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National Institutes of Health National Toxicology Program  Updates Webpage on Cell Phone Radiation

DNA Damage in Rats and Mice from Cell Phone Radio-frequency Radiation

The National Toxicology Program (NTP) has updated their webpage on cell phone radiation. The webpage  now includes their published research findings of DNA damage in both rats and mice. In addition the webpage has an extensive Q and A section.

The website link can be found at https://ntp.niehs.nih.gov/whatwestudy/topics/cellphones/index.html

Note: National Toxicology Program scientist Michael Wyde  recently presented to the New Hampshire commission on 5G health effects and stated that, “A lot of people believe unless you heat tissues, you won’t see health effects with RF. This study disproves that as we did not have over heating but we did see damage.” (New Hampshire Commission Minutes, PDF on EHT )

The NTP webpage now includes the recent publication finding DNA damage from cell phone radiation.

  • Smith-Roe SL, Wyde ME, Stout MD, Winters JW, Hobbs CA, Shepard KG, Green AS, Kissling GE, Shockley KR, Tice RR, Bucher JR, Witt KL. Evaluation of the genotoxicity of cell phone radiofrequency radiation in male and female rats and mice following subchronic exposure. Environ Mol Mutagen. 2019. https://doi.org/10.1002/em.22343

The NTP webpage now states the following:

“NTP conducted two-year toxicology studies in rats and mice to help clarify potential health hazards, including cancer risk, from exposure to RFR like that used in 2G and 3G cell phones which operate within a range of frequencies from about 700–2700 megahertz (MHz). These were published as Technical Reports in November 2018.

What did the studies find?

The NTP studies found that high exposure to RFR (900 MHz) used by cell phones was associated with:

  • Clear evidence of tumors in the hearts of male rats. The tumors were malignant schwannomas.
  • Some evidence of tumors in the brains of male rats. The tumors were malignant gliomas.
  • Some evidence of tumors in the adrenal glands of male rats. The tumors were benign, malignant, or complex combined pheochromocytoma.

It was unclear if tumors observed in the studies were associated with exposure to RFR in female rats (900 MHz) and male and female mice (1900MHz).

The results are based on NTP’s four categories of evidence that a substance may cause cancer: clear evidence (highest), some evidence, equivocal evidence, no evidence (lowest).

As a follow-up, NTP submitted a manuscript accepted for publication in October 2019 that evaluated DNA damage in three regions of the brain, the liver, and in blood cells in rats and mice that were removed at an earlier timepoint from the ongoing 2-year toxicology study. DNA damage, if not repaired, can potentially lead to tumors. This work was also included in NTP’s published Technical Reports, but this study includes analyses of the data in the supporting information not included in the Technical Reports.

NTP scientists found that RFR exposure was associated with an increase in DNA damage. Specifically, they found RFR exposure was linked with significant increases in DNA damage in:

  • the frontal cortex of the brain in male mice,
  • the blood cells of female mice, and
  • the hippocampus of male rats.

There are many factors that influence whether damaged DNA will lead to tumors. NTP plans to conduct additional studies to learn more about how RFR might cause DNA damage. Please see the FAQs below for more information about the specific studies and NTP’s cell phone RFR program.

What are NTP’s future plans for studying cell phone RFR and 5G wireless technology?

5G is the emergent technology that will eventually overtake the existing 2G, 3G, and 4G technology. In the meantime, people will continue to be exposed to RFR in the 700–2700 MHz range. As the 5G network is implemented, some of the signals used by the 5G network will use the same lower frequencies used by the older technology previously studied by NTP, but the 5G network will also use higher frequencies—up to 60,000 MHz—thereby exposing wireless users to a much broader spectrum of frequencies. The higher frequencies, known as millimeter waves, can rapidly transmit enormous amounts of data with increased network capacity compared with current technologies. Millimeter waves do not travel as far and do not penetrate the body as deeply as do the wavelengths from the lower frequencies. Millimeter waves are likely to penetrate no deeper than the skin, whereas the lower frequencies have been shown to penetrate at least three to four inches into the human body.

