Methyl mercury: acute toxicity, tissue distribution and decay profiles in the guinea pig

Acute toxicity studies with methyl mercuric chloride showed that the guinea pig was quite susceptible to methyl mercury intoxication. LD50 values were 5.5 mg Hg/kg ip and 16.5 mg Hg/kg po. One to 2 weeks after dosing, several animals began to display signs of neurotoxicity.Tissue distribution and pharmacodynamic studies with radiolabeled methyl mercuric chloride ([²⁰³Hg]CH₃HgCl) at 1 and 10 mg Hg/kg revealed that while most tissues decreased in mercury concentration from day 1 to day 7, cerebrum, cerebellum and muscle showed a delayed uptake of the alkyl mercurial. In CNS tissue the concentration of mercury decreased in the order cerebrum > cerebellum > spinal cord. Kidney and liver consistently contained the highest levels of mercury, and plasma the lowest, during the 49-day sampling period. One week after dosing the blood: brain ratios were less than 1. The tissue concentration of mercury was generally directly proportional to the dose administered; however, mercury levels in the gall bladder were significantly higher than anticipated on 5 of the 7 sacrifice days.Most of the tissues displayed a biphasic decay profile with a half-life of 2–3 days for the initial rapid phase of decline. This initial phase was followed by a slower tissue excretion rate for which the mean half-life for mercury was 15 ± 0.9 days and 15 ± 0.8 days for the low and high dose, respectively. The similarity of these values again indicates no dose-related effects.     

Distribution of mercury in rabbits subchronically exposed to low levels of radiolabeled methyl mercury

The metabolism of methyl mercury (MeHg) has been studied in rabbits administered 203Hg-labeled methyl mercuric chloride, 0.125 mumol/kg body weight, twice a week for 9 weeks, by intravenous injection. Twelve weeks after cessation of treatment, about 54% of the administered dose had been excreted in faeces and 5% in urine. After one week, the highest concentration of 203Hg was found in fur (8.6 nmol Hg/g). Substantially lower concentrations were found in kidney (2.5 nmol/g), liver (0.9 nmol/g), brain (0.4 nmol/g), muscle (0.3 nmol/g) and blood (0.1 nmol/g). The rate of elimination of 203Hg from brain, muscle and blood was faster (t1/2 about 12 days) than that from kidney and liver (t1/2 about 28 days). The relative amount of inorganic Hg in kidney and liver increased with time after cessation of treatment. The highest fractions were 85 and 70%, respectively. In brain, no significant demethylation of MeHg could be detected.     

Effect of rubratoxin B on adenosine triphosphatase activities in the mouse.

Half the animals in groups of selenium-deficient and control rats were given mercury in the drinking water for 6 weeks. The other half of the animals in both groups received tap water ad libitum. Selenium-deficient rats gained significantly less weight when given mercury, but weight gain of controls was unaffected by mercury administration. In another experiment with rats given mercury for 8 weeks, serum creatinine and renal histology were normal in selenium-deficient and control rats. Selenium-deficient rats injected with ²⁰³HgCl₂ 12 days after mercury was added to their drinking water excreted up to 10% of the ²⁰³Hg in the urine in the first 24 hr whereas control animals excreted less than 2%. This trend continued for several days and was shown to be due primarily to a loss of ²⁰³Hg from the kidney in the selenium-deficient rats. The control kidneys contained 4 times as much mercury as the kidneys in selenium-deficient rats at the end of the experiment, and the mercury content appeared to be increasing further. Selenium-deficient kidneys, however, had achieved maximum mercury accumulation by 13 days. Despite the large differences in mercury accumulation due to selenium status, in both groups about 80% of kidney ²⁰³Hg was found in the soluble fraction. Also, regardless of selenium status, about 90% of the soluble fraction ²⁰³Hg was found in a symmetrical peak on gel filtration which probably represents metallothionein. Thus a major effect of selenium status on the metabolism of inorganic mercury seems to be in facilitating the accumulation of mercury by the kidney. Since most of the kidney mercury is bound to metallothionein, selenium may mediate the binding of mercury to this protein or be a permissive factor in the induction of metallothionein by mercury.     

