Title: CERN Course
1Surviving in space the challenges of a manned
mission to Mars
- Lecture 2
- Dosimetry and the Effects of the Exposure of
Humans to Heavily Ionizing Radiation
2What Are the Problems Associatedwith Human
Radiation Exposure?
- Acute (High Intensity-Short DurationDeterministic
Effects) - Serious Debilitation and Death (within Hours to
Months) - NOT GENERALLY THE BIGGEST PROBLEM FACED in Long
Term Human Space Travel (Because the potential
sources of this kind of threat are easier to
mitigate). - Chronic (Low Intensity-Long Duration Stochastic
Effects) - Increased Risk of Cancer in the Future
(Acceptable lt3 Increase) - Potential Increased Risk of Other Diseases
(Coronary, Brain Cell Loss) - Increased Risk of Debilitations Like Cataracts
- THE REAL HURDLE (Due to Bureaucratic Career
Dose Limits)
3Contrasting Acute v. Chronic
- Imagine having to set limits on blood-loss
- For Acute loss situations over a few hours, the
amount of loss (without replacement) before
serious health effects may occur is perhaps as
much as a few liters - On the other hand, for Chronic loss situations
like blood-donors, one might safely donate one
liter every 6 weeks, or almost 350 liters over a
40 year career. - The reason for the difference is the human bodys
ability to replace (blood-loss) and repair
(radiation damage) in cases of such insults
4The General Problem
- NASA needs to be able to PREDICT DOSES or at
least estimate conservative maximums - GCRSolar Modulation Fluctuations
- (OR any Interstellar Spectral fluctuations???)
- Solar Particle Events
- CMEs lower flux events
- In LEO, Trapped Radiation fluxes are significant
in low shielding situations
5A Short Primer on Dose
- Radiation Dose
- Energy deposited per gm (cm3) of tissue by
Ionizing Radiation - For Dose D, the Rad (100 ergs/gm) has been
replaced by - the Gray (Gy) J/kg 100 Rad,
- or more commonly 1 cGy 1 Rad
6Acute v. Chronic Equivalent Dose
- Equivalent Dose Dose Modified by Effect in
Generic Human Tissue - Quality Factor Modifiers, WR (RBE) with respect
to gamma radiations effect for each kind of
radiation R, summed over all tissues, T HTR
SR WR DRT - For CHRONIC Doses, the Rem has been replaced by
the Sievert (Sv) 100 Rem - For ACUTE Doses, the Dose is given in
Gray-Equivalent (Gy-Eq) 100 Rads of X-Rays
7Effective Dose Equivalent
- Effective Dose Equivalent Uses a Different
Weighting Factor for EACH kind of tissue, WT ,
summed over EACH Organ and then over the whole
body - Also quoted in Sieverts (for ChronicStochastic
Effects) - E S WT HT ST WT SR ò WR DRT dT
8Effects of Dose
- ACCUTE DOSES (High Short Time Exposures)
- 4.5 Gy LD 50/60 (50 Lethal in 60 Days)
without medical intervention - 1.0 Gy Radiation Sickness (Nausea, Diarrhea)
- No Macroscopically Observable effects lt 0.1 Gy
- CHRONIC DOSES (Low Continual Exposure)
- Increased Cancer and other risks (Coronary, Eye)
- No Observable Short-Term effects
- Long-Term Effects from High LET (Linear Energy
TransferEnergy deposited per unit track-length
by ionizing radiation) exposure such as Heavy
Ions are UNKNOWN - Acute Dose Limits are NOT related to Chronic
Limits
9Where do we get Data on the Effects of Doses?
- Actual Human Exposures
- Hiroshima Survivors represent the best extant
cohort for long term effects - AccidentsSporadic and low statistics.
