NCRP SC 1-24P2 NOT TO BE DISSEMINATED OR REFERENCED OCTOBER 2018 NCRP DRAFT SC 1-24P2 REPORT Radiation Exposures in Space and the Potential for Central Nervous System Effects (Phase II) October 2018 Note: Copyright permission is being sought for the figures and tables requiring such permission prior to their use in the final NCRP publication. National Council on Radiation Protection and Measurements 7910 Woodmont Avenue, Suite 400, Bethesda, Maryland 20814 1 2 1 NCRP SC 1-24P2 NOT TO BE DISSEMINATED OR REFERENCED OCTOBER 2018 3 Preface 4 This report has been prepared at the request of the National Aeronautics and Space 5 Administration (NASA). It is the second phase of a two-phase effort intended to provide 6 guidance to NASA concerning the effects of space radiation exposures on the central nervous 7 system of crew members, the implications for them and possible impacts on their missions. The 8 first phase of this effort resulted in NCRP Commentary No. 25, Potential for Central Nervous 9 System Effects from Radiation Exposure During Space Activities Phase I: Overview, which 10 described the critical issues surrounding the potential short- and long-term consequences of 11 space radiation on the CNS and laid the groundwork for a more comprehensive investigation, 12 that is the basis of this report. This report summarizes the steps and approaches needed to more 13 fully understand the risk of CNS effects following radiation exposures in space and provides 14 guidance for risk management and radiation protection. The Committee has identified 15 knowledge gaps regarding the implementation of a comprehensive and effective radiation safety 16 program to protect astronauts against the potential for early and late CNS effects from space 17 radiation. 18 This Report was prepared by Scientific Committee 1-24P2 on Radiation Exposures in 19 Space and the Potential for Central Nervous System Effects (Phase II). Serving on Scientific 20 Committee 1-24P2 were: 21 22 23 Leslie A. Braby, Chair 24 Texas A&M University 25 College Station. Texas 26 27 Jacob Raber, Vice-Chair 28 Oregon Health and Science University 29 Portland, Oregon 30 31 32 33 34 35 36 37 38 39 40 41 2 NCRP SC 1-24P2 NOT TO BE DISSEMINATED OR REFERENCED OCTOBER 2018 42 Members 43 Polly Chang Thomas J. MacVittie SRI International University of Maryland Menlo Park, California School of Medicine Baltimore, Maryland David F. Dinges University of Pennsylvania M. Kerry O’Banion Philadelphia, Pennsylvania University of Rochester Rochester, New York Dudley T. Goodhead Medical Research Council Michael Qin Harwell, United Kingdom Naval Submarine Medical Research Laboratory, Groton, Connecticut David Herr (2016-17); Office of Naval Research, Environmental Protection Agency Arlinton, Virginia (2017-19) Durham, North Carolina John Hopewell James C. Root Oxford University Memorial Sloan Kettering Cancer Oxford, United Kingdom Center New York, New York Janice L. Huff Wyle Laboratories Susanna Rosi Houston, Texas University of California San Francisco, California Kevin Krull St. Jude Children’s Research Hospital Peter Winsauer Memphis, Tennessee Louisiana State University Health Sciences Center Richard M. Linnehan (2016-2017) New Orleans, Louisiana NASA Johnson Space Center Houston, Texas 44 NASA Observer 45 46 Gregory A. Nelson (NASA IPA) 47 Loma Linda University 48 Loma Linda, California 49 50 NCRP Secretariat 51 Lawrence W. Townsend, Staff Consultant 52 Cindy L. O’Brien, Managing Editor 53 Laura J. Atwell, Office Manager 54 Kathryn D. Held, Executive Director 3 NCRP SC 1-24P2 NOT TO BE DISSEMINATED OR REFERENCED OCTOBER 2018 55 56 57 The Council expresses appreciation to the Committee members for the time and effort devoted to 58 the preparation of this Commentary, and to NASA for financial support. 59 60 John D. Boice, Jr. 61 President 62 63 64 4 NCRP SC 1-24P2 NOT TO BE DISSEMINATED OR REFERENCED OCTOBER 2018 65 Contents 66 67 Preface ………………………………………………………………………………………..2 68 69 1. Executive Summary ..........................................................................................................9 70 71 2. Introduction .....................................................................................................................18 72 73 3. Background ......................................................................................................................22 74 3.1 Long Duration, High Radiation Exposure Missions………………………………..22 75 3.1.1 Exploration Mission Profile Summary……………………………………….22 76 3.1.2 Radiation Exposure Estimates for Exploration Missions…………………….23 77 3.2 Current NASA Radiation Protection Policy .............................................................27 78 3.2.1 Health Risks Associated with Space Radiation Exposure……………………27 79 3.2.2 NASA Human Health and Performance Standards for Radiation Protection..27 80 3.3 Characteristics of Radiation in Space .......................................................................34 81 3.4 Phase 1 Report Recommendations……………………………………………..