## Low-level Long-term Irradiation of Humans

#3182

Individual-Based Approach to Assessment of Risk of Low-Level Long-Term Irradiation to Humans: Elaboration the Mathematical Tools

**Tech Area / Field**

- ENV-MRA/Modelling and Risk Assessment/Environment

**Status****3** Approved without Funding

**Registration date****12.01.2005**

**Leading Institute**

Research Testing Center for Radiation Safety of Space Objects, Russia, Moscow

**Supporting institutes**

- NIIIT (Pulse Techniques), Russia, Moscow

**Collaborators**

- Universitat Leipzig / Institut fuer Medizinische Informatik, Statistik und Epidemiologie, Germany, Leipzig\nNASA / Lyndon B. Johnson Space Center, National Aeronautics and Space Administration, USA, TX, Houston\nUniversity of Alberta / Faculty of Science, Canada, AB, Edmonton\nUniversity of Tennessee / College of Arts and Sciences, USA, TN, Knoxville

**Project summary**

The Project is a basic research in the field of ecology. Its implementation will result in the development of a new inpidual-based approach to the assessment of risk of low-level long-term irradiation to an inpidual and to an inhomogeneous (in radiosensitivity) human population. A special attention will be paid to the elaboration of the relevant mathematical tools. The project corresponds to new challenges (manned missions to Mars and Moon, a danger of nuclear terrorism, ensuring the radiation safety for people residing in regions with elevated radiation background). As noted in Recommendations of the International Commission on Radiological Protection (ICRP 1990), the present risk-estimation methods are not always applicable in the case of low-level long-term irradiation because of non-linear effects of such exposures on humans, as well as in view of inhomogeneity of inpidual radiosensitivity.

The basis of our approach to radiation risk assessment is the conventional radiobiological concept of critical system. According to this concept, for definite ranges of doses and dose rates of acute and chronic irradiation, one can pick out a specific critical cell system in mammalian organism, the radiation damage of which will play a key role in development of radiation sickness and ultimately in the death of mammals. In turn, the damage of the critical system manifests itself in reducing the number of its functional cells below the level required for survival. A distinctive feature of our approach is the allowance for the inhomogeneity of human populations in radiosensitivity which proves to be essential in this field.

In accordance with these concepts, the key points of the inpidual-based approach to the radiation risk assessment to humans are the following. It is assumed that the situation, when the deviation of the number of functional cells from the normal level in the critical system of an inpidual exceeds the critical value, can be treated as a death analogue. It is supposed that the reasons of such an deviation are irradiation impact, natural aging processes, and random fluctuations. It is also assumed that distinctions of inpiduals composing a population in their sensitivity to a certain radiation exposure are due to the different radiosensitivity of the cells of the relevant critical system in the inpiduals.

Basing on these considerations and applying the stochastic method, a mathematical model will be elaborated, which describes the dynamics of radiation mortality for an inhomogeneous (in radiosensitivity) human population exposed to low dose rate chronic irradiation. In the framework of this model, the statistical biometric functions (the mortality rate, the probability density and the probability of the life span) will be calculated proceeding from the dynamics of the concentration of the critical system functional cells and from the statistical characteristics of this physiological index in the inpiduals composing the population. In order to describe the dynamics of granulocytopoietic system, which is the critical one in humans under the exposure in question, a specially developed mathematical model will be used. It is important that the model of the granulocytopoietic system will include, as the key parameters, a dose rate of chronic irradiation and coefficients which determine the cell radiosensitivity in this critical system.

A major advantage of the inpidual-based approach to radiation risk assessment is the following. Identification of the radiation mortality model does not require data on the mortality dynamics of irradiated human populations. It is needed only data on the population's mortality in the absence of radiation and a limited number of clinical observations concerning the dynamics of the granulocytopoietic system in humans in the absence of irradiation, as well as under acute or chronic irradiation. Therefore, the proposed model can be employed to predict the mortality dynamics and the life-span shortening for an inhomogeneous (in radiosensitivity) human population exposed to low dose rate chronic irradiation, even when the exposure duration is commensurable with the average life span. In turn, the simplified version of the radiation mortality model for a homogeneous human population can be used to calculate the probabilistic characteristics of the death and the life-span shortening for an inpidual. Thus, this model enables one to estimate the risk of low-level long-term irradiation to an inpidual and to a human population.

The project investigations are important for the fundamental science because they develop system and quantitative approaches in radiation biology and ecology, afford quantitative estimations of key parameters characterizing the processes running in the critical body system in humans exposed to low-level long-term irradiation. The studies in the framework of the project will provide a new knowledge concerning the effects of low dose rate chronic irradiation on human mortality. Without doubts, this field of studies is of special theoretical significance. The proposed investigations will be a substantial contribution into the search for new methods of the radiation risk assessment with allowance for the inpidual variability of radiosensitivity.

