NO NEETL TEterest G -11- ae gross disturbances in physiology are unlikely without Vargqer cases (2). "Of the manytypes of changes which radiation can cause in cells cr tissues, none 1s. considered to bs unique for rediaticn. Many, if not all, such changes can presumably resuit from a variety of other agents. This summary view on carcinogenesis is compatible with the ideas leading to the conclusion reached earlier, that fictitious dose averaging to larger tissue masses need not be conservative. The possibility of various . modes of carcinogenesis is acknowledged, and in particular, mention is exception. also. Cancer is no e oh a ode weds ww > oO v4 5s] ate Q wy ate Disease profil s are highly vo a ie) oO (i made of a pathway mediated by tissue disruption. Gross characteristics are obviously highlyspecies specific A rat and a mouse are distinct and yet incredibly similar. The gross tissue differences are articulated out through subtly different “informational resonances amongst cell populations, - the collective behavior being phased ultimately, though perhaps remotely, by the genetic controls of the cells. Not to belabor this point unnecessarily, - cancer profiles ° are species specific; gross characteristics and, of course, genetic material _ are also species specific. Collective detuning of tissue, by tissue disruption seen as acceptable an origin for the tissue instabilities of cancer as does an isolated single cell event. . . Return now to the problem of risk estimates associated with radioactive particulates in human lungs. Most of what has been said earlier in this comment has been general, and has been aimed at showing that there was no inherent conservatism in the riathod of estimating cancer risks set forth in the first sentence of 4.4.5, and that moreover the method could -- be far from conservative. The conclusion could as wel] ba applied to lymphatic tissue or to bronchial tissue. 40