# CENTER FOR OEVICES & RADIOLOGICAL HEALTH

> Briefs, arguments, decisions, and more.

URL: https://www.frixlaw.com/law-library/documents/tribal%3Around_valley%3Ab7a39fbd4fe2ab57

## Record

- **Collection:** Tribal code
- **Document type:** Tribal code

## Text

U.S. FOOD & DRUG
CENTER FOR OEVICES & RADIOLOGICAL HEALTH

Review of Published Literature between
2008 and 2018 of Relevance to
Radiofrequency Radiation and Cancer
February 2020

Ii

Review of Published Literature between
2008 and 2018 of Relevance to
Radiofrequency Radiation and Cancer

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TABLE OF CONTENTS.
I.

EXECUTIVE SUMMARY.................................................................................................................................... 4

II.

ABBREVIATIONS ......................................................................................................................................... 7

III.

INTRODUCTION .......................................................................................................................................... 8

IV.

IN VIVO STUDIES....................................................................................................................................... 11

A.
B.

SEARCH STRATEGY ............................................................................................................................................11
SUMMARY AND LIMITATIONS OF IN VIVO STUDIES...................................................................................................14
1.
National Toxicology Program RF Reports 2018.......................................................................................14
2.
Papers Meeting the In vivo Review Criteria. ...........................................................................................18
C.
CONCLUSIONS FROM IN VIVO REVIEW. .................................................................................................................32

V.

EPIDEMIOLOGICAL STUDIES...................................................................................................................... 35
A.
B.

SEARCH STRATEGY............................................................................................................................................35
SUMMARY OF RESULTS. .....................................................................................................................................36
1.
Studies reporting overall evidence that does not counter a global null hypothesis on tumor risk in
relation to cell phones...................................................................................................................................................36
2.
Studies Reporting Cvidence on Possible Tumor Risk Modification in Relation to Tumor Types and/or
Cell Phone Usage Practices. ..........................................................................................................................................37
3.
Outcome of Interest – Brain Tumors (Glioma and Meningioma)............................................................38
4.
Outcome of Interest – Acoustic Neuroma, or Vestibular Schwannoma. .................................................39
5.
Outcome of Interest – Parotid Gland Tumors. ........................................................................................39
6.
Outcome of Interest – Skin Cancers. .......................................................................................................40
7.
Outcome of Interest – Leukemia. ............................................................................................................40
8.
Putative Effect Modifier – Laterality of Tumor in Relation to Laterality of Phone Use. ..........................40
9.
Putative Effect Modifiers – Location and Size of Tumors in Relation to Mobile Phone Use....................41
10.
Evidence on Tumor Risk in Relation to Cell Phones from Studies Using RF Exposure Estimates Other
Than Phone Usage Practices.........................................................................................................................................42
C.
OVERALL LIMITATIONS OF EPIDEMIOLOGY DATA.....................................................................................................44
1.
Data Quality Affected by Limitations of RF Exposure Measurements.....................................................44
2.
Strong Biases Affecting Data Analysis and Interpretation. .....................................................................44
3.
Lack of Evidence Based on the U.S. Population.......................................................................................45
4.
No Overall Risk Increase, with Some Evidence Pointing at Possible Subgroup Effects. ...........................46
D.
SUMMARY AND LIMITATIONS OF INDIVIDUAL EPIDEMIOLOGY STUDIES REVIEWED..........................................................48
E.
CONCLUSIONS FROM REVIEWED EPIDEMIOLOGICAL STUDIES.....................................................................................87
VI.

REFERENCES ............................................................................................................................................. 88

A.
B.
C.
D.
E.
F.

IN VIVO ARTICLES, INITIAL SEARCH.......................................................................................................................88
IN VIVO ARTICLES INCLUDED IN EMF PORTAL SEARCH. ............................................................................................96
IN VIVO ARTICLES FOUND BY GENOTOXICOLOGY RELEVANT SEARCH. ..........................................................................96
IN VIVO ARTICLES FOUND IN NULL RESULT SEARCH. ................................................................................................98
IN VIVO ARTICLES SUGGESTED BY PEER REVIEWER. .................................................................................................98
IN VIVO ARTICLES MEETING SEARCH CRITERIA......................................................................................................100

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G.
IN VIVO ARTICLES NOT MEETING SEARCH CRITERIA...............................................................................................104
H.
REFERENCES USED FOR EPIDEMIOLOGICAL REVIEW. ..............................................................................................106
I. OTHER EXTERNAL (NON-FDA) REVIEWS. ................................................................................................................112

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I.

EXECUTIVE SUMMARY

As part of our core mission to protect and promote the public health, the FDA continually
monitors new scientific evidence that might impact our understanding of the safety profile of
medical devices and radiation-emitting electronic products that Americans are exposed to every
day. The Agency has taken a comprehensive approach to evaluating the available scientific
evidence regarding the impact of radiofrequency radiation (RFR) exposure on human health.
The FDA has completed an updated radiofrequency (RF) exposure risk analysis based on
relevant peer-reviewed in vivo (animal) and epidemiological studies published from January 1,
2008 to August 1, 2018 for in vivo studies, and from January 1, 2008 to May 8, 2018 for
epidemiological studies. This risk analysis was scoped to assess any possible causal relationship
between RFR exposure and the formation of tumors.
In this technical report we provide a detailed summary of the substantial body of scientific
evidence that has informed our determination regarding potential adverse health effects in
humans caused by RFR exposures and the risk analysis we performed. As discussed in this report,
this determination is supported by the considerable body of peer-reviewed scientific publications
as well as public registries of, for example, cancer rates that show a slight decrease in brain
tumors despite the enormous increase in cell phone use over the last two decades. This technical
report summarizes the information on which the FDA has based its conclusion and was peerreviewed by scientists specialized in areas such as epidemiology, health physics and public health,
and the report incorporates comments by these external scientific reviewers. Subsequently, the
report and our analysis were updated with more recent, relevant peer-reviewed publications
through August 2019.
In the period covered by this risk analysis, there have been approximately 125 articles that
are most relevant for the study 1 of any effects of RFR on animals. However, none have adequately
demonstrated that localized exposure of RFR at levels that would be encountered by cell phone
users can lead to adverse effects. Section IV of the report provides a detailed description of the in
vivo studies.
In vivo studies assessing possible adverse or other effects of RFR are extremely challenging
studies to design and undertake for several reasons, including the engineering considerations of
applying an RFR field to animals that may specifically simulate, for example, the localized
Note that in this technical report, the terms study, experiment, investigation, and similar terms are used
interchangeably.
1

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exposure of tissue to a cell phone held to the ear. Many researchers therefore undertake wholebody exposure of the animals to RFR exposure to avoid the need to restrain the animals during
each exposure. However, the effects of whole-body exposure do not reflect the real-world
situation of localized exposure to the ear and head from a handset as used by humans.
It is difficult to measure and model with adequate accuracy and precision the specific dose
of RFR that each animal absorbs in each study. Additionally, it is difficult to separate the effects of
direct RFR exposure, if there are any that occurred, from the well-documented indirect effects of
temperature rise (the only established biological effect of RFR on tissue) and the stress
encountered by experimental animals, which confounds reported outcomes.
Given the difficulties of conducting in vivo studies on the effects of RFR exposure
experienced by humans as described above and the widespread use of cell phones, strong
epidemiological studies generally provide more relevant and accurate information. In vivo studies
are of immense value in medical science, but they are less useful than studying effects on the
human population, where that is feasible.
Based on the FDA’s ongoing evaluation, the available epidemiological and cancer incidence
data continues to support the Agency’s determination that there are no quantifiable adverse
health effects in humans caused by exposures at or under the current cell phone exposure limits.
In the last decade, there have been approximately 70 relevant epidemiological studies that
have been published as peer-reviewed scientific evidence. As part of our ongoing monitoring
activities, we have analyzed these publications for specific outcomes, including brain and other
tumors as well as other potential adverse events. While some studies suggest a possible link
between, for example, “heavy” users of cell phones and some tumors, there is no clear and
consistent pattern that has emerged from these studies and these studies were subject to flaws
and inaccuracies.
Epidemiological studies can also be subject to significant limitations; for instance, exposure
assessment is understandably limited and potentially problematic. Specifically, cell phone usage is
not necessarily an appropriate proxy for total RF exposure compared with, for example, the ability
to capture total cumulative RF exposure from all relevant sources, including for example other
communications devices. There are no direct measurements of RF exposure outside of a
laboratory setting; rather, studies generally rely on the participants to track and self-report.
Therefore, the actual RFR exposure remains an estimate at best. Based on the available data,
there is no clear evidence as to whether frequency, duration, or intensity of exposure is the most
important factor in assessing exposure and, as discussed above, there is no clear way to measure
or estimate each of these factors. Additionally, there are generally various biases (e.g., recall
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accuracy) and misclassification issues when individuals are asked to recollect behavior patterns.
See Section V of the report for a summary of the epidemiological studies.
Based on the studies that are described in detail in this report, there is insufficient evidence
to support a causal association between RFR exposure and tumorigenesis. There is a lack of clear
dose response relationship, a lack of consistent findings or specificity, and a lack of biological
mechanistic plausibility.

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II.
ASP
APC
APD
BS
CDMA
CNS
DCS
DMBA
EMF
FDA
GFAP
GSM
HR
IARC
ICNIRP
IEI- EMF
IRR
NAS
NeuN
NTP
OR
RF
RFR
ROS
RR
SAR
SCENHIR
SEER
SSM
TCSE
UMTS
USC
WB
WCDMA

ABBREVIATIONS

Annual Summarized Power
Annual Percentage Change
Annual Power Density
Base Station
Code-Division Multiple Access
Central Nervous System
Digital Cellular System
12-Dimethylbenz(a)anthracene
Electromagnetic Field
US Food and Drug Administration
Glial Fibrillary Acidic Protein
Global System for Mobile Communications
Hazard Ratio
International Agency for Research on Cancer
International Commission on Non-Ionizing Radiation Protection
Idiopathic Environmental Intolerance attributed to Electromagnetic Fields
Incidence Rate Ratio
National Academy of Sciences
Neuron-Specific Nuclear Protein
National Toxicology Program
Odds Ratio
Radiofrequency
Radiofrequency Radiation
Reactive Oxygen Species
Relative Risk
Specific Absorption Rate
Scientific Committee on Emerging and Newly Identified Health Risks
Surveillance Epidemiology, and End Results
Swedish Radiation Safety Authority
Total Cumulative Specific Energy
Universal mobile telecommunications system
United States Code
Whole Body
Wideband Code Division Multiple Access
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III.

INTRODUCTION

The FDA is responsible for, among other things, ensuring the safety of electronic products
that emit radiation, such as televisions and cell phones. These types of products are part of
Americans’ daily life, and we take our duty to protect consumers with the utmost gravity.
The FDA is required under 21 USC § 360ii(b)(1) to collect and make available, through
publications and other appropriate means, the results of, and other information concerning,
research and studies relating to the nature and extent of the hazards and control of electronic
product radiation; and make such recommendations relating to such hazards and control, as
appropriate. The FDA continually monitors new information and, when appropriate, undertakes
formal risk analysis.
The FDA’s doctors, scientists, and engineers have reviewed many sources of scientific and
medical evidence related to the possibility of adverse health effects from RFR exposure in both
humans and animals. We have relied extensively on a myriad of scientific evidence developed
over many years to help inform our regulatory thinking regarding RFR exposure. Standard practice
in scientific evaluation is to use the broadest set of credible information available and then to
assess the significance of that information to the question at hand. The most commonly used
source of information is the set of peer-reviewed publications that are indexed through Medline
and typically retrieved through PubMed. The FDA uses this source as well as more specific sources
of information, where appropriate. For the ongoing monitoring of possible effects of RFR, for
example, we also use the Electromagnetic Frequency (EMF) Portal 2 as a potential source for peerreviewed papers to ensure as wide a coverage as possible.
The FDA also considers independent studies that are separately published, although the
Agency often undertakes its own review of the papers analyzed in those reports in order to assess
validity and applicability to the United States. Recent examples of independent studies that the
FDA considered include the 2013 International Agency for Research on Cancer (IARC) study3, the
European Commission’s Scientific Committee on Emerging and Newly Identified Health Risks 4, the

EMF Portal (https://www.emf-portal.org/en/article/overview/mobile-communications-med-bio/g-85/t85002?pageSize=50&pageIndex=0&view=list#level-4).
3
IARC (2013). “Non-Ionizing Radiation, Part 2: Radiofrequency Electromagnetic Fields” Monograph 102.
2

Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR). 2015. 'Potential health
effects of exposure to electromagnetic fields (EMF) ', European Commission Report.
4

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Swedish Radiation Safety Authority’s (SSM) Scientific Council reports on EMF 5, and the 2017
reports from the National Toxicology Program studies on the effects of whole body irradiation of
rodents6, as well as other sources as discussed in this report.
In this peer-reviewed technical report, we are providing a detailed summary of our updated
RF exposure risk analysis based on relevant and available peer reviewed scientific information
published from January 1, 2008 to August 1, 2018 for in vivo studies, and from January 1, 2008 to
May 8, 2018 for epidemiological studies. This technical report is peer-reviewed by scientists
specialized in areas such as epidemiology, health physics and public health, and the report
incorporates comments by these external scientific reviewers.
The conclusions presented in this report are the result of a comprehensive analysis of
information published within the following scope:
i.

