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.     

Combined Oral Treatment with racemic and meso-2,3-Dimercaptosuccinic Acid for Removal of Mercury in Rats

Abstract: Racemic dimercaptosuccinic acid (DMSA) was found more efficient than the meso-isoform in enhancing the removal of mercury in rats. However. racemic-DMSA has recently been found more toxic. The efficiency of combined oral treatment with the two isoforms of DMSA for removal of mercury has now been evaluated. Female albino rats were treated orally for four days with meso- (M) and/or racemic- (R) DMSA (1 mmol/kg each), five days after a single intraperitoneal administration of ²⁰³Hg with 0.5 mg HgCl₂/kg. The animals were divided into six groups according to the number of treatments with each isomer: control (untreated), 4M, 1R + 3M, 2R + 2M, 3R+1M, and 4R. Whole body, kidney, liver and brain mercury contents were measured nine days after ²⁰³Hg administration. In all treated groups retention in the whole body and kidneys was greatly reduced. The groups treated with racemic-DMSA, regardless of the number of doses, showed a greater removal of mercury than the group treated with meso-DMSA alone (4M). All treatments were less efficient in reducing liver retention, and the brain retention was not affected. It was concluded that even a single application of the more toxic racemic-DMSA during a four-day oral treatment regimen is sufficient to improve the removal by meso-DMSA of mercury from rats.     

Effect of four thiol-containing chelators on disposition of orally administered mercuric chloride.

Acute toxicity and the disposition of inorganic mercury depends on the route of exposure. Most previous studies on effect of chelators on inorganic mercury toxicity and toxicokinetics employed parenteral administration of both metal and chelator. However, the most prominent routes for human inorganic mercury exposure are the oral or pulmonary. BAL was previously considered the drug of choice in human intoxications with most heavy metals. This recommendation has been questioned during recent years due to the advent of the less toxic hydrophilic BAL analogues DMSA and DMPS. The present study, using oral administration of HgCl2 labelled with 203Hg, demonstrates that DMPS is superior to the other chelators in preventing mortality. Moreover, both DMSA and DMPS are superior to BAL and NAPA in alleviating acute toxicity and in preventing the undesirable distribution of orally administered mercury, especially to the brain. Further, oral administration of these chelators were more efficient than parenteral administration in reducing whole-body retention and organ deposition of orally administered mercuric chloride, most likely due to the prevention of intestinal uptake of mercury.     

More data on mercury absorption in relation to dietary treatment in rats

The kinetics of mercury (Hg) absorption in relation to diet by determining whole body (WB), carcass (C) and gut (G) retention in control and milk-fed rats 6, 9, 12 and 15 days after oral administration of ²⁰³Hg have been studied. All retention values were higher in the milk-fed than in control rats during the experimental period. The higher WB retention in the milk-fed animals was primarily due to increased G retention especially at shorter time intervals. Animals on the milk diet had in the C, higher retention values, and in the G, higher retention and longer residence time. There was no evidence that Hg from the gut compartment entered into other parts of the body within the observation period. More evidence is needed about the effect of other dietary treatments on Hg metabolism.     

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     

The effect of selenium on the brain uptake of methylmercury

Twenty-four h after the subcutaneous administration of 0.5 moles selenite labelled with ⁷⁵Se to rats of 200 g body weight, the retention of selenium at the injection site was significantly increased by the presence of equimolar amounts of methylmercury in the injection solution. The retention of Me²⁰³HgCl was not affected by the presence of selenite. The most significant shift caused by interaction was a decrease in the blood content and an increase in the brain content of ²⁰³Hg. The brain content of ⁷⁵Se was also increased to a lesser extent. The shift in the distribution — which was the same whether the two metals were injected at the same site or separately — continuously decreased from 6–48 h. The same interaction pattern was observed when methylmercury and selenite were administered by gastric gavage and differences in distribution increased when the dose was increased from 1.25 moles/kg to 2.5 moles/kg. The increase in the brain content of mercury caused by selenite was not restricted to simultaneous administration and occurred when selenite was given 2–7 days after methylmercury.Supported partly by International Atomic Energy Agency Grant Number 1530/RB     

The influence of age on the efficiency of delayed therapy with Ca-DTPA for cerium in rats

The influence of age on the effectiveness of chelation therapy starting 24 h after cerium administration was studied in 2- and 6-week-old rats. ¹⁴¹Ce was administered IP, followed after 24 and 48 h by IP administration of trisodium calcium diethylenetriaminepentaacetate (Ca-DTPA). The whole body and organ retention of ¹⁴¹Ce was determined 6 days after its administration. The chelation therapy significantly reduced cerium retention in both age groups but was more efficient in older animals. This age-related effect was, however, less pronounced than after immediate treatment with DTPA observed in our previous experiments, indicating that age as one of the factors which influence the efficacy of chelation treatment is probably more important in conditions of early than in conditions of delayed therapy.     

