Radiation Protection Guidance for Activities in Low-Earth Orbit: Recommendations of the Nattional Council on Radiation Protection and Measurements (Ncrp Report, No. 132)

NCRP R e ~ o r No. t 132 Radiation Protection Guidance for Activities in Low-Earth Orbit Recommendations of the NATIONA...

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NCRP R e ~ o r No. t 132

Radiation Protection Guidance for Activities in Low-Earth Orbit Recommendations of the NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS

Issued December 31, 2000

National Council on Radiation Protection and Measurements 7910 Woodmont Avenue, Suite 8001Bethesda, Maryland 2081 4

LEGAL NOTICE This Report was prepared by the National Council on Radiation Protection and Measurements (NCRP).The Council strives to provide accurate, complete and useful information in its documents. However, neither the NCRP, the members of NCRP, other persons contributing to or assisting in the preparation of this Report, nor any person acting on the behalf of any of these parties: (a) makes any warranty or representation, express or implied, with respect to the accuracy, completeness or usefulness of the information contained in this Report, or that the use of any information, method or process disclosed in this Report may not infringe on privately owned rights; or (b) assumes any liability with respect to the use of, or for damages resulting from the use of any information, method or process disclosed in this Report, under the Civil Rights Act of 1964, Sectwn 701 et seq. as amended 42 U.S.C. Section 2000e et seq. (Title VIZ) or any other statutory or common law theory governing liability.

Library of Congress Cataloging-in-PublicationData Radiation protection guidance for activities in low-earth orbit. p. cm. - (NCRP report ; no. 132) Includes bibliographical references and index. ISBN 0-929600-65-7 1. Radiation-Safety measures. 2. Space flight-Physiological effect. 3. Astronauts-Health and hygiene. 4. Manned space flight-Safety measures. I. National Council on Radiation Protection and Measurements. 11. Series. RC1151.R33 R325 2000 616.9'80214-dc21 00-046466 Copyright O National Council on Radiation Protection and Measurements 2000 All rights reserved. This publication is protected by copyright. No part of this publication may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotation in critical articles or reviews.

[For detailed information on the availability of this and other NCRP publications see page 196.1

Preface This is the second National Council on Radiation Protection and Measurements (NCRP) report that provides radiation protection guidance for astronauts working in low-earth orbit. The guidance in this Report supercedes the radiation exposure limit recommendations provided in NCRP Report No. 98 that was published in 1989. Readers may find some of the radiobiological information in Report No. 98 to continue to be relevant and of interest and, therefore, Report No. 98 will continue to be available from NCRP Publications. This work has been performed at the request of the National Aeronautics and Space Administration (NASA)and NCRP gratefully acknowledges NASA's support. This Report was prepared by Scientific Committee 75 on Guidance on Radiation Received in Low-Earth Orbit. Serving on Scientific Committee 75 were:

R. J. Michael Fry, Chairman Oak Ridge, Tennessee Members

E. John Ainsworth Bethesda, Maryland

Charles E. Land National Cancer Institute Bethesda, Maryland

Eleanor A. Blakely Lawrence Berkeley Laboratory Berkeley, California

Donald E. Robbins Abilene, Texas

John D. Boice, Jr. International Epidemiology Institute Rockville, Maryland

Warren K. Sinclair Escondido, California

Stanley B. Curtis Fred Hutchinson Cancer Research Center Seattle, Wasbigton

Lawrence W. Townsend University of Tennessee Knoxville, Tennessee

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PREFACE

Advisor Marvin L. Meistrich M.D. Anderson Cancer Center Houston, Texas

Consultants Seymour Abrahamson University of Wisconsin Madison, Wisconsin

R. G. Richmond Lockheed Martin Engineering Services NASA Johnson Space Center Houston, Texas

Gautam D. Badhwar NASA Johnson Space Center Houston, Texas

NCRP Secretariat William M. Beckner, Senior Staff Scientist (1990-1997) Eric E. Kearsley, Staff Scientist (1998-2000) The Council wishes to express its appreciation to the Committee members for the time and effort devoted to the preparation of this Report.

Charles B. Meinhold President

Contents Preface ............................................................................................. 1 Executive Summary ........................................................... 1.1 Background ..................................................................... 1.2 Reasons for a Reappraisal of the Current Guidance. on Radiation Limits ........................................................ 1.3 Radiation Environments ................................................ 1.4 Radiation Effects ............................................................ 1.4.1 Early Deterministic Effects ................................. 1.4.2 Late Deterministic Effects ................................... 1.4.3 Cancer Risks ......................................................... 1.4.4 Hereditary Effects ................................................ 1.5 Career Dose Limits ......................................................... 1.6 Uncertainties in the Risk Estimates ............................. 1.7 Impact of Career Exposure Limits on Space Activities .......................................................................... 1.8 Future Research ............................................................. 2 Introduction ........................................................................ 2.1 Background of Space Radiation Safety Standards ........ 2.2 Radiation Standards for the National Aeronautics and Space Administration ..................................................... 2.3 Development of 1989 Recommendations ...................... 2.4 Reappraisal of the Guidelines Given in NCRP Report No . 98 .................................................................. 3 Radiation Environment in Low-Earth Orbit .............. 3.1 Introduction .............................. . . .................................... 3.2 Trapped-Particle Radiation ............................................. 3.2.1 Sources and Sinks ................................................ 3.2.2 Motions of Charged Particles in a Magnetic Field ....................................................................... 3.2.3 Description of the Belts ....................................... 3.3 Galactic Cosmic Rays ....................................................... 3.3.1 Abundance ............................................................ 3.3.2 Solar Modulation of Galactic Cosmic Rays ........ 3.3.3 The Anomalous Components ............................... 3.4 Solar Particle Events ....................................................... 3.4.1 Propagation Characteristics ................................ 3.4.2 Solar Particle Event Spectra and Composition .... 3.4.3 Solar Particle Event Measurements ...................

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CONTENTS

4 Radiation Exposure to Personnel .................................. 4.1 Introduction 4.1.1 Absorbed Dose and Dose Equivalent .................. 4.1.2 Current Recommendations of the International

......................................................................

Commission on Radiological Protection and the National Council on Radiation Protection and Measurements ...................................................... 4.2 Dosimetry Instrumentation Used in Low-Earth Orbit Missions................................................................... 4.2.1 Heavy-Ion and Neutron Measurement ............... 4.2.2 Linear Energy-Transfer Spectral Measurement ........................................................ 4.2.3 Charged-Particle Spectrometry ........................... 4.3 Space Crew Member Exposures in Low-Earth Orbit .... 4.3.1 Dose Rate .............................................................. 4.3.2 Space Radiation Environments for Low-Earth Orbit Space Programs .......................................... 4.3.2.1 Mercury ................................................... 4.3.2.2 Gemini ..................................................... 4.3.2.3 Apollo ....................................................... 4.3.2.4 Skylab ...................................................... 4.3.2.5 Space Transport Shuttle ........................ 4.3.2.6 Mir Space Station ................................... 4.3.2.7 International Space Station ................... 5 Radiobiology of Space Radiation ................................... 5.1 Introduction ...................................................................... 5.1.1 Space Flight and Ground-Based Sources of Data ....................................................................... 5.1.2 Physical and Biological Variables ....................... 5.1.3 Complexity of Time-Dose Relationships ............. 5.2 General Biological Effects of Components of the Space Environment .......................................................... 5.2.1 Protons .................................................................. 5.23 Neutrons ............................................................... 5.28 Electrons ............................................................... 5.2.4 Heavy Ions ............................................................ 5.2.4.1 Introduction ............................................. 5.2.4.2 Physical and Biological Characteristics .. 5.2.4.3 The Microlesion Concept ........................ 5.2.4.4 Bystander Effect ..................................... 5.3 Dose-Limiting Effects for Tissues a t Risk in Space ...... 5.3.1 Bone Marrow ........................................................ 5.3.2 Eye ......................................................................... 5.3.2.1 Radiation-Induced Cataracts ................. 6.3.2.2 Protons and the Lens .............................

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CONTENTS

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........................... ....................... .................................................

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89 90 90 5.3.3 Skin ....................................................................... 91 5.3.3.1 The Responses to Radiation ................... 92 5.3.3.2 The Influence of Radiation Quality ....... 93 5.3.3.3 Summary ............................................... 94 5.4 Health Effects Related to the Reproductive System ..... 95 5.4.1 Hereditary Effects ................................................ 95 5.4.2 Summary of Hereditary Effects .......................... 99 5.4.3 Radiation-Induced Sterility ................................. 100 5.4.3.1 Male ......................................................... 100 5.4.3.2 Female ..................................................... 104 5.4.3.3 Summary ................................................. 104 5.5 Radiation Carcinogenesis ................................................106 5.5.1 Introduction .......................................................... 106 5.5.2 Mechanisms of Radiation Carcinogenesis .......... 107 5.5.3 Dose-Response Relationships ..............................109 5.5.4 Epidemiology and Derivation of Risk Estimates .............................................................. 113 5.5.4.1 Leukemia ................................................. 113 5.5.4.2 Breast ....................................................... 115 5.5.4.3 Thyroid .................................................... 115 5.5.4.4 Lung ......................................................... 116 5.5.4.5 Gastrointestinal Tract ............................ 116 5.5.4.6 Liver ......................................................... 117 5.5.4.7 Kidney and Bladder ................................ 117 5.5.4.8 Skin .......................................................... 118 6.5.4.9 Sources of Uncertainty ........................... 119 5.5.5 An Approach to Estimation of Cancer Risk Associated with Space Travel .............................. 119 5.5.5.1 The Epidemiological Basis for Risk Assessment .............................................. 119 5.5.5.2 Cancer Mortality ..................................... 120 5.5.5.3 Age a t Exposure. Time afier Exposure, and Attained Age .................................... 121 5.5.5.4 Baseline Cancer Rates ............................ 122 5.5.5.5 Transfer of Risk Coefficients Between Populations .............................................. 123 5.5.5.6 Dose Response ......................................... 126 5.5.5.7 Individual Factors ................................... 126 5.5.6 Risks of Radiation Carcinogenesis ...................... 127 5.5.6.1 Method of Estimating Carcinogenic Risk .......................................................... 127 5.3.2.3 Neutrons and the Lens 5.3.2.4 Heavy Ions and the Lens 5.3.2.5 Summary

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CONTENTS

5.5.6.2 Calculation of Excess Lifetime Cancer Mortality .................................................. 128

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6 Radiation Protection Standards for Missions in Low-Earth Orbit ................................................................. 136 6.1 Principles of Radiation Protection .................................. 136 6.2 Biological Considerations for Setting Dose Limits for Space Missions .................................................................. 137 6.3 Basis for Limits for Low-Earth Orbit Missions ............. 138 6.3.1 Basis for Stochastic Limits .................................. 138 6.3.2 Basis for Deterministic Limits ............................ 141 6.4 Recommended Limits for Low-Earth Orbit Missions .... 142 6.4.1 Limits for Stochastic Effects ............................... 142 6.4.2 Careers Different in Length from Ten Years ..... 143 6.4.3 Careers Starting a t Other than Designated Ages ....................................................................... 143 6.4.4 Deterministic Limits ............................................ 144 6.4.5 Recommendation Concerning Pregnant Females .................................................................145 6.4.6 The Meaning of Career Dose Limits and Uncertainty in Risk Estimates ............................ 145 6.4.6.1 Specification of the Dose ........................ 146 6.4.6.2 Uncertainty in Risk Estimates .............. 146

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148 7 Future Research ................................................................. 7.1 Recommendations for Research Required to Meet the Needs of the National Aeronautics and Space Administration Concerning Radiation Effects ............... 148 7.1.1 Dosimetry and Physics ........................................ 148 7.1.2 Radiobiology and Health Effects ......................... 149 7.2 Conclusion ......................................................................... 151

........................ 153 Glossary ..................................................................................... 156 References .................................................................................162 The NCRP ................................................................................. 187 NCRP Publications ............................................................... 196

Appendix A. Site-SpecificIncidence Data

Index

.........................................................................................

206

1. Executive Summary The purpose of this Report is to: (1)examine the new information about radiation environmentsin space, especially the radiation environment within vehicles in low-earth orbit (LEO), (2) to assess the risks to both women and men of various ages exposed to radiation in the light of the current risk estimates of excess cancer and other radiation effects, and (3)update the radiation protection recommendations given in the National Council on Radiation Protection and Measurements (NCRP) Report No. 98 (NCRP, 1989). Other NCRP reports will deal with extrapolation of radiation risks from other biological systems to humans, biological research needs for deep space missions, evaluation of fluence and microdosimetric techniques as the basis for a radiation protection system for astronauts, and an operational radiation safety program for astronauts.

1.1

Background

The guidelines that currently form the basis of the National Aeronautics and Space Administration (NASA)radiation exposure limits for astronauts were recommended in 1989 (NCRP, 1989). At that time considerable changes were made in the guidance given in 1970 by the National Academy of Science/National Research Council [NAS/NRC(197Q)l.The major changes in the career limits were that (1)the risk estimates for cancer were based on the actual excess of solid cancers and leukemia and not on the excess of leukemia alone, as was the case in 1970, and (2) both age at time of first exposure and gender were taken into account for the first time. On the basis that a lifetime excess risk of cancer mortality of three percent was acceptable, it was recommended that the 10 y career limit for females of 25 y of age at the time of first exposure should be 1Sv, increasing with age to 3 Sv for those first exposed at 55 y of age and greater. The corresponding career limits for males were 1.5 to 4 Sv. The short-term dose limits for protection against deterministic effects in certain critical organs were also changed.

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1. EXECUTIVE SUMMARY

1.2 Reasons for a Reappraisal of the Current Guidance on Radiation Limits

First, the current recommendations for radiation protection limits for terrestrial workers are in the International Commission on Radiological Protection (ICRP) Publication 60 (ICRP, 1991a) and NCRP Report No. 116 (NCRP, 1993a) and these recommendations were based on analysis from the United Nations Scientific Committee on the Effects of Atomic Radiation [UNSCEAR (1988)l and the Committee on the Biological Effects of Ionizing Radiation [BEIR (NAS/NRC, 1990)l. UNSCEAR (1988) and BEIR V (NAS/NRC, 1990) reported risk estimates based not only on new data but also on new dosimetry and methods of analysis. I n these reports the estimates of cancer mortality were increased from about one percent per sieved to about four percent per sievert for low dose, low dose rate exposure. A review of the basis of these risk estimates can be found in NCRP Report No. 115 (NCRP, 199313). Second, changes were made in terrestrial dose limits for radiation protection. ICRP Publication 60 (ICRP, 1991a) and NCRP Report No. 116 (NCRP, 1993a) took into account the information about the risks of cancer and genetic effeds fiom UNSCEAR (1988) and BEIR V (NAS/NRC, 1990) in the formulation of new and more restrictive recommendations for radiation protection of workers. Third, it is reasonable to consider radiation limits for space workers in relation to limits recommended for those occupationally exposed on the ground (NCRP, 1997a). Additional data on risk have become available since UNSCEAR (1988) and BEIR V (NAS/NRC, 1990) on both cancer mortality and cancer incidence in the atomic-bomb survivors as well as other populations (i.e., Pierce et al., 1996; Preston et al., 1994; Thompson et al., 1994). In this Report the new data for cancer mortality based on Pierce et al. (1996) is applied to the development of recommended limits. It should be noted that changes in the current risk estimates may occur a s new epidemiological and experimental data from many sources become available. About 50 percent of the atomic-bomb survivors are still alive, and while the data for most relevant age groups are a t hand, much is still to be learned from this important population. For the purpose of this Report, it is also useful to note that risk estimates from the atomic-bomb survivors a s evaluated by international committees like UNSCEAR (2000) have remained stable a t about four to five percent for workers for about a decade. In NCRP Report No. 98 (NCRP, 1989) a section on mission scenarios with estimates of radiation exposure during missions to the moon and Mars was included. Perhaps because of that inclusion, some

1.3 RADIATION ENVIRONMENTS

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have assumed that the guidance on dose limits in that report applied not only to missions in LEO but to all space missions. That was not the intention since the guidance provided was limited to exposures in LEO. In this Report, the guidance is also only intended to be applied for radiation exposures incurred during missions in LEO. Future NCRP reports will deal with other space situations.

1.3 Radiation Environments Galactic cosmic rays (GCR) and trapped-belt radiation (mostly protons) are the two main sources of radiation exposure of importance for missions in LEO such as the Space Transport Shuttle (STS or Space Shuttle), the Mir Space Station, and the International Space Station (ISS). Solar particle radiation, which is of greater concern in missions in deep space, contributes to the radiation environment of LEO when very large solar particle events (SPE) occur and especially when they occur in conjunction with large geomagnetic storms. SPE occur most frequently in the solar maximum phase of the solar cycle. The level of radiation exposure within spacecraft in LEO is influenced by altitude, orbital inclination with Earth's equator, spacecraft shielding, position in solar cycle, and atmospheric density fluctuations. An additional important variable that influences the level of exposure is the time spent traversing the South Atlantic Anomaly (SAA), a region of space in which the trapped proton radiation belt dips in towards Earth resulting in higher dose rates in LEO. Shielding onboard spacemaR reduces the level of radiation but also results in secondary radiation inside the craft consisting of protons, neutrons and ion fragmentation products. Since the publication of NCRP Report No. 98 (NCRP, 1989),there has been a considerable increase in the understanding of the variations and changes in the trapped belt radiation and GCR, and particularly the level of exposure to crew members in spacecraft in various orbits. The dynamic nature of the trapped radiation belts is illustrated by the increase in the rate of loss of trapped particles during solar maximum resulting in lower fluences. Because of the change in Earth's magnetic field, the location of the peak proton fluxes in the SAA has drifted both westward and northward. The increased knowledge about GCR and the radiation belts together with the detailed measurements made on the Space Shuttle and Mir Space Station have made it possible to improve the models of the radiation environments. Measurements of the relative contributions of GCR and the trapped protons and their energy in the SAA as well as the

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1. EXECUTIVE SUMMARY

linear energy transfer (LET)spectra of the GCR have made it possible to describe with confidence the radiation environments to which space vehicles are exposed. The development of both transport codes with modifications for fragmentation and computerized anatomical models make it possible to improve dose estimates in the organs of crew members. It has long been known that there is a neutron component to the radiation environment in spacecraft. Measurements on the Mir Space Station indicate that the contribution of neutrons is quite large, perhaps 40 percent of the effective dose (E). The neutron contribution to the total E depends on the neutron energy spectrum. The biological effects are known only in qualitative terms. For example, the values of relative biological effectiveness (RBE)for a variety of endpoints generally decrease at energies greater than 1MeV. Improvements in dosimetry since the publication of NCRP Report No. 98 (NCRP, 1989) have increased confidence in the estimates of the relevant organ doses and therefore the risks that may be incurred by crew members. GCR originate from sources outside our solar system that have not been identified. They consist of charged particles, ranging in energy, with the majority between 10 MeV n-' to 10 GeV n-'. The fluence rate is greatest in the 100 MeV n-I to 10 GeV n-' range. About 98 percent of particles are protons and heavier ions and two percent are electrons and positrons. Of the protons and heavier ions, approximately 87 percent are protons, 12 percent are helium ions, and one percent are heavier ions. Most of the dose from GCR can be accounted for by the contributions from hydrogen, helium, carbon, neon, oxygen, silicon and iron. Iron is usually considered the most important of the heavier ions for biological effects because of its abundance and its high-LET. GCR enter the atmosphere in the polar regions and contribute to the radiation environment at LEO. In these orbits, the fluence rate of GCR is affected by solar activity, being highest during solar minimum. The total observed dose rates in the environment in which the Mir Space Station orbits are about 145 pGy d-l during solar minimum and about 40 pGy d-I in solar maximum. In the Mir Space Station, about 80 percent of the dose equivalent (H)to the bone marrow is from GCR. The orbital inclination of the Mir Space Station and that for the ISS is 51.6 degrees. At this orbital inclination the H rate is 2.5 to 3 times greater than at 28.5 degrees, the orbital inclination of many of the Space Shuttle flights at approximatelythe same altitude. Higher altitudes can also result in higher dose rates. In NCRP Report No. 98 (NCRP, 1989),an average quality factor of 1.3 was used for protons and secondaries in the SAA. The

(a)

1.4 RADIATION EFFECTS

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estimates of H rates of GCR in space vehicles have been based on the LET spectra calculated from knowledge of the free space environment, the shielding distribution, and a radiation transport model. The development of an appropriate tissue-equivalent proportional counter (TEPC) has now made it possible to make measurements.' In 1991, ICRP (1991a)introduced a new relationship of quality factor (Q)to unrestricted LET. The major change reflected the consensus of scientific opinion that the effectiveness of heavy ions with LET values greater than 100 keV pm-I decreases with increasing values of LET. Although the contribution to the dose from particles with LET >I00 keV pm-I is small in the space environment, the contribution - to H is significant. f i r reviewing the relevant information, an Q of about 1.6 to 1.9, depending on altitude and orbit is now considered appropriate for the radiation resulting from trapped protons for the Space Shuttle, Mir Space Station, and the ISS. Similarly an Q in the range of 3.2 to 3.5 is now considered appropriate for the contribution to the dose from GCR. Quality factors and radiation weighting factors (WR)are used for stochastic effects but these factors do not apply to deterministic effects. In this Report it is recommended for deterministic effects that the organ dose in gray for each type of radiation be weighted by multiplying by an appropriate RBE value for deterministic effects and the limits be expressed in gray equivalents (Gy-Eq).RBE values for radiation qualities and endpoints have been collated in ICRP Publication 58 (ICRP, 1989).Threshold or tolerance doses have been reported by Rubin and Casarett (1968).With the construction of the ISS, the accuracy of the estimates of the RBE values used to modify dose rates to which the construction workers and crew members will be exposed is a matter of some importance (NAS/NRC, 2000).

1.4 Radiation Effects

For radiation protection purposes the effects that may result from exposure to radiation have been divided into deterministic and stochastic effects.

'The TEPC does not directly measure the LET spectra. However, it does measure the lineal energy O.1 spectra and the difference between the LET and y spectra in a mixed field of large energy and charge variation is small. Under these circumstances y spectra can be used to estimate LET spectra. The maximum effect of this substitution on Q can be as much as 20 to 40 percent.

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1. EXECUTIVESUMMARY

Radiation protection limits for occupationally exposed persons are set to prevent clinically significant deterministic effects. Radiationinduced cell killing is central to both early and late effects with the exception of cataract induction. Both the probability and severity of deterministic effects increase with dose above a threshold dose where clinical effects can be observed. The existence of a dependence of cell killing and chromosome aberrations on LET has long been known. It is clear that the damage to DNA (deoxyribonucleicacid) becomes more complex with increasing LET and that double-strand breaks occur in clusters, resulting in less efficient repair. These findings help in understanding that heavy ions have a greater probability of significant biological effects than most other radiations. With missions of long duration on the ISS, the number of cells traversed by high-Z, high-energy (HZE) particles may be considerable;however, the lack of information about their effects on various tissues is one of the main causes of uncertainty in the estimates of radiation risks for such missions.

1.4.1

Early Deterministic Effects

Early deterministic radiation effects that result directly in clinically significant syndromes should not occur as a result of exposure to radiation on missions in LEO because either the dose rate or the projected dose of the radiation is too low to exceed the thresholds for these effects. This is generally true even in the case of an SPE. However, during a very large SPE, mission activities may need to be controlled to keep exposures below the relevant thresholds. There could be concern about possibly exceeding a threshold if an extravehicular activity (EVA) continued over a number of hours and all other conditions that maximize the exposure occurred.

1.4.2

Late Deterministic Effects

While cancer is the late effect of major concern, recommendations are made that are designed to prevent deterministic effects or noncancer effects such as cataracts and damage to the bone marrow and skin that could lead to significant clinical conditions. One year limits, which are not to be considered annual limits, i.e., not repeated year

after year, have been recommended in the past and are recommended in this Report (Table 1.1). Previously in Report No. 98 (NCRP, 1989), the recommendations for limits of radiation exposure to blood-forming organs, skin and the lens of the eye were given in sievert. The use of sievert followed the practice of ICRP Publication 26 (ICRP, 1977). In ICRP Publication 60 (ICRP, 1991a) annual equivalent dose (HT) limits of 500 and 150 mSv for the skin and the lens of the eye, respectively, were recommended for workers occupationally exposed. It is not clear that sievert is the appropriate unit for use in expressing deterministic limits since equivalent dose is obtained by applying w~ or Q values which are applicable to stochastic effects. For deterministic effects, in this Report, it is recommended that organ doses be multiplied by an appropriate RBE value to adjust for radiation quality. Thus recommendations for dose limits for deterministic effects are given in gray equivalents which are the organ doses in gray multiplied by the best estimate of RBE for the specific effect and radiation quality (see Table 1.2). The recommendations for the career limits in this Report, 4 Gy-Eq for the lens of the eye and 6 Gy-Eq for skin, are based on the thresholds for clinically significant lesions in these organs exposed to fractionated doses. It is considered likely that at the low dose rates experienced in space that the effects will be less than with fradionated doses. The main difficulty in recommending dose limits for deterministic effects is the lack of complete human data and even data for TABLE1.1-Recommended organ dose limits for deterministic effects (all ages). Bone Marrow (Gy-Eq)

Eye (Gy-Eq)

Skin (Gy-Eq)

Career

1Y 30 d "The career limits for stochastic effects given in Tables 1.3 and 6.2 are considered to be more than adequate for protection of the bone marrow against deterministic effects for a career. The career limits are expressed in terms of E and the w~ values used to convert absorbed dose to E (see Section 4.1.2) are based on Q(L)values and are higher than the RBE values used to convert absorbed dose to gray equivalent. Therefore, there is no need for a career deterministic limit for the bone marrow. The career stochastic limit is more restrictive and would always be expected to result in a lower absorbed dose to the bone marrow for the irradiation conditions in space.

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1. EXECUTIVE SUMMARY

TABLE1.2-RBE values for converting D to gray equivalents for deterministic effects based on ICRP Publication 58 (adapted from ICRP, 1989j." Radiation Type

Recommended RBEb

Rangeb

1to 5 MeV neutrons 5 to 50 MeV neutrons Heavy ions (helium, carbon, neon, argon) Proton >2 MeV

6.0b 3.5b 2.5" 1.5

(4-8) (2-5) (1-4) -

"RBE values for late deterministic effects are higher than for early effects in some tissues and are influenced by the doses used to determine the RBE. bThere are not sufficient data on which to base RBE values for early or late effects induced by neutrons of energies <1 MeV or greater than about 25 MeV. However, based on the induction of chromosome aberrations, using 250 kVp x rays as the reference radiation, the RBE for neutrons <1MeV are comparable to those for fission spectrum neutrons. It is reasonable to assume that the RBE values for >50 MeV will be equal to or less than those for neutrons in the 5 to 50 MeV range. "There are few data for the tissue effects of ions with a Z > 18 but the RBE values for iron ions (Z = 26) are comparable to those for argon. Based on the available data a value of 2.5 for the RBE of heavy ions is reasonable. One possible exception is cataract of the lens of the eye because high RBE values for cataracts in mice have been reported.

experimental animals exposed to the dose rates and to the mixed radiation fields encountered in space. The selection of single values of RBE for three types of radiation; protons, neutrons and heavy ions are given along with the ranges from ICRP Publication 58 (ICRP, 1989). Clearly, providing single values of RBE is a gross simplification, for example the distribution of neutron energies is broad and the values of the RBE is neutron-energy dependent. However, the estimate of an appropriate RBE value based on the average energy of 5 MeV is justified because the information about the RBE as a function of energy for the specific endpoints is inadequate for greater precision. The available data for neutrons and heavy ions suggest RBE values for effects on the bone marrow are in the two to three range. In the case of lens of the mouse eye, high RBE values have been reported. Two factors influence the results: (1)a minimal lesion has been used as the endpoint and (2) the high RBE values reflects the marked reduction in effect with lowering the dose of the reference (low-LET) radiation. The reasons for the recommendations in this Report are that 1,2 or 4 Gy-Eq received respectively over 30 d, a year, or a career will not cause significant cataracts.

1.4

RADIATION EFFECTS

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The atomic-bomb survivors are the largest population exposed to total-body irradiation in which both cancer and noncancer effects have been monitored. The most recent results (Shimizu et al., 1999) indicate a relative increase in noncancer mortality of about 10 percent at 1Sv. Diseases of the cardiovascular, respiratory and digestive systems are the major cause. The estimated number of excess noncancer cases is now about half of those of cancer. The dose-response relationship has not been established unequivocally, especially at low doses where a threshold cannot be excluded and may even be likely if the effects are deterministic. The exposure of the atomicbomb survivors was at a high dose rate and the excess mortality would be significantlyless for exposures at the low dose rates encountered in space. Therefore, it is not expected that any noncancer excess mortality should occur with the recommended career limits. Spermatogonia and oocytes are radiosensitive with spermatogonia being the most sensitive. These effects are considered under late effects because, for example, in males, no effect is observed for about two months and recovery may take up to 2 y after high doses. The doses that induce temporary loss of fertility in males range from 0.5 to 1 Gy-Eq, and estimates of the doses that cause permanent sterility range from 2.5 to 6 Gy-Eq of high dose rate radiation. There is considerable uncertainty in any recommendation of a dose limit that will prevent temporary sterility in all males because: (1) the lack of precise knowledge about the effect of protraction (lowering the dose rate does not appear to be as protective as in other tissues), and (2) the lack of information about the influence of radiation quality, in particular for protracted radiation exposures. For these reasons, estimates of doses that may cause temporary sterility must await further work. An RBE value of three has been reported for 5.5 MeV neutrons (Gasinka, 1985) and an RBE value of two for carbon (Alpen and Powers-Risius, 1981)has been reported for weight loss of the testis of the mouse, which is used as an assay of loss of spermatogonia. In the case of females, the risk of reduced fertility, sterilization, and loss of estrogen production increase with age. For example, doses of approximately 2 Gy will sterilize 100 percent of women over 40 y of age, whereas, a t younger ages (20to 40 y), 3 to 5 Gy will sterilize most women. Such doses will not occur in the LEO missions that are being considered. As in the case of effects on spermatogenesis, there is insufficient information about the effects of protraction and radiation quality. The data for the RBE values for deterministic effects of radiations encountered in space have been determined to only a limited extent and further work is needed for RBE values for neutrons of the relevant

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1. EXECUTIVE SUMMARY

energies and for heavy ions. Currently, the following values may be used for external exposures: protons (>2 MeV), 1.5; neutrons (1to 5 MeV), 6; neutrons (5 to 50 MeV), 3.5; heavy ions, 2.5 (see Table 1.2). Protons <2 MeV have a higher RBE value (Belli et al., 1989) but the penetration is so low that there is no significant contribution to dose in humans. The career limits recommended to limit excess cancer mortality to three percent (Table 1.3) are considered adequate for protection against noncancer effects assuming that the total dose is not received a t a high dose rate, an assumption that is reasonable considering the low dose rate of radiations in space. 1.4.3

Cancer Risks

The concern about exposure to radiation in space is the possibility ofincreased risk of late effects which, in general, will not be expressed until much later when the individual's career is over. The most important of these late effects is cancer. In the years since NCRP Report No. 98 (NCRP, 1989) there has been an increase in the information about excess mortality from solid cancers in various populations exposed to radiation. In the case of the atomic-bomb survivors, not only have the data for cancer mortality increased (Pierce et al., 1996) but also comprehensive reports on the incidence of leukemia (Preston et at., 1994) and solid TABLE1.3-Ten-year career limits based on three percent excess lifetime risk of fatal ~ancer.4~ E (SV) Age at Exposure ( y )

Female

Male

"Limitsare expressed in effective dose (E). bA three percent excess lifetime risk of cancer mortality has additional components of detriment associated with it, namely the risk of heritable effects (0.6 percent) and of nonfatal cancer (also 0.6 percent) for a total detriment of 4.2 percent. These nominal risks are as given in ICRP (1991a) and NCRP (1993a).

1.4 RADIATION EFFECTS

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11

cancers (Thompson et al., 1994) have been published. In addition, further information on the influence of age at exposure and gender differences have also become available (Pierce et al., 1996). Data on radiation-induced cancer incidence are given in Table 5.14 and in Appendix A. In NCRP Report No. 98 (NCRP, 1989), as noted above, both age at first exposure to radiation in space and gender were taken into account in both estimating the risks and in setting limits. In the current Report that practice is continued with revised information for age and gender differences. This policy was initiated because the risk of cancer is greater in females than males. For example, the estimated excess cancer deaths associated with chronic exposure of 10 mSv y-l starting a t age 35 for 10 y is 0.52 percent for females and 0.31 percent for males. Since it is considered that the riska to female and male astronauts should be equivalent the exposure limits are adjusted appropriately resulting in lower limits for females than for males. The new recommended career dose limits for males and females of ages 25,35,45 and 55 at first exposure, based on a three percent career fatal cancer risk derived from the risks in Pierce et al. (1996) are given in Table 1.3. As noted earlier, the revised risk estimates on which these career dose limits are based have remained essentially the same for a decade now and further revisions, hopefully, should not be necessary.

1.4.4

Hereditary Effects

The question of hereditary risk associated with exposure to radiation in space has been examined in every report on the potential health effects of radiation in space since 1967. In the NAS/NRC (1967) report, based on the assumption of an average total dose of 2 Gy to 50 astronauts over a 10 y period, it was estimated that there would be a very small increase of about 0.008 percent in the collective genetically significant dose (GSD) normally received by the United States population from natural radiation sources (NCRP, 1987a). In the early space missions the crews consisted of males, most of whom were at least 40 y of age. Today the astronaut corps are made up of both males and females. The average age of flight personnel has decreased, the number of astronauts has increased, and the duration of the missions is increasing. Such changes will increase the collective dose, but the contribution to GSD will remain insignificant. Thus, concern about hereditary risks will continue to be an individual issue.

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1. EXECUTIVE S U M M Y

There remains considerable uncertainty in the estimate of hereditary effects in humans. No significant increase in these effects has been detected in the progeny of the atomic-bomb survivors. A doubling dose (DD) of 1Sv, which is based on studies of the mouse, has been used, but the bounds that can be put on the risk estimated from the human studies suggests a DD of at least 2 Sv. Both the ICRP (1991a) and NCRP (1993a) have concluded from the current information that the risk of severe hereditary effects in all generaSv-l compared with fatal cancer tions is approximately l x risk at 5 x Sv-' (for all ages). The recommendation of this Report is that crew members be informed of the nature and the level of the hereditary risk. Appropriate scheduling of missions and procreation should further decrease hereditary risk. Personal counseling should be given to those of a reproductively active age. Furthermore, because of the possibility of direct radiation effects on the embryo/fetus (NCRP, 1993a), women should be disqualified for service in space during pregnancy.

1.5 Career Dose Limits Both stochastic and deterministic effects, discussed earlier, must be considered in the guidance about radiation limits. Shielding can reduce the dose received by crew members in space, but it cannot eliminate completely the exposure, principally because of the generation of penetrating secondary radiations. Missions of long duration, such as those contemplated for the ISS, will involve significant doses. The total E on a six-month mission on the ISS may reach 0.20 Sv, high in comparison to the annual limit recommended for workers occupationally exposed on Earth, but equivalent to about one-third of the risk associated with the limit recommended for a working lifetime on Earth. Using current nominal risk coefficients for an adult population (4 X Sv-I),the ICRPrecommendationto limit a worker's occupational exposure to no more than 20 mSv y-I averaged over a 5 y period can lead to a maximum lifetime risk of fatal cancer of between three and four percent (NCRP, 1993a).The NCRP recommendations of 50 mSv y-' with a cumulative limit (age x 10 mSv) after age 18, result in an estimated average maximum lifetime risk of fatal cancer of approximately three percent (NCRP, 1993a). The average lifetime risk of accidental death in occupations such as construction and agriculture is about 1.5 to 3 percent and for much more dangerous occupations, such as test pilots and deep-sea

1.6 UNCERTAINTIES IN THE RISK ESTIMATES

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13

fishing, the lifetime risks approach and may exceed 10 percent. Accidental deaths result in a greater loss of lifespan than does cancer, primarily a disease of older age. The use of comparative risks as a basis of dose limits is complicated by the welcome and remarkable reduction in the accidental death rate in the last decade in many occupations in developed countries such as the United States. Nevertheless, this comparison with other occupations is useful to put the risks associated with radiation exposures in the workplace into perspective. Given these limits for occupational exposure and the accidental death rates for other occupations,the choice of a three percent career excess risk of cancer mortality made in NCRP Report No. 98 (NCRP, 1989)remains reasonable and justified. Because of the importance of the choice of an acceptable level of risk and the many factors not necessarily related to health hazards, dose levels corresponding to other rates of excess lifetime cancer mortality could be considered. Career dose limits based on three percent excess lifetime cancer mortality are recommended in this Report (see Table 1.3). As discussed earlier, the risk coefficients for radiation-induced cancer have been increased in the years since NCRP Report No. 98 (NCRP, 1989), and the estimates are reflected in the lower career limits based on three percent excess lifetime risk of fatal cancer that are now recommended (Table 1.3).

1.6 Uncertainties in the Risk Estimates

The estimation of risk (of cancer, for example) is not an exact science and inevitably is subject to many uncertainties. However, if these uncertainties can be evaluated quantitatively, a much clearer picture ofthe risk in any given circumstance emerges and it is clearer as to the range over which the risk should apply. Sources of uncertainty in the estimation of risks from the exposure to radiation in space include: (1)difficulties in estimating astronaut exposures, (2) uncertainties in the low-LET radiation risk coefficients, and (3) our limited knowledge of the risks associated with heavy charged particles exposures either in an absolute sense or relative to low-LET radiation. NCRP Report No. 126 (NCRP, 199713)comprehensively addresses the uncertainty associated with the current low-LET radiation risk coefficients for fatal cancers. The most important component of that uncertainty is our lack of knowledge of the dose and dose rate effectiveness factor (DDREF) that scales the risks for an acute exposure

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1. EXECUTNE SUMMARY

to the low dose and low dose rate environment expected for astronauts in LEO. For high-LET exposures, the second major uncertainty is the lack of human data and only a small amount of in vivo and in vitro laboratory data that can provide the basis for risk estimates for cancer induced by heavy charged particles. There is also uncertainty, which is very difficult to quantify because of the lack of data for humans exposed to protons, neutrons, and heavy charged particles and the availability of only a limited amount of relevant experimental data.

1.7 Impact of Career Exposure Limits on Space Activities The guidance given in this Report on the selection of career exposure limits is more restrictive than NCRP Report No. 98 (NCRP, 1989).This is a consequence of the new and increased risk estimates of cancer that come from the new data from the atomic-bomb survivors and the methods of analysis. The most marked restriction is for the young female astronaut. For those exposed for the first time at older ages, multiple missions in LEO of relatively long duration will be possible. It should be noted that the relevant measurements and estimates of doses and dose rates given in this Report are for solar minimum during which the dose rate of the GCR is, perhaps, twice as high as in solar maximum. Innovative design of the ISS and other space vehicles, thoughtful planning and mission management can make it possible for individuals to have very full careers without unreasonably increasing their risks of late effects of radiation.

1.8 Future Research

There has been a great deal ofnew information about LEO environments since NCRP Report No. 98 (NCRP, 1989), as well as the introduction of new dosimetric equipment. The new measurements have revealed discrepancies with the models used for predicting the exposures of crew members, and therefore there is a need for revision of the models of the trapped-belt radiation; the proton environment for solar maximum and minimum (Sawyer andvette, 1976), trapped electron's model AE-8 and proton's model AP-8 (Bilitza, 1987). New models should take into account the dynamics of the radiation belts to improve long-term predictions of the radiation environments. Models of the LET spectra that include the secondaryradiations are

1.8 FUTURE RESEARCH

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15

required. The radiation environments within space vehicles, especially after a long duration in space, which depend in part on the materials used in the construction, will have to be known. A recent report of the NASfNRC (2000) estimates the possible exposures, especially during SPE, that could be incurred in EVA during orbits at high inclinations. An accurate assessment of the environment within space suits is required. A recent report of the N A S M C (2000) estimates the possible exposures, especially during SPE, that could be incurred as a result of extravehicular activities during orbits of high inclination. In summary, all the available information about the energy and LET spectra of all the relevant radiations in relation to altitude, inclination, shielding, and the phase of the solar cycle should be integrated and any important gaps should be filled. In the fields of radiobiology and health-effects research, considerable progress has been made since NCRP Report No. 98 (NCRP, 1989). However, the lack of data on the effects of protons, neutrons and HZE particles in humans forces a reliance on data from animal experiments and in vitro studies. Neither the data for the effects in cells and animals are complete enough nor are the methods of extrapolating risk estimates currently satisfactory. There is a need for information about the influence of protraction of space radiations and the dependence of biological effects on the energy and the charge of the radiation. Experimental data are required to improve the selection of a dose rate effectiveness factor (DREF). Alternatives should be examined, namely, different factors for different tissues, or the selection of a single factor weighted for the frequencyof cancer in different tissues. Similarly, data are needed for the carcinogenic effects in representative organs of radiations of different LET to define the relationship of Q to LET (or some surrogate). The current values of Q are derived from meager information about the carcinogenic effect of charged particles. New approaches for estimating risks of late effects should be assessed and the data, such as RBE values for induction of cancer by high-LET radiation should be obtained. There is a lack of information about the induction of cancer and deterministic effects by low dose rate proton radiation and neutrons in the 2 to 50 MeV range. The deterministic effects of low- and high-LET radiation, in particular effects on male fertility require investigation. Since RBE values for the induction of deterministic effects by highLET radiation are required for selection of dose limits, and it is suggested that RBE values be based on threshold doses, there is a need for estimates of threshold doses, in particular for protracted exposures to protons, neutrons, and heavy charged particles.

16

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1. EXECUTIVE SUMMARY

Other areas requiring further research or assessment are: (1)age dependency for both stochastic and deterministic effects, (2) HZE particles, (3) biodosimetry, and (4) radioprotectors. The research required for the estimation of the radiation hazards to crews of interplanetary missions has been discussed in a report of a Task Group on the Biological Effects of Space Radiation, Space Science Board, NAS and is the subject of a report being prepared by NCRP Scientific Committee 1-7 on Information Needed to Make Radiation Protection Recommendations for Travel Beyond LowEarth Orbit. Much of the research discussed in those reports is pertinent to the improvement in the estimates of risk incurred from undertaking missions in LEO.

2. Introduction The purpose of this Report is to: (1)examine the new information about radiation environments in space, especially the radiation environment within the Space Shuttle, Mir Space Station, and the future ISS in LEO, (2) to assess the risks to both women and men of various ages exposed to radiation in the light of the new risk estimates of excess cancer and other radiation effects, and (3) modify where necessary, the radiation protection recommendations made in NCRP Report No. 98 (NCRP, 1989).