The main health outcome focused on relates to the onset of cancer formation, known
as tumorigenesis.
We reviewed articles on RF exposure in general and did not limit the analysis to any
specific power levels or modulations used by cell phones.
The frequency range considered was 100 KHz to 6 GHz 7.
These articles were indexed on Medline and typically retrieved through PubMed. The
EMF portal (https://www.emf-portal.org/en) was also used to ensure as wide a coverage
of the search as possible.
Only articles that had been peer-reviewed were included, other than the final NTP in
vivo reports which were published in November 2018, and are available from

ii.
iii.
iv.

v.

https://ntp.niehs.nih.gov/

vi.

The literature review was conducted using articles published from January 1, 2008 to
August 1, 2018 for in vivo studies, and from January 1, 2008 to May 8, 2018 for

See e.g., Swedish Radiation Safety Authority (SSM)’s 2018. "Recent Research on EMF and Health Risk
Twelfth report from SSM’s Scientific Council on Electromagnetic Fields, 2017." In.: Swedish Radiation Safety
Authority (SSM); Swedish Radiation Safety Authority (SSM)’s SSM's Independent Expert Group on
Electromagnetic Fields. 2010. "Recent Research on EMF and Health Risk Seventh annual report from SSM:s
Independent Expert Group on Electromagnetic Fields, 2010."
5

National Toxicology Program (2018) Technical Report TR-595. Toxicology and Carcinogenesis Studies in
Hsd:Sprague Dawley SD Rats Exposed to Whole-Body Radio Frequency Radiation at a Frequency (900 Mhz) and
Modulations (GSM and CDMA) Used by Cell Phones; and National Toxicology Program (2018) Technical Report
TR-596. Toxicology and Carcinogenesis Studies in B6C3F1/N Mice Exposed to Whole-Body Radio Frequency
Radiation at a Frequency (1,900 MHz) and Modulations (GSM and CDMA) Used by Cell Phones.
6

This is the frequency range in which limits are based on specific absorption rate (SAR). Above 6
GHz power density is the appropriate metric for determining safe exposure limits.
7

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vii.

epidemiological studies. These time periods overlap with the timeframe from the prior
review on RF research needs undertaken by the National Academy of Sciences
(available from https://www.nationalacademies.org/) and published in 2008.
In vitro studies were excluded as the analysis was focused on assessing evidence for
tumorigenesis in vivo.

There were two main foci for the review: i) epidemiological evidence for the existence of
any tumor risk from cell phone usage, and ii) in vivo (animal) studies assessing any causality of
tumorigenesis from of RFR exposure.
The following sections of this technical report provide a summary of the currently
available scientific evidence related to RF exposure safety and any causal relationship
between such exposure and the formation of tumors that might impact the previous FDA
findings.

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IV.

In vivo Studies

This section provides a summary of the in vivo studies reviewed. Section IV.A. describes the
search strategy and search terms we used to find relevant in vivo studies. Section IV.B. provides a
summary of the studies reviewed along with a description of the limitations. In Section IV.C, the
FDA’s conclusions based on the reviewed and assessed in vivo studies is provided.
A. Search Strategy
The literature search to identify all relevant in vivo studies was conducted in 3 parts. The
goal of the review was to consider all evidence from in vivo animal exposure to RF from peerreviewed papers which had endpoints related to tumorigenesis and involved a broad set of
search terms as described below. The date range used for in vivo studies was January 1, 2008
through August 1, 2018. A wide search was initially conducted, which identified only a few
relevant articles. The criteria were then expanded to include in vivo genotoxicity studies
where the protocols involved exposure of animals to RF. Finally, a search identifying null
results was undertaken to identify studies involving tumorigenesis, but which failed to find
evidence for any link. This review is focussed on human cancer risk and consequently does not
directly investigate RF mechanistic studies (in vitro) or review articles that pertain to in vitro
RF exposure. The pool of potential papers was identified using the following search on
PubMed:
("radio waves"[MeSH Terms] OR ("radio"[ALL FIELDS] AND "waves"[ALL FIELDS]) OR "radio waves"[ALL
FIELDS] OR "cell phone?"[ALL FIELDS] OR “mobile phone”[ALL FIELDS] OR "Radio Waves/adverse
effects"[MeSH] OR "Electromagnetic Fields/adverse effects"[MAJR] OR "Electromagnetic Fields"[MeSH] OR
“radiofrequency"[ALL FIELDS] AND (cancer[sb] OR "Neoplasms"[MeSH] OR “carcinogenicity”[ALL FIELDS])
AND ("Rodentia"[MeSH] OR "Lagomorpha"[MeSH] OR rat? OR mouse OR mice OR rabbit?) AND
English[lang]) NOT ("Humans"[MeSH] OR "MRI"[ALL FIELDS] OR "ablation"[ALL FIELDS] OR "Ablation
Techniques"[MeSH] OR "Imaging"[ALL FIELDS] OR "Therapy"[ALL FIELDS] OR "ELF"[ALL FIELDS] OR
"Synthesis"[ALL FIELDS] OR "cognitive"[ALL FIELDS] OR "60 Hz"[ALL FIELDS] OR "50 Hz"[ALL FIELDS] OR
"hyperthermia"[ALL FIELDS] OR "healing"[ALL FIELDS] OR "adaptive"[ALL FIELDS] OR "In vitro"[ALL FIELDS]
OR "extraction"[ALL FIELDS] OR "microwave-assisted"[ALL FIELDS] OR "paramagnetic"[ALL FIELDS] OR
"Expression of "[ALL FIELDS]) AND ("2008/01/01"[Date - Publication] : "2018/08/01"[Date - Publication])

This initial search found 93 papers for consideration. The parameters after the ‘NOT’
term removed many, but not all, results that were outside the scope of the criteria for
inclusion. The 93 articles were evaluated according to the search criteria. Articles not included
in this review included many that were not assessing evidence of an adverse health effect
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from RF exposure, many others had endpoints that were unrelated to tumorigenesis, and
smaller sets of papers that either did not include exposure of live animals or in which the
exposures were to extremely low frequency electromagnetic radiation rather than to RF.
The search results were compared to the bibliography of the International Agency for
Research on Cancer’s (IARC) Monograph 102’s, Non-ionizing radiation, Part 2: Radiofrequency
electromagnetic fields, animal experiments chapter (IARC 2013: 281 - 83). There were 4
papers in that bibliography that were not found by the search, but they were all published
before 2008. Similarly, the search results were compared with the articles in an EMF portal
search 8 for experimental studies relevant to RF and cancer and found 3 papers published after
2008 that were missed by the search. The 3 EMF portal papers were added to the pool of
papers for consideration.
Search terms for the two supplementary searches are below:
o

Genotoxicity Search, which added 20 papers.

(("radio waves"[MeSH Terms] OR ("radio"[All Fields] AND "waves"[All Fields]) OR "radio
waves"[All Fields] OR "cell phone?"[all fields] OR “mobile phone”[all fields] OR "Radio Waves/adverse
effects"[Mesh] OR "Electromagnetic Fields/adverse effects"[MAJR] or "Electromagnetic Fields"[Mesh]
or “radiofrequency”[all fields]) AND (micronucleus or comet or genotox*) AND ("Rodentia"[Mesh] OR
"Lagomorpha"[Mesh] or rat? or mouse or mice or rabbit?) AND English[lang]) NOT ("Humans"[Mesh]
OR "MRI"[ALL Fields] OR "ablation"[ALL FIELDS] OR "Ablation Techniques"[Mesh] OR "Imaging"[ALL
FIELDS] OR "Therapy"[ALL FIELDS] OR "Synthesis"[ALL FIELDS] OR "cognitive"[ALL FIELDS] OR "60
Hz"[All Fields] or "50 Hz"[All Fields] or "ELF"[All Fields] OR "hyperthermia"[all fields] OR "healing"[All
Fields] or "adaptive"[all fields] or "In vitro"[all fields] or "extraction"[all fields] or "microwaveassisted"[all fields] or "paramagnetic"[all fields] or "Expression of "[all fields]) AND ("2008/01/01"[Date
- Publication] : "2018/08/01"[Date - Publication])
o

Studies null (negative) results, which added 6 papers.

(("radio waves"[MeSH Terms] OR ("radio"[All Fields] AND "waves"[All Fields]) OR "radio
waves"[All Fields] OR "cell phone?"[all fields] OR “mobile phone”[all fields] OR "Radio Waves/adverse
effects"[Mesh] OR "Electromagnetic Fields/adverse effects"[MAJR] or "Electromagnetic Fields"[Mesh]
or “radiofrequency”[all fields]) AND (“no evidence”[ALL Fields] or “does not alter”[ALL Fields] or “not
provide any evidence”[all fields] or ((“not” OR “no”) NEAR “effect”) or ((“not” OR “no”) NEAR
“evidence”) or “not promote”[ALL FIELDS] or (“not” NEAR “cause”)) AND ("Rodentia"[Mesh] OR
"Lagomorpha"[Mesh] or rat? or mouse or mice or rabbit?) AND English[lang]) NOT ("Humans"[Mesh]
OR "MRI"[ALL Fields] OR "ablation"[ALL FIELDS] OR "Ablation Techniques"[Mesh] OR "Imaging"[ALL

8

https://www.emf-portal.org/en

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FIELDS] OR "Therapy"[ALL FIELDS] OR "Synthesis"[ALL FIELDS] OR "cognitive"[ALL FIELDS] OR "60
Hz"[All Fields] or "50 Hz"[All Fields] or "ELF"[All Fields] OR "hyperthermia"[all fields] OR "healing"[All
Fields] or "adaptive"[all fields] or "In vitro"[all fields] or "extraction"[all fields] or "microwaveassisted"[all fields] or "paramagnetic"[all fields] or "Expression of "[all fields]) AND ("2008/01/01"[Date
- Publication] : "2018/12/31"[Date - Publication])

The list was compared with bibliographies from recently published expert reports to
ensure a thorough assessment. The expert reports used for bibliographic comparison included
the European Scientific Committee on Emerging and Newly Identified Health Risks report,
Potential health effects of exposure to electromagnetic fields (EMF)(SCENIHR 2015), the
Swedish Radiation Safety Authority (SSM)’s Scientific Council on Electromagnetic Fields’ 7th
(2010) through 12th (2018) reports (SSM's SCEF 2014, 2010, 2013, 2015, 2016, 2018), and the
series of reports from the Health Council of the Netherlands (Health Council of the
Netherlands 2013, 2014, 2016). No other animal experiment papers that might fit the criteria
from the January 1, 2008 through August 1, 2018 timeframe were identified.
The pool of papers identified via the above process was then narrowed down to papers
that considered experiments on live mammals (rats, mice, or rabbits) with endpoints related
to cancer, carcinogenesis, tumorigenesis, oncogenesis, or genotoxicity. This reduced the list to
26 papers that were reviewed. After an initial review, 3 papers were found to be outside the
report scope and were eliminated from further analysis (one had been retracted, one was an
exposure of excised bones, and the third involved exposure of animals to pulsed magnetic
fields not RF).
A peer reviewer identified 31 papers more papers as possibly relevant. About half of
these papers fell outside our inclusion criteria. There were a few papers regarding RFR
exposure of non-mammal animals. A few papers used frequencies above 6 GHz. A couple of
papers had endpoints outside of our scope. The other papers that were excluded used cell
phones as the source of RFR which renders these studies results uninterpretable. Dosimetry
and modeling to calculate the SAR of the exposed animas animals is difficult with a defined
RFR source. A normal cell phone is not a reproducible source of RFR.
A review of the 39 papers that met the inclusion criteria is described below. Additionally,
the final National Toxicology Program reports on exposure of rats and mice to radiofrequency
radiation and an associated paper, Effect of cell phone radiofrequency radiation on body
temperature in rodents: Pilot studies of the National Toxicology Program's reverberation
chamber exposure system (Wyde et al. 2018) were also reviewed. A complete list of the
papers found by the searches for this section appears in Section VI References.