Simultaneous administration of sodium selenite and mercuric chloride decreases efficacy of DMSA and DMPS in mercury elimination in rats

Two chelating agents meso-2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercapto-propane-1-sulphonate (DMPS) were tested for their efficiency in mercury removal from the body of rats in the presence and in the absence of selenium. Female Wistar rats were given a single intraperitoneal injection of mercuric chloride or an equimolar mixture of mercuric chloride and sodium selenite (1.5 micromol/kg body weight). The chelating agents were given orally, in excess (500 micromol DMSA/kg body weight; 300 micromol DMPS/kg body weight), 30 min after the administration of mercury and selenium. The animals were euthanized 24 h after the treatment and mercury in the kidney, liver, and 24 h urine was determined using cold vapour atomic absorption spectrometry (CV-AAS). The simultaneous administration of mercuric chloride and sodium selenite led to a redistribution of mercury in the organs, so that accumulation of mercury in the kidneys was decreased and in the liver increased. Selenite also caused decrease in the level of urinary mercury excretion. Both chelating agents were effective in mercury removal from the body, by increasing its urinary excretion. However, when animals were simultaneously treated with mercury and selenite, the rise of mercury excreted in the urine due to the treatment with chelating agents was lower when compared to animals receiving mercury without selenite. It is concluded that sodium selenite decreases the efficiency of DMSA and DMPS in mercury removal from the body of rats.     

Effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on tissue and urine mercury levels following prolonged methylmercury exposure in rats.

Methylmercury, a potent neurotoxicant, accumulates in the brain as well as the kidney during chronic exposure. We evaluated the capacity of 2,3-dimercapto-1-propanesulfonic acid (DMPS), a tissue-permeable metal chelator, to reduce brain, kidney, and blood Hg levels and to promote Hg elimination in urine following exposure of F-344 rats to methylmercury hydroxide (MMH) (10 ppm) in drinking water for up to 9 weeks. Inorganic (Hg2+) and organic (CH3Hg+) mercury species in urine and tissues were assayed by cold vapor atomic fluorescence spectroscopy (CVAFS). Following MMH treatment for 9 weeks, Hg2+ and CH3Hg+ concentrations were 0.28 and 4.80 microg/g in the brain and 51.5 and 42.2 microg/g in the kidney, respectively. Twenty-four hours after ip administration of a single DMPS injection (100 mg/kg), kidney Hg2+ and CH3Hg+ declined 38% and 59%, whereas brain mercury levels were slightly increased, attributable entirely to the CH3Hg+ fraction. Concomitantly, Hg2+ and CH3Hg+ in urine increased by 7.2- and 28.3-fold, respectively, compared with prechelation values. A higher dose of DMPS (200 mg/kg) was no more effective than 100 mg/kg in promoting mercury excretion. In contrast, consecutive DMPS injections (100 mg/kg) given at 72-h intervals significantly decreased total mercury concentrations in kidney, brain, and blood. However, the decrease in brain and blood mercury content was restricted entirely to the CH3Hg+ fraction, consistent with the slow dealkylation rate of MMH in these tissues. Mass balance calculations showed that the total amount of mercury excreted in the urine following successive DMPS injections corresponds quantitatively to the total amount of mercury removed from the kidney, brain, and blood of MMH-exposed rats. These findings confirm the efficacy of consecutive DMPS treatments in decreasing mercury concentrations in target tissue and in reducing overall mercury body burden. They demonstrate further that the capacity of DMPS to deplete tissue Hg2+ is highly tissue-specific and reflects the relative capacity of the tissue for methylmercury dealkylation. In light of this observation, the inability of DMPS to reduce Hg2+ levels in brain or blood may explain the inefficacy of DMPS and similar chelating agents in the remediation of neurotoxicity associated with prolonged MMH exposure.     

