The revised model is used to make predictions of fatal cancer and circulatory disease risks for 1-year deep space and International Space Station (ISS) missions, and a 940 day Mars mission. We analyzed the contribution of the various model parameter uncertainties to the overall uncertainty, which shows that the uncertainties in relative biological effectiveness (RBE) factors at high LET due to statistical uncertainties and differences across tissue types and mouse strains are the dominant uncertainty. NASA's exposure limits are approached or exceeded for each mission scenario considered. Two main conclusions are made: 1) Reducing the current estimate of about a 3-fold uncertainty to a 2-fold or lower uncertainty will require much more expansive animal carcinogenesis studies in order to reduce statistical uncertainties and understand tissue, sex and genetic variations. 2) Alternative model assumptions such as non-targeted effects, increased tumor lethality and decreased latency at high LET, and non-cancer mortality risks from circulatory diseases could significantly increase risk estimates to several times higher than the NASA limits.
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