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_ a a a Vv Fd Cosmet Toxicol Vol 15. pp 589 593Pergamon Press 1977. Printed in Great Britain i LEACHING OF RADIONUCLIDES FROM NEUTRON- ACTIVATED TALC IN SERUM AND IN DILUTE HYDROCHLORIC ACID C. L. WILKERSON A. P. WEHNER and L. A. RANCITELLI Radiological Sciences Department and Biology Department Battelle Pacific Northwest Laboratories Battelle Blvd Richland WA 99352 USA Received 24 May 1977 Abstract activated talc was suspended in bovine serum 0.5 of the 60Co and % of the 46Sc occurring in the sample was found in the supernatant of the centrifuged and filtered suspension A maximum of about % of each radionuclide can be attributed to small particles passing through the filter This indicates that very little Co and about 2.5 46Sc leached from the talc The findings indicate that from the pulmonary talc burden of about 45 gobserved in a previously conducted pulmonary deposition translocation and clearance study the equivalent of about 2 or 1 gtalc may have leached depending on whether 60Co or 46Sc data were used for this computation was Leaching effects on the lung burden thus appear to be negligible When activated talc suspended in 2 HCl from 2 to % of the induced 60Co 51Cr Fe and 46Sc was removed primarily by leaching This suggests that leaching of radionuclides from talc may take place in the acid environment of the stomach This leaching and the subsequent absorption of the radionuclide in the intestinal tract could account for the quantities of 6"Cofound in the urine of the hamsters in the earlier study INTRODUCTION The objectives of the experiment were to estimate In a pulmonary deposition translocation and clear- ance study previously conducted in these laboratories activated talc was used to determine talc burdens in hamster tissues and excreta following a single hr inhalation exposure Wehner Wilkerson leaching of selected radionuclides 6"Co51Cr 59Fe and 46Sc from activated talc and to evaluate the effect of such leaching on the estimated talc burdens reported for the pulmonary deposition translocation and clearance study Cannon Buschbom & Tanner 1977 Reported talc burdens were based on direct instrumental measure- EXPERIMENTAL ments of 60Co tracers and in a number of cases also of 46Sc tracers induced in talc prior to the inhalation exposure A fundamental presumption relevant to the validity of this technique is a direct quantitative correlation between measured radionuclides and talc A g sample of Johnson's Baby Powderfisubse- quently called talc was irradiated to an integrated neutron exposure of 14 ^ 1017 cmFollowing a decay period of 3 wk the irradiated talc was thor- particles However following contact with biological fluids the tracers may leach from the talc and thus oughly mixed to provide a homogeneous specific ray activity Several g aliquots were then compromise this correlation weighed into ml polyethylene vials Three ran- Direct instrumental measurements made in the pulmonary deposition translocation and clearance study indicated that from 20 to 80 gtalc was retained in hamster lungs and following mucociliary clearance and subsequent swallowing from 220 to 940 g passed through the intestinal tract and was domly selected containing vials were subjected to ray analysis on a state Ge detector to determine the specific counting activities of the radionuclides Co 51Cr 59Fe and 46Sc Solutions of bovine serum Grand Island Biological Company Santa Clara Cal and of HCl were eliminated in the faeces If significant leaching from talc occurs in the lung and intestinal tract soluble 60Co and 46Sc may be absorbed and translo- prepared and 100 aliquots of each were poured into separate 250 polyethylene bottles The pH of the serum was 8 and that of the dilute HCl was 1.8 cated to other organs or to the urine If it does represent translocated talc a calculated talc burden should be similar whether it is based on measure- The serum was treated with sodium azide 0-1 litre immediately after thawing to inhibit bacterial growth during the experiment Aliquots containing 0.1g 0.1g of ments of 60Co or 46Sc Since this definitive verifica- tion was not always possible due to 46Sc decay and since without verification measured radionuclide ac- tivities due to leaching may be incorrectly interpreted as translocated talc particles the extent and significance of tracer leaching into body fluids needed to be determined activated talc were suspended in the prepared . solutions The suspensions were then placed in a agitating water maintained at 37 It was assumed that the solution