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B. Summary and Limitations of In vivo Studies.
1. National Toxicology Program RF Reports 2018.
The National Toxicology Program released reports on whole-body exposures of rats and
mice to radiofrequency radiation that was modulated using the signal patterns commonly used by
third generation wireless mobile telecommunications technology (3G). The NTP study is the most
comprehensive study of the impact of RFR on tumorigenesis to date. While the FDA does not
agree with all the conclusions of the NTP RFR study, we do acknowledge that the study has added
to the collective database and provided possible pathways for further investigation. The effects of
a whole-body RFR exposure are not predictive of the results for a local RFR exposure in the same
animal. Thus, results of whole-body RFR exposure to rats and mice cannot be directly related to
the results of the local RFR exposure a human receives while using a cell phone.
There were three components to the NTP study. The first component was a 5-day thermal
pilot study at specific absorption rates (SARs) of 4 – 12 W/kg (Wyde et al. 2018) which was
published separately from the remaining portions of the study covered in NTP’s reports. The
second component was a 28-day pre-chronic toxicology study in mice and rats. The last
component was a 2-year toxicology and carcinogenicity study in mice and rats9. The exposure
system used in all three components of this study was a specially engineered reverberation
chamber designed with the goal of providing nearly uniform whole-animal exposure without the
need for stress inducing animal restraint systems (Capstick et al. 2017). The exposed rats and
mice were exposed to either global system mobile communication (GSM) or code division
multiple access (CDMA) modulated signals for 18 hours and 20 minutes / day in 10 minutes on
and off cycles. The rats were exposed starting in utero to GSM- or CDMA-modulated signals at 900
MHz. The mice were exposed to either GSM- or CDMA-modulated signals at 1900 MHz. The
results discussed here are from Wyde et al. 2018 and the NTP technical reports released to the
public in November 2018.
The 5-day pilot study examined the impact of animal size on the subcutaneous
temperatures in mice and rats, aged mice and rats, as well as pregnant rats. The aged rats in the
NTP report on Rats https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr595_508.pdf?utm_source=direct&utm_medium=prod&utm_cam
paign=ntpgolinks&utm_term=tr595 &
9

NTP report on Mice https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr596_508.pdf?utm_source=direct&utm_medium=prod&utm_cam
paign=ntpgolinks&utm_term=tr596
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pilot study were at most 270 days old while rats in the 2-year study reached 763 days old. The
effect of animal age increasing from 270 days to 763 days was not investigated and could have
resulted in further age-related weakening of the rats’ thermoregulatory capacity. The
temperatures measured were subcutaneous and not a measure of the core temperature of the
animal. No temperature measurements were taken in the animals housed in RF environments
during the 2-year study. The pilot study confirms that aged animals or pregnant animals cannot
thermoregulate as well as young, non-pregnant animals. The study revealed that there were
some incidences of increased subcutaneous temperature (>1°C) in aged rats exposed to 6 W/kg
GSM radiation or 900 MHz CDMA RF radiation but not in young rats. Likewise, there were
sporadic temperature increases in young or old mice exposed up to 12 W/kg GSM and CDMA
1900 MHz RFR. Measurements were made when RFR was off, and as such, allowed for external
surface cooling which likely reduced the measured subcutaneous temperatures.
Additionally, NTP’s assessment of organ SAR showed that local SAR in skin and fat was less
than the whole-body and internal organ SAR which was higher. An animal’s core temperature
cannot be accurately estimated from subcutaneous temperature measurements. Considering the
information, the animals’ core temperature was likely to have exceeded the measured
subcutaneous temperature. It is probable that during the 2-year study, as the male rats aged their
core temperatures eventually routinely exceeded a 1 °C rise in the 6 W/kg SAR exposure group.
We believe that this study indicates a need for a greater understanding of the impact of cyclic
heating and declining thermoregulation capacities of aged mammals.
The NTP has established 5 levels of evidence of carcinogenic activity that are used in NTP
reports. The highest level is Clear Evidence. This is a dose-related (i) increase of malignant
neoplasms, (ii) an increase of a combination of malignant and benign neoplasms, or (iii) marked
increase of benign neoplasms if there is an indication from this or other studies of the ability of
such tumors to progress to malignancy. The next lower level of evidence is called Some Evidence.
For this level the test agent-related increased the incidence of neoplasms in which the strength of
the response is less than that required for clear evidence. Equivocal Evidence is the next lower
level. This is a marginal increase of neoplasms that may or may not be test agent-related. The two
lower levels are No Evidence and Inadequate Study.
The histopathological analysis of the RF-exposed mice was reported as Equivocal Evidence.
For GSM-modulated exposed male mice, the combined incidence of fibrosarcoma, sarcoma, or
malignant fibrous histiocytoma of the skin and the combined incidence of alveolar/bronchiolar
adenoma or carcinoma in the lung were described as marginally increased. For GSM-modulated
exposed female mice, there was a marginally increased incidence of malignant lymphoma. For
CDMA-modulated exposed male mice there was increased incidence of hepatoblastoma of the
liver. For CDMA-modulated exposed female mice malignant lymphoma incidence was marginally
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increased. All other tissues examined showed no test agent-related increase in neoplasms. The
results shown for some of these equivocal results are above the rate for the sham control, but
many are within the historical control range. This suggests that the equivocal results are
describing fluctuations in the natural background of these tumors and not an increase caused by
exposure to RF radiation.
Genetic toxicology testing was performed using the micronucleus assay and the comet assay
in the RF-exposed mice and rats as part of their 14-week intermediate analysis. There was an
increase in apparent DNA damage in male rats exposed to CDMA RFR, but the increase was not
statistically significant. Other noted increases in DNA damage were also considered to be
equivocal, and no statistically significant increases in DNA damage was observed in female rats or
in either mouse sex. All results from the micronucleus assay in rats and mice were negative.
The two-year carcinogenesis and toxicology study showed an unexpected finding in male
rats. The exposed groups of animals had greater survival rates than the animals in the sham
control. This might be attributed to amelioration of chronic progressive nephropathy: animal core
temperature elevation resulting in reduced food consumption and increased water consumption
in the RFR exposed animals could have improved the survival of the exposed animals. NTP’s
stated that their statistical analysis took these differences in survival rate into account during
study analysis. The public health impact of these observations is unclear.
NTP’s study conclusions in their final report for the two-year exposures in rats were:
Clear evidence of carcinogenic activity
o

Incidences of malignant schwannoma in the heart of male rats for both GSM and CDMA.

Some evidence of carcinogenic activity (considered to be related to cell phone RFR
exposure)
o
o

Incidences of malignant glioma in the brain of male rats for both GSM and CDMA
Incidences of pheochromocytoma (benign, malignant, or complex combined) in the adrenal
medulla of male rats for GSM

Equivocal evidence of carcinogenic activity (may have been related to cell phone RFR
exposure).
o
o
o
o

Incidences of adenoma or carcinoma (combined) in the prostate gland of male rats for GSM.
Incidences of benign or malignant granular cell tumors in the brain of male rats for GSM.
Incidences of adenoma in the pars distalis of the pituitary gland of male rats for GSM and CDMA
Incidences of pancreatic islet cell adenoma or carcinoma (combined) of male rats for GSM.
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o
o
o
o
o

Incidences of adenoma or carcinoma (combined) in the liver of male rats for CDMA.
Incidences of malignant schwannoma in the heart of female rats for GSM
Incidences of malignant glioma in the brain of female rats for CDMA
Incidences of malignant schwannoma in the heart of female rats for CDMA
Incidences of pheochromocytoma (benign, malignant, or complex combined) in the adrenal
medulla of female rats for CDMA.

NTP reported that two-year exposure to GSM- or CDMA-modulated RFR revealed an
increase in malignant schwannoma in in the heart of male rats. NTP also reported that the
incidence of schwannomas in all locations was not statistically significant compared to the control
group. Cardiomyopathy was also seen in rats exposed to higher SARs (3 or 6 W/kg). The historical
controls reported in NTP’s preliminary reports published in 2016 (tumor incidence over time in a
larger population of similar control rats in NTPs experiments) had approximately 9 out of 699
control rats that had malignant heart schwannomas (1.3% and a range of 0-6%). Only male rats
exposed to higher SAR (6 W/kg) have higher percentage of malignant schwannoma then the
maximum range of historical controls. However, NTP chose to use only three studies for historical
controls in the final report. This set of studies had control groups of 50 rats each. There was a 2%
incidence of cardiac schwannoma in 2 of the studies and no occurrences in the third study. NTP
also determined (Wyde et al. 2018) that old, large male rats did not thermoregulate as well as
younger rats. This is a possible indication of thermal confounding at 6.0 W/kg. It is not clear if
there is a relationship between malignant schwannoma and cardiomyopathy.
NTP reported weaker responses to both modulations were found in other tissues. Glioma
was one of the weaker responses and was not statically significant. The sham controls for gliomas
show 0% incidence while the tumor incidence over time in a larger population of similar control
rats in NTP experiments has a percent incidence of approximately 2-4%. Only the lowest RF
exposure, 1.5 W/kg CDMA-modulation exceeds this historical control. Other tumors with
increased incidence included pituitary tumors, benign and malignant pheochromocytoma,
adenoma and carcinoma of the prostate. However, the highest increases were not consistently in
the highest SARs and in some cases (adrenal medulla) the tumor incidence over time in control
animals from other NTP experiments was as high as 28%.
The specific criteria for the categorization of data into the specific outcomes (e.g., clear
evidence, etc.) remains unclear and there are inconsistencies in some of the interpretation of the
data and the conclusions that have been drawn. As an example, the incidence of adenoma or
carcinoma of the prostate gland in male rats subjected to GSM modulated RF was characterized
as showing equivocal evidence of carcinogenicity with an incidence of 2.2%, 2.2%, 7.8% and 3.3%
for the four doses of RF, whereas fibromas of the skin which showed incidences that are higher
than the above (2.2%, 5.6%, 7.8% and 5.6%) were not classified as equivocal or any level above
that.
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In addition to the inconsistencies in the data interpretation, the importance attributed to
dose response was also unclear in the final conclusions of the NTP reports. The incidence of
benign, complex, or malignant pheochromocytoma in the adrenal medulla in male rats subjected
to GSM modulated RF (12.5%, 26.7%, 31.5%, 16.1%) were classified as some evidence of
carcinogenicity despite there being no clear dose response and no statistical difference between
the highest RF dose and the control animals (P=0.472).
The strongest evidence found in the study was for malignant schwannomas of the heart in
male rats, which were characterized originally as some evidence and after peer review changed to
clear evidence and showed statistical significance at some doses of RF. It is notable that there was
no incidence of heart schwannoma in the control group. An NIH reviewer noted that if there had
been even one case in the control group then the statistical significance of this finding would not
exist. It has also been noted that the histology review of samples was only partially blind in that
the pathologists knew which group of samples was from the control group. This result was not
consistent between the male rats and female rats or either sex of mice. As has been noted before,
these extremely large whole-body RFR exposures (6 W/kg is 75 times higher than the limit for the
public which is 0.08 W/kg) in rodents cannot be directly compared to real world partial body
exposures to people using mobile phones 10.
We do not know if there is a causal effect or if these results are due to weakening of the
immune response due to animal stress from cyclic heating and thermoregulation decline in aging
animals leading to whole-body temperature increase, possible sleep disruption due to the cyclic
heating, or due to an RF-specific effect that has not been identified and has an adverse effect
before heating becomes the dominant safety issue. It is possible that any form (ambient, IR,
ultrasound) of cyclic whole-body heating of this magnitude may cause similar findings, but no
such studies have been conducted to date.
2. Papers Meeting the In vivo Review Criteria.
In this section we summarize other relevant in vivo studies that we carefully considered
and reviewed. Below is a summary of the results and limitations of these studies.
The largest animal exposure study published to date was conducted at the Ramazzini
Institute’s Cesare Maltoni Cancer Research Center in Italy (Falcioni et al. 2018). The goal of the

Note that the terms “wireless phone,” “cell phone,” and “mobile phone” are used interchangeably in
this and other studies.
10

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study was to examine the carcinogenic effect of 1.8 GHz simulated GSM in the far field whole
body exposure for 19 hours/day for life on 2,448 Sprague Dawley rats. The size of the stacked
dipole array antenna was not given but based on FDA expert analysis of the picture provided, the
exposure may have been in the near-field. Exposure was based on fixed field strengths (V/m) and
SAR (dose rate) estimates were based on a fixed “coupling factor”. However, for a given electric
field SAR changes with the change of mass, which will change over the animal’s lifetime. As such,
the estimation of the dose using a fixed “coupling factor” was not accurate.
The exposure groups were reported to be 0 (0 W/kg), 5 (0.001 W/kg), 25 (0.03 W/kg) or 50
V/m (0.1 W/kg). The animals were irradiated in their home cages, initially 5 rats per cage, but
pictures show cages containing only one rat. The number of rats per cage is an important factor
for the evaluation of potential stress and the possibility of localized RF current flow when animals
touch. Because cages were exposed horizontally, rats could shield each other during exposure. As
rats die and fewer are left in a cage their potential exposure increases unless survivors are
rearranged to maintain full cages. Moreover, it was unclear if five animals per cage resulted in
conflict and fights between animals, hence inducing stress.
There was no indication that animal core or other temperature was measured or recorded.
Tissues from the heart and the brain were examined for malignancies and pre-malignancies.
There was no mention of any other tissue being assayed. The authors state that the expected
spontaneous tumor incidence and its fluctuations were based upon data derived from more than
20,000 historical controls; however, no reference to these data is provided. There were no
differences in food or water consumption, mean body weight or survival index among the four
exposure groups. This finding is different from the NTP rat exposure results where the water
consumption was not monitored, and RF-exposed rats lived longer than control rats.
Histopathological evaluation of the hearts and brains detected a statistically significant increase in
the tumor incidence of heart schwannoma in the highest exposure for male rats (1.4%). The
authors refer to historical controls with an incidence of schwannoma in male rats of 0.6% (10 out
of 3,160 rats). Again, these historical control data were not available for analysis, and
demonstrate very high inconsistencies with other reported historical rates of rodent
schwannomas.
No statistically significant increases in malignant brain tumors and pre-malignant brain
tumors were observed. The authors found a non-statistically significant exposure dependent
increase in the incidence of malignant glial tumors in exposed female rats. After comparing this
non-significant trend to historical control data where the amount of malignant glial tumors in

