[SUBSTANTIATION OF DOSE LIMITS FOR A NEW NORMATIVE DOCUMENT ON RADIATION SAFETY OF LONG-DURATION SPACE MISSIONS AT ORBIT ALTITUDES OF UP TO 500 KM].

Review of the data of experimental radiobiology and epidemiological follow-up of large groups of people subjected to radiation exposures on Earth has been undertaken to substantiate dose limits for critical organs of cosmonauts in order to ensure good performance and vitality while on long-duration orbital missions. The career dose limits for cosmonauts and astronauts established earlier in the USSR and USA amounted to nothing more but banning the risk of cancer death increase to 3%. To apply more rigorous criteria of delayed radiation risks, the Russian limits for cosmonauts were revised to substantiate a 4-fold reduction of the average tissue equivalent dose maximum to 1 Sv. The total of cancer and non-cancer radiation risks over lifetime and probable reduction of mean life expectancy (MLE) were calculated using the model of radiation-induced mortality for mammals and taken as the main damage to health. The established dose limit is equal to the career dose for nuclear industry personnel set forth by Russian standard document NRB 99/2009. For better agreement of admissible threshold doses to critical human organs (bone marrow, lens and skin) in the revised radiation limits for long-duration space missions and radiation safety limits on Earth, reduction of dose limits for the critical organs were substantiated additionally; these limits comply with those for planned over-exposure on Earth in document NRB 99/2009.

METHOD FOR ANALYSIS OF HEART RATE REGULATION STRAIN BY APPLICATION OF THE OVERALL LOGARITHMIC INDEX TO THE HOLTER ELECTROCARDIOGRAM MONITORING.

Studies of human adaptation to extended exposure in extreme environments necessitate the development of integral indexes for quantitative evaluation of the functional systems of organism. The study was performed using an integral overall logarithmic index to analyze changes in heart rate variability (HRV)' over 20-hour monitoring of patients examined in a hospital. HRV-evidenced adaptation processes were compared to the data of Holter monitoring of patients and normal values for healthy people under 30 years of age.

[BIOLOGICAL EFFECTIVENESS OF FISSION SPECTRUM NEUTRONS AND PROTONS WITH ENERGIES OF 60-126 MEV DURING ACUTE AND PROLONGED IRRADIATION].

Neutrons of the fission spectrum are characterized by relatively high values of linear energy transfer (LET). Data about their effects on biological objects are used to evaluate the risk of delayed effects of accelerated ions within the same LET range that serve as an experimental model of the nuclei component of galactic cosmic rays (GCR). Additionally, risks of delayed consequences to cosmonaut's health and average lifetime from certain GCR fluxes and secondary neutrons can be also prognosticated. The article deals with comparative analysis of the literature on reduction of average lifespan (ALS) of animals exposed to neutron reactor spectrum, 60-126 MeV protons, and X- and γ-rays in a broad range of radiation intensity and duration. It was shown that a minimal lifespan reduction by 5% occurs due to a brief exposure to neutrons with the absorbed dose of 5 cGy, whereas same lifespan reduction due to hard X- and γ-radiation occurs after absorption of a minimal dose of 100 cGy. Therefore, according to the estimated minimal ALS reduction in mice, neutron effectiveness is 20-fold higher. Biological effectiveness of protons as regards ALS reduction is virtually equal to that of standard types of radiation. Exposure to X- and γ-radiation with decreasing daily doses, and increasing number of fractions and duration gives rise to an apparent trend toward a less dramatic ALS reduction in mice; on the contrary, exposure to neutrons of varying duration had no effect on threshold doses for the specified ALS reductions. Factors of relative biological effectiveness of neutrons reached 40.

[Morphologic changes in mice trachea, bronchi and lungs after prolonged combined radiation and inhaled chemical exposure].

Investigations of morphology and morphometry of the breathing organs (trachea, bronchi and lungs) and immunogenesis of mice subject to a combined sequential exposure to fractionated external γ-irradiation by the total dose of 350 cGy and a mix of acetone, ethanol and acetaldehyde in MPCs for piloted spacecrafts simulating the estimated levels in crewed exploration missions were conducted. Morphologic changes in the breathing organs of animals after space missions point to immunogenesis activation and appearance of a "structural trace" as a chronic inflammation with the growth of fibrous connective tissue in tracheal, bronchial and lung walls, increase in volume fractions of glands and vessels and reduction in loose fibrous connective tissue. Formation of the fibrous connective tissue was particularly noticeable in respiratory parts of the breathing organs suggesting a high risk of long-term adverse effects.