ratio of 100 0.1 g was adequate to make the experiment independent of solution equilibrium effects and would thus allow maximal leaching of the radionuc- lides of interest Registeredtrademark of Johnson & Johnson The extent of radionuclide leaching into bovine 589 JNJ 000262760 590 C. L. WILKERSON A. P. WEHNER and L. A. Rancitelli 3.5 ; % % 3.0 serum serum serum 2.5- bovine bovine bovine t in 2.0 talc talc from Radionuclides Radionuclides Radionuclides 1.0 t I Radionuclides Radionuclides 0.5 Radionuclides Radionuclides , #: 1 Hap y hoy play 2 4 16 32 64 128 Talc - serum contact time hr Fig 1. Removal of 46Sc 0 6"Co0 5"Fe an d 51Cr ^ from talc suspended pH 8 in a concentration of 0.1 100 ml Error bars represent the combined error mean -1s and supernatant counting errors 1s in bovine serum of the standards serum or HCl as a function of time was investi- gated by controlling the period of contact between each solution and the talc Periods for contacting a total of ten aliquots of activated talc with bovine serum were 0.5 1 2 4 16 32 64 and 128 hr aliquots for the hr contact time being measured in triplicate to determine experimental precision Contact periods for a total of three aliquots of neu- activated talc with dilute HCl were 1 4 and 128 hr At the end of each contact period the appropriate suspension was removed from the water and centrifuged A ml aliquot of the supernatant was removed by pipette and filtered through a glass filter Gelman Type E with a rated filtration efficiency of 99 for particle sizes > ...mThe filtered 50 ml of supernatant was analysed on the Ge detector used previously After application of appropriate radioactive and geometry corrections the fraction of each radionuclide that had leached from the talc was determined RESULTS AND DISCUSSION The corrected specific counting activities of the radionuclides 6"Co5,,Cr59Fe and 46Sc in talc and in the filtered supernatant solutions of bovine serum and 2 HCl are shown in Table 1. Measured specific counting activities for the three randomly selected ali- quots of irradiated talc showed close agreement and served as standards Computed fractions of each radionuclide removed from activated talc as a function of the period of contact with bovine serum or HCl are shown in Figs 1 and 2 respectively Results of contacting activated talc with bovine serum Fig ) indicate that 60Co 51Cr 59Fe and 46Sc were essentially retained by the irradiated talc particles Retained fractions were 96 for 46Sc and 99 for 60Co 51Cr and 59Fe as measured over the entire contact period Removed fractions of 6"Co51Cr and 59Fe were within a narrow range around 0.5 Considering experimental precision and accuracy the close agreement between these three radionuclide fractions suggests that the removed frac- tion represents small talc particles which may have escaped filtration This assumption is in good agree- ment with the rated > 99 efficiency of the glass filter for particle sizes 0.3 ...mIn view of these observations it is reasonable to conclude that measured fractions of 6"Co51Cr and Fe in filtered bovine serum represented talc particles Leached fractions of these three radionuclides can be considered negligible Preferential removal of 46Sc was observed for all serum exposures The gradual increase in removed 46Sc as a function of time suggests that leaching effects contributed to the measured 46Sc activities The observed maximal fraction of 46Sc removed was 3.1 after the 128 contact period Assuming that this value represents maximally extractable 46Sc and assuming a 0.5 contribution from small talc particles an estimated fraction of 2.6 represents leached 46Sc Alternative explanations for the raised 46Sc levels in the serum supernatant involve the fast neutron JNJ 000262761 Elemental leaching from talc in serum and HCl 591 +m 4A2W 607 TTF 9 L 80 80 60 8-0 + F F F F F 60 60 Ol Ol FFF Cl tl CI F F F61 ayelido e 711 8p 96p p&p 88p HL 64 O11 r-01 +11 V2 pl 27-91 1-97 29-47 9-57 Sor yy IDH ainjip puv wnsa (2}8} AAW Burtjdiynur VF VF 9 9 9 02% 9-0 80 60 Ol LT lt 0-1 OT FFFF F F SL 9-1 Ll # + 680 gg 879 209 909 F276 Fue 1-01 U2 9-61 L <1-21 $-91 8-91 8-41 8-SZ 9-62 <-0 < fq s[e) 9 L 9 ZI 4AaW POF + F 0 $0 $0 $0 60 L0 9.0 90 LO Zl pl G1 F + F F F F F F F F149 F791 8/uid 67-1 $69 199 289 EI 60 2 42 Lz 21 6 6< <P <9 S<Z 57 0} 2A6s aujaog 3/uid) Table neutron neutron neutron activated activated talc filtered filtered filtered supernatants supernatants supernatants bovine bovine activties activated of serum neutron neutron activated activated talc filtered supernatants supernatants supernatants