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female rats was lower: 15 glial cell tumors out of 3,165 rats, or 0.5% 11, it was determined that the
50 V/m exposure group had a greater incidence of glial cell tumors than the historical (but not the
experimental) control.
Bartsch et al. (2010) reported on two long term and two life-long experiments that
examined the effects of chronic exposure of rats to 900 MHz, pulsed at 217 Hz to stimulate a GSM
signal on unrestrained animals. The exposure system was far-field simulated GSM 900 MHz
exposure via a circularly polarized antenna. Fixed field strength, rather than SAR, was maintained
throughout the experiments and thus the effective SAR changes over time as animals age and
grow larger. The mean whole-body SAR was estimated to be 80 mW/kg by means of
computational modeling and simulations based on an approach that has been extensively used in
RF dosimetry literature. Twelve female rats per cage were exposed vertically so resonance effects
are more likely. The exposure was for 23 hours and 45 minutes/day. Radiation exposure started
at 52-70 days of age. The experiment was designed with animals irradiated in four different
experiments with different time lengths, I. 24 months, II. 17 months, III. 36 months and IV. 37
months. The experimental endpoints included: animal general health, necropsy and
histopathology but there was no mention of temperature monitoring, which could lead to
confounding results. Experiments I and II recorded adverse health effects. Experiments III and IV
showed, unlike the NTP study, that survival was decreased with RF exposure. It is unclear how the
sham controls were treated or what elements the sham setup duplicated of the real exposure.
Animal temperature measurement was not mentioned. The investigators concluded that chronic
exposure to RF may exert negative health effects and shorten survival if exposure is applied
sufficiently long. The investigators also noted that the month of birth may affect life span and
stated that an experiment should be run to determine if the 11-year sunspot cycle could affect a
rat’s lifespan.
A series of investigations from Korea examined the impact of radiofrequency exposure on
laboratory animals (Jin et al. 2011; Kim et al. 2008; Lee et al. 2011). Kim et al. (2008) exposed the
heads of mice to 849 or 1763 MHz RFR for up to 12 months in a carousel-type head exposure
system with a specifically-designed exposure chamber with real CDMA signal. The chamber was
made of aluminum, the external size of which is 745 mm × 1,060 mm × 1,980 mm. To reduce
reflections from the walls, absorber foam with a thickness of 4.5 inches was used. The SAR
measurement was simulated. The SAR estimate was validated against thermal probe temperature
measurements. The actual temperature within the animal was not validated. There was no animal
core or head temperature monitoring to evaluate thermal impact. There was also no mention of
blinding. The heads of the restrained mice were irradiated 1 hour/day, 5 days a week for 6 or 12

