ABSTRACT

CONTENTS 2.1 Introduction ....................................................................................................................... 22 2.2 Animal Toxicity Bioassays of Electromagnetic Fields ................................................ 24

2.2.1 General Toxicologic Bioassays of Electromagnetic Fields ............................. 24 2.2.2 Developmental and Reproductive Toxicity Studies of

Electromagnetic Fields.......................................................................................... 25 2.2.3 Immunotoxicity Studies of Electromagnetic Fields......................................... 26

2.3 Assessment of the Possible Oncogenic Activity of Electromagnetic Field Exposure Using Chronic Exposure Studies in Rodents................................... 27 2.3.1 Design of Chronic Exposure Studies ................................................................. 27 2.3.2 Results of Chronic Rodent Oncogenicity Bioassays........................................ 28

2.3.2.1 IIT Research Institute (United States): Chronic Oncogenicity Bioassays in Rats and Mice .................................................................. 28

2.3.2.2 Institut Armand Frappier (Canada): Chronic Oncogenicity Bioassay in Rats...................................................................................... 29

2.3.2.3 Mitsubishi Kasei Institute (Japan): Chronic Oncogenicity Bioassay in Rats........................................................................................ 30

2.3.2.4 Overview of Chronic Rodent Oncogenicity Studies.......................... 31 2.3.3 Results of Site-Specific Oncogenicity Bioassays in Rodents ............................ 31

2.3.3.1 University of California at Los Angeles (United States): Lymphoma and Brain Tumor Bioassay in Mice................................. 31

2.3.3.2 Technical University of Nova Scotia (Canada): Lymphoma Bioassay in Mice....................................................................................... 32

2.4 Assessment of the Possible Cocarcinogenic or Tumor-Promoting Activity of Electromagnetic Field Exposure Using Multistage Rodent Models...................... 33 2.4.1 Design of Multistage Oncogenicity Studies ....................................................... 33 2.4.2 Multistage Oncogenicity Studies in the Brain.................................................... 34

2.4.2.1 Institut Armand Frappier (Canada): Brain Tumor Promotion Study in Rats ............................................................................................ 34

2.4.2.2 University of California at Los Angeles (United States): Brain Tumor Promotion Study in Mice .......................................................... 34

2.4.3 Multistage Oncogenicity Studies in the Mammary Gland .............................. 35 2.4.3.1 Oncology Research Center (Georgia): Mammary Tumor

Promotion Studies in Rats...................................................................... 36 2.4.3.2 Hannover School of Veterinary Medicine (Germany):

Mammary Tumor Promotion Studies in Rats..................................... 36 2.4.3.3 Battelle-Pacific Northwest Laboratories (United States):

Mammary Tumor Promotion Studies in Rats..................................... 37 2.4.3.4 National Institute for Working Life (Sweden): Mammary

Tumor Promotion Studies in Rats......................................................... 37 2.4.4 Multistage Oncogenicity Studies in the Hematopoietic System..................... 37

2.4.4.1 Zhejiang Medical University: Lymphoma Promotion Study in Mice ........................................................................................... 38

2.4.4.2 University of California at Los Angeles (United States): Lymphoma Promotion Study in Mice.................................................. 38

2.4.4.3 Overview of Multistage Oncogenicity Studies ................................... 38 2.5 Assessment of the Possible Oncogenic Activity of Electromagnetic Field

Exposure Using Genetically Modified (Transgenic and Gene Knockout) Rodent Models .................................................................................................................... 39 2.5.1 Design of Oncogenicity Studies in Genetically Modified Animals................ 40 2.5.2 Results of Oncogenicity Studies in Genetically Modified Animals ............... 40

2.5.2.1 IIT Research Institute (United States): Lymphoma Bioassays in PIM Transgenic and Heterozygous p53 Knockout Mice.............. 40

2.5.2.2 Walter and Eliza Hall Institute of Medical Research (Australia): Lymphoma Bioassay in PIM Transgenic Mice ................................... 42

2.5.2.3 Overview of Oncogenicity Studies in Genetically Modified Animals ..................................................................................................... 42

2.6 Proposed Mechanisms of Electromagnetic Field Action in Oncogenesis ................. 42 2.6.1 Genetic Toxicology Studies of Electromagnetic Field Exposure..................... 43 2.6.2 Alterations in Gene Expression ............................................................................ 44 2.6.3 Biochemical Changes Associated with Regulation of Cell Proliferation....... 44 2.6.4 Alterations in Immune Function .......................................................................... 45 2.6.5 Alterations in Melatonin Levels or Action ......................................................... 45

2.7 Conclusion ........................................................................................................................... 46 References ..................................................................................................................................... 46

Over the past two decades, the possible relationship between exposure to power frequency (50 and 60 Hz) electromagnetic fields (EMF) and adverse human health outcomes has received significant attention in both the scientific community and the general population. Based onwidely circulated accounts in the popular press [1], and onmassmedia reports of the results of selected epidemiologic investigations [2,3], a public perception has developed that human exposure to EMF may be associated with a range of adverse health effects, including reproductive dysfunction, developmental abnormalities, and cancer. The results of a number of epidemiologic studies provide limited support for the hypothesis that EMF exposure may be associated with an increased risk of neoplasia in several organ sites in humans. Among these sites, the hematopoietic system, breast, and brain have been identified most commonly as possibly sensitive targets for EMF action (reviewed in [4]).