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Reproductive tract functions were studied in adult male Wistar rats given 10 ppm thallium as thallium sulfate in the drinking water. After 60 days of treatment, spermatozoa isolated from the cauda epididymides and vas deferens showed reduced motility and immature germ cells were found in the tubular lumen. Histological examination of testes in thallium-treated animals revealed disarrangement of the tubular epithelium and ultrastructural changes in the Sertoli cells with cytoplasmic vacuolation and distension of the smooth endoplasmic reticulum. The activity of testicular beta-glucuronidase was significantly reduced whereas acid phosphatase and sorbitol dehydrogenase activities were unchanged. Plasma testosterone levels were within normal limits. No abnormalities in testicular morphology and biochemistry were seen in animals sacrificed at the end of the first month of thallium exposure. These findings indicate that the male reproductive system is a susceptible target site to toxic effects of thallium under chronic exposure. They also suggest a major involvement of Sertoli cells in the mechanism underlying thallium-induced testicular damage.

The placental transfer of thallium was studied in rats treated with a toxic dose of thallium sulphate (10 mg Tl/kg b.wt. p.o.), as well as in animals injected intraperitoneally with 201Tl-labelled thallium in amounts as low as 2 micrograms Tl/rat. Rapid uptake and retention of thallium in both maternal and fetal organs were observed. The administration of potassium ferrihexacyanoferrate II (100 mg/kg b.wt. twice daily by gavage) to rats acutely intoxicated with thallium on day 17 of pregnancy resulted in significant decrease of thallium concentrations in various maternal tissues including brain, in the placenta as well as in the fetal liver and brain. Potassium ferrihexacyanoferrate II also reduced the mortality of pregnant animals in the 72-h interval after the intoxication.

Placental transfer of thallium was evidenced in rats treated with a single intraperitoneal dose of 2 micrograms 201T1-labelled thallium/rat on the 13th day of pregnancy. Both maternal and fetal organs showed remarkable thallium retention, approx. 10% of the dose being unexcreted 8 days after injection. The highest thallium accumulation was found in maternal muscle and brain tissues. Fetal brain exhibits higher thallium uptake and faster decay rate of thallium levels than maternal brain. It is suggested that the reduced activity of the mechanisms regulating ion movements and composition of nervous tissue and the immaturity of the blood-brain barrier play a role in the peculiar pattern of thallium kinetics in the developing rat brain.

The presence of high concentrations of boron in community water supplies has been reported as a localized problem in certain areas of United States, USSR and Italy. In this paper, current information on sources, occurrence, pollution potential and toxicity of environmental boron is reviewed. In animals, chronic low-level boron exposure has been shown to cause reduced growth, cutaneous disorders and suppression of male reproductive system function. The mechanisms underlying these effects and available data on dose-response relationships are discussed in connection with human health hazards possibly associated with continuous low-level absorption of boron compounds.

Hepatic microsomal aniline hydroxylase and aminopyrine N-demethylase in vitro activities and the biliary excretion of sulfobromophthalein (BSP) were significantly reduced in rats treated with triphenyl tin (TPT) in daily doses of 1 mg/kg i.p. for 3 days. Bile flow, liver weight, serum enzyme activities, and hepatic sulfhydryl groups and thiobarbituric reactant levels were unaffected in TPT-treated animals. Moreover, TPT failed to induce any appreciable change in the biliary excretion of both the organic base procainamide ethobromide and the organic acid amaranth which is excreted into the bile in the unmetabolized form. TPT has been shown to be an effective inhibitor of rat liver glutathione-S-transferase activity. Reduced conjugation with glutathione may play a role as a factor determining the low rate of biliary BSP excretion in the TPT-treated rats.

The administration to the rat of the inhibitors of microsomal mixed function oxidase, SKF 525A and Oxine-5-sulphonic acid (OSA) caused a significant decrease of the hepatic aminopyrine N-demethylase activity, as well as an increase in the plasma levels and antipyretic activity of orally administered aminopyrine. The plasma concentrations of the aminopyrine metabolite 4-aminoantipyrine were reduced in SKF 525-A treated animals while they were slightly increased in those pretreated with OSA. These findings suggest that the in vivo changes of aminopyrine disposition and activity brought about by SKF 525-A were the result of an inhibited hepatic drug metabolism, while the effects produced by OSA were due to a more rapid intestinal absorption of aminopyrine.

Rats treated intravenously with 51Cr-labelled sodium chromate, 0.1 or 100 microgram Cr/rat, excreted more 51Cr into bile in a 2-hr period than did the animals given equal amounts of chromium in the trivalent state. Distinct patterns of hepatic intracellular distribution of the radiotracer were also observed. In the Cr-VI rats over 50% of the liver chromium was present in the supernatant fraction whereas in the Cr-III rats almost all the liver radioactivity was localized in the cell organelles. Fractionation of bile on Sephadex G-75 demonstrated binding of chromium to low-molecular weight substances. It is suggested that complexes of chromium with low-molecular weight components of liver cytosol are involved in the passage of this element from the liver to bile. A low cytosolic content of diffusable Cr-complexes associated with the incorporation of a large fraction of liver chromium in cell organelles may be a factor contributing to the low rates of 51Cr biliary excretion in the animals given Cr-III. 24 hr after the injection of 51Cr to bile duct-ligated rats appreciable levels of radiotracer were found in the gastrointestinal tract. The animals given Cr-VI exhibited significantly higher values of chromium content in the gut than those treated with Cr-III.

The gastrointestinal transport of 201Tl-labelled monovalent thallium has been studied in normal and rats with cannulated bile ducts using an in vivo ligated loop technique. A marked difference in the Tl absorptive capacity among the various sections of the gut was observed. 201Tl was taken up more quickly from the colon than from any other segment and the uptake from the ileum and jejunum was higher than from the stomach. In addition, considerable amounts of the intravenously administered thallium were excreted into the intestinal lumen. The biliary excretion was very low compared with the direct transfer of 201Tl across the gastrointestinal wall that occurred against a tissue-to-plasma concentration gradient. In the rat, the large intestine seems to be the major area for the enteral reabsorption and recycling of thallium (I) ions.

The biliary excretion of vanadium was studied in bile duct cannulated rats at various times after the iv administration of a single dose of 48V-labelled pentavalent vanadium. The tissue disposition, hepatic intracellular distribution and binding of 48V to plasma, bile and liver components were also investigated. During the first 6 hours after the injection of V, 0.9 to 30 microgram/kg, less than 2 per cent of the dose was excreted into the bile and up to 20 per cent of vanadium was eliminated in urine. The bile flow was markedly decreased in rats cannulated 24 hours after the injection of V, 30 microgram/kg, while higher doses produced signs of severe toxicity immediately after the administration. Evidence was also obtained that a concentration gradient triggers the passage of vanadium from plasma to the liver, where only a fractional amount becomes available from canalicular excretion, due to the extensive binding of the metal to organelles and other tissue ligands.