ID Number		752
Study Type		In Vivo
Model		NTP/NIEHS Long Term Animal Study: 800, 1900 MHz (GSM, CDMA) exposure to rats and mice and analysis of pathology and dosimetry.
Details		Rats and mice (male and female, n = 100-200 per group, 3000 in total) exposed to 800 and 1900 MHz (GSM, CDMA) RF from gestation day-6 to two years of age using large reverberation chambers. Three RF exposure levels will be used, with the highest exposure level determined by an initial thermal pilot study (exposing animals to RF 20 hrs / day for 5 days at various RF energy levels to determine the threshold of a 1 degree temperature rise). Following the determination of appropriate RF exposure groups, animals will be exposed chronically for 20 hrs / day for 2 years. End-of-study analysis will include whole body histopathology as well as other toxicity endpoints (blood brain barrier permeability, lens optical quality, miconuclei induction, and DNA strand breaks in brain cells). AUTHORS' ABSTRACT: Capstick et al. 2017 (IEEE #6715): In this paper, we present the novel design features, their technical implementation, and an evaluation of the radio frequency exposure systems developed for the National Toxicology Program (NTP) of the National Institute of Environmental Health Sciences studies on the potential toxicity and carcinogenicity of second and third generation mobile-phone signals. The system requirements for this second-year NTP cancer bioassay study were the tightly controlled lifetime exposure of rodents (1568 rats and 1512 mice) to three power levels plus sham simulating typical daily, and higher, exposures of users of GSM and CDMA (IS95) signals. Reverberation chambers and animal housing were designed to allow extended exposure time per day for free-roaming individually housed animals. The performance of the chamber was characterized in terms of homogeneity, stirred to unstirred energy and efficiency. The achieved homogeneity was 0.59 and 0.48 dB at 900 and 1900 MHz, respectively. The temporal variation in the electric field strength was optimized to give similar characteristics to that of the power control of a phone in a real network using the two stirrers. Experimental dosimetry was performed to validate the SAR sensitivity and determine the SAR uniformity throughout the exposure volume; SAR uniformities of 0.46 and 0.40 dB, respectively, for rats and mice were achieved. AUTHORS' ABSTRACT: Gong et al. 2017 (IEEE #6716): In this paper, we present the detailed life-time dosimetry analysis for rodents exposed in the reverberation exposure system designed for the two-year cancer bioassay study conducted by the National Toxicology Program of the National Institute of Environmental Health Sciences. The study required the well-controlled and characterized exposure of individually housed, unrestrained mice at 1900 MHz and rats at 900 MHz, frequencies chosen to give best uniformity exposure of organs and tissues. The wbSAR, the peak spatial SAR, and the organ specific SAR as well as the uncertainty and variation due to the exposure environment, differences in the growth rates, and animal posture were assessed. Compared to the wbSAR, the average exposure of the high-water-content tissues (blood, heart, lung) were higher by $\sim$4 dB, while the low-loss tissues (bone and fat) were less by $\sim$9 dB. The maximum uncertainty over the exposure period for the SAR was estimated to be <49% (k = 2) for the rodents whereas the relative uncertainty between the exposure groups was <14% (k = 1). The instantaneous variation (averaged over 1 min) was <13% (k = 1), which is small compared to other long term exposure research projects. These detailed dosimetric results empowers comparison with other studies and provides a reference for studies of long-term biological effects of exposure. AUTHORS' CONCLUSIONS: Wyde et al. 2018 (IEEE #6922): Under the conditions of this 2-year whole-body exposure study, there was some evidence of carcinogenic activity of GSM-modulated cell phone RFR at 900 MHz in male Hsd:Sprague Dawley SD rats based on the incidences of malignant schwannoma in the heart. The incidences of adenoma or carcinoma (combined) in the prostate gland, malignant glioma and benign or malignant granular cell tumors in the brain, adenoma of the pars distalis in the pituitary gland, pheochromocytoma (benign, malignant, or complex combined) in the adrenal medulla, and pancreatic islet cell adenoma or carcinoma (combined) may have been related to cell phone RFR exposure. There was no evidence of carcinogenic activity of GSM-modulated cell phone RFR at 900 MHz in female Hsd:Sprague Dawley SD rats administered 1.5, 3, or 6 W/kg. There was some evidence of carcinogenic activity of CDMA modulated cell phone RFR at 900 MHz in male Hsd:Sprague Dawley SD rats based on the incidences of malignant schwannoma in the heart. The incidences of malignant glioma in the brain, adenoma of the pars distalis in the pituitary gland, and adenoma or carcinoma (combined) of the liver may have been related to cell phone RFR exposure. There was equivocal evidence of carcinogenic activity of CDMA-modulated cell phone RFR at 900 MHz in female Hsd:Sprague Dawley SD rats based on the incidences of malignant glioma in the brain and pheochromocytoma (benign, malignant, or