Biliary excretion of manganese in rats, rabbits, and dogs

The disappearance of ⁵⁴Mn from the blood and plasma of rats and its excretion into bile was measured for 2 hr after the iv administration of 0.3, 1.0, 3.0, and 10 mg/kg of manganese. The maximal rate of excretion of manganese into the bile was approximately 8.5 μg/min/kg after the 2 higher doses. The bile concentration was found to be 100–200 times that in the plasma for the 3 lower doses. This was due both to the higher concentration of manganese in the liver than the plasma (15- to 20-fold) and in the bile than the liver (6- to 10-fold). Bile had about 50% the affinity for manganese as plasma, and about 20% the affinity as did liver. This suggests that manganese does not pass from plasma to bile because of a higher affinity for bile than plasma. These results show that manganese is excreted into the bile of rats against an apparent concentration gradient and suggest that an active transport mechanism for the excretion of manganese may exist. Lead does not decrease the excretion of manganese, and the excretion of manganese is not highly temperature-dependent as is that of lead, suggesting that manganese is excreted by a different pathway than lead. Manganese is also excreted into the bile of rabbits and dogs with a species variation in the rate of excretion. Manganese did not decrease bile flow in rats when it was given alone or when bilirubin was given 15 min before manganese administration; however, a marked decrease in flow was observed when bilirubin was given 15 min after manganese administration.     

Biliary excretion of cadmium in the rat,rabbit, and dog

The fecal elimination of cadmium is more important than urinary elimination. Within 1 week after iv administration of cadmium to the rat (1 mg/kg), 17% is excreted into the feces and less than 0.5% into the urine. However, of the amount excreted into the feces in 1 week, 85% is excreted within 2 days. The disappearance of ¹⁰⁹Cd from the plasma and its excretion into bile were measured for 2 hr after the iv administration of 0.1, 0.3, 1.0, and 3.0 mg/kg of cadmium to rats. The bile/plasma concentration ratio of cadmium was highly dose dependent; at the lowest dose, it was 2.6, and, at the highest dose, it was 133. The bile/plasma ratio was greater than 1 because the concentration of cadmium in the liver was 100 to 700 times higher than in the plasma. However, the bile concentration of cadmium was equal to or much lower than that in the liver; at the lowest dose (0.1 mg/kg), the concentration of cadmium in the bile was less than 1% of that in the liver. The relationship of the dose of cadmium to its biliary excretion was also reflected in the percentage of cadmium excreted into the bile within 2 hr, which ranged from 0.23 to 9% as the dose was increased from 0.1 to 3 mg/kg. The biliary excretion of cadmium was increased approximately four times as the temperature of the rat was increased from 30 to 40°C. The effect of 4 days of pretreatment with phenobarbital, spironolactone, pregnenolone-16α-carbonitrile, or 3-methylcholanthrene on the biliary excretion of cadmium was measured; only phenobarbital significantly increased its excretion. Marked species variation in the biliary excretion was observed. Rabbits excreted cadmium at a rate of about $\text{1}\text{6th}$, and dogs excreted cadmium at a rate of about $\text{1}\text{300th}$ of that observed in the rat. These results suggest that, while biliary excretion is the main route for cadmium elimination, the rate at which it is excreted appears to be highly dependent on the time after administration, the dose, and the species employed. This rate is not as responsive to alteration in the temperature of the animal or to administration of microsomal enzyme inducers as is that of some other metals.     

Distribution and Biotransformation of Methyl Mercuric Chloride in Different Tissues of Mice

Abstract: The distribution of ²⁰³Hg radioactivity has been studied in various organs of adult male and female mice from one hour to 21 days after treating with ²⁰³Hg-labeled methyl mercuric chloride (MMC). The amount of methyl mercury (MeHg) and inorganic mercury (Hg) has also been determined by injecting single doses of non-radioactive MMC, and subsequently measuring total, organic and inorganic Hg content by atomic absorption technique. In addition, photoemulsion histochemical method (PEHM) was used to demonstrate localization of Hg grains in various cellular compartments of organs and tissues. The highest levels of radioactivity were attained at 7 hours post-treatment in all organs except for brain and testis. The testis showed the highest radioactivity at one day and the brain at two days post-treatment. MeHg persisted in brain over a longer period though the level was not as high. The content of MeHg and inorganic Hg was maximum in kidneys as compared to other organs. The brain and the reproductive organs contained the least amount of inorganic Hg. By PEHM, Hg grains were most prominently observed in the sinusoids, Kupfer cells, hepatic cells and bile duct epithelium of liver; in the lumen of blood vessels, convoluted and collecting tubules of kidneys; and in the gastrointestinal epithelium. The pattern of uptake and distribution of MeHg correlated well with the morphological demonstration of Hg grains in tissue sections.     