2.1 Background of Space Radiation Safety Standards The assessment of radiation risks in space dates back to 1961 when an a d hoc working group was set up by the Space Science Board of NAS. This group was reconstituted 3 y later and proceeded to make the first full systematic examination of the scientific and philosophical bases for establishing radiation protection criteria for manned spaceflights. The panel's report, Radiobiological Factors in Manned Space Flight, appeared in 1967 (NASMRC, 1967). The concept ofrisk and questions raised by the idea of acceptability ofrisk are not new (NCRP, 1954;198713; 1993a)in relation to ionizing radiation. Thus, when the Radiobiological Advisory Panel of the Space Science Board's Committee on Space Medicine was requested in 1969 to formulate radiation protection guides, both an accepted approach and some quantitative data on which to base risk estimates already existed. It was realized that any recommendations would be "tentative" but should be useful to the designers of manned space vehicles and to the planners of manned missions. There was concern about keeping recommendations in perspective since it was clear that the risks of leaving Earth and traveling in space at that time were far from negligible, and by comparison, radiation risks were not a significant problem. This perception proved to be prescient since radiation exposures have remained low up to now, while the other risks associated with flight have been significant. Nevertheless, the Panel looked to the future and considered the possible effects of protracted radiation exposure that would be involved in interplanetary missions and space stations. It was this concern, and

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2. INTRODUCTION

not knowing all the determinants required for a risk-benefit analysis, that encouraged the Panel to adopt the concept of reference risk. They said, "It seems reasonable to recommend a primary reference risk that may be used as a point of normalization for plans and operations involving different numbers of personnel, different riskversus-gain eva2uations, and different degrees of operational complexity" (NAS/NRC, 1970). This philosophy was a continuation of the Panel's position in 1967 that, "radiation-protectionaspects of each type of manned space operation should be considered individually in context with a risk-versusgain philosophy and the other risks inherent in the operation." It was also felt that the Panel had neither the competence nor the responsibility to evaluate the gain or benefit but should evaluate potential radiation risk in probabilistic terms. The Panel considered radiation effects under three main headings: genetic effects, early effects, and late effects. The Panel, noting that only small numbers of individuals would be involved, most of whom would be over 30 y of age, considered that the question of genetic effects was not one of immediate concern in relation to the population gene pool. It was suggested that counseling could provide an appropriate method of addressing this component of potential radiation risk. Somatic effects, which were considered a greater concern, were divided arbitrarily into early effects, occurring within 60 d, and late effects. Early effects were a concern because they might impair performance and thus threaten the completion of the mission. The Panel also stated that doses and dose rates that could cause the dose and dose rate-dependent threshold effects were likely to occur only if an anomalously large SPE was encountered. While dose rates may vary between different SPE, it is currently thought that the dose rates in LEO will be in the range of what is considered low dose rate for acute deterministic effects, e.g., below 10 to 20 mGy min-l. Late effects were the predominant concern when accumulated career exposures were considered. Although nonspecific life shortening was still considered a late effect in 1970, it was appreciated that cancer was the principal somatic late effect of concern, and that the risk of cancer should be the foundation of a recommendation for career exposure limits. Recently, reports of noncancer late effects such as effects on the cardiovascular system in the atomic-bomb survivors who received 20.5 Sv have appeared (Shimizuet al., 1999). The information on risk of incurring noncancer late effects, especially in persons exposed to high doses early in their careers, should be kept under review. The Panel proposed that "the primary reference risk, should correspond to an added probability of radiation-induced neoplasia over

2.2 RADIATION STANDARDS FOR NASA

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19

a period of about 20 y equal to the natural probability for the specific population under consideration." The population under consideration consisted of men who would begin their careers as astronauts between 30 and 35 y of age. In brief, it was determined from the data available at that time that 4 Sv would be the DD for the specific age group. The Panel expressed clearly that the exposure limits and exposure accumulation rate constraints for skin, lens of eye, testes, and bone marrow were recommendations and not standards. Since exposures were considered to be whole body, the recommended bonemarrow exposure of 4 Sv was identical to the career limit (N-/ NRC, 1970). Only a few of the astronauts have incurred a small fraction (10 to 30 percent) of the exposure limits. The highest average mission dose was about 43 mGy on Skylab. The average career dose from diagnostic x rays and nuclear medicine procedures in the 1960s was about 50 to 90 mSv (NCRP, 1989). Since that time these exposures have been reduced greatly and in 1990 were less than 3 mSv. The radiation exposures experienced by the astronauts in space have been low for a number of reasons. For example, most of the missions have been short in duration, low in altitude, and at favorable inclinations. The prediction that SPE would contribute relatively low additions of dose to the crews on missions in LEO, for example, 30 to 40 mGy to the dose inside the Mir Space Station during the October 1989 SPE appears to have been borne out.

2.2 Radiation Standards for the National Aeronautics and Space Administration

The federal regulations governing radiation standards for NASA manned spaceflight programs are the responsibility of the U.S. Department of Labor's Occupational Safety and Health Agency (OSHA). In 1971, OSHA established federal regulations for limiting radiation exposuresofworkers and the general population to ionizing radiation. These regulations, 29CFR 1910.96, were part of a larger document, Code of Federal Regulations for Occupational Safety and Health. An Executive Order, 12196, February 26, 1980, made all government agencies subject to the Occupational Safety and Health Act. This policy was later supplemented by OSHA Regulation 29CFR 1960.18. Entitled "Basic Program Elements for Federal Employees Occupational Health and Safety Program and Related Matters," this regulation was updated by Residential document "Radiation Protection Guidance to Federal Agencies for Occupational Exposure:

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2. INTRODUCTION

Recommendations Approved by the President" (Federal Register Vol. 52, page 2822, January 27, 1987). Under this regulation agencies are allowed to adopt supplementary standards (limits) with OSHA approval. That approval is based on whether the benefit outweighs and justifies the risk.

2.3 Development of 1989 Recommendations

In the period 1970 to 1988, there were two NASMRC reports, BEIR I (NASMRC, 1972)and BEIR I11 (NAS/NRC, 19801, and three reports by UNSCEAR (1972; 1977; 1988)that dealt with the accumulating human experience with radiation and the estimates of risk from external radiation. These reports took into account, to varying degrees, the understanding of radiation carcinogenesis derived from experimental work. Two reports that considered the radiation risks of a specific mission and activity in space had also been produced. The proposal of a Satellite Power System called for workers to construct the satellite in a LEO at an altitude of about 500 km, and then to transfer it to a geosynchronous Earth orbit at 36,000 km. It was proposed that the workers' tour would last about 90 d and involve considerable time in EVA. A U.S. Department of Energy report (DOE, 1980) concluded that there would be a four percent excess risk of cancer mortality in workers completing 10 missions. A NASMRC (1981) report on the Satellite Power System suggested the excess cancer mortality would be six percent for males and about eight percent for females. The estimates were very sensitive to the shielding model assumed, and therefore the confidence limits were wide. Casarett and Lett (1983) drew attention to the need for examining the guidelines for radiation protection of those venturing into space. Much had been learned about the effects of different radiation qualities, including HZE particles (Blakely and Edington, 1985; Blakely et al., 1984; Leith et al., 1983) in the years since 1970. Also, the estimates of risk of late effects, particularly cancer, had improved. Sinclair (1983) examined the radiation protection guides and constraints for space mission and vehicle design studies involving nuclear systems proposed in 1970 by the Radiobiological Advisory Panel of the Committee on Space Medicine (NASMRC, 1970)in light of what had been learned in the intervening years. Sinclair showed that when the newer estimates of risk were applied to the approach of 1970, the career limit would be about 2 Sv instead of 4 Sv. In the early 1980s, NASA requested the NCRP to re-examine the question of radiation risks in space and to make recommendations

2.3 DEVELOPMENT OF 1989 RECOMMENDATIONS

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about career radiation limits. Because there had been no comprehensive review of space radiation in relation to the acute and late effects of radiation since the NASLNRC documents in 1967 and 1970, the NCRP (1989) report encompassed radiation environments in space, radiation effects, the basis of risk estimates and recommendations of career limits. The risk estimates and the recommendations for career limits in the 1989 report (NCRP, 1989) applied only to exposures in LEO,a fact, perhaps, not stressed sufficiently. I t was clear that exposure of crew members could be reduced but not eliminated. Consequently, for various reasons the occupational limits recommended for workers on Earth were not considered to be appropriate it was important to set career exposure limits. The principle of restricting exposure to levels as low as reasonably achievable (ATARA) was a n important aspect of the recommendations. Cancer was considered the principal risk and the career limits were set to limit the risk of fatal cancer. The limits were based on three percent excess lifetime cancer mortality, a risk less than the lifetime risk of fatal accidents in the most hazardous occupations. Cancer is mainly a disease of old age and fatal accidents tend to occur a t younger ages. Therefore, the loss of lifetime would usually be greater with fatal accidents. The risk of radiation-induced cancer is both age and gender dependent. For the first time in recommending radiation protection standards, age and gender were taken into account. The career whole-body dose equivalent for a three percent risk recommended by NCRP (1989) are shown in Table 2.1 and can be seen to range from 1to 4 Sv depending on gender and age a t the time of first exposure to radiation in space.2 The recommendations TABLE2.1-Career whole-body exposure limits for a lifetime excess risk of fatal cancer of three percent as a function of age at exposure (NCRP, 1989). Age (Y)

Female (Sv)

Male (Sv)

'ICRP in recommendations adopted in 1990 (ICRP, 1991a) defined E as the sum of the weighted equivalent doses in all the tissues and organs of the body: E = XT W T HT,where HTis the equivalent dose in tissue or organ (T)and W T is the = W RDT where DTis the weighting factor for tissue (T). The equivalent dose (HT) average absorbed dose in tissue (T) and W R is the radiation weighting factor which is selected for the type and energy of the radiation (R).

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2. INTRODUCTION

for shorter term limits and career limits for deterministic effects are shown in Table 2.2. Following the publication of NCRP Report No. 98 (NCRP, 19891, the NASA Administrator petitioned OSHA for approval of supplementary exposure standards for flight crews involved in space a~tivities.~ NASA's request for adoption of supplementary exposure standards was based on the following:

1. Limited risk to a small population. The career limits for flight crews would be based on an increase in the risk of cancer mortality of three percent higher than the risk of cancer in the general population, and these limits would apply only to flight crews during the actual performance of the mission. 2. Before each mission NASA would conduct a formal radiation hazards appraisal. This appraisal would include preflight exposure calculations, including an extensive and sophisticated premission determination of potential exposures for each element of each mission (e.g., exposures during an EVA). This appraisal would be based on the proposed mission plan and time line, the model of the radiation environment, a detailed mass distribution model of the spacecraft, components and inhabitants, and a radiation transport program. Each element of the hazards appraisal strategy would be developed and updated as appropriate. 3. Detailed crew exposure records would be maintained. Passive dosimeters would be worn by every crew member during the mission. These dosimeters, which have been the backbone of the operational dosimetry program since Project Mercury, are continually evolving with the availability of new materials and 2.2-Recommended organ dose-equivalent limits for all ages TABLE (NCRP, 1989).

Time Period

Career 1Y 30 d

Blood-Forming Organsn (Sv)

Lens of the Eye (SV)

Skin (SV)

see Table 2.1 0.50 0.25

"This term has been used to denote the dose at a depth of 5 cm. %etter from NASA Administrator, Admiral R. Truly,to the Assistant Secretary of OSHA, dated December 4, 1989.

2.4 REAPPRAISAL OF THE GUIDELINES

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23

techniques. International comparisons of calibrations are routinely performed. Advanced dosimetry systems are being conceived, developed and evaluated. In addition, extensive records of both flight exposures and ground-based exposures are part of each crew member's medical history. 4. Adherence to the ALARA principle. The flight planning by NASA's Space Radiation Analysis Group would ensure crew exposures were "as low as reasonably achievable." 5. Formal operational procedures. Formal protocols, including the use of calibrated active and passive measurement radiation systems, and flight rules covering any radiation exposure contingency would be developed and documented. On-call personnel are available for anomalous events andlor readings. Operational activities include interfacing directly with the Mission Flight Surgeon and Flight Director. The approval of these supplementary standards was granted by OSHA in 1990.4

2.4 Reappraisal of the Guidelines Given in NCRP Report No. 98 By 1990, UNSCEAR (1988) and NASJNRC (1990) had issued reports that contained estimates of fatal cancer risks that were significantly higher than those used in NCRP Report No. 98 (NCRP, 1989). This information suggested that there would have to be a reappraisal of the earlier recommendations. It is important to note that the 1989 recommendations nor this Report were considered necessary because of concern about past practices of NASA. As pointed out above, the doses incurred by the astronauts have been low, in fact, well below the lifetime radiation levels permissible for terrestrial occupational exposure (Peterson et al., 1993). New recommendations for radiation protection of terrestrial occupational radiation workers were issued by ICRP (1991a) and by NCRP (1993a) based on the risk estimates reported by UNSCEAR (1988) and BEIR V (NAS/NRC, 1990). The basis of these estimates was reviewed by NCRP (199313). Since then, data for the atomicbomb survivors has accumulated and risk estimates based on both cancer mortality (Pierceet al., 1996)and on incidence of solid cancers (Thompson et al., 1994) and leukemias (Preston et al., 1994) have been published. 'Letter from the Assistant Secretary of OSHA, dated March 7, 1990.

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2. INTRODUCTION

There has been a remarkable decrease in mortality from industrial accidents and for this and other reasons it is considered reasonable now to consider radiation limits for space workers in relation to recommendations made for radiation protection of terrestrial workers instead of the basis being that of comparative risks in various occupations. In 1989,ICRP issued Publication 58 on RBE for deterministic effects (ICRP, 1989)which provides a review of both the available data and approaches to the derivation of RBE values for deterministic effects. NCRP has made use of this report in its reappraisal of the recommendations for limits to prevent deterministic effects. Radiation protection in space is an international task as is the protection of occupationally exposed workers and the general population on Earth. Kovalev (1983)noted that radiation protection in space is a pressing but complex problem and in the case of the ISS will require coordination of the views on radiation protection of the countries involved. The recommendations in this Report may well require modifications as more is learned about the radiation environment in space and how radiation risks can be estimated with greater precision.

3. Radiation Environment

in Low-Earth Orbit

3.1 Introduction The radiation environment in LEO consists of several types of energetic charged particles: electrons, protons, helium and heavier ions. The relative importance of each of these components to the radiation dose of members of a given space mission depends strongly on many details of the mission itself; for example, the spacecraft trajectory, the time the mission occurs during the solar cycle, altitude, the mission duration, and the shielding provided by the spacecraft. Also, there are the poorly known physical factors, such as the chance of large emissions of particles from the sun, and the broad temporal and spatial fluctuations of several of the trapped radiation components. Generalizations of the importance of the various radiation components must be made with some caution and adequate margins of error must be built into any dose estimates in order to assure that worst-case scenarios are adequately treated in spacecraft design and mission planning. Space radiations are placed into three main categories according to their source: (1)trapped particles, (2) galactic cosmic rays (GCR), and (3) solar particles. The trapped particles consists mostly of electrons and protons trapped in closed orbits by Earth's magnetic field. Both the GCR and the solar particles consist mostly of protons, with a small admixture of helium ions and an even smaller component of heavier ions. The differences between these two categories are mainly in the vastly different distributions of particle energies involved and in the sporadic nature of the solar disturbances producing the solar particles as compared with the more slowly varying nature of the galactic particle intensities. Good reviews, such as that of Rust (1982)and Smart and Shea (1997)have appeared periodically to summarize the knowledge accumulated concerning the nature and intensities of the radiations produced by each of these sources. Therefore, we shall only briefly describe here the general features of each, and provide a few quantitative estimates for specific situations.

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3. RADIATION ENVIRONMENT IN LOW-EARTH ORBIT

3.2 Trapped-ParticleRadiation

In 1958 the first United States satellite, Explorer I, containing a large Geiger counter provided by Iowa State University scientists to study cosmic rays, detected an unexpectedly large fluence of energetic charged particles. These were attributed to particles trapped by Earth's magnetic field, a fad later confirmed by Explorer IIL The discovery of these "belts" of charged particles was first reported by Van Allen (1960).

3.2.1 Sources and Sinks Trapped belts are chiefly composed of protons and electrons, but energetic helium, carbon, oxygen, and other ions are also observed. The most plausible source of the very energetic protons and electrons at lower altitudes is the decay of albedo neutrons produced by nuclear reactions between GCR and atmospheric constituents (Singer, 1958). At higher altitudes, the ionosphere and the solar wind are sources of the trapped particles. The anomalous cosmic rays (ACR) component is probably a source of the heavy ions (see Section 3.3.3). During the late 1950s and early 1960s a number of artificial radiation belts were created by high-altitude nuclear detonations. In some instances some of the radioactive fission fragments from the weapons reached altitudes sufficientlyhigh to inject electrons from beta decay of the fragments into trapped orbits. One series of tests (Argus)was designed primarily to test the geomagnetic trapping theory and were made a t high altitude in a region of low magnetic field over the Atlantic Ocean. The most important and long-lasting enhancement to the radiation belts was caused by the Starfish test, a low-latitude burst over the Pacific Ocean. Because the Starfish test was not initiated with trapping as an objective, the intensity and persistence of the enhancement was unexpected. Three high-altitude nuclear tests by the former Soviet Union in 1962 resulted in significant trapping, but the particle densities decayed much more rapidly than Starfish (Hess, 1968). Nuclear test-ban treaties now prohibit this type of testing. Several loss mechanisms of trapped particles via interactions with atmospheric constituents are feasible. Collisions reduce their velocities below that required for trapped orbits. Electrons, being less massive than other charged particles, are more likely to be scattered into loss cones by Coulomb interactions. In addition, electrons are scattered into loss cones by wave-particle interactions. Outer belt electrons can be scattered and diffuse out of the magnetosphere during large geomagnetic storms.

3.2 TRAPPED-PARTICLE RADIATION

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The constant pressure applied to Earth's magnetic field system by the solar-wind plasma compresses it as illustrated in Figure 3.1. The compression produces a collision-less stationary bow shock at about 15 RE (where 1RE = 6,371 km,the mean radius of Earth) on the sunlit side. A seasonal distortion in the field configuration occurs because the dipole is inclined 23.5 degrees with Earth's orbital plane about the sun. Other asymmetries arise because the dipole is tilted by 11.1degrees from Earth's axis of rotation and offset from the axis of rotation. For the 1990 epoch, the dipole is displaced by 0.0809 RE (515 km) toward 21.1°N and 145.7"E7and the eccentric dipole axis cuts Earth's surface at (82.5"N791.1°W) and (75.2"S7119.loE).This displacement moves the belts lower in altitude in the South Atlantic near Brazil, a phenomenon known as the SAA (South Atlantic Anomaly). Earth

Fig. 3.1. Interaction of the solar wind and Earth's magnetic field produces a shock front on the sunlit side (i.e., from the left side of the figure). The tilt of Earth's axis of rotation with respect to the orbital plane about the sun produces a seasonal distortion of Earth's magnetic field that is particularly pronounced on the sunlit side (Ness, 1969).

28

1

3. RADIATION ENVIRONMENT IN LOW-EARTH ORBIT

3.2.2 Motions of Charged Particles in a Magnetic Field

As illustrated in Figure 3.2, the motion of a trapped particle in Earth's magnetic field is characterized by three components: a helical trajectory about the magnetic field line B, a bounce between polar mirror points, and a longitudinal drift around Earth. The equation of motion for the helical trajectory is obtained from the Lorentz force:

where q and v are the particle charge and velocity, respectively. The angle a between v and B is called the pitch angle and varies with the particle's motion along the magnetic field line, being 90 degrees at the mirror points and a minimum in the equatorial regions. As a particle bounces between mirror points, a longitudinal drift is introduced by the altitude gradient of the magnetic field. The gyration radius of the particle decreases at lower altitudes where the magnetic field is stronger and increases a t higher altitudes. This tightening of the orbit a t low altitudes and loosening a t high altitudes introduces a drift perpendicular to the field lines. Positive particles drift westward and negative particles (primarily electrons) drift eastward. The combined motion of a particle traces out a shell or tube of constant force that resembles a toroid.

(pitch angle of helical trajectory

= 90")

Magnetic field line

Fig. 3.2. The motion of a charged particle in a dipole magnetic field consists of three components; a helical trajectory about the magnetic field line, a bounce between polar mirror points, and a longitudinal drift around Earth (Hess, 1968).

3.2 TRAPPED-PARTICLE RADIATION

3.2.3

1

29

Description of the Belts

In the simplest terms, the trapped radiation component can be described by an inner belt consisting of protons and electrons for which the protons are the most important contributor to dose and an outer belt consisting predominantly of electrons. All the particles travel in helical trajectories determined by the magnetic field lines and their associated field strengths. Popularly described as the 'Van Allen" belts, they occur at maximum altitude at the geomagnetic equator and approach closer to Earth's surface at polar latitudes, making the launch inclination of manned spacecraft an important consideration. The protons form a continuous distribution of particles in radial distance from Earth with a peak ffuencerate for 400 MeV protons, 4 MeV protons, and 0.3 MeV protons at 1.3 R E , 2 RE, and 3 RE, respectively. Figure 3.3 is an analytical representation of typical

-

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lo1

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a m

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!2

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100

200

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400

500

Proton energy (MeV)

Fig. 3.3. Trapped-belt proton spectrum for the ISS orbit (51.6 degrees inclination, 470 k m altitude) using AP-8 models for solar maximum and minimum (Atwell, 1999)5. 'Atwell, W. (1999).Personal communication. Data generated using Space Environment Information System (SPENVIS) on-line capability of the Belgian Institute for Space Aeronomy, Brussels, Belgium (Boeing Company, Houston, Texas).

30

1

3. RADIATION ENVIRONMENT IN LOW-EARTH ORBIT

trapped proton energy spectrum expected for the ISS orbit (51.6 degrees inclination circular orbit at 470 k m altitude). The proton spectrum decreases sharply for energies above 500 MeV because higher energy protons are not as easily controlled by the magnetic field. Decreases a t lower energies are attributed to loss by interactions with atmospheric constituents. An important feature of the trapped radiation belts is the SAA. The SAA feature of the magnetic field is not a true anomaly, but the result of magnetic field lines dipping closer to Earth because of the eccentricity of the geomagnetic field with respect to Earth's center. The feature is important for two reasons: it is the primary source of radiation exposure of crew members whose spacecrafi orbits are low altitude and low inclination, and for radiation studies it is a region where particle losses due to atmospheric scattering are enhanced as a consequence of the denser atmosphere encountered by the particles traversing the minimum altitudes. An east-west anisotropy in trapped particle fluence rates, which was predicted by Lenchek and Singer (19621, was reported from measurements on a n unmanned spaceflight by Heckman and Nakano (1963).At the bottom of their helical path, protons are traveling eastward while those at the top of the helix are traveling westward. Thus, a satellite traveling east will be struck on the trailing edge by particles traveling east, and vice versa for the leading edge. Those particles traveling west have emerged from a region of the atmosphere lower i n altitude where they are more efficiently removed from orbit by the greater density. The difference in incident particle fluence rates caused by this phenomenon can be very substantial. Harmon et al. (1992) measured doses 2.5 times higher on the trailing edge of the Long Duration Exposure Facility than on the leading edge. Similar differences can be expected on the ISS. The trapped electrons occupy two distinct regions of the magnetosphere separated by a "slot" at about 2.8 RE.In fact, the distinction between inner and outer belts exists only for electrons. The most pronounced difference is the location of the "center" of the outer belt which moves out from 4.5 RE at solar maximum to about 5.1 RE at solar minimum. Figure 3.4 shows the energy spectrum of trappedbelt electrons a t an altitude of 400 k m and inclinations of 28.5 and 57 degrees for both solar minimum and solar maximum.

3.3 Galactic Cosmic Rays

3.3.1 Abundance Interstellar space is filled isotropically with high-energy charged particles, collectively called galactic cosmic rays (GCR), ranging from

3.3 GALACTIC COSMIC RAYS

/

31

0 57.0 - M A X

A 57.0 - MIN 28.5 - M A X

Electron energy (MeV) Fig. 3.4. Trapped-belt electron spectra a t 400 km for solar minimum and maximum inclinations of 28.5 degrees and 57 degrees using AE-8 environment model (Atwell, 1999)6.

protons (Z = 1)to uranium ions (Z = 92). They consist of 98 percent protons and heavier ions and two percent electrons and positrons. Their energy spectra in free space, outside Earth's magnetic field, range from a few tens of MeV n-l to above loz0eV n-l. In the energy range of 100 MeV n-l to 10 GeV n-l, where the fluence rate is greatest, the baryon component consists of 87 percent protons, 12 percent helium ions, and one percent heavier ions (Simpson, 1983a). Typical energy spectra for four of the most numerous and important components (protons, helium ions, carbon ions, and iron ions) are given in Figure 3.5 (Simpson, 1983a). Their relative abundances vary only slightly with energy of the ion species. A compilation of relative abundances in the 2 GeV n-I energy region is shown in Figure 3.6 (Mewaldt, 1988). The notable features of these data are: (1)the sharp drop in abundance between protons (Z = I), helium 'Atwell, W. (1999). Personal communication. Data generated using Space Environment Information System (SPENVIS) on-line capability of the Belgian Institute for Space Aeronomy, B ~ s s e l s Belgium , (Boeing Company, Houston, Texas).

32

/

3. RAnIATION ENVIRONMENT IN LOW-EARTH ORBIT

Kinetic energy (MeV n-') Fig. 3.5. Typical energy spectra for protons, helium ions, carbon ions, and iron ions from "top to bottom," respectively, at solar minimum. The solid line is the local interstellar spectrum (Simpson, 1983a).

1

3.3 GALACTIC COSMIC RAYS

33

1a2 10

20

30

40

50

60

70

80

90

100

Nuclear charge (2) Fig. 8.6. Nuclear composition of GCR (-2 GeV n-I) (Mewaldt, 1988). (Z = 21, and the heavier nuclei; (2) the relative maxima in the abundances of the carbon-oxygen group (Z = 6 and 8), the neonmagnesium-silicon group (Z = 10, 12 and 14), and the iron group (Z = 26); and (3) the very sharp drop in abundance for nuclei heavier than iron. More extensive reviews of these and other features can be found in Mason (1987), Mewaldt (1983), Meyer (19851, and Simpson (1983b).

34

1

3. RADIATION ENVIRONMENT IN LOW-EARTH ORBIT

The slight energy dependence of the abundances is shown in Figure 3.7. Ratios of the abundance of each nuclear species at 0.2 GeV n-l to that at 2 GeV n-I are shown as a function of Z in the top graph, while the ratios at 15 GeV n-I to that at 2 GeV n-I are shown in the bottom graph. Species that are mainly of "secondary" origin (the odd Z elements), that is, those that were produced primarily by cosmic-ray collisions with interstellar gas, are shown as crosses. There is a noticeable decrease in the ratios of high-energy (15 GeV n-I) "secondary" nuclei to 2 GeV n-I "secondary" nuclei. The integral composition of GCR is shown in Figure 3.8 (modified from a graph from Mewaldt, 1988). Here the fluence of particles having a charge greater than or equal to Z is plotted as a function of the charge. The scale gives the number of particles per meter squared per year at solar minimum. It is interesting to note that roughly three nuclei per day with a charge greater than 78 pass through an area of 1m2. Therefore, if the nuclei were to penetrate the spacecrafl shielding without fragmenting, a space traveler might experience one such particle per day through the body. If 10 percent of the particles survive the shielding, a penetration of the body would occur once in 10 d. More accurate calculations such as high-Z hit frequencies require information on fragmentation cross sections as a function of energy for these very heavy high-energy nuclei.

3.3.2 Solar Modulation of Galactic Cosmic Rays The theory of GCR modulation by the sun and its environment has been developed extensively over the years. The fundamental equations were presented by Parker (1965) and involve parameters such as the size of the modulation region, the values of the components of the so-called "interplanetary diffusion tensor" and their spatial and energy dependencies, the values of which are largely unknown. The standard modulation model is considered to be quasisteady (time-independent) and spherically symmetric (McKibben, 1988). Time variations are the result of changing conditions in the solar wind. Maximum GCR fluence rates occur during the period of solar minimum activity. Reductions from the maximum level are typically symmetric around the maximum but on occasion are rapid and unexpected. Some early models relate the fluence rate at low energy to the fluence rates at energy levels measured by sea level neutron monitors and are accurate to about 20 percent (Evenson et al., 1983). The boundary of the heliosphere containing the solar wind is presently unknown but is certainly greater than 50 AU [astronomical

1

3.3 GALACTIC COSMIC RAYS

13-1

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O . l - " l ' l l l l l l l ~ l l l l l l t I 130l l l I I 1 l l b 0 10 20

Nuclear charge (Z) Fig. 3.7. (Top)Comparison ofthe cosmic-ray elemental composition measured a t -0.2 GeV n-l (Garcia-Munoz and Simpson, 1980) relative to that a t -2 GeV n-I (Englemann et al., 1983; 1990). (Bottom) Comparison of the -15 GeV n-' composition (Englemann et al., 1983) with that measured a t 2 GeV n-'. Elements that are mainly of "secondary" origin, produced by collisions of cosmic rays with the interstellar gas, are differentiated from "primary" species accelerated by sources of cosmic rays.

~

~

'

~

36

1

3. RADIATION ENVIRONMENT IN LOW-EARTH ORBIT

lo'

Nuclear charge (Z)

Fig. 3.8. The number of GCR per meter squared per year with charge greater than or equal to Z plotted as a function of Z for solar minimum conditions in free space (adapted from Mewaldt, 1988).

unit (where 1AU is equal to the mean distance of Earth from the sun or approximately 93 million miles)]. The total energy content in the GCR is small compared to the energy content in the solar wind. The boundary is thus not seen by the GCR as a barrier, and the particles respond only to the bulk properties of the solar wind

3.4

SOLAR PARTICLE EVENTS

1

37

medium through which they propagate. The solar wind is seen as a collection of radially moving scattering centers that appear as irregularities and fluctuations in the interplanetary magnetic field. The three main processes controlling the modulation are: (1)difision of the particles through the scattering centers with a mean free path of typically 0.3 AU in the vicinity of Earth; (2) convection of the particles by the solar wind which is moving outward from the sun at roughly 400 km s-I; and (3) adiabatic deceleration, that is caused by the expansion of the solar wind, effectively "cooling" the cosmic rays to lower energies. Energy losses can be quite large (hundreds of MeV for a 1GeV proton). Models using the diffusion coefficient as a function of momentum and position and the distance to the boundary as adjustable parameters have been quite successful in describing the modulation over recent solar cycles.

3.3.3

The Anomalous Components

At low energies, there is an "anomalousn component of the GCR, i.e., a component that causes a sharp increase in intensity with decreasing energy and that appears to be of a different origin than that of the high-energy component (Mewaldt, 1988). This ACR component is known to consist of six elements: helium, carbon, nitrogen, oxygen, neon and argon, with increased abundances below -50 MeV n-'. ACR have a larger radial gradient (- 15percent per astronomical unit) from the sun than do the GCR. The peak in the energy spectrum of the ACR is around 10 MeV n-' at solar maximum, slowly decreasing to less than 5 MeV n-' as solar minimum is reached (Cummings and Stone, 1988). The intensity of the ACR component is very sensitive to solar modulation, varying by a factor of 100 over the solar cycle. It is not expected that doses from the ACR component will contribute to astronaut radiation exposure since helium ions with of water equivalent shielding 50 MeV n-I can penetrate only 2 g and the heavier ACR components fail to penetrate even that far.

3.4

Solar Particle Events

As discussed by Smart and Shea (1997),there has been a significant change in thinking regarding the source of solar particle events (SPE). For nearly four decades it was assumed that SPE were produced by solar flares because the sometimeslarge transient increases in the particle fluence rate appeared to be associated with them.

38

/

3. RADLATION ENVIRONMENT IN LOW-EARTH ORBIT

Recently, a new paradigm has emerged where the generation of very energetic particles is thought to be the result of acceleration associated with interplanetary shocks generated by fast coronal mass ejections (Reames, 1995). Both scenarios have some merit. About one-half of the SPE observed at 1AU can be associated with specific solar flares, and the intensity time profiles for many SPE leave no doubt that acceleration by interplanetary shocks has occurred. SPE can vary widely in intensity and duration. At the present time there is no definitiveindicator that a particular region of activity on the solar surface will generate a significant SPE.

3.4.1 Propagation Characteristics Solar x rays and other types of electromagnetic radiations, traveling at the speed of light, reach Earth in approximately 8 min. Times for energetic solar particles to reach Earth vary from a few minutes for relativistic particles, whose kinetic energies are greater than several hundred MeV per nucleon, to hours for lower energy particles. Enhanced solar plasma emissions usually arrive at Earth within 1to 2 d and manifest themselves by geomagnetic disturbances and the familiar auroral displays. The duration of SPE can last from hours to days or weeks. For the extremely intense SPE of August 1972, nearly all of the hazardous energetic protons arrived at 1AU over a 15 h period beginning at 0700 on Greenwich mean time on August 1(Townsend et al., 1991). For the intense SPE of October 19 to November 10,1989, the hazardous energetic protons reached 1AU in several bursts over a 10 d period ending on October 29 (Simonsen et al., 1991; also see Golightly et al., 1992). Because solar x rays and other electromagnetic emissions travel in straight lines, their intensities a t Earth's orbit are nearly independent of the location of the event on the solar disk. The charged particles, however, travel along the interplanetary magnetic field lines which, during quiet conditions, are approximated by an Archimedean spiral. Therefore, the observed particle fluence rate during SPE is strongly dependent upon the heliolongitude of the flare with respect to the observation point in space. The time-intensity profile of typical SPE at 1 AU is depicted in Figure 3.9 (Shea and Smart, 1990).The general features are a propagation delay from the time of the event until the first particles are detected, a rise in intensity to some maximum, and a slow decay back to background levels. The onset time of SPE, the time of maximum intensity, the peak particle fluence rate, and the total fluence are all functions of the distance between the intersection ("footpoint")

3.4

SOLAR PARTICLE EVENTS

1

39

Start of increase Solar

I

Time of

Amplitude of maximum flux

Relative time -+ -am Propagation delay

to max

Fig. 3.9. Illustration of the general characteristics of SPE observed at 1AU (Shea and Smart, 1990).

of the interplanetary magnetic field line connecting the observer location with the sun and the heliolongitude of the flare itself. SPE in the eastern hemisphere (left half) of the solar disk, as seen by an observer looking a t the sun, typically have slower rates of rise. Those in the western hemisphere typically have a more rapid rise to maximum intensity because they occur closer to the "footpoint" of the interplanetary magnetic field line. Aside from the heliolongitude of the event itself, interplanetary conditions at the time of event occurrence will also affect the profile features. 3.4.2 Solar Particle Event Spectra and Composition In interplanetary space, SPE can significantly increase radiation levels above the GCR background. The largest SPE can have a fluence greater than 101° protons ~ m with - ~energies greater than 10 MeV arriving a t the orbit of Earth over a period of several days. They occur sporadically during the active period (solar maximum) of the 11y solar cycle. Typical integral fluence spectra are shown in Figure 3.10 for various events which occurred over the time span 1956 to 1989. The event of August 1972 is one of the largest ever recorded. SPE have softer (less energetic) spectra than GCR particles. During the period of August through December 1989, a series of large SPE occurred. One of these, the October 1989 event, was comparable in fluence and spectral intensity to the event of August 1972 (see Figure 3.10). A risk assessment comparison of interplanetary

40

1

3. RADIATION ENVIRONMENT IN LOW-EARTH ORBIT

1011 ,

Large Flare Fluence Spectra

Kinetic energy (MeV)

Fig. 3.10. SPE integral fluences (Townsend et al., 1991).

space crew exposure for these two SPE in terms of total dose equivalent has been performed (Townsend et al., 1991). In addition to protons, alpha particles and heavier nuclei have been measured in SPE. Most measurements are relatively recent and generally for particle energies less than 20 MeV n-l. The elemental composition is consistent with coronal material which has been accelerated to high energies. Because of the paucity of data for heavy ions in SPE, their potential contributionto the risk from SPE cannot be accurately quantified and is usually ignored because they are thought to be negligible. This assumption requires further study and analysis. 3.4.3

Solar Particle Event Measurements

Measurements of SPE-generated particles have been available on Earth since the early 1940sand systematic spacecraft measurements since the mid-1960s. A useful, continuous data base extends from the present back to about 1955 (Solar Cycle 19). The data base for Cycle 19 comes mainly from riometer (radio ionosphere opacity meter) and some spacecraft measurements. The data base for Solar Cycle 20 is derived from Earth-orbiting satellite measurements plus

3.4 SOLAR PARTICLE EVENTS

1

41

simultaneous polar riometer measurements. The data for Cycles 21 and 22 are primarily from sensitive spacecraft instruments (Smart and Shea, 1997) on board geosynchronous and polar-orbiting weather satellites. The Geostationary Operational Environmental Satellite provides continuous proton monitoring and constant data transmission. Polar orbiting National Oceanic and Atmospheric Administration weather satellites will provide actual particle fluence rates detected over the polar caps when polar-orbiting spaceflights begin. The level of solar activity is usually correlated with sunspot number or ground-level neutron monitor count rates. The temporal distributions of relativistic SPE and smoothed sunspot number are displayed in Figure 3.11. All events were detected by ground-level neutron monitors and are called ground-level events. The largest ground-level event ever recorded occurred on February 23, 1956. The associated flare, at 80°W heliolongitude, was a t the footpoint of the magnetic field lines connectingEarth with the sun. Particles with kinetic energies in excess of 17 GeVwere recorded from this event. Most SPE yield proton spectra which are either too sparse or too soR (few, if any, relativistic protons) to present any significant

Frequency

Year

Source posilion

To &rth

Fig.3.11. The observed high-energy solar-proton events (E> 450 MeV) over three solar cycles. The top part of the Figure shows the smoothed sunspot number. The bottom part of this Figure shows the number of high-energy SPE (ground-level events) each year. The right part of the Figure shows the location of the source of the solar flare on the sun (Shea and Smart, 1990).

42

/

3. RADIATION ENVIRONMENT IN LOW-EAFtTH ORBIT

radiation hazard to crews in space. Occasionally, an extremely large event occurs, such as the one in August 1972 or in October 1989. Generally, even for these extremely large events, the radiation exposure to crews conducting missions in LEO will be small because the intrinsic shielding provided by Earth's magnetic field is adequate. For example, during the larger flare of October 1989, no measurable SPE doses were received by Space Shuttle crews (Golightly et al., 1994) and only 30 to 40 mGy additional dose was received in the Mir Space Station. However, if a large SPE is accompanied by a large geomagneticdisturbance, such as actually occurred during November 1960 or August 1972, then doses to blood-forming organs on the order of 100 mGy (Wilson et al., 1990) may occur for a high-inclination orbit in LEO. Although the probability of occurrence of such a scenario is thought to be small, this scenario deserves further study, especially for the ISS shield configuration and orbital parameters.

Radiation Exposure to Personnel -

4.1 Introduction

In order to arrive a t realistic assessments of the risk posed by the radiation to which astronauts will be exposed on a given mission, estimates or measurements must be made of the amount and type of radiation to which various critical body organs might be exposed. Quantitative, prospective estimates of such exposures are fraught with many uncertainties, including: (1)the definition of the space radiation environment; (2) the effective shielding available within the spacecraft, taking into account the movement of the astronauts throughout the vehicle and outside in EVA, orientation of the spacecraft in an anisotropic radiation environment, and the movement of consumables during the mission; (3) the predictions of the onset, severity, and duration of SPE; and (4) quantities and methods used to assess exposure. This Section describes the measurements that have been made during LEO missions.

4.1.1 Absorbed Dose and Dose Equivalent The SI unit of absorbed dose (D), the gray (Gy), is defined such that 1 Gy is equal to the net absorption of 1J of energy in 1kg of any material. For radiation protection purposes, the material absorbing the energy is usually taken to be muscle tissue. However, bone marrow or other tissues are used when appropriate. Since it has been well established experimentally that radiations with different qualities have different degrees of effectiveness for producing biological effects, quality factor (Q)for stochastic effects was introduced to weight D to account for these differences. The product of Q and D at a point in tissue is the radiation protection quantity, dose equivalent (H). The special name for the unit of dose equivalent is the sievert (Sv).Recommended values for Q have generthe unrestricted linear collision ally been made in terms of LET (La),' 'In this Report, L, is denoted by L or LET.

44

4. RADIATION EXPOSURE TO PERSONNEL

stopping power in water. The dependence of Q on LET is shown in Figure 4.1. For a radiation environment consisting of mixed components of low- and high-LET radiation, the distribution of D a t the point of interest was multiplied by Q a t the appropriate LET when integrating over the total LET spectrum to obtain H a t a point in tissue as follows: where Q(L) is the quality factor a t LET (L), and D(L) dL is the absorbed dose a t a point in tissue between L and L + dL. The absorbed dose (D) is J D(L) dL. The average value of Q a t a point in tissue could then be written as:

4.1.2

Current Recommendations of the International Commission on Radiological Protection and the National Council on Radiation Protection and Measurements

In 1991, the ICRP revised its recommendations in this area (ICRP, 1991a). To quote: "The Commission now believes that the detail and precision inherent in using a formal Q-L relationship to modify absorbed dose to reflect the higher probability of detriment resulting from exposure to radiation components with high LET is not justified 30

-

20

--

L

2

0

.-

r

.-m

ZI

s -10

0,

0.1

1

10 LET (keV pm-')

100

1000

Fig. 4.1. Q as a function of LET in keV pm-'based on the recommendation in ICRP Publication 60 (ICRP, 1991a; NCRP, 1993a) and ICRP Publication 26 (ICRP, 1977).

4.1

INTRODUCTION

45

1

because of the uncertainties in the radiobiological information. In place of Q, or more precisely g,the Commission now selects radiation weighting factors, WR, based on a review of the biological information, a variety of exposure circumstances and inspection of the results of traditional calculations of the ambient dose equivalent." The NCRP (1993a) endorsed the values for wRselected by ICRP (1991a) with the exception of the wRfor protons. The ICRP and the NCRP recommended values for wR for various types of radiation are given in Table 4.1. The product of wRand the dose averaged over a specific organ or tissue (T) due to radiation (R) incident on the body is called equivalent dose and is denoted HT: For radiations not included in Table 4.1, the NCRP (1993a) endorsed the ICRP (1991a) Q(L) relationship provided in Table 4.2, as an approximation for WR. The new Q(L)relationship is illustrated in Figure 4.1. For w~values not given in Table 4.1, the ICRP and the NCRP recommend that Q(L) be averaged over the D(L) spectrum at a depth of 10 mm in an ICRU sphere. Even for the radiations given in Table 4.1, the differences between Q determined at the recommended depth in the ICRU sphere and the depths that correspond to tissues or organs of interest are thought to be small in comparison to the uncertainties associated with the radiobiological TABLE 4.1-Radiation

weighting factors (NCRP,1993~).

