Quarterly Technical Report October 1 Thru December 31, 1953

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Health and Biology THE UNIVEXSITY OF ROCHESTER Atomic Energy Project Rochester 20, New York It should be noted t h a t the Quarterly Technical Reports of The University of Rochester Atomic Energy Project do not attempt t o describe progress in all of the research programs but only in those in which some significant results have been achieved but which are not sufficiently complete t o be written up as final reports. Submitted by: Henry A. Blair Date of Report: 2/9/54

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Screening Toxicity Studies on 8 Number of Alcohols and Their Phosphate Esters by William L. Downs, Charles J. Preliminary Studies of the Relationship of Radioactivity t o Particle Size of "Fall-out'' Material by Charles J. Spiegl and Donald M. Eldredge 6. ............... THERAPY AGAINST RADIATION INJURY The Effects of Various Treatments on the Acute Radiation TOXICITY OF URANIUM The Toxicity of Inhaled Uranium Dioxide Fume by Leonard ABSTRACTS OF PAPERS PRESENTED AT MEETIMGS Calcium i n Blood Serum by Flame Photometry by Taft Y. Use of Infrared f o r Study of Isoleted Biological Systems TECIINICAL REPORTS ISSUED FOR DISTRIBU!MON ............ 31

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and Elliott A, Maynard Diisobutyl carbinol, capryl alcohol and a heavy-fraction alcohol with a molecular weight of about 185 as well as the phosphate e s t e r s of each were scyeened for toxicity. All of these materials were rated as H practical l ynontoxic'( t o "lelatively harmless" hen administered orally, intraperitoneally o r percutaneously. Rats, rabbits and mice were used as t e s t species. As part ofa program for screening for toxicity materials of special interest to the Al3C and its contractors, a nunher of Rolvents were investigated. Diisobutyl carbinol, capryl alcohol and a heavy-fraction alcohol with a molecular weight of about lS5 (Heavy Oxo) were tested a e received. Phosphate esters of each of these were synthesized immediately before u s e both i n kerosene and f Fee of eo lvent . Single intraperitoneal injections given t o about 50 rats and 20 mice showed all of these mate rids to be practically non-toxic. The preeence of kerosene had little effect on the toxicity of the phosphate estera,(Table L). Single oral doses by stomach tube t o about 65 rate and 25 mice gave the same toxicity classification a8 did intraperitoneal admi'nistration, (Table 2.)0 The amounts used were 5to 10 times larger but such a finding

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Table 1. Approximate Intraperitoneal Dosage to Produce 50% Rats Mice Bats Mice Table 2. Approximate Oral Dosage (ml/kg) t o Produce 5096 Mortality Skin tests on rabbits showed the alcohols and the phosphate ester e to be en ly slightly irritating when the undiluted chemical was applied t o the hairf r e e skin and kept i n contact with the* animal for 24 home. rabbits was used for this screening procedure and gave the results shown in

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carb in ol) 95% and some stiffness of skin some swelling after4 days Table 3 . Summary of Skin Tests on Rabbits 0,125 ml/kg gives some drying of skin; as light peeling occur8 0.125 ml/kg gives raised bleb turning t o dark leathery skin. Healing in about 30 days. 0.222 ml/kg givee slight erythema; some drying of skin after 2 days.

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OF ‘IHE REUTIONSHIP OF RADIOACTIVITY TO SIZE OF “FALL-OUT“ MATERIAL Spiegl and Donald Er,. Eldredge Preliminary studies on two samples of “fall-mt” material from an atomic detonation seem t o indicate that the radioactivity of particles below 25 pin diameter is proportional t o the number of particle e rather than t o any dimensional parameter. verify this finding. Further study with refined methods i s needed t o Two samples of “fall-out“ material collected within the state of Nevada were separated by sedimentation into 5fractions ranging in size from lees than 1pto 25 B; i n each case, the first separation was followed 25 p W ~ Rdiscarded because of the short sedimentation time and the indeterminate upper limit of sizes. thus represent the diRtribution of the particles that were radioautographed rather than of the original “fall-out” samples. A sixth fraction containing material larger than The count-size distributions in this paper Each of the sedimented fractions wa ~spread out in a shallow aluminum cup and then counted with a thin-window beta counter for a sufficient period of time t o ensure a probable error of less than 5%. sequently covered with a plastic film of a few ten-thousands of & inch thickness and radioautographed with type K x-ray f i l m : D-19 under standard conditions was used t o develop the film after & hour8 of exposure. spots, regardless of size o r density, were counted with the aid of a 10 x The samples were sub-

