Some of the more important concepts used in the derivation of radiation standards, and problems in their application, are reviewed. In particular, the application of various models for carcinogenesis and the influence of differing cell susceptibilities for various sizes of animals are considered.SINCE the previous speakers have done such an admirable job of covering most of the historical perspective of my subject, I find with gratification that I have to abandon my text and bear down on a few points that I consider especially important. As a footnote to the history, however, let me tell the story of how beagles got into the act.By the beginning of 1945 we had already put together a prediction of the clinical picture of acute and chronic plutonism-a condition that has not yet been seen in man-on the basis of a few small-rodent experiments, together with what was known about the clinical effects of radium. It became clear that a larger animal was required to bridge the biological gap. What was needed was a suitable supply of fairly uniform dogs. This entailed a security problem, among other things, lest attention be drawn to the fact that a metallurgical laboratory-whose name was itself something of a cover-was ordering a quantity of pedigreed canines.A study of the kennel journals showed that the most readily available breeds at that time were beagles and cocker spaniels: beagles were more tractable, had shorter hair and better veins, and were chosen.To get to the subject of this paper, it appeared reasonable to expect malignancies to occur following absorption of plutonium, and to anticipate that bone would be the most likely site. The sporadic nature of carcinogenesis determined the design of the early experiments; while the term "threshold" was borrowed from the jargon of occupational health it was viewed with some skepticism, and radium was used to provide a link with medical experience-which, itself, has proven to present some difficulties that are still in the process of resolution.A great trouble in studying chronic effects on experimental animals is that there is never time to do all of the things that turn out to be needed. Sequential experiments are separated by very long intervals. Many trials with breeding animals, which should have been carried out many years ago, have yet to be done. The carefully devised Utah protocol had to be revised after many years; in the case of 90Sr, an intermediate dose-level was later inserted because of the steepness of the dose-effect curve; while with plutonium, lower levels were added much later when the flatness of the curve became obvious within the range originally chosen. You have heard this morning that similar problems have occurred in the Hanford inhalation study.Using tumors as the end-point, considerable difficulty results from the multidimensional nature of the carcinogenic process. One cannot adequately express findings on a single scale or on two-dimensional paper, although this has often been attempted. For example, one must consider the times at w...
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