Biliary excretion of lead in rats rabbits,and dogs

The disappearance of ²¹⁰Pb from the blood and plasma of rats and its excretion into bile was measured for 2 hr after the iv administration of 0.1, 0.3, 1.0, 3.0, or 10 mg/kg of inorganic lead. The maximal rate of excretion of lead into the bile was approximately 1.0 μg/min/kg after the 3 higher doses. The concentration of lead in the bile was found to be 40–100 times that in the plasma for the 3 lower doses. This was due largely to the higher concentration of lead in the liver than in the plasma (10- to 35-fold higher) and partially to the higher concentration in the bile than in the liver (3- to 4-fold higher). Essentially none of the lead in the bile, plasma, and liver was dialyzable. Lead exhibited a 5-fold greater affinity for liver than bile and a 3-fold greater affinity for liver than plasma. The mitochondrial fraction contained the highest concentration of lead. Changing the rectal temperature of rats altered the biliary excretion of lead markedly; when the temperature was increased from 30 to 40°C, the biliary excretion of lead increased 20-fold. Marked species differences in the biliary excretion of lead were observed. Rabbits excreted lead into the bile at a rate less than one-half, and dogs excreted lead at a rate less than one-fiftieth, that observed in the rat. The results indicate that lead is excreted into the bile of rats against an apparent concentration gradient and that an apparent transport maximum exists. This suggests that the liver may have an active transport mechanism for the excretion of metals.     

Biliary excretion of arsenic in rats,rabbits, and dogs

The disappearance of ⁷⁴As from blood and plasma of rats and its excretion into bile was measured for 2 hr after the iv administration of 0.01, 0.46, 1.0, 2.1, and 4.6 mg/kg of arsenic given as the trichloride. Arsenic disappearance from plasma was biphasic; the half-life during the late phase was greater than 2 hr. Even though the arsenic was injected iv, the concentration in the blood increased through the first 2 hr. Arsenic was rapidly excreted into the bile, reaching its highest rate of excretion 6 min after administration, after which it rapidly decreased. This rapid decrease in excretion is due to redistribution of arsenic from the liver to the blood. Arsenic enters bile against an apparent bile/plasma concentration gradient of 630, 8 min after 1 mg/kg of arsenic. At this time the liver/plasma gradient is 17 and the liver/bile gradient is 37. Twenty-five percent of the arsenic administered to bile duct-cannulated rats is excreted into the bile within 2 hr. However, less than 10% of the administered dose is excreted into the feces of intact rats over a 7-day period. In the rabbit and dog, arsenic is excreted into the bile at a much slower rate. These data demonstrate that arsenic is excreted into the bile, and this occurs against a large bile/plasma concentration gradient in rats, suggesting excretion by an active transport mechanism. However, the overall importance of bile as a route of elimination for arsenic is minimized due to enterohepatic circulation and species variations in its biliary excretion rate.     

Influence of spironolactone on the mercury biliary excretion mechanism in rats

Spironolactone (SPL), administered intragastrically to rats 24 and 2 h prior to i.v. application of ²⁰³HgCl₂, was found to change the pattern of ²⁰³Hg distribution among the individual bile fractions. In spironolactone-pretreated rats there was a more rapid biliary excretion of ²⁰³Hg which was ascribed to the presence of mercury in the low-molecular bile fraction (fraction 2). This accelerated mercury excretion persisted for as long as the spironolactonemercury complex was present in the animal organism.     

Biliary excretion of silver in the rat, rabbit, and dog.

The fecal elimination of silver is more important than urinary elimination. Within 4 days after iv administration of silver to the rat (0.1 mg/kg), 70% is excreted into the feces and less than 1% into the urine. The disappearance of ¹¹⁰Ag from the plasma and its excretion into the bile were measured for 2 hr after the iv administration of 0.01, 0.03, 0.1, and 0.3 mg/kg of silver to rats. The concentration of silver in the bile was 16–20 times higher than that of the plasma. With the two lower doses of silver used, the overall plasma-to-bile gradient was due almost equally to the plasma-to-liver gradient and the liver-to-bile gradient and with the two higher doses of silver the liver-to-bile gradient became more important. Marked species variation in the biliary excretion of silver was observed. Rabbits excreted silver at a rate about $\text{1}\text{10}$, and dogs excreted silver at a rate about $\text{1}\text{100}$ of that observed in the rat. These results suggest that while species variation exist, biliary excretion is an important route for the elimination of silver.     

