Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.

Belgian Nuclear Research Center SCK CEN Mol Belgium

Bundesamt für Strahlenschutz Oberschleißheim Germany

Bundeswehr Institute of Radiobiology Munich Germany

CEA Saclay Gif sur Yvette Cedex France

Columbia University Irving Medical Center Center for Radiological Research New York New York

Cytogenetic Biodosimetry Laboratory Oak Ridge Institute for Science and Education Oak Ridge Tennessee

Dalat Nuclear Research Institute Radiation Technlogy and Biotechnology Center Dalat City Vietnam

Department of Radiation Biology and Protection Nagasaki University Japan

Department of Radiation Life Sciences Fukushima Medical University School of Medicine Fukushima Japan

Department of Radiation Measurement and Dose Assessment National Institute of Radiological Sciences National Institutes for Quantum Science and Technology Chiba Japan

Department of Radiobiology Singapore Nuclear Research and Safety Initiative National University of Singapore Singapore

Department of Safety and Radiation Protection Forschungszentrum Jülich Jülich Germany

Genevolution Porcheville France

Ghent University Radiobiology Research Unit Gent Belgium

Health Canada Ottawa Canada

Hospital General Universitario Gregorio Marañón Laboratorio de dosimetría biológica Madrid Spain

Institut de Radioprotection et de Surete Nucleaire Fontenay aux Roses France

Institut de Recherche Biomédicale des Armées Bretigny Sur Orge France

Institute of Nuclear Chemistry and Technology Warsaw Poland

Institute of Nuclear Physics Polish Academy of Sciences Krakow Poland

Institute of Radiation Emergency Medicine Hirosaki University Hirosaki Japan

Instituto Superior Técnico Campus Tecnológico e Nuclear Lisbon Portugal

Italian National Agency for New Technologies Energy and Sustainable Economic Development Rome Italy

Laboratori Nazionali di Legnaro Istituto Nazionale di Fisica Nucleare Legnaro Italy

Laboratory of Biological Dosimetry Korea Institute of Radiological and Medical Sciences Seoul Republic of Korea

Medical University of Gdansk Department of Physics and Biophysics Gdansk Poland

National Centre for Scientific Research Demokritos Health Physics Radiobiology and Cytogenetics Laboratory Agia Paraskevi Greece

National Centre of Radiobiology and Radiation Protection Sofia Bulgaria

National Institute of Public Health Radiation Hygiene Laboratory Bucharest Romania

Naval Dosimetry Center Bethesda Maryland

Paris Lodron University of Salzburg Department of Environment and Biodiversity 5020 Salzburg Austria

Radiation Cytogenetics Laboratory S P Grigoriev Institute for Medical Radiology and Oncology of Ukrainian National Academy of Medical Science Kharkiv Ukraine

Radiation Dosimetry Laboratory Oklahoma State University Stillwater Oklahoma

Radiation Medicine Unit Department of Radiobiology and Radiohygiene National Public Health Centre Budapest Hungary

Radiation Protection Centre Vilnius Lithuania

Ruðer Boškovic Institute Division of Physical Chemistry Zagreb Croatia

Serbian Institute of Occupational Health Belgrade Serbia

Servicio de Protección Radiológica Laboratorio de Dosimetría Biológica Valencia Spain

Stockholm University Stockholm Sweden

TENMAK Nuclear Energy Research Institute Technology Development and Nuclear Research Department Türkey

UK Health Security Agency and Office for Health Improvement and Disparities Cytogenetics and Pathology Group Oxfordshire England

UK Health Security Agency Radiation Chemical and Environmental Hazards Division Oxfordshire United Kingdom

Universidad de Sevilla Departamento de Biología Celular Sevilla Spain

Università Degli Studi di Palermo Dipartimento di Fisica e Chimica Emilio Segrè Palermo Italy

Universitat Autònoma de Barcelona Barcelona Spain

University of Arizona Center for Applied Nanobioscience and Medicine Phoenix Arizona

University of Defense Faculty of Military Health Sciences Hradec Králové Czech Republic

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