Type and Energy Range

Photons, all energies Electronsn, positrons and muons, all energiesb Neutrons, energy I00 keV to 2 MeV >2 MeV to 20 MeV >20 MeV Protons, other than recoil protons, energy >2 MeV Alpha particles, fission fragments, nonrelativistic heavy nuclei

20

"Excludingauger electrons emitted from nuclei bound to DNA which must be measured by microdosimetry, bAllvalues relate to the radiation incident on the body or, for internal sources, emitted from the source. 'In circumstances where the human body is irradiated directly by >I00 MeV protons, a W E of about unity would be appropriate. dICRP (1991a) suggested a value of five.

46

/

4. RADIATION EXPOSURE TO PERSONNEL

TABLE 4.2-Quality factor-LET relationships." Unrestricted Linear Energy Transfer, L. in Water (keV km-l)

100

&GIb 1 0.32 L, - 2.2' 300 (L,)-%

"Adapted from Table A-1 of ICRP (1991a). bWithL expressed in keV pm-l. 'For example, for L = 60 keV pm-l, Q = (0.32 x 60) - 2.2, or 17. All calculations of Q using the data in Table 4.2 should be rounded to the nearest whole number.

information that forms the basis for the Q ( L ) relationship. The energy dependence of the calculated using the ICRP Q(L)relationship, is illustrated in Figure 4.2 (Shim and Wilson, 1991). The effective dose (E) has associated with it the same probability of the occurrence of effects whether received by the whole body via uniform irradiation or by partial body or individual organ irradiation.

a,

1

10

100

1,000

10,000

Energy (MeV n-l) Fig.4.2. Q of various ions as a function of energy using the Q(L) relationship in ICRP Publication 60 (Shinn and Wilson, 1991).

4.1 INTRODUCTION

1

47

While an assumption of uniformity may be a sufficient approximation in many external irradiation cases, in others more precise evaluations of individual tissue doses will be necessary. With external irradiation, differences may arise with depth in the body and with orientation of the body in the generally nonuniform radiation field. Tissues also vary in their sensitivity to radiation. Effective dose (El is a concept similar to the effective dose equivalent used by ICRP (1977) and NCRP (1987b). Effective dose (E) is intended to provide a means for handling nonuniform irradiation situations, as did the earlier effective dose equivalent. The effective dose (E) is the sum of the weighted HTfor all irradiated tissues or organs. The tissue weighting factor (wT)takes into account the relative detriment to each organ and tissue including the different mortality and morbidity risks from cancer, the risk of severe hereditary effects for all generations, and the length of life lost due to these effects. The risks for all stochastic effects will be the same whether the whole body is irradiated uniformly or nonunifomly if:

where WT is the tissue weighting factor representing the proportionate detriment (stochastic)of tissue (TI when the whole body is irradiated uniformly, and HT is the equivalent dose received by tissue (T). The ICRP (1991a) showed that for the evaluation of the relative contribution of cancer in various organs to the total cancer risk, that the model used for the transfer of risks from one population to another, as well as the special characteristics of some national populations, can be more important than variables such a s sex and age. The derivation of w~values included primarily the relative fatal cancer probabilities for each tissue as noted above. There were modifications to reflect the relative length of life lost for each cancer. The derivation also included a component of the nonfatal cancer risk, an average of about 20 percent and a genetic component which was also about 20 percent was included. The values of wT are rounded and simplified values developed for a reference population of equal numbers of both sexes and a wide range of ages. In addition, the astronaut exposure is external and primarily whole body in which case the small differences in the values of wTare considered of minor importance. This Report adopts wTvalues given in Table 4.3. For completeness the excess lifetime risk of radiation-induced cancer (incidence) by organ, sex and age at exposure are given in Table 5.14 and Appendix A for different exposure scenarios. In addition, lifetime cancer

48

1

4. RADIATION EXPOSURE TO PERSONNEL

TABLE 4.3-wT for different tissues and organsa (adapted from ICRP, 1991a and NCRP,1 9 9 3 ~ ) . 0.01

0.05

0.12

0.20

Bone surface Skin

Bladder Breast Liver Esophagus Thyroid RemainderbsC

Bone marrow Colon Lung Stomach

Gonads

"The values have been developed for a reference population of equal numbers of both sexes and a wide range of ages. In the definition of E, W Tvalues apply to workers, to the whole population, and to either sex. These W T values are based on rounded values of the organ's contribution to the total detriment. bForpurposes of calculation, the remainder is composed of the following additional tissues and organs: adrenals, brain, small intestine, large intestine, kidney, muscle, pancreas, spleen, thymus, and uterus. The list includes organs which are likely to be selectively irradiated. Some organs in the list are know to be susceptible to cancer induction. If other tissues and organs subsequently become identified as having a significant risk of induced cancer, they will then be included either with a specific W T or in this additional list constituting the remainder. The remainder may also include other tissues or organs selectively irradiated. 'In those exceptional cases in which one of the remainder tissues or organs receives an HTin excess of the highest dose in any of the 12 organs for which a weighting factor is specified, a weighting factor of 0.025 should be applied to that tissue or organ and a weighting factor of 0.025 to the average dose in the other remainder tissues or organs (ICRP, 1991a).

incidence risks from radiation exposure on the STS and ISS have recently been addressed (Peterson and Cucinotta, 1999). In view of the extensive data for the radiations encountered in space activities, this Report adopts the determination of the dose equivalent at a point (H)as calculated by Equation 4.1, i.e.:

The integration of Equation 4.5 over the tissue of interest results in the organ dose equivalent (ICRU, 1993). The effective dose (El is then taken to be equal to the summation of the product of the organ dose equivalents and w T .This approach produces an acceptable approximation to the formulation given in Equation 4.3.

4.2

DOSIMETRY INSTRUMENTATION USED IN LEO

/

49

4.2 Dosimetry Instrumentation Used in Low-Earth Orbit Missions Space radiation measurements are made for three fundamental reasons: recording of crew exposures for medical history records, measurement of the temporal and spatial variations in the radiation environment as a function of radiation species and energy distribution, and for the development andlor improvement of radiation environment models and radiation transport (shielding) codes. The creation of an artificially trapped electron belt by the highaltitude nuclear explosion Starfish on July 9, 1962, mandated the use of some radiation dosimeters aboard the Mercury Spacecraft MA-8 launched October 1962. It was determined that some electrons in the area of the SAA might be encountered at altitudes as low as 100 km.Dosimeters selected for that flight included a self-indicating ionization chamber (pocket type), lithium fluoride thermoluminescent dosimeters, and nuclear emulsion film packets. This system, with some significant modifications, is currently used to monitor crew radiation exposures on the Space Shuttle.

4.2.1 Heavy-Ion and Neutron Measurement Benton (1986) used plastic track detectors to detect ions of Z > 6 on Space Shuttle flights. CR-39 polycarbonate, cellulose nitrate, and Lexan were arranged in a stack. High-energy ions which pass through the plastic produce trails of ionization which are later enlarged by chemical etching and analyzed using optical microscopy. The LET of the ion which made the track can be obtained from the hole diameter and track cone. The detectors are calibrated using ions of known energy and charge. A particle spectrometer designed specifically to measure the heavy-ion spectrum has been recently developed and flown by Badhwar et al. (1995a). Designated the PHIDE (Proton Heavy-Ion Detection Experiment), the system also has the capability to measure proton spectra. Total energy response range of PHIDE is approximately 15 to 420 MeV n-l, using dE/dx, total E, and Cerenkov techniques. The system can measure mass, energy and charge up to 100 MeV n-', and charge and energy only beyond 100 MeV n-l. The system is essentially a solid-state telescope utilizing positionsensitive lithium-drifted detectors, and a 1 cm thick Cerenkov detector, all of which are surrounded by anti-coincidence plasticscintillator detectors. The system is triggered by charged particles depositing energy that is equivalent to a 13 MeV proton in the first

50

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4. RADIATION EXPOSURE MPERSONNEL

two solid-state detectors. Signals in the detectors (dE/b: and total E ) are pulse-height analyzed using a 4,096 channel analog-to-digital converter, with information stored on two 20 mb hard disks. Keith and Richmond (1987)measured the thermal and epithermal neutron fluence aboard Space Shuttle Mission 61-A using iridium, tantalum and scandium activation foils. They measured average thermal and epithermal neutron fluence rates within the spacecraft of 2.36 n ~ r n min-I -~ and 0.51 n cm-= min-l, respectively. Jn an experiment to measure the fast-neutron spectrum inside the spacecraft, Keith et al. (1992) compared secondary-neutron and trappedproton H rates measured on Space Shuttle flights (Table4.4).Activation foils were placed in plastic (Bonner) spheres of different diameters to detect the neutrons. The neutron fluence rate is a fbnction of the amount of high Z spacecraft shielding. A neutron Q of 20 was assumed. Dose-equivalent rates for neutrons were 2.5 times less than for trapped protons at 300 km and 14 times less at 600 km. Badhwar et al. (1996a) measured the average dose equivalent from neutrons with energies less than 1MeV to be 2.53 pSv d-I on STS-60. This value is consistent with the findings of Keith et al. (1992). Lobakov et al. (1992) have flown an active neutron spectrometer on the Mir Orbital Space Station, and have mapped the SAA, with peak fluence rates of secondary neutrons reported a t approximately 25 n s 'I. Dudkin et al. (1994), using a proton recoil technique, have measured the neutron energy spectra on two Space Shuttle missions a t 28.5 degrees. The technique permits the calculation of the fast-neutron spectrum using the measured recoil-proton energy spectrum generated as a result of the elastic (neuton, proton) scattering of neutrons from the hydrogen in a nuclear emulsion. They showed that the dose equivalent from 1 to 15 MeV neutrons in the Space Shuttle middeck varies from 54 FSV d-' at a 290 km altitude to 174 pSv d-I a t 462 km in the middeck locker. Similar TABLE 4-4-Comparison of secondary-neutron and trapped-proton dose equivalent rates." Duration Flight

(d)

Altitude (km)

STS-4 STSd STS-6 STS-31

7.0 5.1 5.0 5.0

297 297 284 617

Proton Dose Equivalent Rate (mSv d-')

Neutron Dose Equivalent Rate (mSv d-')

0.054 0.043 0.048 1.660

0.022 0.023 0.013 0.118

"The dose rates were computed using measurements made on Space Shuttle flights with an inclination of 28.5 degrees (Keith et al., 1992).

4.2 DOSIMETRY INSTRUMENTATION USED IN LEO

1

51

neutron spectral measurements (from 1to 15 MeV) have been made on STS-65. Badhwar et al. (1998a) showed that the fast-neutron contribution (1to 20 MeV) increases rapidly with altitude indicating that trapped-belt protons are the major source in this range. A workshop was held by NASA in 1998 to discuss the relative contribution of secondary neutrons to H that may be incurred by the crews on ISS based on the measurements made on the Space Shuttle and Mir Space Station. It was concluded that neutrons could contribute a significant fraction of the total H and that improvements in dosimetry and transport models were required?

4.2.2

Linear Energy-TransferSpectral Measurement

Benton and Parnell(1988) measured average LET spectra on several United States and Soviet manned spaceflightsusing plastic etch detectors. More recently, Badhwar et al. (1992; 1994; 1995a; 1995b) estimated LET spectra inside the Space Shuttle using a TEPC.3At lower altitudes the only contribution from trapped-belt radiation is obtained during orbits which pass through the SAA. Outside the anomaly region, GCR are the dominant source of radiation a t low altitudes. For that reason it is possible to easily separate the LET spectra from trapped-belt particles and GCR radiation. Figure 4.3 shows the LET spectral measurements in the middeck location and payload bay for several Space Shuttle flights (Badhwar et al., 1994). When the calculated AP-8 spectrum is normalized to these measurements, there is good agreement in the 5 to 100 keV km-l region, but the model overpredicts the fluence rate below 5 keV pm-l. TSPC measurements made on 14 Space Shuttle flights obtained an Q for trapped radiation is in the range 1.7 to 2.1, or approximately 30 to 50 percent higher than given in NCRP Report No. 98 (NCRP, 1989). These differences are attributed to the f a d that Q based on environment and radiation transport models in the past have not included all nuclear cross sections important in the production of high-LET secondaries.

sNASAWorkshop: Predictions and Measurementsof Secondary Neutrons in Space, September 1998, University Space Research Association, Houston, Texas. Vhe TEPC does not directly measure the LET spectra. However, it does measure the lineal energy (y) spectra and the difference between the LET and y spectra in a mixed field of large energy and charge variation is small. Under these circumstances y spectracan be used to estimate LET spectra. The maximum effect of this substitution on Q can be as much as 20 to 40 percent.

1

52

4. RADLATION EXPOSURE TO PERSONNEL

106

,lo"

I

I

'

"'""I

'

'

"""I

'

'

'""'I

'

.

I . .

JUN '93

Linear energy transfer (tissue, keV Fm-') Fig. 4.3. Integral fluence rate of trapped particles in the Space Shuttle middeck from three missions, STS-57, STS-60, and STS-61 as measured by a TEPC (Badhwar et al., 1996a).

4.2.3

Charged-Particle Spectrometry

Charged-pa~ticlespectrometers have been used on manned spacecraft since the Gemini program. Two proton-electron spectrometers were flown on Gemini N and VII by Reagan in 1965 (Reagen et al., 1968). These spectrometers measured protons from 23.5 to 80 MeV and electrons from 0.45 to 6 MeV in 16 discrete channels. During analysis of PHIDE data (see Section 4.2.1), a scatter plot of energy losses in the first two detectors revealed an easy separation of all light ions. Figure 4.4 shows that there was a rather significant production of 2H and 3Hions as well as 3He and 4Heions within the spacecraft at the PHIDE location during STS-48. These ions are produced by interactions of the trapped protons with the Space Shuttle vehicle structure, and imply that there is also a substantial

4.2 DOSIMETRY INSTRUMENTATION USED IN LEO

F

E

1

53

20 ' 5 ,

W

10

. .. 0

.

0

'

' - !

" '

10

20

30

40

50

Energy loss in A, (MeV)

Fig. 4.4. Scatter plot of the energy loss in the first two solid-state detectors on PHIDE. These preliminary data from STS-48 clearly show a distribution of light ions in the Space Shuttle middeck (Badhwar et al., 1996a).

fluence of secondary protons that cannot be separated from the primary trapped protons. The proton spectra measured by PHIDE on STS-37 contains both primary and secondary particles and is shown in Figure 4.5. Results from a vector fluence model of Kern (1994) which used AP-8 model data are also shown. The agreement between observations and model is quite poor. The observed fluence rate at energies below 50 MeV, if pitch-angle corrections are not applied to the model, is as much as a factor of five greater than that predicted by the model at the lower energies where the contribution of secondary protons is quite significant. Similar comparisons of observed secondary 2Hand 3H enerm spectra with the AP-8 MAX model also have substantial disagreements.

54

1

4. RADIATION EXPOSURE TO PERSONNEL

.

1 .

,

.. .

.

:.

. ......

:+ 28.5"u 443 km

.

ObS8wsd

. . :P APE MAX -Vector Flux

0

50

100

150

200

250

300

350

400

Kinetic energy (MeV)

Fig. 4.5. Observed differential energy spectrum of protons in the Space Shuttle middeck compared to the AP-8 MAX model, with vector fluence rate corrections by Kern (1994). The presence of light ions implies a substantial fluence rate of secondary protons as well. The proton spectrum measured by PHIDE on STS-37 contains both primary and secondary particles (Badhwar et al., 1996a).

4.3 Space Crew Member Exposures in Low-Earth Orbit With the exception of a few selected Apollo missions, the bulk of crew member exposure to space radiation has resulted from GCR and trapped protons. Electrons have contributed very little to total dose. Figure 4.6 shows the relative contributions of trapped protons and electrons, computed from the AP-8 and AE-8 models versus shielding. 4.3.1

Dose Rate

Dose rate is an important factor that influences the biological effects of ionizing radiation. The risk resulting from exposure

4.2 SPACE CREW MEMBER EXPOSURES IN LEO

1

55

Indination = 28.5' o TolalDose Proton Dose

10-61 1v3

10"

10-1 lo0 Shield thickness [g cm-* (aluminum)]

10'

Fig. 4.6. Relative contributions to the total dose from trapped protons and electrons computed from AP-8 and m-8models for aluminum shielding. Protons are the dominant source of dose for shielding thicknesses >0.15 g ~ m - ~ aluminum. of Proton doses are 100 times greater for shielding thickness >I g ~ m - The ~ . bremsstrahlung contribution was also calculated from web based public domain software (SPENVIS) (Atwell, 1999)'".

depends on the total dose, the radiation quality, and the dose rate. In general, the dose rate of the radiation in LEO increases with altitude, but of greater importance is whether or not the exposure occurs within the radiation belts. In LEO a spacecraft traverses the SAA. The length of time spent in the SAA depends on the altitude and orbital inclination of the spacecraft. In the case of Space Shuttle mission STS-40, for which the orbital inclination was 39 degrees and the altitude was between 278 and 296 km,the duration of the traversals varied from 8 to 31 min with an average of 19 min (Badhwar et al., 1992). Measurements of dose rate and lineal energy spectra have been made on a number of Space Shuttle missions. The lineal energy spectrum measurements have allowed the separation of the contribution 'OAtwell, W. (1999).Personal communication. Data generated using Space Environment Information System (SPENVIS) on-line capability of the Belgian Institute for Space Aeronomy, Brussels, Belgium (Boeing Company, Houston, Texas).

56

1

4. RADIATION EXPOSURE TO PERSONNEL

of the trapped particles from GCR. Both the altitude and orbital inclination of these missions varied ranging from about 215 to 594 k m and from an inclination of 28.5 to 57 degrees. In Figure 4.7, the dose rate measured on the STS-40 is shown. The spikes in the data for dose rate reflect the traversals through the SAA. It can be seen that even within the SAA the dose rate rises to less than 2 pGy min-l. Integrating over 1 d, the dose is about 0.096 mGy. In the Space Shuttle mission STS-31 at 617 k m and 28.5 degrees, the dose rate was considerably greater, 1.642 mGy d-', but at a level at which the biological effects are independent of dose rate. These results indicate that the exposures experienced on missions in LEO will all be in the low dose rate range. A low dose rate has been defined by UNSCEAR (1993) as less than 0.1 mGy min-l. In the case of SPE during deep-space missions the dose rate will rise, but

Mission elapsed time (min) Fig. 4.7. Dose rate in mGy min-I x as a function of elapsed time in minutes. Measurements made on STS-40with an orbital inclination of 39 degrees and an average altitude of 287 km (278to 296 km) (Badhwar et al., 1992).

4.2 SPACE CREW MEMBER EXPOSURES IN LEO

1

57

will still remain in the low dose rate range for biological effects with the exception of a short period in the largest SPE (Parsons and Townsend, 2000). The mean daily dose rates experienced by the crews of 35 Space Shuttle missions measured by passive TLD dosimetry are shown in Table 4.5. It can be seen that the dose rates vary considerably and are influenced by both altitude and the orbital inclination.

4.3.2

Space Radiation Environments for Low-Earth Orbit Space Programs

4.3.2.1 Mercury. The last two missions of the Mercury program represented the first radiation measurements in space made by the United States on manned spacecraft. A significant enhancement of the electron population of the trapped belts was produced by the Starfish high-altitude nuclear detonation on July 9, 1962. The creation of this artificial electron belt approximately three months prior to the eighth Mercury-Atlas mission (MA-8) on October 3, 1962 led to the placing of radiation dosimeters aboard the spacecraft. The last three orbits of the mission passed through the SAA. Dosimeters used on the mission included a 0 to 100R self-indicatingion chamber, lithium fluoride thermoluminescent dosimeters, and nuclear emulsion packages. The ionization chamberwas attached to the inner wall of the egress hatch, while the epoxy package of thermoluminescent dosimeters, films and nuclear emulsions were located near instrumentation consoles. The results, reported by Warren and Gill (19641, demonstrated that the bulk of the dose was due to protons in the SAA, and very little of it was attributable to electrons. Essentially the same instrumentation was flown the followingyear on MA-9, which was launched on May 15, 1963. One significant difference however was the inclusion of a dual Geiger counter system (one shielded and one collimated) exterior to the spacecraft. The Geiger counters, with thresholds higher than the anticipated proton fluence rates, demonstrated that the Starfish electrons had decayed to a level between 10 and 20 percent of the July 1962 value (Warren and Baker, 1965). 4.3.2.2 Gemini. By the time of the launch of the first two manned missions in the Gemini program in 1965, it was recognized that judicious selection of the spacecraft orbit could be used as a missionplanning criterion to minimize crew radiation exposures. For example, EVA could be planned to be conducted in passes not involving the SAA. Thus, for the first time, premission calculations of expected

58

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4. RADIATION EXPOSURE TO PERSONNEL

TABLE 4.5-Mean daily dose rates of Space Shuttle crews measured by passive TLDs (adapted from Richmond and Hardy, 1994)." Flight

STS-1 STS-2 STS-3 STSd STS-5 STS-6 STS-7 STS-8 41-A 41-B 41-C 41-D 41-G 51-A 51-C 51-D 51-B 51-G 51-F 51-1 515 61-A 61-B 61-C STS-26 STS-27 STS-29 STS-30 STS-28 STS-34 STS-33 STS-32 STS-36 STS-31 STS-41 STS-38 STS-35 STS-37 STS-39

Launch Date

12 Apr 81 12 Nov 8 1 22 Mar 82 02 J u n 82 11Nov 82 04 Apr 83 18 J u n 83 30 Aug 83 28 Nov 84 03 Feb 84 06 Apr 84 30 Aug 84 05 Oct 84 08 Nov 84 24 Jan 85 12 Apr 85 29 Apr 85 27 J u n 85 29 J u l 8 5 27 Aug 85 03 Oct 85 30 O d 85 26 Nov 85 12 J a n 86 29 Sep 88 02 Dec 88 13 Mar 89 04 May 89 08 Aug 89 18 Oct 89 22 Nov 89 09 Jan 90 28 Feb 90 24 Apr 90 06 Oct 90 15 Nov 90 02 Dec 90 05 Apr 91 28 Apr 91

Duration (h)

Altitude

(km)

Inclination (degrees)

Dose Rate (mGy d-')

4.2 SPACE CREW MEMBER EXPOSURES IN LEO

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59

TABLE 4.5-Mean daily dose rates of Space Shuttle crews measured by passive TLDs (adapted from Richmond and Hardy, 1994)." (continued) Duration Flight

Launch Date

(h)

Altitude (km)

Inclination (degrees)

Dose Rate (mGy d-l)

05 J u n 91 02 Aug 91 09 Sep 91 24 Nov 91 22 J a n 92 24 Mar 92 07 May 92 25 J u n 92 12 Sep 92 22 Oct 92 02 Dec 92 13 J a n 93 08 Apr 93 26 Apr 93 21 J u n 93 12 Sep 93 18 Oct 93 02 Dec 93 03 Feb 94 09 Apr 94 08 Jul94 09 Sep 94 30 Sep 94 03 Nov 94 02 Mar 95 "Data added from Hardy, A.C. and Golightly, M.J. (1996). Personal communication (NASA Johnson Space Center, Houston, Texas).

radiation exposures could be used in mission-planning activities. As an example, Gemini XI was specifically programmed to miss the SAA, to protect a nuclear-emulsion cosmic-ray experiment although two of its 44 orbits were at apogees of almost 1,400 km.The total average dose for the mission was less than 0.40 mGy (Richmond, 1972). With two other notable exceptions, all of the Gemini flights were conducted at low altitudes and noncircular orbit with apogees of 300 ? 40 km.For these missions, average daily crew doses were consistent with exposures expected from GCR and the traversals of the SAA.

1

60

4. RADIATION EXPOSURE TO PERSONNEL

Crew radiation exposures for the Gemini missions were measured with packets containing lithium fluoride and nuclear emulsions placed in four locations on each crew member. A portion of the Gemini X mission had two passes through the SAA a t an altitude of 760 Inn.A special active dosimeter system, consisting of two 10 cm3 tissue-equivalent ionization chambers, measured a dose for that mission of 9.1 mGy (Richmond, 1972). Average doses to the crew for the Gemini program are presented in Table 4.6.

Apollo. Although not LEO missions, the measurements made on the Apollo mission traversing the radiation belts are of interest. These missions demonstrated that the trapped radiation belts would be of negligible importance in total crew exposure because of the short time spent in the belts. Since the advent of the Mercury program in 1961, much effort has been directed toward the analysis of the hazards associated with exposure to extraterrestrial sources of radiation and toward adequate measurement of those sources. The Mercury and Gemini programs showed that radiation presents few problems to low altitude, limited duration Earth orbital flights. Limited excursions at moderate altitudes were also made without significant exposure to astronauts. The more complex nature of the Apollo lunar missions, however, involved a greater uncertainty in radiation exposures.Once the spacecraft leaves the protection of Earth's magnetic field, it becomes vulnerable to energetic particles produced in SPE. Since t of crew this radiation environment could be ~ i ~ c a inn terms safety and mission success, it was recognized that a more sophisticated operational dosimetry system was required (Richmond, 1969). 4.3.2.3

TABLE 4.6-Gemini mission parameters and averaged D using TLD (Richmond, 1972). Gemini Mission

I11

Iv v

VII VI-A VIII IX-A X XI XI1

Launch (date)

23 Mar 65 03 Jun 65 21 Aug 65 04 Dec 65 15 Dec 65 16 Mar 66 03 Jun 66 18 Jul66 12 Sep 66 11 Nov 66

Apogee

(km)

Perigee (km)

Number of Orbits

Inclination (degree)

D (mGy)

4.2 SPACE CREW MEMBER EXPOSURES IN LEO

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61

Dose measurements of the Apollo program are presented in Table 4.7. These results a r e compared to t h e integrated dose values obtained by the Van Allen Belt Dosimeter (VABD). Differences in measurements are attributed to the differences in localized shielding around the detector systems. The VABD was in a fmed location, whereas the passive dosimeters were worn by crew members who moved freely about the spacecraft and on the lunar surface. Skylab. Skylab was placed into a 435 k m circular orbit a t an inclination of 50 degrees in July 1972. Skylab was visited during three subsequent flights by groups of three astronauts. It was vacated on February 8,1974. The mean mission doses measured by crew thermoluminescent dosimeters on these three Skylab missions are shown in Table 4.8 (Bailey et al., 1977). The uncertainty is a measure of the variation between doses measured for the various 4.3.2.4

TABLE4.7-Apollo calculated a n d measured dose comparisons using TLD and the VABD, a n active ionization chamber system (adapted from Richmond and Hardy, 1994). Apollo Mission

Calculated Skin TLD Skin Dose Dose ( r n G ~ ) ~ (rnG~)~

10 11 12 13 14 15 16 17

6.8 2.1 9.2 4.6 8.3 3.6 6.1 5.5

4.8 1.8 5.8 2.4 11.4 3.0 5.1 5.5

VABD Skin Dose (rnGyY

VABD Depth Dose (mGy)

6.6 2.0 12.0 3.1b 8.2 3.2 4.9 5.1

4.3 1.8 7.3 2.2 5.1 2.8 3.6 3.7

"Calculated skin dose using AP-8 proton model and Apollo shielding distribution. bBaileyet al. (1977). White et al. (1972).

TABLE4.8-Skylab

crew member exposures (Bailey et al., 1977)."

Skylab Mission

Duration (d)

Mean Dose (mGy)

2 3 4

28

17.0 1.0 38.7 + 3.0 73.9 -C 6.1

59 90

+

"TheSkylab orbit was at 435 km and 50 degrees inclination.

62

1

4. RADIATION EXPOSURE TO PERSONNEL

crew members rather than an indication of the accuracy of the measurements. The estimated accuracy of the measurements is about -+ 10 percent. The values are considered to be equivalent to a skin dose. The doses obtained by crew members on Skylab 4 are the highest to which United States astronauts have been exposed to date. The differences in the average daily dose rate from the above table are attributable to moving from solar maximum to solar minimum, i.e., the proton fluence rates were increasing a t that altitude. Dose rate on Skylab 4 was in excess of that predicted for the ISS. The reasons for this excess are differences in shielding, altitude and stage of the solar cycle between Skylab 4 and the planned ISS. 4.3.2.5 Space Transport Shuttle. STS-1, the first Space Shuttle flight, was launched on April 12,1981. As of May 1995, there have been 67 successful Space Shuttle flights with crew sizes ranging from two to eight. Mission durations have been as short as 2 d and as long as 16 d. Orbital altitudes have been between 215 and 617 km; inclinations have been between 28.5 and 62 degrees. Table 4.5 lists the daily mean dose rates (equivalent to skin doses) measured by crew passive thermoluminescent dosimeters on Space Shuttle flights. Figure 4.8 is a plot of the daily dose rates versus altitude for a sample of flights. For altitudes greater than 450 km, higher dose rates were measured on flights with inclinations <38 degrees. Below 450 km, GCR contribute a significant fraction of the dose. Above that, trapped protons become the dominant source of the radiation dose. Measured dose rates vary between 0.035 mGy d-l a t 215 km (STS-38) and 1.642 mGy d-l a t 617 km (STS-31). The uncertainty of these measurements is about seven percent. Using a Q of two, the dose-equivalent rates are between 0.07 and 3.2 mSv d-'. For LEO a t 28.5 degrees inclination, the skin and bone-marrow daily dose rates are 0.1 to 4 mSv d-l and 0.08 to 3 mSv d-', respectively. The maximum instantaneous H rates for skin and bone are 0.2 and 0.15 mSv min-', respectively.

Mir Space Station. The Russian Mir Space Station has a slightly elliptical orbit with a mean altitude of about 400 km and an inclination of 51.6 degrees. Nguyen et al. (1989) measured doses with a low-pressure TEPC during the FrenchlSoviet space mission, Aragatz. The mean dose rate and dose-equivalent rate obtained during near-solar-maximum in December 1988 were 0.32 mGy d-l and 0.62 mSv d-', respectively. A neutron component of 0.023 mSv d-' was obtained using a bubble detector. The mean dose rate and dose-equivalent rate measured during March and April 1989 are 4.3.2.6

4.2 SPACE CREW MEMBER EXPOSURES IN LEO

1

63

Inclination <38 degrees Inclination >38 degrees

Shuttle altitude (km) Fig. 4.8. Mean dose rates measured using crew passive dosimeters on Space Shuttle flights (Hardy et al., 1992). Below 425 km, GCR are the predominant source; above that, trapped-belt protons become dominant. Straight lines are added for viewing perception only.

0.45mGy d-' and 0.80mSv d-l, respectively. The mean Q calculated from the LET spectra was 1.9 k 0.3.The maximum dose-equivalent rate and D rate measured on the Mir Space Station during passes through the SAA were 1.05mSv h-I and 0.76mGy hT1,respectively. LET spectra yielded a mean Q of 1.4 during these passes. More recently, additional LET spectra were measured on the Mir Space Station as a result of a joint United StatestRussian program (Badhwar et al., 1996b).Separation of trapped-belt particles and GCRwas straightforward. These preliminary measurements, made during solar minimum in September 1994,provided a D rate of 0.278mGy d-I with an g of 1.94(ICRP, 1977)and 1.74(ICRP, 1991a). Peak rates through the SAA were 12 mGy min-', and nearly constant from one pass to another. These data again demonstrate the inadequacy of the AP-8 proton environment model, which predicts a much higher proton fluence rate than was measured. LET spectra measured by three different instrumentation systems on the Mir Space Station are shown in Figure 4.9.The TEPC has been previously described. The NAUSICAA is a French1

-

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4. RADIATION EXPOSURE TO PERSONNEL

Linear energy transfer (tissue, keV pm-')

Fig. 4.9. Comparison of integral LET spectra measured on the Mir-16 Space Station mission by a TEPC with the AP-8 calculated LET spectra a t locations of the RussianIFrench NAUSICAA and Russian LYULIN instruments (Badhwar et al., 199613).

Russian instrument with general TEPC capabilities. The LYULIN is described by Lobakov et al. (1992). 4.3.2.7 International Space Station. The ISS is designed for an operational altitude of 360 to 450 km and an inclination of 51.6 degrees. Atmospheric drag is expected to reduce the altitude by about 9 krn between planned "nominal" reboosts. The latest measurements on the Mir Space Station which are relevant to the radiation environment of the ISS were made during Mir-18 and -19 missions (Badhwar et al., 1998b). There was nearly a factor of two in the difference between dose rates at different sites in the Station, the difference being accounted for by differences in the shielding. The daily D, measured by a TEPC, was about 0.3 mGy

4.2 SPACE CREW MEMBER EXPOSURES M LEO

/

65

with the contributions by trapped protons and GCR being roughly equal. The Q, based on ICRP Publication 26 (ICRP, 1977) was 2.6 giving a daily H of about 0.780 mSv. A number of sources of uncertainty are recognized, and the estimates are only for solar minimum.

5. Radiobiology of Space Radiation 5.1 Introduction

5.1.1 Space Flight and Ground-Based Sources of Data

Our present knowledge about the biological and medical effects of radiations encountered in space and especially in LEO has been greatly advanced during the last two decades by measurements made on United States and Russian spaceflights. Available information on the composition and quality of the radiation-exposure histories in Skylab, the Space Shuttle program, and the Russian Mir Space Station is summarized in Section 4. This Section will summarize the radiobiological features of components of the radiation environment present in LEO and indicate where critical deficiencies exist in our understanding of the risks associated with exposure to radiations i n space. Human radiation-risk estimates for cancer mortality, including those for astronauts and space workers, are based primarily on information from the Japanese survivors of the atomic bombs. Ground-based studies of the biological effects of radiation that are relevant to space stem largely from experiments in fundamental radiation biophysics and radiation-therapy research. This literature has been reviewed in the past in several documents including the 1967 report of the Space Radiation Study Panel of the Life Science Committee of NASINRC (1967) entitled, Radiobiological Factors in Manned Space Flight, and also in Tobias and Todd (1974). NCRP Report No. 98 (NCRP, 1989), Guidance on Radiation Received in Space Activities, summarized information available i n the mid1980s. New data became available in the late 1980s that changed risk estimates for radiation-induced cancer and added to our understanding of some biological effects of space radiations. Based on this new work, reports by UNSCEAR (1988) and BEIR V (NAS/NRC, 1990), the ICRP (1991a) and NCRP (1993a) recommended new dose limits for radiation protection standards. New experimental data have added to our understanding of some biological effects of

5.1 INTRODUCTION

I

67-

radiations in space. Many of the reports and reviews of these studies can be found in COSPAR (1989;1994;2000) and Kiefer et al. (1996).

.

5.1.2 Physical and Biological Variables There are a large number of variables that determine the radiation response of an organism. Relevant biological parameters include the species, age, gender and health of the organism. In the assessment of radiation health risks, two classes of effect are generally considered, termed "stochastic" and "deterministic." Stochastic effects are assumed to result from damage induced in single cells and are the most important for setting radiation protection standards. It is assumed that their severity is independent of dose, and that their frequency increases with dose without a threshold. Stochastic effects include the induction of cancer and hereditary effects (ICRP, 1977). Deterministic effects, previously termed nonstochastic effects, occur only after high doses, a threshold is exceeded, and they are detrimental to tissues or the whole organism. Deterministic effects are dosedependent with respect to their severity, after a threshold dose is exceeded. Even though the threshold may vary somewhat between individuals, after the threshold is reached all exposed individuals suffer such effects. Examples of deterministic effects are impaired hctioning of various organs, e.g., lung, kidney and skin. Pertinent physical parameters that determine radiation response are the ambient radiation dose levels, exposure interval, exposure rate, and the quality and composition of the radiation field.

5.1.3

Complexity of Time-DoseRelationships

Dose rate, total exposure time, andlor dose fractionation materially influence both early and late radiation responses in many biological systems. Physical as well as biological factors are involved in issues that relate to temporal aspects of radiation injury. Biological factors that relate to temporal aspects include: cell-cycle stage sensitivity, changes in distribution of cells in the stages of the cell cycle, changes in the size of stem cell or other cell populations, and a myriad of agerelated physiological changes that may alter responses to radiation. The number of combinations and permutations between physical and biological factors is large. Much has been learned from clinical radiotherapy about how these combinations and permutations determine the cellular/tissue/organ tolerances during the course of treatment. The general rule is that in the case of low-LET radiations,

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the fractionation of exposures a t either high or low dose rates reduces most early and late effects. With high-LET radiations, low dose rates or dose fractionation produce little or no sparing effect, and in the case of fission spectrum neutrons, fractionation of high total doses enhances late effects (Ainsworthet al., 1977).Subsequent sections will illustrate the basic principles of the importance of temporal factors in radiobiology. For biological endpoints (such as deterministic effects) for which cell killing is important, it is observed that cells and tissues can withstand larger doses of low-LET radiation if given at a lower dose rate. This observation seems to hold in the range ofdose rate between roughly 0.1 to 1 Gy h-l. This variation of effect with dose rate is understood to be due to the repair that occurs during the low dose rate irradiation. Damage occurring early in the period of irradiation is repaired during the radiation interval and cannot "interact" with damage occurring later. With the accumulation of more experimental evidence, it has become clear that some generalities may apply to most cell inactivation and repair data, as well as results for oncogenic transformation and mutagenesis in vitro. However, data from leukemogenesis or solid tumorigenesis experiments in vivo do not allow generalizations about dose rate, protraction or fractionation effects of high-LET radiation (Charles et al., 1990). This fact contributes a cautionary note to estimates of risk where densely ionizing radiations are involved. In LEO, a spacecraft traverses the SAA on several passes through the southern latitudes off the coast of Brazil. Typically, for seven passes every 24 h, the spacecraft spends some 20 to 22 min traversing the region where protons trapped in the inner radiation belt are present. The dose rate in this region is highly variable and depends strongly on altitude. The dose rate profiles of STS-40 (altitude of about 287 km and an inclination of 39 degrees) are shown in Figure 4.7. The maximum dose rates measured on the Space Shuttle in low inclination (28.5 degrees) were on STS-61, which flew at an altitude of about 594 km, well above the altitude expected for the ISS. In the SAA the peak rate was about 6 mGy h-I (Badhwar et al., 1992).At this dose rate, no dependence on dose rate for deterministic effectswould be expected. Viewed in another way, 6 mGy h-I translates into an average of two electron events per hour per cell nucleus of 6 p,m diameter, assuming a track-averaged LET of 0.3 keV p,m-l. For a larger trackaveraged LET, there would be fewer events per cell nucleus at the same dose. Since the transit time from the beginning to the end of the SAA is around 20 min per orbit, less than one event would be expected on the average in a cell nucleus per pass, with an interval

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of about 90 min elapsing between passes. Taking into account the temporal and spatial relationships necessary for lesion interaction, it is reasonable to conclude that the probability for interaction will be extremely low. It can therefore be confidently concluded that neither deterministic nor stochastic effects will be influenced by dose rate in LEO. For large SPE outside Earth's magnetosphere, the dose rate can attain significantly higher values and pose extra risks in missions in deep space. In LEO even large SPE do not pose an important risk. However, there is one unusual combination of events that could result in a significant increase in the dose rate. If a geomagnetic storm that results in a reduction of the shielding provided by the radiation belts was concurrent with a very large SPE, the amount of solar radiation reaching the space vehicle in LEO would rise significantly and would be of some concern, especially for those in EVA (NAS/NRC, 2000). With suitable design of the vehicle and the maneuvering of the vehicle to maximize shielding, it should be possible to prevent any untoward outcome that might occur with this unlikely combination of events.

5.2 General Biological Effects of Components of the Space Environment

The unique feature of the space radiation environment in terms of radiation exposure is the abundance of different types of particulate radiations, including protons, helium and heavier ions of higher atomic mass emanating from SPE and GCR. Other radiation exposures in space travel arise from trapped electrons and protons, and neutrons produced by interaction of the primary radiation with material of and within the spacecraft Each of these individual radiation types have been studied a t various levels of biological organization. Many of the quantitative molecular and cellular effects have been measured in ground-based in vitro studies, and there is a significant amount of information on tissue effects for these radiations in animals. Moreover, all of these radiations have been used to varying degrees in clinical radiotherapy and, therefore, there is some information about acute effects in humans. Reports on dose fractionation and late effects are becoming available, and there is some information on tumor induction and neoplastic transformation in mammalian cells in culture. Most of the effects that are known are due to relatively high doses of each type of radiation. There are very few data at low dose levels in the range comparable to the doses that

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can be experienced by humans in space, or under the potential mixedradiation fields possible in the space environment. The importance of theoretical modeling to extrapolate to low dose effects and to predict outcome from exposure to combined agents has therefore assumed increasingly greater significance in risk assessment. The most recent characterization of the radiation environment in LEO shows protons in the energy range of 6 to 500 MeV and neutrons from 10 keV to 2 MeV. SPE rarely contribute a significant radiation hazard in LEO. Within a shielded spacecraft, most of the dose an astronaut receives in LEO is from low-energy protons, with contributions from neutrons and electrons. Helium and heavy ions do not contribute significantly to H. Described below is a brief overview of some of the experimental information available for each of the most important component radiations (i.e., protons, neutrons and electrons) in the LEO space environment.

