TY - JOUR T1 - THE METABOLISM OF MERCURY IN THE RAT STUDIED BY ISOTOPE TECHNIQUES JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 166 LP - 176 VL - 130 IS - 2 AU - Aser Rothstein AU - Alastair D. Hayes Y1 - 1960/10/01 UR - http://jpet.aspetjournals.org/content/130/2/166.abstract N2 - The metabolism of mercury by the rat has been studied following intravenous or intramuscular injection, using Hg203 as a tracer. By the intravenous route, mercury is rapidly distributed to all organs. In the first few hours, a large fraction is taken up by the liver but this is rapidly (few days) cleared via fecal excretion. The kidney is the major site of deposition. As the mercury content of other tissues decreases after the first day, that of the kidney increases for about 2 weeks to about 85 to 90% of the total body burden. The mercury in the kidney is excreted via the urine at a rate of about 1% of the body burden per day. By the intramuscular route, the clearance from the site of injection takes about 2 weeks. No particularly large amounts of mercury appear in the liver. By the end of 2 weeks, as in the intravenous studies, most of the mercury is localized in the kidney. The excretion pattern reflects the organ distribution to some extent. During the first few days after intravenous administration, the bulk of the mercury is excreted via the feces, representing clearance through the liver. Thereafter, ⅔ of the mercury is excreted via the urine, related to the high kidney levels. The whole body counts indicate three phases in the clearance of mercury from the rats, a rapid phase involving 35% of the dose, lasting for a few days; a slower phase involving 50% of the dose with a half-time of 30 days, and finally a slow phase phase involving 15% of the dose with a half-time of approximately 100 days. After the first few days, most of the mercury is located in the kidney so that the two slow phases of excretion represent mainly the clearance from the kidney. The patterns were the same for mercury whether administered by the intravenous or the intramuscular route. With different dose levels (5 to 50 µg per rat) the clearances by whole body counting were approximately the same on a percentage basis. The pattern of distribution in the organs was also similar for all dosages except for a somewhat smaller localization in the kidney at lower doses. This, in turn, may be related to changes in excretion patterns. With lower doses the urinary excretion was diminished, but the fecal excretion was increased, so that total excretion was only slightly altered. With a series of five injections at 21-day intervals, each dose was handled in the same way with respect to total clearance from the body and tissue distribution. No special localization was found in the brain which might be related to the chronic toxic manifestations of mercury on the central nervous system. ER -