‘ Sea ooo ag Daeg woh toa Mey ate - ay esa at yf a) Noe Tat cet se siatbini s iid Te die z here dlae ea ge a noe os! ae, See be TUNNARD TONICOLOGY OF RADIONUCTIDES tee kere Dee lae dag “vases. Also a dose-effect relationship( stated so wank body burden or calculated dos e) dic coms were largely breaks(5.86 per hoa dred hone BAH Mot deletions or rings. The rela tionwf chsdacnee Is, of course, sl in the spec ula- divlure that ihe mammoch scientific and ~ “aurents will be soived in time to make this “sme of the cthers but it is hone d that the AE eaeik, ie ental mcidenits of cadcer in man trom the deposicturh there have been some depo sitions in stodets largely the effectiveness of contral vely short Ume during which these low body “ts, because of the importance ef plutonium ale animal studies have been underway va nied considerably since the early and midfm man extending over man y years. These wf reinterpreted (76), = eral milestones have been passed in the yand Mays et al (4), report that the chief sclony exposed to one of sevet 7 a] boneaa? “Ra (mesothorium , 7?8Ta, and 2S is wah osteesarcoma 8 vear s after injection of 4 bs likely ton an activity basis) as for as exceeded only by that for 228Tp. + ht bins fitneicg, and all Studies reiterate tel di erence in toxi city between pluto4 ark wth rodonzs (80, 81), This empirica l] es uiag of maximum allowable exposures In an independent study on inhaled aerosols of 77°Pu and 73%Pu in the dog, Yuile, Gibb & Morrow(90) report increasing pulmonary pathology, typical of radiation effects, from about 1500-2000 rads to 15,000 rads. They do not, however, report frank pulmonary carcinoma. Damage to accessory pulmonary structures, especially pulmonary Ivmph nodes, is commonly seen, especially if the compound inhaled !s insoluble and is cleared from the lungs primarily by nonsolubilization processes. With plutcn.um axide, maior ceeumulations occur m1 tracheebroncival-lyiigh nodes: 20-100 umes the concentration in lung. Fibrosis. scarring, and loss of bh mphatic aadutes are common, but frank neoplasia ov hese structures has wot lo ound shower. {9} reports chat iwo dogs and several rais that mhaled “selikic 7 nletoansys developed matignant lymphoma, and Leber et al (92) report ivmipaomia ai die regional lymph nodes of a dog receiving sir-oxidized pluteniim $7 sivoutsnecus cad to radium as a volume sane ee Aa TA. deposits oF pluton ium . sod sad han This has ted Nave (8-4) to Teel Clinger With Par enicre tly injected fey RE Sh traysPOER UooET . A :LM v S A D Sie 2 7 oe RETBRIER . PlulomuM dtu Lu We Comeiustoni Uidl alc disk ls AOU CQL ee Uist: depends on the rewte ef entry. Hence the relative risk will also vary with ¢ 2 diode of administration and this conclusian cannon bo extended te plusonar > enlerng OF reutes Cloer Li dgeenon, The mean skeletal rad dese at the lowest level showing ostcusarecemuato daic is 78 rads at ] year before death, @6@ rads ut the time ot ceath and the years hetween injection and death: 9.92 (79). If we campare these to the numbers seen in other avimals gerd mon for 7°°Ra the empirical toxicity ratie of slightly above 5 anpears to be fully confirmed tn this ‘arge experiment. Recent work also makes possible coranarison of the effective doses for cstecsarcoma in rodents to those in beagles. Buldakov & Lyubcranski (85) summarized work with 2208 rats recetving niutonium 239 at about 3 months or age. Incidence rates of about 3°) are seer at averege caiculated skeletal doses af from. 25-76 rads depending on rouie of entry and cormpound. Mays (personal communication) calculates the lifetime risk of bone sarcoma in this experiment as 0.06°4 per rad. But this may not be a smooth function, as many grouns at low doses showed no ostecsarcomas. The data of Finkel & Biskis (86) using CFI female mice showas calculated by Mays & Lioyd (79) 3.994 incidence at 40 rads dose accumulated up to 140 days before death. This is less than 0.194 incidence per rad. Neither of these rates are markedly different from those for the dog, e.g. 0.37%, per rad at estimated start of tumor growth or perhaps lower. Since this figure is for monomeric piutoniun: {see pace 336), which maybe about twice as carcinogenic as the polymeric form, the difference among the species becomes even less signiticant. This relative confluence lends credence to extrapolation to man and the expectation that the carcinogenicity of plutonium in the bones of man may well be a factor of 5 ar more greater than thai of radium. Thisis the figure currently used in assaying hazards oy man. Lloyd & Marshall (87) suggest that the relative eMectiven.ss factor may be higher in man than in dog because of cifferences in bone struciure The development of lung cancer in animals inhaling aerosols of plutonium has nowbeen fully documented (19. &8. 89). STE SOT Ussue. Whhe scunewhat oY “ee2 Tamers af ce TSSke, e.g Le, Cg, 2 ietaps 335 and the higher rate of burial of surface deposits of *7°Pu in the dog. “'Prrence hive now bee n all but settled as oo cuthdes in bone (4, 77, 81, 83, and many Ls on bone Surfaces, whereas radium ' tees With caleiu :n and deposits rotys ‘ugh sill not uni formly). This has “wah ae “ser Sete “eesiar velacialan ad aten Sem tana tos. LO mebapaeaied teete an dads ae ead cual dies “jon vealed gee adh deve « Bones ~s Re foot ~ Peatint aeae Se Pee MENT ¥r g bree eNT ‘ t ean Re een ete a TO Meee. . 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