11

No reference was provided for these data

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months with SAR of 7.8 W/kg. The weights of the irradiated animals were not significantly
different from the controls. Furthermore, brain tissue taken from the animals showed no
difference in histology, cell proliferation rate, cell death by TUNEL assay, and in the expression
and distribution of NeuN and GFAP (markers of specific neuronal cell types) in the hippocampus
and cerebellum between exposed and control animals. No evidence of brain tumorigenesis
associated with RFR was found under microscopic examination. The authors concluded that
exposure to the RFR at two different wavelengths did not result in alterations in cell proliferation,
cell death, or gliosis.
Jin et al. (2011) whole-body irradiated rats in a reverberation chamber with two combined
RF modulations, but without any core body temperature monitoring. The first was code division
multiple access (CDMA), at 849 MHz and the second represents wideband code division multiple
access (WCDMA), at 1.95 GHz. The animals were irradiated for 45 minutes/day, 5 days a week for
one year. The SAR for these experiments was 2 W/kg for CDMA and 2 W/kg for WCDMA for a
total combined SAR equal to 4 W/kg. No core temperature measurements were made to assess
thermal effects. To prevent treatment bias, all the exposure and data analysis were performed
using blinded methods. No significant differences in body weight or tumor incidence between
exposed and control rats were found. There were some notable alterations in physiological
parameters (complete blood count and serum chemistry) among exposed animals. However, the
authors concluded that a 1-year simultaneous exposure to 4 W/kg CDMA and WCDMA did not
increase chronic illness.
Lee et al. (2011) exposed AKR/J mice to CDMA and WCDMA RFR for 45 min/day, 5
days/week for 42 weeks at a total SAR of 4 W/kg. Exposure was given by using a reverberation
chamber. SAR was calculated in rat voxel models by means of computational modeling and
simulations based on the Finite Difference Time Domain (FDTD). Only whole-body SAR values
were reported and no information on local SAR was included. Rectal temperature measurements
were made before and after exposure and there was no elevation of temperature. Notably, AKR/J
mice showed a high incidence of spontaneous lymphoma that was followed in these experiments.
After examining body weight, survival, lymphoma incidence and splenomegaly, no differences
were found between sham irradiated and irradiated animals. There were observed differences in
infiltration of the brain by lymphoma: RFR-exposed male mice had lower brain infiltration
compared with the controls and female mice had higher levels of brain infiltration compared with
the controls. However, the authors concluded that RFR exposure did not affect lymphoma
development in AKR/J mice.
Several investigations examined the impact of RFR exposure on the brain. Kesari, Behari,
and Kumar (2010) examined the mutagenic response of 2.45 GHz RFR exposure on the brains of
12 male Wistar rats. The animals were whole-body exposed to a horn-antenna for 2 hours per day
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for 35 days and sacrificed immediately after the last exposure and the brains of exposed and
control animals assayed for DNA strand breaks (comet assay), antioxidant enzyme activity
(glutathione peroxidase, catalase and superoxide dismutase) and histone kinase activity. The
whole-body SAR was reported to be 0.11 W/kg. They detected an increase in DNA strand breaks,
a decrease in glutathione peroxidase, superoxide dismutase and histone kinase activity and an
increase in catalase activity. They concluded that chronic exposure may cause significant damage
to the brain. Animal temperature measurement was not mentioned.
Chaturvedi et al., (2011) examined the impact of 2.45 GHz RFR exposure on circadian
organization, spatial memory, DNA damage in the brain and blood counts of Parks strain male
mice. The mice were exposed to RFR 2 hours per day for 30 days. RFR exposure was from an
analog signal generator and horn antenna. Five of the ten animals were exposed individually and
the whole-body SAR was 0.035 W/kg. The remaining 5 animals were sham exposed. Locomotor
activity via a running wheel was recorded prior to and during RFR exposure. The Morris water
maze was used from the 17th to the 22nd day of RFR exposure. After completion of the exposure
blood was collected for hematological parameters, brain tissue for DNA strand breaks (comet
assay), epididymis for sperm count and motility and serum for serum gluSGOT and SGPT. The
authors concluded that RFR caused an increase in leukocyte and erythrocyte counts as well as
altered the rate of DNA damage in exposed mice. Furthermore, the authors believe that RFR
exposure altered the circadian system.
Deshmukh et al. (2013) studied the impact of 900 MHz (SAR= 0.595 mW/kg), 1800 MHz
(SAR= 0.58 mW/kg) and 2450 MHz (SAR=0. 6.7 mW/kg) on the brain of rats. There were 24 rats
that were organized into 4 groups (6 rats each). Three groups were exposed, and one group was
sham exposed. The restrained rats were exposed for 2 hours/day, 5 days/week for 30 days. There
were no statements regarding measurement of the animals’ temperatures. Using the results from
their modified alkaline comet assay, the authors concluded that low SAR exposures with any of
the three frequencies may induce DNA damage.
Two other studies in rats from the same group evaluated the impact of RFR on cognitive
function, heat shock protein levels and DNA damage (comet assay) in the brains of Fischer rats
(Deshmukh et al., 2015, Deshmukh et. al., 2016). This group used a Gigahertz Transverse
Electromagnetic cell as their exposure system. There were 24 rats in each study that were
organized into 4 groups (6 rats each). In each study three groups were exposed, and one group
was sham exposed. Restrained animals were irradiated 2 hours / day 5 days / week for 90 days
(Deshmukh et. al., 2016) or 180 days (Deshmukh et al., 2015). The SARs were 0.5953, 0.5835 and
0.6672 mW/kg for exposures of 900, 1800 or 2450 MHz respectively. Body temperature of rats
was noted by rectal measurements immediately before and after the MWR exposure in all the
groups. There was no change in body temperature. For both exposures, (90 or 180 days) the
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authors found cognitive function decline, elevated HSP synthesis and DNA damage and they
concluded that chronic low-intensity microwave exposure may cause hazardous effects on the
brain. The authors state that HSP synthesis can be from non-thermal effects. However, thermal
effects even at these low SARs cannot be ruled out.
Sahin et al. (2016) evaluated the impact of 2100 MHz RFR on the brain of rats. The exposure
system was composed of a vector signal generator and horn antenna. There were 30 rats divided
into 4 groups. Exposure groups had 9 animals and sham exposure groups had 6 animals each. The
exposed animals were exposed for 6 hr/day 5 days a week for 10 or 40 days. The SAR was
reported to be 0.4 W/kg. No core temperature measurements were made to assess thermal
effects. The authors assessed oxidative DNA damage (8-hydroxy-2’deoxyguanosine
determination) and the level of lipid peroxidation (malondialdehyde determination) in the brain
of RFR exposed rats. The authors found no difference in oxidative DNA damage when exposed
animals were compared to their individual controls, however, increased oxidative DNA damage
was found in animals exposed for ten days compared to the 40-day exposed animals. Decreased
lipid peroxidation was observed after 40 days of exposure. The authors postulated that the longer
exposure may have increased DNA repair mechanisms.
Ibitayo et al., (2017) investigated the effect of RFR on the brains of male rats. There were 16
rats in 4 groups of 4. The authors described the exposure set up as follows: “The animals were
pair housed in groups of four in steel mesh cages and placed about 10 cm away from installed
devices that emitted RF EMF. The control group (𝑛𝑛 = 4) was kept in a steel mesh cages with a glass
barrier separating the control from the experimental animals.” It appears the animals were whole
body exposed to 2.5 GHz RFR for 30, 45 or 60 days. No description of the RF source nor a SAR
determination was provided. No core temperature measurements were made to assess thermal
effects. Histopathology and DNA damage was determined. The authors concluded that vascular
congestion and DNA damage indicative of oxidative stress are evident in RFR exposed animal
brains. The authors found that the 45-day exposed samples did not show severe histopathological
changes seen in the 30- or 60-day exposed samples. There was also no report of malignant
change in the investigation.
Three investigations examined the impact of 1800 or 2100 MHz on bladder cells of rats
(Gurbuz et al. 2010; Gurbuz et al. 2014; Gurbuz et al. 2015). In these experiments, the rats were
exposed to RF radiation and the bladder cell micronuclei were assayed for micronuclei in vitro.
Gurbuz, et. al. (2010) exposed 6 female Wistar rats to 1800 MHz GSM-like RF for 20 minutes/day,
5 days/week for a month and assigned 6 others to a control group. Near field exposure was used
to simulate cell phone exposure. Field strengths were controlled with a Narda EMR 300 meter and
probe. The E-field was 4 V/m. The authors claim that because E-field values are much lower than
the 41 V/m of ICNIRP, exposure is assumed to be non-thermal. However, temperature was not
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monitored, and those statements cannot be confirmed. RFR exposure did not increase the
frequency of micronuclei in exposed rats compared with the controls.
Gurbuz et al (2014) examined exfoliated rat bladder cells for micronuclei after whole body
exposure (30 min/day, 6 days/week for one and two months) to 1800 MHz and 2100 MHz RF
radiation. The animals were free to move in their cages during the RF exposure. The control
animals were housed in their home cages during the entire experimental period without being
subjected to any experimental manipulation. A vector signal generator was used to create a GSM
modulated RF radiation in the experimental setup. The E-field was 17 V/m. The calculated
average SAR was estimated to be 0.23 W/kg. No significant increase in micronuclei found in the
exfoliated rat bladder cells was detected in cells from RF exposed rats compared to control rats.
Finally in a third study, the same group (Gurbuz et al. 2015) examined the influence of RFR
on micronucleus formation in bladder cells of diabetic rats. They postulated that diabetes may
accelerate oxidative damage in DNA molecules through glucose auto-oxidation and nonenzymatic glycation. The diabetic rats were exposed to 2100MHz RF for 30 min/day, 5 days/week
for 30 days at a low SAR (0.24 W/kg). As in previous experiments, they used a near field exposure
and the dosimetry was unclear. Again, this group found no statistically significant difference
between the exposed population and the diabetes control or the non-diabetes control. Overall,
based on the results presented, the studies indicate that rat bladder cells are not sensitive to RF
exposure at low SARs.
Two separate experiments examined the co-carcinogenic potential of RF exposure in
combination with a known carcinogen (Lerchl et al. 2015; Tillmann et al. 2010). In both cases the
known carcinogen was ethylnitrosourea. Tillmann et al. (2010) exposed mice over the whole-body
to a universal mobile telecommunications system (UMTS) signal. RF exposure lasted up to two
years starting at embryo-fetal stage. Whole body SARs were estimated to be up to 4 W/kg. The
animals were exposed once per day (2 GHz, continuous wave signal, 2 h/d) with a stepwise
increased power density in one radial waveguide of a three-decker exposure system. Rectal
temperature measurements simultaneously obtained in 10 mice (2 mice per cage) directly after
termination of the RF exposure revealed regular body temperatures (37.1°±0.38°C to
37.7°±0.68°C) regardless of the RF power density applied. The low field intensity group was also
given 40 mg ethylnitrosourea. The high UMTS exposure (48 W/m2), the sham exposure and the
cage control all showed comparable tumor incidence. Animals exposed to ethylnitrosourea and
4.8 W/m2 RF showed an increased incidence of lung carcinoma. Notably, the authors identified a
Helicobacter hepaticus infection in these animals and discounted the high RFR liver tumor results.
A review of the neoplastic and pre-neoplastic lesions in the protocol organs shows that UMTS RF
exposure (48 W/m2) for up to two years did not produce tumors or other lesions of the cerebrum.
Also, other tissues examined such as the lungs, kidneys, spleen and hematopoietic /
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lymphopoietic system did not show increased tumors or increased pre-neoplastic lesions when
the UMTS exposed animals were compared to the cage control or sham control animals.
Lerchl et al. (2015) also examined the co-carcinogenic potential of RFR exposure in
combination with a known carcinogen (ethylnitrosourea). This investigation used 5 groups of 96
mice. Four groups were treated with ethylnitrosourea and exposed at SAR equal to 0 W/kg
(sham), 0.04, 0.4 or 2 W/kg SAR for 23.5 hours per day up to 72 weeks. The fifth group was an
untreated unexposed cage control. Details of the RFR exposure and exposure system were
previously published (Reinhardt et al. 2007), presenting the 900 MHz UMTS waveguide exposure
system and simulations to estimate whole body SAR based on typical arrangement of mice in the
exposure area. The E-field inside waveguides was monitored. There was no data, either simulated
or measured that correlated E-field with the desired treatment levels of whole-body SAR. There
was no temperature monitoring. Further, this large experiment did not include an RFR only
control. The authors concluded that the combination of ethylnitrosourea and RFR produces a
greater number of tumors in the lungs and livers of exposed animals compared to the sham
irradiated controls. Also, the results found lymphoma in RFR-exposed animals. The results do not
demonstrate a clear dose response. A review of the neoplastic and pre-neoplastic data shows no
significant tumors or pre-neoplastic lesions of the cerebrum compared to the cage control or the
sham irradiated control.
Hruby (Hruby et al. 2008) examined the impact of 902 MHz GSM-type wireless RF radiation
on 7, 12-Dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. DMBA is widely
used in animal research as an immunosuppressor and a powerful organ-specific carcinogen. All
animals received DMBA, there were two control groups (cage control, sham irradiation control)
and three RFR exposure groups (0.4, 1.3 and 4.0 W/kg). Each group had 100 animals and another
20 were kept as sentinel animals for disease surveillance. RF exposure was simulated GSM at 902
MHz for 4hr/day, 5 days/week for 6 months. The animals were exposed individually, held in
restraining tubes fitted into a 17 spoked waveguide exposure system. The authors cited
references on the exposure system which provide credible evidence that the system was
accurate, monitored in real-time, and well supported by simulations to estimate whole body SAR.
The authors found the following statistically significant results: All RFR exposed groups, at
different times had significantly more palpable masses; There were fewer animals with benign
lesions in the RFR exposed groups and more malignant tumors in the highest RFR exposure group;
The cage control group had more palpable tissue masses and more benign and malignant tumors
compared with the sham irradiated control. However, the RFR exposure groups did not show a
dose response. The authors concluded that, “In the context of the results of the cage-control
group, in the light of controversial results reported in the literature, and given the fact that the
DMBA-mammary tumor model is known to be prone to high variations in the results, it is the
authors’ opinion that the differences between the groups are rather incidental ones.”
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Paulraj and Behari (2011) investigated the impact of 2 frequencies of RFR on carcinogenesis
in mice. There were 18 mice in each of the 7 groups. The study was divided into two parts. The
first, involved the topical administration of DMBA on the skin followed by exposure to 112 MHz or
2.45 GHz 2 hours/day, 3 days / week for 16 weeks. There was insufficient information to
determine how SAR was estimated but reported SARs were 0.75W/kg for 112 MHz and 0.1 W/Kg
for 2.45 GHz. No core temperature measurements were made to assess thermal effects. The
study also employed a positive control, DMBA + croton oil (a well-known tumor promoter). The
positive control produced tumors in animal skin. However, no tumors were detected in the
controls or the exposed populations. The second part consisted of transplanting Ehrlich ascites
cells (originally established to produce ascites tumors in mice) intraperitoneally followed by
exposure to 112 MHz RF for 14 days. There were no significant changes in mortality or cell
proliferation between the control and the exposed groups. It is unclear if this was a sham or cagecontrol.
Two studies from the same group investigated the cytotoxic effects of 1800 or 900 MHz RFR
exposure to rat bone marrow cells (Atli Sekeroglu, Z., Akar, and Sekeroglu 2013; Sekeroglu, V.,
Akar, and Sekeroglu 2012). The first study (Sekeroglu, V. , Akar, and Sekeroglu 2012) examined
the effects of 1800 MHz RFR on immature and mature bone marrow cells (RIM and RMM). In each
study a total of 48 animals were divided into 6 groups of 8 animals each. Rats with RIM and RMM
were exposed to 1800 MHz RFR for two hours/day for 45 days. Some of the animals were tested
immediately and others returned to their cage for 15 days before testing. Insufficient information
was provided on dosimetry and there was no discussion about measuring the animals core
temperature. The reported whole-body average SARs were 0.37 W/kg and 0.49 W/kg for RIM and
RMM cells, respectively. The bone marrow cells were scored for common signs of bone marrow
cell toxicity including differences in mitotic index, chromosomal aberrations, and micronucleus
formation. Significant differences between control and exposed bone marrow cells were found in
chromosomal aberrations, micronucleus formation, mitotic index, and the ratio of polychromatic
erythrocytes. The authors found that the damage detected was greater in RIM cells than RMM
and that an unirradiated recovery period after exposure did not improve the RIM cells.
Additionally, it is not clear if the control animals were sham irradiated while in the irradiation
restraining device.
The same group, (Atli Sekeroglu, Z., Akar, and Sekeroglu 2013) repeated the experiment
with exposure to 900 MHz RF. The animals were exposed for 2 hours /day for 45 days. The
estimated SARs were 0.38-0.78 W/kg for RIM and 0.31-0.52 W/kg for RMM. Significant
differences between control and exposed bone marrow cells were found in chromosomal
aberrations, micronucleus formation, mitotic index, and the ratio of polychromatic erythrocytes.
The comet assay was not blinded, and the OECD approved %tail DNA was not used as the comet
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assay damage metric. The authors found that the damage detected was greater in RIM cells than
RMM and that an unirradiated recovery period after exposure did not improve for bone marrow
cells. Conclusions from this study must be made with caution because no positive control with a
known cytotoxic agent was included in this experiment and there was only one timepoint for the
recovery experiment reported.
Ziemann (Ziemann et al. 2009) examined the genotoxic potential of 902 MHz GSM and 1747
MHz digital cellular system (DCS) communication signals in a two-year study in mice. Each group
contained 65 animals, with the 15 animals used for interim examinations. There were additionally
30 male and 30 female mice assigned as sentinel animals. The animals were chronically exposed
to RFR for 2 hours/day, 5 days/week for two years at whole-body averaged SARs of 0.4, 1.3 and 4
W/kg. There was no indication that animal core temperature was measured or recorded.
Micronuclei frequency was determined in blood smears of cage control animals, sham irradiated
animals, with animals exposed to SAR equal to 0.4, 1.3 and 4 W/kg as well as mitomycin C (MMC)
as a positive control. MMC alkylates and cross-links DNA. No significant differences in micronuclei
frequency were found between RFR exposed animals and cage controlled or sham irradiated
animals. Only animals in the positive control group showed significant increase in micronucleus
frequency.
Furtado-Filho (Furtado-Filho et al. 2015) examined the impact of 950 MHz RFR on ROS
metabolism and DNA damage in the brains of young rats. RFR exposure was applied during
pregnancy to 6 animals and to 6 pups for 6 days after birth, with estimated SAR ranging from
1.14-1.32 W/kg. Another 6 pregnant rats were sham exposed. 6 pups from both exposed parents
and from sham exposed parents were dissected at 0 days old. Another 6 pups that continued
exposure and those that had no exposure were dissected after 6 days. There was no temperature
monitoring and no apparent blinding for the endpoint analysis. No positive control was included
in this study. No genotoxicity and oxidative stress were identified in neonates and 6-day old mice.
Another small study investigated the impact of 915 MHz with GSM modulated RFR on DNA
of brain, liver and kidney of rats (Trosic et al. 2011). 9 rats were in the exposed group and 9 rats in
the sham exposed group. The animals were irradiated at 37oC for one hour/day, seven days a
week for two weeks at a SAR of 0.6 W/Kg. Exposure was generated by a Gigahertz Transversal
Electromagnetic Mode Cell and a signal generator. The elevated environmental temperature
during exposure may have influenced thermal regulation of the exposed animals and thus
increased the chance of thermal confounding. Before and after exposures a ThermoScan
thermometer was used to measure body temperature. No significant changes were observed in
the treated animals compared to the sham exposed animals. Genotoxicity was assessed via the
comet assay used tail length and not the OECD approved endpoint %tail DNA to detect DNA
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damage, which demonstrated no statistically significant correlation between dose and comet tail
length.
Akdag et al. (2016) investigated the impact of long-term exposure to 2450 MHz RFR
exposure on DNA damage in the brain, liver, kidney, skin, and testicular tissue of rats. There were
two groups of 8 rats each. The control group was sham exposed. The animals were exposed 24
hours/day for 12 months using a signal generator. The animals’ core temperature was not
measured or not documented. There was no mention of blinding. Results from the comet assay
appeared to show more DNA damage in the RFR-exposed rats compared to the sham irradiated
rats. However, the results were not statistically significant for the DNA damage in brain, liver,
kidney and skin. The only tissue in which RFR significantly increased DNA damage was in the
testis.
Pandey et al. (2017) investigated histology and DNA damage in testicular cells in mice after
900 MHz RFR exposure. There were 5 groups of 15 mice each. The animals were exposed for
either 4 hours or 8 hours/day for 35 or 70 days and the SAR was calculated to be from 5.4 to 5.16
mW/kg. The animals’ temperatures were not measured. There was no blinding of quantitative
endpoints. There is no description of a sham exposure for the control group. The authors
concluded that oxidative stress caused DNA damage in germ cells of exposed mice without
measuring oxidative stress, and the precise link between the apparent oxidative stress and DNA
damage remains unclear.
Pandey and Giri (2018) investigated DNA damage with the comet assay and other oxidative
stress endpoints in germ cells of male mice exposed to 900 MHz RF radiation. There were 60
animals in 4 groups of 12 animals each. The groups were: controls, mice dosed with melatonin,
mice exposed to RFR, and mice dosed with melatonin and exposed to RFR. There was no mention
of sham controls. The animals were irradiated for 3 hours/day, twice a day for thirty-five days.
The SAR ranged between 0.052 and 0.0054 W/kg. The authors state that the samples and slides
were carefully blind coded before analysis; however, blinding is mentioned specifically only in the
histology section. The authors found that melatonin administration reduced DNA damage that
they attributed to RFR exposure.
Megha et al. (2015) examined the impact of microwave exposure on oxidative stress and
DNA damage in the hippocampus of Fisher Rats. There were 24 animals in 4 groups of 6 rats each.
The rats were exposed in a GHz transverse electromagnetic cell to 900, 1800 and 2450 MHz at
SARs of 0.59, 0.58 and 0.66 mW/kg respectively. The control group was sham exposed. Body
temperature of rats was noted by rectal measurements before and after the microwave exposure
in all the groups. The exposures were given to restrained animals for two hours/day, five
days/week for 60 days. The slides prepared were randomized and coded to blind the comet
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scorer, but no other blinding was done. The authors report that DNA damage was significant in all
microwave-exposed animals and they believe that the increase in DNA damage is frequency
dependent.
Guler et al., (2016) investigated the impact of 1800 MHz RFR on the brains of developing
rabbits. The endpoints were oxidative DNA damage (8-hydroxy-2’deoxyguanosine determination),
lipid peroxidation (malondialdehyde determination) and apoptotic cell formation TUNEL assay). A
signal generator with an integrated pulse modulation unit and horn antenna was used to expose
the animals. The estimated SAR was 18 mW/kg. 36 female rabbits were exposed for 15 minutes
/day for 7 days. 36 males were exposed for 15 minutes / day for 14 days. 36 of the infant rabbits
were exposed for 15 minutes / day in the intrauterine gestational period. Animals were also
exposed a month after birth. The animals were divided into 4 groups. Group I: no intrauterine +
no extrauterine exposure; Group II: no intrauterine + extrauterine exposure; Group III:
intrauterine exposure + no extrauterine exposure; Group IV: intrauterine and extrauterine
exposure. Blinding was used to prevent bias during sample analysis. There was no measurement
of the animals’ temperatures reported. The authors found that intrauterine and extrauterine
1800 MHz RFR exposure may cause oxidative and DNA damage in the brain tissue of baby rabbits
which are exposed while they are fetus and after they are 1-month old. However, there was no
evidence of apoptosis in any of the groups.
Turedi et al. (2014) studied the effect of 900 MHz RFR prenatal exposure on the 21-day old
male rat heart. The exposure system used was an ultra-high frequency oscillator attached to an
uninterrupted power supply and a dipole antenna installed into a plexiglass box. The whole-body
SAR was 0.025 W/kg. Three pregnant rats were exposed for 1 hour / day on days 13 to 21 of their
pregnancy. Three other pregnant rats were assigned to the control group and there was no sham
exposure. Six control and six exposed male pups were sacrificed on day 21 and hearts collected
for microscopy, malondialdehyde, superoxide dismutase, catalase, and glutathione activity
determination. There was blinding used to prevent analysis bias. Apoptotic changes and
irregularities in the heart muscle of exposed animals were shown by microscopy. Crista loss,
mitochondrial swelling, degeneration in myofibrils and structural impairments in z-bands were
shown by electron microscopy. Malondialdehyde, superoxide dismutase and catalase values were
found to be significantly higher. Glutathione activity was found to be lower. The authors
concluded that RFR exposure in the prenatal period causes oxidative stress and histopathological
changes in the heart, although the impact of any potential temperature increase during exposure
was not determined and there was no measurement of the animals’ core temperatures.
The genotoxic effects of 2.45 GHz RFR on the testis and ovary of rats was investigated by
Usikalu et al., (2013). The exposure system was a microwave generator and all exposed animals
were whole body irradiated for 10 minutes at various SARs. There were 30 male and 30 female
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rats used in this study and one control and 9 experimental groups. There were 3 male and 3
female rats in each group. SARs were measured by insertion of a thermistor into the rectum. The
animals were exposed to 0, 0.48, 0.95, 1.43, 1.91, 2.39, 2.9, 3.4, 3.8 and 4.3 W/kg. DNA damage
was assessed by direct amplification of length polymorphism and the comet assay. Organ damage
was assessed by histopathology. There was no blinding described in the paper nor was there a
sham control described. The authors conclude that 2.54 GHz RFR exposure alters DNA bands
patterns, induces single strand DNA breaks, and reduces the number of male germ cells in rats.
Furthermore, the authors concluded that RFR exposure at 0.48 W/kg and above produces
genotoxic effects on the testis or the ovary.
Ozturk Okatan et al., (2018) evaluated ovarian changes in adolescent rats exposed to 900
MHz RFR. The exposure system consisted of an oscillator, a continuous fixed power source and an
EMF cage. Rats were exposed to 900 MHz for 1 hour a day between postnatal days 35 and 59.
The calculated whole-body SAR was 0.0098 W/kg. Animals were divided into 3 groups: control,
sham-exposed and 900 MHz exposed. Each group contained 8 rats. Animals’ core temperatures
were not measured. Ovaries and blood were collected at the end of the exposure for
histopathological and biochemical analysis. Blinding was used to avoid analysis bias. Among the
results of the histopathological examination was thinning in the zona granulosa and theca layers,
shrinking in granulosa cells, reduced mitotic activity and leukocyte infiltration in the follicles and
stroma of RFR exposed animals. Among the results of the biochemistry examination was an
increase in superoxide dismutase, catalase and anti-Mullerian hormone levels in the RFR exposed
and sham exposed animals. The authors conclude that RFR exposure may cause changes in the
morphology and biochemistry of the ovary, although with changes also seen in the biochemistry
of sham exposed animals, the conclusions appear unclear.
The Influence of 1800 MHz GSM RFR exposure on oxidative DNA and Lipid damage in liver of
pregnant, non-pregnant, and new born rabbits was studied by Tomruk et al. (2010). Six groups of
nine rabbits each were used. A signal generator, pulse modulator and horn antenna were used as
the exposure system. Pregnant and non-pregnant rabbits were exposed whole-body to 1800 MHz
GSM-like RFR signal for 15 minutes / day for a week. No estimation of SAR was provided. Core
temperature measurements and blinding are mentioned. Oxidative DNA damage (8 OHdG/106DG
level) and lipid damage (malondialdehyde assay and ferrous oxidation in xylenol orange level) was
determined in control and exposed pregnant and non-pregnant as well as in new born control and
exposed rabbits. There was no difference in oxidative DNA damage between exposed and control
livers. However, lipid damage was detected in the exposed groups. No increased oxidative DNA
damage was detected in new born rabbits exposed to 1800 MHz RFR in utero. Increased lipid
damage was detected in new born rabbits exposed to 1800 MHz RFR in utero.

