239py and 236Ra, but 7 32u, 233y, 9%S5r, and “Sca,* Figure 1 from her paper is reproduced herewith as Figure 3. The greater effectiveness of 233pu on a Others have calculated the relative uCi/kg injected dose basis is very clear. radiation doses and while the ratios change somewhat, the basic relationships between plutonium and radium are the same on either an administered dose or calculated radiation dose basis. In Figure 4 (Dr. Finkel's Figure 2), the comparative lethality is shown using radium-226 as the baseline. It was this information which, more than anything else, influenced the decision in 1950 to consider plutonium-239 as at least five times as effective as radium-226 in producing osteogenic sarcoma (Langham, et al., 1973). We are now accustomed, particularly in considering environmental exposures to plutonium, to regard inhalation as the most likely route of entry. Nearly all of the above toxicity studies involved intravenous injection. Was there anything in the early work pertinent to our present concerns regarding the production of lung cancer by plutonium? r 1 T T Fe tT FUT T 1 ' ro 3 { OTH 1 wee — F F r r 7 3 4 220 { Ra MsTh | \239 & F F 228 239 Th > ye bene eeewe woe o> 37 x 28 Pu 7 43 1 (mon) s Pu 1 Mey 4 %c, ’ 2 INHALATION STUDIES 100 RBE RELATIVE TO 778pg These toxicity studies led directly to the founding of the beagle dog experiment at the University of Utah. After all, there was still a large gulf in probable effective doses, lifespan, tumor susceptibility, etc., between the CFl female mouse and man. The beagle experiment was a much needed intermediate step. But while its inception date might fit the caption of "early work," the results have been coming to full flower only recently. Suffice it to say here that the basic relationships seen in the mouse have appeared also and held in the dog. Also, the addition of 228Th to the Utah experiment helped to sustain the suspicion, based on earlier radiochemical data, that plutonium and thorium might have more in common than plutonium and radium-226. A brief glimpse at some of the Utah results on comparative toxicity is shown in Figure 5, taken from Dougherty and Mays (1969}. Admittedly, inhalation studies were slower in coming about because of the large technical difficulties of preparing and administering controlled aerosols of radioactive materials. There were some rather crude inhalation experiments performed using hot wires to produce the aerosols. But the primary early information was obtained by the technique of intratracheal intubation. We now know that this direct instillation of material is not a satisfactory substitute for true inhalation experiments. But the results were useful in giving first approximations regarding pulmonary retention and clearance, even effects. aot i oO 2 L i L i 1 on i 3 4 5 6 ? 8 9 YEARS FROM INJECTION TO DEATH L 10 ] UN 12 ’The fact that 2320 and 2330 were employed in this work has only recently been fully appreciated. The relationships shown here are entering into current thinking about uranium standards. Figure 3. Bone tumor induction in the CFl female mouse. 9 From Finkel (1953).