[Cytogenetic investigations of mice marrow cells after isolated chronic exposure to radiation and chemical factors, and combined sequential exposure to these factors].

The article presents data on chromosomal aberrations in bone marrow cells of mice following isolated exposure to gamma-radiation and chemical factor within the existing MPCs for piloted spacecraft, and also combined sequential exposure in the ranges predicted for interplanetary missions. In the event of chronic exposure the relative number of chromosomal aberrations goes up till reaching plateau and is governed strictly by the mathematical dependence on effective residual gamma-dose and effective damage of organism from inhaled chemical factor. Sequential exposure to the radiation and chemical factors within the ranges specified for orbital and remote space missions caused a tangible reduction of the speed of cytogenetic damages reparation in postexposure period which may be interpreted as depletion of the body reserve and compensatory-recovery potential.

[Overall logarithmic index for the characterization of adaptation and regulatory systems straining under chronic action of extreme environmental factors].

The article advertizes some optional capabilities of the overall logarithmic index as an integral parameter for quantifying adaptation processes triggered by chronic exposure to stress factors of varying intensity. Consideration is given to the principles of damage formation in different systems of organism with time and subsequent compensatory processes depending on the level of regulation system straining, rate of functional potential depletion, probability of remote consequences such as early aging, increased risk of lethality and reduction of the mean remaining life expectancy. The overall logarithmic index will be used to analyze the transition from normal to active insufficient adaptation, and possible adaptation failure because of a drastic decline of organism resistance. In fact, an attempt was made to use the index to quantify adaptation cost, loss of resistance, and possible increase of the risk of remote consequences.

[Adaptation processes in mice during chronic combined exposure to radiation and chemical compounds (acetone, ethanol, acetaldehyde) innate to exploration missions].

The paper reports the results of experimental investigation with mice subjected to 63-day of daily 10-fold fractionated gamma-irradiation at the total dose of 350 cGy followed by 70-day exposure to chemical mixture (acetone, ethanol, acetate aldehyde) at close to maximum permissible concentrations innate to piloted space vehicles (MPCpsv). Measured levels of radiation and known radiation sensitivity of mice were used to model absorbed dose to cosmonauts on an exploration mission. Functional shifts in the hematopoietic system and changes in biochemical parameters of erythrocytes indicative of energy exchange and redox potential were tracked up during the combined radiation-chemical exposure and 90 days of recovery. It was shown that adaptation caused pronounced and strongly pronounced tension of regulatory mechanisms, particularly under the effects of radiation. High tension still persisted in the recovery period.

[Evaluation of the risk of delayed adverse effects of chronic combined exposure to radiation and chemical factors with the purpose to ensure safety in orbital and exploration space missions].

The work had the aim to anatomize the existing issues with providing safety in extended orbital and exploration missions for ensuing estimation of actual values of the total radiation risk for the crew, and risks of other delayed effects of simultaneous exposure to ionizing radiation and chemical pollutants in cabin air, and a number of other stressful factors inevitable in space flight. The flow of chronic experiments for separate and combined studies with reproduction of air makeup and radiation doses in actual orbital and predicted exploration missions is outlined. To set safety limits, new approaches should be applied to the description of gradual norm degradation to pathologies in addition to several generalized quantitative indices of adaptation and straining of the regulatory systems, as well as of effectiveness of the compensatory body reserve against separate and combined exposure.

[Radiation lesion formation and character of repair processes in the hematopoietic system of primates exposed to continuous and fractionated gamma-irradiation by equally effective doses].

The article is dedicated to comparison of the biological effectiveness of continuous and fractionated gamma-irradiation of rhesus macaques by equally effective doses. These radiation conditions are broadly used in radiobiological experiments. Specifically, they are applied in modeling radiation effects on cosmonauts during extended exploration mission. A model of radiation damage and repair on the cell, tissue and organism levels, i.e., a model of effective residual dose responsible for change in mammals' resistance to irradiation of varying duration was used to calculate equally effective doses in the experiment with primates subject to continuous and fractionated exposure. The authors publish data related to formation of radiation lesion and rate of ensuing hemopoiesis reparation. Two groups of animals were compared in resistance modification followed after testing by acute irradiation. The test was to reproduce a radiation situation for cosmonauts in the event of a cannonade of powerful solar proton events resulting in an effective residual dose of 1 Sv total The experiment evidenced close resemblance of the hemopoietic effects in primates exposed to the compared radiation conditions.