NTP is currently evaluating the existing literature on the higher frequencies intended for use in the 5G network and is working to better understand the biological basis for the cancer findings reported in earlier studies on RFR with 2G and 3G technologies. Additionally, work is ongoing to develop smaller RFR exposure chambers for additional short-term studies that will take weeks and months to complete rather than years. The exposure system is also being designed to have the capability to conduct studies with various RFR frequencies and modulations to keep up with the changing technologies in the telecommunications industry.

NTP also aims to repeat studies in the smaller RFR exposure chambers and to identify biomarkers of damage from RFR exposure. The biomarkers would be measurable physical changes, such as molecular changes, that can be seen in shorter amounts of time than it takes to develop cancer and that might be predictive of the disease. If scientists can better understand biological changes in animals, they will know more about what to look for in humans. Additional studies could also identify whether the behavior of animals is affected by RFR exposure.”

Under FAQs the webpage now states:

“Results/Human Relevance

Q: How do the cancer findings in male rats translate to what we might see in people?
A: NTP concludes that the findings from these studies show a link between cell phone radiofrequency radiation (RFR) exposure and heart tumors. These findings were also supported by other precancerous changes, called cardiomyopathy, in heart tissue. The type of brain cancer observed is similar to a type of brain tumor associated with heavy cell phone use in some human studies. Still, the effects observed were relatively rare. Heart cancer was observed in approximately 2% of rats that were exposed at a lower level of RFR. Heart cancer was seen in 5–6% of rats exposed to a higher power level—four times higher than the maximum human exposure.

Q: Does the fact that the animals were exposed to radiation all over their bodies (unlike humans who expose only certain body parts to cellphones) and for longer periods of time than humans generally used their phone make it difficult or impossible to extrapolate these results for human health?
A: NTP’s studies were conducted with whole-body exposures to evaluate the potential hazard to exposure across the entire body and not just particular regions. This allowed study scientists to identify particular organs that may be more at risk to the potential effects of RFR, as was the case in the hearts of male rats. When extrapolating from animal studies to human risk assessment for the effects of RFR, many complicating factors make the evaluation of exposure challenging, including the various ways people use their cell phones during normal usage conditions, such as via Bluetooth or speakerphone, or by putting the device directly next to their ear. It also includes variation in individual exposure due to disparities in signal strength depending on location. When extrapolating from highly controlled studies in laboratory animals to the less-ordered exposure scenario that occurs in humans, many factors need to be addressed and these findings should not be directly extrapolated to human cell phone usage.

Q: Why is it so difficult to understand the effect of these radiation-emitting devices on human health?
A: Studying RFR is complicated. In addition to the toxicologists, statisticians, geneticists, pathologists, and animal care staff, NTP scientists worked with electrical engineers and experts in RFR to design and build the exposure systems and monitor the exposures used in these studies. The goal was to identify what health effects could potentially be seen in humans. These studies will hopefully help other scientists have some ideas about what to watch for in humans as our RFR exposures change over time. This is why NTP conducts toxicology studies—to give other researchers a starting point.

Q: What issue that researchers are studying is most worrisome in terms of public health?
A: Most concern has focused, historically, on the potential health effect of cell phone RFR exposure on the brain in humans. This concern was based on the fact that people used their cell phones in close proximity to their heads. Over the years, however, as the devices have become more capable, with greater connectivity at increased speed, the way consumers use their devices has been evolving. Cell phones are no longer only used to make and receive phone calls, which means that the devices may be held at locations other than against the head.

Q: Is there a way to convert the amount of exposure experienced by the male rats that developed tumors to what humans might be exposed to?
A: Extrapolation of NTP findings to humans is not straightforward, and the studies were not designed with that as a primary purpose. Rather, the purpose was to test whether exposures to RFR could cause biological effects at levels of exposure that did not significantly raise the body temperature of the animals. Current RFR human exposure limits by the Federal Communications Commission (FCC) and the U.S. Food and Drug Administration (FDA) for cell phone use mandate that the temperature of tissue next to where the phone is held does not increase by more than 1 degree Celsius.