The project results will be a matter of interest to practical use, too. The inpidual-based approach to the assessment of risk of low-level long-term irradiation can be applied for the resolving the problems of radiation safety. In particular, the estimation of radiation risks to populations in areas with elevated radiation background, which can be done in the framework of the approach, should help the decision makers to evaluate the real hazards and, on this basis, to distribute, in an optimal way, the available resources pursuing the goal of reducing the total risk for the populations. This approach will enable one to evaluate the inpidual radiation risks to persons subjected to irradiation and, proceeding from the estimations, to carry out preventive measures with greater efficiency and with lesser expenses. The inpidual-based approach to radiation risk assessment will be also useful in ensuring the radiation safety of manned missions to Mars and Moon. Thus, the project results will be of great interest for research institutions and governmental organizations dealing with the problems of environmental protection and radiation safety.

The foundation for successful implementation of the project is the high competence and experience of the project manager in the field of radiation risk assessment and in the field of mathematical modeling of radiation effects on vital body systems in mammals. She is a Doctor of Science in Physics and Mathematics (1992). The scientific achievements of the project manager are well-known in the international scientific community. The results of her studies have been presented and discussed at 31 International Conferences and published in leading international scientific journals (Mathematical Biosciences, Health Physics, Acta Astronautica, Physics of Particles and Nuclei, Folia Microbiologica). The project manager is the author of 112 publications. She is a member of the Scientific Commission F (Life Sciences as Related to Space) of the Committee on Space Research (COSPAR). Smirnova O.A. was awarded by the IBC's Medal of Honour "International Personality of the Year 2001". The pledge of success of the project implementation is also the high expertise of the rest members of the project team in the field of physical and mathematical sciences: 1 specialist is Kandidat of Science in Physics and Mathematics and 3 specialists are engineers.

The Project meets goals and objectives of the ISTC. Implementation of the Project will enable weapon scientists to redirect their research activity to peaceful areas. In the framework of the project, they will be integrated into the international scientific community due to the interchange of information with abroad collaborators. In addition, the realization of the Project will support basic research for peaceful purposes, namely, in the field of ecology.

The most representative publications of the project manager:

1. Kovalev E.E., Smirnova O.A. Estimation of radiation risk based on the concept of inpidual variability of radiosensitivity. AFRRI Contract Report 96-1. Defense Nuclear Agency Contract DNA001-93-C-0152. Bethesda, Maryland, USA: Armed Forces Radiobiology Research Institute, 1996, 203 p.

2. Stepanova N.V., Petrova T.A., Smirnova O.A. Dynamical models of cell populations (monograph). 1992, Dep. in VINITI N 239-V92, 23.01.92, two volumes, 421 p. (Russian).

3. Smirnova O.A., Yonezawa M. Radioprotection effect of low level preirradiation on mammals: modeling and experimental investigations. Health Physics, 2003, v. 85(2), p. 150-158.

4. Sakovich V.A., Smirnova O.A. Modeling radiation effects on life span of mammals. Physics Particles and Nuclei, 2003, v. 34, No.6, p. 743-766.

5. Smirnova O.A. Mathematical modeling of radiation-induced autoimmunity. Mathematical Modelling & Computing in Biology and Medicine. 5th ECMTB Conference 2002. Editor: V. Capasso. Milan: Milan Research Centre for Industrial and Applied Mathematics, 2003, p. 392-402.

6. Smirnova O.A. Mathematical model for assessment of radiation risk on long space mission. Advances in Space Research, 2002, v. 30, No 4, p. 1005-1010.

7. Smirnova O.A. Mathematical modeling of mortality dynamics of mammalian population exposed to radiation. Mathematical Biosciences, 2000, v. 167, p. 19-30.

8. Smirnova O.A. Mathematical modeling of the effect of ionizing radiation on the immune system of mammals. Physics of Particles and Nuclei, 1996, v. 27, No 1, p. 100-120.

9. Kovalev E.E., Smirnova O.A. Life-span of irradiated mammals. Mathematical modeling. Acta Astronautica, 1994, V. 32, P. 649-652.

10. Zukhbaya T.M., Smirnova O.A. An experimental and mathematical analysis of lymphopoiesis dynamics under continuous irradiation. Health Physics, 1991, V. 61, P. 87-95.

11. Smirnova O.A. Comparative risk assessment for homogeneous and nonhomogeneous mammalian populations exposed to low level radiation. Proceedings of NATO Advanced Research Workshop, Rome (Anzio), Italy, 13-16 October 2002. Dordrecht: Kluwer Academic Publishers Group, 2004, p. 389-396.

12. Shatkin J.A., Andreas I., Apul D.S., Attia A., Brambilla M., Carini F., Elshaeb Y., Girgin S., Gitis I., Mandarasz T., Small M., Smirnova O., Sorvary J., Tal A. A proposed framework for multinational comparative risk analysis: pesticide use, impacts and management. Proceedings of NATO Advanced Research Workshop, Rome (Anzio), Italy, 13-16 October 2002. Dordrecht: Kluwer Academic Publishers Group, 2004, p. 149-170.

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