…..39 82 3.5 Possible CNS Effects of Space Radiation Exposure .................................................46 83 84 4. Observations of Humans ................................................................................................49 85 4.1 Side Effects of Medical Exposures………………………………………………….49 86 4.1.1 Juvenile Exposures…………………………………………………………….51 87 4.1.2 Adult Exposures……………………………………………………………….59 88 4.1.2.1 Whole Brain and Prophylactic Cranial Irradiation…………………....64 89 4.1.2.2 Prophylactic Cranial Irradiation………………………………………65 90 4.1.2.3 Hippocampal Sparing Radiotherapy………………………………….65 91 4.1.2.4 Stereotactic Radiosurgery…………………………………………….67 92 4.1.2.5 Radiation Treatments in Head and Neck Cancers…………………….67 93 4.2 Other Radiation Exposures…………………………………………………………..70 94 4.2.1 Exposure to Protons and Heavier Ions………………….……………………..72 95 4.2.2 Other Effects of Exposure …………………………………………………….76 96 4.2.3 Exposure to Neutrons………………………………………………………….76 97 4.2.4 Health Risks Following Chronic Exposure to Brain Tissue From High-LET 98 Radiation in Radiation Workers………………………………………………….76 99 4.2.5 Recommendations……………………………………………………………..78 100 4.3 Interaction and Synergistic Effects of Cosmic Radiation with Other 101 Neurobehavioral and Physiological Stressors in Spaceflight…………..……………79 102 4.3.1 Other Stressors in Spaceflight……………….…………………………... …..80 103 4.3.1.1 Stress, Memory and Hippocampus…………………...........................80 104 4.3.1.2 Stress, Negative Affect and Right Prefrontal Cortex…………………81 105 4.3.1.3 Stress from Social Isolation, Confinement and Crowding…………...82 106 4.3.2 Circadian Biology and Cosmic Radiation …………………………………….82 107 4.3.3 Sleep Duration, Sleep Quality, Stress and Physical Exhaustion 108 in Spaceflight………………………………………………………………….85 109 4.3.4 Cumulative Neurobehavioral Deficits from Chronic Sleep Restriction ………87 110 4.3.5 Biomarkers for Phenotypic Differential Vulnerability to Spaceflight Stressors 89 5 NCRP SC 1-24P2 NOT TO BE DISSEMINATED OR REFERENCED OCTOBER 2018 111 4.3.6 Immune and Inflammatory Responses to Sleep Deprivation 112 and Confinement................................................................................................89 113 4.3.7 Sleep Deprivation and the Effects of Cosmic Radiation……………………...91 114 4.3.8 Carbon Dioxide (CO2) Effects………………………………………………..92 115 4.3.9 SPACECOT Study: Head-down Tile plus CO2………………………………93 116 4.4 Future Direction and Recommendations ............................................................…..94 117 118 5. Observations with Rodents ............................................................................................95 119 5.1 Inbred and outbred animals .......................................................................................95 120 5.1.1 Mutants ..........................................................................................................100 121 5.1.2 Sex Differences ..............................................................................................101 122 5.2 Descriptions of Behavioral and Cognitive Endpoints .............................................102 123 5.2.1 Behavioral and Cognitive Endpoints Relate to Both Simple and Complex 124 Human Behaviors (Including Possible Post-Traumatic-Stress-Disorder-Like 125 Changes) ........................................................................................................102 126 5.2.1.1 General Health and Housing Conditions ...........................................106 127 5.2.1.2 Sensorimotor Function .......................................................................107 128 5.2.1.3 Circadian Activity Levels in the Home Cage ....................................108 129 5.2.1.4 Exploratory Behavior in a Novel Environment and Measures of 130 Activity and Anxiety ..........................................................................108 131 5.2.1.5 Depression Tests; Forced Swim and Tail Suspension Tests .............110 132 5.2.1.6 Emotional Learning and Memory; Passive Avoidance, Contextual 133 and Cued Fear Learning and Memory, and Fear Potentiated Startle .110 134 5.2.1.7 Object Recognition ............................................................................115 135 5.2.1.8 Spatial Learning and Memory Involving Navigation; Y Maze, Water 136 Maze and Barnes Maze……………………………………………...122 137 5.2.1.9 Social behavior and Recognition……………………………………126 138 5.2.1.10 Executive Function ..........................................................................127 139 5.2.1.11 Operant