- Clinical ExposuresLow Doses or in Radiation
Therapy exposures, localized high doses No
Controls - Existing Astronaut cohort
- Animal Exposures
- Inter-species extrapolation uncertainties
- Isolated Cell Culture Exposures
- In Vitro cells do not behave like there
conterparts In Vivo
10Energy Loss by Heavy Ions in Tissue
From NASA SPP
11On The Baseline Mars Mission 1 Fe Traversal PER
CELL
- The Deep Space GCR Fe 1 per m2 Ster Sec
- Human Body 1 m2 4p Ster or 10 Fe/sec
- Baseline Mission 3 Years 108 sec
- So, there will be 109 Fe traversals per mission
- 1 m2 1012 mm2 each human cell 103 mm2
- Or, 109 cells in a typical cross section view
- Thus, 1 Fe traversal PER CELL !!!
- The Mission Volunteer Sign-Up Sheet will be
Available After My Talk
12DNA-Double Strand BreaksComplex Lesions
Biological Dose
- The latest idea is that multiple breaks within 30
base pairs on a DNA strand is a better measure of
the likelihood of causing a cancer to form than
other measures of dose. - We cannot yet calculate that liklihood from
first principles. - We can estimate it from empirical radiation
exposure data
13Current Cancer Risk Model (NCRP-132)
- 1) Estimates of radiation induced cancer
mortality are based on the atomic-bomb death
certificate data for 1950 through 1990. - Other human data (reactor workers, patients) used
as checks for consistency - 2) A minimum latency period following exposure
for radiation induced cancers of 10-years for
solid cancers is assumed. For leukemia, minimum
latency of 2-years, however risks are multiplied
by 0.1, 0.25, 0.5, 0.75, 0.9, and 1 for years 3,
4, 5, 7, and 8 or more years after exposure,
respectively. - 3) The excess relative risk for solid cancer is
assumed to be constant over time following
exposure. For leukemia a decline in excess risk
with time after exposure is assumed. - 4) The baseline survival and cancer rates for
astronauts are assumed as those of the US
population (SEER, 2000).
Slide Courtesy of F. Cucinotta, NASA/JSC
14Current Cancer Risk Model (NCRP-132)(Continued)
- 5) The transfer of risk from the Japanese to the
US population for solid cancers is made using the
average of the multiplicative and additive
transfer models, and for leukemias using the
additive transfer model. - 6) The dose response for the acute exposures of
the Japanese survivors is assumed to be a linear
function of dose. For leukemia a linear-quadratic
dose response function is used. - 7) For chronic exposures a dose and dose-rate
reduction factors of two is assumed. The
quadratic term in the leukemia response model is
set to zero. - 8) For high-LET radiation, an LET dependent
radiation quality factor, Q(L) recommended by the
ICRP is used to scale the doses (No other factors
in the model are assumed to depend on radiation
quality).
Slide Courtesy of F. Cucinotta, NASA/JSC
15Current Model- continued
- q(a) probability to die for age a and a1 based
on US mortality rate, M (all causes) and exposure
dependent cancer rate, m - Probability to survive to age a
-
- Mortality rate for ion fluence F, of LET, L
(ntransfer model weight) - Excess Lifetime Risk (ELR)
- Risk of Exposure Induced-Death (REID)
Slide Courtesy of F. Cucinotta, NASA/JSC
16Transfer ModelsAvailable data? Populations ?
Individuals
- Cohort baseline BJ (unexposed group)
- US Baseline BA
- aA linear coefficient fit to exposed cohort
- Additive Transfer
- RiskA BA aJ x Dose
- Multiplicative Transfer
- RiskM BA/ BJ x aJ x Dose
- Accuracy?
