Background and Objectives
Extremely low frequency magnetic fields (ELF-MF), associated with the use and transmission of electric power, have been classified as possibly carcinogenic to humans based on reasonably consistent epidemiological data for childhood leukaemia. However, the evidence for a causal relationship between ELF-MF at the microtesla level and malignant disease based on laboratory studies in animals and cells is weak and is unsupported by biophysical studies.
The ARIMMORA project applies of the most advanced tools in a comprehensive approach that maximizes the likelihood of detecting interaction mechanisms of ELF-MF with organisms or, alternatively, showing their absence in the selected studies, by addressing the following objectives:
Studying ELF-MF interactions by recent advances in the molecular biology of leukaemia – In vitro Studies:
- Investigations on how ELF-MF are perceived by cells and transformed into biological signaling
- Clarification if and how and how ELF-MF exposure influences epigenetic dynamics in hematopoietic differentiation and in leukaemic cells
Studying ELF-MF interactions by recent advances in the molecular biology of leukaemia – In vivo Studies:
- Cutting-edge genetic engineering and animal modelling technologies to generate advanced models of leukaemia, and to test the effects of ELF-MF exposure on disease development in a way that has not been explored previously
Closing the most important knowledge gaps in ELF-MF exposure of children:
- Personal exposure assessment of exposure pattern as functions of location and behavior (locations: Switzerland and Italy);
- Determination of the contributions of near-field sources in comparison to power line fields;
- Development of novel measurement equipment for accurate assessment of induced fields in the human body (0 to 10 MHz)
- Translation of the incident fields into field quantities in tissues and organs, particularly blood and bone marrow using anatomical models;
- Development of an exposure model that could enable prediction of tissue exposures.
Biophysical modelling fosters more informative protocols using modern numerical models and solvers:
- Determination of induced magnetic and electric fields on a macroscopic level (averaged fields induced in the cell medium of the in vitro studies and in specific tissues of the in vivo experiments will be put in relation to the values induced in human);
- Assessment of the ratio of the fields on a macro-dosimetric level with the induced electric and magnetic fields for the different structures of the cell (micro-dosimetry);
- To evaluate the most promising targets with an expert group in molecular dynamics and conducting sensitivity analysis of interferences with the weak microscopic ELF fields.
Risk assessment & dissemination:
- risk assessment for the carcinogenicity of extremely low-frequency magnetic fields (ELF-MF) based on studies conducted within ARIMMORA and setting them in context of recent studies conducted outside.
Work Packages
WP1: Literature database
The multidisplinary nature of the ARIMMORA Consortium makes it necessary to provide all the members with up-to-date bibliographic references describing the most relevant recent findings in the different fields of research involved in the project. Each project member has access to the relevant publications in their field of expertise, but not necessarily to the other fields. Therefore, one of the first aims of the Consortium is to put together a complete cross-disciplinary database covering all the scientific and engineering aspects relevant for the development of the project. The generation and maintenance of this database are the aims of WP1.
WP2: Exposure matrix for children including power lines, transformers & near-field sources
The aim of the work package is to improve the knowledge of exposure to ELF-MFs in children from prenatal life to adolescence (0-16 years old) by:
1) Personal exposure assessment of exposure pattern as functions of location and behavior;
2) Determination of the contributions of near-field sources in comparison to power line fields;
3) Translation of the incident fields into field quantities in tissues and organs, particularly blood and bone marrow;
4) Validation of exposure models that could enable prediction of tissue exposures.
WP3: Exposure systems, dosimetry and quality control
The objectives of the WP are:
- to develop, manufacture and install the exposure systems for WP5 and 6 and provide all the dosimetry (in terms of incident and induced fields);
- to ensure a quality control framework that will provide the best possible characterization of the exposure from the systems;
- to provide exposure data and the environmental conditions at the measurement times by post-exposure analysis;
- to permit correlation of exposures of in vitro and in vivo systems with human exposure scenarios, i.e., induced electric and magnetic fields, area-averaged current densities (ICNIRP), volume-averaged E-fields (ICNIRP), and time-averaged E-fields (IEEE C95.1).
WP4: Development of instrumentation for exposure assessment and surveillance
The objective of WP4 is to develop measurement equipment and extensions of numerical tools to close the current gap for sound ELF-EMF exposure assessments.
WP5: ELF-MF perception, signalling and impact on epigenetic stability
WP5 aims to to elucidate the mechanism by which ELF-MF is absorbed by lymphocytes and other cell lines and transformed into various biological signalling cues and important physiological processes. Furthermore, ELF-MF effects on the establishment and maintenance of epigenetic states during haematopoietic differentiation will be explored and effects on epigenetic stability in leukaemic cells, including biological consequences will be monitored at the level of gene expression, cell proliferation and death. Biomarkers (chromatin signatures, cellular signals, …) of MF exposure in haematopoietic, leukaemic and other cells shall be identified and validated.
WP6: Mechanisms and animal models
There is a lack of models adequate for studies of the in vivo effects of ELF-MF exposure on the haematopoietic system. The aim of WP6 is to apply cutting-edge genetic engineering and animal modelling technologies to generate advanced models of leukaemia, and to test the effects of ELF-MF exposure on disease development in a way that has not been explored previously. Methodology:
- Investigation of the influence of ELF-MF on the haematopoietic and immune system (mice) by quantification of proliferation and cytokine pattern, gene -expression profiling and classical genotoxicity assays;
-Usage of new, advanced, genetically-modified mouse models to investigate whether ELF-MF exposure plays a role in the genesis of childhood B-cell leukaemia and/or influences the course of the disease;
- In vivo investigation of adrenergic receptors in tissues and cells with impact on haematopoiesis and lymphopoiesis in rats to examine if these receptors mediate ELF-MF effects.
