Radiation protection in space

AcraAsrronau!icaVol.35,No. 415,pp. 31>338. 1995 Copyright 0

0094-5765(94)00256-S

RADIATION

PROTECTION

1995 Elsevier Science Ltd

Printedin Great Britain.All rightsreserved 0094-5765195$9.50+0.00

IN SPACE

G. REITZ’, R. FACIUS’ and H. SANDLER’ ‘DLR, Institute of Aerospace Medicine, K6ln 51140, Germany ‘Department of Community Medicine, Wright State University. Dayton, OH 45401, U.S.A.

I. INTRODUCTION Radiation is an acknowledged primary concern for manned spaceflight and is a potentially limiting factor for interplanetary missions. Results from numerous space probes demonstrate heightened radiation levels compared to the Earth’s surface and a change in the nature of the radiation field-particularly the presence of high energy heavy ions. To date less than 300 individuals have participated in the combined programs of the U.S. and CIS, with the vast majority of crew members (-250 persons) having flight exposures of less than 2 weeks. Only a few Russian cosmonauts have been exposed for 1 year, but still at levels for which the excess risk of fatal cancer is lower than the recommended risk limit for U.S. spaceflight activities, namely 3% for the career. However, very little is really known concerning the biological effects of human low level radiation exposure in space. Studies using lower life forms demonstrate a synergistic interaction between microgravity and radiation[ 11.More experiments are needed to confirm these findings, as are measures to counteract potentially harmful medical effects. Plans to extend man’s activities to visits of nearby planets and to spend significant periods of time on the lunar surface demand a reassessment of the presently available databases and the potential for adverse medical outcomes. 2.

RADIATIONENVIRONMENT

Average yearly terrestrial radiation exposure for a normal individual is given in Table 1[2]. Table 2 shows comparative values for routine medical exams, long-haul and transcontinental airflights, for living at various altitudes and the maximal permissible exposure limits for terrestrial and space-based radiation workers. Ordinarily, aggregate background and diagnostic medical levels pose little risk to a given individual and total around 3 mSv/yr. Radiation workers receive, in addition to the natural exposure, about 1 mSv/yr, only a few exceed the limits. Medical procedures (e.g. mammograms, barium enemas) can increase overall levels five-fold. Absolute levels of background radiation increase markedly as one ascends above sea level. Background radiation is twice that in San Francisco (sea level) when living in Denver (1.6 km) and thirteen-fold greater, when living in the

Himalayas. Radiation exposure during a single transcontinental commercial airplane flight can be as high as 100 $jv[3,4]. Exposure levels inside spacecrafts at 300 km altitude have been as much as 0.5 mSv day-’ and still increase with higher altitude. Radiation conditions during spaceflight are quite different from those on Earth. Typical spectra of the radiation components in space are shown in Fig. 1[S]. These radiations are of galactic and solar origin. Solar cosmic rays (SCR) originate from magnetically disturbed regions of the Sun that sporadically emit bursts of charged particles with high energies. These events (solar flares) are composed primarily of protons with a minor component (S-10%) of helium nuclei (alpha particles) and an even smaller part (1%) of heavy ions and electrons. Solar flares develop rapidly and generally last no more than a few hours, however some proton events observed near Earth may continue for several days. The emitted particles can reach energies of up to several GeV. Solar flare particles arrive on Earth in tens of minutes to several hours depending on their energy. Anomalously large events with potentially life-threatening consequences usually occur at the beginning or end of maximum solar activity. During the last three 1l-year cycles of solar activity, in total four of those events were observed. Doses as high as 10 Gy could be received in a worst case scenario and would be lethal to humans within a short time. No method exists that can predict time of occurrence, frequency, intensity or duration of such events[6]. Their buildup can be detected approximately 10 tnin before it occurs, since thete is a dramatic increase of visible light, X-rays and radiofrequency radiation. Galactic cosmic radiations (GCR) originate outside the solar system. They have their origin in previous cataclysmic astronomical events such as supernova explosions. Detected particles consist of 98% baryons and 2% electrons. The baryonic component is composed of 85% protons (hydrogen nuclei), with the remainder being alpha particles (14%) and heavier nuclei (about 1%). All elements are present. Figure 2 shows the abundances of these elements up to tin in relation to silicon[7]. The fluence of GCR is isotropic and energies up to 10’OeVmay be present. Ions heavier than alpha particles have been termed HZE particles (high 2 and high energy). Although iron ions are 313

G. Reitz et al.

314 Table

I. Annual

effective

dose equivalent Annual

Source

of irradiation

Comic

ram:

from

effective

natural

sources[2]

dose equivalent

Total

._

0.30

Directly

ionizing

Neutron

component

(mSv)

Internal

External

0.30 0.055

0.055

radionuclides: Primordial radionuclides: *‘K “‘Rb ?lxU series: ?I*” to?“” ?“‘Th

0.015

Cosmogennic

0.15

0.015

0.18

0.33

0.006

0.006 1.34

0.1 0.005 0.007

R ?“Ra to “‘PO ““Pb to ?“‘po

0.007

I .24

I.1 0.12 0.34

0.16 0.003 :‘XRa

to

‘?JRa

0.013

2:“Rn

to

:,Wl-1

0.16

one-tenth as abundant as carbon or oxygen, their contribution to the GCR dose is substantial, since dose is proportional to the square of the charge. This is also indicated in Fig. 2. Differential energy spectra for hydrogen, helium, carbon and oxygen, and iron are shown in Fig. 3[8]. For high energies, the ion energy spectra are represented by a power law N(E)-E- ’ with ~2.5. The decrease in the intensities for low energies jnside the interplanetary space is due to the attenuation by the magnetic fields of the solar wind. The intensity of the solar wind which consists mainly of ionized hydrogen with an equal number ofelectrons varies during the 11-year cycle of solar activity. During high solar activity the solar wind is stronger and so are the magnetic fields transported by it, resulting in a decrease of the cosmic ray flux. The reverse is true when the solar activity is low. The modulation is effective for particles with energies below some GeV per nucleon. For increasing solar activity the maximum of the energy spectrum is shifted to higher energies. At 100 MeV per nucleon the particle fluxes differ by a factor of about 10 between maximum and minimum solar activity conditions, whereas at about 4 GeV only a variation of about 20% is observed. A cosmic ray particle has to penetrate the Earth’s magnetic field in order to reach orbiting spacecrafts. 2. Radiation medlcal

exposures

in dilferent

exams and exposure

limits

altitudes

and for

for radiation

This penetrating ability is related to the ion’s magnetic rigidity and is given by its momentum divided by its charge. All particles with the same rigidity follow a track with the same curvature in a given magnetic field.

For each point inside the magnetosphere and each direction from that point there exists a rigidity threshold below which the cosmic rays are not able to reach this point. This rigidity is called the geomagnetic cut-off. This value is much lower for high inclination orbits than for low inclination orbits. This means that in low inclination orbits only particles of high energy have access. Towards higher inclinations particles of lower energies are allowed to do so. At the poles (90’ inclination) particles of all energies can impinge in the direction of the magnetic field axis. For a geomagnetic latitude B the vertical cut-off rigidity R, can be given approximately by R, = 14.9 cos4B. The rigidity for particles arriving from directions other than vertical is dependent on the angle of incidence. Due to the

latitude-dependent shielding the number of particles incident in the altitude of orbiting spacecrafts increases from lower inclinations towards higher inclinations. The radiation field around the Earth comprises a third radiation source, the Van Allen belts, which are a result of the interaction

of GCR and SCR with the

routine

mSv

Long-haul

roundtrip

airflight.

dose to awrew

Chest exam-per Lateral

jet at 13 km

on long-haul

film.adults

Posterior~anterior

only.

0.15t

flights (bone

7.5t

marrow

dose)

projection

0.046

proJectlo”

Gonads

0.01

(posterior-antenor

proJectIon)

-

0.001

Lwing

one year m San Francwx

1.0

Living

one year in Denver

2.0

Xeromammography Banurn Living

2.4

workers

Values

Yearly

1.6

0.8

Total

Table

0.18

enema

(breast

(Intestinal

one year I” Kcrala.

dose)

3.83

dose)

x.75

India

13.0

Maximum

allowed~yr

Earth-based

radiation

worker

Maximum

allowediyr

space-based

radiation

worker

tRepresents median values. Dose varies with regard duration, attitude. altitude and solar activity (see[3.4]).

gaiocllc COSrnlCrays 2

,0-5L--LLL 10-L

10-z

100 051

1L

102

51 5 10 50 Ok', ~; ii0 ;O

-

101

Part,cle energyiMeVl

electron range I” All(glcm2I prOtOn range I"All(Qkm'I

50

500 to flight

Fig. I. Radiation environment near Earth. Parallel to the energy axis, the range of protons and electrons in aluminium is indicated[5].

315

Radiation protection in space

ATOMIC

NUMBER,

Z

Fig. 2. Relative abundances of the even numbered galactic cosmic ray nuclei (solid bars) in comparison to their abundances weighted by the square of the charge of the particle to give a measure of the “ionizing power”[‘l].

Earth’s magnetic field and the atmosphere. The radiation belts consist of electrons and protons, and some heavier ions, trapped in the magnetic field. The inner belt is formed by neutrons, produced in cosmic particle interactions with the atmosphere, which have decayed into protons and electrons. The outer belt consists mainly of trapped solar particles. In each zone, the charged particles spiral around the geomagnetic field lines and are reflected back between the magnetic poles, acting as mirrors. At the same time, because of their charge, electrons drift eastwards, while protons and heavy ions drift westwards. Electrons reach energies of up to 7 MeV and protons up to 600 MeV. The energy of trapped heavy ions is less than 50 MeV, and because of their limited penetration capacity, they are of no consequence for satellite electronics or humans. The radiation belts extend over a region from 200 to about 75,000 km around the geomagnetic equator. The trapped radiation is modulated by the solar cycle: proton intensity decreases with high solar activity, while electron intensity increases, and vice versa. Diurnal variations of a factor of between 6 and 16 are observed in the outer electron belt, and short-term variations due to magnetic storms may raise the average flux by two or three orders of magnitude. The centre of the inner belt is quit stable. especially with respect to protons. However, in the atmospheric cut-off region, electron and proton intensity may vary by up to a factor of 5. For the majority of space missions in low Earth orbit (LEO), protons deliver the dominant contribution to the radiation exposure inside space vehicles. Because of their higher energies and correspondingly longer range, their total dose surpasses that of electrons at mass shielding above about 0.3 g/cm’ aluminium. At lower shielding[e.g. in the case of extravehicular activities (EVA)] the absorbed dose is dominated by the electron contribution and may reach up to 10 mSv per day.