5.2.1

Protons

The most prevalent particles contributing to radiation doses in space are protons. Protons lose energy as they pass through tissues principally by interacting with atomic electrons. Secondary particles are produced by nuclear interactions and they contribute a small, but important fraction of the total dose. The secondary radiations consist of secondary protons, neutrons, pions, heavy particles, and gamma rays. As the proton slows down, the rate of loss of the energy increases. At lower velocities, the rate of energy loss then decreases, in part because a slow positive ion can capture and lose electrons. The depth-dose distribution in tissue exposed to a beam of monoenergetic protons is characterized by a Bragg curve which reflects the relative ionization as a function of depth. The depth of the peak in tissue is dependent on the energy. The dose a t the peak of the Bragg curve is, of course, greater than in the relatively flat plateau region that precedes it. The dose decreases to almost zero after the Bragg peak as the particles stop. The LET, which influences the degree of biological effect, increases with decreasing proton energy. The LET in the plateau region is low, about 0.2 keV Fm-l, but rises considerably over a very short range of the track as the particles come to a stop. In general, the RBE values for cell inactivation by high-energy protons are the same as for 250 kVp x rays and protons are, therefore, somewhat more effective than 'Wo gamma rays. The RBE values for protons of less than 30 MeV and short range (less than 1 cm) are higher (Belli et al., 1989). For example, the RBE values for early responses of the skin for 250 MeV protons compared to 290 kVp

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x rays were 0.6 to 1 and 0.7 to 1.2 for the spread out Bragg peak and the peak, respectively (Tatsuzaki et al., 1987). The influence of depth on the value of the RBE has been studied with 65 MeV (Tang et al., 1997) and 200 MeV protons (Gueulette et al., 1997).Wouters et al. (1996) have determined the RBE value for lethality of 70 MeV protons a t the TRIUMF facility. The acute effects of whole-body exposures have been assessed in a primate by LD, values for protons with energies in the range of 32 to 400 MeV (Dalrympleet al., 1966a; 1966b; 1966c; 19668 and the RBE value is 10 to 20 percent higher than the sparsely ionizing radiation. There are RBE values (Urano et al., 1984) for murine jejunal crypt cells, skin and lens range between 0.8 and 1.3. Tatsuzaki et al. (1994) reported an RBE value of 1.02 to 1.03 for the late effect, skin contraction, after 10 fractions spread over 11d of 250 MeV protons. In the case of proton-induced tumors, Clapp et al. (1974) found no RBE values greater than one for 60 MeV protons in their study of life shortening and tumor induction. Casey et al. (1968) reported skin tumors in rats after whole-body irradiation with 13 MeV protons. Single doses ranged from 2 to 25 Gy. The number of rats in each dose group was small, but all irradiated rats developed tumors. Burns et al. (1975) exposed rats to 10 MeV protons and compared the induction of skin tumors with that resulting from exposure to electrons. They estimated the value of the RBE to be about three. The reduction of the tumorigenic effect with fractionation of the exposures to protons suggested repair, and the curnilinear response to single doses was typical of low-LET radiation. Bettega et al. (1985) found that neoplastic transformation of cells in vitro was characterized by a curvilinear response, and while no RBE value was estimated, the response was similar to x and gamma rays. An important study of proton-irradiated monkeys has been underway for about two decades (Wood, 1991;Wood et al., 1986; Yochmowitz et al., 1985). The study involved exposures to 32, 55, 138, 400 and 2,300 MeV protons. In females, a predominant finding was endometriosis that appears to be radiation-induced (Wood et al., 1986).There is no evidence that this lesion is related to the radiation quality or that humans will show comparable susceptibility. Eight of 72 monkeys that have died and were exposed to 55 MeV protons (4 to 8 Gy surface dose) had glioblastomas. These animals were rotated during exposure and a region of the brain, about 2.5 cm below the surface, may have received much larger doses due to the Bragg peak. It is not known whether or not this species, Macacca mulatta, is unusually susceptible to this tumor. The fact that brain tumors have been reported (Ron et al., 1988)in persons exposed to x rays in childhood to doses as low as 1Gy suggests that the results are not due to an

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unusual susceptibility of the monkeys. Wood et al. (1994) did not find an increase in glial tumors in rats within 2 y of receiving 2 to 4 Gy of 55 MeV protons given at 70 d of age. When data for different proton energies and all tumor types in both genders are pooled, the dose response appears curvilinear and similar in its general form to low-LET radiation responses for tumor induction. Late effects in stem-cell populations of the skin of these monkeys have been determined by the propagation of primary cultures of skin biopsies to terminal senescence (Cox et al., 1986). The results suggest some radiation-induced loss of proliferative capacity. Intermediate and, especially, late cataractogenesis (greater than 24 y) (Lett et al., 1991), post-irradiation, have been observed and are of concern.

5.2.2 Neutrons The interaction of neutrons with tissues differs from that occurring with low-LET radiation. The neutron is an uncharged particle and is, therefore, more penetrating than charged particles. Neutrons interact with the nuclei of atoms, whereas x rays interact primarily with the orbital electrons. A principal mode of interaction of neutrons that have not been slowed down to thermal energies is elastic scattering with atomic nuclei. In a single elastic collision, a fraction of the neutron's energy is transferred to a nucleus, which recoils as a highLET charged particle. Since hydrogen is in abundance in tissues and has a large collision cross section, interaction between neutrons and hydrogen is a dominant feature of the transfer of the neutron energy and results in recoil protons. The recoil protons lose energy by ionization and excitation as the particles traverse the cells, and they contribute the major fraction ofD in the case of neutrons of low energies. The major fraction of the energy deposited by recoil protons is at LET values of less than 30 keV pm-', but as the protons come to a stop, the LET rises to about 100 keV pm-l. Because the neutron and proton masses are essentially equal, the proton can acquire essentially all of the neutron's energy in a single, head-on elastic collision. Interactions between neutrons and elements other than hydrogen also produce recoiling heavy nuclei by elastic and inelastic processes. Although the contribution to the dose in the tissue is smaller than that for interactions with hydrogen, the deposition of energy is at a high-LET. In addition to elastic scattering, when neutrons with energies above about 5 MeV interact with the nuclei of atoms, such as carbon or oxygen, they can produce alpha particles, protons, deuterons, and other neutrons. Nuclear disintegration and

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the resulting densely ionizing alpha particles increase in frequency with increasing neutron energy. Since 1990,neutrons have been taken into account in the HZETRNI BRNYNTRN codes. These codes have been shown to be in good agreement with most space-flight measurements (see Section 4.2.1). The measurements that have been made aboard the Space Shuttle and the Mir Space Station suggest that the contribution of neutrons to the dose is significant. Neutrons are produced by interactions between particles and spacecraft materials, and neutron dosimetry within the spacecraft must be carried out to more firmly establish the contribution they make to the total dose. The average energy of the neutrons in ISS is estimated to be about 5 MeV, an energy less biologically effective than fission spectrum neutrons. The characteristics of the neutron dose deposition in tissue, cells and DNA are responsible for the marked biological effects of this type of radiation. At doses of the order of 10 mGy, the fraction of the cells in a tissue that are traversed by a particle is quite small, but the density of the ionization in the track is very high. This energy deposition results in high RBE values for all biological endpoints. The RBE values for neutrons for induction of cytogenetic effects, mutation, neoplastic transformation, carcinogenesis, and life shortening have been reviewed (NCRP, 1990). Neutrons induce a higher ratio of double-strand breaks to single-strand breaks than do x or gamma rays, and the repair of double-strand breaks is much less efficient than the repair of single-strand breaks (Coquerelle et al., 1987; Ward, 1985). Neutron irradiation causes more marked late effects than lowLET radiation and more severe late effects than would be predicted from the acute responses. Neutrons are more effective than low-LET radiations because of their cytocidal effectiveness, perhaps due to a higher cross section in lipid containing cell constituents and tissues. The range of neutron tolerance doses for various organ systems has been summarized from the experience of workers in the field of neutron radiotherapy. Laramore and Austin-Seymour (1992) reviewed the clinical literature on organ-specific toxicities to neutrons. There is a hierarchy ofrelative organ sensitivities from partialorgan exposures covering a range of total neutron doses (including the gamma component) from 6 Gy to over 22 Gy. Of interest to the question of threshold doses for cataract induction is the finding that limiting the scattered dose to lens to a range of 1to 3 Gy prevented major clinical effects on the eye. There are few data for the effects of the range of neutron doses to which crew members will be exposed. In general, the biological effects

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of the higher energy neutrons are less than those of neutrons of approximately 1 MeV. The carcinogenic effects of neutrons have been reviewed (Broerse and Gerber, 1982;NCRP, 1990;Sinclair, 1982; 1985). It is clear that the RBE value for neutrons and other high-LET radiations is dependent on dose, dose rate, fractionation, and the tissue in question, as well as LET and neutron energy. The RBE values for tumor induction by neutrons range from one to high values in different tissues, and this makes the selection of a single Q for neutrons a very difficult task (ICRP, 1991a; ICRU, 1986;NCRP, 1990). The ICRP (1991a)has recently recommended new w~ for different neutron energies, for purposes of risk assessment. While recognized as not ideal, w x and Q values selected on the basis of the RBE of the specific types of radiation have been considered adequate for radiation protection purposes. At the dose levels experienced in space there will be negligible, if any, enhancement of the effects of highLET irradiation due to the low dose rate.

5.2.3

Electrons

Electrons are very small, light, negatively charged particles. The negative charge of the electron is of the same magnitude as the positive charge of the proton. There is much less information about the biological effects of exposure to electron beams than other lowLET radiations, but the effects can be inferred from the results of studies of photon irradiation because photons generate electrons in tissue by well known interaction processes (Alper, 1979;Elkind and Whitmore, 1967;Hall, 1994). There are few data on late effects of electron irradiation, but their carcinogenic effects have been studied in skin (Burns and Albert, 1986). The results indicate that repair of potentially carcinogenic damage occurs in fractionation regimes and that the dose-response curve for single exposures is curvilinear (Figure 5.1). I t is assumed with confidence that late effects of electron irradiation in space can be predicted on the basis of knowledge of the effects of photon irradiation.

5.2.4

Heavy Ions

Introduction. About 98 percent of particles in GCR are protons and heavier ions and about two percent are electrons and positrons. Of the protons and heavier ions, about 87 percent are

5.2.4.1

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Skin surface dose (GY) Fig.5.1. Cancer yield in rat skin as a function of surface dose (single dose, 3 to 5 Gy min-l0.34 keV p,m-l electrons or 'Ohions); in rats exposed at 28 to 58 d of age. Emors are estimated from total number of tumors. The curves are least-squares fit to the power function y = bn (Burns et al., 1989).

protons, 12 percent are helium ions, and about one percent are heavier ions in the range of 10 MeV n-I to about 10 GeV n-I. The ions that are heavier than helium are known as HZE particles. Iron ions are the most important because of their relative abundance and high-LET. Heavy ions, despite their low fluence, make a significant contribution to the GCR dose which is proportional to Z2. In the orbit for the ISS about 65 percent of the organ H will be contributed by GCR. The radiobiology of heavy ions is becoming better understood (Blakely and Kronenberg, 1998)but there are still important gaps in the knowledge about such potential effects as cancer induction. It is not possible to predict quantitatively the effects of heavy ions based on knowledge of the effects of other types of radiation because the pattern of energy deposition is so different. The densely ionizing particle tracks traverse many cells and the delta rays associated with the particle tracks deposit energy in cells adjacent to the particle track.

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6.2.4.2 Physical and Biological Characteristics. Like all energetic charged particles passing through matter, heavy ions (i.e., nuclei of atoms heavier than hydrogen)lose energy almost continually by their electromagnetic interaction with atomic electrons as they penetrate matter. This energy loss is well characterized by stopping power relationships first derived by Bethe (1930). Unlike lighter particles such as electrons, the trajectories of energetic ions tend to be straight unless the particle encounters the dense nucleus of an atom. In such cases, the energetic ion can be scattered, or at high energies, this collision can result in the fragmentation of the target nucleus. Fragmentation is a major process that occurs when matter is irradiated by a beam of heavy ions at high energies. Some fragmentation products are radioactive and are deposited near the end of the path of the primary beam. Tobias et al. (1971) named this "autoactivity." The RBE value for chromosomal, cellular and tissue effects increase with LET, reaching a maximum between 100 and 200 keV ~ m - ' . However, it is not possible to assign just one RBE value for a given heavy ion and a given tissue. As the LET of a single ion species is increased beyond the maximal effective LET, the action cross sections (probability of effect per unit of fluence) decreases. There are several possible interpretations of this result, but from the space radiation protection standpoint, it implies that action cross sections of very heavy ions do not exceed the area of the cell nucleus and that every particle track has a maximally efficient segment (Blakely et al., 1984). When single-cell endpoints such as the killing of cells with "normal" radiosensitivity are compared with multi-cellular effects, such as the gut-colony assay, a maximum RBE value occurs around 200 keV ~ r n - 'and the RBE value decreases at higher LET in tissue studies (Alpen and Powers-Risius, 1981; Alpen et al., 1980; Todd and Walker, 1984). Goldstein et al. (1978) reported RBE values for mouse crypt clonogenic cell survival of 1.2,1.5 and 2.2 for the plateau regions of helium, carbon and neon beams, respectively. While repair damage in these cells was indicated from the results of fractionated exposures to helium and carbon, none was noted with neon. Ainsworth et al. (1983) reported an RBE value of 2.1 for 10 percent survival of colony forming unit-spleen (CFU-S)exposed to a spread Bragg peak of 40Ar, 1.01 for lower energy ' O A r ions, and 1.5 to 1.6 for low energy 12C and "Ne. The values of RBE of various heavy ions for acute effects in some normal tissues are shown in Figure 5.2. Yang et al. (1985), using C3HlOT3-5 cells, demonstrated an increase in the RBE value for neoplastic transformation up to about 10 with increasing LET of the heavy-ion beams up to about 100 to

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Dose average LET (keV pm-') Fig. 5.2. A plot of RBE values for acute effects in normal tissues obtained from the ratio of the intercept values from the reciprocal dose plots for skin, jejunal crypt cells, and spinal cord. RBE values are plotted versus the approximate dose-average LET values associated with the positions within the depth-dose distribution curves a t which exposureswere given. Responses for jejunal cells are denoted by G, for skin by S, and for spinal cord by the C. Irradiation with different heavy ions is denoted by the symbols, = carbon ions, 0 = neon ions, or A = argon ions. Responses after irradiation with different heavy ions are boxed to indicate general trends in the response data (Leith et al., 1983).

200 keV pm-'. At higher LET values the RBE value fell to about The authors suggested that the lesions induced one for 960MeV 238U. by high-LET particles (greater than 100 keV pm-') involved in neoplastic transformation of both plateau H phase and proliferating cells are not repaired. Yang et al. (1986)reported that lowering the dose rate of the exposure of plateau H phase cells increased the transformation rate. There are very few studies on the carcinogenic effects of heavy ions and some important questions remain to be answered about the relative carcinogenic effectiveness of HZE particles. Burns and Albert (1981)and Bums et al. (1989)studied the effect of 40Aron skin tumor induction. The dose-response curve is shown in Figure 5.1. Clearly there is no single RBE value (argonlelectron),even at low doses, if the dose-response relationship for one or both of the radiations is a power function. Such a relationship would also result in a high-RBE value.

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Fry et al. (1985) reported RBE values of about 30 for induction of Harderian gland tumors by the heavy ions 40Arand 56Feand lower RBE values with radiation beams of lower LET (Figure 5.3). The results suggested that there may be no peak in the curve of the value of the RBE versus LET in the vicinity of 100 to 200 keV pm-', but rather a plateau. Based on the ratios of initial slopes of the doseresponse curves for exposure to an %Febeam and "Co gamma radiation, the RBE value for carcinogenesis appears to be about 30. The RBE values for 40Ar,56Fe,and fission neutrons in this system are of the same order. More recent reports (Alpen et al., 1993; 1994)extend the findings to 4He, nickel, and lanthanum. The results indicate that the RBE-LET relationship reaches a plateau a t about 100 to 200 keV pm-l, but unlike the data for cell killing and mutations, the value of the RBE does not appear to decrease at higher LET values. An analysis of the Harderian tumor data using particle fluence rather than dose as the independent variable (Figure 5.4) allows the calculation of a risk coefficient and another measure of correlation with LET (Alpen et al., 1994).This approach also indicates that the risk coefficient appears to be a monotonic function of LET for the particles studied, reaching a maximum effect a t about 200 keV pn-'. Curtis et al. (1992) have suggested the use of fluence-based

U C

-Neon

1

i 20C

Iron

4 em

600

platenu

Cul~eltGO r rnvs SOBP: Sl,rr.rcl O u t Bragg Pcnk

A

'

10 em

.:Argon

1

1

Dose (Rad)

Fig. 5.3. Prevalence of Harderian gland tumors as a function of dose of heavy ions as indicated (Fry et al., 1985).

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Particles ~ r n - ~

Fig. 5.4. The proportion of mice with Harderian gland tumors as a function of fluence of the particles indicated (Alpen et al., 1994).

risk coefficients for estimating the risk of cancer from exposure to radiation in space. In a later report, Curtis et al. (1995), examined the concept of a risk cross section or risk per particle fluence and derived human cancer risk cross section for low-LET radiation from the data from the atomic-bomb survivors (Figure 5.5). A risk crosssection function for mortality h m cancer was assumed as a function of LET and compared with the plots for various experimental endpoints. Because the appropriate cross-section functions for cancer induction by all of the heavy ions were not available, Q was used as a n approximation to obtain the numerical results for risks of excess cancer mortality. Risk cross sections for total cancer mortality and seven of the most sensitive organs were obtained and are shown in Figure 5.5. For details of the calculations the reader is referred to Curtis et al. (1995). 5.2.4.3 The Microlesion Concept. NASINRC (1973) suggested that the localized damage by a single HZE particle could be described

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0.1

1

10 LET (keV prn-')

100

1000

Fig. 5.6. The risk cross sections for stomach (---I, colon and lung (--- -1, bone marrow (- --), bladder and esophagus (-..--), breast (..*.*), and as a function of LET (Curtis et al., 1995). total (-1

as a "microlesion" without a counterpart in medical experience. The concept of a microlesion has been supported by some studies (Malachowski, 1978; Nelson, 1980; Nelson et al., 1983), but not by others (Koniarek and Worgul, 1992). Clearly the damage that can be caused along the particle track that is heavily ionizing and traverses many cells cannot be assessed on the experience with other radiation qualities. A definitive study, in particular, on the effects of HZE particles to the central nervous system could settle the matter.

5.2.4.4 Bystander Effect. Interpretations of the mechanisms of the action of ionizing radiations are, in general, based on the belief that the responses, such as strand breaks and chromosome aberrations, occur only in the cell in which the energy is deposited. However, it has long been known that after partial-body radiation, effects can occur in unexposed tissues, the so-called abscopal effects. Furthermore, it was shown many years ago that clastogenic agents were produced and liberated into the medium in which cells had been irradiated (Littlefield et al., 1969). More recently there has been intense interest in the finding that after exposureto very low fluences of alpha particles many more cells had sister chromatid exchanges than could have been traversed by an alpha particle (Nagasawa and Little, 1992).This has been called the bystander effect, a term that

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has been used to describe the transfer of bioactive material between cells through cell gap junctions. In the case of radiation, in some cell systems, the bystander effect is mediated through cell gap junctions but in others reactive oxygen species have been shown to be involved (Deshpande et al., 1996). Other responses such as mutation and signal transduction have also been shown. The bystander effect is dependent on the cell type, the radiation quality, and the influence of the microenvironment. I t is clear that a more complete understanding of the mechanisms is required, especially in tissues, and about the dependence on LET. If risk estimates were to be made based on models of the mechanisms, as was attempted for the induction of lung cancer by alpha particles in the report of BEIR VI (NASINRC, 1999), the bystander effect would be important. As long as risk estimates are expressed in terms of absorbed dose or equivalent dose the impact of any bystander effects are automatically taken into account.

5.3 Dose-Limiting Effectsfor Tissues at Risk in Space The organs of the body are known to vary in their radiosensitivity and in their susceptibility for both deterministic and stochastic effects of ionizing radiation. Ionizing radiation can cause deterministic effects in all organs, provided the dose is high enough, although the sensitivity varies greatly. The relative radiation sensitivities of human organ systems have been reviewed in Altman and Lett (1990; 1992),ICRP (1989), and Lett and Atman (1987). Early deterministic effects in organs occur with high doses at high dose rates and are mainly due to killing of proliferative cells. Such levels of acute doses and dose rates will not occur in LEO. The question is whether protracted low dose rate irradiation, that will occur on long-duration missions in both LEO and in deep space, will cause late deterministic effects. In most organs such late effects result from either a direct loss of parenchymal cells or secondarily from vascular damage. Relatively low doses protracted over long periods can result in loss of stem cells that could result in clinically significant effects in the hematopoietic system and gonads. The effects of irradiation on the reduction of fertility and the induction of sterility are discussed in Section 5.4.2. Dose limits have long been recommended for the lens of the eye and the skin for both terrestrial workers and the public. Currently, the occupational annual dose limit to the eye is 150 mSv and 500 mSv for the skin (ICRP, 1991a; NCRP, 1993a).From the beginning of the

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manned space program, recommendations for dose limits based on deterministic endpoints have been made for bone marrow, skin, and the eye. The current recommended limits for deterministic effects are given in Tables 1.1, 2.2, and 6.3. These recommendations are discussed in Sections 2 and 6. In this Section, the composition and the biology of these three tissues as well as their acute and late deterministic effects of irradiation are reviewed.

5.3.1

Bone Marrow

Bone marrow contains sensitive progenitor cell populations that are highly susceptible to radiation injury. This sensitivity is reflected in the susceptibility for the induction of leukemias. In terms of absolute risk estimates, however, the risk coefficients for both the breast and thyroid tissue are greater. The cells of the blood system are derived from self-renewable pluripotent progenitor cells (commonly referred to as stem cells) in the bone marrow and spleen which give rise to a continuum of multipotent and committed progenitor cells with the ability to produce large numbers of mature lineage-specific blood elements (Metcalf, 1977; 1988; 1991; Metcalf and Moore, 1971; Moore, 1991). The progenitor cells of the bone marrow are responsible for production of at least eight types of morphologically identifiable mature blood cells in the peripheral blood. These include erythrocytes, neutrophilic granulocytes, eosinophilic granulocytes, basophilic granulocytes, monocytes (macrophages), platelets and B- and T-lymphocytes. The anticipated exposure in space is spread over weeks or months, at low exposure rates. Two essentially independent processes influence the effects of such protraction: (1)repair of sublethal injury (Elkind and Sutton, 1960; NCRP, 1980) and (2) proliferation of the surviving cells between the small dose increments, or repair and regeneration during continuous low dose rate exposures. In the dog (Seed et al., 1982), an important change in the radiation response of the granulocyte macrophage-colony forming cells was noted with continuous low dose irradiation. The Do(i.e., the dose required to reduce a viable cell population to e-' or 37 percent where e is the base of the natural logarithm system -2.718) increased and a distinct shoulder to the survival curve appeared. These changes suggested a more radioresistant cell population and probably an increased capability of repair. Although these changes were greatest with gamma rays, they were still significant with exposures to 1MeV neutrons (Seed and Kaspar, 1992). After termination of the chronic

exposure, a reversion of these changes occurred in the progenitor cells of the majority of the animals; the radiosensitivity and the minimal repair characteristic of the phenotype of the progenitor cells returned (Seed and Kaspar, 1992). The responses of the hematopoietic system and its component progenitor cells are intimately related to the survival of the individual after exposure to ionizing radiation. It is not surprising therefore that there are similarities in the survival patterns among different species, from rodents to primates, with similar relationships to the responses of their progenitor cell populations (Boyum et al., 1978; Carsten et al., 1976; Cronkite et al., 1987). A range of radiosensitivities has been reported for various classes of progenitors from different species. Despite this, the current and general consensus is that the most primitive, quiescent, multipotential progenitors with marrow repopulating capacity are relatively radioresistant with Do values in the range of 0.9 to 1.1 Gy (Wagemakeret al., 1995). Less quiescent, slightly more mature, but still clearly multipotential CFU-S, day seven type progenitors, are more radiosensitive with'D, values in the range of 0.5 to 0.9 Gy of low-LET radiation, whereas the more mature, more actively cycling, lineage-restricted bipotential and unipotential (e.g., granulocyte macrophagecolony forming cells, macrophage-colony forming cells, etc.) are considerably more radioresistant with Dovalues well above 1Gy (Cronkite et al., 1987; Meijne et al., 1991; van Bekkum, 1991; Wagemaker et al., 1995). With all progenitor subpopulations, however, repair capacity, assessed in terms of sublethal damage repair, is generally considered to be minimal under normal, steady-state hematopoietic conditions, with radiation exposure threshold levels, i.e., Do r 0.2 Gy (Cronkite et al., 1987; Neumann et al., 1981; Seed and Kaspar, 1992). As can be seen in Figure 5.6, some depression of the number of CFU-S occurs throughout 100 fractions of either 0.005, 0.01, 0.02 or 0.03 Gy given three times per week. Although the circulating levels of the functional blood cells can be maintained under these conditions, the recovery of the CFU-S population does not occur during irradiation. Under chronic radiation stress, however, as noted above the repair capability of progenitor cells can increase substantially (Seed and Kaspar, 1992).

5.3.2

Eye

Apart from cataract development, the major influence of radiation on the eye is generally mediated by effects on the vasculature. Merriam et al. (1972) and Gordon et al. (1995) have made an extensive survey of radiation-induced damage of the cornea, conjunctiva,

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0

1

0

I

0.5

I

I

I

1.5 2 Accumulated air kerma (Gy) 1

I

2.5

3

Fig. 5.6. CFU-Sfor four differentdose regimens. 0.005 Gy three times a week for a total of 0.5 Gy (-0); 0.01 Gy three times a week for a 0.02 Gy three times a week for a total of 2 Gy total of 1 Gy (V-V); ( 0 4 ) ;and 0.03 Gy three times a week for a total of 3 Gy (A--A) (adapted from Cronkite et al., 1987).

sclera, iris and retina, and also of the adnexal tissues such as the eyelids and lacrimal glands. These tissues show damage of clinical significance only at high single doses and even higher doses in the case of fractionated or protracted doses on the order of tens of gray. The estimated threshold doses for radiation-induced effects on the ocular tissues are shown in Table 5.1.The threshold doses for the effects on the eye, with the exception of the lens, are in excess of doses expected to occur in LEO missions over a period of a few years. The threshold dose for opacification of the lens, known as a cataract, is considerably lower than that for other ocular lesions.

5.3.2.1 Radiation-Induced Cataracts. The role of radiation in the induction of cataracts was recognized soon after the discovery of x rays (Bendel et al., 1978).The pathological changes occur in a well defined cell population and can be examined both non-invasively and repeatedly. Thus, the development of cataracts can be followed after exposure to radiation. While the mechanism of the radiation induction of cataracts is not known precisely, it was assumed by various committees that radiation-induced cell killing was central to the mechanism of cataractogenesis (ICRP, 1969;NASfNRC, 1972). Currently, damage to the genome resulting in altered transcription and abnormal lens

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TABLE 5.1-Summary of estimated low-LET threshold doses for certain deterministic effects of radiation on tissues of the human eye (Merriam et al., 1972; UNSCEAR, 1982) Tissue

Lid skin

Effect

Early erythema

Lachrimal gland Atrophy Conjunctiva

Single

Dose (Gy) Fractionated

4 to 6 20

Late telangiectasia

50 to 60 (30 fractions per 6 weeks) 30 to 50 (3 to 5

weeks) Cornea

Early edema and keratitis

Sclera

Late atropy

Retina

Early edema Late degeneration

Lens

Cataract

10

2 to 10

fiber protein is considered to be the salient injury. All the evidence is consistent with the belief that most cataracts are due to damage to the cells of the germinative zone which, in turn, results in abnormal differentiation of the developing fibers. The latent period between exposure and the detection of opacities is consistent with the time taken for differentiation and migration of the cells that form the fibers. At very high doses, the damage may cause metabolic changes and subsequently a loss of transparency. At the doses of concern in radiation protection, the evidence that the induction of cataracts is not due to cell killing, but damage to the genome of the epithelial cells ofthe lens seems compelling. If so, the classification ofradiationinduced cataracts as a deterministic effect must be called into question. Radiation-induced cataracts develop in a sequence which is pathognomonic. Typically, the changes first appear in the posterior subcapsular areas followed by anterior involvement and an increase in the posterior lesion. Eventually, the anterior changes become so severe that light cannot be directly transmitted through the region, and a total cataract is observed. An early radiation-induced cataract can be distinguished from cataracts caused by other agents and from those occurring naturally, but with time and progression of the cataract, the distinguishing features are lost. Lens opacities may, or may

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not, progress and what determines the outcome is not clear. The possibility of regression or resolution has not been considered in setting protection standards. It should be noted that although the formation of a cataract is considered a deterministic effect for radiation protection purposes, there is little or no evidence that cell killing is the dominant mechanism as it is for deterministic effects in other tissues. In a longitudinal study, Lett et al. (1988; 1991) illustrated the importance of time in the assessment of cataracts. For example, assuming a specific grade of cataract will be deemed clinically significant, the results of the studies ofrabbits exposed to 56Feions indicate that after 4 to 5 Gy a significant cataract will occur in a few months, but if the dose is decreased, the appearance of the cataract will be delayed. The interaction of time and dose complicates the setting of a dose limit that will prevent a cataract. Obviously, age at exposure, the protraction of the exposure as well as dose are important. The marked difference in both the natural incidence and apparent radiosensitivity between species raises questions about which of the experimental model systems is appropriate for estimating riska of radiation-induced cataracts. Intuitively, the experimental animals that have a low probability of naturally occurring lens opacities seem to be the systems of choice. Extrapolation of RBE values obtained from data for small rodents must be approached with caution. An examination of the extrapolation of risk estimates for radiationinduced cataracts across long-lived species has been made (Cox et al., 1993). The question of whether or not susceptibility to cataract induction is age dependent is important for protection standards. In a study of atomic-bomb survivors, the results suggest that there was a greater effect on the lens of those exposed early in life compared to later, but only in Hiroshima and not in Nagasaki. Those exposed at an age of less than 15 y showed a greater effect than the older persons (Choshiet al., 1983).In experiments with rats, Merriam and Szechter (1975)found that young animals were not significantly more susceptible to radiation-induced changes in the lens than the older rats. However, the age dependency of the latent period and progression of lens opacities is complex. For example, with doses of 2 to 3 Gy, changes in the lenses occurred sooner and progressed faster in adult rats than in the young, but in the range of 3 to 9 Gy opacities developed earlier in the lenses of the young than in the adults. Lett et al. (1985) found that cataractogenesis was less marked in "middle-aged rabbits at early times after exposure to neon ions (LET 30 keV wm-l) than in young rabbits, but progression to total opacity and blindness was more rapid in the older animals.

-

The estimate of risk of induction of cataract in humans by exposure to low-LET radiation has, in the past, been based largely on the studies of Merriam and Focht (1957; 1962). These studies on radiotherapy patients were the basis of the following conclusions: (1)the threshold dose ofx rays for the induction of minimally detectable lens opacities for single exposures was 2 Gy, and 5.5 Gy with exposures fractionated over three months or longer (see Table 5.2 and Figure 5.7); (2) the threshold dose to cause a progressive cataract was about 5 Gy; (3) all patients developed cataracts after single dose of 7.5 and 14 Gy fractionated exposures; and (4) the time between exposure and detection of the cataracts was inversely related to dose. In other studies of radiotherapy patients, no loss of vision due to cataracts was found with less than 14 Gy of exposures to low-LET radiation fractionated over six to seven weeks (Britten et al., 1966;Morita and TABLE 5.2-Cataractogenic

doses in humans (Merriam and Focht, 1962).

Maximum NonCataractogenic Dose (Gy)

Minimum Cataractogenic

Radiation Exposure

Single 3 weeks to 3 months Over 3 months

2.0 10.0 10.5

2.0 4.0 5.5

Dose (Gy)

Total duration of treatment (d)

Fig. 5.7. Strandquist plot of cataract and non-cataract cases in radiotherapy patients receiving x rays (Merriam and Focht, 1962).

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Kawabe, 1979).The sparing effects of fractionation has been observed by Deeg et al. (1984)in patients that have had total-body irradiation and marrow transplantation. Based on a proportionalhazard regression analysis, the relative risk of developing a cataract was 4.7 times greater in patients that had single total-bodyirradiation compared to those given fractionated irradiation or chemotherapy. 5.3.2.2 Protons and the Lens. There are no analyses of the data for the induction of cataracts in humans by protons that may be applied to the estimate ofriskin space. In one study, Rhesus monkeys were exposed to acute high dose rate exposures of protons of energies from 32 to 2,300 MeV and followed over two decades (Lett et al., 1986;1991).Minimal lesions were detected at doses of 1 Gy of 55 MeV protons and above, but there was no evidence that the effect of protons was much greater than that of photons (Niemer-Tucker et al., 1999). It is not known what reduction in effect would result from a reduction in dose rate. In summary, the current evidence does not indicate that protons are significantly more cataractogenic than photons (Figure 5.8), and the occurrence,latent period, and severity of cataracts are dependent

photons (TNO) 5.0 Gy 6.0 Gy 0 8.0 Gy 0 8.5 Gy 55 MeV protons (DEC) 2.5 Gy M5.0 Gy r 7.5 GY

V

Post-irradiation time (y)

Fig. 5.8. Average cataract index in Rhesus macaques exposed to 55 MeV protons or 300 kV or 6 MV x rays as a function of time in years after irradiation (Niemer-Tuckeret al., 1999).

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on the dose of low-LET radiation. Minimal stationary opacities may occur with single doses of 1to 2 Gy, and with 7.5 Gy the probability of some degree of opacity is one. The human experience suggests a single-dose threshold of about 2 Gy. Fractionation reduces the cataradogenic effect of radiation by about a factor of two to three. Doses of greater than 10 Gy and less than 14 Gy spread over weeks are required to induce a 100 percent incidence of cataracts (UNSCEAR, 1982). The threshold for cataracts with doses fractionated over 3 to 13 weeks is about 5.5 Gy (Merriam and Focht, 1962). 5.3.2.3 Neutrons and the Lens. A number of physicists exposed to fast neutrons from cyclotrons developed cataracts (Abelson and Kruger, 1949), and it was thought that opacities had occurred with exposure to less than 1 Gy of a mixed gammatneutron radiation. However, because the precise dose levels that were involved are not known, it is impossible to compare the effectiveness of these exposures to those of other radiation qualities (Ham, 1953). The data for induction of cataracts by neutrons in humans is limited. Roth et al. (1976) reported that in some patients treated with 2.2 Gy of 7.5 MeV neutrons in 12 fractions, there was a small loss of vision. When compared to the 5.5 Gy of fractionated exposures to x ray, reported by Merriam and Focht (1962) to be the threshold dose, the RBE value is about 2.5. It was hoped that the studies of the atomic-bomb survivors would provide reliable estimates of the risk of induction of cataracts by both gamma rays and neutrons. The new dosimetry has diminished that hope because, in the case of neutrons, the estimate of the contribution of neutrons to the doses has been lowered. A report by Oraki and Schull re-examined the quantitative relationship of exposure to ionizing radiation to the occurrence of posterior lenticular cataracts seen among 2,124 Hiroshima and Nagasaki atomic-bomb survivors examined in 1982with known DS86 (Dosimetry System 1986) doses (Otake and Schull, 1990). Among several dose-response relationships with or without two thresholds, the best fit based on binomial odds-regression models is achieved with a linear gamma, linear neutron dose-response relationship that assumes different thresholds for the two types of radiation. The estimates of the two thresholds differ significantly from zero: 0.06 Gy with 95 percent bounds of 0.03 and 0.10 for the neutron dose, and 1.08 Gy with 95 percent bounds of 0.51 and 1.45 for the gammaray dose. These values are significantly less than the commonly accepted low-LET threshold dose of 2 Gy for cataract induced by a single acute exposure (Merriamand Focht, 1962).However, the value of the RBE for induction of cataracts by neutrons was estimated

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using DS86 eye organ doses, linear dose-response relationships for both gamma rays and neutrons, and a threshold for each radiation. The RBE value was calculated to be 32 (12 to 89,95 percent confidence limits) (Otake and Schull, 1990). If a linear-quadratic model had been used to fit the data for the gamma rays, the value of the RBE would, presumably, be higher. So far, the results from animal experiments have not reduced the uncertainty about the RBE values for neutron induction of cataracts. There are very limited data available from large animals, in particular non-human primates. In monkeys exposed to 14 MeV neutrons (Brown, 1960), opacities that were considered too small to impair vision were observed after 75 rep, more severe lesions were seen after 250 rep and mature radiation cataracts occurred after 850 rep.'' Based on exposure to 6Cogamma radiation, Brown (1960) estimated an RBE value of four for the induction of cataracts by 14 MeV neutrons. Recently, Worgul et al. (1996) reported the occurrence of opacities of the lens in young rats (28 d of age) exposed to 400 keV monoenergetic neutrons and 250 kVp x rays. The severity of the opacities was graded. The authors state that the RBE value of the neutrons increases, reaching 250 to 500 a t doses of 2 mGy neutrons and 0.5 Gy x rays. The results do not indicate a threshold dose for neutrons. The authors claim that there is broad agreement, across species, of a trend showing RBE values increasing to more than 100 as the dose is reduced to less than 10 mGy. The question is whether the small percentage of the lens epithelium that incurs deposition of radiation energy at very low doses produces clinically significant cataracts in humans or only lesions that can be detected. It is not clear whether this analysis is applicable to radiation protection. 5.3.2.4 Heavy Ions and the lens. It is possible that the low fluence of heavy ions in LEO could induce the least severe category of opacification. However, the threshold dose required for clinically significant cataracts is not expected to be reached.

Summary. The available data suggests that damage to the eye including cataract induction should not pose a risk to crews involved in LEO missions. The low dose rate of the space radiation and the unlikelihood of acute doses of sufficient magnitude decrease the probability of clinically significant cataracts. There is uncertainty 5.3.2.5

"The unit "rep"(roentgen-equivalent physical) was used for radiation protection purposes as a measure of the effect produced in tissue by radiation. One rep was considered to be 9.5 x Gy in soft tissue, equivalent to an exposure of 1 R.

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91

about the effect of the broad range of neutrons that occur within the spacecraft and the effect of the low fluence of heavy charged particles. 5.3.3

Skin

The surface area covered by the skin in a so-called standard man of 70 kg is about 2 m2.The skin consists of an epidermis and dermis that are distinct in structure and function (Figure5.9).In the epidermis, The Integument Stratum corncum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale

Duct of sweat gland

Subcutancous tissue Sweat gland

Fig. 5.9. General view of the skin (Hamilton, 1956).

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about 96 percent of cells are keratinocytes; the other four percent consisting of melanocytes, that produce the protective pigment melanin, and Langerhans and other cells that are components of the immune system. The thickness of the epidermis ranges from -20 pm on the face to 300 to 400 pm on the fingertips. The turnover time of the normal human epidermis varies in different parts of the body from about 7 to 10 d. 5.3.3.1 The Responses to Radiation. A number of reviews of the effects of radiation on skin have been published (Hopewell, 1986; 1990;ICRP,1991b;Potten, 1985).The information about the damage that radiation can cause in skin, the temporal pattern of its appearance, and the recovery that occurs are well documented from clinical observations. No effects of irradiation can be seen so easily as those in the skin. f i r exposure to ionizing radiation a t levels above the threshold ( 2 2 Gy of x rays for the early erythematous reaction) the skin shows several distinct phases of damage. The severity of the acute damage is dependent on dose and pattern of irradiation in relation to time (Figure 5.10). Low dose rate irradiation, especially if it is protracted over periods of more than six weeks, is considerably less effective than acute high dose rate exposures in producing damage to the epidermis. For late effects in the dermis, the role of time over which the exposure occurs is less certain. The classification of deterministic

L 0

I

I

I

10

20

30

1

40 Days aher irradiation

1

I

I

50

0

10

, 20

30

I

40

50

Dose (Gy)

Fig. 5.10. Assessment of the response of mouse skin to irradiation. (a) The skin reaction (mean of a group of mice) assessed on a n arbitrary scale as indicated is plotted as a function of time after a dose of radiation (30 Gy). The average reaction calculated over a certain time range (e.g., 7 to 30 d) as indicated is determined and plotted as a function of radiation as shown in (b) (Tannock and Hill, 1987).

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effects has evolved as the understanding of the underlying mechanisms have been elucidated. The time of occurrence for the acute deterministic effects range from hours for early transient erythema to about four weeks for dry and moist desquamation. Late effects such as dermal atrophy and telangiectasia may not appear for more than six months and a year, respectively (Hopewell, 1990; ICRP, 1991b).The response ofthe skin depends on the number of exposures, the total dose, the dose per exposure, the volume of tissue irradiated, and the energy of the radiation. The early damage to microvasculature is reflected in increased permeability of the superficial capillaries caused by the activation of a proteolytic enzyme. This early erythematous reaction occurs within a few hours of exposure and may last up to 2 d. The threshold dose for low-LET radiation is about 2 Gy when the field is large. The main erythematous reaction, which occurs two to four weeks after exposure, is due to an inflammatory reaction that is secondary to the death of basal cells. The threshold dose is about 5 to 6 Gy. The more severe acute effects that are due to killing of the basal cells such as moist desquarnation and ulceration only occur after very large doses, about 20 Gy (see Hopewell, 1990 for a review). Fractionation and protraction of the exposures increases the threshold doses for the acute effects which increases the confidence in the opinion that acute deterministic effects in the skin will not occur in astronauts who are exposed in LEO. The later deterministic effects, all of which occur only after large doses (Archambeau, 1987; Hopewell, 1986),include dermal necrosis resulting from the damage to the vasculature, dermal atrophy, depigmentation telangiectasia, and invasive fibrosis. Telangiectasia is an abnormal dilation of the superficial capillaries in the dermis which occurs a year or more after exposure. Both the severity and its rate of progression are dose dependent. A more subtle change may be the loss of proliferative capacity and lack of wound healing. A study has been carried out on the monkeys exposed in 1964 and 1965 to protons of different energies that are encountered in space. The results have been interpreted to indicate radiation-induced "acceleratedcellular aging" (Cox et al., 1986). There is also some evidence of less efficient healing in the irradiated animals. 5.3.3.2 The Influence ofRadiation Quality. The value of the RBE for protons for acute effects in skin, based on experimental studies, is unlikely to exceed 1.5 (Urano et al.,1984). In the case of neutrons the RBE increases with decreasing dose and is influenced by neutron energy. Based on experimental studies with very small doses per

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fraction, the RBE value for high-energy neutrons was three to four and about eight for lower energy neutrons. The effects of helium (Leith e t al., 1975; 1977), neon (Leith et al., 1976; 1977; Raju and Carpenter, 1978), carbon (Leith et al., 1983; Raju and Carpenter, 1978), and argon (Raju and Carpenter, 1978) on early skin reactions in rodents have been reported. The values for RBE are shown in Table 5.3. The data of Brown e t al. (1973) for nitrogen ions indicate RBE values of 1.1to 1.5 for dry and moist desquamation. Leith et al. (1981)found an RBE value of 2.1 for fractionated exposures of carbon ions in hamster skin using 2 Gy fractions of x rays as the reference radiation. While the evidence suggested somewhat less repair of damage with exposure of the skin to heavy ions than with low-LET radiations, it does not indicate marked differences in the effectiveness between heavy ions and x rays in the induction of acute effects in the skin. More recent studies of Blakely and Castro (1994) suggest that the main erythematous reaction in humans is LET-dependent. The reaction is increased in severity and the time of appearance is decreased with increasing LET. The influence of the LET of carbon ions has been studied by Ando et al. (1998). The isoeffect for 50,60, 70 and 100 keV urn-' carbon ions increases with the number of fractions. The value of the RBE increases with the increase in the number of fractions. The value of the RBE increases linearly with LET for all fractionation regimens. 5.3.3.3 Summary. It is unlikely that deterministic effects in the skin will occur in astronauts who are exposed in LEO because of the magnitude of the threshold doses and the fad that the dose rates of the radiation in space are low. When a very large SPE and a magnetic storm are coincident, the shielding by Earth's magnetic field is altered. However, even in EVA during LEO, the dose should not reach the level of the threshold dose for skin. For example, the early erythematous reaction is only seen with acute doses of 2 2 Gy of low-LET radiation.

