vexEPA United States Environmental Protection Agency Environmental Monitoring and Support Laboratory Las Vegas NE 89114 Research and Development EPA-600/PS3-80-085 Sept. 1980 Project Summary Biliary Excretion and Tissue Distribution of Cadmium-109 Administered to Rats A.A. Mullen and R.E. Mosley This report is part of a series of in- vestigations undertaken to establish the absorption/excretion character- istics of various metal pollutants in order to provide information for selec- tion of relatively rapid mammalian tests for estimating exposure. This study was designed specifically to ascertain the role of bile in the excre- tion of cadmium following oral or in- travenous administration of cadmium- 109 to rats. Results of the study show that bile concentrates cadmium and transports it into the gastrointestinal tract where it may be either reab- sorbed or excreted in the feces. Tissue distribution of the cadmium was also determined in the study. Regardless of the route of administra- tion, the liver retained the highest cad- mium concentration, although kidney and bone also retained a large percen- tage of the administered radionuclide. This publication is a summary of the complete report, which can be pur- chased from the National Technical Information Service. Introduction Cadmium is present as a trace metal in the earth's crust and as an impurity in ores of other metals. Concentration of ores and use of cadmium in industrial pro- cesses have caused cadmium to become an environmental pollutant producing a variety of toxic effects. Because the body appears to lack an effective mechanism for eliminating cad- mium, cadmium burden gradually in- creases with age. In addition, complex in- teractions that occur between cadmium and other divalent cations make predic- tions of intestinal absorption very dif- ficult. This study was undertaken to provide further information on the absorption, ex- cretion, and tissue distribution of cad- mium in the rat, in an effort to select universally available biological monitors, and to provide a reliable method for quick- ly estimating potential exposure of critical segments of a population to a potentially hazardous pollutant. Results The difference in the excretion of cad- mium in urine and feces was measured in rats with either ligated or intact bile ducts. Three days following a single oral- administration of cadmium-109 plus stable cadmium chloride, 4 x 10 3 percent of the dose was excreted in the urine of rats with intact bile ducts, while 5 x 10 2 percent was excreted in urine of rats with ligated bile ducts. While 82 percent of the dose was excreted via the feces of intact rats, 71 percent was recovered in feces from rats with ligated bile ducts. The amount of the dose recovered in tissue was 13 percent for intact rats and 30 per- cent for ligated rats. Following intravenous administration of cadmium, rats with intact bile ducts ex- creted about 5 x 10-1 percent of the dose in urine versus 2 percent for rats with ------- Table 1. Average Percent of Cadmium Dose Recovered Per Tissue Tissue Oral Ligated Non-Ligated Intravenous Ligated Non-Ligated Liver Spleen Kidney Heart Brain Skull Bone* 1.86 + 0.89 4.65 ± 0.79 x 10-2 0.21 ± 0.08 3.20 ± 0.27 x 10-2 2.20 ± 0.24 x 10-2 4.36 + 0.93 x 10-2 4.23 ± 0.55 x 10-2 1.64 ± 0.67 4.49 ± 0.81 x 10-2 6.88 + 3.58 x 10-2 3.05 ± 0.40 x 10-2 2.01 ± 0.35 x 10-2 3.02 ± 1.01 x 10-2 1.90 ± 0.32 x 10-2 39.3 ± 14.8 4.37 ± 3.51 x 10-1 7.45 ± 1.95 2.96 ± 0.57 x 70-1 2.85 ± 0.76 x 10-2 4.20 ± 1.13x 70-i 2.82 ± 0.22 30.1 ± 10.4 4.60 ± 0.98 x 70-1 7.36 ± 4. 16 2.30 ± 7.52 x 70-1 2. 19 ± 1.50 x 70-i 2.09 ± 7.72x 70-1 3. 16 ± 0. 12 ^Estimation based on percentage of body weight assigned to the bone of adult rats as reported by Sikor and Mahlum. ligated bile ducts. About 8 percent of the dose was excreted via the feces of rats with intact bile ducts, compared to only about 6 x 10-1 percent by ligated rats. The amount of the dose recovered in the tissues was 91 and 96 percent respectively for intact and ligated rats. As shown in Table 1, the liver, retaining the highest concentration, appears to be the organ of primary concern in this study, although cadmium was also re- tained in the kidneys and bone. Conclusions This investigation clearly demonstrated that bile plays and important role in the concentration and transport of cadmium for subsequent reabsorption or excretion. Collection of bile from animals endemic to a potentially polluted area would enable an investigator to easily determine an ear- ly increase in biologically available cad- mium. However, caution must be exer- cised when attempting to correlate the amount of cadmium in the bile with the dose of cadmium received, as dose threshold effects and possible synergistic reactions with other pollutants may affect the kinetics of bile production. Authors are EPA employees with the Environmental Monitoring Systems Laboratory, Las Vegas, NV (see below) The complete report, entitled "Biliary Excretion and Tissue Distribution of Cadmium-109 Administered to Rats," {Order No. PB 8021 7995; Cost: $5.00. subject to change) will be available from: National Technical Information Service 5285 Port Royal Road Springfield, VA 22161 Telephone: 703-487-4650 EPA authors can be contacted at: Environmental Monitoring Systems Laboratory U.S. Environmental Protect/on Agency Las Vegas, NV 89114 United States Environmental Protection Agency Center for Environmental Research Information Cincinnati OH 45268 Postage and Fees Paid Environmental Protection Agency EPA 335 Official Business Penalty for Private Use $300 r ~i L ------- |