Of special importance for low-Earth orbits is the so-called ‘South Atlantic Anomaly’ (SAA), a region over the coast of Brazil, where the radiation belt reaches down to altitudes of 200 km. This behaviour is due to an 11” offset of the Earth’s geomagnetic dipole axis from its axis of rotation and a 500 km displacement towards the Western pacific, with corresponding significantly reduced field strength values. Almost all radiation received in LEO at low inclinations is due to passages through the SAA. At the 28.5” inclination planned for the Space Station, six orbital rotations per day pass through the anomaly, while nine per day do not. Although traversing the anomaly takes less than about 15 min and occupies less than 10% of the time in orbit, this region accounts for the dominant fraction of total exposure. Before the various components of ionizing radiation in space can interact with biological systems or man, they have to penetrate the matter in protective shielding. For EVA, this will amount to thicknesses of fractions of a g/cm’. while within space vehicles it will amount to a few g/cm’. The dominant physical mechanism for the modification of spectra1 fluxes is energy loss through ionization of orbital electrons in the shielding material via the Coulomb interaction. For protons and heavy ions continuous deceleration can be assumed. With electrons, slowing is not continuous, straggling effects occur. Bremsstrahlung, as a consequence of deceleration, is important only for electrons. For higher particle energies, collisions between the primary ions and the nuclei of the shielding material represent a significant interaction. Through fragmentation of the incoming particles and disintegration of the target nucleus, new particles such as mesons, pions. secondary protons, neutrons, alpha particles and some heavier components will be produced. which again can interact with the shielding material. 3. BASIC CONCEPT

The absorbed dose, D, is usually used as the basic physical quantity that measures radiation exposure. The absorbed dose is the quotient of the energy imparted by ionizing radiation to the matter in a volume element by the mass of the matter in that volume element. The absorbed dose is measured in units of Gray, Gy[l Gy = 1 J kg ’ (= 100 rad)]. Whereas different radiations produce the same type of effect, the magnitude of the effect per unit absorbed dose is different. The inverse ratio of the absorbed dose from one radiation type to that of a reference radiation (usually 6oCo or 2OC-250 keV X-rays) required to produce the same degree of effect is defined as relative biological effectiveness (RBE). For a given type of radiation, RBE depends upon the tissue, the cell. the biological effect under investigation, the total dose and the dose rate. A large number of RBEs in a wide variety of biological systems have been determined. Dependent

G. Reitz el al.

316

on the biological endpoint and the radiation type the values range between 0.35 up to 200[9]. Endpoints important for radiation protection are tumour induction, life shortening, cell transformation and chromosome aberrations. In addition to the fact that only few data from experiments in human subjects exist, a very small extent of these data is relevant to low dose and dose rate conditions. For radiation protection, the quality factor (Q) was introduced in order to account for the different biological efficiencies of different types of ionizing radiation. This factor depends not only on appropriate biological data, but primarily it reflects a judgement concerning the importance of the biological endpoints and how their empirical RBE values should be weighted. RBE values observed at the lowest absorbed dose should guide the selection of values of Q. The biological effectiveness of a given absorbed dose

d>+yrogen

is dependent on the microscopic distribution of energy deposition. This distribution is described by the number and the nature of charged particles that traverse an infinitesimal volume located at the point of interest and deliver the dose. This quantity, the flux density or fluence rate can refer to directly ionizing radiation (i.e. charged particles) or indirectly ionizing radiation (e.g. photons, neutrons, etc.). The linear energy transfer (LET) is used as the quantity that describes the energy loss of a charged particle per unit distance in a medium. The dependence of RBE on LET leads to the relationship of Q to LET which is applied to weight radiations of different radiation quality. Q is specified as a function of the unrestricted linear energy loss, LET, of charged particles in water. It ranges from I for LET < 3.5 keV/pm to 20 for LET > 175 keV/pm[lO]. Based on new data, such as the higher RBEM values for intermediate energy

nuclei (x5)

-4-

lo-’

1 10 102 Kinetic energy (GeV.nucleon-‘)

Fig. 3. Energy spectra of the cosmic ray nuclei. In the left part of the curves the influence of the solar modulation is shown. High solar activity leads to a decrease of the flux of the nuclei[8].

Radiation protection in space neutrons, the reduced effectiveness of heavy ions with LET > 100 keV/pm and the induction of tumours in the Harderian gland of mice for argon and iron ions[ 111,ICRP defined a new Q-LET relationship. It is set at 1 for LET < 10 keV/pm, 0.32 x LET-2.2 in the range of 10-100 keV/pm and 300 x (LET)05 for LET > 100 keV/pm[l2]. In addition to Q, in radiation protection other dose modifying factors (DMFs) have to be applied if the conditions of exposure differ from those under which the experimental “reference” dose-effect relations have been obtained. Among these factors is the “dose distribution factor” (DF) which accounts for differences of the “geometry” of irradiation such as depth dose distribution or partial-body irradiation. The “dose rate effectiveness factor” (DREF) accounts for differences in the effect level which occur if the dose rate or the temporal pattern ofexposure (fractionation or protraction) differ between the reference exposure and the field to be evaluated. The “physiological factor” (PF) addresses the modification of the biological response due to changes of the internal biological state of irradiated tissue, the degree of oxygenation of irradiated tissue and other stress factors. The product of the absorbed dose, Q, and other dose modifying factors finally yield the biologically weighted “dose equivalent” (H) which correlates better to the absorbed effects than the purely physical quantity of the absorbed dose. The dose equivalent is measured in units of Sievert, Sv[Sv = 1 J kg-’ (= 100 rem)]. For a radiation field consisting of different radiation qualities i, the dose equivalent for uniform whole body irradiation, H, is the sum of the dose equivalent of its individual components, H,, where D, is the absorbed dose due to radiation component i and N, is the product of the other dose modifying factors relevant to radiation component H,. Under terrestrial exposure conditions N, is set to 1. H = I: H, = X N,Q,D,

Recently, ICRP released its publication No. 60 in which new radiation weighting factors have been selected to account for the differences in the biological effectiveness of different types of radiation. The equivalent dose (HT.R) is defined as the product of the average absorbed dose (DT.R) in a tissue or organ (T) due to radiation (R) and the weighting factor (rvR).An approximation of ~1~ can be obtained by the calculation of a mean Q at 10 mm depths in the ICRU sphere. In the case of non-uniform distribution of the absorbed dose in the human body, the effective dose, E, has to be calculated as the weighted sum of the dose equivalents of various tissues with the weight factors recommended by ICRP[12]. It should be noted that the other dose modifying factors are disregarded when establishing radiation protection guidelines for space, although exposure

conditions in space are considerably those on Earth.

317 different from

4. SPECIFIC ASPECTS OF THE SPACE RADIATION FIELD

Immediately evident in the simplified version of the calculation of the dose equivalent as a function of the quality factor alone is the huge range of LET values occurring in the terrestrial space radiation field. Application of the “adopted” dependence of Q as a function of LET rests on the assumption that the underlying terrestrial experience, gained from completely different sources of ionizing radiation, can be applied to the space radiation and is the same for the relevant effects in critical organs. In particular, for the extremely densely ionizing radiation of HZE particles and nuclear disintegration stars this approach loses its conceptual basis since the definition of absorbed dose as a measure of radiation exposure, and hence that of RBE and Q, breaks down. The combined action of the two different processes of ordinary ionization and nuclear collision leads to rather complex relationships concerning the attenuation of HZE particles in matter. Particles of low energies in the incident radiation, which have an ionization range substantially shorter than the collision mean free path, have a high probability of escaping nuclear collision completely and spending their entire kinetic energy in ordinary ionizations. Particles of high and very high energies in the incident flux, on the other hand. with ranges substantially greater than their interaction mean free paths, have a high probability of being removed, or at least transformed into a lighter fragment by nuclear collision, before they come to rest. Since the primary galactic radiation in space is heterogeneous concerning both the Z and Espectra, i.e. contains a continuum of different mean free path values and energies, the transition in its spectral composition during attenuation in shielding layers or the human body is extremely complex. Since the radiation incident on the human body is scattered, fragmented and degraded in energy as it penetrates to the deeper organs, the effective LET, as well as the dose and dose rate, all change with depth; all three are factors that influence RBE, but not necessarily in the same direction. Fragmentation might lead to an enhancement (build up) of high LET components on the costs of low LET components. Of particular importance for dose modifications towards higher quality factors is the increase of the number of nuclear disintegration stars with higher multiplicities near the bone marrow in osseous structures. Radiation exposures in space will not result in uniform whole-body dose distribution. Dose distribution will be non-uniform both with respect to depth and with respect to the area or region of the body involved. Rapidly decreasing absorbed dose with depth in tissue results from the spectral characteristics of the significant space radiations. As an example the

318

G. Reitz et al

integral-energy spectrum (and consequently the absorbed-dose deposition) of primary solar flare protons is a continuum with negative slope that varies from flare to flare with time during thecourse of a flare, and with prefilteration. Qualitatively, it is generally accepted, that partial or non-uniform exposure in man entails less damage than uniform total-body exposure. With respect to time depending factors, it is evident that the radiobiological conditions in space differ quite substantially from those which usually apply for “reference” experiments on Earth. Compared to typical dose rates in terrestrial experiments with photon sources and particle accelerators, the fluxes in space are lower by orders of magnitude. Thus the spread of dose rate effects observed with low and high LET radiation impacts the calculation of dose equivalents under spaceflight conditions. Basically, in space the irradiation of the body is chronical. However, in low-Earth orbits there are variations due to geomagnetic shielding and solar cycle variations. Both are regular and predictable. Time scales range from minutes for the first and years for the latter variation. Secondly, there are solar particle events, which are irregular and unpredictable with time scales in the order of hours to days. Even in geomagnetically well shielded low inclination orbits there are influences of solar particle events due to magnetic storms in the Earth’s magnetic field, and by that changes in the trapped particle environment.

5. PHYSICO-CHEMICAL

5.1.

AND SUBCELLULAR EFFECTS

RADIATION

Introduction

The effects that ionizing radiation produces in living matter result from energy transferred from radiation to the molecules of which cells are made. The primary effects start with physical interactions and energy transfer, changed molecules interact by chemical reactions and interfere with the regulatory processes within the cell. Chemical reactions are important if they affect molecules essential for life processes that are needed for proper functioning of the cell. Among the molecular hierarchy in the cell the DNA (deoxyribonucleic acid) plays an important role in cell proliferation, but also many other molecular structures support the integrity of the cell. Irreversible cellular changes, produced by the radiation, can alter the function of the cellular pathways and can lead to a situation in which cells may lose the ability to perform one or more functions permanently. This damage may play a role in the cell after different cell cycles, or the damaged cell as a part of an organ leads to changed or altered functions of the organ. The time scale for the events on the physical, chemical, macromolecular and cellular or organ level ranges from lO-‘+Js to years.