[New data for proving the presence of significant effects of electromagnetic exposure (to autoimmune changes in rats)].

The study using statistical analysis methods and the generalized logarithmic parameter describing the change in the condition of biological systems represents additional substantiations and proofs of the presence of the expressed amplification of the immune reaction in experimental animals after a long exposure to EMF RF non-thermal intensity with a power density of 500 microW/cm2. A substantial growth of titers of antibodies to the brain tissue on the 14th day and to a number of other antigens on the 7th and 14th days after irradiation is shown with high reliability of 99.9%. It is shown that EMF RF exposure to non-thermal intensity within 30 day causes transition of an organism to an active adaptation described by an amplified strengthening of intensity of the regulation systems of the organism.

[Problems of ensuring human radiation safety during interplanetary flights].

The work contains the analyses and discussion of the main sources of space radiation specified for interplanetary flights, the dosimetric functionals used for describing the processes of radiation lesions and reparation of the organism in the conditions of the complex radiation impact with a broad charge composition of cosmic rays and a peculiar spatial and temporal dose behavior. It represents the results of calculations of the radiation risks during the flight and the total lifelong radiation risk with taking into account all the delayed unfavorable biological consequences. The main uncertainties in the calculated values of radiation risk leading to its undervaluation are analyzed. In addition, also provided is the range of theoretical and experimental investigations necessary for the adjustment of coefficient values used in the algorithm of radiation risk calculations, as well as in the nomenclature of experiments for estimating the individual resistance of man to the extreme influence and investigations aimed at estimating and increasing the reliability of the operator activity of cosmonauts.

[Dose loads on and radiation risk values for cosmonauts on a mission to Mars estimated from actual Martian vehicle engineering development].

The current design philosophy of a Mars orbiting vehicle, takeoff and landing systems and the transport return vehicle was taken into consideration for calculating the equivalent doses imparted to cosmonaut's organs and tissues by galactic cosmic rays, solar rays and the Earth's radiation belts, values of the total radiation risk over the lifespan following the mission and over the whole career period, and possible shortening of life expectancy. There are a number of uncertainties that should be evaluated, and radiation limits specified before setting off to Mars.

[Autoimmune processes after long-term low-level exposure to electromagnetic fields (the results of an experiment). Part 2. General scheme and conditions of the experiment. Development of RF exposure conditions complying with experimental tasks. Animal's status during the long-term exposure].

This paper describes the conditions for handling and exposure of experimental animals (Wistar rats) and methods used in the study of immunological effects of long-term low-level (500 microW/cm2) exposure to radiofrequency (2450 MHz) electromagnetic fields, performed under auspices of the World Health Organization.

[Autoimmune processes after long-term low-level exposure to electromagnetic fields (the results of an experiment). Part 5. Impact of the blood serum from rats exposed to low-level electromagnetic fields on pregnancy, foetus and offspring development of intact female rats].

This study evaluated possible adverse effects of injection of blood serum from rats exposed to microwaves at a power density of 500 microW/cm2 on pregnancy and foetal and offspring development in intact female rats. The study was performed with 59 pregnant Wistar rats. In utero mortality, embryo and foetal body weights and placenta weight were used for the evaluation of embryo and foetal development. Generally accepted integral and specific parameters were used for the evaluation of postnatal development of offspring during the first 30 days of life. It was shown that intra peritoneal injection of blood serum from IMF exposed rats (chronic 30-day RF exposure at 500 microW/cm2) to intact rats on the 10th day of pregnancy resulted in adverse effects on foetal and offspring development. Total mortality (in utero + postnatal) as well as delay in offspring development was higher in this group.

[Investigation of the processes of post-radiation reparation of the corneal epithelium cells of mice irradiated by helium ions with various LET values].