5.3-RBE TABLE

values for acute skin response in mouse skin.

Radiation

Helium Carbon (400 MeV n-l) Neon (400 MeV n-I) Neon

RBE Plateau Peak

1.0 1.2 2.0 1.5

1.3 1.5 1.7

Reference

Leith et al. (1975) Raju and Carpenter (1978) Raju and Carpenter (1978) Leith et al. (1976)

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Health Effects Related to the Reproductive System

There are two effects of potential concern that are related to the reproductive systems of space crews exposed to ionizing radiation while conducting missions in LEO:the effects on future offspring of exposed persons (hereditary effects) and temporary or permanent sterility.

5.4.1

Hereditary Effects

The Space Radiation Study Panel, Life Sciences Committee (NAS/ NRC, 1967) stated that the increment of hereditary risk that might be incurred by anticipated manned flight operations could be viewed as insignificant in relationship to the spontaneous incidenceof hereditary defects in the population as a whole. This judgment was based on the rather conservative assumption that an average total dose of 2 Gy might be received by each of 50 flight personnel over a 10 y period of accumulation (an average annual dose of 0.2 Gy). A total collective dose of 102 person-gray would have been added to the estimated collective GSD of 12 x 105person-gray accumulated in the general population during the same 10 y. This would have been an increase of about 0.008 percent in the collective GSD normally generated in the population of the United States from natural radiation sources (NCRP, 1975; 1987a). A subsequent report from the Radiobiology Advisory Panel, Committee on Space Medicine (NAS/NRC, 1970) suggested that an annual maximum dose of 0.38 Gy to the testes could be employed, with certain assumptions and limitations specified in the report, as a guide for mission and vehicle-design studies involving nuclear systems. This high value for gonadal dose was allowed because the panel did not consider genetic risks to be an important issue because of the greater expected age of the crew, the small number of crew members involved, and the unavoidable exposure related to either nuclear propulsion or on-board nuclear power supply systems. The guidelines, at that time, were directed toward potential concerns of the crew about such matters as induced oligospermia or aspermia, more as a psychological variable than a physiological problem. Present day concerns, and those that might prevail over the next several decades, must take new and different factors into consideration. These include the fact that both genders are now actively employed in flight programs, the average age of flight personnel, while still above the average reproductive age, will probably steadily decline, the number of personnel involved will probably increase

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significantly, and the average duration andlor frequency of missions can be expected to increase. Total levels of individual exposure and accumulated person-sievert should increase accordingly, though the contribution to GSD of the United States population will remain a t a n insignificant level. Despite the larger number of personnel involved and their expected younger age, the concern about genetic risks continues to be a more personal or individual issue (Grahn, 1983). To address individual concerns, good estimates of total dose, dose rate, and LET will be required, because the rate of induction of chromosome aberrations or gene mutations is quite sensitive to these variables. It is usually not possible to predict the total dose and the magnitude of associated factors in the absence of specific flight plans. Therefore, the simplest approach is to rely on certain basic or known parameters of genetic risk and then apply the appropriate corrections to account for such factors as dose rate or LET. The basic risks related to low-LET radiation exposure have been thoroughly reviewed and set down by the Advisory Committee on the Biological Effects of Ionizing Radiations (NASLNRC, 1972; 1980; 19901, commonly referred to as the BEIR committees. Its report, BEIR V (NAS/NRC, 1990),can be accepted as the source of basic genetic risk coefficients. These can be added to, or adjusted to allow for variation in LET, dose rate, germ cell stage, and gender, as appropriate. The question of gender differences in sensitivity to mutation induction is complex and lacks an entirely satisfactory resolution. Most information is based on experimental work with mice, and mostly with males, because the female mouse is sterilized by low doses (0.5 to 1Gy) and is, therefore, a poor surrogate for the human female. Over the past decade, the various expert committees, when faced with establishing a coefficient that relates the female to the male in terms of relative genetic sensitivity, have taken positions ranging from zero to one (zero means insensitive and one means equal to the male). A simple, conservative approach is to assume equality of the two genders with regard to their sensitivity to mutation induction by radiation. This is either the correct estimate, or it overestimates the risk by a factor of about two. With the assumption of equality, one can then proceed with any analysis of genetic risks by using the abundant data derived from irradiated males. Germ cell stage is an important variable, especially for the male. The mutation rate for the post-spermatogonial stages (meiotic and postmeiotic cells)is higher than for the premeiotic or spermatogonial stages. Damage induced in the premeiotic stage is subject to rigorous selection due to the number of mitotic divisions that the cell must pass through. The unbalanced aberrations and other cell

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lethals would be culled from the cell population before the spermatocyte stage is reached. In the last stages of germ cell maturation (meiotic and postmeiotic), lethal mutations are not as rigorously culled. This leads to a higher mutation rate and one that contains more lethal and sublethal damage. This post-spermatogonial period has well defined time limits, however, so that the potential genetic problems can be avoided by simply refraining from reproduction for the 74 d that are required for a full cycle of spermatogenesis in man (Lyon, 1981). Once the first post-irradiation wave of spermatogenesis is completed, the genetic damage induced in the spermatogonial stem cells will be transmitted through the stages in the subsequent cycle of spermatogenesis. Though the realized mutation rate will be significantly lower than that from the exposed postspermatogonial stages, this rate will potentially persist for the lifetime of the individual. Dose rate is a significant variable for low-LET radiations. The average DREF that is used for low-LET irradiation of the spermatogonia is three (NASLNRC, 1972; 1980; 1990). The genetic risk coefficients recommended by BEIR V (NASINRC, 1990) and other committees have used low dose rate exposure as the standard. The value of three, however, is really limited to specific locus mutations induced in stem cells and should realistically be greater for the induction of chromosome aberrations (Grahn, 1983), wherein the DREF may be as high as 8 or 10. No DREF is assumed for highLET radiations, though there is a possibility that a fador less than unity might be reasonable, as there is evidence for the induction of an augmented level of the effect on the genome following low dose rate and low total-dose exposure to a high-LET radiation (Grahn, 1983; NCRP, 1987~). The dose rate of the proton radiation, which is the largest component of the radiation encountered in space, is low. LET is the last of the subsidiary variables and it is both important and complex. Within this variable are contributing factors such as dose rate, exact LET, total dose, genetic endpoint, cell stage, and gender. Much of this has been discussed elsewhere (Grahn, 1983; NCRP, 1987c; 1990) and will not be repeated here other than to note that the value of the RBE may vary between 5 and 50, and possibly more, using data from males exposed to neutrons, but may be as low as one in the case of females. The highest values are those relating to the induction oftransmissible balanced chromosome aberrations when the comparison is between protracted fission neutron irradiation and very low intensity, near continuous gamma irradiation. HZE particles will probably have an RBE value below those noted for neutrons, or certainly no greater than those values, because of the extreme heterogeneity of energy deposition in the gonads and

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the high probability of cell killing being the dominant biological effect. The BEIR V Committee (NAS/NRC, 1990) estimates of genetic risks from exposure to low-LET radiation delivered at low dose rates are 20 to 50 x Sv-l for the first generation offspring and 115 to 215 x lod4Sv-' per generation at genetic equilibrium following continuous exposure to 10 mSv every generation. These estimates are only for dominant, sex-linked, chromosomal and congenital genetic diseases, but not for the larger class of complexly-inherited diseases which are estimated to comprise about 90 to 95 percent of all genetic disease. BEIR V (NASNRC, 1990) stated, "Because of great uncertainties in the mutational component of these traits and other complexities, the committee has not made quantitative risk estimates. The risks may be negligibly small, or they may be as large or larger than the risks for all other traits combined." The 1988 UNSCEAR genetics committee (UNSCEAR, 1988) also did not provide risk estimates for complexiIy inherited diseases. However, Sankaranarayanan, on behalf of ICRP, used a mutational component of five percent and a weighting factor of one-third for severity of effects, estimated about 70 x Sv-l cases could be expected in the first two generations and about 355 x Sv-l over all generations (ICRP, 1991a). Abrahamson et al. (1991) used a higher mutational component of 13 percent and the BEIR V (NAS/NRC, 1990) estimate of the current incidence of complexly inherited genetic disease of 120 percent (1.7 times larger than ICRP) to produce risk estimates of 70 x Sv-I for the first generation and 1,600 x Sv-l for all generations. Given the different initial assumptions utilized by ICRP (1991a) and Abrahamson et al. (1991), it is not surprising that the risk estimates differ by factors of as much as four to five. Thus, the first generation risk estimates could range from 0.2 to 1.3 x Sv-' and the all generation risk estimates from 1.2 x Sv-l to 18.2 x Sv-I depending on whether the irregular inherited class is considered and depending on the assumptions made in the calculation of the contribution of the multifactorial component. For the small population of flight personnel, the first generation risk is probably the significant risk for consideration of exposure limitations. Because of the important contribution from both major and minor chromosome aberrations to the genetic defects seen in the first generation, LET, cell stage, and dose rate become the critical factors to be considered in limiting exposures and risks. If care is taken to avoid conceiving offspring during the first few months after exposure (eliminating cell stage as a factor), the risk coefficients

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stated previously may only need adjustment for LET, because it is unlikely that truly high dose rate exposures will occur. The RBE values may not be trivial. However, the risk of hereditary effects for all generations is of such importance that ICRP (1991a) and NCRP (1993a)have included a risk value of 1x Sv-' for all generations in their estimates of total detriment.

5.4.2

Summary of Hereditary Effects

Terrestrial radiation protection standards are set at levels that allow for a designated mutation load being added to the gene pool of the population. In the past, the number of astronauts was small and, therefore, concern for potential genetic effects on an individual basis was more a matter of personal counseling than population protection. In the future, it is reasonable to assume that the number of space workers of a reproductively active age will increase. Longer and more numerous missions, with more space workers, will raise the total GSD aver that in the past, but the contribution to the United States population will remain at an insignificant level. The estimate of genetic risk must be in the perspective of the spontaneous mutation rates. While such rates are based on limited studies, an incidence of 10,000 cases per million live born has been used by the committees estimating genetic risk from radiation. The incidence is subdivided into severe disorder (2,500 cases per lo6 live born) and "clinically mild" cases (7,500 per lo6 live born). The importance of the risk is to individuals and their descendants rather than to an entire population. A recent estimate for genetic risk for the first generation is of the order of 1.3 x 10 Sv-'and for all generations it is 18.5 x Sv-' (Abrahamsonet al., 1991).There is considerable uncertainty in the estimate of radiation-induced genetic effects in humans, and no significant increase in genetic effects has been detected among the offspring of the atomic-bomb survivors. Full information about genetic risks should be given to crew members, and with appropriate counseling, genetic risks that are already small may be reduced by appropriate timing of pregnancy. However, the risk estimate of hereditary effects for all generations recommended by ICRP (1991a) and NCRP (1993a) is 1 x Sv-I and for the purposes of this Report is still considered appropriate. The introduction of women into the ranks of the astronauts and payload specialists does not introduce a further consideration into possible genetic effects since the female is considered less sensitive to radiation-induced genetic effects than are males. But the prudent

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approach to protection is to consider male and female genetic sensitivity equal; at worst this approach may overestimate the risk by a factor of two.

5.4.3

Radiation-InducedSterility

Male. The seminiferoustubules of the testis consist of two separate cell populations that differ in origin, function and radiosensitivity. The spermatogenic cells are very radiosensitive, but the Sertoli cells which provide nutrition and support are not. The Leydig cells which are located in the interstitial tissue between the tubules are the source of testicular hormones and are radioresistant. Irradiation may reduce fertility but not libido. The effects of radiation on the human testis were reviewed by Meistrich and van Beek (1990). The data for the response of the human testis to irradiation comes from studies of: (1)the atomic-bomb survivors (Jordan et al., 1966); (2) nuclear accident victims (Hasterlik and Marinelli, 1956; Hempelmann et a l . , 1952; MacLeod et al., 1964; Oakes and Lushbaugh, 1952); (3) volunteers a t the state penitentiaries in Washington (Clifton and Bremner, 1983; Paulsen, 1973; Thorslund and Paulsen, 1972) and Oregon (Clifton and Bremner, 1983; Heller, 1967;Rowley et al., 1974);(4)radiotherapy patients; and (5)occupational exposure (Popescu and Lancranjan, 1975). The endpoints of importance are temporary and permanent sterility. Sterility results from decreased sperm counts caused by killing of spermatogonia and lack of maturation of the surviving spermatogonia. In the human the mechanisms regulating the differentiation of spermatogonia appear to be more sensitive to inactivation by irradiation than are the stem spermatogonia themselves (Meistrich and van Beek, 1990).The broad distribution of sperm counts in the population and the existence of a background level of infertility, makes it probable that there may be no threshold for temporary infertility caused by radiation-induced reductions in sperm counts (Meistrich, 1992; Meistrich and Brown, 1983). It is estimated that a two-fold reduction in sperm counts in a population would raise the incidence of infertility in the population from a background of 15 percent to about 18.5 percent. The most complete data relevant to the estimation of effects of single doses of radiation on spermatogonial killing and sperm-count reductions come from the study at the two state prisons of healthy volunteers whose testes were exposed to 250 kVp x rays. The results of the quantitative histological analyses of spermatogenesis are 5.4.3.1

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shown in Table 5.4. The results indicate that A, and B spermatogonia (Table 5.4) are the most sensitive to irradiation, a finding that is consistent with those for experimental animals. The low number of early spermatocytes reflects the loss by normal maturation and the lack of production from the type B spermatogonia. The effects on sperm counts in man become apparent a t different times after irradiation and the times are dictated by the stages of spermatogenesis. For about eight weeks after irradiation the sperm count remains within normal levels. This phase is followed by a decreased production of sperm, with the nadir about three to eight months after exposure. Transient four-fold reductions in the sperm count have been reported a h r 0.15 Gy, and a lack of sperm, azoospermia or aspermia after doses of about 0.2 Gy and greater. Based on the available data the probability of azoospermia as a function of dose is shown in Figure 5.11. It can be seen that the probability of azoospermia is 50 percent in men exposed to about 0.35 Gy and is 90 percent after approximately 1 Gy. The third phase is the onset of recovery of sperm production. The time of onset of recovery is dose dependent, for example, a h r exposure to 0.2 Gy sperm production may s t a r t a t six months

TABLE 5.4-Germ cells two weeks after irradiation of testes." Percentage of Remaining Cellsb Cell Type

I GY

6 GY

Spermatocytes Early Pachytene Spermatids Round Elongated -

-

-

"Calculatedby Meistrich and van Beek (1990) fiom data of Rowley et al. (1974). bThe percentage of remaining cells are based on pre-irradiation values normalized to the number of Sertoli cells. 'A, are the pale staining spermatogonia in contrast to the & spermatogonia which are deeply staining and appear not to proliferate but act as a reserve of stem cells. B cells are a later stage of differentiation of spermatogonia.

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0.2

0.5

1 2 Radiation dose (Gy)

4

6

Fig.5.11. Percentage of men who develop azoospermia at any time after various total doses of radiation (doses plotted after square-roottransformation). Different symbols are used to indicate experimental (e = single-dose x ray), accidental (A = single-dose neutron and gamma radiations), and = therapeutic (fractionated x or gamma rays: V = testicular cancers; nontesticular cancers) irradiations. Doses from accidental exposures presented as the equivalent x-ray doses. Horizontal error bars are used to indicate the range of doses pooled to obtain some of the points. Vertical bars are used to indicate points for which the value is a lower limit because of infrequent sampling (Meistrich and van Beek, 1990).

post-irradiation, but not for 2 y or more after 6 Gy. The final phase is the return of sperm counts to normal levels. This occurs at about 1 y after single doses of 0.5 Gy. The studies of survivors of radiation accidents suggest that H to cause azoospermia a t 1 y after exposure in 50 percent of those irradiated is 1.5 Sv, whereas the data for the prisoner volunteers suggested a dose of 3 Gy. The difference between these results may be due to the considerable problems in the dosimetry in the accident cases, in part because of the mixture of radiation qualities. It is concluded that more than 6 Gy of acute radiation is required to produce permanent sterility. The exposures in LEO are a combination of the protracted low dose rate irradiation and a somewhat higher dose rate during traversal of the space vehicle through the SAA. For almost all tissues, this type

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of exposure pattern would result in a lesser effect than would be caused by acute single doses, but this is not so for the testis. Lushbaugh and Casarett (1976)reported that 7.74 x C kg-' (3R) d-' over a 25 week period was at least four times more effective in reducing spermatogenesisthan single doses. Informationrelevant to the exposure in LEO can be obtained from the study of patients receiving radiotherapy. Based on Meistrich and van Beek's (1990) review, fractionation appears to be about 2.5 times more effective in reducing spermatogenesis in man than single doses. The estimated dose that results in permanent azoospermia, and therefore sterility, based on studies of patients receiving radiotherapy in conventional fractionation regimens is 2.5 to 4 Gy. It can be seen from earlier studies, Table 5.5, that estimates of the threshold doses for temporary and permanent sterility based on radiotherapy cases show considerable variation. The mechanisms responsible for sensitization of the testis to fractionated irradiation are unknown. The major difference between exposures to the testes occurring during radiotherapy for various types of cancer and radiation exposures in space is in the dose rate. For example, a patient that has received a dose of 0.5 Gy to the testis during radiotherapy would have received multiple fractions over a period of weeks, each fraction at a high dose rate. The current recommendation for the 1 y dose limit is 0.5 Gy. This dose rate spread over 1 y is equal to a dose rate of 1.37 mGy d-l. Based on the experimental data, this level of protraction should reduce the effect on the spermatogonial cells materially. Oakberg and Clark (1961)reported a threshold of about 130 mGy d-' in mice for the induction of sterility and Stadler and Gowen (1964)reported a maintenance in mice of the germline for 11 successive generations exposed to 30 mGy d- l. In the dog, Casarett and Eddy (1968)found no effect vrrith 0.31 X C kg-' d-' (0.12 R d-'1. A reduction in sperm count occurred after 20 weeks of daily doses of 1.55 x C kg-' (0.6R). TABLE 5.5-Doses received in multiple exposures that have been reported to cause long-term azoospermia. Total Dose

(GY)

Follow-Up (months)

Reference

2.77 2.80 2.89 3.12 2.5

60 168 84 156 26

Sandeman (1966) Sandeman (1966) Sandeman (1966) Sandeman (1966) Speiser et al. (1973)

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Kumatori et al. (1980) reported severely decreased sperm counts in the Japanese fisherman exposed to about 1.4 to 6 Gy from fallout over a two week period as a result of an atomic-bomb test. Sperm counts recovered within 2 y and many of the men fathered normal children. The only report of the effects of occupational exposure is by Popescu and Lancranjan (1975), who found reduced sperm counts in workers exposed from 2 to 27 y with annual doses that ranged from 5.5 to 29 mGy. There were no data for effects on fertility. 5.4.3.2 Female. Although the human ovary is less sensitive to radiation-induced damage than is the testis, the consequences of ovarian failure which is generally irreversible include not only sterility but also the loss of hormone (i.e., estrogen) production and induction of premature menopause (Meistrich et al., 1996). The threshold dose for ovarian failure is highly age dependent, primarily because of the loss of oocytes with age (Rubin and Casarett, 1968). The dose to induce ovarian failure decreases continuously with age and the differences are most dramatic over 40 y of age. Doses below 1 Gy are likely to have no long-term effect on fertility. However, there is some risk of ovarian failure from 1.5 Gy in women over 40. Doses of 3 Gy are required to produce ovarian failure in 50 percent of women around age 35, but at age 20,5 Gy is necessary to produce that effect (Meistrich et al., 1996). Protraction or fractionation of doses reduces injury to the ovary (Sanders et al., 1988). The estimates of threshold doses for radiation-induced sterility in females based on data from multiple radiotherapeutic exposures are shown in Table 5.6. 5.4.3.3 Summary. The cells of the testis are very sensitive with the exception of the cells responsibIe for the hormones involved in libido. Fractionation of exposures has less effect in decreasing the radiation effect on the testis than in other tissues. In fractionation regimens the dose rate of the individual fractions is high. Fortunately, the testis has considerable powers of recovery, albeit slowly. For example, sperm production recovers in virtually all cases within 2 y, even after a dose as high as 6 Gy, and with a year after about 0.5 Gy. The estimates for dose rates for exposures on the ISS, based on the experience with the Mir Space Station, indicate that the equivalent dose rate is unlikely to exceed 300 mSv y-I (about 0.8 mSv d-l). There is a paucity of data for the effects of low dose rate exposures of the gonads in humans. However, male and female mice continuously exposed (22 h d-l) up to about 20 mGy d-I), of 60Cogamma rays reproduced normally for 10 generations. There was a striking lack

Women 15 to 40 y of Age

Women Over

TABLE 5.6-Threshold doses to the ovaries reported to cause permanent ovarian failure in women re radiotherapy in multiple exposures (adapted from Ash, 1980; Damewood and Grochow, 1986) Dose (Range)

-

No deleterious effect Some risk of ovarian f 100% permanent ovar

No deleterious effect No deleterious effect in most women About 60% permanent ovarian failure

-

100% permanent ovar

60% to 70% permanent ovarian failure Nearly 100% permanent ovarian failure

0.6 Gy 1.5 Gy 2.5 to 5.0 Gy 4.0 to 7.0 Gy 5.0 to 8.0 Gy >8.0 Gy

"Ovarian failure includes loss of estrogen production and premature menopause.

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of evidence of effects on fertility or visible gene mutations even aRer a total dose of about 13 Gy. Such an exposure given in a single dose would have sterilized humans, both female and male. Thus, the evidence suggests that marked sparing of the low-LET radiation effects on the gonads can be expected with exposures that will be encountered in LEO. The fluence of heavy ions is low and the RBE value for spermatogonial damage is also low. The ovary is less sensitive than the testis but the sensitivity increases with age, mainly due to the loss of oocytes with age. As is the case for effects in the male, the lack of data hampers accurate estimation of the risk of infertility. The data from fractionated exposures of women and the data from mice exposed at very low dose rates, but at rates higher than are likely to occur in LEO, indicate that the expected radiation levels on the ISS will not affect function of the ovary. Although there is a need for more definitive data for the effects of low dose rate exposures on fertility in both women and men, the 1y and career limits should provide protection from infertility.

5.5 Radiation Carcinogenesis 5.5.1 Introduction In the past decade, knowledge about the late effects of radiation in humans has increased because of the accumulation of data from studies of:(1)the atomic-bombsurvivors, who were exposed to wholebody irradiation; (2) patients exposed to partial-body irradiation; and (3) to a lesser extent, worker populations. For the estimates of risk of induction of cancer by radiation, the major source of data has been the atomic-bomb survivors. The data from atomic-bomb survivors and some populations treated with radiation have been reviewed by ICRP (1991a), NAS/NRC (1990), NCRP (1993a; 1993b), and UNSCEAR (1988; 1994). The data from the atomic-bomb survivors, the basis of current risk estimates for radiation protection, have appeared in a series of papers, the most recent being, for mortality (Pierce et al., 1996) and for incidence (Preston et al., 1994; Ron et al., 1994; Thompson et al., 1994). The national and international committees concerned with risk estimates of the induction of cancer by radiation, for radiation protection purposes, have had to derive estimates based on data from populations exposed a t a high dose rate. Estimates of the risk incurred by worker populations, in particular nuclear workers, have

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been made (Beral et al., 1985;1988;Cardis et al., 1995;Checkoway, 1985;Gilbert, 1983; Gilbert et al., 1989;Kendall et al., 1992; Muirhead et al., 1999). The exposures to these populations, while protracted over their working lifetime, are complex. In some cases all the irradiation is at low dose rates, but in others the irradiation consists of a mixture of small fractions a t high dose rates and protracted low dose rate irradiation. Some exposures have been to various radiation qualities and to both internal and external radiations. More important, however, has been the low statistical power at low exposures for all of these studies coupled with the strong potential for confounding (e.g., by the influence of various chemical agents to which workers may have been exposed)when relative risks are small. However, worker studies have confirmed that risks are not grossly overestimated even if they have not been able to precisely quantify them. Despite the remarkable efforts to determine radiation effects in humans, there is considerablecontroversyconcerning the magnitude of the biological effects at low doses of radiation. There are substantial difficulties in studying, directly, the effects of low doses of radiation, such as the size of the population sample required (Land, 1980) and the difficulty in controlling the many factors that influence cancer incidence. The risks from low doses, and particularly a t low dose rates that characterize the proton irradiation in space, have to be obtained by extrapolation from data obtained a t high doses and high dose rates. It is for this reason that the choice of dose-response models and data for humans exposed to low dose rate irradiation have become so important. Of fundamental importance is the lack of human data on many of the kinds of radiation exposure likely to be encountered (e.g., neutrons) in space.

5.5.2

Mechanisms of Radiation Carcinogenesis

While each tumor type has a distinct age-distribution pattern, cancer, in general, is a disease of old age. It has been suggested that the increasing incidence of cancer with age reflects the effects of lifetime exposure to noxious environmental agents. Data h m experimental animals protected from the vicissitudes of life belie this argument as the increase in cancer incidence with age shows the same pattern seen in humans. Since carcinogenesis is a multistage process, knowing the number and temporal relationships of the stages is important to understand the dose-response relationships. Not only may these differ among various types of solid cancers, it is likely that induction of carcinomas

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and leukemias differs in the number and nature of the stages. The idea that chromosomal alterations plays a role in cancer is an old idea (Boveri, 1929). The identification of the specific chromosomes involved in different types of cancer has now been made for many cancers and in the case of leukemias, specific chromosome aberrations that are causally related. The evidence from studies of myeloid leukemia in mice is that the same specificaberration on chromosome 2 occurs in both the naturally occurring and the radiation-induced leukemia. It is reasonable to believe that this lack of a difference in the initiating lesion holds for leukemias in humans. In other words, there is no signature lesion specific to radiation. Intuitively, it seems possible that leukemias may develop without all of the multiple stages considered necessary in the development of solid cancers. It is the possible differences in the multiplicity and the kinetics of the stages in development of the cancers that is reflected in the differences in the shape of the dose-response curves between different types of leukemia and between solid cancers and leukemias. Colorectal cancer has been a paradigm for modeling multistage carcinogenesis. Genetic analysis has provided the evidence of multiple mutations and some evidence of association of specific mutations with specific stages (Fearon and Vogelstein, 1990).For example, it has been suggested that the initial event leading to hyperproliferative epithelium in the colon results from mutations in the APC and MCC tumor suppressor genes; 15 to 20percent of these benign colorectal tumors progress to malignancy. Loss of DCC and p53 genes appear to be related to the progression. One of the difficulties in modeling carcinogenesis is the distinction of the roles of mutation and selection in tumor progression. Radiation is capable of inducing mutations at the several loci involved, but the possibility that a single exposure to radiation could induce mutations of several loci is attractive (Loeb, 1998).The fact that radiation can induce genomic instability and thus an increased mutation rate has been offered as an explanation ofhow a single dose induces mutations in the multiple genes involved in carcinogenesis (Morgan et al., 1996). It should be noted that while genomic instability (Morgan et al., 1996)and bystander effects (Nagasawa and Little, 1992)are of interest in the interpretation of mechanisms, they do not influence risk estimates based on epidemiological studies. The initiation events, involving radiation-induced damage to the genome, are essential for the development of a cancer, but they are not the sole determining factor of the probability of a cancer occurring because host factors play a major role in whether or not the initial events are expressed and the potential for cancer is realized. In the case of many cancers, there is a long latent period between exposure

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and the clinical appearance of a cancer. In the case of some cancers, such as breast cancer, the length of the latent period is related to the age at exposure. The radiation-induced excess incidence does not appear until the age at which there is an increase in the natural incidence in the unexposed population. This observation suggests that age is a host factor and may reflect changes, such as hormonal levels, important to the development of the cancers. The effect of genetic susceptibility on the risk of radiogenic cancer not only affects the probability of incidence but, also, may influence the time of appearance. For example, it has been found that breast cancers induced by radiation in most persons exposed at a very young age do not appear until the time at which the so-called spontaneous breast cancers are beginning to appear in the unexposed population. It has been noted that a number of women who were exposed at a young age developed breast cancer before the age of 35 (Tokunaga et al., 1994). It is thought that these cases represent a small susceptible subpopulation that may have an alteration in one of the genes associated with breast cancer.

6.6.3 Dose-Response Relationships For many cancer sites the data are insufficient for the task of delineating dose-response relationships, especially in the low dose region. An excess radiation-induced cancer mortality has been demonstrated for doses down to and perhaps lower than 0.2 Gy in the atomic-bomb survivors, and the possibility of a threshold dose for the induction of certain cancers, for example, skin, has not been unequivocally dismissed. For radiation protection purposes, however, prudence suggests that a threshold not be considered in estimating risks at low doses. The data for leukemia, excluding chronic lymphocytic leukemia, which is not thought to be induced by radiation, conforms to a linearquadratic relationship. Such a relationship would be consistent with the role of chromosome aberrations, suggested by the experimental data and an assumption that any further events in the development of leukemia do not alter the nature of the response from a linearquadratic function. Nevertheless, it has also been suggested that an initial linear slope and a threshold are about equally likely in the Radiation Effects Research Foundation (RERF) data (Hoe1 and Li, 1998:lbut Little and Muirhead (1997) reported an absence of evidence for a threshold. However, it is unsatisfactory to rely on a single doseresponse curve based on data pooled from various types of leukemia (Little et al., 1999).

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When all cancers other than leukemia are pooled, the relationship of excess mortality as a function of dose is not significantly different from linear. In the case of individual cancers, the dose-response relationships may depend on the cancer site, an observation consistent with the variation in the forms of the dose-response relationships in experimental animal systems. The dose response of a number of murine tissues can be fitted by the linear-quadraticmodel. However, in some tissues the linear component of the response may dominate over a dose range of zero to about 0.5 Gy or more, whereas, in other tissues the linear component may predominate over a smaller dose range. In the dose range over which it is practical to obtain data for induction of tumors by low-LET radiation, there will be multiple tracks per cell nucleus, perhaps as many as 100 tracks at 100 mGy (Goodhead, 1988).For model building it is important to know how many tracks traverse the relevant targets. If a linear response indicates a single-track event, the marked difference in the extent of the linear component of the responses in different tissues may indicate a difference in the number or size (or both) of the targets in the nuclei. Such differences may also underlie differences in the mechanisms of carcinogenesis. It has been suggested that the DNA lesions responsible for the biological effects result from single-track events which can be repaired up to doses at which the capability for repair saturates (Goodhead and Nikjoo, 1989; Thacker, 1986). Dose-response curves for both low- and high-LET radiation bend over at higher doses. This change in the shape of the curves has been attributed to cell killing, and currently the dose-response model for low-LET radiation is described as follows: F(D) = (a,

+ alD + a2D2>exp(-@ID - bD2),

(5.1)

where F(D) is the effect, such as incidence of cancer as a function of a given dose, a. is the natural or baseline rate, D is the absorbed dose, al, and a2are positive coefficients ascertained from the data. The exponential terms and are the coefficients of dose for cell killing. The evidence that the killing term is appropriate appears to be based on the analysis by Gray (1965)of the dose response for myeloid leukemia (Upton et al., 1958).Unfortunately, Gray and other modelers based their analysis on a dose-response curve that had not been corrected for competing risks. When this correction is made, the slope of the curve decreases at the high doses, but does not become negative as would be the case with the cell killing term in Equation 5.1. It is reasonable to believe cell killing occurs and influences the shape of the dose-response curves but not as described by

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Equation 5.1. In the case of high-LET radiation it is probable that cell killing contributes to the change in shape of the response curve, but it is improbable that cell killing alone accounts for the bending over of the dose-response curves that may occur at moderate to low doses. The evidence suggests that the current dose-response models are simplistic, especiallyas the evidence that carcinogenesisinvolves a number of steps becomes increasingly convincing. There is a need for a systematic re-examination of the factors that influence doseresponse relationships for cancer induction, which takes into account the new information about the molecular and cellular changes involved in the carcinogenic process. This is particularly true for dose-response relationships for high-LET radiation. A linear doseresponse relationship is assumed for charged particles with LET 0 pm-l. In the case of some experimental systems values ~ 1 0 keV the linear component may dominate only over a small dose range of high-LET radiation and then the curve bends over. There is no general model that describes the complete dose-response curve for the induction of cancer by high-LET radiation. Although the dose rates within space vehicles in LEO can be expected to vary significantly, particularly for those missions that involve repeated traversals of the SAA, it is expected that the dose response for carcinogenic effects from these exposures will be independent of dose rate. This conclusion is based on the observation that multiple energy deposition events that are close enough in time and location within the cellular nucleus to permit interactions between the events are extremely unlikely at these dose rates. This analysis holds regardless of the shape of the dose-response curve for the individual high dose, high dose rate exposures on which our knowledge of human risk is largely based (i-e., the atomic-bomb survivor data). The critical and most difficult question is how to relate the high dose, high dose rate human-risk data to the low dose, low dose rate risk information that is needed. In 1980, the NCRP examined all the available data (NCRP, 1980) and found that the experimental evidence indicated that a reduction of the dose rate of low-LETradiation reduced a broad range ofbiological effects, from mutations to life shortening. In the report, the term dose rate effectiveness factor (DREF) was introduced and was defined as the factor by which linear interpolation from data obtained a t high doses and dose rates overestimates the risk per unit D of radiation delivered at very low doses andlor dose rates. Currently the NCRP has recommended a DREF of two (NCRP, 1993a). The ICRP (1991a)introduced the term dose and dose rate effectiveness factor (DDREF) to include low dose effects consistent with the use of a linear-quadratic dose-response model. The linear-quadratic

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model implies an equivalency of the effect of very small doses at high dose rates, whether as a single exposure or as fractions of a larger total dose and of doses incurred at low dose rates. Both UNSCEAR (1988) and BEIR V (NASNRC, 1990)found that a linear dose response fitted the data for solid cancers and that the linear-quadratic model, which was used in earlier reports was not appropriate. An important consequence of the use of a linear doseresponse model is the question of how to estimate the effects of reducing the dose rate. The experimental evidence is that reduction of the dose rate of low-LET radiation reduces the biological effects, and an apparent linear dose-response for cancer induction which is found for the data for solid cancers in the atomic-bomb survivors, does not imply a lack of a dose rate effect. A DDREF, or ideally, individual DDREFs for specific types of cancer, should be applied to data obtained at a high dose rate. Based on the evidence that a t 1Gy the DDREF is about two, the ICRP (1991a) and the NCRP (1993a) have recommended the application of a single DDREF of two for the low doses and dose rates pertinent to radiation protection. UNSCEAR re-examined this issue in its 1993 report and concluded that a small value of DDREF of not greater than three should be applied at low doses and dose rates (UNSCEAR, 1993). I t is clear that as the understanding of the mechanisms of radiation-induced carcinogenesis increases it will be possible to formulate a model that takes into account the multiple steps and the way the time relationships of the various steps influence the shapes of the dose-response curves. Until the basis of the models for doseresponse relationships is sound, it is prudent to use a linear response for the induction of solid cancers by both low-and high-LET radiations and a linear-quadratic model for the induction of leukemia. However, it is unsatisfactory to have a single-dose response for a group of quite different diseases currently grouped with the designation of leukemia. A DDREF should be used for low-LET radiation because the experimental evidence is overwhelming. There is no evidence that even if a linear dose response extends over a range of doses greater than 1 Gy that lowering the dose rate will not reduce the effect. This is important because the current analysis of the data for solid cancers in the atomic-bombsurvivors indicates linear dose-responserelationship for solid cancers. This should not preclude the application of DDREF, the question is what level of DDREF and should individual DDREFs be applied to different types of tissues. Hopefully the biophysical models, the experimental findings, and the understanding of mechanisms will become consonant. It is not surprising that the choice of the value of DDREF is the major contributor to the uncertainty of the risk estimates of excess cancer mortality (NCRP, 199713).

5.5 RADIATION CARCINOGENESIS

5.5.4

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Epidemiology and Derivation of Risk Estimates

In evaluating radiation hazards, epidemiologic studies have been of the cohort type, where persons exposed and not exposed to radiation are followed forward in time for determination of disease experience, or of the case-control type, where persons with and without a specific disease are evaluated for previous exposure to radiation. The studies of the atomic-bomb survivors which have provided the primary data for risk estimated for radiation protection purposes are of the cohort type (Pierce et al., 1996; Shimizu et al., 1989; 1990). Important information about specific cancers in particular populations exposed to partial-body irradiation has been obtained from various studies (Boice et al., 1991a; 1991b; Darby et al., 1994; Harvey et al., 1985; Howe, 1984; 1995; Ron et al., 1989; Shore et al., 1984a; 1984b). A comprehensive review of the epidemiological studies of radiation carcinogenesis appears in an UNSCEAR report (UNSCEAR, 1994) and an update is available (UNSCEAR, 2000). The susceptibility for the induction of specific cancers by radiation varies between populations and depends on gender and age. It is assumed that all tissues and organs are a t risk for induction of cancer by radiation. However, a causal relationship between radiation and chronic lymphocytic leukemias or Hodgkin's disease has not been established. For this reason, chronic lymphocytic leukemia has been excluded from the analyses of radiation-induced leukemia. It is clear that both susceptibility for induction of cancer and the dose-response relationships vary between different tissues, and the range of doses that double the natural incidence of specific types of cancer is broad. Despite the remarkable body of information about radiogenic cancer, the number of organs for which there are estimates of excess risk with narrow confidence limits is relatively small. The recommendations for dose limits for persons on missions in LEO in this Report are based on the mortality data for atomic-bomb survivors (Pierce et al., 1996)for all cancer which includes leukemia, cancer of esophagus, stomach, colon, lung, female breast, ovary, bladder, liver, thyroid, skin and multiple myeloma, and the remaining sites for which the data have been pooled. Estimates of excess cancer mortality for these individual sites have been made (Pierce et al., 1996).Incidence data can also be of importance, particularly in the case of cancers of low mortality such as cancers of the thyroid and skin (see Appendix A) and UNSCEAR (2000). 5.5.4.1 Leukemia. Leukemia is a frequently reported cancer associated with radiation exposure. For many years the only cancer found in significantly excess rates in the atomic-bombsurvivorswas leukemia.

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This was because the latent period for leukemia is shorter than for solid cancers. It is only in the recent years that excess rates of solid cancer in those exposed in childhood have been noted. The number of excess solid cancers has increased steadily in recent years. In contrast, the mortality rate for radiogenic leukemia has decreased to almost the rates found in the unirradiated population. In most studies the risk estimates for radiogenic leukemia have been based on data pooled for different types of leukemia, and therefore the incidence data (Preston et al., 1994)which are for specific types of leukemia are particularly important. The dose-response relationships, latent periods, and mechanisms of induction are not thought to be the same for all types of leukemia. The data used in this Report come from the Life Span Study Cohort of the atomic-bomb survivors. A total of 202 deaths from leukemia were recorded for the period 1950 to 1985 (Shimizu et al., 1990). A total of 290 leukemia, 229 lymphoma, and 73 myeloma cases have been reported in the leukemia registry (heston et al., 1994).Analysis was camed out on the 231 leukemias, 208 lymphomas, and 62 myelomas in survivors for whom the doses estimated using DS86 ranged from 0 to 4 Gy. The excess absolute risk estimates were 0.6 cases per lo4 PY Sv-' for acute lyrnphocytic leukemia and 1.1 cases per 104 PY Sv-' for acute myelogenous leukemia. The lower estimate of risk of radiation-induced leukemia in the study of the patients with ankylosing spondylitis (Darby et al., 1987; Smith and Doll, 1982)may be explained in terms of the age of the patients, but also by the fact that the doses were fractionated and only a portion of the bone marrow was irradiated. The importance of the amount of active bone marrow that is irradiated is also indicated by the finding that the increase in risk in the patients treated for cervical cancer with radiation was related to the fraction of total bone-marrow irradiated (Boice et al., 1987). The data for radiation-induced leukemia in the atomic-bomb survivors appear to fit a linear-quadratic dose-response model. Since there is no a priori reason to assume that the dose-response curves are similar for different types of leukemia, it is not surprising that studies of different populations of different age patterns and distributions of types of leukemias suggest different fits to the data. The influence of protraction on the induction of leukemias in humans is not clear. Despite claims of increased mortality from leukemia in workers exposed to low dose rate protracted irradiation (Wing et al., 1991),the causal relationships of excess leukemia in persons exposed to low dose rate irradiation is not established in a way that quantitative risks can be estimated. I n experimental systems, a reduction in the leukemogenic effect has been found with

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a reduction in dose rate. If the dose response for leukemia induction is linear-quadratic, there should be a dose-rate effect and the doserate-reduction factor should be about two when the data for high dose rate have been obtained for doses of 1 Gy. There are no data for the induction of leukemia, or for that matter other cancers, in humans by protons or heavy-charged-particleradiation. Thus, estimates of risk for exposures in space must depend on the use of Q based on the LET of the radiation to convert doses to H. Breast. The induction of cancer of the breast has been studied in a number of different populations (Boice and Monson, 1977; Hrubec et al., 1989; Miller et al., 1989; Shore et al., 1986; Tokunaga et al., 1984) and data for mortality and incidence rates are available. The incidence of cancer of the breast is influenced by many factors. The differences between incidence rates in Japan, Europe and the United States are perhaps due to differences in diet. The importance of the hormonal influence in all populations is clear. This type of cancer is reduced by ovariectomy and pregnancy at an early age. The importance of genetic factors is indicated by the finding that family history is a strong predictor of risk. The multiplicity of influencing factors (Hoe1 et al., 1983;Kelsey, 1979;Kelsey and Berkowitz, 1988;MacMahon et al., 1973)presents a problem in the study of the interaction between the various factors and radiation, and requires special analytic approaches (Land et al., 1992).Women exposed to radiation when young, less than 20 y of age, are at a higher relative risk than those exposed at other ages, and exposures after 40 y of age are associated with relatively low excess risk of breast cancer (Boice and Monson, 1977;Boice et al., 1981;Howe, 1984;Howe and McLaughlin, 1996;Tokunaga et al., 1984; 1994). The histological types of breast cancer induced by radiation and the distribution of age at appearance are similar to breast cancer from other causes. Based on the epidemiologicalevidence, in particular the studies of tuberculosis patients who were examined many times by fluoroscopy, it has been suggested that fractionation does not reduce the carcinogenic effect. However, experimental studies on breast cancer in mice (Ullrichetal., 1987)demonstrate the importance of the size of the dose per fraction and also that reduction in dose rate reduces the carcinogenic effect. 5.5.46

5.5.4.3 Thymid. Excess rates of thyroid cancer have been reported in exposed populations such as those irradiated in childhood for various benign diseases (Colman et al., 1976;DufYy and Fitzgerald, 1950;Hempelmann et al., 1975;Ron and Modan, 1984; Ron et al., 1989;1995;Schneider et al., 1985;Shore, 1992;Shore et al., 1984a;

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Simpson et al., 1955), in atomic-bomb survivors (Prentice et al., 1982; Thompson et al., 1994; Wakabayashi et al., 1983), and the Marshall Islanders exposed to nuclear fallout. The many aspects of radiationinduced thyroid cancer have been reviewed by NCRP (1985) and Shore (1992). Papillary thyroid cancer is the most frequent type induced by radiation. This type of thyroid cancer is slow growing and the mortality rate is low (the rate of mortality to incidence is about 0.1), and therefore incidence is the more informative index of the effect of radiation. The risk of thyroid cancer is influenced by hormonal factors. The susceptibility,in both unirradiated and irradiated populations, is about three times greater in females than males in the populations that have been studied, thus the excess relative risks (ERR) are about the same in both genders. The young are also more susceptible. In the case of the atomic-bomb survivors, persons who were exposed a t the age of 10 y or younger had three times greater risk than those exposed a t older ages. The risk of radiation induction of thyroid cancer decreases by a factor of two with every 5 y increase in age and there is little or no evidence of excess thyroid cancer among those exposed at 30 or more years of age (Ron et al., 1995). Considering the current age distribution of astronauts, a risk of radiation-induced thyroid cancer is not a concern.