5.2. Mechanisms

qf’ Radiation

Action

The principal means by which ionizing radiation dissipates or transfers energy to matter is by the ejection of an orbital electron, which is called ionization. The production of an ion pair, constituted by the ionized atom and the ejected electron, needs an average energy of 34 eV. Ionizing radiations with higher energies transfer kinetic energy to the electrons which lose energy by secondary collisions[ 131.Ionizing radiation acts not only by ionization but also by a process called excitation, which is about 20% of the energy transfer. Excitation involves the valence electrons responsible for chemical combinations with other atoms[ 13,141. Excited molecules are altered with respect to the chemical forces that may lead to a regrouping of affected atoms or will result in different molecular rearrangements or, by further energy transfer, breaking of bonds occurs. Traversing the matter, ionizing particles have a certain probability to collide with the atomic nuclei of the absorbing material. Depending on the mechanism during this collision, two main processes can be observed, the nuclear disintegration and particle fragmentation. The first describes the reaction of the absorbing nucleus while the other describes that of the incoming particle. It is unknown if the nuclear disintegration of a nucleus within an essential molecule has considerable radiobiological consequences; but it is an important fact for both reactions that from the point of collision more than one particle will be ejected which enhances the chance of high energy depositions within a close volume and can change molecules that are essential for the radiation damage under consideration. Bremsstrahlung is an electromagnetic radiation generated by the deceleration of charged particles, in particular, in the Coulomb field of a nucleus. The energy loss due to Bremsstrahlung for electrons begins to be very important for energies above 100 MeV in water but above 50 MeV for aluminium. For high energetic electrons this process is the dominant mode ofenergy loss and with the pair production ofphotons, both processes result in an electron-photon cascade[13,14,15]. The two major modes by which the photons give up their energy are photoelectric absorption and Compton scattering. For low energy photons the most likely result is to transfer the whole energy to the electron which by itself produces ionization or excitation. For higher energies the probability of this effect decreases. In soft tissue photo-electric absorption is the predominant energy absorption effect for energies of up to 100 keV. The absorption depends on the atomic number of the materials and is preferential for elements with high atomic numbers such as bone compared to materials having low atomic numbers such as soft tissue. Bone will absorb five to six times as much energy per gram as will soft tissue. For medium energy photons (100 keV-10 MeV),

319

Radiation protection in space scattering is the predominant process where the photons transfer only a portion of their energy to the electrons as kinetic energy. The photon itself will be scattered. This interaction does not depend on the atomic number. It depends only on the density of electrons. In this energy range this process is the most important in soft tissue. Bone and soft tissue essentially absorb the same energy per gram. For photons with high energy (10 MeV), a process differing exclusively from those described above occurs by interaction of the photons with the electric field of the nuclei of the material, which does not involve the ejection of orbital electrons. The energy is converted into the mass of a positive and a negative electron and is called pair production. Excess energy will be shared as kinetic energy between the two newly formed electrons. Pair production is dependent upon atomic number. Larger nuclei having strong force fields thus increase the probability of the occurrence of this process. Bone absorbs approximately two times as much energy per gram as soft tissue[l3,14,15]. Charged particles interact with matter by direct collisions with the electrons of the atoms and also by interactions between their charge and that of the orbital electrons. Both processes result in ionizations. The rate of energy loss along the track of a charged particle depends upon the square of the charge of the particle. The influence of the electric force field depends on the velocity of the particle. Slower moving charged particles will produce more ionizations per unit path length than faster moving ones. Since the probability of ionization is inversely related to the velocity, decreasing velocity will mean an increase in ionization density which reaches a maximum just before the particle comes to rest. A unit that has been devised to account for all energy transfers along the particle’s path irrespective of the mechanism is the linear energy transfer (LET)[13,14,15]. Neutrons as uncharged particles affect atomic nuclei or electrons by direct collisions. Since their interaction depends upon a chance to collide with atoms, neutrons have a high penetration depth in all kinds of matter. Neutrons are classified by their energy. Fast (high energy) neutrons lose energy mainly through collisions with atomic nuclei. Because hydrogen atoms are the most numerous in tissue with about 70-80% water and since the average energy transferred to hydrogen is greater than to any other nucleus, the major mode of energy loss in soft tissue is the ejection of high speed protons. These act as charged particles by ionizing the atoms along their paths. Slow (low energy) neutrons interact in matter mainly by the process of capture. The neutron enters the nucleus and. through its energy, may put the nucleus in an excited, unstable state. This nucleus emits nucleons and ends up as a stable or radioactive nucleus. Besides all other primary phenomena, more secondary physical effects take place and are called spike or shock wave phenomena[l6]. They are caused Compton

by the high energy density within a small volume deposited by heavy particles. This energy density leads to a high disordered state of the atoms interacting with the particle. This state can be described as a temperature of several thousand degrees Kelvin depending on the type of particle. Shock waves can be caused by the repulsion forces of the highly ionized atoms reacting with the heavy particle and resulting in a shock front with a high pressure. Both phenomena can be used to describe experimental findings, e.g. sputtering. The radiobiological consequences of these phenomena are only speculative at this time but they could, in addition, be further physical parameters to describe the unique heavy ion effects. 5.3. Cellular Consequences Ionizing radiation represents a natural environmental factor that living organisms have had to cope with since the beginning of biological evolution. In a living cell, ionizing radiation can cause damage to all cellular components. The probability of damage is largely reflected by the target size of the component under consideration. The biological significance of the damage depends on the redundancy of the macromolecules in the cell and on their functions regarding cellular integrity. A variety of different primary lesions are induced in cellular DNA-the informational active chemical component of genetic material---by ionizing radiation, such as single or double strand breaks (SSB or DSB), base damage of different types, DNA-DNA and DNA-protein crosslinks, as well as apurinic and apyrimidinic sites. Damage to DNA, if remaining unrepaired, may have fatal consequences for the cell, such as cell death or induction of mutations. In contrast, damage to RNA, which is readily synthesized in the cell with high multiplicity, will easily be coped with by de noco synthesis. Radiation damage to the proteins that occupy so many essential structural and enzymatic functions in a cell, may lead to severe impairment. However. after lethal doses of radiation, protein damage merely implies an additional weakness of cellular activity. but is not the decisive event to cell death. Likewise, radiation-mediated breakdown of the permeability functions of membranes are not considered to be the deciding factor for cell death, however they do represent additional stress to the cells. Though radiation damage to any of the essential structures and components can imply considerable impairment ofcellular integrity, damage to DNA is the most likely to be lethal or mutagenic. Since DNA damage is an inescapable aspect of life in the biosphere, nature has developed a complex system for repair of damaged DNA molecules[ 17.181. The most general DNA repair mode observed in nature is one in which damaged or inappropriate bases or nucleotides are excised from the genome and replaced to reach the normal nucleotide sequence and chemistry of DNA. This cellular response, called excision repair[ 191. is a

320

G. Reitz er al.

multistep biochemical pathway, with a variety of alternative enzymatic mechanisms. In mammalian cells, DNA is in intimate association with histones in the nucleosomes. By this organization DNA is protected from the attack of excision repair enzymes. Transient alterations of nucleosome confirmation, such as partial dissociation of DNA from histones, are necessary to allow excision repair events. After repair, a repackaging of the nucleosome occurs. Such repair processes are capable of restoring DNA molecules, that have obtained a SSB due to ionizing radiation. In diploid cells even DSBs can be effectively repaired, where the undamaged homologous chromosome serves as a template for the reconstitution of the broken one. DSBs are conjectured to be directly involved in chromosomal aberrations. Mutations are potentially heritable changes in the genetic information of a cell. They occur spontaneously, however, the rate is significantly increased in cells exposed to ionizing radiation. Mutations may result from direct alterations of a base in the DNA (point of mutation), from the shift in the genetic code (frame shift mutations) which frequently appears after SSBs in the DNA, or from attacks to the whole chromosome (chromosomal aberrations, such as deletions or translocations). Somatic mutations, i.e. mutation of body cells, may have consequences for the individual, whereas genetic mutations, i.e. mutations of the germ cell, may have consequences for the population. There is some indirect proof, that in mammalian cells, mutagenesis proceeds via an inducible errorprone repair mechanism, the so-called SOS-repair, which has been extensively studied in prokaryotic cells. Following DNA damage, an inducing signal activates the expression of a whole battery of genes that are normally under the control of a common regulatory system. Products of these genes are involved in the error-prone repair processes of DNA which cause nucleotide sequence alterations with high probability. Mutagenesis by ionizing radiation is suggested to follow this mechanism in most cases[l9]. According to the general theory of carcinogenesis there exists a strong relation between DNA damage and neoplastic transformation via somatic mutations. Carcinogens are agents that cause damage to the DNA of cells. If cellular response to such damage results in mutations that are affecting the growth-regulating genes, the phenotype of the descendants of the affected cell may show neoplastic transformation. Neoplastic transformation of human fibroblasts in culture was induced by treatment with ionizing radiation[20]. The neoplastic state is of a heritable nature and is peculiar to multicellular organisms. Therefore, cellular transformation is of special interest in mammals, particularly humans. After exposure to ionizing radiation, the final fate of a cell will be either recovery, which means complete return death.

to the pre-irradiation Full recovery requires

level, mutation or cell energy and time (up to

several days). The consequences of cell death for the system depend on the replacebility of the affected cell. 6. RADIOBIOLOGICAL 6.1.