Biological effectiveness and post-radiation recovery of corneal epithelium cells of mice were studied. Mice were exposed to a broad range of doses from accelerated helium ions with the energy of 4 MeV/nucleon and 4 GeV/nucleon once and twice with a 24-hr. interval. LET values for these energies were 120 and 0.88 keV/microm, respectively. Gamma-source 137Cs (LET = 0.3 keV/microm) was used as a radiation standard. Animals irradiated by 25-400 sGy were sacrificed in 24 and 72 hrs. by way of cervical dislocation. Total corneal preparations made from enucleated eyeballs were analyzed for the mitotic index and aberrant mitoses using the anaphase method. High damaging properties of accelerated helium ions with the energy of 4 MeV/nucleon were manifested by a considerable reduction of the mitotic index and a more marked rise in the number of aberrant mitoses following the single and repeated exposure. Fractional irradiation by helium ions with the energy of 4 MeV/nucleon resulted in inhibition and even arrest of reparation suggesting additivity of separate radiation fractions. From the dose values that produced the double reduction of the mitotic index, coefficients of the relative biological effectiveness (RBE) for helium ions with the energy of 4 MeV/nucleon and 4 GeV/nucleon were estimated to be 5.3-8.6 and 1.3-1.8, respectively. In the context of the number of aberrant mitoses, RBE coefficients were significantly lower ranging 2.3-3.5 and 1.1-1.3 for these energies, respectively.

[Radiation conditions and radiation risks for cosmonauts flying to Mars using electrical jet microthrusters].

According to recent workups, the Mars mission spacecraft will be designed with an electrical jet microthrusters rather than a power reactor facility. The article contains analysis of the main sources of radiation hazard during the exploration mission using this cost-efficient, ecological, easy-to-operate propulsion powered by solar arrays. In addition, the authors make predictions of the generalized doses of ionizing radiation for mission durations of 730 and 900 days behind various shielding thicknesses, and on the Martian surface. Calculation algorithms are described and radiation risks are estimated for the crew life span and possible life time reduction in consequence of participation in the mission.

[Radiation safety provisions in a piloted mission to Mars based on calculated risks of overdose behind shielding].

The article deals with the prime sources of radiation hazard in a mission to Mars, compares the radiation risk values in flight and over the life span with consideration for various shielding thicknesses in habitable compartments and radiation shelter, and estimates possible life shortening. Given the stochastic nature of solar cosmic rays effects in a two-year mission and probability of powerful solar proton events, calculated were not only the mean tissue-equivalent doses behind various thickness of the shelter but also probability of their violation, risks of immediate and delayed radiation consequences and conceivable approaches to risk mitigation.

[Relative biological effectiveness of accelerated heavy ions and fast neutrons estimated from frequency of aberration mytoses in the retinal epithelium].

Analyzed was the literature and authors' experimental data concerning lesion and recovery of epithelium cells of mice retina immediately and long after irradiation at different sources including single and partly fractionated irradiation by gamma- and X-rays, accelerated protons, helium, carbon and boron ions, and fast neutrons of the reactor range in a large spectrum of doses and LET. Reviewed are some new techniques of determining the RBE coefficient for these types of radiation; large values of the RBE coefficients for accelerated ions and neutrons (5-10 times higher than RBE coefficients calculated for the next day following irradiation) are a result of integration into calculation of the available data about the delayed disorders in retinal epithelium cell regeneration.

[The quantitative criteria of the transition from norm to pathology at chronic exposure of physical factors].

In this work the quantitative approaches for the characteristic of the change in the condition of separate systems and stability of an organism are considered at chronic exposure of electromagnetic fields of a radio-frequency range. The quantitative criteria for the substantiation of transition from norm to pathology and definition of the thresholds of harmful action of physical factors are developed. The results of the experimental research of the immune system condition at EMF RF exposure were considered. It can be a basis for the definition of maximum permissible levels of these factors for professional workers and for the population.

[Biological effects of microwave radiation of low nonthermal intensity (regarding the maximal admissible values)].

There is still much controversy in scientific approaches to setting limits of exposure to radio-frequency electromagnetic radiation in Russia, Europe and USA. The stumbling stone is recognition or denial of potential risk of biological effects from nonthermal electromagnetic radiation (to 1 mW/cm2). The authors review results of experimental investigations performed in Russia over the years since 1960s to study the direct and delayed effects of ultra-high and microwave frequencies of low non-thermal intensity EMR, and delayed negative effects in employees based on the data of several follow-up epidemiological studies. This evidence was used as a baseline for establishing the Russian limits for chronic exposure to, thresholds of harmful effects and the maximal admissible values of EMR within the above frequencies.