Transplacental and Lactational Exposure to Mercury in Hamster Pups after Maternal Administration of Methyl Mercury in Late Gestation

Abstract: Pregnant Syrian golden hamsters were given a single oral dose of ²⁰³Hg-labelled methyl mercury (MeHg), 1.6 μmol/kg body weight, on day 12 of gestation. The uptake, retention and tissue distribution of ²⁰³Hg in the dams and pups was studied by γ-counting during the following three weeks. The average transplacental transfer of ²⁰³Hg was 1.1% of the administered dose per pup, corresponding to 11% of the administered dose to a whole litter. This was considerably more than in our previous studies when the dams were treated on gestational day 2 (1.3%) or 9 (4.6%). The amount of ²⁰³Hg transferred to each pup in utero was independent of the litter size. The average additional transfer of ²⁰³Hg to a litter via milk was 1.7% of the administered dose. In the pups, the content of ²⁰³Hg in the liver and brain decreased, while the content in the kidneys and pelt increased during the second and third week. The highest amount of ²⁰³Hg was generally found in the pelt, which indicated that unweaned hamster pups primarily excrete MeHg by binding to hair. The chemical form of mercury in the liver and kidneys of the pups was determined by ion-exchange separation of inorganic Hg and MeHg followed by γ-counting. The amount of inorganic Hg in the liver of the pups remained constant throughout the experiment, while it increased in the kidneys after one week due to the demethylation of MeHg. The inorganic Hg in the liver of newborn pups was probably due to maternal demethylation of MeHg and transplacental transfer of inorganic Hg. This hypothesis was supported by the observed transplacental transfer of inorganic Hg in pregnant dams administered ²⁰³HgCl₂ on day 12 of gestation.     

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.     

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.     

Effects of age and sex on retention of mercury by methyl mercury-treated rats

Male and female Long Evans rats 7, 15, 20, 24, or 56 days old received a single subcutaneous injection of 1 μmol of methyl mercury-203/kg and the whole body retention of radiomercury was determined for up to 139 days thereafter. For rats dosed at 7 or 15 days of age, whole body clearance of mercury was extremely slow until animals reached 17 to 18 days of age. Subsequent excretion was monoexponential in the 7-day-old group and biexponential in the 15-day-old group. For rats dosed at 20, 24, or 56 days of age, onset of excretion was immediate and the pattern of clearance was biexponential. In rats dosed at 56 days of age, the retention of mercury by the average male and average female was significantly different (p = 0.001). No sexual difference in the estimate of whole body retention of mercury was seen in the other age groups. The presence of an interval of very slow excretion of mercury in young rats and the subsequent slower excretion of mercury in these animals than in rats dosed with methyl mercury later in life suggest that increased hazards of methyl mercury exposure in early life may be related to increased retention of the organomercurial or inorganic Hg.     

Biliary excretion of mercury compounds.

The disappearance of ²⁰³Hg from the plasma of rats and its excretion into bile was quantitated for 2 hr after the iv administration of 0.03, 0.1, 0.3, 1.0, and 3.0 mg Hg/kg as ²⁰³mercuric chloride. The concentration of ²⁰³Hg in the bile was usually about 0.66 that in the plasma. The concentration of ²⁰³Hg in the liver was 1.8–3.4 times higher than that in the plasma, and the bile concentration was about three times lower than that in the plasma. Methyl mercuric chloride was given to rats at dosages of 0.1, 0.3, 1.0, and 3.0 mg Hg/kg, iv. The concentration of ²⁰³Hg in bile averaged about nine times higher than that in the plasma, the liver concentration was about 25-fold higher than that in the plasma and the bile concentration about 0.33 that in the liver. Thus the radioactivity associated with either mercuric chloride or methyl mercury were not highly concentrated in bile as are some other heavy metals. Over a 2-hr period, regardless of the dose or the form of Hg administered, less than 0.5% of the dose was excreted into the bile. The effect of 4 days pretreatment with phenobarbital, spironolactone, pregnenolone-16-carbonitrile (PCN), and 3-methylcholanthrene on the biliary excretion of mercuric chloride and methyl mercury was also measured. PCN was the most effective, doubling the amount of ²⁰³Hg excreted into the bile.     

Effect of glutathione depletion on tissue deposition of methylmercury in rats.