EFFECTS

Unique Aspects of HZE Particle Effkcts

The radiobiological aspects of high-LET radiation to be discussed here focus on the features of densely ionizing radiation, which render the conventional assessment of the radiation quality of different types of ionizing radiation inapplicable by means of the relative biological effectiveness, RBE, or its derivative in radiation protection, the quality factor, Q. “The present RBE concept obviously cannot be applied, when the concept of radiation “dose” itself fails. An example would be, when a special type of biological effect is produced by the passage of a single particle of high LET. There is some evidence from radiation studies at high altitudes that such processes occur, but their biological importance is uncertain. Another example might be in nuclear “stars”, where several ionizing particles are emitted from a common center, but at the present time very little is known about the biological consequences of such processes.” ([I3 I], Section 104). 6.1.1. Spacejightjndings

The studies referred to in this quotation, without proper references, presumably concern the experiments performed with mice in a high altitude balloon flight in the 195Os[21,22,23]. Summarizing discussions of these[24] and other additional[25] experiments emphasized two common features of these results. The biological effects observed-grey spots and streaks in the fur-were ascribed to the passage of single cosmic HZE particles, and the lateral extensions of these streaks were much larger than any physical explanation, in terms of ionization pattern around the particles’ trajectories, might provide. In subsequent experiments[26,27,28,29,30,31] these studies were extended to histological examinations of the brains of mammals exposed to cosmic HZE particles in high altitude balloon flights. Again, the large lateral extensions of track-like regions found in these brain sections stimulated speculations about the biophysical mechanisms responsible for this “long range” effect[29,30]. However, apart from potential artefacts from the preparative techniques, these findings were affected-as well as the earlier ones-by the lack of a firm geometrical correlation between the observed biological effects and independent information on the trajectories of the presumably causative single heavy ions. although physical track detectors had been employed for this purpose in most of these experiments. This crucial methodological prerequisite was fully accomplished in the subsequent Biostack space flight experiments, where a variety of biological test organisms in resting state could be attached, in monolayers, to the surfaces of thin sheets of visual nuclear track detectors in such a way that a permanent and precise correlation between the positions of the individual test organisms and the trajectories of the

Radiation protection in space

HZE particles could be recorded[32,33,34]. Evaluation of the effects observed in bacterial spores [35], plant seeds[36] and animal embryos[37,38,39] demonstrated that single HZE particles in all these test organisms, although with varying efficiency, induce significant biological perturbations comprising gross somatic mutations. severe morphological anomalies and complete inactivation of development. Biophysical analysis of some of these results again yielded the conclusion that the magnitude of these effects could not be explained in terms of accepted mechanisms[40,41], and, in particular, that the lateral extension of effectiveness around the trajectories of single particles exceeds the range where secondary electrons could be considered to be effective[42]. Investigations on yeast cells in Russian space flight experiments[43], which were set up in a similar way to the Biostack experiments, also produced in these organisms an inexplicably large lateral extension around the trajectories of the single HZE particles[44]. Investigations on the effectiveness of nuclear disintegration stars also demonstrated significant levels of mutations and inactivation to be engendered by single such events in bacterophages[45,46,47], although the task of independently localizing these events has not yet adequately been solved. Indirect evidence for the action of stars had also been found in one of the Biostack test organisms[38,39]. single

6.1._‘. T~,rrr.striul,findings 6.12. I. (tr) On HZE particle mechanisms. The findings to be discussed are (1) the effects of accelerated heavy ions on cells and tissues, (2) the observation of microlesions engendered in various tissues by irradiation with a single heavy ion, (3) the non-additive effect on tissue cultures of sequential irradiation with heavy ions and sparsely ionizing radiation. (4) the different kinetics of expression of late effects in mammals and (5) the reversed dose rate effect observed in the life shortening of mice and the induction of neoplastic transformations in tissue cultures by high-LET radiation in the context of other endpoints and systems. Extensive ground control work with spores of Buci//u.s suhtilis corroborated the Biostack findings in two independent ways. On the one hand, analysis of the effects of single accelerated heavy ions on single cells reproduced the essential features of the spaceflight results[48,49,50]. On the other hand, conventional analysis of the inactivation cross-section corroborated the conclusions of the spaceflight results that current quantitative models of radiobiological heavy ion effects do not reproduce the observed cross-sections, As far as the “long range” effect is concerned. the results of the accelerator experiments with this organism and with yeast cells were also indicative in its operation[49,50,51,52,53,54]. One of the most spectacular findings so far, in terms of radiobiological HZE particle effects, namely the

321

microlesions produced by single heavy ions, were, once again, first discovered via spaceflight experiments as channel-like or tunnel lesions in the retina of rats. In subsequent accelerator experiments these microlesions have been shown to be caused by the passage of single heavy ions through various biological tissues. Although the quantitative interpretation of these results in terms of physical “quality” parameters remains somewhat controversial, these observations unequivocally represent unique radiobiological responses to the penetration of single heavy ions. The implications of these microlesions for assessment of radiation hazard in space were summarized in[133]. The literature relating to biological HZE particle effects is full of caveats about the applicability or not of absorbed dose and hence of RBE or quality factors. One of the implicit assumptions of those assessing space radiation environment hazards has been the independence or additivity of the effects of sparsely and densely ionizing components. However, when this basic postulate was subjected to experimental testing, it was found to be incorrect. Pre-irradiation with either X-rays or heavy ions rendered V79 cells more sensitive to subsequent irradiation with the another radiation modality, with X-ray pre-irradiation resulting in greater synergism rather than vice versa[55,56,57,58]. Results displaying this non-additivity in cultures of the same mammalian cell line irradiated with such light ions as deuterons or helium ions were also described[59] and also even results for simultaneous irradiation with fast neutrons and gamma rays[60]. In the experiments reviewed so far the radiobiological endpoints under investigation can vaguely be classified as early effects. The increasing importance of radiobiological late effects adds additional weight to recent experimental findings concerning the late effects of densely ionizing radiation. In a series of heavy ion experiments the temporal distribution of the incidence of late effects in various rabbit tissues was investigated and compared with corresponding findings for sparsely ionizing radiation. Apart from the reduced amount of recovery, an acceleration of the development of the late effects, together with an increased severity of these effects, was observed in the heavy ion experiments as compared to the X-ray results[61,62,63,64,65]. This difference in recovery pattern from certain types of injury implies that for heavy ion irradiation the term RBE will have little meaning. In the already-mentioned investigations on the additivity and kinetics of damage expression[56.6 1,651 and in[66], the observation reported was that fractionation of the high-LET irradiation did not result in the reduction of the radiobiological effects, as in the case of protraction of low-LET radiation exposures-with the telling exception of a particular class of biological endpoints to be discussed below. On the contrary, in[56.65,67,68,69] fractionation of heavy ion exposures resulted in an enhancement of the early and late radiobiological effects.

322

G. Reitz et a/

6.1.2.2. (b) On neutrons. A “reversed dose rate effect” for mutation induction in the spermatogonia of mice under fast neutron irradiation has also been reported[70]. For this type of high-LET radiation the evidence accumulated for the absence of a sparing effect or, more often, even the enhancement of radiation damage by protracted irradiation is so far the most impressive. For life shortening the corresponding results in[71,72,73,74,75] have been regarded in[76] as a, by now, established general feature of neutron irradiation. For genetic endpoints under neutron irradiation the reversed dose rate effects were reported in[75,77]. For tumour induction in uiuo, which also according to[76,78] accounts for practically all of the life-shortening effect, and for which no satisfactory explanation is at hand[79], this reversed dose rate effect was also described in[80] and for total exposure levels down to 20 mSv at “average” dose rates as low as 2 mSv/day in(8 11. Cell transformation by chronic neutron irradiation in vitro demonstrated the same dependence on dose rate at dose levels down to 0.86 mSv/min[82,83]. Despite the amount of empirical data accumulated by now, the physical and biological mechanisms underlying these phenomena remain obscure. Biological speculations differ, depending on whether effects at the cellular level or at the tissue level are considered. For cellular effects, hypotheses concentrate on the modification of DNA repair mechanisms, either by damaging the responsible system(s) or by bypassing them, the latter being due either to the generation of specific non-repairable lesions or to the concentrations of lesions being too low to trigger the repair mechanisms. For the disruption of structure and function at the tissue or is a organ system level, damage to membranes conceivable early step in the development of these lesions. especially with respect to shock wave interactions[41]. Potential amplification of microlesions by responses of the surrounding tissue or, vice versa, perturbations of its normal activities as discussed in[l33], augment the complexity of these phenomena to an extent that is beyond our present capabilities. The potential participation of membranes in the conveyance of the observed radiobiological effects merits some further comments which increase the likelihood of such speculations in the light of the following sets of empirical findings: (I) enzymes associated with membranes are not inactivated directly by ionizing radiation but indirectly owing to membrane lipid peroxidation, and DNA and its functions are intimately associated with its proper connection to membranes; (2) oxygen enhances radiation damage to membranes, and for very high LETS the oxygen enhancement ratio rises again above 1:(3) structural and functional changes can be induced in membranes at sublethal dose levels, and membranes (natural as well as artificial) are known to display a reversed dose rate effect under irradiation with

sparsely and densely ionizing radiation. Combined with the known thermophysical phenomena and the known susceptibility of membranes to thermodynamical changes, these facts, especially the reversed dose rate effect as a kind of characteristic signature for radiation effects from densely ionizing radiation, raise the question of possible involvement of membranes in these effects.

6.2. Analysis of Somatic Radiation Efects on Critical Organs

and Efects

The primary empirical database pertains in the overwhelming majority of cases of exposures to sparsely ionizing radiation (photons and electrons) under terrestrial exposure conditions only, with a quality factor of one. Therefore, the units of exposure in this section are not given, as they should be, in Sievert, but in Gray. Exposure for the NUREG[88] report is quantified as organ-specific absorbed dose, and as whole body dose for the PSR report[89,90]. 6.2.1. Tissue/organ

response

As far as radiation protection of man is concerned, the subcellular and cellular radiation effects mentioned above are relevant only insofar as they finally give rise to deterioration of tissue or organ functions with the expression of clinically observable symptoms. Symptoms becoming manifest from within minutes to 30-60 days subsequent to exposure are classified as early effects. Radiation effects not occurring within this period generally do not become manifest for many months or even years of a latent period and these effects are then classified as late or delayed effects. Among the late effects, those which do not become manifest in the irradiated individual but in its progeny are classified as genetic or, more properly, as hereditary effects and they arise if radiation damage either directly or indirectly affects the cells of the germline. Non-genetic effects are the result of radiation damage to the soma and hence are called somatic effects. Radiation effects in complex organisms are further divided into stochastic and non-stochastic radiation effects. For non-stochastic radiation effects the magnitude or severity of effect depends on the dose, with a possible lower threshold dose below which no response at ail will be produced. For stochastic radiation effects, however, no threshold dose exists and here the probability for the manifestation of a radiation effect rather than its magnitude becomes a function of the dose. Although the biological pathways which link cellular radiation damage with final symptoms in tissue or organs remain largely enigmatic-epecially for late radiation effects-for early effects the biologically plausible hypothesis can be advanced that the severity of tissue response will depend on the fraction of constituent cells having been killed and on the tissue’s intrinsic capacity to regenerate this

Radiation protection in space fractional cell loss[78,84]. For late effects, however, the transformation (mutation) of cells rather than cell killing is probably the primary relevant cellular effect, especially for cancerogenesis, although additional interfering and contributing biological mechanisms assume greater importance for the final outcome. Very recently, however, evidence is increasing that cell killing per se in cells surrounding the initiated (transformed) cells is also an important factor in the promotion (towards the full malignant status of a tissue) of the initiated progenitor cells. For a recent review see[85] and references given therein and also[133], who have already speculated about the importance of this relationship for radiobiological heavy ion effectiveness, especially in carcinogenesis. To the extent that universal findings can be obtained for the relations observed in animal systems between dose-modifying factors, such as radiation quality or dose-rate, and cell killing or transformation, these findings might tentatively be drawn upon to supply the information lacking for human response data, available only for radiation qualities and exposure conditions vastly different from those prevailing in the space radiation field. The general principles which can be derived from the vast amount of data covered by the general literature on radiobiological effects are even necessary as guidance into the interpretation of the database concerning the specific human response to ionizing radiation under purely terrestrial conditions. The most important source of human exposures for the dose-effect relations for stochastic radiation effects, i.e. radiation-induced cancer, is the Japanese atomic bomb survivors. But even this source suffers from severe restrictions concerning either the dosimetry and/or the medical or epidemiological methodology. A summary of the database is given in[86]. For early (acute) radiation effects, part of the same database as used for stochastic effects and, in addition, findings from therapeutic exposure in cancer therapy and from accident victims in the nuclear industry constitute the respective database. For a condensed description of these accidents given by Lushbaugh see[87]. The primary and secondary sources of human exposures are reviewed and updated constantly by national and international committees as well as adhoc study groups. The UNSCEAR reports are widely recognized as the most thorough and balanced summaries of the field. 6.2.2. Early @iws Manifestations of early effects in man usually appear to be threshold phenomena and occur only after acute exposures to comparatively high doses, which under terrestrial standards would have been ruled out as impermissible under regular circumstances. In the pioneering era of manned spaceflight, however, the hazards of exposure to space radiation had to be evaluated in the context of the high

g 100 ”

r

323

/-

5 E 2

9o

s” 7 E ._

80-

.E

70

-

s, 2 m r

60-

i x T

so-

z v3 0

40-

5 ‘C i

30 !