Lung. The estimates of risk of radiation-induced lung cancer come from the studies of the atomic-bomb survivors (Pierce et al., 1996; Thompson et al., 1994), the ankylosing spondylitis patients (Darby et al., 1987; Smith and Doll, 19821, and the uranium miners (Lubin, 1997; NASINRC, 1988; NCRP, 1984a; 1984b; UNSCEAR, 1994) who were exposed to alpha-particle irradiation. The analyses of the risk of radiogenic lung cancer is complicated by the role of smoking. The baseline rates of lung cancer are higher in males than females because smoking is more prevalent in males. The absolute risk estimates for radiogenic lung cancer are similar for the two genders, but because of the baseline rates, the relative risk is higher in females. The latent period for radiation-induced lung cancer appears to be inversely related to age at exposure (Land and Tokunaga, 1984)but the dose response for lung cancer increases with age (Pierce et al., 1996).The dose-response relationship for single acute doses is considered to be linear. In the case of the tuberculosis patients examined by fluoroscopy, no increase in lung cancer has been found (Davis et al., 1989; Howe, 1992; 1995), suggesting t h a t fractionation decreases the risk of radiogenic lung cancer considerably. 5.5.4.4

5.5.4.5 Gastrointestinal Tract. The types of cancer considered in this category are those of the esophagus, stomach and colon, and

rectum. Risk estimates for these cancers come from the atomicbomb survivors (Pierce et al., 1996; Thompson et al., 1994). The contribution of a total risk estimated by ICRP for persons exposed to radiation that is due to cancers of the gastrointestinal (GI) tract is about 45 percent. The baseline rates for these cancers are very different among different populations, suggesting the importance of dietary and perhaps other factors. These differences also pose problems in the transfer of risk from one population to another. However, the differences in the baseline rates between populations is less when the rates for all types of cancers of the GI tract are combined. The high relative contribution of these tumors to radiation risk found in the atomic-bomb survivors may overestimate the risk for the United States population (Boice and Fry, 1995). The dose-response relationship for these types of cancer has been assumed to be linear although the possibility of a fit of the data for radiation-induced colon cancer to a quadratic model cannot be dismissed. There is no information about the effects of fractionation or dose rate.

6.5.4.6 Liver. The mortality studies of neither the atomic-bomb survivors (Pierce et al., 1996)nor the ankylosing spondylitis patients revealed significant excess radiation-induced liver cancer. The first indication that exposure to external low-LET radiation induces liver cancer is the study of incidence rates in the atomic-bomb survivors (Thompson et al., 1994). There is a disturbingly low rate of histological confirmation (about 39 percent) of the cancers in this study, and the role of hepatitis-B virus is suspected but not understood. The risk of radiation-induced liver cancer has been based on the finding of the studies of patients given thorotrast, a thoriumcontaining contrast medium used in diagnosticradiology (NASINRC, 1988; van Kaick et al., 1984; 1999). Risk estimates for induction of liver cancer by low-LET radiation have been obtained from the highLET radiation studies and the application of a Q of 20 for alpha particles. 6.5.4.7 Kidney and Bladder. The risks of cancer at these sites are derived from ICRP (1991a),Pierce et al. (19961, and Thompson et al. (1994). These sites are at risk, and although the number of excess cases is lower, ERR is somewhat higher than for cancer of the GI tract. In the case of mortality, all the excess risk is attributed to the bladder, but the incidence data suggests an excess of cancer of the kidney as well. There is little or no influence of gender, and the dose response appears to be linear. The finding for the ankylosing spondylitis patients suggested a comparable risk to that in the atomic-bomb survivors (Darby et al., 1985; Land, 1986).

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5.5.4.8 Skin. Skin cancer is the most common cancer in Caucasians in the United States. The incidence rate increases with age and is clearly related to exposure to ultraviolet (W)radiation. Susceptibility is influenced by genetic factors, in particular those that determine both the amount and distribution of pigmentation in the skin. More recently, however, a site-specific study of skin tumor risk among atomic-bomb survivors in Japan (Ron et al., 1998) found a marked, and statistically significant, radiation-related excess of basal cell carcinoma, but not squamous cell carcinoma. Positive but statistically nonsignificant risks were observed for malignant melanoma and for Bowen's disease. The ERR for basal cell carcinoma decreased about 11percent for each 1y increase in age at exposure. Excess relative risk per sievert was significantly higher for basal cell carcinoma occurring in areas of the skin normally protected by clothing from W radiation, compared to the face and hands. The authors concluded that the carcinogenic effect of ionizing radiation (in terms of absolute risk) was fairly constant over the body and that, possibly, the high melanin content of skin among Japanese relative to Europeans minimizes any interaction between W and ionizing radiation. Another possibility is that the apparent interaction seen in other studies may be an artifact, resulting from comparing adults exposed in UV-shielded sites to children and infants exposed in W-exposed sites. There are at least three major problems in the determination of accurate risk estimates for skin cancer induction by ionizing radiation. First, the latent period is very long, on average about 25 y. Second, the reporting of skin cancer is haphazard, thus the method of follow-up is an important factor in the reliability of epidemiological studies. Third, the interaction of W and ionizing radiation is an important factor in the risk of skin cancer. The risk of skin cancer induced by ionizing radiation is about three times greater in areas of the skin exposed to sunlight. In epidemiologicalstudies it is thus important that the anatomical area from which the skin cancer arose be carefully evaluated. Recent epidemiological (Shore et al., 1984b) and experimental work (Fry et al., 1986) have made it clear that Caucasian skin exposed to both low-LET radiation and to sunlight is at significantly greater risk than skin that is normally protected from sunlight by adequate pigmentation or by hair or clothing. An excess incidence of both basal and squamous cell carcinomas has been associated with ionizing radiation, but in the case of melanoma, by far the most malignant of the skin cancers, no unequivocal association has been found.

5.5 RADIATION CARCINOGENESIS

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5.5.4.9 Sources of Uncertainty. The estimates of risk from exposure to low-LET radiation, even at high doses, have considerable uncertainty, and the estimates of risk for protracted low dose rate exposure in LEO to mainly protons and a very low fluence of heavy charged particles have considerably greater uncertainty. An inadequate understanding of cancer induction makes it difficult to confirm the appropriateness of the models selected to fit the data or how to allow for the effect of dose rate and fractionation. The models in use are simplistic, and the more appropriate multistage models have only recently been applied to epidemiological data from irradiated populations on the carcinogenic effect of radiation. In order to make lifetime risk projections based on data from the atomic-bomb survivors, an appropriate model must be used because a t this time only about 50 percent of the atomic-bomb survivors have died. Currently the relative risk projection model is favored, either with a constant risk over the lifetime after a latent period, or with a risk decreasing in later life. NCRP completed an analysis of the uncertainties associated with fatal cancer risk estimates used in radiation protection (NCRP, 1997b). Major contributions to the uncertainty included the choice of the DDREF, transfer of the risk from a Japanese to a United States population, and extrapolation to lifetime risks (NCRP, 1997b). The NCRP report concluded that lifetime risks of fatal cancer for a Sv-' with United States adult population had a mean of 3.69 x a range (90 percent confidence interval) from 1.15 X Sv-l to Sv-l. 8.08 X

5.5.5 An Approach to Estimation of Cancer Risk Associated with Space Travel

A general approach is provided from which estimates of lifetime cancer risk can be obtained for a variety of exposure situations. While there are other immediate risks associated with space travels that currently outweigh the potential future risk of cancer development among astronauts, radiation exposures could reach levels of concern if the frequency of missions increases for each individual or if missions last for extended periods of time. Furthermore, the radiation risk persists after the individuals have returned from their missions and perhaps after completing their careers. 5.5.5.1 The Epidemiological Basis for Riskdssessment. Increased cancer risk is thought to be the most important adverse health effect of exposure to low doses of ionizing radiation. That risk is estimated mainly from observations of cancer incidence and mortality in

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defined populations with documented radiation exposures. Study populations include the cohort of survivors of the atomic bombings of Hiroshima and Nagasaki (Beebe and Usagawa, 1968)and various medically and occupationally exposed cohorts. Individuals in these populations are characterized by their exposure histories, including estimated radiation doses to various organs, age, year of exposure, gender, follow-up interval, history of cause-specific mortality and morbidity including cancer diagnosis, and (partially) by other information such as smoking and reproductive history. Risk estimation is essentially a matter of fitting observed disease frequency to parametric functions of radiation dose and other variables. The estimates thus obtained are valuable to the extent that they can be used to predict risks accurately in other radiationexposed populations. Predictive value is enhanced if the study population is large and includes a substantial higher dose subset in which risk is markedly increased over the baseline, if there is a suitable low dose subset or comparison population, if information on disease and radiation dose is accurate, if follow-up extends over many years following exposure, if the study population is not too different from those populations to which the estimates are to be applied, and if the fitted model is biologically plausible. The atomic-bomb survivors' cohort is most often used as the basis for predicting radiation-related risk to a general population because it is the most thoroughly studied exposed population and because it was unselected for disease and is otherwise representative of a general population. Both genders and all exposure ages are represented among the 93,696 survivors in the cohort. There is complete coverage of mortality at the level of death certificate diagnosis, most recently for the period 1950 to 1990 (Pierce et al., 1996). The RERF tumor and leukemia registries provide a high level of surveillance of sitespecific cancer incidence for the majority of survivors who still reside in the environs of Hiroshima and Nagasaki. Recent comprehensive reports cover this subpopulation for the periods 1958 to 1987 (Thompson et al., 1994) and, for leukemia, 1950 to 1987 (Preston et al., 1994).Although the atomic-bomb exposure took place in 1945 and the leukemia registry was begun 2 y later, the study cohort was defined on the basis of the 1950 Japanese National Census; furthermore, the tumor registry began operations in 1957 to 1958. Thus, there are gaps with respect to risk during the early years following the bombings, which must be filled using information from other sources. Cancer Mortality. About 20 percent of the United States population eventually dies of cancer (SEER, 1995),and early mortality

6.6.5.2

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is one of the most important reasons to be concerned about any increase in cancer risk. For this Report, estimated risks of radiationrelated cancer mortality, and of the associated loss in expected lifetime, are based on atomic-bomb survivor death certificate data for 1950 through 1990 (Pierce et al., 1996). Comparisons of autopsy findings with death certificate diagnoses in this population (Ron et al., 1994;Steer et al., 1976)have shown that, while there is great variation in accuracy of death certificate diagnoses by cancer site and age at death, the most usual errors are in assigning the site. Death from cancer, as such, is usually recorded correctly. Thus, an estimate of excess cancer mortality for combined sites may be more reliable than the sum of separate site-specific estimates from death certificate data. Risks of mortality from leukemia and other cancers (solid cancers, considered as a group) have been estimated separately because the distribution of risk over time following exposure has been shown to be very different for the two diagnoses. The mortality associated with cancer varies considerably by site, as does the susceptibility of different organs to radiation carcinogenesis. Site-specific studies at the level of incidence utilize diagnostic information from a much wider variety of sources than the death certificates on which the atomic-bomb survivors' mortality studies are based, and are consequently less prone to misclassification by site. As previously mentioned, the RERF leukemia registry has enabled intensive studies of leukemia for many years. Recently, major improvements in the RERF tumor registry have greatly facilitated site-specific studies of solid-cancer incidence including a comprehensive report in which estimates based on tumor registry diagnoses have been presented for a number of different sites. Other sitespecific studies have relied on the tumor registry for initial identification of cases, but have included special reviews of diagnostic materials and ascertainment of cases originally diagnosed during the period 1950 to 1957 (e.g., Tokunaga et al., 1994). 6.6.5.3 Age a t Exposure, Time after Exposure, and Attained Age. Mortality coefficients for excess relative and absolute risk for all solid cancers as a group, and for excess absolute risk of leukemia, are presented in Table 5.7 (Pierce et al., 1996).Site-specific lifetime mortality coefficients (and ERR per sievert) are presented in Table 5.8 (Pierce et al., 1996).Note that corresponding data on incidence are available in Ron et al. (1994)and Thompson et al. (1994). Breast cancer ERR coefficients were calculated according to a fitted model, continuous in age at exposure and constant over time following exposure (Figure 5.12) (Tokunaga et al., 1994). The assumed minimal latent period was 12 y or to age 30, whichever occurred

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TABLE 5.7-Average ERR per sievert and lifetime risk at 1S v of mortality as a function of sex and age a t exposure for solid cancers and leukemia. A. Solid cancer, based on weighted colon dose.8 Age at Exposure

10 30 50

Sex

ERR Sv-I

Lifetime Risk at 1Sv

M F M F M F

0.81 1.67 0.38 0.77 0.17 0.36

0.18 0.25 0.10 0.14 0.03 0.05

B.

Life Lost per Excess Death (Y)

Background

13 14 12 13 10 11

0.26 0.19 0.28 0.20 0.18 0.15

Risk

Leukemia, based on bone-marrow dose.b

"Pierceet al. (1996), Tables VII and VIII. bPierceet al. (19961, Table M.

later. The entries in Tables 5.7 and 5.8 were calculated for discrete, consecutive intervals of age at exposure. For sites other than breast cancer or leukemia, a minimum latent period of 10 y was assumed. ARer the minimum latent period, excess absolute risk for solid cancers due to exposure was assumed to increase or decrease over time (i.e., with increasing attained age) in direct proportion to age-specific population rates; i.e., ERR was assumed constant over time following exposure. Leukemia mortality projections are based on a fitted model obtained by Pierce et al. (1996). The assumed minimum latent period was 2 y, and modeled risks were multiplied by zero for years one and two following exposure, and by 0.1,0.25,0.5,0.75,0.9 and 1for years three, four, five, six, seven and eight or more after exposure, respectively. 5.5.5.4 Baseline Cancer Rates. Age and gender-specific population rates for mortality for cancers of various sites in the United States population for 1973 to 1989 were obtained from the NCI Cancer Surveillance Research Program (SEER, 1991).

5.5 RADIATION CARCINOGENESIS

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0

/

123

I

I

I

I

I

,

10

20

30

60

50

60

Age ATB (Y) Minimum feasible value for lower limit

Fig. 5.12. Estimated ERR(D,a) for radiation-related breast cancer a t 1 Sv weighted breast-tissue dose (neutron weighting factor = 10 relative to gamma rays) as a function of age at exposure: female atomic-bomb survivors, 1950 to 1985 (Tokunaga et al., 1994) plotted according to the following equation: where D is weighted absorbed dose in sievert and a is age in years a t exposure. Attained age is assumed to be 30 y or older, and time following exposure is assumed to be 12 y or more.

5.5.5.5 Transfer of Risk Coeficients Between Populations. The risk coefficients presented in Tables 5.7 and 5.8 and Figure 5.13 pertain to the population of atomic-bomb survivors. A n unavoidable, but very difficult, problem for risk estimation is transfer across populations. How to predict the consequences of exposure to one population, like the population of astronauts, based on the experience of another population, like the atomic-bomb survivors, whose baseline cancer rates m a y be very different is fraught with problems. The problems occur because we have insufficient data from different irradiated populations to determine which transfer models work best, and yet the predictions must be made. There are two simple and logical approaches which seem consistent with current thinking about carcinogenesis, but, unfortunately, these approaches often provide markedly different estimates for the second population (Land,

0.44 0.27 1.28 0.36 0.38

0.22 0.31 0.79 1.99

-

0.15 0.33 0.52 0.57

ERR Sv-I

0.6 0.5 0.1 3.5 28

9.7 5 .O 3.7 1.3 1.0 1.1 1.3 0.8 0.2

(5%)

Male Background

0.3 0.1 0.1 1.2 10

0.2 0.4 0.6 0.4

-

1.5 1.6 1.9 0.7

Lifetime Risk % Sv-' Excess

0.65 0.75 0.11 1.08 0.59 0.10 3.3 0.41 0.44 0.23 0.79 0.87

0.6 0.2 2.4 20

5.5 2.5 1.6 1.1 0.8 1.1 0.3 1.0 0.1 2.6 1.1 0.7

(%)

Female Background

-0.17 1.25 0.84 0.77

Sv-'

ERR

Lifet Sv

TABLE 5.8-Site and sex specific lifetime risk (absolute) and ERR per sievert of mortality for exposure a

Stomach Lung Liver Colon Rectum Pancreas Esophagus Gall bladder Bladder Uterus Breast ovary Prostate Lymphoma Myeloma Other solid

All solid

aPierceet al. (1996),Tables XI and VIII (for similar incidence data see Thompson et al., 1994,Table 5.14,and A

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I

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Age 10 at Exposure

5

/

-

-Males

----- Females

-

84-

00

2

-

L.3-

$ V)

s

-

-

$ 0 V)

I l 0

G . 0Attained age (y)

Fig. 5.13. Postulated model (Pierce et al., 1996)for the excess mortality risk of leukemia (all types) by gender, age in years a t exposure, and attained age. Curves show estimated excess leukemia rate per 100,000y-' for a 1Gy chronic dose of low-LET radiation over a period of less than 1y. Excess mortality risk

(D

-

+ 1.53 DZ)exp[P+ PI., + (y + yfe,) X

log (t/25)1,

where D is the acute weighted absorbed dose in sievert (the 02 term is = -0.335 ignored for chronic dose), t is time in years after exposure, for females and zero for males, yr,, = 0.483 for females and zero for males, and beta and gamma depend on age at exposure, as follows:

a,

Age at Exposure (a)

The estimates are based on observations from October 1, 1950 through December 31, 1990, but the minimal latent period is assumed to be 2 y. Therefore, the modeled estimates for years one to seven following exposure have been multiplied by 0, 0.1, 0.25, 0.5, 0.75, and 0.9, respectively.

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1990; Land and Sinclair, 1991). One such approach (here called "multiplicative"), might be appropriate if, e.g., population differences were ascribable to differential exposure to cancer promoters or latestage carcinogens that might be expected to act similarly on cells initiated by radiation or by other early-stage carcinogens; the approach is simply to apply ERR coefficients in Table 5.7 to the baseline rates for the United States population. A second approach (Rall et al., 1985), which might apply if population differences were ascribable to differential exposure to early-stage carcinogens with effects similar to those of radiation, is to adjust ERR estimates in Table 5.7 by the difference between the United States and Japanese population rates over the appropriate ages of follow-up (or, equivalently, to assume that absolute risks are the same in the two populations when averaged over the period of follow-up), so that the estimated numbers of excess cancers over that period are the same (additive transfer). This method appears to describe very we11 the observations of breast cancer incidence among atomic-bomb survivors and medically-irradiated North American populations, which clearly do not fit the multiplicative model (Land, 1980; 1990; 1995; Mattson et al., 1999).It cannot be said with any confidence, however, that either model is superior for any other solid cancer site for which population rates differ markedly. Reasoning that differential promotion and initiation both may play roles in population differences, we have chosen to use the average of multiplicative and additive model transfer estimates for solid cancers, and to use the additive method for leukemia. 5.5.5.6 Dose Response. The risk estimation for leukemia mortality in Figure 5.13 is linear-quadratic in bone-marrow dose for acute exposure to low-LET radiation. For chronic exposure, the dosesquared term is set equal to zero. The effects of acute exposures received a t different times are calculated separately and then accumulated; fractionated exposures, in which the fractions are more than several hours apart, can be treated similarly. Since the dose-squared component is important only for doses greater than 100 mSv, use of the quadratic dose-responsefunctionhas an intrinsic reduction factor for low dose and dose rate (DDREF). The ERR values for mortality as tabulated in Tables 5.7 and 5.8, are linear-model dose-response coefficients, determined largely by high dose data. For these sites, a DDREF of two is assumed for low doses and dose rates, i.e., total dose less than 200 mGy or dose rate less than 0.1 mGy min-l. 5.5.5.7 Individual Factors. It seems likely that there may be individual differences in susceptibility to carcinogenesis from ionizing

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radiation and other causes. Except for certain rare genetic conditions, however, we do not know enough to identify individuals with innate susceptibility or resistance to carcinogenesis. We are beginning to learn more about lifestyle factors or exposures to agents that may interact with ionizing radiation to increase cancer risk. We know, e.g., that exposure to W radiation from sunlight can greatly enhance the likelihood of nonrnelanoma skin cancer following exposure to ionizing radiation in Caucasians (Shore, 1990)but not in the Japanese survivors (Ron et al., 1998). It appears likely that the risk of radiation-induced lung cancer may be higher among smokers than among nonsmokers if the exposure is from inhaled alpha-particle emitters, but there is much less evidence of an interaction of smoking with gamma-ray exposurefrom an external source (NASMRC, 1988; 1990). Nulliparous women, and women whose first full-term pregnancies occurred after age 30 have about three times the baseline risk of breast cancer compared to women whose first full-term pregnancies occurred before age 20, and that ratio also appears to hold for the risk of radiation-induced breast cancer (Land et al., 1994).

5.5.6

Risks of Radiation Carcinogenesis

5.5.6.1 Method of Estimating Carcinogenic Risk. The mortality estimates in Tables 5.7 and 5.8 are based on models developed by Pierce et al. (1996) for baseline rates and dose-specific ERR of solid cancer mortality and excess absolute risk of leukemia mortality for the atomic-bomb survivor population. Pierce et a2. (1996) calculated lifetime risks for a Japanese population following different exposure scenarios. To do this, they computed age-specific excess mortality rates which were accumulated, along with the age-specific baseline rates, over remaining expected lifetime using sex-specific actuarial tables (life tables) of age-specific, all-cause mortality for a Japanese population. Essentially, this involved modification of the life tables to include the estimated excess mortality from radiation-related cancer, creating so-called "doubly decremented" life tables which give the estimated probabilities of surviving to ages a + 1, a + 2, etc., given exposure a t age (a). Cumulative lifetime excess risk was obtained by summing the estimated age-specific excess mortality rates over age, weighted by the corresponding survival probabilities: exposure related lifetime risk = Z(S, x r,),

(5.2)

where S,, represents the (doubly-decremented) lifetable probability of surviving to age a and r,, is the estimated risk of dying from radiation-related cancer at age a following the postulated exposure

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5. RADIOBIOLOGY OF SPACE RADIATION

history. The estimated age-specific risks (r,) incorporate minimum latency periods of 2 y for leukemia and 10 y for solid cancers; thus, for example, r,+~= 0 since it is assumed that leukemias occurring within 2 y of exposure and cancers occurring within 10 y of exposure are unlikely to be related to the radiation exposure. Application of the Pierce et al. (1996) mortality risk estimates to an American population requires, first, the use of United States life tables, which are numerically different from those for a Japanese population. Second, the estimated excess rates themselves may need to be modified for a United States population, as discussed in Section 5.5.5.5 above. For this Report, i t has been assumed that the excess leukemia mortality rates estimated by Pierce et al. (1996) apply without change to a United States population. Except for chronic lymphocytic leukemia, which is rare in Japan (and in any case does not appear to be increased by radiation exposure),Japanese and United States leukemia rates are similar. Thus, the question of multiplicative versus additive transfer of risk estimates (see Section 5.5.5.5) does not arise for leukemia. For solid cancers, however, there are differences, especially for individual sites but also for all solid cancers combined. In this case, the approach of Land and Sinclair (1991), of using the arithmetic average of the agespecific risk estimates obtained by multiplicative and additive transfer between the two countries is followed. For a Japanese population, the excess rate is: where ERR, is the estimated excess relative risk of solid cancer mortality a t age a obtained using the model of Pierce et al. (1996) and B,,J,, is the corresponding baseline solid cancer mortality rate for a Japanese population. This is also the value that would be obtained by an additive transfer to a United States population. For a multiplicative transfer, on the other hand, the Japanese baseline rate would be replaced by the corresponding United States baseline rate, denoted Basus.Thus, by using the arithmetic mean of the multiplicative and additive transfer estimates, the age-specific excess rate for a United States population is calculated as:

5.5.6.2 Calculation of Excess Lifetime Cancer Mortality. In this Section, a heuristic illustration is given of excess risk of solid cancer mortality from a single, 100 mSv exposure to uniform, whole-body, low-LET radiation and from a 10 y history of chronic exposure

5.5 RADIATION CARCINOGENESIS

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129

beginning at age 35, to 10 mSv y-l. Pierce et al. (1996) give ERR of solid cancer per sievert for an acute exposure as: ERRS,-1 = 0.375 x exp[-0.038 x (exposure age - 3011

(5.5)

for males and ERRS,-1 = 0.744 x expi-0.038 x (exposure age - 30)l

(5.6)

for females. For chronic exposures, a DDREF of two is applied, i.e., values obtained using Equations 5.5 or 5.6 are reduced by one-half. A 10 y minimum latent period is assumed. For a single, 100 mSv exposure a t age 35, ERR of mortality from solid cancer would be estimated as zero at ages 35 to 44 and 0.5 x 0.1 x 0.375 exp[ - 0.035 X (35 - 30)l = 0.0155 at ages 45 and older for a male and 0.5 x 0.774 exp[- 0.035 x (35 - 30)l = 0.0320 for a female. In the absence of radiation exposure, lifetime risk of solid cancer mortality is about 22.5 percent for males and 19.7 percent for females, and little of that risk (about 0.12 percent for males and 0.13 percent for females) occurs before age 45 (SEER, 2000). Thus, the lifetime excess risk would be about 22.5 x 0.0155 = 0.35 percent for a male and 19.6 x 0.0320 = 0.63 percent for a female. The "shortcut" method used in the above example assumes that an ERR estimate based on Japanese data can be applied without change to a United States population. Because Japanese cancer mortality rates tend to be slightly smaller than United States rates, the values computed are slightly greater than the corresponding values of 0.32 and 0.58 percent presented for all solid cancers for age 35 in Table 5.9, which were computed allowing for the possibility (treated as equally likely) that excess rates, rather than ratios of excess to baseline rates, may be the same in different populations. That is, ERR values were multiplied by the average of United States and Japanese baseline rates, rather than by the United States rates alone. A more complex "lifetable* approach is required for exposure to 10 mSv y-l for 10 y beginning a t age 35. As before, with a 10 y latent period, ERR at ages less than 45 is assumed to be zero, whereas at age 45 the ERR is estimated as one-tenth that in the previous example, i.e., 0.00155 for males and 0.00320 for females. At age 46, ERR reflects exposure at ages 35 and 36, i.e., ERR = 0.00155 + 0.5 X 0.01 X 0.0375 expI-0.035 x (36 - 30)l = 0.001551 + 0.001492 = 0.03043 for males and 0.00320 + 0.00308 = 0.00628 for females, and so on (see Table 5.10). Note that, because no exposures occurred after age 44, ERR does not increase hrther after age 54. For brevity, further calculations are carried out only for males, and the ERR values in Table 5.11 are reduced to average values for 5 y intervals of age. To get estimated numbers of excess solid cancers

F

0.316 0.045 0.361

M

29.22 2.60 31.82

0.580 0.030 0.610

F

8.30 2.87 11.18

0.206 0.052 0.258

M

17.58 2.30 19.88

0.388 0.042 0.430

F

3.72 1.45 5.17

0.113 0.034 0.147

M

45

0.824 0.036 0.860

13.99 4.04 18.02

35

0.451 0.051 0.502

43.33 3.76 47.10

25

20.65 5.70 26.35

M

exposure totaling 100 mSv in 1 y, by gender and age at exposure."

TABLE 5.9-Estimated excess cancer deaths and loss of expected lifespan in days associated with a c Age at Exposure Gender

Excess cancer deaths (%) All solid cancers Leukemia All cancers Expected lifespan lost (dlb AU solid cancers Leukemia

AU cancers

"Based on colon dose for solid cancers and bone-marrow dose for leukemia. bThese estimates are not based on an individual dying of cancer which could result in years of lifespan lost. The on the impact to a population.

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RADIATION CARCINOGENESIS

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131

TABLE5.10-ERR of solid cancer mortality at ages 45 and older, corresponding to a 10 y history of exposure beginning at age 35, to 10 mSv y-' of chronic, uniform, whole-body, low-LETradiation. Attained Age

ERR for Males

ERR for Females

45 46 47 48 49 50 51 52 53 54 55 56 etc.'

0.00155 0.00304 0.00448 0.00586 0.00720 0.00848 0.00971 0.01090 0.01204 0.01315 0.01315 0.01315 0.01315

0.00320 0.00628 0.00925 0.01210 0.01485 0.01750 0.02005 0.02250 0.02486 0.02714 0.02714 0.02714 0.02714

"Becauseexposure stopped after age 44,the ERR remains constant from age 54 on.

per 100,000, the average ERR values are multiplied by baseline United States solid cancer rates for the same intervals (the excess per 100,000 applies to the whole 5 y age group). Then, to calculate the total excess deaths per 100,000, the estimated 5 y excess is weighted by the probability of surviving to the beginning of the 5 y period, given that those exposed survived to age 35, and the results are summed over age intervals. The estimated excess solid cancer mortality in Table 5.11, of 284 per 100,000 (or 0.28 percent) was obtained under the assumption that ERR for exposed populations are similar in populations with different baseline cancer rates. The slightly lower estimate for males in Table 5.12 (0.263 percent) was calculated using single years of age, a more accurate method, and using a different method of transferring ERR estimates between populations, as explained above. Excess leukemia mortality was calculated using a different formula (Figure 5.13) which yielded a direct estimate of the estimated excess per 100,000, but otherwise the calculation was similar to that for solid cancers as a group. It is assumed that, insofar as such exposures can be controlled, radiation exposures to astronauts may be limited at least partially on the basis of estimated excess cancer risk. At any point during a career, an individual may have a history of exposures for which an estimate of future lifetime risk may be calculated, and a mission or

Attained Agea

0.004437 0.010866 0.013156 0.013156 0.013156 0.013156 0.013156 0.013156 0.013156

ERR

Specific

Age-

101.6 203.3 364.1 589.8 843.7 1,098.3 1,355.7 1,640.2 1,866.9

Yearly Rate

U.S.

2.25 11.04 23.93 38.77 55.46 72.19 89.11 107.81 122.71

Estimated Excess

0.973 0.952 0.919 0.869 0.794 0.691 0.557 0.400 0.237

Life Table Probability of Survival from Age 35 to Beginning of Interval

Expec De 100,0

TABLE5.11-Continuation of the calculation of Table 5.10, for males, of excess risk of solid cancer mo following a 10 y history of exposure beginning at age 35, to 10 n S v y-' of chronic, uniform, whole-body radiation.

45 to 49 50 to 54 55 to 59 60 to 64 65 to 69 70 to 74 75 to 79 80 to 84 85+

Total "Forsimplicity of presentation, the calculation is carried out for 5 y intervals of attained age.

totaling 10 mSv y-I for 10 y, by gender and age at exposure.*

TABLE 5.12-Estimated excess cancer deaths, loss of expected lifespan (days), associated with chronic e

M

0.490 0.038 0.528

F

5.95 2.14 8.09

0.159 0.043 0.201

M

12.88 1.71 14.59

0.306 0.034 0.340

F

2.29 0.99 3.28

0.07 0.026 0.104

M

45 to 54

F

0.263 0.050 0.313

23.76 2.58 26.33

35 to 44

M

0.705 0.033 0.738

11.25 3.55 14.80

25 to 34

0.384 0.048 0.432

36.52 3.22 39.74

Gender

Excess cancer deaths (%) All solid cancers Leukemia All cancers

17.38 4.90 22.27

Age at Exposure

Loss of expected lifespan (d)b All solid cancers Leukemia All cancers

"Based on colon dose for solid cancers and bone-marrow dose for leukemia. bTheseestimates are not based on an individual dying of cancer which could result in many years of lifespan los on the impact to a population.

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series of missions may be contemplated that would involve additional exposures and a further increase in estimated cancer risk. At such a point, it would be appropriate to estimate the individual's excess risk from the exposures already sustained, and also the additional risk associated with the anticipated exposure from the contemplated mission. Example 1. A male astronaut, age 40, has participated in Space Shuttle flights a t ages 35, 37 and 39 with estimated doses of 0.5, 0.9 and 4.3 mSv, respectively, of chronic radiation exposure. He is being considered for a n extended Space Station mission, during which the anticipated exposure, to chronic, low-LET irradiation, corresponds to a dose of 400 mSv. The mission will occur when he is 42. As shown in Table 5.13, his predicted lifetime risk at that age can be summarized as a 0.018 percent chance of death due to cancer induced by radiation received in space activities so far, and an estimated loss of 0.89 d of expected remaining lifetime. In terms of sitespecific incidence, his risks are also very small (Table 5.14). At age 42, following completion of the contemplated mission, his estimated lifetime risk due to his earlier exposures would be almost exactly the same (the only difference is that he will have lived an additional 2 y, in good health), but the additional excess risk from the planned mission of 400 mSv would be much higher than the excess risk associated with the lower exposures up to then. The anticipated post-mission excesses, a 1.18 percent chance of premature cancer mortality (a loss of 53.9 d of expected remaining lifetime) is to be compared to normal lifetime cancer mortality rate of 23 percent in males. Example 2. Afemale astronaut, also age 40, has the same exposure history as the man in Example 1, and is being considered for the TABLE 5.13-Estimated

excess lifetime risk of cancer mortality for Examples 1and 2.

Age at Projection

(before mission)

40"

42

Cancer Sites Solid cancer Leukemia Total Solid cancer Leukemia Total

Deaths (%) M F

Expected Life Lost (dl M F

0.69 0.20 0.89 40.0 13.8

53.9

1.44 0.13 1.57 84.2 11.1 95.3

"Projected risk from previous missions of 0.5, 0.9 and 4.3 mSv received at ages 35,37 and 39,respectively. bProjectedrisk including mission receiving 400 mSv at age 42 y.

5.5 RADIATION CARCINOGENESIS

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TABLE 5.14-Estimated excess lifetime risk of cancer incidence, in percent, for Examples 1 and 2. Mission at age 42 involves an increase in cumulative space-related skin dose equivalent from 4.7 to 404.7 mSv. Before Mission

Cancer Site

M

F

After Mission

M

F

All solid cancers Leukemia Total Stomach Colon Liver Lung Nonmelanoma skin

Breast Ovary Bladder Thyroid

same extended mission. Her anticipated doses are the same, except that her risk estimates will also take into account doses of 372 mSv to the breasts and 268 mSv to the ovaries. Her projected risks, in Tables 5.10 and 5.11, reflect a generally higher risk of radiationinduced cancer among women, which can be attributed to (1)the inclusion of two additional radiation-sensitive organs; (2) higher risk coefficients for some sites, partially counterbalanced by lower risks for others; and (3) a longer expected lifespan. Pre- and post-mission risks are estimated to be 0.032 and 1.97 percent, respectively, in terms of lifetime excess cancer mortality (1.57 and 95.3 d of expected remaining lifetime). Normal lifetime cancer risks for women are somewhat lower than those for men (20percent for mortality). However, the number of days of life lost will be somewhat greater, 95 d versus 54 d, see Table 5.13.

6. Radiation Protection Standards for Missions in

Low-Earth Orbit 6.1 Principles of Radiation Protection

In 1993, the NCRP (1993a) reiterated the following principles of radiation protection (NCRP, 1987b): 1. any activity which involves radiation exposure must be justified on the basis that the expected benefits to society exceed the overall societal cost Gustification); 2. the total societal detriment from such justifiable activities or practices is to be maintained ALARA, economic and social factors being taken into account; and 3. individual dose limits are applied to ensure that the principles of justification and ALARA are not applied in a manner that would result in individuals or groups of individuals exceeding levels of acceptable risk (limitation).

Radiation exposure is one of the risks incurred in space activities.

Of particular concern to those involved is the question of risk of late effects occurring after the end of their careers. It is these risks on which this Report has concentrated. Once an action or practice (in this case, a space mission) has been justified, the principle of ALARA should be applied to optimize radiation protection. For example, if a higher exposure anticipated in an EVA, while the spacecraft is repeatedly traversing the SAA has been justified, it is still important to consider ways to reduce the exposure. Thus, if the objectives of the EVA can be met by scheduling it for a period of lower exposure, then a decision to make this change may be warranted. Such decisions should be based on an appropriate balance between the dose averted and the mission objectives. In the discussion of the basis for recommended exposure limits that follows,all three principles ofradiation protection are important

6.2 CONSIDERATIONS FOR SETTING DOSE LIMITS

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in ensuring that sound decisions are made with respect to the exposure of space crews. That is, simply ensuring that limits are not exceeded is inadequate radiation protection policy in space as it is on the ground.

6 9 Biological Considerationsfor Setting Dose Limits for Space Missions The earliest occupational and public limits were based mainly on experience and judgment. In radiation protection practice, it is essential to set limits below threshold doses for any and all effects, if such a threshold exists. Deterministic effects (see Section 5.3), both early and late, by their nature, have threshold doses below which these effects do not occur. These thresholds have been reasonably well-established in most cases by radiobiologicalinvestigations. Consequently,deterministic effects can be avoided entirely by setting dose limits below these thresholds. This is a first consideration in ICRP and NCRP recommendations. Radiation protection considerations are then confined to the principal late (stochastic)effects, namely carcinogenesis and genetic damage for which no thresholds are known or assumed. They are presumed to have a probability of occurrence that is proportional to dose at low dose. The risk coefficient is the probability of the effect occurring per unit dose. Since stochastic effects are presumed to occur at all doses, but with less frequency at lower doses, judgment must be exercised about levels that are assumed to be acceptable. Considering the space radiation environment and the types of missions that space crews are likely to conduct in LEO,the following observations with respect to radiation risks are of greatest relevance in setting exposure limits:

1. The risk of fatal cancer depends on age and gender (see tables Sv-I in Section 5.5) and for adults is of the order of 4 x (ICRP, 1991a;NCRP, 1993a; 1993b).As discussed in Section 5, this value represents an increase i n the risk coefficient of approximately a factor of two from what was assumed when NCRP Report No. 98 was published (NCRP, 1989).The dependence of risk upon age at exposure has also changed since NCRP Report No. 98. 2. The risk of serious genetic defects, if the exposed space m w member is to later have children, is of the order of 1 X Sv-' for all generations (see Sections 5.4.1 and 5.4.2).

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3. The risk of cataracts can be avoided by limiting career doses to below threshold values, i.e., 2 Gy acute and 5.5 Gy protracted exposures, for low-LET radiation and similar values weighted for radiation quality in the case of high-LET radiations (see Section 5.3.2). 4. Effects on the gonads, although not life threatening, can reduce fertility and are of importance for crew members. Reduction of ovarian function, which is age dependent, may occur after high dose rate exposures greater than 1.5 Gy. Exposures in space are low dose rate and, therefore, no deleterious effects on ovarian function would be expected at doses below the 3 Gy-Eq range. The testis is more sensitive than the ovary. It is estimated that fractionated exposures of 2 to 6 Gy-Eq can cause sterility. A temporary reduction in fertility can occur with lower doses (Section 5.4.3). The above observations are the main determinants of the recommended exposure limits, but such limits may permit other deterministic effects ifthe exposure occurs acutely, or if some organ is exposed to a dose significantly greater than the rest of the body. For these reasons, as noted later, specific additional limitations are provided for shorter time periods than an entire career and for specific organs.

6.3 Basis for Limits for Low-Earth Orbit Missions In 1989the NCRP (1989) recommended astronaut career exposure limits based on lifetime risk per unit dose coefficients and on a lifetime excess risk of fatal cancer of three percent. To prevent deterministic effects from occurring, the NCRP also recommended career, 1y and 30 d limits for the bone marrow, eye and skin. The career limits were based on two separate approaches discussed below.

6.3.1 Basis for Stochastic Limits The first approach involved a comparison with exposure limits recommended for workers occupationally exposed on the ground. It seemed unreasonable to limit space workers, whose careers are generally of comparativelyshort duration, to the same annual limits as those of workers on the ground. However, it was considered appropriate that space workers be limited to the same overall lifetime risk as terrestrial workers. This was done by applying a career limit to space workers in which the overall career risk would not exceed

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139

that for a terrestrial worker. In 1989, both the ICRP and the NCRP had a limit of 50 mSv y-I corresponding, at that time, to a lifetime risk of fatal cancer of about five percent.12 However, limits for terrestrial workers at that time were in a state of flux.Because annual repeated exposures at the limit were discouraged and because the NCRP had recently issued guidance that the cumulative exposure for a worker should not exceed the age of the worker multiplied by 10 mSv, the NCRP concluded that it was more reasonable to use a three percent risk of fatal cancer as the basis for career exposure limits for this population (i.e., space crew members conducting missions in LEO).13 The second approach used by the NCRP (1989) was based on an analysis of risks of fatal accidents in other occupations. Given the exceptional character of space travel, comparison of radiation risks with the safest occupations on the ground, with lifetime risks on the order of one percent, seemed unreasonable. On the other hand, comparison of the radiation risks with the most hazardous occupations on the ground (e.g., test pilots) was also considered unreasonable because crew members already had the additional high risks of space travel. Consequently, comparison of the radiation risks with the middle group of "less safe" occupations with lifetime risks of about three percent seemed reasonable and reinforced the conclusions based on the first approach. Since 1989 the situation with respect to risk estimates for cancer and to recommendations on radiation limits for the exposure of terrestrial workers has changed with revised recommendations of the ICRP in 1990 (ICRP, 1991a) and the NCRP in 1993 (NCRP, 1993a). Using current nominal risk coefficients for an adult population (4 x Sv-l), the ICRP recommendation to limit a worker's occupational exposure to no more than 20 mSv y-' averaged over a 5 y period can lead to a maximum lifetime risk of between three and four percent (NCRP, 1993a). The NCRP recommendations of 50 mSv y-I with a cumulative limit (age x 10 mSv) after age 18, permit a maximum lifetime risk of about three percent (NCRP, 1993a). In addition, the opinion that after astronaut's careers are over, that their radiation risk should not exceed that of workers on the ground has been expressed by astronauts themselves (NCRP, 1997a). The second approach used in NCRP Report No. 98 (NCRP, 19891, based on the comparison with average accidental death rates in industry, would involve some change since 1989. For the less safe ''At the time, the lifetime risk for fatal cancer was assumed to be 2 x lo-' ST' (NCRP, 1989). I3The NCRP subsequently changed this guidance to a limit (NCRP, 1993a).

