NTP T R M E R (1,900 Mh

NTP TechNical RePoRT oNThe Toxicology aNdcaRciNogeNesis sTudies iNB6c3F1/N M ice exPosedTo Whole - Body R adioFRequeNcy RadiaTioN aTa FRequeNcy (1,900 Mhz)aNd ModulaTioNs(gsMusedaNdByNTP TR 596NOVEMBER 2018cdMa)cell PhoNes

NTP Technical Report on theToxicology and Carcinogenesis Studies inB6C3F1/N Mice Exposed to Whole-body RadioFrequency Radiation at a Frequency (1,900 MHz)and Modulations (GSM and CDMA)Used by Cell PhonesTechnical Report 596November 2018National Toxicology ProgramPublic Health ServiceU.S. Department of Health and Human ServicesISSN: 2378-8925Research Triangle Park, North Carolina, USA

GSM- and CDMA-modulated Cell Phone RFR, NTP TR 596ForewordThe National Toxicology Program (NTP) is an interagency program within the Public HealthService (PHS) of the Department of Health and Human Services (HHS) and is headquartered atthe National Institute of Environmental Health Sciences of the National Institutes of Health(NIEHS/NIH). Three agencies contribute resources to the program: NIEHS/NIH, the NationalInstitute for Occupational Safety and Health of the Centers for Disease Control and Prevention(NIOSH/CDC), and the National Center for Toxicological Research of the Food and DrugAdministration (NCTR/FDA). Established in 1978, NTP is charged with coordinatingtoxicological testing activities, strengthening the science base in toxicology, developing andvalidating improved testing methods, and providing information about potentially toxicsubstances to health regulatory and research agencies, scientific and medical communities, andthe public.The Technical Report series began in 1976 with carcinogenesis studies conducted by theNational Cancer Institute. In 1981, this bioassay program was transferred to NTP. The studiesdescribed in the Technical Report series are designed and conducted to characterize and evaluatethe toxicologic potential, including carcinogenic activity, of selected substances in laboratoryanimals (usually two species, rats and mice). Substances selected for NTP toxicity andcarcinogenicity studies are chosen primarily on the basis of human exposure, level of production,and chemical structure. The interpretive conclusions presented in NTP Technical Reports arebased only on the results of these NTP studies. Extrapolation of these results to other species,including characterization of hazards and risks to humans, requires analyses beyond the intent ofthese reports. Selection per se is not an indicator of a substance’s carcinogenic potential.NTP conducts its studies in compliance with its laboratory health and safety guidelines and FDAGood Laboratory Practice Regulations and must meet or exceed all applicable federal, state, andlocal health and safety regulations. Animal care and use are in accordance with the Public HealthService Policy on Humane Care and Use of Animals. Studies are subjected to retrospectivequality assurance audits before being presented for public review.The NTP Technical Reports are available free of charge on the NTP website and cataloged inPubMed, a free resource developed and maintained by the National Library of Medicine (part ofthe National Institutes of Health). Data for these studies are included in NTP’s Chemical Effectsin Biological Systems database.For questions about the reports and studies, please email NTP or call 984-287-3211.ii

GSM- and CDMA-modulated Cell Phone RFR, NTP TR 596Table of ContentsForeword . iiTables .vFigures. viAbout This Report. viiExplanation of Levels of Evidence of Carcinogenic Activity . xiPeer Review . xiiiPublication Details .xvAcknowledgments.xvAbstract . xviGSM . xviTwenty-eight-day Study. xviTwo-year Study . xviCDMA . xviiTwenty-eight-day Study. xviiTwo-year Study . xviiGenetic Toxicology . xviiiComet Assay . xviiiMicronucleus Assay . xviiiConclusions . xixIntroduction .1Overview .1Radio Frequency Radiation (RFR) Measurement and Applications.1Cell Phones and RFR .3Cell Phone RFR Signal Modulation.3Modulation Schemes (GSM and CDMA).4Sources, Use, and Human Exposure .6Safety Guidelines for Exposure .7Absorption of RFR .8Toxicity .8Thermal Effects .9Experimental Animals .9Humans .10Carcinogenicity .10Experimental Animals .11Humans .11Genetic Toxicity .12Study Rationale .13Materials and Methods .15Overview .15Reverberation Chamber Method of Exposure.16iii