5

Total exposure

IO

(Gy)

Fig. 4. Dose dependence for causes of early mortality for ;L fractionation scheme of 99% instantaneous and I Ob protracted exposure.

competing risks of those missions. Appraisal of these hazards therefore focused on the possibilities that radiation effects might impair performance of crew members and thereby might result in failure of the mission. Thus early radiation effects assumed prime importance. Although radiation protection standards for the Space Station era will primarily be based on late radiation responses as the limiting effect. inclusion of early effects is still warranted by the non-negligible probability of high exposures during emergency situations such as failure in orbit control or large solar particle events especially in polar orbits or during extravehicular activities, which at least during the construction phase of a Space Station could conceivably form a substantial part of the work schedule. The risk on early mortality is given in Fig. 4 for a fractionation scheme, where 99% of the dose is applied within 1 day while the remaining 1% is deposited during the next 2 weeks, a scheme that may be representative of a single solar particle event[88]. Event probabilities below 5% are shaded to indicate that the uncertainties of the used models and their parameters are too big to asign much confidence to these tails of the distribution function. Apart from early mortality that is rarely to be expected at instantaneous exposures below 2 Gy. early forms of radiation sickness, which already occur at lower doses and might impair the functional performance of space personnel, have to be considered as relevant effects. Figure 5 displays the risk for complex clinical symptoms which are comprised in the

G. Reitz et al

324 100 r

90 -

80 -

g

70 -

, /

ycataracts

1

1

Total

;A EWema

,‘,/

exposure

(Gy)

Fig. 5. Dose dependence for causes of early morbidity fractionation scheme of 80% instantaneous and protracted exposure.

for a 20%

6.2.3. Delayed or lute efects

the risk of early skin damage (erythema) and early development of cataracts of the ocular lens. In order to estimate confidence ranges of the parameters for early morbidity, which are not provided by the NUREG report[88], estimates of Lushbaugh[87], NUREG and PSR[89,90] were compared. This is shown, for example, in Fig. 6 which shows for anorexia and early mortality the estimated prodromal

100 90

syndrome,

r

Nureg,

,’

/.-

Anorexia

Lethality

80 70 g

x E

60

so

P 2

40 Upper and lower dose-response relations for acute hematologic symptoms in patients

30 20 10

0

I/‘- I 50

I

I

I

I

I

100

200

300

400

500

Epigastric

incidence as a function ofdose as given by Lushbaugh. The shaded areas, representing confidence regions, correspond to about 25% uncertainty in the ED,,, (dose of radiation required to engender a specified radiobiological affect in 50% of exposed organisms) for anorexia and 22% uncertainty in the LDcl, (dose of radiation required to kill 50% of exposed organisms). The dashed+Iotted curve for anorexia represents the NUREG central estimate of anorexia under instantaneous exposure. This is fully included in the shaded area of uncertainties given by Lushbaugh. Comparison of the NUREG central estimates with the estimates of another study, the PSR report, show an overall agreement for the incidence of anorexia, nausea, fatigue, vomiting and diarrhea which suggests that a simple variation of the ED,,, by a factor of 1.25 fairly reasonably covers the range of uncertainty pertaining to the incidence of such symptotns[9l]. The threshold, below which no symptoms of the prodromal syndrome-the most sensitive symptom complex-should occur, is about 20 cGy if the model of the NUREG is taken with parameter values for instantaneous exposure. The risk drops below 5% around this dose value. The PSR report uses a lower threshold of 50 cGy (free-in-air!), below which no early radiation-related symptoms should be observable.

dose (cGy)

Fig. 6. Comparison of the NUREG estimate for incidence of radiation- induced anorexia with estimates from Lushbaugh. with approx. 25% variation of EDso.

In contrast to the pioneering era of manned spaceflight, radiation protection standards for a permanently manned Space Station in near-Earth orbits will, for several obvious reasons, have to refer to late radiation effects rather than to early effects as the limiting risk from exposure to space radiation. Instead of a few dedicated astronauts who have been recruited mainly from the military, such as test pilots. at an age near the end of their active career. future crew populations will be larger in size, will comprise both males and females of substantially younger age and will spend a larger fraction of their occupational life time in the space environment. In short, in the context of radiation protection, they will assume the status 01 occupationally exposed (space) radiation workers. Thus, life shortening as the most severe consequence of exposure to ionizing radiation will be the primary reference risk for which acceptable risk levels and thereofexposure limits are to bedetermined. (Fixation of “acceptable” risk levels, of course. is primarily the task of politically or legally responsible agencies or bodies and not that of scientific committees. since this is not a scientific problem.) 6.2.3.1. Stochastic qjf>cts. Life shortening. the primary reference risk, is presently considered to be mainly due to either the induction or the acceleration of appearance of neoplastic diseases. Hence the dose-response relationship for cancerogenesis is the basic empirical datum from which exposure limits are to be derived. The human database. again, consists mainly of observations on the atomic bomb victims. Less specific data on general life shortening exist for

32 5

Radiation protection in space Table 3. Factors that influence the risk estimates of radiation-induced Biolwical

Phvsical

Radiation quality

Age Sex Genetic factors

Dose Dose rate Fractionation Protraction

the shortened life expectancy of American radiologists prior to 1950 while data on the induction of leukemia can be supplemented by observations on patients irradiated for ankylosing spondylitis. Table 3 lists those factors, which-in addition to the uncertainties of the primary data-affect the results of any estimation procedure. The physical factors have been discussed above. The genetic factors include the uncertainty, to what extent the experience from the atomic bomb survivors might be representative for the racially different populations of North America or Western Europe. At least the natural incidence of some cancers is significantly different in these populations. Figure 7 exhibits the principle forms of analytically different dose-response functions from which the actual model has to be chosen. All these forms are realized in some of the experimental test systems. Considering actual data, such as those in Fig. 8, it is evident that the error bars of the data points-given neither for the abscissa nor for the ordinate in this figure-prohibit any statistically based decision to be made regarding the choice of the “correct” model. The insert in Fig. 8 demonstrates that a difference of about two orders of magnitude results for the value of the risk at 1 cGy, depending on whether model A or B is being fitted to the data. Unfortunately, the theories for neither general radiation biology nor for radiation induction of cancer are far enough developed to allow a unanimously accepted solution of this problem.

cancer

Analytical Choice of: (a) models for dose responses (b) projection models, relative risk absolute risk

Discrepancies of similar magnitude can arise between the results of risk projection depending on whether an absolute or relative risk projection model is applied. For the absolute projection model, the excess risk as a function of time after exposure within the expression period, the “plateau time”, is assumed to be constant. Since the natural incidence, the baseline risk, varies with time (age), the excess risk for the relative projection model varies with time also. The basic model adopted in the NUREG report is the linear dose-effect model, i.e. model curve 2 in Fig. 7. The quadratic component reflects the attempt to account for the “dose rate effectiveness factor” (DREF) in the case of “low-dose” and/or “low-dose rate” exposures. This modification then converts the basic linear model into a linear-quadratic dose-effect model. Excess fatal cancers after 0.1 Gy exposure are shown in Table 4 for the three models. In NCRP report 98[93] the linear-quadratic model is used for all cancer sites, too, except breast and thyroid where a linear model is applied. Tables 5 and 6 comprise estimates of the number of fatal cancers after acute exposure to 1 Gy of low-LET radiation and that following an identical level of exposure, but over a IO-year period of time given in this report. The target areas chosen represent the organ systems ordinarily showing the highest cancer rates per 100,000 population in the U.S. For men. acute exposure to

Leukemia

: Nagasaki+

B. ! = (c + aD + 60’) rxp (-&!I’) Estimate of excess risk at I rad: n* /-A. 2.47 2 0.6 cases (IOh PY) B. 0.03 + 1.X cases ( lOh PY) , ’ ’

0

1

2

3

4

Dose (arbitrary

5

6

units)

Fig. 7. Typical dose-response curves for radiation-induced turnours. Curve I, downwards concave; curve 2, linear; curve 3. upwards concave; curve 4, threshold type; and curve 5, a high spontaneous tumour rate declining with dose. The shaded area represents the spontaneous (control) incidence.

I

on

200

Dose (rad)

Fig. 8. Dose-response of leukemic incidence during 1950-1971 in atomic bomb survivors at Nagasaki. Curve A is a linear fit of the data and curve B has been fitted according to the linear quadratic model taking into account (I Gy = 100 rad)[l32].

ceil killing

326

G. Reitz t-6 al. Table 4. Excess fatal cancers per year per million persons exposed to low-LET different dose-response models? Model

Equation

Linear Quadratic Linear-quadratic

for excessi

radiatlon

Excess after 0. I Gy (IO fad)

5.159 x D 0.03228 x D* (2.408 x D) + (0.0207 x D*)

for three exposure

57.6 3.2 26.2

tAdapted from[92.127]. TD = Absorbed dose in rad.