Metabolism of Mercury in Hamster Pups Administered a Single Dose of 203Hg-Labeled Methyl Mercury

Abstract: Golden Syrian hamster pups were administered a single subcutaneous dose of ²⁰³Hg-labeled methyl mercury (MeHg), 0.4 nmol/g body weight, seven days after birth, and were sacrified 2, 7, 14, 21 or 28 days later. The excretion of ²⁰³Hg followed a biphasic elimination pattern with an average half-time of 8.7 days for the rapid component. The slow component had a much longer half-time and probably reflects binding of ²⁰³Hg to growing hair. The concentration of ²⁰³Hg in the liver, kidneys and brain two days after administration was 0.44, 0.38 and 0.19 nmol/g, respectively. The retention of ²⁰³Hg was higher in the kidney than in the liver and the brain. The content of inorganic ²⁰³Hg in the liver and kidneys increased the first weeks after administration, demonstrating that hamsters are able to demethylate MeHg before two weeks of age.     

Localization of Gastrointestinal Deposition of Mercuric Chloride Studied in Vivo

Abstract: During the last 5 years, the site of gastrointestinal absorption of inorganic mercury has been attempted identified mainly by experiments using perfused intestinal segments in vitro or in situ. The present investigation will discuss the localization of the absorption site for mercuric chloride based on a completely undisturbed in vivo experimental model in mice. As the mice were allowed to eat their normal diet during the experimental period, the present results would independently add to existing knowledge on intestinal absorption sites for inorganic mercury. The mice were given ²⁰³Hg labelled mercuric chloride orally, either through stomach tube or in the drinking water, and were killed after various time intervals. Mercury was localized and quantified in various segments of the gastrointestinal tract by gamma-counting. Time course analysis of the segmental deposition of mercury demonstrated that the deposition mainly takes place in the proximal jejunum and suggested that a larger part of the jejunum than previously reported is involved in absorption of mercury. Using this in vivo model, tetraethylthiuram disulfide was demonstrated to increase the intestinal deposition and absorption without changing the site of deposition.     

The effects of spironolactone on the biliary excretion of mercury,cadmium, zinc,and cerium in rats

The effect of spironolactone (Sp) pretreatment on the biliary excretion of intravenously injected heavy metals (mercury, cadmium, zinc and cerium) was investigated in rats, using five metal compounds (four inorganic metals in chloride form, and methyl mercuric chloride). The oral administration of Sp ($\text{5 mg}\text{100 g}$) 1–3 hr before the bile excretion study increased the biliary recovery of mercury more than ten times over a period of 4 hr in rats injected with mercuric chloride, but did not increase the biliary excretion of the other three metals (Cd, Zn and Ce). Multiple-dose pretreatment (2 doses a day for 3 days) also increased the biliary excretion of mercury but much less than in the acutely treated rats. Cadmium excretion was significantly decreased by multiple dose pretreatment. Sequential nuclear imagings after intravenous injection of ¹⁹⁷HgCl₂, demonstrated clear differences in the tissue distribution of mercury between control and Sp-treated rats.     

Enterohepatic circulation of 64Cu, 52Mn and 203Hg in rats

The intestinal absorption of ⁶⁴CuCl₂, ⁵²MnCl₂ and ²⁰³HgCl₂ was compared with those of biliary excreted radiometals in rats during 24 h after intraduodenal administration. Biliary excreted metals were obtained from rats (donors) given previously intravenously ⁶⁴CuCl₂, ⁵²MnCl₂ and ²⁰³HgCl₂. The metals in form of chloride salts as well as the metals excreted via bile were given to control or acceptor rats in the same dose intraduodenally. In manganese, given as ⁵²MnCl₂ 15.04±8.48%, whereas given biliary excreted ⁵²Mn 35.45±5.72% was absorbed. Biliary excreted manganese is probably in the bile in form suitable for intestinal absorption. In both other metals the intestinal absorption was higher when metal in form of chloride salt was administered (in ⁶⁴Cu 46.45±11.46% respectively 16.74±8.53%; in ²⁰³Hg 40.9±8.52% respectively 21.08±10.7%).A possibility of treatment of metal's intoxication by influencing of enterohepatic circulation of metals is shortly discusses.     