- large variations for specific tissue sites
- healthy workers or individuals
- genetic background
- dietary/environmental
- untested for space radiation non-cancer risks
Additive Transfer radiation acts independent
of spontaneous cancer risks Multiplicative
Transfer radiation risk depends on spontaneous
cancer risks
LSS Transfer to US (NCRP Report 126)
Slide Courtesy of F. Cucinotta, NASA/JSC
17Methods for Uncertainty Estimates
- Method Monte Carlo sampling over each factor in
model based on current knowledge to form
Probability Distribution Function (PDF) - PDF defined to bound values of each factor
(quantile) x - Cancer mortality rate for ions
- Physics PDF based on comparisons to flight data
- Use of REID corrects for competing risks
(important for Mars mission)
Factors (NCRP 126) xD DS86 (dosimetry of
A-bombs) xS Statistical errors xT pop.
transfer xP Bias xDr Dose-rate effects xQ
Quality factors xL physics (transport/dosimetry)
Slide Courtesy of F. Cucinotta, NASA/JSC
18Radiation Quality Effects
- Tradition- Effects increase to about 100-200
keV/mm and then decline due to overkill - Mechanisms
- Energy deposition in Biomolecules
- Cluster DNA damage site
- Gene deletion/mutation
- Chromosomal aberrations
- Sterilization term in dose-response
- Genomic instability
- LET or dose thresholds in activating molecular
pathways (epigenetic effects)
Cell Death is good
Slide Courtesy of F. Cucinotta, NASA/JSC
19Uncertainties in Biological Effectiveness
- Trial Function, Q(L)
- Sampling
- L0 1, 15 (flat 5 to 10)
- Lm 50, 250 (flat 80 to 150)
- Declining slope, p 0,2
- Qp 30 log-normal with GSD1.8
- Space missions-trial Q convoluted with trial LET
spectra to form sample rate
Slide Courtesy of F. Cucinotta, NASA/JSC
20Accuracy of Physics Models 20(environments,
transport, shielding)
ISS Mission
Slide Courtesy of F. Cucinotta, NASA/JSC
21PDF for Physics Uncertainties- GCR
Slide Courtesy of F. Cucinotta, NASA/JSC
22Fatal Cancer Risk per Rad vs. LET
- Average Life-loss from radiation cancer death
- (40-yr at exposure) low LET
- Leukemia 20 yr
- Solid Cancers
- Multiplicative Transfer 12-yr
- Additive Transfer 20-yr
- HIGH LET???
Slide Courtesy of F. Cucinotta, NASA/JSC
23Uncertainties not Included
- Deviation from linear-additivity models
- Radiation quality and latency or progression
- Models assume a constant ERR (Equivalent Relative
Risk) for solid cancers with no time-dependence
on radiation quality - Animal and cellular models suggest decreased
latency with increasing LET and ERR declines
after saturation - Possible uncertainties for mixed fields and
progression not modeled - Radiation quality and susceptibility
- Population averaged values do not account for
dispersion due to genetic factors (familial, high
and low penetrance genes, SNPs-Single Nucleotide
Polymorphisms) - Neutron carcinogenesis studies show RBE
variations across mouse strains for same tissue - Non-cancer mortality
- Dose limits need to consider life-loss per death
across each cause - For Mars mission non-cancer risks may be a
significant competing risk to radiation
carcinogenesis
Slide Courtesy of F. Cucinotta, NASA/JSC
24High LET- Protraction Effects
Pulmonary Tumors - fission neutrons in B6CF1
mice (Fry et al., Env. Int. 1, (1972))
Slide Courtesy of F. Cucinotta, NASA/JSC
25Radiation Risqué- transgender estimates(M(a)
Net Mortality MC(a) Cancer Mortality)
Differences between males and females are
approximate level of change for calendar year
changes
Slide Courtesy of F. Cucinotta, NASA/JSC
26Summary of Issues
- Acute effects are more predictable than Chronic
effects for Space Radiation Exposures - Cancer Risk is the Primary Chronic Effect.
- Big uncertainties exist in estimating risks
because - Effects from high LET radiation are poorly known
- Cancer causes themselves are not well understood.
- Current Policies Require Limiting Risks to the
same values as for Earth-based workers.
27Possible Strategies
- Classical Solutions Time, Shielding Distance
- Distancewe can do nothing about
- TimeMore powerful rockets to reduce mission
durations and thus exposure time - ShieldingDoable from the physics standpoint but
Expensive from the standpoint of weight ( ) - Long Surface StaysUse local soil overburden as
shielding material