently needed to protect public health worldwide.
  4. It is not in the public interest to wait.
Canadian Panel of Experts do not cite these papers or others providing clear and focused views that contradict the views advocated in the Report, showing again that the Report fails to provide an objective assessment of the scientific literature. The current paper adds a number of specific considerations to the needed debate:
  1. VGCC activation produces most, possibly even all microwave and lower frequency EMF health-related responses. Each of the studies on VGCC activation or on changes in calcium fluxes and signaling following low level exposure clearly falsifies the thermal/heating paradigm.
  2. This VGCC activation mechanism by low level microwave and lower frequency fields, rather than individual photons, is biophysically plausible based on the special properties of the voltage sensor and its localization to lipid region of the plasma membrane.
  3. Downstream effects of VGCC activation (Figure 1) can generate each of 13 different health effects repeatedly found to be produced by microwave exposure (Table 1).
  4. Studies document roles of pulsation in influencing biological responses to microwave exposures, influences that are incompatible with these being produced by heating.
  5. “Window” effects occur, where specific intensities of microwave EMF exposure produce higher biological effects than those produced by both lower and higher intensities, observations incompatible with heating effects.
  6. Thousands of studies have reported biological effects at intensities well within safety standards, each of which appear to falsify the heating/thermal paradigm, none of which have been considered in this light by the Panel of Experts, despite the scientific requirement to do so under well-accepted scientific principles.
  7. The claims in the Report that microwave induction of cataracts is produced by heating has been tested in three studies, each contradicting this claim; two of them produce clear falsification, but none of these three studies are cited in the Report. Because VGCC activation can cause cataracts and elevated [Ca2+]i has essential roles in producing cataracts, a VGCC mechanism for microwave-induced cataracts is much more strongly supported than is the claimed heating mechanism.
  8. The claim in the Report of widespread “inconsistency” in the literature is tested here through examination of the literature cited on genotoxic effects. No inconsistencies were found in this literature despite the Report claiming such. Furthermore, no identical studies are cited anywhere in the Report showing inconsistency of results, these being the only types of studies that can clearly show inconsistency. Claims of widespread “inconsistency” or “conflict” in the literature must be viewed as, at best, undocumented.
  9. Each of the 8 considerations listed immediately above clearly show that the Report fails to provide anything resembling an objective assessment of the evidence on biological effects of microwave EMF exposures and provides therefore no scientifically valid support for Safety Code 6, ICNIRP or other current safety standards.
  10. Development of biologically-based safety standards has been called for and approaches to using cell culture-based tests that may be used to develop such safety standards are discussed.
It has been clear for a long time that the heating paradigm is indefensible and that a new paradigm is much needed. We now have that with VGCC activation, and while VGCC activation may not be the entire story behind the biological actions of such EMFs in humans and other mammals, it clearly is most of the story. It is time therefore for a paradigm shift away from strictly thermal effects and toward a central role for VGCC activation in the cellular response to microwave and lower frequency EMFs.

Joel M. Moskowitz, Ph.D., Director
Center for Family and Community Health
School of Public Health
University of California, Berkeley

Electromagnetic Radiation Safety

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