Dose-response Relationships for Bone Tumors in Beagles Exposed to 226Ra and 90Sr

Abstract

The development of bone tumors found in beagles injected with 226Ra or fed 90Sr has been under evaluation in lifetime experiments. In these studies 385 dogs were exposed to graded dosage levels of 90Sr in food beginning at mid-gestation and continuing until 540 days of age. Protracted ingestion of 90Sr represents the possible exposure of people to fallout or environmental releases from nuclear waste. To temporally imitate the past exposure of people to 226Ra and to provide a basis for interspecies scaling, 243 young adult dogs 435 days of age were given eight fortnightly intravenous injections of graded dosages of 226Ra. Comparison was made with available mouse and human 226Ra bone tumor data. The major findings were: (a) The occurrence of bone tumor related deaths was much less for 90Sr-exposed dogs than for 226Ra-exposed dogs. (b) Relative biological effectiveness (RBE) for bone tumors from 90Sr-Y (reference to 226Ra) varied as a function of average dose rate to bone (RBE = 1.5 at 16 rad/day, RBE = 0.05 at 1.6 rad/day). (c) The relative biological sensitivity of people was lower than of beagles and mice for 226Ra-induced bone tumors; people were found to require 10 times as long as mice and 3.6 times as long as dogs to develop bone tumors at a given skeletal dose rate and these response ratios were well correlated to the normal life expectancy for unexposed individuals. (d) The average cumulative radiation dose to death for those individuals that died of bone cancer was found to vary with dose rate and was much smaller at low dose rates (small bone burdens) than at high dose rates. (e) The time required to manifest tumors was longer at lower dose rates and could exceed the normal lifespan. (f) On this basis a practical threshold for bone cancer from 226Ra was estimated to exist at cumulative doses of about 50–110 rad (500–1100 rem with Q = 10) for dogs, mice and people.