Q: Why did you see more cancer in male rats than in female rats?
A: NTP scientists aren’t sure why male rats appear to be at greater risk for developing tumors compared with female rats.

Q: If the studies on DNA damage were included in the Technical Reports, why did NTP publish a stand-alone study on these findings?
A: The stand-alone study provides more information on how the DNA damage data were analyzed in the Supporting Information section. The conclusions of the stand-alone study are the same as the conclusions in the Technical Reports.

Q: How does NTP study the amount of DNA damage in a cell and what are the implications of the results of this kind of experiment?
A: To study DNA damage NTP used a test called a comet assay, also known as a single cell gel electrophoresis assay. This experiment provides a general indication of DNA damage in a cell. Cells have many enzymes that repair DNA, so the amount of DNA damage that is observed at one time is dependent on how much damage was caused initially and how quickly and effectively the cell can repair the damage. Hypothetically, a cell could repair all of the damage, or it could experience so much damage that it dies. In both of these scenarios, the DNA damage is eliminated. However, if the DNA damage is not repaired, or if it is repaired but incorrectly, then when that cell divides, the daughter cells may have those damaged areas in their DNA that potentially could lead to tumors. NTP did not do a time course study, so they don’t know if the cells were able to repair all of the damage and, therefore, would have been at lower risk of potentially becoming a cancer cell. NTP scientists did learn that RFR exposure leads to DNA damage under the conditions of the study, but they do not know the mechanism by which RFR caused DNA damage.

Q: Did you find any health benefits of exposure to cell phone RFR?
A: Interestingly, exposure to RFR extended the lifespan of male rats, although NTP scientists are not yet sure why. They did notice that exposure to cell phone RFR appeared to lessen chronic kidney disease in aging male rats, which is often the animals’ cause of natural death.

Q: How do the animal exposures in this study relate to human exposures from modern cell phones?
A: A major difference is that, in the studies, the animals were exposed over their whole bodies, in contrast to human exposure, which is typically from a single point of exposure at a more localized area. Most previous studies had focused on exposure to the brain, but NTP researchers wanted to make sure that they were considering effects to the whole body, especially since people don’t hold their phones next to their head much of time.

Q: Can the findings be directly extrapolated to humans?
A: There are two ways to look at this. Do they directly apply? No. There were differences between how the animals were exposed to RFR in the studies and the exposure experience by someone who uses a cell phone. On the other hand, some of the tumors in exposed animals have also been seen in humans, so they may have relevance.

Q: Have you changed your cell phone use or what you recommend to your family?
A: NTP scientists have become more aware of my usage, but most haven’t really changed their habits. If people are concerned about their exposure, they can follow the FDA’s tips for reducing exposure to cell phone RFR:

  • Reduce the amount of time spent using your cell phone, and
  • Use the speaker mode or a headset to place more distance between your head and the cell phone.

Study Methods

Q: How much did the study cost? Why did it take so long?
A: The study cost $30 million and took about 10 years. It took a significant amount of time because NTP first evaluated existing studies of the topic and then decided to design a new system for exposing rats and mice to cell phone RFR. This new system improved on what was being used at the time. NTP scientists conducted preliminary studies testing body temperature increases or overt toxicity before finally getting to the two-year toxicity studies in rats and mice. Then they evaluated 40 tissues from nearly 3,000 animals for cancer and other tissue changes, followed by statistical analysis and writing the reports.

Q: Can you tell us more about how the studies were conducted?
A: The studies were conducted in three phases. First, because radiofrequency radiation generates heat when absorbed by the body, NTP did pilot studies to determine exposure levels that did not exceed the ability of the animals to maintain normal body temperatures. Next, the scientists did short duration studies to determine exposure levels that did not affect the normal growth and development of rats and mice. And finally, they performed studies in which pregnant rats and their offspring, and young adult mice, were exposed to radiofrequency radiation for the better part of their natural lifetime, or approximately two years.

Q: Where were the studies conducted?
A: NTP conducted the study at the Illinois Institute of Technology Research Institute in Chicago, Illinois.

