Scaling of fatal cancer risks from laboratory animals to man.
The functionally injurious and carcinogenic responses after exposure to 226Ra in mice, beagles, and people are reviewed. The observed bone-cancer response ratios from beagle data are used for examples of scaling carcinogenic risks to man for inhaled 239PuO2 and, in a similar manner, those from rat data are used for ingestion of diethylnitrosamine. Scaling fatal cancer risks from laboratory animal data to human risk predictions is described as a three-step process involving a three-dimensional analysis. The three dimensions used in this study for chronic exposure to chemical toxicants or ionizing radiation are average dose rate to target tissue (proportional to tissue concentration), elapsed time, and risk. The first step involves determination of dose rate delivered to target tissues. The second step is evaluation of the independent dose-response relationships observed in animals and prediction of human risk distributions by normalizing time units with respect to species natural life span. The third step involves predicting induced cancer occurrence (dependent risk) using the convolution integral for each of the competing risks, including those associated with natural life span. The use of computer graphics in conjunction with three-dimensional models of dose-response relationships dramatically clarifies the separate and interactive roles of competing risks. Low dose rates result in spontaneous deaths from natural aging, yielding a quasi-threshold for fatal induced cancer.
Raabe
O G
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Department of Veterinary Pharmacology and Toxicology, University of California, Davis 95616.
D000818:Animals; D001859:Bone Neoplasms / Q000209:etiology* / Q000401:mortality; D004052:Diethylnitrosamine; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced* / Q000401:mortality; D009374:Neoplasms, Experimental / Q000209:etiology / Q000401:mortality; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000401:mortality; D011005:Plutonium; D011883:Radium; D051381:Rats; D012306:Risk; D013045:Species Specificity
D004052:Diethylnitrosamine; D011005:Plutonium; D011883:Radium