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Furtado-Filho et al., (2014) also investigated the impact of RFR on the liver of rats. These
investigators used a generator and a half-wave dipole antenna to produce RFR at a power of 1
Watt and a frequency of 950 MHz. The SAR was 0.88 W/kg for neonate rats, 0.51 W/KG for 6-day
old rats, 0.18 W/Kg for 15-day old rats and 0.06 W/kg for 30-day old rats. Six pregnant rats were
exposed to SARs ranging from 0.01 to 0.03 W/kg. 6 other pregnant rats were assigned to the
control group. The animals were exposed to RFR for thirty minutes / day for up to 51 days. The
exposure was divided into 21 days of gestational exposure and up to 30 days outside the womb.
Temperature was not measured and there is no mention of blinding. Damage to lipids, proteins
and DNA (comet assay) was assessed. The authors found 950 MHz exposure does not cause
oxidative stress and is not genotoxic to neonates or rats up to 15-days old. However, the authors
also found that RFR exposure is genotoxic to 30-day old animals.
The excretion of 8-oxodG, an oxidative DNA marker in the urine of rats exposed to 1800
MHz RFR was conducted by Khalil et al. (2012). A GSM signal generator and antenna were used to
expose the rats to 1800 MHz for 4 hours. There were 24 rats in two groups of 12. Sample analysis
was blinded. The SAR was 1.0 W/kg. The results indicate that RFR exposure increased the urinary
excretion of 8-oxodG compared to the control. The authors concluded the following: “the present
results suggest that (a) exposure to RFR may augment oxidative stress; (b) urinary excretion of 8oxodG may be a good and specific marker of oxidative stress. Further work is also required to
understand the origin and validity of excreted urinary 8-oxodG as a marker of oxidative stress.”
Two investigations from the same group investigated the adaptive response in mice exposed
to 900 MHz (Jiang et al., 2012; Jiang et al., 2013). Jiang et al., (2012) examined the impact of prior
exposure of 900 MHz RFR for 4 hours / day for 1, 3, 5, 7 and 14 days to subsequent exposure to 3
Gy of ionizing radiation. There were 3 exposure groups containing 5 mice each. There was no
blinding. The exposure system consisted of a GTEM chamber, power amplifier and an antenna. The
calculated SAR was 0.548 W/kg. The exposed mice were restrained during exposure. DNA damage
was assessed with the alkaline comet assay. One exposure for 4 hours to 900 MHz plus 3 Gy was
not significantly different from 3 Gy alone. Mice pre-exposed for 3 or more days to 900 MHz show
progressively less damage to 3 Gy suggesting adaptive response triggered by the conditions of the
RFR exposure or the RFR.
Jiang et al. (2013), conducted a similar experiment that investigated the impact of prior
exposure to 900 MHz RFR for 4 hours / day for 7 days on subsequent exposure to 3Gy of ionizing
radiation. There were 6 groups of 10 mice each used in this study. The exposure system consisted
of a GTEM chamber, power amplifier and an antenna. The calculated SAR was 0.548 W/kg.
Genotoxicity was assessed via the micronucleus assay in immature erythrocytes in peripheral blood
and bone marrow. Results of the micronucleus assay were similar for the non-exposed control mice
and the 900 MHz RFR exposed mice. Exposure to 900 MHz RFR for 7 days before 3 Gy of ionizing
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radiation resulted in a significant decrease in micronuclei compared to 3 Gy ionizing radiation only.
This may indicate the conditions of RFR exposure or the RFR exposure activated an adaptive
response.
Meena et al., (2013) studied the protective effects of Melatonin (antioxidant) on oxidative
stress-mediated testicular impairment due to long- term exposure from RFR. The exposure system
consisted of an anechoic chamber in a far field region from a horn antenna. The rats were exposed
to 2.45 GHz RFR for 2 hours per day for 45 days. There were 24 rats in 4 groups of 6 rats each. The
samples and analysis were blinded. There was no data regarding the animals’ core temperature.
The SAR was estimated to be 0.14 W/kg. Four groups were tested in this investigation: sham
exposed, melatonin treated (2g/kg), 2.45 GHz RFR and 2.45 GHz plus melatonin. Oxidative stress
related parameters were documented including lactate dehydrogenase activity, xanthine oxidase
activity, reactive oxygen species, protein carbonyl content, DNA damage (comet assay) and
malondialdehyde concentration. The authors found that melatonin reduced oxidative damage by
increasing lactate dehydrogenase, decreasing malondialdehyde and reactive oxygen species.
Melatonin also reversed the effects of 2.54 GHz RFR on xanthine oxidase, protein carbonyl content,
sperm count, testosterone level and DNA strand breaks. The authors concluded that melatonin has
a strong effect on the RFR mediated oxidative stress in testicular cells.
The effect of RFR adaption on bleomycin-induced DNA and oxidative damage and repair was
studied by Zong et al. (2015). The exposure system was a GTEM chamber. 900 MHz RFR exposure
was for 4 hours / day for 7 days. The mice were restrained. The SAR was estimated to be 50 mW/kg.
There were 48 mice total. Six groups were tested. The animals’ core temperatures were not
measured. The samples were blinded. The groups included unexposed controls, RFR only, sham
exposure only, Bleomycin only, RFR exposure plus bleomycin and sham exposure plus bleomycin.
DNA damage was assessed via the comet assay. Oxidative damage was assessed via
malondialdehyde levels and antioxidant status by superoxide levels. There was no indication for
increased DNA and oxidative damage in mice exposed to RFR alone. Mice exposed to RFR plus
bleomycin significantly reduced bleomycin damage and decreased malondialdehyde concentration
in the plasma and lung and increased SOD levels in lung. The conclusion was that RFR exposure
induced an adaptive response to bleomycin DNA and oxidative damage by activating certain cellular
processes. There was no evidence for DNA strand breaks or oxidative damage caused by RFR
exposure in this experiment. The authors suggested that RFR exposure activates an adaptive
response through cellular processes that are not DNA or oxidation dependent.

C. Conclusions from In vivo Review.
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The in vivo studies conducted between January 1, 2008 and August 1, 2018 and summarized
here have contributed to our collective understanding of the potential effects of RFR on
mammals. Overall, based on certain limitations, these studies have not produced any clear
evidence that RFR exposure has any tumorigenic effect. In some cases, the authors of these
studies suggested the need for more research based on the reported results. Other authors
stated that RFR exposure does not result in tumor-initiating or -promoting effects.
Most of the referenced literature did not include measurement of animal temperatures. The
impact of potential temperature elevation from RFR exposure is a confounding factor in such
studies and critical to assess. The NTP reports examined temperature increases in their 5-day pilot
study. However, they did not adjust their highest exposure groups, exposures up to 6 W/kg in rats
and 10 W/kg in mice, to address concerns with geriatric thermoregulation. The NTP pilot study
confirms that pregnant animals and older animals have difficulty regulating body temperature
when they are exposed to sources of heat such as RFR exposure. NTP reports indicate a need to
further evaluate how mammals’ thermoregulatory abilities decline as they age and how to
address this issue to remove confounding heating as a factor in any future RFR exposure research.
Similarly, some of the other literature we reviewed have results that are confounded by heating
issues.
As with many areas of active investigation, the variety of experimental methods employed
can result in significant differences in conditions experienced by the experimental animals, and in
turn this can lead to a high degree of variability in study conclusions. For RFR studies, there are
large differences in, for example, methods for dosing and restraining animals during the
experimental procedure that will affect the specific stress levels of the test animals, confounding
some conclusions. There are also important differences in the overall experimental designs,
including the use (or lack) of both a control and sham exposed control group. Such differences
may be one reason why there are many diverging and conflicting conclusions of the in vivo effects
of RFR.
Another experimental issue that has an impact on the understanding of the interaction
between RFR with animals and needs further research is how samples are handled and evaluated.
The method of sacrifice (time since last exposure) and time from an animal’s death to sample
preparation have a large impact on the results of sensitive tests like the comet assay. In these
experiments, there were differences in how biological samples were collected and processed that
added confounding factors. One of the most prevalent problems we observed in these studies
was the lack of adequate blinding of samples which generally leads to an unconscious bias in the
evaluation of data. More clarity regarding potential confounders is needed in this area of
research.
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The FDA has followed RFR research developments for over 20 years. More than 100 peer
reviewed articles about in vivo animal exposures were assessed for to determine if they met the
scope of this review. 37 peer reviewed articles met our criteria and are included in this review. In
vivo studies are of great value and contribute to our understanding of this topic. However, as
described above, due to the critical limitations of in vivo studies in assessing the effects of RFR
exposure to humans (e.g., whole-body RFR exposure), we cannot draw conclusions about the
impact of such exposure to humans based on these in vivo animal studies. The results from such
studies should not be applied to human cell phone usage as further research is needed.