WP7: Biophysical modeling
There is a critical need for a transformation matrix derived from detailed macro-dosimetry to micro-dosimetry for determining the fields induced in different cell compartments. The objectives of WP7 comprise:
- Determination of induced magnetic and electric fields on a macroscopic level (averaged fields induced in the cell medium of the in vitro studies and in specific tissues of the in vivo experiments will be put in relation to the values induced in human);
- Assessment of the ratio of the fields on a macro-dosimetric level with the induced electric and magnetic fields for the different structures of the cell (micro-dosimetry)
- To evaluate the most promising targets with an expert group in molecular dynamics and conducting sensitivity analysis of interferences with the weak microscopic ELF fields.
WP8: Dissemintation to standards
To carry out direct dissemination of the results of WP2 and WP4 to the product standard committees and the synthesis of the results of WP5, 6, and 7 performed in WP9 to the EM safety standard committees.
WP9: Risk assessment
A risk assessment for the carcinogenicity of extremely low-frequency magnetic fields (ELFMF) will be performed based on studies conducted within ARIMMORA and setting them into the context of recent studies conducted outside the consortium. The risk assessment procedures of WP9 will be adapted from those developed and outlined by the International Agency for Research on Cancer (IARC) for their Monograph Program on the evaluation of carcinogenic risks to humans.
WP10: Management
This WP is especially designed to organize the project as a whole and accomplish all administrative tasks. The objectives are to create the organizational prerequisites for successfully carrying out the ARIMMORA project in accordance with the terms and conditions of the Grant Agreement.
List of Deliverables
Nr | Name | Expected date |
1.1 | Literature database | M2 |
10.1 |
Minutes of the General Assembly |
M2 |
10.2 |
ARIMMORA website and leaflet |
M3 |
10.3 | Dissemination plan | M3 |
3.1 |
Exposure system requirements |
M3 |
2.1 |
Ethical approvals and informed consent form for WP2 |
M4 |
3.2 |
In vivo exposure monitoring systems |
M5 |
3.3 |
In vitro exposure system sXcELF |
M6 |
6.4 |
Authorization for animal experiments |
M6 |
4.1 |
Prototype of measurement equipment for sound ELF-EMF exposure assessments |
M12 |
6.5 |
TEL-AML-1 mouse models |
M12 |
10.4 |
Minutes of the General Assembly |
M12 |
10.5 |
Updated plan for the dissemination of results |
M12 |
10.6 |
Status report on access rights and IPR issues |
M12 |
10.7 |
Status report on exploitable results |
M12 |
4.2 |
Prototype hardware |
M14 |
3.4 |
In vitro exposure system sXvELF |
M14 |
6.1 |
T and B Cell maturation |
M15 |
2.2 |
Report on personal exposure measurements |
M18 |
6.2 |
Genotoxicity and (epi)genetics in vivo |
M18 |
6.8 |
Influence of ELF-MF on proliferation and cell cycle in rats |
M18 |
7.1 |
Report on induced spatial averaged (0.5mm) induced EMF (macrodosimetry) w.r.t. human exposure |
M18 |
2.5 |
Report on development of exposure models |
M19 |
2.3 |
Report on the assesment of the exposure from near-field sources |
M24 |
4.3 |
Final hardware |
M24 |
5.1 |
MAPK and AKT signalling |
M24 |
6.6 |
Role of ELF-MF in the in vivo initiation of TEL-AML1+ B-ALL in genetically modified mice |
M24 |
6.9 |
Influence of ELF-MF on senescence and apoptosis |
M24 |
10.9 |
Status report on exploitable results |
M24 |
10.10 |
Status report on access rights and IPR issue |
M24 |
10.11 |
Minutes of the General Assembly |
M24 |
10.12 |
Updated plan for the dissemination of results |
M24 |
7.2 |
Report on ind. Field distribution on the sub-cellular level (micro-dosimetry) w.r.t. human exposure |
M25 |
7.3 |
Report on the selected biophysical interaction model hypotheses list |
M33 |
4.2 |
Report on determination of induced fields |
M33 |
1.2 |
Finalization of literature database |
M36 |
3.5 |
Report on quality control |
M36 |
5.2 |
Cellular sensors of ELF-MF |
M36 |
5.3 |
Epigenetic dynamics in haematopoietic differentiation |
M36 |
5.4 |
Impact of ELF-MF on epigenetic stability of leukaemic cells |
M36 |
6.7 |
Role of ELF-MF in the in vivo initiation, progr. And evol. of TEL-AML1+ B-ALL in genetically modified mice |
M36 |
6.3 |
Haematopoietic changes in CD-1 mice |
M36 |
6.1 |
Report on the involvement of andrenergic receptors |
M36 |
8.1 |
Dissemination to standards |
M36 |
9.1 |
Risk assessment report |
M36 |
9.2 |
Risk assessment manuscript for publishing |
M36 |
10.13 |
Minutes of the General Assembly |
M36 |
10.14 |
Updated plan for the dissemination of results |
M36 |
10.15 |
Final exploitation plan |
M36 |
10.16 |
Status report on access rights and IPR issue |
M36 |
10.17 |
Report on the awareness and wide social implications |
M36 |