1 Gy would lead to an overall increased cancer rate of 15SO/l000 crew persons exposed, and for women an increased incidence of 20-60/1000 crew persons. In contrast, exposure to the same level, but distributed as low-dose over a IO-year period would lead to 8-20 new cancers/1000 in men and l&30 new cancers/1000 in women. For comparison, based on the normal life expectancy of a U.S. adult population, 220-300 persons/1000 die from cancer causes unrelated to occupational X-ray exposure[94]. Acute exposure to 1 Gy in space would then be expected to shorten life expectancy and significantly increase subsequent cancer and deaths, while long-term low-level exposure would still pose problems, but at considerably reduced risk levels. Those at greatest risk would be younger aged individuals at the time of onset of exposure, with increased possibilities for lung cancer in men and breast cancer in women. Genetic manifestations will never place a limit on radiation exposure as far as population dose is concerned, due to the vanishing contribution of the space crew population to the gene pool of the general population. However, on an individual basis the gonads have to be considered as an additional critical organ. For genetic effects, the human database consists practically entirely of the experience from the atomic bombings of Hiroshima and Nagasaki. To date, these studies do not demonstrate a statistically significant increase in the incidence of genetic defects in the survivors’ children. Risk estimates therefore are based, in the main, on extrapolations from animal studies[95]. Genetic risks for subsequent offspring may be computed from knowledge of each parent’s exposure and is assumed to be 3 in 1,000,000/mSv[96]. Total risk is the sum of the risks from the mother and father. If a female crew member flies in space regularly

Table 5. Predicted

lifetime risk of excess cancer deaths among 1000 persons experiencing acute exposure of I Gy (low-LET, 20 day period at a rate t 0.05 Gy/day) (from[93])

Sex

Age at exposure

Lung

Male

2s 35 45 55 2s 35 45 55

13.7 9.2 6.7 4.8 9.8 8.1 1.4 6.3

Female

for the 5 years before conceiving a child and was allowed to accumulate the maximal dose allowed for an Earth-based radiation worker each year (50 mSv), then the total dose would be 250 mSv (5 x 50). The risk would be 3 x 250 in l,OOO,OOO or 75 in 100,000. If the father were to act similarly, he would then contribute another 75 in 100,000 for a total risk of 15 in 10,000. In this worst case scenario the chances for a genetic problem would be considerably less (but still finite) compared to the general population, where 2-3% (200-300 in 10,000) of children are born with serious anatomic abnormalities[96]. With regard to an unborn child, risk of harm depends on the stage of development, as well as on the amount of radiation during the first week after conception and before implantation into the uterine wall, the principal radiation risk is death in utero. The risk coefficient is 8 in 10,000/l mSv[97]. If the crew person receives 0.2 mSv/day during a week-long shuttle flight the risk of radiation-induced prenatal mortality is 1.4 x 8 or 11 in 10,000. During the weeks induces structural 3-8 of pregnancy, radiation abnormalities. The risk is 5 in 10,000/l mSv[98]. 100 mSv received over a 34 month period while in a Space Station would lead to a 5 in 1000 risk of a deformed infant. During weeks 9-26 of pregnancy, the principal concern from exposure is mental retardation, l-4.5 in 10,000/l mSv[98,99]. Exposure levels received over a typical Shuttle flight would not be considered excessive by present standards which dictate that once pregnancy is known (presumably by the end of the second month), the dose equivalent to the unborn child from occupational exposure should not exceed 0.5 mSv[lOO]. Still, concerns for possible risks and harm to an infant from spaceflight have led to recommendations limiting female participation in both short and long-term missions. These data also provide a basis for assessing possible radiation risks

Breast

Colon

Pancreas

9.9 6.1 I.1 0.5

4.0 1.9 1.0 I.0 4.4 2.3 1.3 I.3

5.1 2.3 1.5 I.5 7.9 3.4 2.1 2.1

Acute leukemia 2.2 2.5 2.8 2.8 1.4 I .6 2.0 2.2

Chronic

leukemia 0.9 0.9 0.9 0.9 0.5 0.6 0.6 0.6

received over a

Total cancers 48.0 26.5 18.4 15.5 59.7 35.5 22.1 19.7

327

Radiation protection in space Table 6. Predicted

lifetime risk of excess cancer deaths among 1000 persons experiencing chrome exposure of I Gy (low-LET. a 10 year period at 0.1 Gy/year by age of first exposure) (from[93])

Sex

Age at exposure

Lung

Male

25 35 4s 55 25 35 45 55

6.2 4.3 3.1 2.2 4.8 4.2 3.7 2.9

Female

Breast

COlO”

Pancreas

8.1 3.3 0.8 0.4

1.6 0.8 0.5 0.5 1.8 0.9 0.7 0.7

1.9 1.0 0.8 0.8 2.9 1.4 1.1 I.1

of stress combinations

Combined

Chronic

1.2 1.4 1.5 1.4 0.8 0.9 I.1 I.1

leukemia 0.5 0.5 0.S 0.5 0.3 0.3 03 0.3

radiation protection of human embryos.

during population growth once a space colony is established. 6.2.3.2. Non-stochastic effects. Secondary or ancillary reference risks relating to distinct organs are cateractogenesis in the ocular lens and “late” permanent or late skin effects. In humans, the threshold or medically relevant cataract formation appears to be around 2 Gy of low-LET radiation and about 4 Gy if exposure is fractionated. The latent period varies from about 0.5 to 35 years with an average of about 2-3 years. Below 2 Gy, only minimum stationary opacities have been associated with single doses of l-2 Gy. Due to the progress which has taken place in the surgical treatment of this pathological condition it appears it is a matter of judgement whether this effect should continue to be considered as an ancillary reference risk. Dose-response relationships for late skin effects, other than cancer. such as late loss of reproductive capacity of fibroblasts are not available. As discussed by Lett[lOl], who is analysing this endpoint in the USAFSAM colony of Rhesus monkeys which had been irradiated with simulated solar particle event protons, the damage that was observed 20 years after irradiation is unlikely to be acceptable to man. Sensitivities to induction of somatic sequels, both stochastic and non-stochastic by exposure of human foetuses (in utero exposures) are significantly larger than for adults, i.e. about a factor of three for non-stochastic and about a factor of ten for stochastic endpoints. Therefore it appears appropriate that

Table 7. Summary

Acute leukemia

regulations

Total cancers 19.9 12.0 9.2 7.5 29.3 170 II 9 9.9

rule out the exposure

7. IMPACT OF SPACEFLIGHT ENVIRONMENT

The interrelationship between the pathologies of radiation syndrome and the influence of external and internal factors, so far, is merely understood at the level of two factor combinations. The interaction of radiation with the various stressors, relevant to spaceflight conditions, is summarized in Table 7. However, one has to recognize the simplification in this table, since there is such a wide range of end points, levels of stress, durations and sequences of interaction. Furthermore, some interactions are not detectable below a threshold level. According to the general adaption syndrome theory[ 1021, increased resistance during stress provides the necessary resistance of the organism to the effects of stimuli of another nature. Stress leads to an activation of the haematopoietic system and of the immunological and regenerative processes[l03]. According to this theory. the radiation resistance of an organism can be increased by treatment with specific physical or chemical stressors. However. the response of an organism to a combined action of stressors seems to be too complex to simply follow this theory. For early effects at high doses and dose rates of sparsely ionizing radiation. the radiosensitivity was found to be modified by the other spaceflight factors by a factor which ranges between I and 1.2[104,l05,106.107]. For lateeffects at low doses and dose rates, only tentative statements are possible,

and tvpes of interaction

stresses

(modified

froml84li

Interaction

Fhght dynamx factors

radiation-micrograwt> radiation-.acceleration radiation-vibration

additive to synergtstic antagonistic to additive mostly antagonlstlc

Work environment factors

radiation-hypoxia radiation-hyperoxia radiation-hypothermia radiation-hyperthermia radiation-noise radiation-microwave

mostly antagomsuc shghtly synerglstlc antagonistic to syncrg~st~c synergistic synergistic mostly synerglstlc

Internal

radiation--exercises radiation-trauma radiation--infection radiation--altered biorhytms radiation-osvcholoeical

body factors

received over

radiation

synergistic synergistic synerglstw undetermined additive to avnerelstic

to syncrg~t~c

328

G. Reitz et al.

Table 8. Empirical results for the dose modifying factor. PF, accounting for change of radiosensitivity due to the other spaceflight factors Early effects Soars& denseli

ionizine ionizing

Late effects (>2.5)5

‘-

tMost of the experimental results were actually obtained with artificial gamma sources at htgh doses and dose rates[104-1071. ITentative conclusions. no comprehensive inflight dosimetry data recorded[lOS-1121. iEstimated from results of one single spaceflight experiment[ll3].

because of a lack of dosimetry data[108,109,110, 111,112]. For early and late effects of densely ionizing radiation, only data of a single experiment [ 1131 are available. For the most sensitive stage (embryogenesis) of the stick insect egg of Carausius morosus as the lowest value of PF (physiological dose modifying factor) 2.5 can be estimated for low doses with a reasonable confidence, but values of PF up to ten or even more are compatible with the data. A summary of values of PF is given in Table 8. In a recent spaceflight experiment on the IMLI mission it was shown for pre-irradiated yeast cells that under microgravity the repair of radiation damage is reduced compared to that on the ground[l14]. 8. MEASUREMENT

OF RADIATION

EXPOSURE

In due recognition of the complexity of the radiation environment, i.e. its particulate composition, the spatial and temporal variability of its spectral intensities and their modification by shielding material, it has been a standing policy to provide radiobiologically adequate dosimetry during all manned missions. Most of the measurements have been done up to now by use of passive detector packages (no power consumption, no telemetry, post-flight evaluation). Such systems, consisting mainly of plastic nuclear track detectors, nuclear emulsions and thermoluminescence dosimeters, are extremely reliable. The use of multiple detector systems allows for redundancy, and for the measurements of the different types of radiation at several locations. Passive dosimeters are easy to handle, comparatively lightweight and give information about fluences and-within certain limits-on particle types and energy. In general, track detectors do not provide time-resolved data and on-line information. Stacks of moving detectors have been used for a time correlation of particle tracks in a post-flight analysis[ 1151. The temporal resolution of active detector systems with particle discrimination and real time read out advances the potential of radiation analysis: particle energy spectra can be correlated to the different, more or less permanent, radiation sources mentioned above. Dose rates can be derived and contributions of unpredictable statistic radiation events can be determined separately. Some active detecting systems have been flown on previous spaceflights. In 1983, an active dosimeter

