Medical/biological study (experimental study)

Long-term exposure of E-mu-Pim1 transgenic mice to 898.4 MHz microwaves does not increase lymphoma incidence med./bio.

By: Utteridge TD, Gebski V, Finnie JW, Vernon-Roberts B, Kuchel TR

Published in: Radiat Res 2002; 158 (3): 357-364

Aim of study (acc. to author)

To test whether exposure to 0.25, 1.0, 2.0 and 4.0 W/kg of global system for mobile communication (GSM)-modulated radiofrequency fields increased tumor incidence in Eµ-Pim1 transgenic heterozygous mice.

Background/further details

A total of 120 heterozygous and 120 wild-type mice were exposed at each of the exposure levels. 120 mice of each strain were sham-exposed and there were 120 freely moving negative control animals of each strain. 30 heterozygotes and 30 wild-type mice were used as positive controls. 100 sentinel mice were used for health monitoring purposes.

Endpoint

cancer: lymphoma

Exposure

- microwaves
- mobile communications
- GSM

Exposure	Parameters
Exposure 1: 898.4 MHz Modulation type: pulsed Exposure duration: repeated daily exposure for 1 h/day, 5 days/week for up to 104 weeks	SAR: 0.25 W/kg unspecified (unspecified) SAR: 1 W/kg unspecified (unspecified) SAR: 2 W/kg unspecified (unspecified) SAR: 4 W/kg unspecified (unspecified)

Exposure 1

Main characteristics

Frequency	898.4 MHz
Type	electromagnetic field
Charakteristic	far field
Exposure duration	repeated daily exposure for 1 h/day, 5 days/week for up to 104 weeks

Modulation

Modulation type	pulsed
Pulse width	0.6 ms
Repetition frequency	217 Hz

Exposure setup

Exposure source	dipole antenna radial waveguide
Distance between exposed object and exposure source	44 cm
Chamber	The exposure systems were radial electromagnetic cavities (''Ferris wheels'') and have been described in the reference article. The mice were exposed or sham-exposed in a total of 15 exposure systems (three at each exposure level including shams) in five exposure rooms.
Setup	Each of the 15 exposure systems consisted of a cylindrical parallel plate arrangement with mice restrained individually in 40 clear Perspex tubes arranged radially at a distance of 44 cm around a dipole antenna. Mice were loaded into the exposure systems using a two-level randomization supplied by the statistician. Mice sent for necropsy were replaced by phantoms that were both tissue-equivalent and had the average weight of the remaining mice in the cage to maintain constant dosimetry.
Additional info	The study was double-blinded. A total of 120 heterozygous and 120 wild-type mice were exposed at each exposure level; 120 mice of each strain were sham-exposed; and there were 120 freely moving negative control mice of each strain that were only transported to the exposure rooms and immediately back to their home rooms. Thirty heterozygotes and 30 wild-type mice were used as positive controls. They were injected with ethylnitrosourea (pH 5.0) at 50 mg/kg body weight and sham-exposed. One hundred sentinel mice were also used for health monitoring purposes so that a total of 1600 mice entered the study.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
SAR	0.25 W/kg	unspecified	unspecified	unspecified	-
SAR	1 W/kg	unspecified	unspecified	unspecified	-
SAR	2 W/kg	unspecified	unspecified	unspecified	-
SAR	4 W/kg	unspecified	unspecified	unspecified	-

Measurement and calculation details

The dosimetry was monitored independently at regular intervals and remained unchanged throughout the study; values at different exposure levels.

Reference articles

Balzano Q et al. (2000): An efficient RF exposure system with precise whole-body average SAR determination for in vivo animal studies at 900 MHz

Exposed system:

animal
mouse/Eµ-Pim1 (transgenic, C57BL/6Ntac) and the wild type of that strain
whole body

Methods Endpoint/measurement parameters/methodology

cancer: tumor incidence (lymphoblastic and non-lymphoblastic lymphomas, neurological or other tumors)
morphol./histopathol. changes: microscopic examination of major tissues (lymph nodes, bone marrow, brain, lung, heart etc.) and any identifiable tumor mass or tissue abnormality; histopathological tumor classification
body weigth; survival; incidence of cataracts

Investigated system:

tissue slices
isolated organ
investigation on living organism

Investigated organ system:

brain/CNS
thymus, spleen, lymph nodes, bone marrow in sternum and ribs, lung, heart, liver, kidney, small and large intestine, eyes

Time of investigation:

during exposure
after exposure

Main outcome of study (acc. to author)

The results showed no significant difference in the incidence of lymphomas between exposed and sham-exposed groups at any of the exposure levels. No dose-response effect was found.

Study character:

Study funded by

National Health and Medical Research Council (NHMRC), Australia

Replicated studies

Repacholi MH et al. (1997): Lymphomas in Eµ-Pim1 transgenic mice exposed to pulsed 900 MHz electromagnetic fields

Comments on this article

Lin JC (2008): Studies on tumor incidence in mice exposed to GSM cell-phone radiation
Lerchl A (2003): Comments on the Recent Publication on Microwave Effects on Eµ-Pim1 Transgenic Mice (Utteridge et al., Radiat. Res. 158, 357-364, 2002)
Goldstein LS et al. (2003): Comments on "Long-term exposure of Emicro-Pim1 transgenic mice to 898.4 MHz microwaves does not increase lymphoma incidence" by Utteridge et al., Radiat. Res. 158, 357-364 (2002)
Kundi M (2003): Comments on "Long-term exposure of Emicro-Pim1 transgenic mice to 898.4 MHz microwaves does not increase lymphoma incidence" by Utteridge et al., Radiat. Res. 158, 357-364 (2002)
Goldstein LS et al. (2003): Further Comments on "Long-Term Exposure of Eµ-Pim1 Transgenic Mice to 898.4 MHz Microwaves does not Increase Lymphoma Incidence" by Utteridge et al. (Radiat. Res. 158, 357-364 2002)
Lin JC (2003): Health effects - effects of cell-phone radiation on lymphoma-prone mice
Lin JC (2003): Radio-frequency radiation safety and health: Mobile-phone radiation effects on cancers in mice
Lin JC (2002): Cellular-phone radiation effects on cancer in genetically modified mice

Lerchl A et al. (2015): Tumor promotion by exposure to radiofrequency electromagnetic fields below exposure limits for humans
Lee HJ et al. (2011): Lymphoma development of simultaneously combined exposure to two radiofrequency signals in AKR/J mice
Tillmann T et al. (2010): Indication of cocarcinogenic potential of chronic UMTS-modulated radiofrequency exposure in an ethylnitrosourea mouse model
Tillmann T et al. (2007): Carcinogenicity study of GSM and DCS wireless communication signals in B6C3F1 mice
Shirai T et al. (2007): Lack of promoting effects of chronic exposure to 1.95-GHz W-CDMA signals for IMT-2000 cellular system on development of N-ethylnitrosourea-induced central nervous system tumors in F344 rats
Oberto G et al. (2007): Carcinogenicity Study of 217 Hz Pulsed 900 MHz Electromagnetic Fields in Pim1 Transgenic Mice
Zook BC et al. (2006): The effects of pulsed 860 MHz radiofrequency radiation on the promotion of neurogenic tumors in rats
Verschaeve L et al. (2006): Investigation of co-genotoxic effects of radiofrequency electromagnetic fields in vivo
Repacholi MH et al. (1997): Lymphomas in Eµ-Pim1 transgenic mice exposed to pulsed 900 MHz electromagnetic fields