Inhibition of heterolysosome formation and function in mouse kidneys by injection of mercuric chloride

Intravenous or intraperitoneal injections of mercuric chloride (5 mg Hg/kg) into mice resulted in an inhibition of proteolytic activity in isolated kidney heterolysosomes containing intravenously injected denatured (formaldehyde) ¹²⁵I-albumin but not in these particles from the liver. The inhibition occurred if the mercuric chloride was injected up to about 17 hr before injection of labeled protein. The proportion of particle-bound radioactivity which could be released by osmotic shock was substantially decreased in subcellular suspensions from mercury-injected mice. In some experiments therefore, digestive rates were normal in mercury-injected mice if proteolysis was measured in terms of the osmotically releasable radioactivity rather than in terms of the total particle-bound material. This suggest that mercury inhibited either endocytosis of labeled protein or heterolysosome formation. However, in most experiments in which digestion was measured in the presence and absence of mercaptoethanol, stimulation of proteolysis by mercaptoethanol was significantly greater in heterolysosomes from mercury-injected animals than in the controls. This suggests that mercury affected proteolytic activity within the organelles as well as heterolysosome formation.     

Brain,Kidney and Liver 203Hg-Methyl Mercury Uptake in the Rat: Relationship to the Neutral Amino Acid Carrier

Abstract: To investigate the effect of L-neutral amino acids on tissue levels of methyl mercury in the adult animal, rats were infused into the external jugular vein with solutions containing a) 0.05 mM ²⁰³Hg-MeHgCl and saline, b) 0.05 mM ²⁰³Hg-MgHgCl-0.1 mM L-cysteine, c) 0.05 mM ²⁰³Hg-MeHgCl-0.1 mM L-cysteine-0.1 mM L-methionine, d) 0.05 mM ²⁰³Hg-MeHgCl-0.1 mM L-leucine, or e) 0.05 mM ²⁰³Hg-MeHgCl-0.1 mM L-cysteine-0.1 mM L-leucine. Groups of animals were sacrificed at 3 min. 7 hr, and 96 hr. Brain, kidney, and liver ²⁰³Hg radioactivity was measured by means of gamma-scintillation spectrometry. Brain ²⁰³Hg concentrations L-cysteine treated animals were significantly higher compared with saline treated animals (P<0.05) at 3 min., 7 hr and 96 hr. The coinjection or coinfusion of methyl mercury with L-cysteine and L-methionine abolished the L-cysteine-mediated brain ²⁰³Hg uptake (P<0.05), at each sacrifice time. Kidney and liver ²⁰³Hg concentrations were not significantly different in any of the treatment groups compared with controls, irrespective of the sacrifice time. Furthermore, the percentage of diffusible ²⁰³Hg (non-protein bound) at each sacrifice time was not statistically different irrespective of the treatment assigned. These results suggest that methyl mercury L-cysteine conjugates in the plasma may share a common transport step with the L-neutral amino acid carrier transport system and indicate the presence in brain capillaries of a transport system capable of selectively mediating methyl mercury uptake across the capillary endothelial cell membrane.     

Lactational exposure to methylmercury in the hamster

 Syrian Golden hamster dams were administered ²⁰³Hg-labelled methyl mercury (MeHg; 1.6 μmol/kg) 1 day after parturition and milk was collected twice during the 1st week. The excretion of ²⁰³Hg in milk and the uptake, retention and tissue distribution of ²⁰³Hg in the pups was studied using gamma counting. The fraction of inorganic Hg in milk and in the kidneys of the pups was determined following separation of inorganic Hg and MeHg by ion exchange chromatography. The concentration of ²⁰³Hg in milk on the 1st day after MeHg administration was 0.12 nmol/g. ²⁰³Hg was mainly (80–90%) excreted as MeHg during the first 6 days of lactation. The whole body and tissue concentration of ²⁰³Hg in the pups increased for 10–15 days and decreased thereafter. The content of ²⁰³Hg in the pelt and the fraction of inorganic Hg in the kidney increased throughout the study period (4 weeks). The excretion of MeHg in milk corresponded to at least 5% of the dose administered to the dam. Our study demonstrates that breast milk may be a significant source of MeHg exposure during the critical neonatal period. Received: 28 June 1994 / Accepted: 24 October 1994     

Effects of dietary lipids on whole-body retention and organ distribution of organic and inorganic mercury in mice.