Q: Tell us more about the reverberation chambers used in the study.
A: The reverberation chambers used to expose rats and mice to cell phone RFR were conceptualized by the National Institute for Standards and Technology (NIST) and further designed and tested by NIST and the Foundation for Research on Information Technologies in Society (IT’IS Foundation) in Zurich, Switzerland. The reverberation chamber system used allowed lengthy daily exposures to unrestrained rodents lessening the chance for heating and stress as in restrained animal exposure systems used by others.

Q: What were the studies’ strengths?
A: A major strength of the study is that NTP scientists had better control of the RFR exposures. That’s one of the reasons they spent so much time on the exposure system, to make sure they were testing what they wanted to test.

Q: What are some of the studies’ limitations?
A: This study had a lot fewer limitations than much of the prior research conducted on this topic. The main limitation was the unexpected finding of longer lifespans among the exposed male rats, but this may be explained by an observed concurrent decrease in chronic kidney problems that are often the rats’ cause of death.

Q: Exactly how much radiation were the animals exposed to and over what period of time?
A: In NTP’s chronic studies, the rats were exposed to between 1.5 and 6 Watts RFR per kilogram of body weight (W/kg) for two years. In the mouse studies, animals were exposed to between 2.5 and 10 W/kg for two years. These were whole-body exposures, so the animals were exposed evenly across their entire bodies.

Q: What is the difference between CDMA and GSM modulations?
A: Code Division Multiple Access (CDMA) and Global System for Mobile Communications (GSM) are two common ways of transmitting cell phone signals in the United States and Europe. There are substantial differences in signal structure that may result in different exposures to cell phone RFR, so NTP wanted to expose the animals to both modulations. CDMA sends data in small bits over a number of the discrete frequencies available for use at any time in the specified range, a form of transmission known as Direct Sequence Spread Spectrum. CDMA signal modulation is based on code division separation of mobile stations as well as base stations. GSM, which was developed to establish a digital standard throughout Europe, allows the transmission of basic data services such as Short Message Service (SMS), but not large packets of data such as internet access and streaming video.

Q: Were the pathology reviews blinded? How was blinding handled?
A: Yes, the pathology evaluation of the RFR rat and mouse studies was performed according to standard practices in toxicologic pathology. This involved a three-step review process that included: 1) unblinded reads by the initial study pathologist, 2) a second quality assurance pathology review, then 3) a blinded evaluation of target lesions by a group of NTP and outside expert pathologists. All pathology slides from NTP studies are housed in the NTP archives and are available for review by anyone interested.

Q: How does NTP classify evidence of carcinogenicity?
A: The four classifications of evidence of carcinogenicity are:

  • clear evidence (the highest level),
  • some evidence,
  • equivocal evidence, and
  • no evidence (the lowest level).
  • If there is insufficient evidence to draw conclusions, NTP uses the term “inadequate study.”

Q: Could the results be due to thermal changes from RFR, or the result of stress to the animals?
A: It’s unlikely. The NTP studies were performed at power levels that limited heating to less than 1 degree Celsius. (Note: The Federal Communications Commission (FCC) and the U.S. Food and Drug Administration (FDA) currently allow 1 degree Celsius local tissue heating for cell phones operating at maximal power, as would occur when in an elevator or when far away from a base station.) DIFFERENT GENERATIONS OF WIRELESS TECHNOLOGY AND FUTURE PLANS