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industries, the accidental death rate has dropped by about 50 percent between 1987 and 1998 (Table 6.1).This drop is exaggerated because the method used by the National Safety Council to specify "work related deaths was changed in 1992 to reclassify some sources of accident (see Table 6.1).Nevertheless, if this comparison is made, it would indicate a figure somewhat lower than three percent. This approach, which was always imprecise, is now considered useful only in a general sense and does not provide the basis for the present recommendation^.^^^'^ TABLE 6.1-Annual fatality rates porn accidents in different occupations for 1987 and 1998.".b, Occupation

Annual Fatal Accident Rate (per 100,000 workers) 19Wb 199aGd

Safe Manufacturing Trade Services Government Less safe Agriculture Mining Construction Transportation

ALL "Certain occupations have higher annual fatal accident rates than those given here, e.g., deep-sea fishermen, test pilots, and lumber jacks. These are the "most hazardous" or least safe occupations. bNational Safety Council, Accident Facts 1988 (NSC, 1988); 1987 data were used in NCRP Report No. 98 (NCRP, 1989). 'National Safety Council, Injury Facts 1999 (NSC, 1999). dTheNational Safety Council (NSC) changed the basis for counting work related deaths in 1992. In that year, NSC adopted the Bureau of Labor Statistics Census of Fatal Occupational Injuries system of counting. Because of the lower work class total resulting from this change, several thousand unintentional-injury deaths that had been classified by the NSC as work related, had to be reassigned to the home and public classes. For this reason, long-term historical comparisons should be made with caution. I4Notethe risk of an induced cancer (incidence)is one to two times that of mortality, depending on the site. lSTheloss of lifetime from a fatal tumor is less than from a fatal accident.

6.3 BASIS FOR LIMITS FOR LEO MISSIONS

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141

The NCRP now considers the comparison with lifetime risks associated with the occupational exposure limits recommended for workers on theground to be the most direct and the most valid. Consequently, NCRP recommends that the excess lifetime fatal cancer risk due to the radiation exposure of space workers for missions in LEO be limited to three percent excess mortality and that this be the basis of career limits.

6.3.2 Basis for Deterministic Limits

Data relevant to deterministic effects for the eye, skin and bone marrow are reviewed in Section 5.3. The selection of dose limits for deterministiceffects is compromised by the inadequacy of the data for effects in humans caused by protons, neutrons and heavy ions. Therefore RBE values must be based on data from experimental systems. The determination of relevant RBE values is complicated by the fact that RBE values are influenced not only by radiation quality but also dose, dose rate, fractionation, the endpoint and the sensitivity with which it can be measured. The first problem is the determination of the LET spectrum of the radiation at the site of the organ. Measurements in cells in dishes and in organs in small animals may not reflect the situation in a deep organ in humans. The uncertainty of RBE values is high, particularly with very low dose rates and doses. The large values obtained with very low dose rates are due to the marked decrease in the effect of the reference radiation. The data available for the estimation of RBE values have been reviewed by Engels and Wambersie (1998), ICRP (19891, and NCRP (1990). ICRP (1989)suggested a method to derive RBE, (from initial slopes for deterministiceffects),analagous to RBEMused for stochastic effects, and that this approach was preferable to the use of RBE values based on threshold doses. The RBE, is the ratio of the initial slopes of the dose-response curves for the radiation under study and the reference radiation. Assuming a linearquadratic model for the dose response for the low-LET reference radiation and a linear relationship for high-LET radiations the initial slopes of the dose response can be obtained but this entails an extrapolation between the threshold doses. The assumption of a linear-quadratic model does not seem consistent with the characteristic sigmoid curve noted when threshold doses of the effects at the tissue lwel are used rather than the response of cell killing. The values for RBE, are higher than RBE values based on threshold doses.

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LEO

Furthermore, the recent findings (Joiner et al., 1996; Wouters and Skarsgard, 1997) of hypersensitivity to very low-single radiation doses raises doubts of the appropriateness of the linearquadratic model to estimate the initial slopes of cell survival curves. A similar problem affects the approach to determine the so-called biological weighting function (Paganetti et al., 1997) based on a biophysical model and microdosimetic parameters (Morstin et al., 1989; Zaider and Bremer, 1985) and applied to the calculation of the RBE for protons (Paganetti et al., 1997). In this approach it is assumed that the dose-effect relationship can be expressed as a n integral of two separate functions, one describing the ionization events that represent the distribution of energy in the target and the other function describes the relevant cellular response. It is also assumed that the dose-response relationships at low doses are linear. Perhaps the most important point is that any method that involves the estimation of what happens below the threshold doses for the effect a t the tissue level will result in dose limits for protection purposes that will be more stringent t h a n necessary t o prevent clinically significant effects. RBE values based on cell killing alone do not take into account fully the recovery capability, characteristic of tissues. For these reasons RBE values estimated on threshold doses are considered to be the method of choice. Unfortunately the data on threshold doses for the radiation qualities of concern in space are far from satisfactory. For example, most of the available data for neutrons is for energies in excess of 5 MeV and less than 500 MeV protons. In this Report, RBE values published in various papers on the effects of protons, e.g., Urano et al. (1984), and those for neutrons and heavy ions in ICRP Publication 58 (ICRP, 1989) have been used to weight organ doses for radiation quality. The weighted dose limits are expressed as gray equivalents (organ D in gray multiplied by the relevant RBE value for the specific organ and radiation).

6.4

6.4.1

Recommended Limits for Low-Earth Orbit Missions Limits for Stochastic Effects

The NCRP recommends gender and age based dose limits for missions conducted in LEO. The limits are based on a 10y career lifetime probability of excess cancer mortality of three percent specific for a given age and gender. The NCRP continues to recommend gender and age differences in dose limits for space crews because the overall risks per unit dose for women appear higher than for men due to

6.4 RECOMMENDED LIMITS FOR LEO MISSIONS

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143

the greater probability of women developing some radiation-induced cancers, such as stomach, thyroid and breast (see Tables 5.8, 5.9, and 5.13), the longer average lifespan of women, and the decrease in risk with age for both sexes. The career exposure limits (El associated with a three percent excess risk of mortality from cancer are given for men and women of ages 25, 35,45 and 55 y in Table 6.2. These are based directly on the risk estimates given in Table 5.12.

6.4.2

Careers Different in Length from Ten Years

The limits in Table 6.2 are based on a 10 y exposure duration. If the career of the crew member extends over a longer period (for example, 20 y), the total risk per unit dose decreases during the career because the susceptibility for radiation-induced cancer decreases with age. Correspondingly, for shorter intervals of exposure at earlier ages, the risk is higher per unit exposure (see Tables 5.9 and 5.10). If the space worker is exposed to only a fraction of the limit in a 10 y period, his or her career can be extended, as far as radiation exposure is concerned, to an additional period in which the fraction of the limit to which he or she has been exposed is accounted for.

6.4.3

Careers Starting at Other than Designated Ages

The recommended career limits can be plotted as a function of age (Figure 6.1) and values for other ages within the range interpolated from the figure. For example, for age 50 the career E limits for an TABLE 6.2-Recommended 10 y career limits based on three percent excess lifetime risk of cancer mortality." E (SV) Age at Exposure

Female

Male

"A three percent excess lifetime risk of cancer mortality carries with i t an additional 0.6 percent of nominal detriment for both heritable and nonfatal cancer risks for a total detriment of 4.2 percent. This assumes these nominal risks are a s given in ICRP (1991a) and NCRP (1993a).

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6. RADIATION PROTECTION STANDARDS FOR LEO

Fig. 6.1. Career limits of three percent probability of excess mortality from fatal cancer as a function of dose and age a t exposure.

excess lifetime risk of cancer mortality of three percent are approximately 1.3 Sv for females and 2.1 Sv for males. 6.4.4

Deterministic Limits

In addition to the career limit for whole-body exposures, it is necessary to establish other short-term limits in order to avoid deterministic effects in three critical organs: the bone marrow, lens of the eye, and the skin. Recommendations for limits for these organs were discussed in Sections 1 and 2 and are tabulated in Table 6.3. TABLE 6.3-Recommended dose limits for all ages and both genders.

Career 1Y 30 d

Bone Marrow" (Gy-Eq)

Eye (Gy-Eq)

Skin (Gy-Eq)

-

4.0 2.0 1.0

6.0 3.0 1.5

0.50 0.25

"The career stochastic limits for stochastic effects given in Tables 1.3and 6.2 are considered to be more than adequate for protection of the bone marrow against deterministic effects for career. The career limits are E and the Q(L)values used to convert absorbed dose to E (see Section 4.1.2)are considerably higher than the RBE values used to convert absorbed dose to gray equivalent. Therefore, there is no need for a career deterministic limit. The career stochastic limit is more restrictive and would always be expected to result in a lower absorbed dose to the bone marrow for the irradiation conditions in space.

6.4 RECOMMENDED LIMITS FOR LEO MISSIONS

1

145

Table 6.4 provides RBE data for the conversion from D to gray equivalents. 6.4.5

Recommendation Concerning Pregnant Females

The NCRP also recommends that pregnant females not participate in activities in space. The special radiation risks for the embryo/fetus are malformation and mental retardation, and the risk of cancer may be greater than that for adults. These risks can and should be avoided. However, the radiation risk to the embryo/fetus is most likely to be much smaller than the other biological detriments encountered during space activities. 6.4.6

The Meaning of Career Dose Limits and Uncertainty in Risk Estimates

It would be a mistake to think in terms of a given dose (or career dose limit) as corresponding to a precisely known risk of cancer for the two reasons given in Sections 6.4.6.1 and 6.4.6.2 below. TABLE 6.4-RBE values for converting D to gray equivalents for deterministic effects based on ICRP Publication 58 (adapted from ICRP, 1989)." Radiation Type

Recommended RBEb

Rangeb

1to 5 MeV neutrons 5 to 50 MeV neutrons Heavy ions (helium, carbon, neon, argon) Proton >2 MeV

6.0b 3.5b 2.5' 1.5

(4-8) (2-5) (1-4)

-

"RBE values for late deterministic effects are higher than for early effects in some tissues and are influenced by the doses used to determine the RBE. There are not sufficient data on which to base RBE values for early or late effects induced by neutrons of energies <1 MeV or greater than about 25 MeV. However, based on the induction of chromosome aberrations, using 250 kVp x rays as the reference radiation, the RBE for neutrons C1 MeV are comparable to those for fission spectrum neutrons. It is reasonable to assume that the RBE values for >50 MeV will be equal to or less than those for neutrons in the 5 to 50 MeV range. There are few data for the tissue effects of ions with a Z > 18 but the RBE values for iron ions (Z = 26) are comparable to those for argon. Based on the available data a value of 2.5 for the RBE of heavy ions is reasonable. One possible exception is cataract of the lens of the eye because high RBE values for cataracts in mice have been reported.

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6. RADIATION PROTECTION STANDARDS FOR LEO

6.4.6.1 Specification of the Dose. Lifetime risk estimates such as those given in Tables 5.9 and 5.12 are based on organ doses (colon dose is used as a surrogate for all organs in which the principal solid cancers may be formed and bone-marrow dose for leukemia). The colon dose for the gamrnalneutron irradiation of the atomic-bomb survivors is known to be about 0.67 of the skin dose which is taken to be the same as shielded kerma, while bone-marrow dose is about 0.79 of the skin dose (see Roesch, 1987, page 424, average of four cases). For space radiations, which consist of a mixture of protons and GCR,the ratio between colon and skin dose, and bone-marrow and skin dose, is complex and varies with the orbit flown in LEO, solar maximum and minimum and other variables such as EVA versus in spacecraft. These variables and circumstances are being fully evaluated at the present time and when complete data are available it may be possible to specify the doses and the risks more precisely. In the meantime, the ratios for organ dose to skin dose for space radiations seem likely to be even less than for the atomicbomb radiations. Thus, in both circumstances, taking the dose for the limits as the skin or badge dose is likely to exaggerate the effective dose and to be very conservative about the actual risks entailed since they could be substantially less. 6.4.6.2 Uncertainty in Risk Estimates. It is well known that risk estimation is a difficult field in which there are many sources of potential error and therefore uncertainty. For the risk estimates for the atomic-bomb survivors these uncertainties have been evaluated in some detail (NCRP, 1997b) and the results suggest that the risk estimates be presented as a distribution rather than a single value. Frequency Chart

100,000Trials Shown

..a-.-...........................

1.15

Lifetime Risk Coefficient (% per Sv)

8.08

Fig. 6.2. Probability distribution of the lifetime risk coefficient for a United States worker population as obtained from Monte Carol simulation. (The 90 percent confidence interval is shown by the arrows).

6.4 RECOMMENDED LIMITS FOR LEO MISSIONS

1

147

This distribution ranges from 1.15 to 8.1 x Sv-I for the 90 percent confidence intervals about the nominal value of four percent per sievert for an adult United States population (Figure 6.2). Given the magnitude of these uncertainties and the problems of dose specification estimates or risk on which dose limits for astronauts are based should be recognized as very conservative and possibly subject to modified values when more precise information becomes available.

7. Future Research 7.1 Recommendations for Research Required to Meet the Needs of the National Aeronautics and Space Administration Concerning Radiation Effects Research is needed to answer questions relating to radiation effects encountered terrestrially and those that are quite particular to radiation effects in space. This summary attempts to give the highest priority to those areas of research that require funding and are not likely to be supported by agencies other than NASA. Since NCRP Report No. 98 (NCRP, 1989)was published, a number of facilities for research of importance to NASA have been closed and funding of radiobiological research has suffered severe reductions. Both the facilities and the research were funded by the U.S. Department of Energy. Among the facilities that have been lost was the Bevalac accelerator used for studies of heavy ions. This loss has had a severe impact on the studies needed for predicting the effects of GCR. Currently, only one iron ion beam of 1 GeV iron ions is available in the United States. This beam is a t the Brookhaven National Laboratory and it is available for a very limited period of the year for space radiation research studies. The types of heavy ions and the spectrum of energies available are quite inadequate for the research that is needed. While sources of low-energy protons are available, and one, the facility at Loma Linda, is being used for research, sources of high-energy protons are also required. The research needs for the more accurate estimation of risks in LEO are discussed below. The studies and the facilities needed will also provide data required for the planning of missions in deep space. The needs for research that applies to deep-space missions will be discussed further in a subsequent NCRP report.

7.1.1 Dosimetry and Physics 1. Dosimetry. There continues to be a need for the development of "real time" active measurements of all components of the radiation field in LEO with adequate onboard recording. The

7.1 RECOMMENDATIONS FOR RESEARCH

.

1

149

devices should identifj. types of radiation and measure their energy spectra, in particular, the particles Z and velocity. Such equipment should be designed to be adequate for determining dose, radiation quality, and to detect changes in dose and radiation quality with time. This research should concentrate on the details of the radiation environment that will be experienced both inside and outside the spacecraft for the 28.5 and 51.7 degree orbital inclinations. Additional measurements of the fluence rates, energy spectra, and Z of heavy ions are required as there is not agreement about D that will be incurred from HZE particles. There is a need for appropriate transport codes which will use cross-section measurements for the relevant materials over a suitable range of fluences. Also, there is a need for a greater understanding of the probability and effects of fragmentation. Benchmark calculations have a value but studies should be designed so that comparisons with experimental data and theory can be made. For example, computer prediction codes could be checked with irradiations such as energetic iron ion beams degraded by water, aluminum and other pertinent materials. More should be known about the secondary radiations and their LET and energy spectra. Models of radiation environments. There have been many measurements of radiation on the Space Shuttle and the Mir Space Station since NCRP Report No. 98 (NCRP, 1989) that have greatly improved the understanding of radiation environments in space and within the space vehicles. This information is of great importance in the estimation of the doses involved and the influences of orbit and shielding. The new dosimetric equipment, and the assessments that they have made possible, have indicated that the models of the radiation belts need revision. New models should take into account the dynamic nature of trapped protons. Accurate models are needed to improve longterm predictions that may be experienced in space vehicles in orbit for a long period of time. Such predictions will assist the selection of the structural materials, which influence the radiation environment within the space vehicles. In summary, the available information about energy and LET spectra of protons, neutrons and I-IZEparticles in relation to inclination, altitude, shielding, and the phase of the solar cycle should be integrated and the relevant gaps in the information filled.

,2 Radiobiology and Health Effects

. Risk estimates for radiation-induced cancer in individual tissues should be based on tissue doses. Furthermore, particular

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7. FUTURE RESEARCH

tissue doses are needed for the proper calculation of E. Therefore, it is important that tissue H be determined for the various radiation environments both within the space vehicle and EVA. The estimate of tissue H in those exposed in EVA has become increasingly important because of the ISS, since assembly of the ISS will involve more EVA than ever before. 2. The data available on proton effects is limited, and while the assumption of a Q of 1.6 to 1.9 (see Section 1.3) may be justified in light of current information, it is not as well-substantiated as is desirable and further experiments are required to evaluate this assumption. Furthermore, there is a need for information on cataract formation and the effectson gonads from protracted exposures to protons, and in fact, other endpoints with low dose rate high-LET radiation exposures, Neutrons are an important contributor to the total dose and, therefore, there is need for some general research on neutron effects. The current uncertainty for low-energy neutron Q values emphasizes this need. For example, the risks of cancer, cataract and deterministic effects from protracted neutron irradiation are currently based on incomplete information. 3. There is a need for: (a) more complete information about timedose relationships, especially for protons, and (b) for further information about the radiobiology and biophysics of HZE particles. This is particularly true for the estimation of risks that missions in deep space may pose. However, since GCR, which includes HZE particles, contributes significantly to H in LEO, the information is also needed for H estimates in LEO. Since there are no human data for either stochastic or deterministic effects of HZE particles that are adequate for the estimation of risks, data from experimental studies must be relied on. Currently risk estimates for HZE particles are based on risks for gamma rays and H obtained with estimated Q values of between 3.2 and 3.5 (see Section 1.3). There is a need for data on cancer induction in representative tissues by selected heavy ions to obtain RBE values to validate the new Q-LET relationship proposed in ICRP Publication 60 (ICRP, 1991a),especially for LET values near 100 keV Fm-l. In addition, RBE values for deterministic effects based on thresholds are needed. The induction of cancer by HZE particles is of interest not only because of the need for estimates of Q, but with such radiations there is, perhaps, some hope of establishing the relationship of track structure to DNA damage, mutation and cancer induction. Thus, there is a need for sustaining support for

7.2 CONCLUSION

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151

the theoretical or modeling studies of the complex trail from energy deposition to the resulting biological effects. 4. Two types of interaction require assessment: (a) the possibility of interaction between different types of radiation, and (b) the possibility of an interaction between microgravity and radiation. It is not thought that either of these possible interactions will have a significant impact on radiation risk estimates but are, nevertheless, of interest to the general understanding of radiation effects. Adaptive responses might be considered under the heading of interaction but experiments defining the effect of small doses and protraction should provide the relevant information. It is well established that microgravity affects a number of systems includingthe immune system. The evidence for a synergistic effect between radiation and microgravity is much less convincingand the difficultiesin carrying out a definitiveexperiment are formidable. However, the evidence should be collected and a judgment made about whether experiments are required. 5. Research on the effects of partial body irradiation could help in the design of protective shielding especially for EVA. Development is required of satisfactory methods of protection against the acute effects that could occur due to an SPE. Work on development and testing of chemical radioprotectors should be continued. 6. The dependency of susceptibility for cancer induction on age is known for cancer of the breast and thyroid. However, there is a need for both epidemiological and experimental data on susceptibility of other cancers as a function of age. 7. A registry of astronauts and space workers should be continued, and appropriate medical follow-ups carried out, in order that appropriate studies can be carried out in the future, if needed. 8. Radiation exposures in space, that involve a number of different radiation qualities, should be simulated experimentally on Earth and appropriate biological studies performed. In summary, the highest priorities are for improved dosimetry, especially for individual tissues, and for studies of the effects of HZE particles and protons so that the risks of both stochastic effects, such as carcinogenesis, and deterministic effects can be estimated with confidence. Such information is, of course, even more important for polar orbit, lunar, and Mars missions than for missions in LEO. 7.2 Conclusion

All of the research items that have been discussed above are of importance to the understanding of radiation effects in space.

152

1

7. FUTURE RESEARCH

However, these areas of research encompass many disciplines and research programs that will be difficult for NASA to carry out alone. The areas of particular concern to NASA are, first, a more complete delineation of the radiation environments that will be experienced in the various missions; second, the doses these radiations will generate in the body; and third, a better understanding of the late effects of GCR.

F

en

APPENDIX A

Site-Specific Xmcidence Data particular.uge; by cancer .type,age ,at q o s u r e , and sex.'

TABLE A.1-Estima&d lifitime ri& of cancer imii&nce,from.an exposure of 100 mSv in a single y

-

All solid cancers Leukemia All cancers

Stomach Colon Liver Lug Nonmehoma skin ,cancer Breast ovary Bladder Thyroid "Sitespecific incidence data h m Preston et.01. (1994)and Thompson et al. (1994).

F

0.452 0.066 0.518

M

0.068 0.098 0.014 0.310 0.016 0.074 0.047 0.085 0.001

0.919 0.058 0.977

F

0.022 0.088 0.021 0.213 0.006 0.000 0.000 0.048 0.000

0.270 0.062 0.332

M

0.757 0.058 0.815

F

0.182 0.046 0.228

M

cancer type, age at beginning of exposure, and sex."

M

1.038 0.046 1.083

0.051 0.089 0.025 0.153 0.022 0.001 0.000 0.053 0.001

&ge: by

0.613 0.062 0.676

0.128 0.097 0.013 0.309 0.031 0.188 0.053 0.082 0.004

particular

TABLE A.2-Estimated lifetime risk of cancer incidence from an exposure of 10 mSv y-' over 10 y begi

All cancers 0.083 0.086 0.027 0.065 0.042 0.001 0.000 0.054 0.001

All solid cancers Leukemia Stomach Colon Liver Lung Nonmelanoma skin cancer Breast Ovary Bladder Thyroid

"Site specific incidence data from Preston et al. (1994)and Thompson et al. (1994).

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Glossary absolute risk See risk. absorbed dose @f: The energy imparted to matter by ionizing radiation per unit mass of irradiated material a t t h e point of interest; unit of absorbed dose has been the rad and now, in the System International (SI) units, it is the gray (Gy). 1 Gy = 100 rad. ACR (anomalouscosmic rays): Component perhaps of a different origin than that of the high-energy cosmic rays. The peak in the energy spectrum at solar maximum is about 10 MeV m-l. AE-8: Model of the trapped electron radiation. albedo neutron: Secondary neutrons produced by interaction of galactic cosmic rays and the atmosphere. alpha particles: Nuclei of helium atoms consisting of two protons and two neutrons in close association. They have a net charge of + 2 and can therefore be accelerated in large electrical devices similar to those used for protons, and they are also emitted during the decay of some radioactive isotopes. AP-8: Model of the trapped proton radiation. APC (adenomatous polyposis coli gene): One of the genes involved in the control of proliferation of the colonic epithelium. AU (astronomical unit):The average distance from the sun to the earth, 160 x lo8 km. azoospermia: Lack of sperm. baryon: Any of the heavier elementary particles such a s protons and neutrons. bremsstrahlung: Secondary photon radiation produced by deceleration of charged particles. bystander effect: The effect detected in cells not traversed by a particle. cornea: The transparent epithelial structure forming the anterior part of the external covering of the eye. coronal mass ejection: A transient outflow of plasma from or through the solar corona which may be associated with the generation of solar particle events. DCC (deleted colon cancer gene): Loss of this gene is associated with progression of colon cancer. DD (doublingdose):The dose required to double the effect under consideration assuming a Iinear dose response. delta ray: Electrons stripped from atoms a s a charged particle passes through matter. deterministic effects: Previously called nonstochastic effects, may appear early or late after irradiation. These effects occur above a threshold dose and increase in both incidence and severity with increasing dose.

GLOSSARY

1

157

detriment: Health detriment is the sum of the probabilities of all the components of health effects. These include in addition to fatal cancer the probability of heritable effects and the probability of morbidity from nonfatal cancer. dose: A general term denoting the quantity of radiation or energy absorbed; for special purposes, must be qualified; if unqualified, refers to absorbed dose. dose equivalent 0:Quantity that expresses the biological effect of interest in radiation protection for all kinds of radiation on a common scale; defined as the product of the absorbed dose in rad or gray and quality factor (Q)for the particular radiation, i.e., H = DQ; unit of H has been the rem and is now the sievert (Sv) in SI units, 100 rem = 1 Sv. dose rate: Absorbed dose delivered per unit time. dose-response model: A mathematical formulation of the way in which the effect, or response, depends on dose. DS86 (Dosimetry System 1986): A revision of the previous atomic-bomb dosimetry TD65. effective dose (E):The sum of the equivalent doses to the individual organs or tissues multiplied by their respective weighting factors (WT) The unit is the joule per kilogram with the special name sievert. electrons: Small negatively charged particles that can be accelerated to high energy and velocity close to the speed of light. endometriosis: The presence of extrauterine endometrial tissue, a nonmalignant condition. equivalent dose (HTh The absorbed dose averaged over a tissue or organ and weighted for the radiation quality that is of interest called the radiation weighting factor (wd. ERR (excess relative risk): An expression of excess risk relative to the underlying (baseline) risk; if the excess equals the baseline the relative risk is two. erythema: A redness of the skin. eV (electron volt): A unit of energy = 1.6 X 10-l2 ergs = 1.6 X 10-l9 J; 1eV is equivalent to the energy gained by a n electron in passing through a potential difference of 1V, 1keV = 1,000 eV, 1MeV = 1,000,000 eV. EVA (extravehicular activity): Any activity undertaken by the crew outside a space vehicle. exposure: A measure of the ionization produced in air by x or gamma radiation. Exposure is the sum of electric charges on all ions of one sign produced in air when all electrons liberated by photons in a volume of air are completely stopped, divided by the mass of the air in the volume. The unit of exposure in air is the roentgen (R)or in SI units it is expressed in coulombs (C), 1R = 2.58 x C kg-'. a c u t e exposure: Radiation exposure of short duration. chronic exposure: Radiation exposure of long duration, because of fractionation or protraction. fluence: Particle traversals per unit area. GCR (galactic cosmic rays): The charged particle radiation outside the magnetosphere. The GCR fluence consists of approximately 87 percent protons, 12 percent helium ions, and 1percent HZE particles.

158

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GLOSSARY

Geostationary Operational Environmental Satellite: Used for monitoring protons. gray (Gy): The International System (SI)unit of absorbed dose of radiation, 1Gy = 1J kg-l = 100 rad. gray equivalent (Gy-Eq):A dose weighted for relative biological effectiveness. In this Report, dose limits for deterministic effects are expressed as the organ dose in gray multiplied by the relevant RBE for the specific organ and radiation. heavy ions: Nuclei of elements such as nitrogen, carbon, boron, neon, argon or iron which are positively charged due to some or all of the planetary electrons having been stripped from them. heliolongitude: Imaginary lines of longitude on the sun measured east (left) or west (right) of the central meridian (imaginary north-south line through the middle of the visible solar disk) as viewed from Earth. The left edge of the solar disk is 90°E and the right edge is 90°W. heliosphere: A region of the atmosphere from 960 to 2,400 km above Earth's surface. HZE: A heavy ion having an atomic number greater than that of helium and having high kinetic energy. incidence: The rate of occurrence of a disease, usually expressed in number of cases per million. incidence rate: The rate of occurrence of a disease within a specified period of time, oRen expressed as the number of cases per 100,000 individuals per year. inclination: This is the acute angle that the trajectory of an orbit makes with Earth's equator. ionization: The process by which a neutral atom or molecule acquires a positive or negative charge. ionosphere: Region from 80 km above Earth stretching into outer space. An arbitrary upper limit of 960 km is sometimes applied. iris: The circular pigmented membrane behind the cornea perforated by the pupil. Its circular muscle fibers allow the size of the pupil to be varied. kerma (kinetic energy released i n material): A unit that represents the kinetic energy transferred to charged particles per unit mass of the irradiated medium. latent period: Period or state of seeming inactivity between time of exposure of tissue to an injurious agent and an observed response. LDm: Dose of radiation required to kill, within a specified period, 50 percent of the individuals in a population. LET (linear-energy transfer): Average amount of energy lost per unit of particle track length and expressed in keV p,m-l. low-LET: Radiation having a low-linear energy transfer; for example, electrons, x rays, and gamma rays. high-LET: Radiation having a high-linear energy transfer; for example, protons, alpha particles, heavy ions, and interaction products of fast neutrons. lifetime risk: The lifetime probability of dying of a specific disease.

GLOSSARY

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159

l i n e a r model: Also, linear dose-response relationship; expresses an effect of (e.g., mutation or cancer) a s a direct (linear) function of dose. linear-quadratic model: Also, linear-quadratic dose-response relationship; expresses the incidence of (e.g., mutation or cancer) a s partly directly proportional to the dose (linear term) and partly proportional to the square of the dose (quadratic term). The linear term will predominate a t lower doses, the quadratic term a t higher doses. MCC ( m u t a t i o n colon c a n c e r gene): One of the presumptive tumor suppressor genes involved in the control of proliferation of the colonic epithelium. microlesion: Term introduced by NAS/NRC in 1973to describe the localized damage along heavy-charged particle track that is distinct from the damage caused by low-LET radiation. Mir: The Russian (previously Soviet) orbital space station. neutrons: Particles with a mass similar to that of a proton, but with no electrical charge. Because they are electrically neutral, they cannot be accelerated in an electrical field. prevalence: The number of cases of a disease in existence a t a given time per unit of population, usually per 100,000 persons. protons: The nucleus of the hydrogen atom. Protons are positively charged. protraction: Extending the length of exposure, for example, the continuous delivery of a radiation dose over a longer period of time. quality factor (Q):The LET-dependent factor by which absorbed dose is multiplied to obtain (for radiation-protection purposes) the dose equivalent, a quantity that expresses the effectiveness of a n absorbed dose on a common scale for all kinds of ionizing radiation. radiation: 1. The emission and propagation of energy through space or through matter in the form of waves, such as electromagnetic waves, sound waves, or elastic waves. 2. The energy propagated through space or through matter a s waves; "radiation" or "radiant energy," when unqualified, usually refers to electromagnetic radiation; commonly classified by frequencyHertzian, infrared, visible, ultraviolet, x, and gamma ray. 3. Corpuscular emission, such as alpha and beta particles, or rays of mixed or unknown type, such as cosmic radiation. background radiation: The amount of radiation to which a member of the population is exposed from natural sources, such a s terrestrial radiation from naturally occurring radionuclides in the soil, cosmic radiation originating in outer space, and naturally occurring radionuclides deposited in the human body. The natural background radiation received by an individual depends on geographic location and living habits. In the United States, the background radiation is on the order of 1 mSv (100 mrem) y-l, excluding indoor radon which amounts to about 2 mSv y-I on average. ionizingradiation: Any electromagneticor particulate radiation capable of producing ions, directly or indirectly, in its passage through matter.

160

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GLOSSARY

radiation quality: A general term referring to the spatial distribution of absorbed dose. For example, an exposure to neutron radiation may be quantitatively the same as an exposure to gamma rays, in the sense that, for large volumes of tissue on the order of 1 cm3, the absorbed energy is the same, yet a t resolutions of a few micrometers the ionizing events will be more uniformly dispersed for the gammaray radiation than for the neutron radiation, producing quantitatively different biological effects (see RBE). secondary radiation: Radiation resulting from absorption of other radiation in matter; may be either electromagnetic or particulate. radiation weighting factor (loR):A factor used for radiation protection purposes to allow for differences in the biological effectiveness between different radiations. These factors a r e independent of the tissue or organ irradiated. RBE (relative biological effectiveness): A factor used to compare the biological effectiveness of absorbed radiation doses from different types of ionizing radiation; more specifically, the experimentally determined ratio of an absorbed dose of a radiation in question to the absorbed dose of a reference radiation required to produce an identical biological effect in a particular experimental organism or tissue; if 10 mGy of fast neutrons equaled in lethality to 20 mGy 250 kVp x rays, the RBE of the fast neutrons would be two. RE: The mean radius of the earth; 1RE equals 6,371 km. risk: The probability of a specified effect or response occurring. absolute risk: Expression of excess risk due to exposure as the arithmetic difference between the risk among those exposed and that obtaining in the absence of exposure. a n n u a l risk: The risk in a given year from an earlier exposure. The annual risk (average) from an exposure is the lifetime risk divided by the number of years of expression. lifetime risk: The total risk in a lifetime resulting from an exposure(s). It is equal to the average annual risk times the period of expression. relative risk: An expression of excess risk relative to the underlying (baseline) risk; if the excess equals the baseline risk the relative risk is two. risk coefficient: The increase in the annual incidence or mortality rate per unit dose: (1)absolute risk coefficient is the observed minus the expected number of cases per person year a t risk for a unit dose; (2) the relative risk coefficient is the fractional increase in the baseline incidence or mortality rate for a unit dose. risk cross section: The probability of a particular excess cancer mortality per particle fluence (excluding delta rays). risk estimate: The number of cases (or deaths) that are projected to occur in a specified exposed population per unit dose for a defined exposure regime and expression period; number of cases per person-gray or, for radon, the number of cases per person cumulative working level month. roentgen (R): A unit of radiation exposure. Exposure in SI units is expressed in C kg-' of air.

GLOSSARY

1

161

sclera: The tough supporting tunic of the eyeball covering it except for the segment covered by the cornea. sievert (Sv): The SI unit of radiation dose equivalent or equivalent dose. It is equal to the dose in gray times a quality factor (Q)or radiation weighting fador (wR):1SV = 100 rem. solar cycle: The solar-activity cyclic behavior, usually represented by the number of sunspots visible on the solar photosphere. The average length of solar cycles since 1900 is 11.4 y. solar flare: The name given to the sudden release of energy (often more than 1P2ergs) in a relatively small volume of the solar atmosphere. Historically, an optical brightening in the chromosphere, now expanded to cover almost all impulsive radiation from the sun. solar maximum: The period of the 11y solar cycle during which the solar wind is at its most intense resulting in lower levels of GCR radiation about the Earth. solar minimum: The portion of the 11y solar cycle during which the solar wind is a t its least intense resulting in higher levels of GCR radiation about the Earth. solar wind: The plasma flowing into space from the solar corona. The ionized gas carrying magnetic fields can alter the intensity of the interplanetary radiation. SPE (solar particle events): Eruptions a t the sun that releases a large number of particles (primarily protons) over the course of hours or days. stochastic: Describes random events leading to effects whose probability of occurrence in an exposed population (rather than severity in an affected individual) is a direct function of dose; these effects are commonly regarded as having no threshold; hereditary effects are regarded as being stochastic; some somatic effects, especially carcinogenesis are regarded as being stochastic. telangiectasia: Dilation of the capillary vessels and very small arteries. tissue weighting factor (wT):A factor representing the ratio of the risk of stochastic effects attributable to irradiation of a given organ or tissue (TIto the total risk when the whole body is irradiated uniformly. The factor is independent of the type of radiation or energy of the radiation.

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Note TND-1862 (National Technical Information Service, Springfield, Virginia). WHITE, T.T., ATWELL, W. and HARDY, kc. (1972). "Radiation analysis for Apollo lunar missions," presented a t the 18th Annual Meeting of the American Nuclear Society, Las Vegas, Nevada. WILSON, J.W., NEALY, J.E., ATWELL, W., CUCINOTTA, F.A., SHINN, J.L. and TOWNSEND, L.W. (1990). "Improved model for solar cosmic ray exposure in manned E a r t h orbital flights," NASA Technical Paper TP-2987 (National Technical Information Service, Springfield, Virginia). WING, S., SHY, C.M., WOOD, J.L., WOLF, S., CRAGLE, D.L. and FROME, E.L. (1991). "Mortality among workers a t Oak Ridge National Laboratory. Evidence of radiation effects i n follow-up through 1984," JAMA 265, 1397-1402. WOOD, D.H. (1991). "Long-term mortality and cancer risk in irradiated Rhesus monkeys," Radiat. Res. 126, 132-140. WOOD, D.H., YOCHMOWITZ, M.G., HARDY, K.A. and SALMON, Y.L. (1986). "Animal studies of life shortening and cancer risk from space radiation," Adv. Space Res. 6, 275-283. WOOD, D., COX, A., HARDY, K., SALMON, Y. and TROTTER, R. (1994). "Head and neck tumors after energetic proton irradiation in rats," Adv. Space Res. 14,681-684. WORGUL, B.V., MEDVEDOVSKY, C., HUANG, Y., MARINO, S.A., RANDERS-PEHRSON, G. and BRENNER, D.J. (1996). "Quantitative assessment of the cataractogenic potential of very low doses of neutrons," Radiat. Res. 145,343-349. WOUTERS, B.G. and SKARSGARD, L.D. (1997). "Low-dose radiation sensitivity and induced radioresistance to cell killing in HT-29 cells is distinct from the 'adaptive response' and cannot be explained by a subpopulation of sensitive cells," Radiat. Res. 148, 435-442. WOUTERS, B.G., LAM,G.K., OELFKE, U., GARDEY, K, DURAND, R.E. and SKARSGARD, L.D. (1996)."Measurements of relative biological effectiveness of the 70 MeV proton beam a t TRIUMF using Chinese hamster V79 cells and the high-precision cell sorter assay," Radiat. Res. 146, 159-170. YANG, T.C., CRAISE, L.M., MEI, M.T. and TOBIAS, C.A. (1985). "Neoplastic cell transformation by charged particles," Radiat. Res. 104, ,3177-S187. YANG, T.C.H., CRAISE, L.M., MEI, M.T. and TOBIAS, C.A. (1986). "Dose protraction studies with low- and high-LET radiations on neoplastic cell transformation in vitro," Adv. Space Res. 6, 137-147. YOCHMOWITZ, M.G., WOOD, D.M. and SALMON,Y.L. (1985)."Seventeenyear mortality experience of proton radiation in Macaca mulatta," Radiat. R ~ s .102, 14-34. ZAIDER, M. and BRENNER, D.J. (1985). "On the microdosimetric definition of quality factors," Radiat. Res. 103, 302-316.

