Document 0q9aDMRwOZxjBL6w9aL5y5Vmd

Fd Cosmet Toxicol Vol 15 pp 453 455Pergamon Press 1977. Printed in Great Britain . 3 # 11 ABSORPTION OF INGESTED TALC BY HAMSTERS A. P. WEHNER Biology Department T. M. TANNER Radiological Sciences Department and R. L. BUSCHBOM Systems Department Battelle Pacific Northwest Laboratories Richland WA 99352 USA : Received 12 April 1977 Summary determine talc absorption in the intestinal tract of hamsters talc was neutronactivated and suspended in physiological saline and ml aliquots of this suspension were administered by gastric intubation to six old Syrian golden hamsters which were kept in metabolism cages The hamsters were killed 24 after gavage and the skinned carcass intestinal tract lungs liver kidneys and collected urine and faeces were analysed for 60Co and 46Sc by ray spectrometry An average of approximately 3 mg talc was found in the tissues and excreta Of this quantity 74.5 _ was found in the faeces 23.5 in the gut and 1-9 in the carcass The ray counts from the urine accounting for 0-09 of the total were probably due to leaching of 60Co from the talc with subsequent absorption and urinary excretion This study shows that intestinal absorption of talc is negligible and could have contributed only minimally to the body burden of talc found in hamsters in a previously published inhalation study Wehner et al Fd Cosmet Toxicol 1977 15 121 Introduction In a previous study Wehner Zwicker Cannon Watson & Carlton 1977a we investigated the effects of inhaled baby powder talc using the Syrian golden hamster as an animal model In the course of the repeated exposure of these animals to a talc aerosol unknown quantities of talc passed through their gasintestinal tract This talc originated partly from the ciliated part of the respiratory tract from where it was brought up by the mucociliary clearance mechanism and swallowed partly from the pelt on which some powder was deposited during whole exposures and from which it was removed by licking and partly from the hamster feed on which some talc powder was deposited during exposures It was necessary therefore to determine in our animal model to what degree the intestinal tract contributes to the body burden of talc Experimental Neutron activation of talc Johnson's Baby Powder lot 228p hereafter referred to as talc was exposed to an integrated neutron flux of about 7 ^ 1016 cmwhich produced radionuclides by n y reac- tions on the major and minor elements in the talc Wehner Wilkerson Cannon Buschbom & Tanner 1977b The activated talc was allowed to cool for 30 days so that the short neutroninduced isotopes could decay Registered trademark of Johnson & Johnson Animal treatment The activated talc was suspended in physiological saline solution containing 0.6 w % methyl cellulose as the suspending agent While being agitated by a magnetic stirrer ml aliquots of the suspension were aspirated with a syringe for administration by gastric intubation to six old female Syrian golden hamsters Mesocricetus auratus outbred ENG strain from Engle Laboratory Animals Farmersburg Ind maintained in metabolism cages An additional four control hamsters received also by gastric intubation ml aliquots of an identical suspension of irradiated talc to determine whether the suspending agent or the irradiated talc had a cathartic effect The hamsters were killed 24 hr after gavage and the skinned carcass intestinal tract lungs liver kidneys and collected urine and faeces were analysed for radioactive isotopes by ray spectrometry The ray counts were compared with those obtained from four control hamsters which had received no talc Analysis of samples Tissue samples for ray counting were preserved either in formalin or by freezing Small tissues such as the lung and kidney were preserved in formalin placed under a heat lamp to reduce the volume and then transferred to a 7.4 polyethylene vial for analysis Small frozen samples and faecal and urine samples were transferred | directly to vials for ray counting Large samples such as the carcass required temperature ashing to reduce the volume for analysis Previous work in our laboratory has shown that this does not result