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V.

Epidemiological Studies

Section V.A. below discusses the search strategy and search terms we adopted to find
relevant epidemiological literature. Section V.B. of the report provides a high-level narrative
summary of the epidemiological studies reviewed and then followed by a description of the
overall limitations of such studies in Section V.C. Specifically, Section V.B. summarizes general
findings stratified by overall risk trends (e.g., increasing or decreasing), study types and/or sources
(e.g., ecological trend analysis or case-control study), and outcomes of interest represented by
different tumor types (e.g., glioma, meningioma, vestibular schwannoma, etc.). Section V.D.
includes a more detailed description of the individual studies reviewed, including summary of the
methodology and main results, along with the limitations for each referenced study. Section V.E
describes the FDA’s findings based on the review of the available epidemiological literature.
A. Search Strategy.
As the primary source for Medline-indexed journals and peer-reviewed publications,
PubMed was queried using the following search terms and limits:
-

("cell phone*" OR "mobile phone*" OR "non-ionizing radiation" OR "radiofrequency radiation")
AND (cancer OR cancers OR carcinogen* OR tumor OR tumors OR tumorigenesis)
Filters: Full text, English and Humans
The initial PubMed query with no limits resulted in a total of 1,180 records. After applying
PubMed filters for Full Text, English, and Humans, the number of records was reduced to 792
publications, which constituted the pool for 1st pass (i.e., abstract- based) review. The 1st pass
review excluded articles not directly related to the review’s subject (e.g., main outcomes other
than cancer). Note: a relatively high number of excluded articles (343 of the 388) was due to the
fact that in many studies, RF-related wireless technology was a part of the study design, but not
the main research topic (e.g., mobile phones were used for collecting data from cancer patients).
The 1st pass review identified 449 records, which were focused on the RF- related cancer risk, but
included animal (in vivo) studies as well as article formats such as meta-analyses, expert opinions,
etc. The 2nd pass (full-text based) review was aimed to select the original clinical/epidemiologic
studies assessing RF-related cancer risk. Per RF Working Group’s request, the 2nd pass review also
applied the publication date filter (January 2008 – May 2018) for deriving more recent evidence.
After the 2nd pass review, a total of 69 records (with one cross-reference) were selected for the
final review with qualitative evidence synthesis.
Note: this technical report includes some additional references, which have been used to
support the overall data analysis and interpretation. In order to distinguish them from the
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selected clinical/epidemiological publications (which are listed in the References section), the
additional references cited are presented in the footnotes.
B. Summary of Results.
This section only provides a high-level narrative summary of the epidemiological studies
reviewed. For a description of the limitations of these studies see Section V.C below and for a more
detailed description of each of the individual studies referenced here, see Section V.D.
1. Studies reporting overall evidence that does not counter a global null
hypothesis on tumor risk in relation to cell phones.
Negative evidence on associations between use of cell phones and tumor incidence was
shown in a number of ecological trend analyses reporting no population-level risk increases
for the brain and central nervous system (CNS) tumors (Inskip 2010; de Vocht 2011b; Ding and
Wang 2011; Benson 2013; Hsu 2013; Kim 2015; Sato 2016), which included glioma and
meningioma (Deltour 2009, 2012; Chapman 2016), acoustic neuroma 12 (Benson 2014), and
parotid gland neoplasms (de Vocht 2011a). In the study by Barchana (2012), no increasing
incidence in the period after introduction of mobile phones was reported for low-grade (but
not high-grade) gliomas.
Similarly, no evidence for overall tumor risk increase in relation to cell phone use was
shown in a number of case-control and cohort studies on acoustic neuroma (Corona 2012; Han
2012; Schüz 2011), glioma (Gousias 2009), pituitary adenoma (Shoemaker and Swerdlow 2011),
uveal melanoma (Stang 2009), and salivary gland tumors (Soderquist 2012). Some studies
(Lankola 2008; Shrestha 2015) reported overall reduced risk for meningioma (OR=0.76 [95% CI:
0.65; 0.89]) or pituitary tumors (OR=0.39 [95% CI: 0.21; 0.72]), which however indicated the
presence of strong biases as discussed below.
However, some studies (Aydin 2011, 2012; Cooke 2010; Coureau 2014; Frei 2011; Kaufman
2009; Poulsen 2013; Yoon 2015) reported no overall risk increases in the entire study populations
but found elevated risks in certain study subpopulations (for more details, see section IV.D.
below). Risk increases among certain cell phone user categories were found even in the largesample multi-country INTERPHONE (2010, 2011) studies that reported overall reduced risks for
glioma and meningioma (OR=0.81 [95% CI: 0.70; 0.94] and OR=0.79 [95% CI: 0.68; 0.91],
respectively) and acoustic neuroma (OR=0.85 [95% CI: 0.69; 1.04]).
12

Acoustic neuroma is also known as vestibular schwannoma; in this memo, both terms are being used interchangeably, as presented
in original publications.

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No overall risk increase corresponding to the increasing time of cell phone use was found in
the Swedish population-based study on acoustic neuroma, where controls were assigned a
reference date and a laterality for “fictive tumor” corresponding to their matched case
(Pettersson 2014).
No significant risk changes in relation to cell phone use were found in the study on
malignant brain tumors by Spinelli (2010). Positive risk association, however, was reported for
occupational computer exposure for ≤ 4h/day. The lower risk reported for residing near cell
phone towers was speculatively attributed by the authors to possible lack of EMF on the lower
part of the base stations (BS), or to lower emissions from cell phones due to better connections in
the surrounding areas.
2. Studies Reporting Cvidence on Possible Tumor Risk Modification in
Relation to Tumor Types and/or Cell Phone Usage Practices.
Tumor risk increases in relation to use of cell phones were extensively reported by Hardell
and Carlberg (2008-2017, Sweden). A recent ecological trend analysis by this group suggested an
increase in thyroid cancer incidence concordant to mobile phone use (Carlberg 2016). Increasing
rates of brain tumors of unknown type (with joinpoint 2007) were speculatively attributed to the
glioma risk increase due to use of cell phones (Hardell and Carlberg 2015). As a further
speculation, the increased brain tumor risk among users with the first use of a cell phone before
the age of 20 was suggested as possible explanation for the increasing rates (2007–2015) of
unknown type CNS tumors that were shown to be specifically elevated in the age group of 20–39y
(Hardell and Carlberg 2017).
However, possible risk increases in relation to use of cell phones were also suggested in
other ecological trend analyses based on non-Swedish populations. The UK-based study by de
Vocht (2016) showed a faster than expected incidence increase for malignant neoplasms of the
temporal lobe. The Israel-based study by Barchana (2012) found an increasing trend in the period
after mobile phone introduction for high-grade gliomas (including glioblastoma multiforme),
especially among females. Using worldwide GLOBOGAN 2008 data, de Vocht (2013) identified the
rate of mobile/ cell communications subscriptions as a risk indicator for brain/nervous system
cancer. Using data from cancer registries and GLOBOGAN 2012, Neupane (2017) identified
positive associations between the mobile phone and personal computer densities and the
elevated incidence of mortality in prostate cancer. According to the single available ecological
trend analysis involving the US population (Little 2012), glioma incidence trends per US
Surveillance, Epidemiology, and End Results (SEER) program did not confirm the risk increase
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inferred from Swedish studies by Hardell (2010) but were consistent with the modest risk
estimate derived from INTERPHONE (2010) study.
In addition to the aforementioned ecological trend analyses, evidence on possible tumor risk
increases was found in numerous case-control and cohort studies, as presented below in the
sections stratified by outcomes of interest.
3. Outcome of Interest – Brain Tumors (Glioma and Meningioma)
Combined analysis from case-control studies on brain tumors by Hardell and Carlberg
(Carlberg and Hardell 2009, 2014; Hardell 2010, 2011, 2013a,b) showed increased hazards ratios
(HR) for all gliomas with the latency >20 years (HR=1.7 [95% CI: 1.2; 2.3]) and astrocytoma grade
IV (glioblastoma) with the latency >10 years (HR=1.3 [95% CI: 1.03; 1.7]). Highest HR of 2.3 [95%
CI: 1.1; 4.7] was reported among individuals who started using mobile phones before the age of
20. Risk for malignant brain tumors was reported to vary, increasing with the latency 13 >1-5 years,
decreasing in the next latency categories, and then increasing again with the latency >15- 20
years. Per analysis of deceased cases, risk for malignant brain tumors (mostly astrocytoma grade
III-IV) was shown to increase with cumulative lifetime use (Ptrend=0.02). A borderline increased risk
for meningioma (Carlberg and Hardell 2015) was found in the 4th quartile of cumulative phone
use (>1,436 h).
Despite reporting the reduced overall risk as the main finding, INTERPHONE (2010) study
found an increased risk for glioma and meningioma among ‘heavy’ mobile phone users with the
latency of 1–4 (but not >4) years: OR=3.77 [95% CI: 1.25; 11.4] and OR=4.80 [95% CI: 1.49; 15.4],
respectively. Note: some reported values in the ‘heavy’ use (≥1,640h) category, defined as the
10th decile of cumulative call time, were deemed “implausible” by the study authors.
The possibility for increased risks of glioma and meningioma (OR=2.89 [95% CI: 1.41; 5.93]
and OR=2.57 [95% CI: 1.02; 6.44], respectively) among ‘heavy’ users (≥896 h) was also supported
in the CERENAT-based study by Coureau (2014).
In the CEFALO-based study on children and adolescents (Aydin 2011) which did not find the
overall risk increase for brain tumors, elevated risk was found among young individuals with >2.8
years of use (per operator-recorded data): OR = 2.15 [95% CI; 1.07; 4.29].

13

Latency is defined here and in other studies as a time period from first use of mobile phone to diagnosis of tumor.

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In the large cohort study by Frei (2011) which found no indication of dose-response relations
either by subscription years or by tumor location, a borderline increased risk for glioma was found
among men with mobile phone use of 1-4 years: OR=1.20 [95% CI: 0.96; 1.22].
4. Outcome of Interest – Acoustic Neuroma, or Vestibular Schwannoma.
The Swedish studies by Hardell and Carlberg showed a risk increase for acoustic neuroma
among mobile and cordless phone users, especially with the latency >20 years (Hardell and
Carlberg 2009; Hardell 2013c).
INTERPHONE (2011) study found an increased risk for acoustic neuroma in ‘heavy’ users
(≥1640 h) with the latency of 5 years: OR=2.79 [95% CI: 1.51; 5.16]. Note: some values reported in
the ‘heavy’ use category were deemed implausible by the study authors.
Overall increasing risk trends for acoustic neuroma among mobile phone users with >5 min
per call were found in the study by Sato (2011). Substantial risk increases were reported among
users with >20 min/day on average: OR=2.74 [95% CI: 1.18; 7.85] and OR=3.08 [95% CI: 1.47; 7.41]
with the latencies for 1 year and 5 years, respectively.
The study on acoustic neuroma by Pettersson (2014) showed a risk increase among cordless
phone users with higher cumulative use: OR=1.67 [95% CI: 1.13; 2.49]. Among histologicallyconfirmed cases, a risk increase was shown among users of analog phones for 5-9 (but not >10)
years: OR=4.03 [95% CI: 1.07; 15.2].
The case-control study by Moon (2014) did not find evidence for increased incidence of
acoustic neuroma in relation to mobile phone use; however, the case-case analysis from the same
study found correlations between tumor volume and phone usage estimates (see below).
5. Outcome of Interest – Parotid Gland Tumors.
In the study by Sadetzki (2008), elevated risk for parotid gland tumors was associated with
regular use of cell phones and high-exposure conditions. The risk elevation was confined mostly to
rural areas, reaching a 2-fold increase among users with ≥1,035h of cumulative call time: OR=1.96
[95% CI: 1.11; 3.44].
Increased likelihood of parotid gland tumors in relation to ‘heavy’ use of cell phones was
reported by Duan (2011). Risk for epithelial parotid gland malignancy was independently
associated with 13 phone usage variables, with the greatest OR for the user category with >42,000
calls since first use: OR=15.36 [95% CI: 13.34; 17.38]. Possible risk increase was particularly
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suggested for mucoepidermoid carcinoma with an average daily use of >2.5h: OR=31.25 [95% CI:
10.79; 90.45].
6. Outcome of Interest – Skin Cancers.
In the large cohort study on skin cancers (Poulsen 2013), a borderline increase of adjusted
incidence rate ratio: IRR=1.18 [95% CI: 0.98, 1.42] was reported for basal cell carcinoma among
women with 5-9 years (but not 10-12y or >13y) of mobile phone subscription.
7. Outcome of Interest – Leukemia.
Although the case-control study by Cooke (2010) did not find overall risk increase for
leukemia, a borderline increased risk for acute myeloid leukemia was associated with ≥15 years of
use of mobile phones: OR=2.08 [95% CI: 0.98; 4.39].
Possible risk modification due to certain usage practices was also suggested in the casecontrol study by Kaufman (2009) which found no clear overall association with use of cell phones.
Increased risk for leukemia was found among subjects using Global System for Mobile
communications (GSM): OR=2.1 [95% CI: 1.1; 4.1]. Risk increase in relation to cell phones was
shown for myeloid leukemia (acute and chronic combined): OR=1.7 [95% CI: 1.0; 2.9]. Further,
increased risks for combined myeloid leukemia and especially for acute myeloblastic leukemia
(OR=4.3 [95%: 1.3; 15] and OR=5.5 [95% CI: 1.4; 21], respectively) were found among subjects
whose work was affiliated with powerlines. Substantially elevated odds of having myeloid
leukemia were found in cases when ≥2 putative etiological factors (e.g., benzene, pesticides) were
involved.
8. Putative Effect Modifier – Laterality of Tumor in Relation to Laterality
of Phone Use.
The Swedish studies by Hardell and Carlberg (Carlberg and Hardell 2009, 2014; Hardell
2010, 2011, 2013a,b) associated the highest risk for astrocytoma (a type of glioma) with the
latency >10 years of ipsilateral use of mobile and cordless phones. The same authors (Hardell
and Carlberg 2009; Hardell 2013c) also suggested the highest risk for acoustic neuroma among
ipsilateral mobile phone users with >10 years of use.
A greater likelihood for ipsilateral vs. contralateral gliomas among regular users (OR=1.27
[95% CI: 1.19; 1.37]) was also reported in the INTERPHONE (2010) study.
In the case-case and case-specular analyses (Larjavaara 2011) where distances from actual
and specular locations were compared using a hypothetical reference location assigned for each
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tumor, a significant excess of gliomas was found on the self-reported side of use (this finding,
however, was attributed by the authors to recall bias).
In the study by Yoon (2015) which did not find an overall risk increase, increased relative
risks (RR) were reported for among regular users with the same laterality for glioma and phone
use: RR=1.26 (P=0.05) and RR=1.43 (P=0.01) for all respondents and self-respondents,
respectively.
In addition to intracranial tumors such as glioma and meningioma, laterality analysis was
also performed for acoustic neuroma and parotid gland malignancies. INTERPHONE (2011) study
found risk increases for ipsilateral tumors in ‘heavy’ users (≥1640 h) with the latencies for 1 year
and 5 years: OR=2.33 [95% CI: 1.23; 4.40] and OR=3.53 [95% CI: 1.59; 7.82], respectively.
In the study by Sato (2011), a more frequent use of the affected ear was reported in all but
one case (15/16) among ‘persistent heavy’ users (>20 min/day) with acoustic neuroma: OR=5.0
[95% CI: 1.3; 24.8].
In the study by Sadetzki (2008), elevated risk of parotid gland tumors was found among
regular – ipsilateral or bilateral – users with the latency of 5 (but not 10) years. The risk elevation
was especially noticeable among ipsilateral users in the highest categories of cumulative number
of calls and call time: OR=1.58 [95% CI: 1.11, 2.24] and OR=1.49 [95% CI: 1.05, 2.13], respectively.