The effect has been investigated of dietary lipids on the whole-body retention and organ distribution of organic and inorganic mercury in mice. A single oral dose of methylmercury chloride or mercuric chloride labelled with 203Hg was given to female NMRI mice fed semi-synthetic diets containing varying amounts (5, 10, 20 or 50%) of energy derived from lipid (coconut oil, soya oil, or cod liver oil). The whole-body retention and relative organ distribution of mercury depended on diet composition. Thus, a significant reduction of the whole-body retention of mercury was seen in mice fed a diet containing 50% cod liver oil compared with mice fed a diet containing 50% coconut oil. After oral administration of mercuric chloride the relative deposition of mercury in the kidneys increased while that in the liver decreased with increasing concentrations of soya oil or coconut oil in the diet. The whole-body retention of mercury after treatment with methylmercury chloride was significantly decreased in mice fed cod liver oil compared with mice fed coconut oil; there was no difference between mice fed cod liver oil and those fed soya oil. The relative disposition of mercury was significantly higher in all organs of mice fed a diet containing 20% energy from cod liver oil compared with mice fed a diet containing 20% energy from soya oil. The present study demonstrates that diet composition is of major importance to the toxicokinetics of methylmercury and mercuric mercury.     

The Importance of Organ Blood Mercury when Comparing Foetal and Maternal Rat Organ Distribution of Mercury after Methyl Mercury Exposure

Abstract Foetal rat brain has previously been shown to contain twice as much mercury as maternal brain, after methyl mercury injection in the mother rat. However when brain mercury is corrected for the mercury which is present in the blood of the brain, foetal rat brain will contain 4 to 5 times as much mercury as maternal brain (depending on the stage of gestation), 24 hours after methyl mercuric chloride injection in the mother. Even when methyl mercuric chloride was injected in the mother about 14 days before term, near-term foetal brain contains 1.4 times as much mercury as the maternal brain. Likewise when corrected for mercury in the blood of the organ, foetal rat liver contains from 2.0 to 2.6 times more mercury than the maternal liver, and the foetal kidney contains from 13 to 23 times less mercury than the maternal kidney. The amount of mercury in foetal blood is about 65 % of the mercury in maternal blood 24 hours after methyl mercuric chloride injection in the mother, but maternal and foetal blood contain equal amounts 14 days after the injection. Except for the foetal membranes, no inorganic mercury released by biotransformation of methyl mercuric chloride was detected in the foetal-placental unit.     

Effect of spironolactone on the distribution of mercury.

The distribution and biliary excretion of ²⁰³HgCl₂ (0.3 mg Hg/kg) iv was measured in rats treated with spironolactone (SP, 75 mg/kg, ip) for various time intervals. SP had its greatest effect when administered as a single dose 15 min before HgCl₂. SP decreased the concentration of ²⁰³Hg in the plasma from 1.5 to 0.05 μg/ml, while it increased the blood concentration from 1.5 to 5 μg/ml. This treatment increased the content of Hg in the lung 12, heart 6, spleen 3, brain 3, muscle 2, stomach 1.7, and liver 1.5 times control, had no effect on the concentration of ²⁰³Hg in the intestine, bone, and testes, and markedly decreased the amount in the kidney to 10% of controls. Biliary excretion of Hg was not increased. When SP was administered 90 min or 3 hr before administration of the ²⁰³HgCl₂, qualitatively similar but less dramatic effects on the distribution of Hg were obtained. SP administered 15 min after HgCl₂ administration had a similar effect on the distribution of Hg as when administered 30 min before HgCl₂, with the exception that the concentration of Hg in the kidney was not decreased. The two major metabolic products of SP, canrenone and thioacetic acid, were also given to determine their effect on Hg distribution. Canrenone had no effect while thioacetic acid produced an effect similar to that produced by SP. It appears that the alteration in the distribution of Hg after SP treatment is due to the sulfur portion of the molecule. It seems likely that the sulfur moiety complexes the Hg; this complex distributes in the body similar to organic mercurial compounds, which in comparison to inorganic mercurials, reach a lower concentration in the plasma and kidney and a higher concentration in the blood and other tissues. The decrease in the concentration of Hg in the kidney produced by SP is probably responsible for the decreased toxicity of Hg after SP treatment.