in volatilization and consequent loss of the radionuc- 453 JNJ 000262765 454 A. P. WEHNER T. M. TANNER and R. L. BUSCHBOM Table 1. Distribution of talc as indicated by ray counts in tissues and excreta of hamsters 24 hr after administration of a single activated dose by gavage ray counts expressed as gtalc equivalents % of total recovered Sample Mean SD SEM Mean SD SEM intestinal tract Skinned carcass Lungs Liver Kidneys Urine Faeces Total talc accounted for 688-4 56.0 0.0 0.6 1.2 2.6 2187 2936 232-1 24-8 - 0.76 1-19 0.66 769 746 94-8 10-1 0.31 0-53 0.33 314 304 23-5 1.91 0 0.02 0.04+ 0.09 74.5 10-75 0.73 _ 0.02 0-04 0-05 11.3 4.41 0.30 _ 0-01 0.02 0.03 4.61 Derived from a group of six hamsters All data are corrected for background and control values Not significantly different from control values at the 0-05 level lides considered in this study L. A. Rancitelli unpublished data 1976 The ray analyses were performed on several Ge and Na ray spectrometers Talc standards in geometrical arrangements identical to those of the samples were counted on each system used for sample analysis Counting times ranged from 100 to 2000 min depending on the activity in the samples The quantity of talc in the tissue sample was determined by comparing the sample with the standards Results The results of this study are shown in Table 1. The ray counts of the hamster tissues and excreta were equivalent on average to a total of 2.94 mg talc Most some 98 of this quantity was found in the faeces 74.5 and in the intestinal tract 23.5 The carcasses accounted for 1.9 The ray counts of the lungs kidneys and liver did not differ significantly from those of the controls P > 0.05 but the urine counts although accounting for only 0.09 of the counts did No cathartic effect of the suspending agent or of the activated talc was observed Table 2 compares the talc data based on the use of 46Sc with that obtained with 60Co for the gastrointestinal tract carcass and faeces for each animal The ratios of Co values to 46Sc values are also given and indicate that the Sc talc data are in reasonably good agreement with the 60Co data Discussion | The isotope 6"Cowas used to calculate the quantity of talc in all the samples because it has a long half 52 yr and easily detectable coincident Table 2. Quantities of talc in tissues and faeces of individual hamsters given a single neutronactivated dose by gavage as calculated from Co and from 46Sc data Total talc content g calculated from counts of Animal no 1 2 3 4 5 6 Sample GI tract Carcass Faeces GI tract Carcass Faeces GI tract Carcass Faeces GI tract Carcass Faeces GI tract Carcass Faeces GI tract Carcass Faeces 60Co x 944 67.6 1332 294 44.2 2232 615 25-9 2007 869 96-6 2637 633 60-9 3417 775 41.0 1495 46SC y 1007 57.8 1612 271 51.4 2346 730 27.4 2366 933 104.2 2980 663 65.3 3540 858 36-4 1666 Ratio / SD 0.94 -0.051 1.17 -0.077 0.83 -0.050 1.08 -0.115 0.86 -0.062 0.95 -0.012 0.84 -0.080 0.94 -0.151 0.85 -0.015 0.93 -0.080 0.93 -0.077 0.88 -0.014 0.95 -0.064 _ 0.93 -0.087 0.96 -0.014 0.90 -0.054 1.13 0.121 0.90 -0.059 GI tract = intestinal tract Corrected for control values JNJ 000262766 Absorption of ingested talc by hamsters 455 rays In addition 6Sc activity was used to estimate the quantity of talc in a number of samples to permit comparison of the sets of talc values obtained with the 46Sc tracer and with the 60Co tracer The advan- tage of using a pair of radioactive tracers to monitor the transfer of talc lies in observing two elements with different dissolution and transfer coefficients in bio- logical systems If the 60Co data and the Sc data lead to similar talc values it can be concluded with a high degree of probability that the radionuclides were transferred together by particulates An alternative situation producing the same 60Co ratio in the tissues as was observed in the talc would require these radionuclides to be leached and transferred in identical fashion The latter possibility is not - supported by past experience in our laboratory which has suggested that biological systems take up Co more readily than Sc L. A. Rancitelli unpublished data 1976 To obtain additional information on the degree