A mortality kinetics approach to characterizing the fractionated exposure-mortality response relationship of radon...

The utility of mortality kinetics analysis in evaluating mortality data from fractionated exposure studies was demonstrated using radon-progeny induced extra mortality as an example. Gompertz (log-hazard) functions were used to characterize the mortality of male SPF Wistar rats exposed to radon progeny at 100 WL and 1000 WL for total exposures ranging from 20 to 10,240 WLM. There was an upward parallel displacement of the Gompertz functions following the period of radon exposure. The shape of the Gompertz functions for the exposed animals was consistent with a Gompertz model of toxicity resulting from short-term exposure, resulting in non-repaired injury that summates with natural (aging) injury. The parallel upward displacements (epsilon ss) of the Gompertz functions showed an unexpected non-monotonic pattern for rats exposed at 1000 WL. The parallel upward displacements showed a sharp upward increase from 320 to 640 WLM, fell at 1280 WLM, and thereafter increased linearly to 10,240 WLM. These data suggest that the radon progeny exposure-mortality response is non-linear. In contrast, there was no significant parallel upward displacement of the Gompertz functions for rats exposed at 100 WL for total exposures of 20-1280 WLM, but a large displacement began at 2560 WLM total exposure.