based on p-1-u diodes behind 0.55-5.91 g/cm’ shielding was launched on the DMSP/F7 satellite. It measures the energy spectra of electrons (l-10 MeV) and of protons (20-75 MeV)[l16]. Parnell er u/.[117] have flown a combination of active and passive detectors in SLl and SL2 missions. A time-resolving proportional counter correlated the temporal variance of the count rate due to the galactic, solar and trapped particles to the integrated doses measured by LiF for low-LET particles and a stack of CR39 for high-LET particles. In SL2, an active detector system of gaseous Cerenkov detectors and a multiwire proportional chamber was flown in combination with CR39 (Cosmic Ray Nuclei Experiment, CRNE)[ 1181. Tissue-equivalent proportional counters have been flown by Golightly[ 1191on STS-28 using the Air Force radiation monitoring equipment (RME)-3 and by Nguyen[ 1201on the French-Soviet joint space mission ARAGATZ. A summary of measured doses during various space missions has been given by Benton[l21]. ‘These doses represent the contribution of the sparsely ionizing part (fast protons, electrons, gamma rays) to the dose. Table 9 gives a compilation of such doses measured inside spacecrafts in early manned U.S. spaceflights. The data for the Gemini, Skylab and ASTP flights show a strong dependence with altitude, while the data of the Apollo flights reflect the specific path through the radiation belts on the way to and from the Moon. Dose rate measurements from the Space Shuttle missions are shown in Table 10. The dose rate increases with altitude; above 300 km there is a steep dose rate gradient. Changing of the orbital inclination from 28.5 to 57’ has roughly a doubling effect. Approximately the same factor accounts for the decrease of solar activity during this flight period. The highest average dose rate recorded is 1.08 mSv/day for the mission 51J with an altitude of about 510 km. In high inclination orbits at low altitudes (200-300 km) the bulk of the dose is due to galactic cosmic rays, whereas the bulk of the dose at high altitudes comes from the protons in the SAA. Most of the average dose rates from Soviet spacecrafts for the time period 1960-1983 are in the range of 100-300 pGy/day for altitudes between 210 and 410 km and inclinations higher than 52 One flight in an altitude of 500 km shows an average dose rate of 650 pCiy!day. Neutron measurements have been performed on several flights. The accuracy of the thermal and epithermal neutron contribution is thought to be reasonable, however. the high-energy neutron contribution, which is bound to be of the most significance, is fairly uncertain since the shape of the neutron energy spectra is not well known. Measurements on Skylab show a fast neutron flux of 4.1 cm .’ s ‘_ During the first Shuttleflightsat an inclination of28 a fast neutron flux of 0.19-0.41 cm-: s ’ has been observed[l21]. During Shuttle flight STS-28 at an inclination of 57 fluxes from 0.68 to 1.06 cm ’ s ’ have been measured behind different shielding thicknesses[ 1221.

329

Radiation protection in space Table 9. Crew dose rates from early manned Flight Gemini 4 Gemini 6 Apollo 7t Apollo 8 Apollo 9 Apollo IO Apollo I I Apollo I2 Apollo I3 Apollo 14 Apollo I5 Apollo I6 Apollo 17 Skylab 2: Skylab 3 Skylab 4 Apoll@Soyuz test project

Duration

(h/days)

Inclination

(degrees)

91.3 h 25.3 h 260.1 h 147.0 h 241.0 h 192.0 h 194.0 h 244.5 h 142.9 h 216.0 h 295.0 h 265.8 h 301.8 h 28 days 59 days 90 days

32.5 28.9

9 days

50

Apogee-perigee

(km)

lunar orbital

flight

lunar orbital flight lunar flight lunar flight lunar flight lunar flight lunar flight lunar flight lunar flight altitude TZ435 altitude z 435 altitude z 435

50 50 50

altitude

Our own estimates from measurements in Dl, SLl, IMLl (each 57” inclination) and MIR 92 (52” inclination), ranged from 0.8 to 1.3 cm-’ s- ‘. The frequency of nuclear disintegration stars was determined to be between 503 and 743 cm - 3 d - ’ during these missions, see[l23]. Measurements of the heavy ion fluxes as a function of LET on U.S. spacecrafts have been performed exclusively through the use of plastic nuclear track detectors. Such spectra are needed to calculate the contribution of heavy ions to the equivalent dose and were mesured in all flights. The LET spectra were obtained by counting the number of particles per unit area on a specific surface of the individual detector material, taking into account the mission duration and the field of view from which particles are detected. Table IO. Crew dose rates and mission parameters

I ? 3 4 5 6 7 8 41A 41B 4lC 41D 4lG 5lA 51c 5lD 518 SIG 5lF 511 5lJ 61A 618 61C

Launch date 12-04-B I 12-11-81 22-03-82 27-06-82 II-II-82 04-04-83 18-06-83 30-08-83 28-l l-83 03-02-84 06-04-84 30-08-84 05-10-84 08-l l-84 24-01-85 12-04-85 29-04-85 17-06-85 29-07-85 27-08-85 03-10-85 30-10-85 26-l l-85 12-01-86

tData for missions STS-I through to STS-5 supplied Laboratory. NASA/Johnson Space Center.

Average dose (mrad)

296-166 31 l-283

z 220

tDoses for the Apollo flights are skin TLD doses. The doses to the blood-forming at the body surface. fMean TLD dose rates from crew dosimeters.

STS mission number

(I Gy = 100 rad)[lZl]

U.S. spaceflights

Average dose rate (mrad/day)

46 25 160 160 200 480 I80 580 240 II40 300 510 550 1596 3835 7740

II 23 IS 26 20 60 22 57 40 127 24 46 44 57 * 3 65 + 5 86 * 9

106

I2

organs arc approx. 40% lower than the values measured

Figure 9 shows LET spectra obtained from the Apollo lunar missions where the particle flux was not affected by geomagnetic shielding, the Skylab mission, the Cosmos 782 and 936 missions, ASTP and the Spacelab 1 mission, as examples[ 1241.It can be seen that for the same LET value, the particle flux for the different missions changes by more than a factor of 200-300. This dynamic range of particle flux is caused by solar modulation, geomagnetic shielding and shielding by matter. The upper full line is calculated for solar minimum activity and outer space without geomagnetic shielding. The lower full line is calculated for the Skylab orbit, for solar maximum activity and a shielding of 70 g/cm’ cellulose nitrate plastic. From the above-described measurements, which cover the contribution of the biological relevant

for Space Shuttle flights (I Gy = 100 rad) (modified

Mission duration (h) 54 58 I95 169 122 120 I43 I45 248 I91 I68 145 197 192 74 168 I66 170 I91 192 95 169 I65 146 by the University

Altitude

(km)

Inclination

269 254 280 297 284 293 297 297 (max) 250 297 528 (max) 297 352 (mu) 297 x 352 297 x 334 297 x 454 352 380 (max) 322 x 304 378 (max) 5 IO (max) 324 380 324 of San Francisco;

40 38 38 28.5 28.5 28.5 28.5 28.5 57 28.5 28.5 28.5 57 28.5 28.5 28.5 57 2x.5 49.5 28.5 28.5 57 28.5 28.5 remainder

( )

from [121])

Number of crew

Aver. crew dose rate (mrad/d)

2 2 2 2 4 4 5 5 6 5 5 6 7 5 5 7 7 7 7 5 5 8 7 7 supplied by the Radiation

4.0 3.6 6.3 6.3 5.6 5.0 7.4 6.5 12.1 6.0 74. I 8.6 10.7 14.4 12.6 54.4 21.4 18.4 17.3 13.3 107.8 17.2 20.8 II.3 Dosimetry

G. Reitz Edal.

330 10’

102

103

LET, (MeVlcm water) Fig. 9. Measured and calculated LET-spectra for different missions: + , Apollo 17;-, Apollo 16;-, SLI; XZ Skylab; +Y, Kosmos 782;--, D2; +O, Kosmos 782; *O, Kosmos 936; A, Apoll~Soyuz;--, Apollo-Soyuz[ 124).

radiations to the total radiation load well, dose equivalents have been calculated based on quality and weighting factors from ICRP 60. Table 11 shows calculations of absorbed doses and dose equivalents derived from our own data for the SLI, Dl and IMLl Spacelab and the German MIR 92 missions. The absorbed dose rates range from 113 to 3 11 pGy d - ’ and the dose equivalent rates from 400 to 613 ~SV d - I. The mean Q varies between 2 and 4.1. Dose equivalents of about four-fold the above-calculated values may be expected for the orbit of about 450 km for the planned Space Station. The data available in such orbits are too incomplete to provide confident estimates. Much higher doses are involved in interplanetary travel. The dose equivalents calculated by Letaw[ 1251

amount to 180 mSv yr - ’ for solar maximum conditions and 450 mSv yr- ’ for solar minimum conditions. These levels assume an absence of solar flare events during the period of travel and that the only protection would be a normal wall thickness of aluminium of 4 g cm - ?. The mission duration to Mars, as an example, is about 1.5 years. Note that none of these calculations reflects any influences of other spaceflight factors on the radiation exposure and that the present RBE concept is used for the calculation of the contribution of the densely ionizing components, although it is not applicable for these radiations as explained in Section 6.1. But at this time there is no other quantity which gives a better estimate of the radiation action of the densely ionizing components than LET.

331

Radiation protection in space 9. ESTABLISHING RADIATION PROTECTION LIMiTS

9.1. General Approaches to Radiation Protection “The aim of radiation protection should be to prevent detrimental non-stochastic effects and to limit the probability of stochastic effects to levels deemed to be acceptable. An additional aim is to ensure that practices involving radiation exposure are justified. The prevention of non-stochastic effects would be achieved by setting dose-equivalent limits at sufficiently low values so that no threshold value would be reached, even following exposure for the whole of a lifetime

or for the total period of the working life. The limitation of stochastic effects is achieved by keeping all justifiable exposure as low as reasonably achievable, economical and social factors taken into account, subject always to the boundary condition that the appropriate dose-equivalent limits shall not be exceeded”.