of radionuclide leaching from talc in body fluids a leaching study was undertaken in which neuactivated talc was suspended in bovine serum and in dilute HCl for various periods of time Wilkerson Wehner & Rancitelli 1977 A suspending agent was used to prevent rapid sedimentation of the talc particles in the vessel containing the suspension and in the syringe during gavage Total quantities of talc mean -SEM = 2.94 -30 mg found in the hamsters and their excreta were reasonably uniform Most of the talc was recovered in the faeces and intestinal tract of the hamsters as was expected The data show that 24 hr after gavage approximately 75 of the talc had been excreted in the faeces while approximately % was retained in the intestinal tract Additional residence time in the gut prior to complete elimination of containing faecal matter would probably have resulted in only an insignificant increase in talc absorption since the passage of % of the talc through the gastrointestinal tract and retention of % within it for 24 resulted in only % absorption It appears reasonable therefore to assume that additional time until complete elimination of the talc from the gastro- intestinal tract would have contributed not more than a small fraction of % to the total level of absorption The zero values for the lung indicate that none of the administered suspension was aspirated by the ani- mals and that no translocation of talc to the lungs took place The results of the leaching study mentioned above Wilkerson et al 1977 showed that suspending neuactivated talc in HCl removed from 0.5 to % of 60Co and % of 46Sc from the talc primarily by leaching This suggests that leaching of radionuc- lides from talc may have taken place in the acid environment of the stomach of the gavaged hamsters Since according to measurements in our laboratory this particular talc contained 64 ppm Co and since 2.94 mg talc passed through the intestinal tract of the hamsters 0.5 leaching would have removed from the talc and made available for absorption about 940 pg Co. On the basis of a suggested figure of 30 for absorption from the intestinal tract ICRP Committee II 1960 this would have resulted in the translocation of about 300 to the blood If leached Co which translocates to the blood is largely excreted in the urine the excreted Co should be measurable in the latter fluid If 300 were excreted in the urine the resulting urinary counts from 60Co would be equivalent to roughly 4 ...g talc Since the measured urine counts were equivalent to 2-6 gtalc Table ) leaching of 60Co in the acid environment of the stomach with subsequent absorption from the intestinal tract and excretion in the urine 6"Co could well account for the quantities of in the urine found Apparently 1.9 of the talc passing through the intestinal tract was absorbed and translocated to parts of the body other than the lungs liver kid- neys and gut Further differentiation of translocation sites was beyond the scope of this investigation From the results of this study it can be concluded that intestinal absorption contributed only minimally to the body burden of talc demonstrated in the ham- sters in our previously conducted inhalation study Wehner et al 1977a Acknowledgements work was performed by Battelle Pacific Northwest Laboratories for the Johnson & Johnson Baby Products Company under Contract no 2311202587. The cooperation and advice of Dr. M. F. Sullivan and the technical assistance of E. M. Milliman R. M. Campbell J. H. Reeves L. L. Baker and A. L. Crosby are gratefully acknowledged REFERENCES ICRP Committee II 1960 Permissible dose for internal radiation Hlth Phys 3 161 Wehner A. P. Zwicker G. M. Cannon W. C. Watson C. R. & Carlton W. W. 1977a Inhalation of talc baby powder by hamsters Fd Cosmet Toxicol 15 121 Wehner A. P. Wilkerson C. L. Cannon W. C. Buschbom R. L. & Tanner T. M. 1977b Pulmonary deposition translocation and clearance of inhaled neutron vated talc in hamsters Fd Cosmet Toxicol 15 211 Wilkerson C. L. Wehner A. P. & Rancitelli L. A. 1977 Leaching of radionuclides from activated talc in scrum and in dilute hydrochloric acid Fd Cosmet Toxicol 15. In press JNJ 000262767