supernatants bovine bovine Specifc neutron and filtered O11 P20 9901 9 <012TE g Radionuclide Radionuclide Radionuclide Radionuclide activity activity cpm cpm talc Table talc 60Co 60Co ot bb Ol pl 51Cr pl Ol 91 0-7 Fe Contact Contac MeVy elt MeVy 1.10 MeV.y Dts F 1.33 MeVy MeVy 0-32 MeVy +F MeV.y F PIFELS MeV.y 1.29 time MeVy L6st 2294 1.33 MeVy MeVy wp 0-32 MeVy MeVy MeVy 86 1.10 MeV.y MeV.y 6 <L 2]01 695 IL Il 1955 -11 80 80 1607 -10 8-0 80 1017 -8 I-1 9-1 - 2212 1958 1958 -31 1627 1627 -10 F F 27 + F 1036 - - 6761 066) 7.8 -31 FTL L01 2.2 -1.0 POl $01 0.6 102 86 0.5 682 oo - - 4.1 11.2 2 421 tl -0.8 80 8-0 4.4 1.4 8-0 O01 -0.7 181 FF -0.8 F F 9.8 1.5 F + -0.7 F 6 16 2.4 - <2125710-8 -0.8 +6 -01 7.7 -1.5 8-01 PI 4.2 -0.7 L-pZ 6b 32 3.9 128 - -1.2 () 3.4 1 16.4 12.5 - _ _ 20.6 - 1.0 1 z 6.5 - z4.9 - I 1.5 871 J z7 (OU yerA (s] queysadn ur F (3 1-0) ueow) wes ajdwesg oe yey aulAog cpm 10} qwueodns payd1JOD SONI (S{)ayeaydLy aie 4019 ul a[nDiHd TsoVne9]B)-07UOTINJSBunNoD4pourwzmaqt JNJ 000262762 592 C. L. WILKERSON A. P. WEHNER and L. A. RANCITELLI 7 % , 0 , HCI HCI I dilute 50 dilute I filtered filtered TH in talc talc M Radionuclides Radionuclides Radionuclides Radionuclides Radionuclides i om Radionuclides 0 to e 0.5 , { I 2 I 4. 8 1944 16 32 64 128 Ta-l acc id contact time hr Fig 2. Removal of Sc 6"Co0 Fe pH 1-8 in a concentration of 0.1 100 ml Errors mean -s and supernatant counting errors 1s an d 51Cr ^ from talc suspended in dilute HCI bars represent the combined error of the standards reaction Sc If significant this reaction could result in recoiled atoms of 46Sc which might become highly soluble following contact of the irradiated talc with the solution However this possibility appears unlikely due to the unfavourable production parameters of Ti atomic abundance % and the Ti concentration in this talc < 200 ppm as measured by activation analysis in our laboratory Also if recoiled 46Sc atoms were responsible for the increased 46Sc levels in the filtered serum supernatants the expected fractional removal curve in Fig 1 would rise sharply within a short exposure time and then level off asymptotically The data represented by the gradually increasing curve illustrated in Fig 1 do not support this hypothesis A second possibility is that the talc contains a high bearing mineral of small particle size which could preferentially escape the filter or leach Assuming a maximal leaching of 0.5 for 6"Coand 2.5 for 46Sc the maximal fraction of these tracers which may have leached from the talc in the hamster lung can be estimated Using the mean talc burden for hamster lungs 45 gdemonstrated in the pulmonary deposition translocation and clearance study Wehner et al 1977 the fraction of potentially leached 60Co and 46Sc would be equivalent to about 0-2 and 1 gtalc respectively The estimated quanti- ties of elemental Co and Sc leached from the above talc burden may be calculated from the elemental concentration of Co and Sc in the talc As measured in our laboratory by instrumental activation analysis these values were 64 and 1 ppm for Co and Sc respectively The estimated quantities of elemental Co and Sc leached were thus 14-4 ^ 10-12 g Co from 45 ^ 10-6 talc 64 ^ 10-6 Co talc and 0.5 and ^ 10-12 Sc from 45 ^ 10-6 talc 1 ^ 10 Sc talc and % Table 2 shows the average values for background ray counts with twice the standard deviation for 6"Coand 46Sc in various tissues and excreta from control animals expressed as gequivalents of talc It can readily be observed that the estimated quantities of leached 6"Coand 46Sc equivalent to 0-2 and 11 ...gtalc respectively are negligible Thus quantities of 60Co and 45Sc that may have leached and translocated from the hamster lung would also be negligible and would not affect the results of the pulmonary deposition translocation and clearance study Results of the leaching study suggest that a maximum of 0-5 of the induced radionuclides may have passed into the supernatant as unfiltered talc particles Contacting activated talc with HCl resulted in greater removals namely 2-5 This indicates that all four radionuclides were removed from talc primarily by leaching Fig 2 The maximal fraction of 46Sc removed was 5.3 this was recorded after the hr contact time and appears to be the upper limit of extractable 46Sc Removed fractions of Fe measured in filtered 2 HCl supernatants increased linearly as a function of contact time The maximal fraction removed was % after 128 hr .. Removal of the radionuclides 6"Co and 51Cr also showed a linear increase with contact time the maxi- mal fraction removed from