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Sediment at ion Particle of Time Dime ter Part icl es d/ m d/m/particle magnifying projection system. The data thus obtained are summarized i n Aplot of. the count-size dia tribntion on a Hazen logarithmic-probability percentage radi b act iii ty versus particle size. gave apr act icd ly coincident.... ... A - similar plot for the Although the data for this experiment are relatively meager, the unusual conclusions and inferences which it suggests warrant further comment. Thus, the beta activity of "fall-out" particles,within the limitations specified, is proportional t o the number of particles and notto any dimensional parameter. Such a condition @pears t o be satisfied only by the assumption tbat these particles are composed of an active nucleus surrounded by an inert This exper imnt consequently is not of study, however, were a was intended t o be only exploratory i n nature and high precision. Inherent i n the conditions of the nuniber of favorable factors. 1 ) The range of

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Me an Re lat ive Relative d/m/particle assnming activity to be a Diameter p Found ABCD plus Inert or Envelope size Surf ace Mas 8 sedimentation times (10 t o 2400 minutes), and consequently of particle size ranges, was large enough t o decrease the over-lapping of fractions. 2 ) The number of visible spots after radioautography wae essentially constant even though exposure t i m e was varied by t w o times. 3 ) Selfabsorption of radioactivity within the particle did not appear t o be important because the values of d/m/particle varied randomly with size. 4) !Jhe d/m/particle ranged only from 15.1 to 9.2 a8 the size increased from les e than 1 c1. diameter t o 20 p; in order for activity to correlate with size, the d/m/particle would have t o change by a factor of 40 times, for surface a factor of 1600 times, and for volums a factor of 64,000 times, (Table 2.). Table 2. Belat ionship Between Radioactivity and Particle Parameters On the other hand, many of the limitations of this study,are quite 1) Sedimentation i s not a highly precise method for separating 2) The number of particles and the total radioactivity were not a8 large as desirable. 3 ) The term nd/m/particlen is only a etat iet ical expression rather than a description o f the properties of any individual particle ; differences i n density and size of radioautograph spots were seen on a l l films and 4) the relationship shown by these data m a y be applicable

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only to particles smaller than 25 pin diameter, collected conditions, from similar detonatione, and of similar age. examination of some of the particles much larger than 25 p from the original., samples i n this experiment appeared t o show some relationship between size Whatever the explanation for the phenomenon suggested by these data, further studies are indicated. h c h work remains t o be done, if it is not ..*, . : ? .,already i n progress, t o determine the correlation between the radioactivity of 'fall-out" particles and aerosols and the particle parameters. The mewere

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OF VAIUOUS ON This investigation as undertaken model f o r fu%ure exploratory experiments as a pilot study aad to establish base lines for more elaborate and definitive experiments i n t h e therapy of the Acute& Radiation Syndrome. The use of an id zing agent (Bacterin), blood biotic (Aureomycin) i n the treatment of the Acute Radiation Syndrome Under t h e conditions of this experiment, none of these maintenance of the body weight of the irradiated animal. Aureomycin alone appears t o have some influence on the. Twenty-five adult mongrel dogs weighing from 6-17 kg. and ranging i n age from 1 - 5 years were used. against Distemper and Infectious Hepatitis and dewormed prior to time they were observed for any apparent abnormalities. received daily feed in p of commercially prepared dog meal and water ad into groups of five. according t o body weight, age, and sex. These dogs hadbeen idzed All the animals were isolated for 2-4 weeks during which After a l l does vere judged t o be healthy, they were divided ilttempts were made to distribute them uniformly. Control studies performed on

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path dog befoi-e irradiation included white blood cell and differential counts, he m to crit, sedimentation rste,md blood culture by standard procedures, md. coagulation time by the Lee-White Method. ?b p ~ a boli c ,t ar get to skin distance 35 in., rzte 9.2-9.4 r/min.). Animals were irradiated in pairs (exceFt the twenty-fifth dog) and so .zrranged that one dog from each group was irradiated simultaneously Td3h a 3og from each of the other groups. i'her2py was instituted as follows: Group l - Flacebo - consisting of one meatball B.i.d. ad 1 cc sterile irradiation, followed in five days by 4 cc. 63-143 mgm. /kg. ) perorally daily starting on day of ir radi zt ion. after irradiation ami continuing for two weeks. The Bacterin (Bio 682) was supplied through the courtesy Of Pitman-Moore Company, Indimapolis, Indiana. Antabuse I r a s supplied through the courtesy of Ayerst, McKentl3. RE^ Hams on LM., New York, Bew York. Koagamio was supplied through the courtesy of Chatham

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starting $'hours after irradiation, continuing for 10 days &d resnmed after a four dafwaiting period.^ that Amomycin by itself or in conbination with other antibiotics_ . W a t i o n Syndrome in dogs. The use of Aureomycin in this experiment1--. - irradiation body-weightdepression did not appear in the group of dogs. p r i a r to and until death of the & m a l ) determined by blood culture .--, Aureomycin was supplied thrw the courtesy of Lederle Laboratories Division, American Cyammid Company, New York, New York.

