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© 1987 Oxford University Press

research-article

Three-Dimensional Dose–Response Models of Competing Risks and Natural Life Span

OTTO G. RAABE

Department of Veterinary Pharmacology and Toxicology, Department of Civil Engineering, and Laboratory for Energy-Related Health Research, University of California Davis, California 95616

Three-Dimensional Dose–Response Models of Competing Risks and Natural Life Span. RAABE, O. G. (1987). Fundam. Appl. Toxicol. 8, 465–473. Three-dimensional dose-rate/time/response surfaces for chronic exposure to carcinogens, toxicants, and ionizing radiation dramatically clarify the separate and interactive roles of competing risks. The three dimensions are average dose rate, exposure time, and risk. An illustration with computer graphics shows the contributions with the passage of time of the competing risks of death from radiation pneumonitis/fibrosis, lung cancer, and natural aging consequent to the inhalation of plutonium-239 dioxide by beagles. These relationships are further evaluated by mathematical stripping with three-dimensional illustrations that graphically show the resultant separate contribution of each fatal effect. Radiation pneumonias predominates at high dose rates and lung cancer at intermediate dose rates. Low dose rates result in spontaneous deaths from natural aging, yielding a type of practical threshold for lung cancer induction. Risk assessment is benefited by the insights that become apparent with these three-dimensional models. The improved conceptualization afforded by them contributes to the planning and evaluation of epidemiological analyses and experimental studies involving chronic exposure to toxicants.


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