the talc being 2.1 after JNJ 000262763 Elemental leaching from talc in serum and HCl 593 Table 2. Mean ray counts for tissues and excreta of control hamsters based on Co and 46Sc data and expressed in talc equivalents Table 3. Estimated quantities of Co and Sc translocated to blood of exposed animals following absorption from gastro- - intestinal tract Talc equivalent g Sample : Lung Liver Kidneys Ovaries Carcass Urine Faeces 60Co 0.9 2.5 1.4 2.1 -1.7 2.2 1.0 3.0 -1.8 0.4 3.4 46Sc 7-0 -5.8 4.6 7.1 2.2 5.0 -3.8 8.8 -6.8 4.4 2.0 5.8 -2.6 Values are expressed as means -SD and 60Co and 46Sc data for the control animals ary deposition translocation and clearance Wehner et al 1977 are based on in a pulmon- study on talc Parameter Co Sc Concn of element in talc ppm Mean quantity Q of talc passing through gut g Estimated fraction f leached in upper gutt Estimated fraction 2 absorbed in gutt Estimated quantity T of element transferred to blood ^ 10-12 10-12 g Equivalent quantity of talc g 64 455 0.01 0.3 90 1.4 1 455 0-045 0.0001 0.002 0.002 Determined by Wehner et al 1977 Determined experimentally using 60Co and From report of ICRP Committee II 1960 Sc tracers 128 hr in both cases The complex behaviour of the 46Sc removal curve which reaches a maximum after hr supports a mechanism of removal independent of that of Fe Co and Cr The independent behaviour of Sc could be due to the reduction of particles containing high concentrations of Sc to smaller particle sizes or to the leaching of particles containing readily depletable quantities of Sc To estimate the leaching effects of the acid environ- ment of the stomach on 60Co and 46Sc the hr contact data were used During this contact period % 6"Coand % 46Sc were removed from the talc Fig 2 On the basis of the data for intestinal absorption reported in 1959 by Committee II of the International Commission on Radiological Protection ICRP the total quantity of Co and Sc that may have leached from talc and translocated to blood by intestinal absorption can be estimated using the general equation T Q. Q..C w.hCere T is the estimated quantity of stable element translocated Q is the estimated quantity of talc passing through the intestinal tract fi is the estimated fraction of the element or radionuclide tracer leached during passage through the intestinal tract is the estimated fraction of the element or radio nuclide tracer absorbed from the intestinal tract and C is the concentration of the element in this sample of talc Using the average talc burden for hamster carcasses 455 ...gdetermined in the pulmonary deposition translocation and clearance study Wehner et al 1977 the corresponding equivalent fraction of talc potentially translocated calculated on the basis of leached 46Sc is only 0.002 gTable 3 This value far below the levels demonstrated for the control animals in that study Table 2 and would thus be undetectable Leaching therefore would have had no effect on the determined talc burdens in the pul- monary deposition translocation and clearance study The data on 60Co in Table 3 show about 90 pg Co may translocate The corresponding talc equivalent based on the measurement of Co is about 1.4 g Assuming that leached Co translocating to blood would mainly be excreted in the urine one would expect that the 60Co leached from talc could be measured in the hamster urine This contention is supported by a comparison of 6"Codeterminations in the urines of control and exposed animals The average value for control urines Table 2 is equivalent to 5 -4 gtalc The estimated translocation of leached 60Co to blood following intestinal absorption Table 3 resulted in a talc burden equival- ent of 1.4 gAdding the average urine value for the controls 1.5 gto that of the experimentally determined equivalent quantity of talc represented by leached 60Co 4 gyields approximately the values about 5 gfounidn the urine of the exposed ani- mals Wehner et al 1977 This suggests that leached 6"Coaccounts to a large extent for the ray counts recorded for the urine of exposed animals Acknowledgement work was performed by Battelle Pacific Northwest Laboratories for the Johnson & Johnson Baby Products Company under Contract No. 2311202572. We are indebted to Mr. R. L. Buschbom for his review of the statistical analyses REFERENCES Committee II ICRP 1960 Permissible dose for internal radiation Hlth Phys 3 161 Wehner A. P. Wilkerson C. L. Cannon W. C. Busch- bom R. L. & Tanner T. M. 1977 Pulmonary deposi- tion translocation and clearance of inhaled neutron vated talc in hamsters Fd Cosmet Toxicol 15 211 JNJ 000262764