GSM- and CDMA-modulated Cell Phone RFR, NTP TR 596RFR Exposure Facility .17Facility Design and Reverberation Chambers .18Cage Racks and Watering System .19RFR Exposure System Control .22RFR Signal Generation .22Verification of RFR Exposure .23RFR Exposure Monitoring .24Monitoring and Maintenance of Environmental Conditions .25Animal Source.26Animal Welfare .26Twenty-eight-day Studies .26Two-year Studies .27Study Design .27Clinical Examinations and Pathology .28NTP Pathology Review Process .29Statistical Methods .34Survival Analyses .34Calculation of Incidence .34Analysis of Neoplasm and Nonneoplastic Lesion Incidences .34Analysis of Continuous Variables .35Historical Control Data .35Quality Assurance Methods .36Genetic Toxicology .36Results .38Data Availability .38GSM .38Twenty-eight-day Study.38Two-year Study .41CDMA .52Twenty-eight-day Study.52Two-year Study .55Genetic Toxicology .64Discussion .66Conclusions .69References .70Summary of Lesions in Male Mice Exposed to GSM-modulated Cell PhoneRFR for Two Years . A-1Summary of Lesions in Female Mice Exposed to GSM-modulated CellPhone RFR for Two Years .B-1Summary of Lesions in Male Mice Exposed to CDMA-modulated CellPhone RFR for Two Years .C-1Summary of Lesions in Female Mice Exposed to CDMA-modulated CellPhone RFR for Two Years . D-1iv

GSM- and CDMA-modulated Cell Phone RFR, NTP TR 596Genetic Toxicology . E-1Hematology Results . F-1Organ Weights and Organ-Weight-to-Body-Weight Ratios . G-1Reproductive Tissue Evaluations and Estrous Cycle Characterization . H-1GSM- and CDMA-modulated Cell Phone RFR Exposure Data. I-1Ingredients, Nutrient Composition, and Contaminant Levels in NTP-2000Rat and Mouse Ration . J-1Sentinel Animal Program . K-1Peer Reviews of the Draft NTP Technical Reports on Cell PhoneRadiofrequency Radiation . L-1TablesSummary of the Two-year Carcinogenesis and Genetic Toxicology Studies of GSM- andCDMA-modulated Cell Phone RFR Exposure in Mice .xxTable 1. Experimental Design and Materials and Methods in the Whole-Body ExposureStudies of GSM- and CDMA-modulated Cell Phone RFR .31Table 2. Mean Body Weights and Survival of Mice Exposed to GSM-modulated CellPhone RFR for 28 Days .38Table 3. Mean Body Temperatures of Mice Exposed to GSM-modulated Cell Phone RFRfor 28 Days .40Table 4. Survival of Mice Exposed to GSM-modulated Cell Phone RFR for Two Years .41Table 5. Mean Body Weights and Survival of Male Mice Exposed to GSM-modulatedCell Phone RFR for Two Years.44Table 6. Mean Body Weights and Survival of Female Mice Exposed to GSM-modulatedCell Phone RFR for Two Years.45Table 7. Incidences of Neoplasms of the Skin (Subcutaneous Tissue) in Male MiceExposed to GSM-modulated Cell Phone RFR for Two Years .48Table 8. Incidences of Alveolar/bronchiolar Neoplasms in Male Mice Exposed to GSMmodulated Cell Phone RFR for Two Years .50Table 9. Incidences of Malignant Lymphoma in Female Mice Exposed to GSMmodulated Cell Phone RFR for Two Years .51Table 10. Mean Body Weights and Survival of Mice Exposed to CDMA-modulated CellPhone RFR for 28 Days .52Table 11. Mean Body Temperatures of Mice Exposed to CDMA-modulated Cell PhoneRFR for 28 Days .54Table 12. Survival of Mice Exposed to CDMA-modulated Cell Phone RFR for TwoYears .55Table 13. Mean Body Weights and Survival of Male Mice Exposed to CDMA-modulatedCell Phone RFR for Two Years .59Table 14. Mean Body Weights and Survival of Female Mice Exposed to CDMAmodulated Cell Phone RFR for Two Years .60v

GSM- and CDMA-modulated Cell Phone RFR, NTP TR 596Table 15. Incidences of Neoplasms of the Liver in Male Mice Exposed to CDMAmodulated Cell Phone RFR for Two Years .62Table 16. Incidences of Malignant Lymphoma in Female Mice Exposed to CDMAModulated Cell Phone RFR for Two Years .63FiguresFigure 1. Electromagnetic Spectrum.3Figure 2. GSM Frame Showing Peak and Average Transmit Powers .5Figure 3. GSM Multiframe Showing the Missing 26th Frame .5Figure 4. Exposure Facility Floor Plan for the Cell Phone RFR Studies .20Figure 5. Exterior View of Chambers, Empty Chamber Showing the Vertical andHorizontal Stirrers, and Chamber with Cage Racks in Place .21Figure 6. Growth Curves for Mice Exposed to GSM-modulated Cell Phone RFR for 28Days .39Figure 7. Kaplan-Meier Survival Curves for Mice Exposed to GSM-modulated CellPhone RFR for Two Years .43Figure 8. Growth Curves for Mice Exposed to GSM-modulated Cell Phone RFR for TwoYears .46Figure 9. Growth Curves for Mice Exposed to CDMA-modulated Cell Phone RFR for28 Days .53Figure 10. Kaplan-Meier Survival Curves for Mice Exposed to CDMA-modulated CellPhone RFR for Two Years .

NTP TechNical RePoRT oN The 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. NTP TR 596 NOVEMBER 2018