Health concerns from US NTP

and Ramazzini Institute animal

carcinogenic studies

Dr Mike Repacholi
Visiting Professor, University of Rome “La Sapienza”
Former Coordinator, WHO EMF Project
Emeritus member, ICNIRP
and
Prof Rodney Croft
Member, ICNIRP
Australian Centre for Electromagnetic Bioeffects Research
School of Psychology University of Wollongong Australia

International Forum: Latin American Review Update on Radiofrequency

Telecommunications: New Developments, Measurements and Human Health
4-5 October 2018, National University San Marcos, Lima, Peru
 Do RF fields cause cancer?
 Main research question for decades.
 Some epi studies suggest RF might cause cancer; IARC 2B
 High quality animal studies good indicator of cancer in humans.
 Usually requires an agent to cause the same cancer in 2
different animal species for the agent to cause it in humans.
 So NTP tests agent carcinogenicity in both rats and mice.
 NTP and Ramazzini Institute studies
 NTP study started in response to WHO EMF project’s research agenda;
can RF field exposure cause brain cancers among mobile phone users?
 NTP published its full results in rats (NTP 2018a) and mice (NTP 2018b)
 Italian Ramazinni Institute study (Falcioni et al 2018) on rats used base
station to determine whether RF exposures could cause cancer.
 NTP and Ramazzini are good studies; used large numbers of animals,
exposed animals for their whole lives, and used GLP procedures.
 Studies are important for WHO’s health risk assessment and ICNIRP
guidelines update

NTP (2018a) Toxicology and carcinogenesis studies of GSM- and CDMA-modulated cell phone radio frequency
radiation at 900 MHz in Hsd:Sprague Dawley SD rats . NTP TR 595

NTP (2018b) 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. TR 596

Falcioni, L et al (2018), Report of final results regarding brain and heart tumors in Sprague-Dawley rats exposed from
prenatal life until natural death to mobile phone radiofrequency field representative of a 1.8 GHz GSM base station
environmental emission. Environmental Research https://doi.org/10.1016/j.envres.2018.01.037
 NTP RF Exposure
System
NTP used reverberation chambers to expose
Hsd:Sprague Dawley male and female rats to
900 MHz GSM and CDMA-modulated RF
signals at whole-body SARs of 1.5, 3 and 6
W/kg and male and female mice to 1900 MHz
GSM and CDMA-modulated RF signals at
whole body SARs of 2.5, 5 and 10 W/kg.

Both rodent species were exposed 9 hrs and

10 mins/day, (10 mins on and 10 mins off for
18 hrs and 20 mins). beginning in utero
(gestation day 5) and continuing after birth for
up to 107 weeks (rats), or beginning at 5-6
weeks of age and continuing for 106 and 108
weeks in males and females respectively
(mice).
Each animal group had 90 animals.
 Ramazzini Institute (Falcioni et al
2018) RF exposures
Four groups of 817, 811, 411, 409 male and female Sprague-Dawley rats
were whole-body exposed from prenatal life (12th day of gestation) until
natural death to far field 1.8 GHz GSM at 0, 5, 25, and 50 V/m, (equivalent to
0.001, 0.03 and 0.1 W/kg respectively) continuously for 19 h/day. Remaining
time used for cleaning and maintenance.

Far-field, very low-level

RF fields to simulate
exposures from mobile
phone base stations.
 NTP Results GSM mice
For mice exposed to GSM, there was “equivocal evidence of carcinogenic
activity of male B6C3F1/N mice based on”:

 “Combined incidences of fibrosarcoma, sarcoma, or malignant fibrous

histiocytoma in the skin”;
 “Incidences of alveolar/bronchiolar adenoma or carcinoma (combined)
in the lung”; and
 “Incidences of malignant lymphoma (all organs)”.
 No evidence of neoplastic lesions was noted in female mice.
 NTP Results GSM rats
For rats exposed to GSM, there is:
 “some evidence of carcinogenic activity of male Hsd:Sprague Dawley SD
rats based on incidences of malignant schwannoma in the heart”.
 “equivocal evidence of carcinogenicity of male Hsd:Sprague Dawley SD rats”
based on:
 “Incidences of adenoma or carcinoma (combined) in the prostate gland”;
 “Incidences of malignant glioma in the brain”;
 “Benign or malignant granular cell tumors in the brain”;
 “Incidences of adenoma in the pars distalis of the pituitary gland”;
 “Incidences of pheochromocytoma (benign, malignant, or complex combined) in the
adrenal medulla”; and
 “Incidences of pancreatic islet cell adenoma or carcinoma (combined)”.