complex combined) in the adrenal medulla. Increases in nonneoplastic lesions in the heart, brain, and prostate gland of male rats, and of the heart, thyroid gland, and adrenal gland in female rats occurred with exposures to GSM cell phone RFR at 900 MHz. Increases in nonneoplastic lesions of the heart, brain, and prostate gland occurred in males, and of the brain in females exposed to CDMA cell phone RFR at 900 MHz. AUTHORS' CONCLUSIONS: Wyde et al. 2018 (IEEE #6923): Under the conditions of these 2-year studies, there was equivocal evidence of carcinogenic activity of GSM-modulated cell phone RFR at 1,900 MHz in male B6C3F1/N mice based on the combined incidences of fibrosarcoma, sarcoma, or malignant fibrous histiocytoma in the skin and the incidences of alveolar/bronchiolar adenoma or carcinoma (combined) in the lung. There was equivocal evidence of carcinogenic activity of GSM-modulated cell phone RFR at 1,900 MHz in female B6C3F1/N mice based on the incidences of malignant lymphoma (all organs). There was equivocal evidence of carcinogenic activity of CDMA-modulated cell phone RFR at 1,900 MHz in male B6C3F1/N mice based on the incidences of hepatoblastoma of the liver. There was equivocal evidence of carcinogenic activity of CDMA-modulated cell phone RFR at 1,900 MHz in female B6C3F1/N mice based on the incidences of malignant lymphoma (all organs). Exposure to GSM- or CDMA-modulated cell phone RFR at 1,900 MHz did not increase the incidence of any nonneoplastic lesions in male or female B6C3F1/N mice. AUTHORS' ABSTRACT: Hardell and Carlberg 2019 (IEEE #7203): During the use of handheld mobile and cordless phones, the brain is the main target of radiofrequency (RF) radiation. An increased risk of developing glioma and acoustic neuroma has been found in human epidemiological studies. Primarily based on these findings, the International Agency for Research on Cancer (IARC) at the World Health Organization (WHO) classified in May, 2011 RF radiation at the frequency range of 30 kHz300 GHz as a possible human carcinogen, Group 2B. A carcinogenic potential for RF radiation in animal studies was already published in 1982. This has been confirmed over the years, more recently in the Ramazzini Institute rat study. An increased incidence of glioma in the brain and malignant schwannoma in the heart was found in the US National Toxicology Program (NTP) study on rats and mice. The NTP final report is to be published; however, the extended reports are published on the internet for evaluation and are reviewed herein in more detail in relation to human epidemiological studies. Thus, the main aim of this study was to compare earlier human epidemiological studies with NTP findings, including a short review of animal studies. We conclude that there is clear evidence that RF radiation is a human carcinogen, causing glioma and vestibular schwannoma (acoustic neuroma). There is some evidence of an increased risk of developing thyroid cancer, and clear evidence that RF radiation is a multisite carcinogen. Based on the Preamble to the IARC Monographs, RF radiation should be classified as carcinogenic to humans, Group 1.
Findings		Ongoing
Status		Ongoing
Start Date		Sep 1, 2005
End Date		Dec 1, 2009
Principal Investigator		Illinois Inst Technology Research Inst.
Funding Agency		NIEHS, USA, NTP, USA
Country		UNITED STATES
References		Wyde, ME et al. , (2016) bioRxiv preprint (Draft):74 pages-May 19, 2016 Draft Capstick, MH et al. IEEE Transactions on Electromagnetic Compatibility., (2017) Mar 17, 2017:-12 pages Gong, Y et al. IEEE Trans Electromagn Compat. , (2017) 59:1798-1808 Wyde, ME et al. NTP TR (Technical Report) 595 (DRAFT)., (2018) :381 pages- Wyde, ME et al. NTP TR Technical Report 596 (DRAFT)., (2018) :270 pages- Labos, C et al. Skepital Inquirer, (2018) 42:12-14 Wyde, ME et al. Bioelectromagnetics., (2018) 39:190-199 Eaton, D Copied from internet on August 7, 2019 at https://ntp.niehs.nih.gov/ntp/about_ntp/trpanel/2018/march/peerreview20180328_508.pdf, (2018) :- Hardell, L et al. Int J Oncol., (2019) 54:111-127 Smith-Roe, SL et al. Environmental and Molecular Mutagenesis., (2020) 61:276-290 Vijayalaxmi, et al. Environmental and Molecular Mutagenesis., (2019) :- Smith-Roe, SL et al. Environmental and Molecular Mutagenesis. , (2020) 61:294-295 Kuhne, J et al. Bioelectromagnetics., (2020) 41:471-479 Jargin, S Dose Response., (2020) :doi.org/10.1177/1559325820959557- NTP, National Toxicology Program, U.S. Department of Health and Human Services., (2018) https://ntp.niehs.nih.gov/ntp/about_ntp/trpanel/2018/march/actions20180328_508.pdf:-(3 pages) NTP, National Toxicology Program, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Sciences. NTP TR 596. Released 1 Nov 2018., (2018) https://www.niehs.nih.gov/ntp-temp/tr596_508.pdf:- NTP, National Toxicology Program, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Sciences. NTP TR 595. Released 1 Nov 2018., (2018) https://www.niehs.nih.gov/ntp-temp/tr595_508.pdf:- Wyde, M et al. https://www.biorxiv.org/content/early/2016/06/23/055699 (updated version, posted June 23, 2016)., (2018) :- BERENIS, BERENIS Newsletter Website (short version of evaluation at BERENIS Newsletter 15/2018)., (2018) :-
Comments		Exposure systems (reverberation chambers) designed by Kuster