Q: This study was conducted using radiation from 2G and 3G devices. Are the levels the same with 4G? Do we have any idea if the rollout of 5G will expose us to different types of radiation or radiation in a higher volume?
A: Current wireless communication networks like 4G still use 2G and 3G technologies for voice calls and texting; 4G, 4G-LTE, and 5G networks were developed to support increased data needs like streaming video or instantly downloading email with attachments. These newer technologies use different methods of cell phone signal modulation than NTP used in the study. It is difficult to compare 5G to the current and previous generations of wireless networks. In general, NTP scientists are still trying to understand the impact of exposure to RFR on biological tissues, regardless of “G” (generation). But, to complicate matters more, aspects of the 5G networks will use a vastly different set of frequencies (>6000 MHz) than those currently in use with 2G, 3G, and 4G-LTE (700–2700 MHz) networks. It is well known that absorption of RFR at these higher frequencies differs significantly from absorption at the lower frequencies in that the shorter wavelengths of the high frequencies cannot penetrate nearly as deep into the body. Therefore, much of the absorption at the higher frequencies occurs in the skin and would not penetrate deep enough to reach the heart, brain, and adrenal gland, which developed tumors in NTP’s studies at 900 MHz. Additionally, since the higher frequency signals in the 5G network have shorter-reaching distances and are unable to penetrate physical barriers, substantially more transmitters and antenna are required to provide coverage to consumers. Therefore, the proximity of humans to the antenna may decrease, which could potentially lead to higher exposures. However, because the antennas will be widely dispersed, the power levels of RFR for 5G may be lower than those currently used for 2G, 3G, and 4G. At this point, it is unclear exactly whether, or to what degree, human exposure to RFR will change. What is known regarding 5G, however, is that while continuing to be exposed to the current frequencies, wireless consumers will be exposed to the higher frequencies as well.

Q: How do the exposures relate to WiFi?
A: NTP did not study the frequencies and modulations used for WiFi.

Q: Are there additional studies planned by NTP?
A: NTP is collaborating with the National Institute of Standards and Technology (NIST) on additional short-term exposure studies in smaller cell phone RFR exposure chambers. These studies will focus on further clarifying what NTP learned in the long-term studies and investigating the possibility of DNA damage in exposed tissues. Additionally, the new chambers have increased flexibility with respect to exposure scenarios and increased signal generating capabilities, which allow NTP to test the different modulations and frequencies used in 3G and 4G-LTE networks. NTP scientists are also looking at efficient ways to address some of the issues that are emerging regarding RFR exposures and 5G. They hope to begin the new RFR studies in 2020.

Q: How else will the new chambers be used?
A: After verifying that the new, smaller chambers are working properly, NTP scientists want to see if the effect that they saw on DNA damage in their studies is replicable in these follow-up experiments. This will give scientists more confidence in the results of the initial studies, as reproducibility is an important concept in any scientific study, especially one as complex as studying cell phone RFR.

Additional Questions

Q: Does NTP have any say in the regulatory decision of cell phones?
A: Regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the Federal Communications Commission (FCC) are responsible for evaluating the potential risk associated with exposure to RFR from wireless devices and the compliance of the devices to those standards, respectively. These agencies evaluate pertinent data in laboratory animals and the results from any studies that may be available in humans to identify hazards and conduct risk assessments that establish guidelines for safe exposures in humans. Questions regarding the adequacy of current exposure guidelines, regulatory limits, and potential risk should be directed to those agencies.

Q: Can you tell us more about the process for the final review by external experts?
A: A panel of scientific experts from outside of NTP conducted a thorough scientific review of the NTP conclusions during a meeting at NIEHS on March 26–28, 2018. The meeting was open to the public and webcasted, and videos of the meeting are available on the NTP web page at ntp.niehs.nih.gov.

Q: Why did NTP adopt the peer review recommendations rather than sticking with its original draft conclusions?
A: In the end, the peer review recommendations represented the consensus from the three-day peer review meeting in March 2018. These recommendations largely overlapped with conclusions in the draft NTP report, but the panel recommended stronger levels of evidence for several tumors. NTP supports this consensus and appreciates the thoughtful input from all involved. A range of factors are considered when interpreting scientific evidence and drawing conclusions. NTP’s meeting in March gave NTP scientists a chance to examine and debate these factors in detail for the radiofrequency radiation studies.

Q: Why did you release the draft reports to the public prior to peer review?
A: This has been part of NTP’s transparent review process for its entire 40-year history. It gives NTP’s many stakeholders a chance to weigh in before reports are final. The public comments were then collected and provided to the panel of expert reviewers for their consideration, per the usual protocol.”