There was “no evidence of carcinogenic activity of female Hsd:Sprague Dawley

SD rats”.
 NTP Results GSM mice

For mice exposed to CDMA, there is:

 “Equivocal evidence of carcinogenic activity of male B6C3F1/N

mice based on incidences of hepatoblastoma in the liver”; and
 “Equivocal evidence of carcinogenic activity of female
B6C3F1/N mice based on incidences of malignant lymphoma
(all organs)”.
 NTP results GSM rats
For rats exposed to CDMA, there is:
 “some evidence of carcinogenic activity of male Hsd:Sprague Dawley SD
rats based on incidences of malignant schwannoma in the heart”; and
 “equivocal evidence of carcinogenic activity of male Hsd:Sprague Dawley
SD rats” based on:
 “Incidences of malignant glioma in the brain”;
 “Incidences of adenoma in the pars distalis of the pituitary gland”; and
 “Incidences of adenoma or carcinoma (combined) in the liver”.

NTP also concluded that there is: “Equivocal evidence of carcinogenic activity
of female Hsd:Sprague Dawley SD rats” based on:
 “Incidences of malignant glioma in the brain”; and
 “Incidences of pheochromocytoma (benign, malignant, or complex combined) in the
adrenal medulla”.
 NTP results overall
The strongest evidence of carcinogenicity (i.e. ‘some evidence’) was for
male rats, where incidences of malignant schwannoma in the heart (but
not at other locations) increased with both GSM and CDMA exposures. An
exposure-response trend was reported to be statistically significant.
Also the incidence of malignant cardiac schwannomas for 6 W/kg CDMA
male rat exposures were found significantly higher than the controls.

The results for male rats were the strongest findings from the NTP study,
and are evaluated below.

No evidence of increased rates of malignant schwannoma in the heart was

reported for female rats or for male or female mice, from either the GSM
or CDMA exposure groups.
 NTP survival rates
 Huge difference in male rat survival
rates: Controls 28% versus exposed
groups 48-68%.
 High control mortality due to a higher
incidence of chronic progressive
nephropathy (kidney disease), which is
more prevalent in male rats
 Male rat control mortality (28%) well
below historic range (40-60%)
 Exposed groups and control female rat
survival in historic range.
 High control mortality suggests rats
didn’t live long enough to contract late
developing gliomas or schwannomas.
 This can result in no tumours in
controls but tumours in the exposed
groups merely because the exposed
groups lived longer.
 Falcioni et al Results
 No differences in water or food consumption, mean body weight or survival
in male or female rats.
 Non-significant increased incidence of malignant gliomas only in female
rats exposed to 50 V/m (0.1 W/kg).
 A statistically significant increase in heart Schwannomas in treated male
rats only at the highest dose (50 V/m).
 A non-significant increase in heart Schwann cell hyperplasia in treated male
and female rats at the highest dose (50 V/m).
 Hyperplasia numbers similar to tumours; not following normal course of
carcinogenesis since only a small % of hyperplasia cells progress to cancer.
 NTP glioma results
Significant positive trend in glioma incidence for CDMA exposed male rats; not GSM!
Not considered convincing by NTP because of very high mortality in controls. 10/11
gliomas in exposed male rats at 101 weeks or more when most control rats dead.

 Historical mean control incidence from previous NTP studies 0-4%, so

would expect up to 3-4 gliomas in a 90 rat control group.
 If 1 glioma was found in the controls, no significant result!!
 Survival rate in female rats better than historical control rates.
 No significant increased incidence found in female rats, or male or female
mice??
 Brain cancer
 NTP study found only “equivocal evidence” for
an increased incidence of gliomas (brain tumours),
only in male rats; no convincing evidence for brain tumours from RF
exposure. No evidence from female rats or male or female mice study.
 NTP definition: Equivocal evidence of carcinogenic activity is demonstrated
by studies that are interpreted as showing a marginal increase of
neoplasms that may be test agent related.
 Falcioni et al did not find any statistical increase in the incidence of
gliomas in either male or female rats
 These huge studies have provided substantial evidence that RF fields from
mobile phones do not cause brain cancer. A result supported by most high
quality animal and epidemiological studies.
 Cardiac schwannomas
 The strongest NTP results is “some evidence” of increased cardiac
schwannomas in male rats; not in female rats, or in male or female mice.
 NTP definition: “Some evidence” of carcinogenic activity is demonstrated by
studies that are interpreted as showing a test agent-related increased
incidence of neoplasms (malignant, benign, or combined) in which the
strength of the response is less than that required for clear evidence.
 Falcioni et al. reported a significantly increased incidence of schwannomas in
the heart of male rats exposed at the highest SAR (0.1 W/kg)
 Falcioni argued this was consistent with NTP (2018a) schwannoma results.
 Increased incidence of heart Schwann cell hyperplasia (male and female)
and malignant glial tumours (female only) were also reported, but as noted
by the authors, these were not statistically significant.
 We will critique this effect on cardiac schwannomas to determine any health
implications. Most other results are well within historical incidence rates in
controls and will not be discussed further.
 Glial and schwannoma cells

