958 7. MERCURIALS 



occurs or whether it is important for the actions of the mercurials. (6) Hg+ 

 is quite rapidly oxidized to Hg++ in the body and probably acts on the tis- 

 sues in the oxidized form. 



The results of distribution studies are shown in Table 7-23. Further data 

 on the early distribution of several mercurials may be found in Table 7-19; 

 rough values for tissues levels of Hg++ in fatal human poisonings were pre- 

 sented in Table 1-8-1. Although quantitative comparisons are difficult due 

 to the widely different doses and the various routes of administration, the 

 general picture is clear. The concentrations in most tissues are not mark- 

 edly different from those in blood, but there is slight accumulation in the 

 spleen, moderate accumulation in the liver, and striking accumulation in 

 the kidney. The central nervous system levels are generally low, as expected, 

 and this must be due mainly to the small unbound fraction in the blood, 

 .since even the more lipid-soluble mercurials (e.g. MM) do not readily pene- 

 trate into the brain. Berlin and Ullberg (1963) gave single doses of Hg^^^Clg 

 intravenously to mice and determined the changing tissue levels over 16 

 days. The greatest amount in the central nervous system occurs in the brain 

 stem in the area postrema, in the hypothalamus, and in sites adjacent to the 

 lateral ventricles, and the retention in these regions is greater than in other 

 tissues. Essentially no Hg++ appears in the fetus so that the placenta pre- 

 sents a barrier to penetration, most of the Hg++ being bound to proteins 

 and the cellular elements of the blood. With the exception of the kidney 

 and brain there appears to be no obvious correlation between tissue levels 

 and pharmacological or toxic actions, and it is possible that the acute ef- 

 -fects, as on the heart, may be due to the initial binding to the cell mem- 

 branes rather than the result of intracellular uptake. Most of the results in 

 the tables were obtained with subtoxic doses, with the exception of those 

 of Galoyan and Turpaev (1958) and the cases of human poisoning, so it is 

 not possible to obtain a complete picture of the tissue levels during periods 

 of toxic reactions, but it is evident that rather low over-all concentrations 

 occur in most tissues. When it is considered that probably a major fraction 

 of the tissue mercurial is boiind to metabolically or functionally inert com- 

 ponents, it appears that very little mercurial is required to alter tissue 

 activity. 



Loss of mercurials from the body by urinary excretion is usually slow. 

 Rothstein and Hayes (1960) determined the total body content of Hg^"* 

 in rats given small doses of HgCL over a period of 100 days, and found 

 three distinct phases: 40% is lost in 5-10 days, 45% more during the next 

 40-50 days, and not over 5% more in the next 50 days, so that at 100 days 

 there is still some 10-15% of the administered mercury in the body. When 

 jjg203Qj^ is infused intravenously for periods up to 4 hr in rabbits, it is found 

 that the renal excretion does not exceed 10% of the total amount of Hg^°^ 

 passing through the kidneys. About 50% of the total dose is taken up in 



