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Cadmium was preferentially bound to metaliothionein In tissues 24 h after CdCl2 injection. Of a number of chelating agents examined, only 2,3-dimercapto-1-propanol (BAL) was effective in mobilizing Cd from metaliothionein into bile. Structurally similar dithiols such as 1,3-dimercaptopropanol and 2,3-dimercapto-1-propanesulfonic acid were not effective. Diethylenetriamine pentaacetic acid increased only the urinary excretion of Cd. Biliary excretion of Cd increased with increasing dose of BAL, and there was a concurrent decrease in hepatic Cd levels without any increase in renal concentration. BAL was effective even 14 d after Cd injection. The form of Cd excreted in the bile after BAL injection in chronic exposure has not yet been characterized. Initial studies suggested that it was not metaliothionein but was a low-molecular-weight Cd complex, probably with BAL.

The effects of several mono-, di-, and trithiols (400 μmol/kg) in mobilizing Cd from metallothionein were studied in rats 24 h after a single injection of 109CdCI2 (1 mg kg/Cd). BAL (2,3-dimercaptopropanol) and propanetrithiol (1,2,3-trimercaptopropane) were the most effective mercaptans in increasing the biliary excretion of Cd (3.1 and 5.5% of administered dose, respectively, compared to 0.04% in control injected with propylene glycol) in in situ experiments with a significant decrease in hepatic Cd. Propane-1-thiol was inactive and propanetrithiol was the most toxic of the compounds studied. A number of propane dithiols having sulfhydryl groups at different carbon positions with and without substituents (OH or SO-3) and dimercaptoethane were also tested for effectiveness in removing Cd. All the lipophilic compounds with two adjacent sulhydryl groups were effective in increasing the biliary excretion of Cd, but were less effective than BAL and propanetrithiol. The major form of Cd in liver cytosols of rats pretreated with CdCI2 and injected with mercaptans was metallothionein. A small amount of Cd in liver cytosol and a major portion of biliary Cd in propanetrithiol-injected rats were bound to high-molecular-weight proteins when fractionated on Sephadex G-75 columns. On the other hand, after injection of BAL, most of the Cd in the bile was associated with a fraction of molecular weight 10,000. Even though Cd was present mainly as metallothionein in livers of Cd-pretreated rats, the biliary forms of Cd after injection of BAL and propanetrithiol were different. Similar results were obtained when Cd was added in vitro to bile samples collected from control rats that were injected with these chelating agents alone. However, the Sephadex G-75 elution profile of Cd-BAL and Cd-propanetrithiol after direct addition to control rat bile showed Cd complexes of identical molecular weight (<6000). These results suggested that the Cd-binding ligands present in bile after injection of BAL and propanetrithiol were different from and had a higher molecular weight than the complexes in vitro with Cd and the respective chelating agents.

OF MICE AND MOLECULES: POLLUTION AND HUMAN SURVIVAL. by E. Skjei and M. D. Whorton, Dial Press, New York, 1983, 347 pp., US $17.95.CRC HANDBOOK OF NATURALLY OCCURRING FOOD TOXICANTS. Edited by Miloslav Rechcigl, Jr., CRC Press, Boca Raton, FL, 1983, 338 pp., US $63.00.NEPHROTOXIC MECHANISMS OF DRUGS AND ENVIRONMENTAL TOXINS. Edited by G. A. Potter, Plenum Press, New York, 1982.SOCIETAL RISK ASSESSMENT: HOW SAFE IS SAFE ENOUGH? Edited by Richard C. Schwing and Walter A. Albers Jr., Plenum Press, New York, 1980, 374 pp., illus., US $29.50.PEST RESISTANCE TO PESTICIDES. Proceedings of a U.S.-Japan Cooperative Science Program Seminar on Pest Resistance to Pesticides; Challenges and Prospects, Held Dec. 3-7, 1979, in Palm Springs, California. Edited by George Georghiou and Tetsuo Saito, Plenum Press, New York, 1983, 809 pp., US $89.50.BIODEGRADATION TECHNIQUES FOR INDUSTRIAL ORGANIC WASTES. Edited by D. J. De Renzo, Noyes Data Corporation, Park Ridge, NJ, 1980, 358 pp., US$28.00.APPLICATION OF ON-LINE ANALYTICAL INSTRUMENTATION TO PROCESS CONTROL. Proceedings of the First Annual Conference on Activated Sludge Process Control Held in Chicago, November 10-11, 1981. Edited by R. M. Arthur, Ann Arbor Science Publishers, Ann Arbor, Michigan, 1982, 222 pp., US $29.95.ORGAN AND SPECIES SPECIFICITY IN CHEMICAL CARCINOGENESIS. Edited by Robert Langenbach, Stephen Nesnow, and Jerry M. Rice, Plenum Press, New York, 1983, 693 pp., US $79.50.HANDBOOK OF PLASTICS FLAMMABILITY AND COMBUSTION TOXICOLOGY. by Arthur H. Landrock, Noyes Publications, Park Ridge, NJ, 1983, 308 pp., US $36.00.ALCOHOLS TOXICOLOGY Edited by William W. Wimer, John A. Russell, and Harold L. Kaplan, Noyes Data Corporation, Park Ridge, NJ, 1983, 278 pp., US $36.00.INDUSTRIAL WASTE. Proceedings of the Fourteenth Mid-Atlantic Conference Held at the University of Maryland, College Park, Maryland, June 27-29, 1982. Edited by James E. Alleman and Joseph T. Kavanagh, Ann Arbor Science Publishers, Ann Arbor, Michigan, 1982, 612 pp. US$39.95.TRACE ELEMENTS IN HEALTH. Edited by J. Rose, Butterworth Publishers, Woburn, Massachusetts, 1983, 317 pp., US $69.95.EVALUATION AND MANAGEMENT OF HOSPITAL INFECTIONS. Edited by Ralph van Furth, Martinus Nijhoff Publishers, The Hague/Boston/London, 1982, 266 pp. US $39.00.SELENIUM-A POTENTIAL ENVIRONMENTAL POISON AND A NECESSARY FOOD CONSTITUENT. Edited by Charles G. Wilber, Charles C. Thomas, Springfield, Illinois, 1983, 126 pp., US$19.50.