The NCRP The National Council on Radiation Protection and Measurements is a nonprofit corporation chartered by Congress in 1964 to: 1. Collect, analyze, develop and disseminate in the public interest information and recommendations about (a) protection against radiation and (b) radiation measurements, quantities and units, particularly those concerned with radiation protection. 2. Provide a means by which organizations concerned with the scientific and related aspects of radiation protection and of radiation quantities, units and measurements may cooperate for effective utilization of their combined resources, and to stimulate the work of such organizations. 3. Develop basic concepts about radiation quantities, units and measurements, about the application of these concepts, and about radiation protection. 4. Cooperate with the International Commission on RadiologicalProtection, the International Commission on Radiation Units and Measurements, and other national and international organizations, governmental and private, concerned with radiation quantities, units and measurements and with radiation protection. The Council is the successor to the unincorporated association of scientists known a s the National Committee on Radiation Protection and Measurements and was formed to carry on the work begun by the Committee in 1929. The participants in the Council's work are the Council members and members of scientific and administrative committees. Council members are selected solely on the basis of their scientific expertise and serve a s individuals, not as representatives of any particular organization. The scientific committees, composed of experts having detailed knowledge and competence in the particular area of the committee's interest, draft proposed recommendations. These are then submitted to the full membership of the Council for careful review and approval before being published. The following comprise the current officers and membership of the Council: Officers President Vice President Secretary and Assistant Treasurer Assistant Secretary Treasurer

Charles B. Meinhold S. James Adelstein William M. Beckner Michael F. McBride James F. Berg

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S. James Adelstein John F. Ahearne Larry E. Anderson Lynn R. Anspaugh Benjamin R. Archer Harold L. Beck Eleanor A. Blakely B. Gordon Blaylock John D. Boice, Jr. Andr6 Bouville Leslie A. Braby Davi J. Brenner Antone L. Brooks Patricia A. Buffler Shih-Yew Chen Chung-Kwang Chou James E. Cleaver J. Donald Cossairt Allen G. Croff Paul M. DeLuca Carter Denniston Gail de Planque John F. Dice110 Sarah S. Donaldson William P. Dornsife Keith F. Eckerman Marc Edwards Stephen A. Feig H. Keith Florig Kenneth R. Foster

Thomas F. Gesell Ethel S. Gilbert John D. Graham Joel E. Gray Raymond A. Guilmette William R. Hendee David G. Hoe1 F. Owen Hoffman Geoffrey R. Howe Donald G. Jacobs Kenneth R. Kase David C. Kocher Ritsuko Komaki Amy Kronenberg Charles E. Land Susan M. Langhorst Richard W. Leggett Howard L. Liber James C. Lin John B. Little Richard A. Luben C. Douglas Maynard Claire M. Mays Roger 0.McClellan Barbara J. McNeil Charles B. Meinhold Fred A. Mettler, Jr. Charles W. Miller Kenneth L. Miller John E. Moulder

David S. Myers Ronald C. Petersen John W. Poston, Sr. Andrew K. Pornanski R. Julian Preston Jerome S. Puskin Genevieve S. Roessler Marvin Rosenstein Lawrence N. Rothenberg Henry D. Royal Michael T. Ryan Jonathan M. Samet Stephen M. Seltzer Roy E. Shore David H. Sliney Paul Slovic Louise C. Strong Richard A. Tell John E. Till Lawrence W. Townsend Robert L. Ullrich Richard J. Vetter Daniel Wartenberg David A. Weber F. Ward Whicker Chris G. Whipple J. Frank Wilson Susan D. Wiltshire Marco Zaider Marvin C. Ziskin

Honorary Members

Lauriston S. Taylor, Honoray President Warren K. Sinclair, President Emeritus W. Roger Ney, Executive Director Emeritus Seymour Abrahamson Edward L. Alpen John A. Auxier William J. Bair Bruce B. Boecker Victor P. Bond Robert L. Brent Reynold F. Brown Melvin C. Carter Randall S. Caswell Frederick P. Cowan James F. Crow Gerald D. Dodd

Patricia W. Durbin Thomas S. Ely Richard F. Foster Hymer L. Friedell R.J. Michael Fry Robert 0.Gorson Arthur W. Guy Eric J. Hall Naomi H. Harley John W. Healy Bemd Kahn Wilfrid B. Mann Dade W. Moeller A. Alan Moghissi Robert J. Nelsen

Wesley L. Nyborg Chester R. Richmond William L. Russell John H. Rust Eugene L. Saenger William J. Schull J. Newel1 Stannard John B. Storer Thomas S. Tenforde Arthur C. Upton George L. Voelz Edward W. Webster

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Lauriston S. Taylor Lecturers Herbert M. Parker (1977) The Squares of the Natural Numbers in Radiation Protection Sir Edward Pochin (1978) Why be Quantitative about Radiation Risk Estimates? Hymer L. Friedell (1979) Radiation Protection-Concepts and Tmde Offs Harold 0.Wyckoff(1980) From "Quantity of Radiationn and "Dose" to "Exposure" and 'Nbsorbed Dosep'-An Historical Review James F. Crow (1981) How Well Can We Assess Genetic Risk? Not Very Eugene L. Saenger (1982) Ethics, Trade-offs and Medical Radiation Meml Eisenbud (1983) The Human Environment-Past, Present and Future Harald H. Rossi (1984) Limitation and Assessment in Radiation Protection John H. Harley (1985) h t h (and Beauty) in Radiation Measurement Herman P. Schwan (1986) Biological Effects of Non-ionizing Radiations: Cellular Properties and Interactions Seymour Jablon (1987) How to be Quantitative about Radiation Risk Estimates Bo Lindell(1988) How Safe is Safe Enough? Arthur C. Upton (1989) Radiobiology and Radiatwn Protection: The Past Century and Prospects for the Future J. Newell Stannard (1990) Radiation Protection and the Internal Emitter Saga Victor P. Bond (1991) When is a Dose Not a Dose? Edward W . Webster (1992)Dose and Risk in Diagnostic Radiology: How Big? How Little? Warren K. Sinclair (1993) Science, Radiation Protection and the NCRP R.J. Michael Fry (1994) Mice, Myths and Men Albrecht Kellerer (1995) Certainty and Uncertainty in Radiation Protection Seymour Abrahamson (1996) 70 Years of Radiation Genetics: Fruit Flies, Mice and Humans William J. Bair (1997) Radionuclides in the Body: Meeting the Chalknge! Eric J. Hall (1998)From Chimney Sweeps to Astronauts: Cancer Risks in the Workplace Naomi H. Harley (1999) Back to Background S. James Adelstein (2000)Administered Radioactivity: Unde Venimus Quoque Imus

Currently, the following committees are actively engaged in formulating recommendations: SC 1

Basic Criteria, Epidemiology, Radiobiology and Risk SC 1-4 Extrapolation of Risks from Non-Human Experimental Systems to Man SC 1-6 Linearity of Dose Response SC 1-7 Information Needed to Make Radiation Protection Recommendations for Travel Beyond Low-Earth Orbit SC 1-8 Risk to Thyroid from Ionizing Radiation SC 1-9 Radiation Exposure Limits for the Skin Structural Shielding Design and Evaluation for Medical Use of SC 9 X Rays and Gamma Rays of Energies Up to 10 MeV SC 46 Operational Radiation Safety

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SC 46-8 Radiation Protection Design Guidelines for Particle Accelerator Facilities SC 46-10 Assessment of Occupational Doses from Internal Emitters SC 46-13 Design of Facilities for Medical Radiation Therapy SC 46-14 Radiation Protection Issues Related to Terrorist Activities that Result in the Dispersal of Radioactive Material SC 46-15 Operational Radiation Safety Program for Astronauts SC 57-10 Liver Cancer Risk SC 57-15 Uranium Risk SC 57-17 Radionuclide Dosimetry Models for Wounds Environmental Issues SC 64-17Uncertainty in Environmental Transport in the Absence of Site-Specific Data SC 64-19 Historical Dose SC 64-22Design of Effective Effluent and Environmental Monitoring Programs SC 64-23 Cesium in the Environment Biological Effects and Exposure Criteria for Ultrasound Radiation Protection in Mammography Risk of Lung Cancer from Radon Radioactive and Mixed Waste SC 87-1 Waste Avoidance and Volume Reduction SC 87-2Waste Classification Based on Risk SC 87-3 Performance Assessment SC 87-4 Management of Waste Metals Containing Radioactivity Fluence as the Basis for a Radiation Protection System for Astronauts Nonionizing Electromagnetic Fields SC 89-3 Biological Effects of Extremely Low-Frequency Electric and Magnetic Fields SC 89-4 Biological Effects and Exposure Recommendations for Modulated Radiofrequency Fields SC 89-5 Biological Effects and Exposure Criteria for Radiofrequency Fields Radiation Protection in Medicine SC 91-1 Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides SC 91-2Radiation Protection in Dentistry SC 91-3 Medical Radiation Exposure of the U.S. Population with Emphasis on Radiation Exposure of the Female Breast Public Policy and Risk Communication Radiation Measurement and Dosimetry In recognition of its responsibility to facilitate and stimulate cooperation among organizations concerned with the scientific and related aspects of radiation protection and measurement, the Council has created a category

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of NCRP Collaborating Organizations. Organizations or groups of organizations that are national or international in scope and are concerned with scientific problems involving radiation quantities, units, measurements and effects, or radiation protection may be admitted to collaborating status by the Council. Collaborating Organizations provide a means by which the NCRP can gain input into its activities from a wider segment of society. At the same time, the relationships with the Collaborating Organizations facilitate wider dissemination of information about the Council's activities, interests and concerns. Collaborating Organizations have the opportunity to comment on draft reports (at the time that these are submitted to the members of the Council). This is intended to capitalize on the fact that Collaborating Organizations are in an excellent position to both contribute to the identification of what needs to be treated in NCRP reports and to identify problems that might result from proposed recommendations. The present Collaborating Organizations with which the NCRP maintains liaison are as follows: Agency for Toxic Substances and Disease Registry American Academy of Dermatology American Academy of Environmental Engineers American Academy of Health Physics American Association of Physicists in Medicine American College of Medical Physics American College of Nuclear Physicians American College of Occupational and Environmental Medicine American College of Radiology American Dental Association American Industrial Hygiene Association American Institute of Ultrasound in Medicine American Insurance Services Group American Medical Association American Nuclear Society American Pharmaceutical Association American Podiatric Medical Association American Public Health Association American Radium Society American Roentgen Ray Society American Society for Therapeutic Radiology and Oncology American Society of Health-System Pharmacists American Society of Radiologic Technologists Association of University Radiologists Bioelectromagnetics Society Campus Radiation Safety Officers College of American Pathologists Conference of Radiation Control Program Directors, Inc. Council on Radionuclides and Radiopharmaceuticals Defense Special Weapons Agency Electric Power Research Institute

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Electromagnetic Energy Association Federal Communications Commission Federal Emergency Management Agency Genetics Society of America Health Physics Society Institute of Electrical and Electronics Engineers, Inc. Institute of Nuclear Power Operations International Brotherhood of Electrical Workers National Aeronautics and Space Administration National Association of Environmental Professionals National Electrical Manufacturers Association National Institute for Occupational Safety and Health National Institute of Standards and Technology Nuclear Energy Institute Ofice of Science and Technology Policy Oil, Chemical and Atomic Workers Union Radiation Research Society Radiological Society of North America Society for Risk Analysis Society of Nuclear Medicine U.S. Air Force U.S. Army U.S. Coast Guard U.S. Department of Energy U.S. Department of Housing and Urban Development U.S. Department of Labor U.S. Department of Transportation U.S. Environmental Protection Agency U.S. Navy U.S. Nuclear Regulatory Commission U.S. Public Health Service Utility Workers Union of America The NCRP has found its relationships with these organizations to be extremely valuable to continued progress in its program. Another aspect of the cooperative efforts of the NCRP relates to the Special Liaison relationships established with various governmental organizations that have an interest in radiation protection and measurements. This liaison relationship provides: (1)an opportunity for participating organizations to designate an individual to provide liaison between the organization and the NCRP; (2) that the individual designated will receive copies of draft NCRP reports (at the time that these are submitted to the members of the Council) with an invitation to comment, but not vote; and (3) that new NCRP efforts might be discussed with liaison individuals as appropriate, SO that they might have an opportunity to make suggestions on new studies and related matters. The following organizations participate in the Special Liaison Program:

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Atomic Energy Control Board Australian Radiation Laboratory Bundesamt fiir Strahlenschutz (Germany) Central Laboratory for Radiological Protection (Poland) Commisariat A 1'Energie Atomique European Commission Health Council of the Netherlands International Commission on Non-Ionizing Radiation Protection Japan Radiation Council Korea Institute of Nuclear Safety National Radiological Protection Board (United Kingdom) Russian Scientific Commission on Radiation Protection South African Forum for Radiation Protection Ultrasonics Institute (Australia) World Association of Nuclear Operations The NCRP values highly the participation of these organizations in the Special Liaison Program. The Council also benefits significantly from the relationships established pursuant to the Corporate Sponsor's Program. The program facilitates the interchange of information and ideas and corporate sponsors provide valuable fiscal support for the Council's program. This developing program currently includes the following Corporate Sponsors: 3M Commonwealth Edison Consolidated Edison Duke Power Florida Power Corporation ICN Biomedicals, Inc. Landauer, Inc. New York Power Authority Nuclear Energy Institute Nycomed Amersham Imaging Southern California Edison The Council's activities are made possible by the voluntary contribution of time and effort by its members and participants and the generous support of the following organizations:

3M Health Physics Services Agfa Corporation Alfred P. Sloan Foundation Alliance of American Insurers American Academy of Dermatology American Academy of Health Physics American Academy of Oral and Madlofacial Radiology American Association of Physicists in Medicine

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American Cancer Society American College of Medical Physics American College of Nuclear Physicians American College of Occupational and Environmental Medicine American College of Radiology American College of Radiology Foundation American Dental Association American Healthcare Radiology Administrators American Industrial Hygiene Association American Insurance Services Group American Medical Association American Nuclear Society American Osteopathic College of Radiology American Podiatric Medical Association American Public Health Association American Radium Society American Roentgen Ray Society American Society of Radiologic Technologists American Society for Therapeutic Radiology and Oncology American Veterinary Medical Association American Veterinary Radiology Society Association of University Radiologists Battelle Memorial Institute Canberra Industries, Inc. Chem Nuclear Systems Center for Devices and Radiological Health College of American Pathologists Committee on Interagency Radiation Research and Po!icy Coordination Commonwealth of Pennsylvania Consumers Power Company Council on Radionuclides and Radiopharmaceuticals Defense Nuclear Agency Eastman Kodak Company Edison Electric Institute Edward Mallinckrodt, Jr. Foundation EG&G Idaho, Inc. Electric Power Research Institute Federal Emergency Management Agency Florida Institute of Phosphate Research Fuji Medical Systems, U.S.A., Inc. Genetics Society of America Health Effects Research Foundation (Japan) Health Physics Society Institute of Nuclear Power Operations James Picker Foundation Martin Marietta Corporation Motorola Foundation

National Aeronautics and Space Administration National Association of Photographic Manufacturers National Cancer Institute National Electrical Manufacturers Association National Institute of Standards and Technology Picker International Public Service Electric and Gas Company Radiation Research Society Radiological Society of North America Richard Lounsbery Foundation Sandia National Laboratory Siemens Medical Systems, Inc. Society of Nuclear Medicine Society of Pediatric Radiology U.S. Department of Energy U.S. Department of Labor U.S. Environmental Protection Agency U.S. Navy U.S. Nuclear Regulatory Commission Victoreen, Inc. Westinghouse Electric Corporation Initial funds for publication of NCRP reports were provided by a grant from the James Picker Foundation. The NCRP seeks to promulgate information and recommen-dations based on leading scientific judgment on matters of radiation protection and measurement and to foster cooperation among organizations concerned with these matters. These efforts are intended to serve the public interest and the Council welcomes comments and suggestions on its reports or activities from those interested in its work.

NCRP Publications

Information on NCRP publications may be obtained from the NCRP website (http://www.ncrp.com), e-mail ([email protected]), by telephone (800-229-2652), or fax (301-907-8768). The address is: NCRP Publications 7910 Woodmont Avenue Suite 800 Bethesda, MD 20814-3095 Abstracts of NCRP reports published since 1980, abstracts of all NCRP commentaries, and the text of all NCRP statements are available at the NCRP website. Currently available publications are listed below.

NCRP Reports No.

Title Control and Removal of Radioactive Contamination i n Laboratories (1951) Maximum Permissible Body B u r h n s and Maximum Permissible Concentrations of Radionuclides in Air and i n Water for Occupational Exposure (1959) [Includes Addendum 1 issued in August 19631 Measurement of Absorbed Dose of Neutrons, and of Mixtures of Neutrons and Gamma Rays (1961) Stopping Powers for Use with Cavity Chambers (1961) Safe Handling of Radioactive Materials (1964) Radiation Protection in Educational Institutions (1966) Dental X-Ray Protection (1970) Radiation Protection in Veterinary Medicine (1970) Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides (1970) Protection Against Neutron Radiation (1971) Protection Against Radiation from Brachytherapy Sources (1972) Specification of Gamma-Ray Brachytherapy Sources (1974) Radiological Factors w e c t i n g Decision-Making in a Nuclear Attack (1974)

NCRP PUBLICATIONS

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Krypton-85 in the Atmosphere-Accumulation, Biological Significance, and Control Technology (1975) Alpha-Emitting Particles in Lungs (1975) Tritium Measurement Techniques (1976) Structural Shielding Design and Evaluation for Medical Use of X Rays and Gamma Rays of Energies Up to 10 MeV (1976) Environmental Radiation Measurements (1976) Radiation Protection Design Guidelines for 0.1 - 10 MeV Particle Accelerator Facilities (1977) Cesium-137 from the Environment to Man: Metabolism and Dose (1977) Medical Radiation Exposure of Pregnant and Potentially Pregnant Women (1977) Protection of the Thyroid Gland i n the Event of Releases of Radioiodine (1977) Instrumentation and Monitoring Methods for Radiation Protection (1978) A Handbook of Radioactivity Measurements Procedures, 2nd ed. (1985) Operational Radiation Safety Program (1978) Physical, Chemical, and Biological Properties of Radiocerium Relevant to Radiation Protection Guidelines (1978) Radiation Safety Training Criteria for Industrial Radiography (1978) Tritium in the Environment (1979) Tritium and Other Radionuclide Labeled Organic Compounds Incorporated in Genetic Material (1979) Influence of Dose and Its Distribution in Time on Dose-Response Relationships for Low-LET Radiations (1980) Management of Persons Accidentally Contaminated with Radionuclides (1980) Radiofrequency Electromagnetic Fields-Properties, Quantities and Units, Biophysical Interaction, and Measurements (1981) Radiation Protection i n Pediatric Radiology (1981) Dosimetry of X-Ray and Gamma-Ray Beams for Radiation Therapy i n the Energy Range 10 keV to 50 MeV (1981) Nuclear Medicine-Factors Influencing the Choice and Use of Radionuclides i n Diagnosis and Therapy (1982) Operational Radiation Safety-Training (1983) Radiation Protection and Measurement for Low-Voltage Neutron Generators (1983) Protection i n Nuclear Medicine and Ultrasound Diagnostic Procedures i n Children (1983) Biological Effects of Ultrasound: Mechanisms and Clinical Implications (1983) Iodine-129: Evaluation of Releases from Nuclear Power Generation (1983)

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NCRP PUBLICATIONS Exposures from the Uranium Series with Emphasis on Radon and Its Daughters (1984) Evaluation of Occupational and Environmental Exposures to Radon and Radon Daughters in the United States (1984) Neutron Contamination from Medical Electron Accelerators (1984) Induction of Thyroid Cancer by Ionizing Radiation (1985) Carbon-14 in the Environment (1985) SI Units in Radiation Protection and Measurements (1985) The Experimental Basis for Absorbed-Dose Calculations in Medical Uses of Radionuclides (1985) General Concepts for the Dosimetry of Internally Deposited Radionuclides (1985) Mammography-A User's Guide (1986) Biological Effects and Exposure Criteria for Radiofrequency Electromagnetic Fields (1986) Use of Bioassay Procedures for Assessment of Internal Radionuclide Deposition (1987) Radiation Alarms and Access Control Systems (1986) Genetic Effects from Internally Deposited Radionuclides (1987) Neptunium: Radiation Protection Guidelines (1988) Public Radiation Exposure from Nuclear Power Generation in the United States (1987) Ionizing Radiation Exposure of the Population of the United States (1987) Exposure of the Population i n the United States and Canada from Natural Background Radiation (1987) Radiation Exposure of the U.S. Population from Consumer Products and Miscellaneous Sources (1987) Comparative Carcinogenicity of Ionizing Radiation and Chemicals (1989) Measurement of Radon and Radon Daughters in Air (1988) Quality Assurance for Diagnostic Imaging (1988) Exposure of the U.S. Population from Diagnostic Medical Radiation ( 1989) Exposure of the U.S. Population from Occupational Radiation (1989) Medical X-Ray, Electron Beam and Gamma-Ray Protection for Energies Up to 50 MeV (Equipment Design, Performance and Use) (1989) Control of Radon in Houses (1989) The Relative Biological Effectiveness of Radiations of Different Quality (1990) Radiation Protection for Medical and Allied Health Personnel (1989) Limit for Exposure to "Hot Particles" on the Skin (1989) Implementation of the Principle of As Low As Reasonably Achievable (ALARA)for Medical and Dental Personnel (1990)

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108 Conceptual Basis for Calculations of Absorbed-Dose Distributions (1991) 109 Effects of Ionizing Radiation on Aquatic Organisms (1991) 110 Some Aspects of Strontium Radiobiology (1991) 111 Developing Radiation Emergency Plans for Academic, Medical or Industrial Facilities (1991) 112 Calibration of Survey Instruments Used i n Radiation Protection for the Assessment of Ionizing Radiation Fields and Radioactive Surface Contamination (1991) 113 Exposure Criteria for Medical Diagnostic Ultrasound: I. Criteria Based on Thermal Mechanisms (1992) 114 Maintaining Radiation Protection Records (1992) 115 Risk Estimates for Radiation Protection (1993) 116 Limitation of Exposure to Ionizing Radiation (1993) 117 Research Needs for Radiation Protection (1993) 118 Radiation Protection in the Mineral Extmction Industry (1993) 119 A Practical Guide to the Determination of Human Exposure to Radiofrequency Fields (1993) 120 Dose Control at Nuclear Power Plants (1994) 121 Principles and Application of Collective Dose in Radiation Protection (1995) 122 Use of Personal Monitors to Estimate Effective Dose Equivalent and Effective Dose to Workers for External Exposure to LowLET Radiation (1995) 123 Screening Models for Releases of Radionuclides to Atmosphere, Surface Water, and Ground (1996) 124 Sources and Magnitude of Occupational and Public Exposures from Nuclear Medicine Procedures (1996) 125 Deposition, Retention and Dosimetry of Inhaled Radioactive Substances (1997) 126 Uncertainties i n Fatal Cancer Risk Estimates Used in Radiation Protection (1997) 127 Operational Radiation Safety Progmm (1998) 128 Radionuclide Exposure of the EmbryolFetus (1998) 129 Recommended Screening Limits for Contaminated Surface Soil and Review of Factors Relevant to Site-Specific Studies (1999) 130 Biological Effects and Exposure Limits for "Hot Particles" (1999) 131 Scientific Basis for Evaluating the Risks to Populations from Space Applications of Plutonium (2001) 132 Radiation Protection Guidance for Activities in Low-Earth Orbit (2000) 133 Radiation Protection for Procedures Performed Outside the Radiology Department (2000) 134 Operational Radiation Safety Training (2000)

Binders for NCRP reports are available. Two sizes make it possible to collect into small binders the "old series"of reports (NCRP Reports Nos. 830) and into large binders the more recent publications (NCRP Reports Nos.

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32-134).Each binder will accommodate from five to seven reports. The binders carry the identification "NCRP Reports" and come with label holders which permit the user to attach labels showing the reports contained in each binder. The following bound sets of NCRP reports are also available: Volume I.NCRP Reports Nos. 8,22 Volume 11.NCRP Reports Nos. 23,25,27,30 Volume 111.NCRP Reports Nos. 32,35,36,37 Volume IV. NCRP Reports Nos. 38,40,41 Volume V. NCRP Reports Nos. 42,44,46 Volume VI. NCRP Reports Nos. 47,49,50,51 Volume VII. NCRP Reports Nos. 52,53,54,55,57 Volume VIII.NCRP Report No. 58 Volume IX.NCRP Reports Nos. 59,60,61,62,63 Volume X.NCRP Reports Nos. 64,65,66,67 Volume XI. NCRP Reports Nos. 68,69,70,71,72 Volume XII. NCRP Reports Nos. 73,74,75,76 Volume XIII.NCRP Reports Nos. 77,78,79,80 Volume XIV. NCRP Reports Nos. 81,82,83,84,85 Volume XV. NCRP Reports Nos. 86,87,88,89 Volume XVI.NCRP Reports Nos. 90,91,92,93 Volume XVII.NCRP Reports Nos. 94,95,96,97 Volume XVIII.NCRP Reports Nos. 98,99,100 Volume XU(. NCRP Reports Nos. 101,102,103,104 Volume XX. NCRP Reports Nos. 105,106,107,108 Volume XXI. NCRP Reports Nos. 109,110,111 Volume XXII. NCRP Reports Nos. 112,113,114 Volume XXIII.NCRP Reports Nos. 115,116,117,118 Volume XXIV. NCRP Reports Nos. 119,120,121,122 Volume XXV. NCRP Report No. 1231 and 12311 Volume XXVI. NCRP Reports Nos. 124,125,126,127 Volume XXVII.NCRP Reports Nos. 128,129,130

(Titles of the individual reports contained in each volume are given above.)

NCRP Commentaries No. 1 4

Title Krypton-85 in the Atmosphere-With Specific Reference to the Public Health Significance of the Proposed Controlled Release at Three Mile Island (1980) Guidelines for the Release of Waste Water from Nuclear Facilities with Special Reference to the Public Health

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Significance of the Proposed Release of Treated Waste Waters at Three Mile Island (1987) Review of the Publication, Living Without Landfills (1989) Radon Exposure of the U.S. Population-Status of the Problem (1991)

Misadministration of Radioactive Material in MedicineScientific Backgmund (1991) Uncertainty in NCRP Screening Models Relating to Atmospheric Transport, Deposition and Uptake by Humans (1993) Considerations Regarding the Unintended Radiation Exposure of the Embryo, Fetus or Nursing Child (1994) Advising the Public about Radiation Emergencies: A Document for Public Comment (1994) Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients (1995) Radiation Exposure and High-Altitude Flight (1995) A n Introduction to Eficacy in Diagnostic Radiology and Nuclear Medicine (Justification of Medical Radiation Exposure) (1995) A Guide for Uncertainty Analysis i n Dose and Risk Assessments Related to Environmental Contamination (1996) Evaluating the Reliability of Biokinetic and Dosimetric Models and Parameters Used to Assess Individual Doses for Risk Assessment Purposes (1998)

Proceedings of the Annual Meeting No. 1

Title Perceptions of Risk, Proceedings of the Fifteenth Annual Meeting held on March 14-15, 1979 (including Taylor Lecture No. 3) (1980) Critical Issues in Setting Radiation Dose Limits, Proceedings of the Seventeenth Annual Meeting held on April 8-9, 1981 (including Taylor Lecture No. 5) (1982) Radiation Protection and New Medical Diagnostic Approaches, Proceedings of the Eighteenth Annual Meeting held on April 6-7, 1982 (including Taylor Lecture No. 6) (1983) Environmental Radioactivity, Proceedings of the Nineteenth Annual Meeting held on April 6-7, 1983 (includingTaylor Lecture No. 7) (1983) Some Issues Important in Developing Basic Radiation Protection Recommendations, Proceedings of the Twentieth Annual Meeting held on April 4-5, 1984 (includingTaylor Lecture No. 8) (1985)

Radioactive Waste, Proceedings of the Twenty-first Annual Meeting held on April 3-4, 1985 (includingTaylor Lecture No. 9) (1986)

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Nonionizing Electromagnetic Radiations a n d Ultrasound, Proceedings of the Twenty-second Annual Meeting held on April 2-3, 1986 (including Taylor Lecture No. 10) (1988) New Dosimetry a t Hiroshima and Nagasaki and Its Implications for Risk Estimates, Proceedings of the Twenty-third Annual Meeting held on April 8-9, 1987 (including Taylor Ledure No. 11) (1988) Radon, Proceedings of the Twenty-fourth Annual Meeting held on March 30-31,1988 (including Taylor Lecture No. 12) (1989) Radiation Protection Today-The NCRP a t Sixty Years, Proceedings of the Twenty-fifth Annual Meeting held on April 5-6, 1989 (including Taylor Lecture No. 13) (1990) Health a n d Ecological Implications of Radioactively Contaminated Environments, Proceedings of the Twenty-sixth Annual Meeting held on April 4-5, 1990 (including Taylor Lecture No. 14) (1991) Genes, Cancer a n d Radiation Protection, Proceedings of the Twenty-seventh Annual Meeting held on April 3-4, 1991 (including Taylor Lecture No. 15) (1992) Radiation Protection in Medicine, Proceedings of the Twentyeighth Annual Meeting held on April 1-2, 1992 (including Taylor Lecture No. 16) (1993) Radiation Science and Societal Decision Making, Proceedings of the lbenty-ninth Annual Meeting held on April 7-8, 1993 (including Taylor Lecture No. 17) (1994) Extremely-Low-FrequencyElectromagnetic Fields: Issues in Biological Effects a n d Public Health, Proceedings of the Thirtieth Annual Meeting held on April 6-7, 1994 (not published). Environmental Dose Reconstruction and Risk Implications, Proceedings of the Thirty-first Annual Meeting held on April 12-13, 1995 (including Taylor Lecture No. 19) (1996) Implications of New Data on Radiation Cancer Risk, Proceedings of the Thirty-second Annual Meeting held on April 3-4, 1996 (including Taylor Lecture No. 20) (1997) The Effects of Pre- a n d Postconception Exposure to Radiation, Proceedings of the Thirty-third Annual Meeting held on April 2-3, 1997, Teratology 59, 181-317 (1999) Cosmic Radiation Ezposure of Airline Crews, Passengers and Astronauts, Proceedings of the Thirty-fourth Annual Meeting held on April 1-2, 1998, Health Phys. 79, 466-613 (2000) Radiation Protection in Medicine: Contemporary Issues, Proceedings of the Thirty-fifth Annual Meeting held on April 7-8, 1999 (including Taylor Lecture No. 23) (1999)

Lauriston S. Taylor Lectures No.

Title

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The Squares of the Natural Numbers in Radiation Protection by Herbert M. Parker (1977)

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Why be Quantitative about Radiation Risk Estimates? by Sir Edward Pochin (1978) Radiation Protection-Concepts and Tmde Offs by Hymer L. Friedell (1979) [Available also in Perceptions of Risk, see abovel From "Quantity of Radiation" and "Dose" to P%zposure" and "Absorbed Dose7'-An Historical Review by Harold 0.Wyckoff (1980) How Well Can We Assess Genetic Risk? Not Very by James F. Crow (1981) [Available also in Critical Issues in Setting Radiation Dose Limits, see abwe] Ethics, T r d - o f f s and Medical Radiation by Eugene L. Saenger (1982) [Available also in Radiation Protection and New Medical Diagnostic Approaches, see abwe] The Human Environment-Past, Present and Future by Meml Eisenbud (1983) [Available also in Environmental Radioactivity, see above] Limitation and Assessment in Radiation Protection by Harald H. Rossi (1984) [Available also in Some Issues Important in Developing Basic Radiation Protection Recommendations, see abovel !!'ruth (and Beauty) in Radiation Measurement by John H . Harley (1985) [Available also in Radioactive Waste, see above] Biological Effects of Non-ionizing Radiations: Cellular Properties and Interactions by Herman P. Schwan (1987)[Available also in Nonionizing Electromagnetic Radiations and Ultrasound, see above] How to be Quantitative about Radiation Risk Estimates by Seymour Jablon (1988) [Available also in New Dosimetry at Hiroshima and Nagasaki and its Implications for Risk Estimates, see abovel How Safe is Safe Enough? by Bo Lindell (1988) [Available also in Radon, see above] Radiobiology and Radiation Protection: The Past Century and Prospects for the Future by Arthur C. Upton (1989) [Available also in Radiation Protection Today, see abovel Radiation Protection and the Internal Emitter Saga by J. Newel1 Stannard (1990:l [Available also in Health and Ecological Implications of Radioactively Contaminated Environments, see above] When is a Dose Not a Dose? by Victor P. Bond (1992) [Available also in Genes, Cancer and Radiation Protection, see abwe] Dose and Risk in Diagnostic Radiology: How Big? How Little? by Edward W. Webster (1992)[Available also in Radiation Protection in Medicine, see abwe] Science, Radiation Protection and the NCRP by Warren K. Sinclair (1993)[Available also in Radiation Science and Societal Decision Making, see abovel

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204 18 19 20 21 22 23

Mice, Myths and Men by R.J. Michael Fry (1995) Certainty and Uncertainty i n Radiation Research by Albrecht M . Kellerer (1995).Health Phys. 69,446-453. 70 Years of Radiation Genetics: Fruit Flies, Mice and Humans by Seymour Abrahamson (1996).Health Phys. 71, 624-633. Radionuclides in the Body: Meeting the Challenge by William J. Bair (1997).Health Phys. 73,423-432. From Chimney Sweeps to Astronauts: Cancer Risks in the Work Place by Eric J. Hall (1998).Health Phys. 75, 357-366. Back to Background: Natural Radiation and Radioactivity Exposed by Naomi H. Harley (2000).Health Phys. 79, 121-128.

No. 1 2 3

NCRP PUBLICATIONS

Symposium Proceedings Title The Control of Exposure of the Public to Ionizing Radiation in the Event of Accident or Attack, Proceedings of a Symposium held April 27-29,1981 (1982) Radioactive and Mixed Waste-Risk as a Basis for Waste Classification, Proceedings of a Symposium held November 9, 1994 (1995) Acceptability of Risk from Radiation-Application to Human Space Flight, Proceedings of a Symposium held May 29, 1996 (1997)

NCRP Statements No. 1 2

3 4

5 6 7 8

Title "Blood Counts, Statement of the National Committee on Radiation Protection," Radiology 63, 428 (1954) "Statements on Maximum Permissible Dose from Television Receivers and Maximum Permissible Dose to the Skin of the Whole Body," Am. J. Roentgenol., Radium Ther. and Nucl. Med. 84, 152 (1960)and Radiology 75, 122 (1960) X-Ray Protection Standards for Home Television Receivers, Interim Statement of the National Council on Radiation Protection and Measurements (1968) Specification of Units of Natural Uranium and Natural Thorium, Statement of the National Council on Radiation Protection and Measurements (1973) NCRP Statement on Dose Limit for Neutrons (1980) Control of Air Emissions of Radionuclides (1984) The Probability That a Particular Malignancy May Have Been Caused by a Specified Irradiation (1992) The Application of ALARA for Occupational Exposures (1999)

NCRP PUBLICATIONS

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205

Other Documents The following documents of the NCRP were published outside of the NCRP report, commentary and statement series: Somatic Radiation Dose for the General Population, Report of the Ad Hoc Committee of the National Council on Radiation Protection and Measurements, 6 May 1959, Science, February 19, 1960, Vol. 131, No. 3399, pages 482-486 Dose Effect Modifying Factors In Radiation Protection, Report of Subcommittee M 4 (Relative Biological Effectiveness) of the National Council on Radiation Protection and Measurements, Report BNL 50073 (T-471) (1967) Brookhaven National Laboratory (National Technical Information Senrice Springfield, Virginia)

Index Absolute risk 156, 160 Absorbed dose (D)43, 156 Acceptable risk 1 Adenomatous polyposis coli gene W C ) 156 Albedo neutrons 156 Alpha particles 156 Ankylosing spondylitis 114 radiation-induced leukemia 114 Annual risk 160 Anomalous cosmic rays (ACR) 156 Apollo 60,61 calculated and measured dose comparisons 61 space radiation environments 60 Atomic-bomb survivors 9 noncancer effects 9 Azoospermia 102, 103,156 Background radiation 159 Baryon 156 Basal cell carcinoma 118 excess relative risk 118 Baseline cancer rates 122 Bone marrow 82 progenitor cells 82 Breast 115 radiation carcinogenesis 115 Bremsstrahlung 156 Bystander effect 80,156 Cancer induction 150, 151,153 estimated lifetime risk of 153 HZE particles 150 susceptibility for 151 Cancer mortality 120,128, 134 excess lifetime risk 128,134 Cancer rates 122 Cancer risks 10

Carcinogenesis 106, 107, 110,127 mechanisms of 107, 110 risks of radiation 127 Carcinogenic risk 127 method of estimating 127 Career limits 1, 14,21,143 impact of 14 Cataract index 88 Cataractogenic doses 87 Cataracts 8 Cell-cycle stage sensitivity 67 Cell killing 6 Charged-particle spectrometry 52 Chromosome aberrations 6 Colorectal cancer 108 multistage carcinogenesis 108 Conjunctiva 85 threshold doses 85 Cornea 85 threshold doses 85 Coronal mass ejection 156 Cosmic-ray elemental composition 35 Deleted colon cancer gene (DCC) 156 Delta ray 156 Deterministic effects 6,7,8,12, 67,85,150,156 gray-equivalents for 8 HZE particles 150 threshold doses 85 Deterministic limits 7, 141,144 basis for 141 Dose and dose rate effectiveness factor (DDREF) 13,111 Dose equivalent (H)43,167 Dose equivalent rates 50 secondary neutron 50 trapped proton 50

INDEX

Dose limits for space missions 137 biological considerations 137 Dose rate effectiveness factor (DREF) 111 Dose-response relationships 109 Dose-response model 157 Dosimetry instrumentation 49 Dosimetry System 1986 (DS86) 157 Doubling dose (DD) 156 Effective dose (E) 47, 157 Effects 12 Electrons 45, 74, 157 radiation weighting factors 45 Endometriosis 157 Equivalent dose (HT) 157 Erythema 157 Excess lifetime risk 128, 134 cancer mortality 128, 134 Excess relative risk (ERR) 157 Exposure 157 Exposures in low-earth orbit 54 space crew member 54 Extravehicular activity (EVA) 6, 157 Eye 83,84 radiation-induced cataracts 84 Fatal cancer 12 lifetime risk 12 Fatality rates from accidents 140 Females 9 risk of reduced fertility 9 Fluence 157 Galactic cosmic rays (GCR) 3, 4, 30, 33, 34, 37, 157 abundance of 30 anomalous component 37 nuclear composition 33 solar modulation 34 Gastrointestinal tract 116 radiation carcinogenesis 116 Genetically significant dose (GSD) 11

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Genetic susceptibility 109 radiogenic cancer 109 Gemini 57 space radiation environments 57 Gray (Gy) 158 Gray equivalent (Gy-Eq) 8, 158 RBE values 8 Harderian gland tumors 78, 79 Heavy ions 74, 158 Heliolongitude 158 Heliosphere 158 Hereditary effects 11,95 High-LET radiation 158 HZE particles 150 biophysics of 150 cancer induction 150 deterministic effects 150 radiobiology of 150 Incidence 158 Incidence rate 158 Inclination 158 Integral fluence rate 52 International Space Station 64 space radiation environments 64 Ionization 158 Ionizing radiation 159 Ionosphere 158 Kidney and bladder 117 radiation carcinogenesis 117 Kinetic energy released in material (kerma) 158 Lachrimal gland 85 threshold doses 85 Late deterministic effects 6 Latent period 158 LDSo158 Lens of the eye 85,88,89,90 heavy ion effect on 90 neutron effect on 89 proton effect on 88 threshold doses 85

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208

INDEX

Leukemia 108,109,113,125,126 chronic lymphocytic 109 dose response 126 excess mortality 125 radiation induced 108 radiation risk estimates 113 Leukemia incidence 10 Lid skin 85 threshold doses 85 Lifetime risk 12,21, 158, 160 accidental death 12 fatal cancer 12,21 Linear energy transfer (LET) 51,

158 spectral measurement 51 Linear model 159 Linear-quadratic model 159 Liver 117 radiation carcinogenesis 117 Low-earth orbit (LEO) 25, 70 radiation environment 25, 70 Low-earth orbit missions 138 basis for limits 138 Low-LET radiation 158 Lung 116 radiation carcinogenesis 116 Measurements 49 heavy ion 49 neutron 49 Mercury 57 space radiation environments

57 Microlesion 79,159 Mir Space Station 62 space radiation environments

62 Multistage carcinogenesis 108 Mutation colon cancer gene (MCC) 159 Neutrons 45,72,159 radiation weighting factors 45 Noncancer effects 9 Oocytes 9 Organ dose equivalent 48 Organ dose-equivalent limits 22

Partial body irradiation 151 Photons 45 radiation weighting factors 45 Pregnant females 145 recommendation concerning

145 Prevalence 159 Proton effects 150 Proton Heavy-Ion Detection Experiment (PHIDE) 49 Protons 70, 159 Protraction 159 Quality factor (Q) 159 Quality factor-LET relationships

44,46 Radiation carcinogenesis 106,

107, 115,116,117,118 breast 115 gastrointestinal tract 116 kidney and bladder 117 liver 117 lung 116 mechanisms of 107 skin 118 thyroid 115 Radiation effects 5, 6,8,9,11, 12 cataracts 8 cell killing 6 chromosome aberrations 6 deterministic effects 5,8, 12 early deterministic effects 6 gray equivalents for deterministic effects 8 hereditary effects 11 late deterministic effects 6 noncancer effects 9 RBE values 8 stochastic effects 5, 12 Radiation environment 3, 25,26,

28,34,70,,149 galactic cosmic rays 34 low-earth orbit (LEO) 25, 70 models of 149 motions of charged particles 28 trapped-particle radiation 26

INDEX

Radiation-induced cancer 149 risk estimates 149 Radiation-induced cataracts 84 Radiation limits 2 space workers 2 terrestrial workers 2 Radiation protection principles 136 Radiation quality 160 Radiation response 67 cell-cycle stage sensitivity 67 deterministic effects 67 physical and biological variables 67 Radiation risk estimates 113,121 derivation of 113 effect of age a t exposure 121 effect of attained age 121 effect of time after exposure 121 leukemia 113 Radiation risks 126 individual factors 126 Radiation standards for NASA 19 Radiation weighting factors (wA) 5,45, 160 Radiobiology and health effects 149 Radiobiology of space radiation 66 Radiogenic cancer 109 genetic susceptibility 109 Relative biological effectiveness (RBE) 160 Relative risk 160 Retina 85 threshold doses 85 Risk assessment 119 epidemiological basis 119 Risk coeficients 123,160 transfer between populations 123 Risk cross section 160 Risk estimates 13,119,146, 160 sources of uncertainties 119 uncertainty in 13,146 Roentgen (R)160

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209

Sclera 85,161 threshold doses 85 Secondary radiation 160 Sievert (Sv) 161 Skin 91,92,93,94,118 dry desquamation 92 ervthema 92 influence of radiation quality 93 moist desquamation 92 radiation carcinogenesis 118 RBE values for acute response 94 responses to radiation 92 ulceration 92 Skylab 61 crew member exposures 61 space radiation environments 61 Skylab exposures 19 Solar cycle 161 Solar flare 161 Solar maximum 161 Solar minimum 161 Solar particle events (SPE) 3,6, 37,39,40,161 integral fluences 40 measurements 40 spectra and composition 39 Solar-proton events 41 Solar wind 27, 161 South Atlantic Anomaly (SAM 3 Space crew member 54 exposures in low-earth orbit 54 Space crew member exposures 57 low-earth orbit 57 Space radiations 25 categories of 25 Space radiation safety standards 17 background of 17 Space Shuttle crews 58 mean daily dose rates 58 Space Transport Shuttle 62 space radiation environments 62 Spermatogonia 9 Squamous cell carcinoma 118

Sterility 100, 104, 105 doses to the ovaries 105 female 104 male 100 radiation induced 100 Stochastic 161 Stochastic effects 12, 142 limits for 142 Stochastic limits 138 basis for 138 Telangiectasia 161 Temporary sterility 9 effect of protraction 9 Threshold doses 85 conjunctiva 85 cornea 85 lachrimal gland 85 lens 85 lid skin 85 retina 85 sclera 85 Thyroid 115 radiation carcinogenesis 115 Time-doee relationships 67

Tissue-equivalent proportional counter (TEPC) 5 Tissues a t risk in space 8 1 47, Tissue weighting factor (wT) 48, 161 bladder 48 bone marrow 48 bone surface 48 breast 48 colon 48 different tissues and organs 48 esophagus 48 gonads 48 liver 48 lung 48 remainder 48 skin 48 stomach 48 thyroid 48 Trapped-belt electron spectra 31 Trapped-belt proton spectrum 29 Trapped-particle radiation 26 Trapped radiation belts 3 Tumor suppressor genes 108

Research Needs for Radiation Protection: Recommendations of the National Council on Radiation Protection and Measurements (Ncrp Report ; No. 117)

Radiation Protection in the Mineral Extraction Industry: Recommendations of the National Council on Radiation Protection and Measurements (Ncrp, No)

Environmental radiation measurements: Recommendations of the National Council on Radiation Protection and Measurements (NCRP report ; no. 50)

Maintaining Radiation Protection Records: Recommendations of the National Council on Radiation Protection and Measurements : Issued November 30, 1992 (NCRP report)

Operational Radiation Safety Training: Recommendations of the National Council on Radiation Protection and Measurements (Ncrp Report, No. 134)

Control of Radon in Houses: Recommendations of the National Council on Radiation Protection and Measurements (Ncrp Report ; No. 103)

Alpha-emitting particles in lungs: Recommendations of the National Council on Radiation Protection and Measurements (NCRP report ; no. 46)

Tritium measurement techniques: Recommendations of the National Council on Radiation Protection and Measurements (NCRP report ; no. 47)

Tritium in the environment: Recommendations of the National Council on Radiation Protection and Measurements (NCRP report 62)

Specification of gamma-ray brachytherapy sources: Recommendations of the National Council on Radiation Protection and Measurements (NCRP report)

Protection of the thyroid gland in the event of releases of radioiodine: Recommendations of the National Council on Radiation Protection and Measurements (NCRP report ; no. 55)

Operational Radiation Safety Program: Recommendations of the National Council on Radiation Protection and Measurements (N C R P Report)

Atoms, Radiation and Radiation Protection