A Mortality Kinetics Approach to Characterizing the Relative Biological Effectiveness of Short-Term Exposure to Fission Neutrons

Abstract

A Gompertz age-specific mortality rate model was developed for toxicity resulting from a short-term exposure to a toxicant resulting in nonrepaired injury that summates with natural (aging) injury. The model was applied to mortality data for male and female B6CF1 mice subjected to 60 weekly whole-body exposures to fission neutrons and gamma rays (W. F. Thomson and D. Grahn, Radiat. Res. 115, 347-360, 1988). There was no apparent increase in the age-specific mortality rate of mice during the 60-week period of fractionated exposures to fission neutrons. Cumulative toxicity was not exhibited in the Gompertz functions of mice exposed to fission neutrons until after termination of exposure. As a secondary issue, the Gompertz age-specific mortality rate model was modified to incorporate paradoxical "oversurvival" or longevity hormesis in mice exposed to fission neutrons. This modified model was compared to a model that has no allowance for oversurvival. The logarithmic-logistic function was used to relate the parallel upward displacement of the Gompertz function at steady state (i.e., the time after exposure ceased and the mortality effects of oversurvival dissipated) with dose. The data were shown to support the assumption of parallel upward displacement. The relative biological effectiveness (RBE) of fission neutrons compared to gamma rays was calculated using the steady-state displacement of the Gompertz functions. The RBE was defined as the ratio of doses D gamma/DN necessary to produce the same upward displacement by neutron radiation (DN) and gamma rays (D gamma). This definition is proposed as a useful measurement of RBE for studies of short-term exposures to fractionated radiation.