Body retention and tissue distribution of Cd from oral 109 CdCl2 and 109 Cd-metallothionein were studied in C57BL/6J mice given identical doses (60 μg Cd and 2 μCi 109 Cd). Measurement of109 Cd radioactivity in mice showed identical absorption but differences in tissue distribution of Cd from the two forms. A significantly greater deposition of Cd was observed in the kidney of mice fed Cd-metallothionein than in the CdCl2 group where a major portion of Cd was deposited in the liver. Most of the radioactive Cd in the renal and hepatic tissues and in the duodenum was bound to metaltothionein 24 h after oral Cd-metallothionein, whereas only 30 and 38% of the cadmium in liver and kidney supernatants, respectively, were bound to metallothionein after oral CdCI2. These results suggest that the dietary form of Cd may influence the renal deposition of Cd.

The effects of changes in sulfur-containing intracellular ligands on biliary excretion of cadmium were studied in rats. Injection of zinc or copper salts 24 h before intravenous injection of 109CdCl2 (1 mg/kg Cd) decreased biliary excretion of Cd. Pretreatment with cysteine (25 mg/kg) had a similar effect. Depletion of intracellular thiol by injection of diethylmaleate had little effect. The effect of chelating agents on the pharmacokinetics of Cd depended on time of administration of the agents after exposure to Cd. When chelating agents were administered ½> h after Cd injection (before the synthesis of metallothioneinj, the thiol-containing agents (2,3-dimercapto-1-propanol (BAL), DL-penicillamine, N-acetylpenicillamine, and dithioerythritolj increased the biliary excretion of Cd, while the carboxyl-containing ones (EDTA and nitrilotriacetate) increased the urinary excretion of Cd. BAL was the most effective chelating agent, but there was also an increase in the renal concentration of Cd. However, when these chelating agents were administered 24 h after Cd injection (after the synthesis of metallothionein), only BAL increased the biliary excretion of Cd. Renal and hepatic Cd concentrations decreased concurrently after BAL treatment.

Biliary excretion of cadmium was studied in rats after intravenous injection of different doses of cadmium chloride (0.1-2 mg Cd/kg). The rate of bile flow was not affected by cadmium injection and cadmium was excreted into bile during the first 2 hr after injection. The biliary excretion of cadmium increased with increasing dose of CdCl1. Cumulative biliary excretion of cadmium for 5 hr was 0.065% of the administered dose for groups injected with 0.1 mg Cd/kg as compared to 16.9% of the administered dose for 2 mg Cd/kg. During the 5 hr experimental period, most of the cadmium in liver cytosol was bound to high-molecular-weight proteins and less than 10% was bound to the metallothionein fraction. The biliary cadmium was recovered as a low-molecular-weight compound (less than 4,000) in experiments with various doses of cadmium and no cadmium was attached to high-molecular-weight proteins or metallothionein in the bile. The low-molecular-weight cadmium complex in bile was partially characterized as Cd-glutathione by thin-layer chromatography and amino acid analysis.

In protecting the body against the noxious effects of dietary cadmium ions, cadmium is bound to metallothionein in the proximal intestine, and subsequently excreted into the lumen with desquamation of the epithelium. The purpose of this study was to determine the extent to which cadmium in the form of intestinal cadmium-thionein is absorbed from the intestinal lumen and to appraise the toxicity of cadmium-thionein on the intestinal mucosa. With open-ended duodenal perfusion, equivalent amounts of cadmium administered as CdCl2 or cadmium-thionein entered the mucosa, but significantly less cadmium from the perfusate of cadmium-thionein passed into the body. Exposure of the mucosa to CdCl2 for 1 hr led to minor abnormalities in the form of broadening of villi with pseudostratification of epithelium, and swelling of mitochondria, whereas cadmium-thionein produced extensive necrosis of absorptive cells. The results suggest that cadmium-thionein may play a paradoxical role, providing protection against the cadmium ion in the intracellular milieu, but promoting cadmium toxicity when it is present in sufficient amounts in the lumen of the intestine.

Intravenous injection of 109Cd-labeled CdCI2 (I mg/kg) to control rats and rats that had been injected with CdCI2 (0.25 mg/kg) 24 hr earlier showed that there was a decrease in the biliary excretion of 109Cd in the latter group. The 24 hr pretreatment with CdCI2 resulted in induced synthesis of metallothionein in rat liver and kidney. The binding of cadmium to liver tissue was increased and the renal accumulation of cadmium was unaltered on cadmium pretreatment.Rat liver metallothionein was isolated from rats injected repeatedly with CdCl2 Intravenous injection of cadmium-bound metallothionein gave a different distribution of cadmium in the tissues and biological fluids as compared to injection of CdCl2. A major percentage of cadmium was deposited in the kidney with urinary excretion after injection of rat cadmium-metallothionein to control rats. The biliary excretion of cadmium after cadmium-metallothionein injection was minimal. About 90% of cadmium in the kidney cortex and urine could be recovered as cadmium-thionein in sephadex gel filtration, 3 hr after cadmium-thionein injection.