Glial cells: non-neuronal cells that maintain homeostasis,

form myelin, and support and protect nerves in
the central and peripheral nervous systems. In CNS different glial
cells are those shown in the figure, and in the PNS glial cells
include Schwann cells.
 NTP Schwannoma results
Increased positive trend in heart Schwannomas in male rats for GSM and CDMA.
No increased trend in any other tissues studied, or in female rats.
Increase incidence of heart Schwannomas exposed to 6W/kg CDMA but not GSM!!

 Historical control incidence: Heart 0-2% (expect up to 2 lesions in 90 controls)

 All organs 0-4% (expect up to 3-4 lesions in 90 controls)
 One Schwannoma in controls would not change the increased incidence at 6 W/kg,
but the positive trend for heart schwannomas becomes non-significant.
 Combined incidences for all sites (including the heart), were generally higher in
exposed males, but not significantly different from the controls.
 Possible controls did not live long enough to get schwannomas (NTP 2018a, p156).
Evidence: 13/19 schwannomas in controls were found at terminal necropsy (rats
were moribund from kidney disease and then they find schwannoma after pathology
exam).
 Concerns with the NTP study
 Small common control group for all exposure groups, low power
 Kidney disease in controls caused significantly lower survival than in
exposed groups; controls did not survive to get gliomas or schwannomas
 Because of this, when controls show no tumours, this causes unconvincing
comparisons with exposed groups. One lesion in the controls, half the
normal background incidence, would have made most results non-significant
 Schwannomas were found in other organs of the PNS of male rats, but no
significant increases were found. They were also found in other organs of
the control group, but notably, none in the heart.
 Over 12,000 comparisons were made without controlling for multiple
comparisons increasing the probability of finding positive results by chance
 Heating at 6 W/kg could have caused some results; NTP measured
peripheral temperatures not core temperature. Temperature may not return
to normal before the next 10 min exposure.
 Concern with the Falcioni study

 Female control rat cardiac schwannomas were 3x higher than

historical controls
 No cardiac schwannomas in male control rats while at least 2
would be expected from historical control rates
 Female rats exposed at 0.01 W/kg had 4x the number of
schwannomas than those exposed at 0.1 W/kg
 Overall there were more schwannomas in female than male
rats, which is opposite to what NTP found and what would be
expected from historical control incidence rates
 Results are very inconsistent overall.
 Conclusions
 NTP and Falcioni et al are well-conducted, large animal studies
using GLP.
 Neither the NTP or Ramazzini Institute studies found significant
increases in malignant gliomas (brain cancer)
 While Falcioni claims to support NTP results, this is not the
case; an increased incidence of cardiac schwannomas was
found only at 0.1 W/kg while NTP found an increased incidence
only at 6 W/kg, not at 1.5 W/kg or 3 W/kg.
 Both NTP and Falcioni reported approximately equal numbers
of hyperplasias and malignancies, which does not follow the
normal course to carcinogenesis.
 Some epi studies suggest an increase in vestibular
schwannomas (acoustic neuromas), but no increases were
found in the NTP or Falcioni studies.
 ICNIRP RF Guideline Implications

 The results of these two large animal studies support

the conclusion that RF exposures do not cause cancer.
 The basis for ICNIRP guideline limits is to prevent
thermal effects. These two studies do not provide any
evidence against the basis for the exposure limits
 Only NTP result at 6 W/kg, 75x ICNIRP public limit
 Further information: “ICNIRP Note on recent animal
carcinogenesis studies”
www.icnirp.org/cms/upload/publications/ICNIRPnote2018.pdf
 Thank
Thank you for
you
your attention
for your
Gracias por su
attention
atención

Dr Mike Repacholi Prof. Rodney Croft

Department of Information Engineering, Australian Centre for Electromagnetic Bioeffects Research
Electronics and Telecommunications (DIET) School of Psychology | Faculty of Social Sciences
University of Rome “La Sapienza” Rome Italy University of Wollongong NSW Australia
E-mail: mrepacholi@yahoo.com E-mail: rcroft@uow.edu.au