Guinea pigs were given radiolabelled methyl(203)mercuric chloride at a dose of 3 mg/kg p.o. alone or with an equimolar dose of sodium selenite, every second day for 3 weeks (10 doses). Whole-body mercury levels were measured during the course of the study and multi-compartment analysis carried out by computer least-squares curve fitting. Results indicated that mercury given alone behaved according to a single compartment model with half-life of 23.6 days, while in the presence of selenium a two-compartment behaviour resulted with one clearing rapidly (half-life 8.7 +/- 5.3 days) and the other clearing more slowly (half-life 40.8 +/- 13.0 days). Selenium decreased excretion of mercury in feces (2-fold) and urine (7-fold). Approximately 70% of the total mercury in the feces and 90% of that in the urine was in organic form. Tissue distribution of total, organic and inorganic mercury was determined 1, 14 and 28 days after the final dose. Selenium decreased the levels of mercury 1 day after the final dose, but produced a slower clearance after that. In all organs examined most of the mercury was in the organic form, except in the kidney which had over 70% inorganic mercury. Selenium increased the relative amounts of inorganic mercury in the liver, spleen, pancreas, large and small bowels, but not in the kidney.

Upon exposure to methylmercury chloride, the whole-cell oxygen uptake by the yeast Saccharomyces cerevisiae ceases. On a fermentable carbon source, carbon dioxide continues to be evolved after respiration has stopped, indicating that fermentation is still active. Dextrose and glycerol uptake also persists until the respective processes, fermentation and respiration, are totally inhibited. Protein and nucleic acid synthesis are blocked with similar concentrations of methylmercury, while cytochrome c, the terminal component of the electron transport chain, is unaltered by the toxicant. Surprisingly, the intracellular ATP is higher in the treated cells than in the controls, although they eventually fall in response to higher concentration or longer exposure. High-pressure liquid chromatography profiles show that the amounts of the other nucleotides are either unaltered or increased. The entire inhibitory process is reversible with time or fresh medium at low methylmercury concentrations. These results do not support the hypothesis expressed by several authors of an inhibition of ATP biosynthesis resulting from membrane perturbation. These data suggest that the decrease in ATP—when induced by the organomercurial—is a secondary process and is not the result of direct mitochondrial toxicity.

Female guinea pigs were dosed po with 1.0 mg CH3 203Hg/kg as methylmercuric chloride, 10 times over a 3-week period. Tissue distribution, excretion, and accumulation of inorganic and organic mercury were studied. The highest concentration of mercury was found in the kidney. The greatest decreases of mercury levels were observed in the small bowel, red blood cells, liver, and cerebrum. The half-life of whole body clearance, based on a single compartment model, was 31.6 days. Mercury in the kidney, liver, and cerebrum was bound mainly by nuclear and soluble fractions. The highest ratio of inorganic to total mercury was seen in the kidney, 60% of this being as inorganic mercury. Excretion of mercury in the feces was measured throughout the experiment. The relationship of organic to inorganic mercury was relatively constant at about 1:3. Data on the effects of methyl mercury on tissue concentrations of zinc and copper show that the only change in the copper content was a marked increase in the kidney.

The analogy between pharmacology and dynamics of a pollutant in an ecosystem is emphasized in a survey of the state of exposure pathway modelling in the environment It is concluded that, except for the modelling of long-term transport, we are quite able to make quantitative predictions and to specify the errors and uncertainties therein.

The influence of methylmercury (MeHg) on the tissue and subcellular binding of selenium was determined. Adult female guinea pigs received either75Se (as sodium selenite) or MeHg (as chloride) followed 5 h later by an equimolar dose of75Se. Animals were sacrificed 1,3,7, and 13 days after administration. Pretreatment with MeHg significantly altered the organ distribution of75Se, particularly during the first week of the study.75Se concentrations were markedly reduced in most organs of animals receiving both75Se and MeHg except the liver, which contained markedly elevated75Se levels. The subcellular distribution of75Se was also altered by MeHg. Within liver, kidney and brain,75Se was primarily bound to nuclear and mitochondrial fractions in both treatment groups, but nuclear binding was higher in animals receiving both compounds. Within nuclear fractions, most75Se was bound to insoluble-nonhistone proteins. In the presence of MeHg, total nuclear binding of75Se increased, but total binding to insoluble-non-histone proteins decreased. MeHg also reduced the total75Se binding to high molecular weight proteins of the soluble fraction. Alterations in tissue and subcellular binding of MeHg and Se may contribute to the lower degree of toxicity observed in animals receiving both compounds.

Changing values of the pH in natural sediment-water systems did not affect the total amount of methylmercury generated in the sediments. However, partition of methylmercury between water and sediment did change, the amount of methylmercury in the water column doubling for a decrease in pH of 1.0 (sand) to 2.0 (organic sediment) units. This change is enough to explain, quantitatively, the observed elevations in mercury levels in fish taken from lakes of low pH.