These two paragraphs of ICRP Report No. 26[10] summarize the philosophy according to which the radiation protection guidelines for terrestrial exposure fields and conditions have been derived. This report constitutes the basis of legislation in most countries. The estimates identified a nominal risk of 1.25 x 10 - ’ Sv - ’ lifetime for all persons in a general population, but it is rounded to 1 x 10-I Sv -I for adults only. This resulted in an annual occupational limit of 50 mSv and a lifetime limit of 2.5 Sv. The annual limit for members of the public was set to 5 mSv. In the following years, the data of the Japanese survivors of the atomic bomb were reviewed and updated. First, a new dosimetry was established and secondly, of even greater impact, the new data showed that the occurrence of solid tumours, which have latency periods of more than 20 years, are underestimated. The ICRP therefore concluded in their recent assessment[l2] that it would be appropriate to use a nominal value of 10 x 10 - 2 Sv - I for the lifetime risk of fatal cancer for a population of all ages for high dose and high-dose rate exposure; for a working population 8 x 10 - ’ Sv - ’ has been recommended. Thereafter, ICRP chose a dose and dose-rate effectiveness factor (DREF) of two, to convert risk estimates to low dose and low-dose rate

and thus arrived at a risk value of 4 x lo- 2 Sv- ’ for a working population. Since this risk is considerably greater than that assumed in the ICRP Report 1977, consequently the annual recommended limit was reduced from 50 to 20 mSv. The first radiation guidelines for U.S. manned spaceflight were recommended by the Space Science Board’s Committee on Space Medicine in 1970[126]. The panel considered it reasonable to recommend limits based on doubling the natural risk of cancer over a period of 20 years which resulted in a 2.3% lifetime excess risk. This resulted in a career limit of 4 Sv; an annual limit 750 mSv was recommended. Due to new radiobiological data, a reappraisal of the guidelines became necessary. NCRP set up its Scientific Committee 75 which produced the NCRP Report 98 “Guidance on Radiation Received in Space”, which was issued in 1989[93]. Based on risk estimates derived from the National Institutes of Health (NIH) ad hoc working group[127], the committee compared the risks of fatal cancers with fatality data from accidents in various occupations. Although spaceflight is considered by most experts as a risky occupation, the committee found a lifetime excess risk for fatal cancer due to radiation exposure of 3% reasonable, taking into account the fact that space crews have other serious risks besides radiation risk. This risk of 3% is comparable with the risk in less safe but ordinary industries, such as agriculture and construction, and it is lower than that for the more highly exposed radiation worker on the ground, corresponding to a lifetime risk of 5%. Finally NCRP recommends, based on a lo-year career, the age and sex dependent limits which are given in Table 12. Career limits versus age are given in Fig. 10. Still, as a larger segment of the population is asked to participate, this 3% level may be found to be unacceptable and means for its lowering instituted. A more acceptable fatality risk level may be that of I % of the working lifetime which occurs with automobile travel in the U.S. and radiation workers generally. conditions

Table I I. Energy and equivalent dose rates in p Gy d - ’ or b Sv d ’ of the sparsely ionizmg and the three densely ionizmg components the radiation fields in the D1, SLI, IMLl and German MIR mission including the mean Q for these radiants

Mission SLI

DI

IMLI

MIR

Radiation sparsely ionizing radiation stars heavy ions neutrons total sparsely ionizing stars heavy ions neutrons total sparsely ionizing stars heavy ions neutrons total sparsely ionizing stars heavy ions neutrons total

radiatmn

radiation

radiation

Dose rate (p Gy d - ‘)

Q

85. I

1.3

6.2 16.5 5.2 113.0 194.8 4.3 11.8 5.2 216.0 105.0 6.4 11.8 3.6 127.0 286.0 4.3 11.8 6.8 311.0

1.7 15.0 10.0 4. I I.3 7.7 11.9 10.0 2.2 1.3 7.1 II.9 10 2.9 I.3 7.7 11.9 10.0 2.0

Equivalent dose rate (/I Sv d ‘) 110.6 11 7 241.5 52.0 458.0 253 2 33.1 140.4 52.0 479.0 136.5 49.3 140.4 36.0 362 0 371.8 33.1 140.4 68 0 613.0

of

332

G. Reitz et al. Table 12. Recommended

organ dose equivalent

BFOt Career Annual 30 Davs

(Sv)t

see Fig 10 0.50 0.25

limits for all ages

Eye (Sv)I

Skin (SV)~

4.0 2.0 1.0

6.0 3.0 1.5

tBlood forming units. $1 sv = 100 rem.

10. LIMITATIONS IN ESTABLISHING SPACE-BASED RADIATION EXPOSURE LIMITS

Radiobiological conditions in space differ quite substantially from those usually applied in “reference” experiments conducted on Earth. Under spaceflight conditions, the potential influence of the other dose modifying factor, summarized as N in radiation protection, has to be evaluated and included in radiation protection guidelines. N is the product of the dose-rate effectiveness factor (DREF), the depth dose distribution factor (DF) and the physiological factors (PF) (see Section 3). In space, a body is exposed to low particle fluxes, lower by an order of magnitude than typical dose rates in terrestrial experiments with photon sources and accelerators, but the particles of space radiation have a much wider range of atomic masses and energies. Furthermore, irradiation in space is not uniform, either with respect to depth or area of the body region involved. The radiation incident on the body is scattered, fragmented and degraded in energy as it penetrates the deeper organs, and thus the effective LET, as well as dose and dose rate, all change with depth. All three of these factors influence RBE. Calculation of DF during ground-based studies has shown non-uniform radiation to be less effective than uniform[91]. In space this could affect estimates and calculations and lead to possible down-grading of risk.

Points proposed by NCRP Comm. 75 based on 3% lifetime risk of cancer mortality

Males

Career

7c/

Females = 200 + 7.5 (Age - 38)

limit

’

I

I

I

I

I

I

25

30

35

40

45

50

5.5

Age

Fig. 10. Carreer limits vs age[93].

From studies of somatic effects in animals it was discovered that the effectiveness unit dose of low-LET radiation for life shortening and cancer induction was less at lower dose rates. It has been proved to be between 0.5 and 0.1 when the actual absorbed dose was 0.2 Gy or less or with a dose rate of 0.05 Gy/yr or less. There are no data available which are adequate to demonstrate whether a dose rate effect exists for humans, but consistent and systematic evidence of its presence in plants and animals makes it highly probable that such a relationship also applies to the same endpoints in man. This could then also point to a possible lowering of risk. Unfortunately, however, there is increasing evidence that the above-described decrease of biological effectiveness with prolongation and fractionation of low-LET exposures does not occur for high-LET radiation[9]. In low dose studies of high-LET, just the opposite occurs, i.e. an enhancement of effects. Therefore, this Q-LET relationship becomes quite important in assessing the final effects of space radiations which consist primarily of particles with high-LETS and needs further intensive study. Finally, all methods available for assessing risk rely on the use of statistical models where independence of combined effects of absorbed doses is assumed. This means that deleterious effects in a given organ are independent of previous doses whenever received and that each portion of an organ responds autonomously. These conditions may not hold in space where radiations are of markedly different quality and exceptions to these principles have already been shown on the ground[55,59,60]. In summary, previous risk calculations may have short comings which lead to overestimates or underestimates due to: (1) Data are based on gamma radiation only. The spectrum of space radiation is quite different. The Q-LET is not appropriate for the densely ionizing radiation component of the space radiation field. (2) Information regarding cancers is derived from high dose rates in atomic bomb survivors or other accidental high dose exposures and effects at lower dose rates have had to be extrapolated. A linear relation may not pertain. (3) Additive effects from exposures to different kinds of radiation is assumed. (4) Modification of radiobiological response by microgravity or other spaceflight effects is not accounted for. Findings clearly indicate an influence of microgravity on radiation effects.

333

Radiation protection in space In the endeavour to assess the risk for manned spaceflight-especially for long-term missions-the problem of the combined influence of different radiation qualities and stressors man in space has to cope with is a key problem in space biology and medicine that, up to now, is hampered by many unknowns.

II.

RADIATION PROTEffION

MEASURES

The shielding for the Space Shuttle and MIR Space Station varies from 2 to about 30 g cm -‘depending on the type and placement of equipment. Homogeneous shielding is provided only by a single pressure layer of aluminium, 2 g cm - ?in thickness. The protective value of aluminium against the various particles encountered in space is given along the abscissa in Fig. 1. Almost all particles can be stopped with sufficient thicknesses, except GCR which are literally unstoppable. Yet, careful tradeoff must be made in its use, since an increase in weight affects construction and launch costs and subsequent mission accomplishment. A doubling of the presently used wall thickness would decrease the dose by a factor of 1.2, but would increase both weight and cost by more than 30-50%. Installation of an onboard “storm shelter” represents yet another means for reducing total body exposure or providing partial body shielding, particularly in the event of an anomalously large solar event. which represents a critical danger for lunar habitation or during an interplanetary journey. Materials used for shielding should be materials of low atomic number. In situations where EVA may be a heavy requirement in low-Earth orbit, it can always be programmed to minimize exposure to the SAA[128]. Radioprotective chemicals may also have an important future role in protection against anomalous solar events. The Walter Reed Army Institute of Research has developed over 4500 potentially useful compounds, some of which are in clinical trial[ 18,128]. None are presently free of side effects, primarily vomiting. and the need for intravenous administration. Many of these drugs act to repair post-exposure cellular DNA damage through their electron donor properties or through sparing of cellular 0: depletion mechanisms. Finally, bone marrow transfusions of stored frozen autologous marrow may serve as an in-flight emergency reserve procedure for missions lacking the possibility of immediate Earth return during a period of solar flare activity. However, this approach is not recommended, since it would still require at least 4 weeks before the transfused marrow could supply sufficient amounts of blood elements, particularly platelets. This leads to the clear conclusion that adequate and appropriate shielding represents the most effective means for medical radiation protection. Some form of its implementation will be required for any type of long-term manned mission.

12. RECOMMENDATIONS

Current practices of radiation protection are empirical and based on extrapolating potential for harm from experiences during ground-based exposures. These have proved useful to date, but have provided little information for predicting adverse effects due to unique particles encountered when weightless (HZE, high-energy protons, neutrons). The possibility for a permanently manned Space Station and for interplanetary travel within the next century is forcing a reassessment of the many gaps present. Resolution will require definition of the RBE for space-encountered protons and neutrons, as well as the potentially specific effects of HZE. Specific information on the biological effects of HZE carries the highest priority, especially the resolution of the dangers from microlesions produced in the various types of body celIs[l29]. From a practical point of view, the required answers can be provided by approaches taken from three perspectives, that of: operational medicine, radiation biology and health physics[l30]. Operationally this will involve practices that maintain exposure to a level as low as possible. Following present practices, this will necessitate rotation of crews, exclusion of pregnant females or practices that may lead to embryogenesis. Dosimetry will be critical and needs to be expanded to provide the required information on the time duration of exposure, as well as absolute levels and information about the physical characteristics of the radiation, energy and charge spectra and the particle’s fluence. Shift to younger ages for crew members and an increase in absolute crew size will be enabled after potential dangers from HZE particles are resolved. For the radiobiologist, the next several decades provide the challenge of resolving RBEs for space-based radiation, with particular emphasis on long-term or late effects (predominately carcinogenesis). Resultant data will be critical in defining the relevance of Earth-based models and determining whether presently recommended exposure limits can be broadened or restrained. Involved is a careful assessment of potential interactions between radiation and weightlessness. This can be accomplished by extending the previously conducted Biostack-type experiments[32]. Finally, health physics experiments are needed to accurately define the radiation field outside the spacecraft and its resultant inside the capsule. This will require careful attention to vehicle dosimetry and coupling with results from worn personal dosimeters. Specific measurements during passage through the SAA will be very important in this regard. In the end, these activities will lead to improved methods of shielding, assurance as to whether a great segment of the population can participate and ability to handle radiation-based emergencies, should they occur.

G. Reitz et al.

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