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consisted of Escherichia coli bacteremia in 2 out of 5 dogs in this group as compared with 2 out of 5 dogs in the control group. The maintenance of the normal body weight among dogs receiving Auremycin after whole body irradiation is of considerable interest. Post-irradiation body weight loss as an indication of the severity of the physiological response to radiation has been discussed by Lawerton et a1 (1). "his phase of possible radiation therapy w i l l be f'urther Koagarnin - This preparation is composed of oxalic and malonic acids in an aqueous ccid solution (2). dicarboxylic acids is that they mobilize prothrombin by releasing it from its combination with calcium, thus enabling it to be converted into thrombin for rapid coagulation ( 3 ) . It is a l s o suggested that this substance may release an activator of thrombo-plastic substances from the platelets (4), which in turn acts on the inactive thromboplastinogen of the blood (5). An examination of the effect of this preparati.on on the post-irradiation hemorrhagic syndrome was felt The suggested action of the The usual course of the post-irradiation syndrome does not appear to have been altered by the use of this preparation by itself. The usual leukopenia, hematocrit depression, increased sedimentation rate, prolonged blood clotting time (Table 1), relative granulocyte depression and transient relative lymphocytopenia (Table 2) manifested mortality, and necropsy (Table 3) did not reveal any deviations from the course followed by irradiated but untreated dogs. Although one dog did survive (Figure 2), this is not to be unexpected with 550 r

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Bacterin (Bio 682) - This preparation, a standard canine imrmrnizing agent, is a saline suspensfon of killed : infection process, and it was of interest to see... wha t. .effec t..,. this preparation would have on this manifestation. sera of dogs was abandoned because of the large nher of false Among dogs which had..undtrgone this treatment, there was no. appreciable deviation from the response among untreated b u t similarly depression, transient relative lymphocytopenia (Table 2) ; weight Routine blood culture did not-.reveal any process among bacterin treated dogs as compared There i s an indication of some augmentation of onset 0r;r mortality (Figure 2), hawever, this cannot be ascertained i n this small series of animals. Antabuse - This preparation blocks acetaldehyde metabolism.

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An exmination of this activity on the course of the Acute Radiation Spurcme i n aogs is of interest and w6s therefore included i n this series. ;in examination of the data reveals the usual post-irradiation course of weight depression (Figure 1); leukopenia, hematocrit depression, increased sedimentation rate (Table 1); relative granulocyte depression, transient relative lymphocytopenia (Table 2) was not altered by the treatment. group of animals suggests an enhancement of t h e post-irradiation lethal it y, however, the conditions of this experiment do not permit a valid estimate of the significance of this difference nor the pos sibi l - The cumulative mortality chart f o r this ity of drug toxicity. hemorrhage a t necropsy among the animals i n this group (Table 3) appear The short morbidity and lower incidence of t o be directly related to the earlier death of these dogs. The zssistancc of the follckring persons i n the performance of t h i s experiment and preparation of the report is grateRzlly Janet Markham, Joan Root , Ruth Lapides , and Donald 1. Laverton, L. F. et al, The B r i t i s h Journ. of Radiol., Vol.

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Quick, Armand J., Macy Foundation Conference on Blood Clotting and Allied Problems, Vol. 2, p. 202, p. 218, 1949

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THE TOXICITY CIF INHALED URAHIUM DIOXIm Leonard J. Leach, Sidney Laakb, Four groups of adult albino rats were exposed t o uranium dioxide fame at mean concentrationa of 46, 50, 61 and 70 rag. U / J , respectively. of these groups were expoeed f o r four hours, one f o r two hours. Histologic& sections of the kidneys and lungs ahowed that the fume was about as toxic as the uranium oxide dusts of average particle eize approximately 0.5 p previously tested. found in the kidney o r bone; no significant amount of uranium w a s found i n ths deposited in the lunge of rats erpoeed t o the fume than in the case of & U 0 (Wo f 2.6 p ) , while the deposition values for the fume and U02 …