9. Putative Effect Modifiers – Location and Size of Tumors in Relation to
Mobile Phone Use.
The Swedish studies by Hardell and Carlberg (Carlberg and Hardell 2009, 2014; Hardell
2010, 2011, 2013a,b) suggested increasing risk trends for brain tumors located in the temporal
lobe or overlapping tumors in the temporal and adjacent lobes.
INTERPHONE (2010) study also reported higher likelihood of gliomas located in the temporal
lobe, with the higher risk estimate among ‘heavy’ (≥1,640) users: OR=1.87 [95% CI: 1.09; 3.22].
On the other hand, significantly increased risks for gliomas with locations other than
temporal/ frontal lobe were shown in studies by Coureau (2014) and Aydin (2011): OR=3.61 [95%
CI: 1.00; 12.96] and OR=1.92 [95% CI; 1.07; 3.44], respectively. The cohort-based study on brain
tumors by Frei (2011) reported increased risks for other/unspecified type tumors: OR=1.35 [95%
CI: 1.05; 1.75], tumors in the cerebral ventricle: OR=2.58 [95% CI: 1.08; 6.15] as well as tumors in
the occipital lobe among users for 1-4 years: OR=2.50 [95% CI: 1.18; 5.31].
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The aforementioned analysis on the actual and specular tumor locations (Larjavaara 2011)
did not show predominance of gliomas in the brain parts expected to have the highest RF fields.
In the study by Moon (2014) which did not find increased incidence for acoustic neuroma in
relation to mobile phone use, the MRI-based case-case analysis showed a trend for larger tumors
among regular users (p=0.001), indicating correlation between tumor volume and cumulative
hours of use (r2=0.144, p=0.002).
10. Evidence on Tumor Risk in Relation to Cell Phones from Studies Using
RF Exposure Estimates Other Than Phone Usage Practices 14.
In addition to the aforementioned studies using phone usage practices as the proxies for RF
exposure, some studies assessed tumor-related outcomes based on the RF exposure estimates
such as total cumulative specific energy (TCSE) and SAR.
No increased risk for brain tumors (glioma and meningioma) was found in the case-control
study by Takebayashi (2008), which included assessment of SAR-based spatial relationships
between tumor location and intracranial RF distribution.
The TCSE-based analysis using INTERPHONE study components (Cardis 2011) showed an
increased glioma risk (Ptrend=0.01), reaching OR=1.91 [95% CI: 1.05; 3.47] for the highest TCSE
quintile category with mobile phone use for >7 years. The risk estimate was further increased for
gliomas in the most exposed areas with >10 years of use: OR=2.80 [95% CI: 1.13; 6.94].
The INTERPHONE-based analysis using both SAR and TCSE (Grell 2010) showed an increased
risk of observing a glioma within the shortest distance from preferred ear to gravity center of
tumor (0-55 mm) with cumulative use ≥200 h: OR=4.06 [95% CI: 2.03; 11.6]. Overall, shorter
distances were associated with larger tumors: OR=4.09 [95% CI: 1.90; 12.0].
In the SAR-based case-case analysis by Hartikka (2009), a significant risk increase was shown
for gliomas among contralateral (but not ipsilateral) mobile phone users: OR=4.93 [95% CI: 1.13;
21.5]. However, a risk change (OR=0.51 [95% CI: 0.27; 0.96]) based on the distance between
handset and tumor midpoint among regular vs. non-regular users indicated that a distance
increase by 1cm decreased the odds of glioblastoma by 49%.
In the study by Dode (2011), which was conducted in the Brazilian region of Minas Gerais
with a major concentration of cell phone transmitter antennas, SAR-based analysis of spatial
14

Evaluation of the evidence presented in this section is limited to epidemiological aspects only and it does not include the
methodological validity of dosimetry assessments in the cited publications

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correlation between BS clusters and corresponding mortality estimates (1996-2006) showed an
increased risk of death by neoplasia (more details including the subsequent critical comments and
authors’ response can be found in the individual review of this publication in the section below).
In the population-based case-control study on RF exposure in relation to childhood
neoplasms (Li 2012), annual summarized power (ASP, watt-year) was calculated for mobile phone
BSs and annual power density (APD, watt-year/km2) of each township was computed as a ratio of
the total ASP of all BSs in a township. As a result, typically encountered BS-emitted RF levels were
found not to pose substantial childhood cancer risk. However, higher than median APD (168 wattyear/km2) was associated with borderline risk increases for all neoplasms and leukemia in
particular: OR=1.13 [95% CI: 1.01; 1.28] and OR=1.23 [95% CI: 0.99; 1.52], respectively.

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C. Overall Limitations of Epidemiology Data.
As described in this section, despite the sizeable amount of retrieved and reviewed data,
cross-cutting limitations that involved almost all manuscripts impacted the overall data
interpretation and limited comprehensive conclusions on all possible aspects of RF-related tumor
risk for humans.
1. Data Quality Affected by Limitations of RF Exposure Measurements.
Epidemiologic evidence was mostly derived from observational studies that used phone
usage practices as the proxy estimates for RF exposure. None of the available
epidemiologic/clinical studies, including the ones that used SAR and TCSE based RF exposure
measurements, attempted to estimate the entire accumulated RF dose from all possible EMFs in
the individual environments of study subjects. The accuracy of indirect RF assessment per phone
usage practices was further limited by use of self (or kin)-reported questionnaires that had varying
definitions for measurables and that were mostly collected in the non-blind setting. In addition to
possible inaccuracies in the RF exposure measurements based on phone usage patterns (which
are not necessarily directly correlated), exposure misclassification was virtually unavoidable in
ecological trend analyses (de Vocht 2013; Neupane 2017) or cohort studies (Poulsen 2013) that
used mobile phone subscription data, without the means for further classification by actual phone
usage practices at individual levels.
2. Strong Biases Affecting Data Analysis and Interpretation.
Due to inevitable errors in the measurements of RF exposure, all studies were affected, to
varying degrees, by the exposure classification bias. In addition to possible nondifferential bias
with a systematic measurement error (similar between cases and controls), exposure
misclassification, to an even greater extent, was likely caused by differential errors due to recall
bias (e.g., better memory of phone use among study cases vs. healthy controls) or ascertainment
bias (e.g., phone use information was influenced by tumor diagnosis). Recall bias is avoided in
cohort studies as exposure is assessed prior to disease occurrence. Furthermore, the two
available cohort studies, the million women study of Benson et al (2013) and the Danish cohort
study of Schuz et al (2011) both failed to find an association between cell phone use and glioma
or meningioma. Information on estimated RF exposure might have been also affected by mental
status of interviewees with brain tumors or by hearing impairment in cases with acoustic neuroma
(with the latter causing non-random variations in laterality analyses in particular). Many case-case
studies were prone to selection and classification biases due to heterogeneity or limited
availability of cases and/or controls, resulting in the study populations that were not fully
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representative of cell phone use practices or tumor incidences. Some studies were also prone to
possible assumption and interpretation biases due to their study designs based on uncertain
postulations (e.g., hypothetical tumor location assigned for controls, or baseline risk estimates in
ecological trend analyses). Exposure assessment is further limited by the fact that there is an
absence of experimental evidence that can determine if frequency, duration, or intensity of
exposure is the most important factor in potential cancer risk. The component of exposure that
epidemiologists should target is unknown.
Even the most cited international studies such as INTERPHONE (2010, 2011) which collected
individual phone usage data were affected by heavy multi-composite biases that resulted in the
overall reduced tumor risk, undermining the validity of derived evidence. Although the
INTERPHONE study authors rendered a genuine protective effect as implausible and referred to
strong bias as the main explanation, their reports of reduced tumor likelihood (along with a
number of elevated ORs) spurred widespread discussions, involving social and popular science
media and resulting in some ungrounded statements such as “for most people cell phone use
appeared to protect against brain tumors” 15. On the contrary, increased risk trends that stemmed
from multiple publications by the same group (Hardell and Carlberg, 2009-2017, Sweden) were
likely affected by limitations of a single data source limited to one population.
3. Lack of Evidence Based on the U.S. Population.
The vast majority of reviewed studies, including multi-country studies (INTERPHONE 2010,
2011; de Vocht 2013), were conducted outside the US (mostly, in Europe), while very few studies
assessed the risk of tumor in relation to mobile phone use based on the US population (Inskip
2010; Han 2012; Little 2012). There is compelling evidence from the Surveillance, Epidemiology
and End Results (SEER) program, a highly regarded cancer registry, that the incidence of brain
cancer has not increased over the last 20 years despite cell phones becoming nearly ubiquitous16.
It might also be noted here that the failure to detect a real increase in brain cancer rates is
exceedingly unlikely because of the high specificity and sensitivity of the non-invasive diagnostic
modalities of computerized tomography and magnetic resonance imaging.
Finally, it is worthy of note that there are currently no primary or secondary prevention
efforts to reduce brain cancer incidence. There are no countervailing forces that would offset a
potential increase in the rate of brain cancer from cell phone use. With the findings from these
15 https://www.sciencenews.org/blog/science-public/interphone-study-finds-hints-brain-cancer-risk-heavy-cell-phone-users
16 https://www.arpansa.gov.au/news/new-arpansa-study-finds-no-link-between-mobile-phone-use-and-brain-cancers

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three cited US studies mentioned in the Summary, “the very linear relationship between cell
phone usage and brain tumor incidence” reported in an additional US study (Lehrer et al 2011)
cannot be accepted as valid due the study’s flawed statistical assessment (for more details see
Section V.D below).
4. No Overall Risk Increase, with Some Evidence Pointing at Possible
Subgroup Effects.
As discussed by the INTERPHONE (2010, 2011) authors, while systematic bias in these
studies could result in spurious associations inflating certain risk estimates, the elevated ORs
could also indicate small effects detectable only in subsets of the study population. The possibility
of true risk elevations due to the small subgroup effects (rather than due to the falsely inflated
risk estimates) appears even more plausible, when considering the presence of a strong bias that
resulted in the overall reduced risk estimates in both INTERPHONE studies.
The possibility of s

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Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/tribal%3Around_valley%3Ab7a39fbd4fe2ab57. Public record. Not legal advice.