Diethylmaleate and other compounds capable of being metabolized to mercapturic acid derivatives were administered to rats in order to deplete tissue stores of glutathione (GSH). Deposition of mercury was significantly decreased in kidney and erythrocytes of depleted animals when [²⁰³Hg]methylmercuric chloride was administered during the period of maximal depletion of GSH. Increasing doses of diethylmaleate resulted in steadily decreasing GSH concentrations in brain, kidney, erythrocytes, and liver which were accompanied by decreases in mercury deposition in kidney and brain. Increasing the time interval between diethylmaleate and subsequent methylmercury administration resulted in correspondingly greater concentrations of mercury in kidney that were associated with recovery of renal GSH concentrations. Disodium maleate was also effective in lowering GSH values and reducing mercury deposition in kidney and erythrocytes. A second dose of disodium maleate, administered 24 hr after the first, was less effective than the first in depleting renal GSH and reducing mercury deposition. However, a second dose of diethylmaleate was equally as effective as the first. A high degree of correlation (r = 0.85) was found between renal mercury accumulation and renal GSH concentration when data from all depletion experiments were considered. The results suggest that renal GSH may be a determinant in the deposition of mercury in the kidney.     

Organ clearance of 75SeO3(2-) and 203HgCl2 administered separately and simultaneously to mice

A study on organ clearance of mercury (²⁰³HgCl₂) and selenium (⁷⁵SeO₃^2?) given separately or simultaneously in single doses by intraperitoneal injections to mice has been performed. The simultaneous administrations are handled in molar ratios (Hg/Se) less, than equal to or greater than one. Liver, kidneys, spleen and blood contain most of the mercury and selenium, administered, while heart, lungs, skin, muscle and brain only contain small amounts. Both elements are retained to a higher degree in especially kidneys, liver, spleen and blood when co-administered than when administered alone. In kidneys, clearance rate of selenium is found to be independent of mercury administration, with an effective halflife 11.2–13.5 days in accordance with the whole elimination. The clearance of mercury is, however, strongly dependent on coadministered selenium. At low molar ration (Hg/Se ? 1) of administered doses clearance rate is identical to that of selenium, compared to an effective halflife when administered alone. In liver the effective halflife of selenium when administered alone or coadministered with mercury (Hg/Se ratio < 1) is found identical to that of kidneys: 11.2–12.5 days. At increasing molar ratios retention of selenium increases and clearance rate decreases. A marked decrease in mercury clearance from liver is induced by simultaneously administered selenium. The effective halflife becoming extremely administered selenium. The effective halflife becoming extremely long and under certain conditions even an accumulation is found to take place. Concordant relations are found for liver and spleen.Selenium in blood is only affected to a minor degree by mercury. Clearance rate for mercury is decreased by selenium. At a molar ratio between doses (Hg/Se) ? 1 clearance rate is approximately identical to that of selenium. It is indicated that selenium metabolism is quantitatively rather than qualitatively influenced by mercury as mercury administration provokes a higher retention of a given dose of selenium while clearance rate in kidneys and blood is only influenced by high molar ratios (Hg/Se). Contrary to selenium, mercury metabolism is altered both qualitatively and quantitatively as retention as well as clearance rate are influenced by selenium in all organs and in all molar ratios given in kidneys and blood. It is assumed that at least 2 mechanisms exist in the metabolic pathways of mercury: (1) binding to metallothionein; and (2) binding to selenium containing metabolic compounds. As selenium induced an increase in mercury retention it is questioned whether selenium is beneficial in case of chroniic exposure to inorganic mercury. It also implies the question of bioavailability of selenium in animal food items.     

Antidotes for zinc intoxication in mice

Sixteen chelating agents were examined to determine their relative efficacy as antidotes in acute zinc acetate intoxication in mice after i.p. administration. For a i. p. dose of 0.49 mmol/kg (LD₅₀) of zinc acetate, the i. p. administration of chelating agents at a 21 and 51 mole ratio resulted in a significant antidotal action for EDTA, DTPA, CDTA, d-penicillamine (d-PA), DMPS and DMSA. EGTA, l-cysteine, triethylentetraamine (TTHA), N-acetylcysteine (NAC), 4,5-dihydroxi-1,3-benzenedisulfonic acid (Tiron), sodium salicylate, glutathione, sodium diethyldithiocarbamate (DDC), 6-mercaptopurine and N-acetyl-d, l-penicillamine (NAPA) were not effective for acute zinc acetate poisoning. The therapeutic indices and therapeutic effectiveness of the most effective chelators were, respectively: EDTA (5.0, 7.0), DTPA (7.3, 13.7), CDTA (8.6, 6.3), d-PA (4.6, 1.9), DMPS (1.3, 1.0), DMSA (3.2, 5.4). DTPA, CDTA, and EDTA appear to be the most effective agents of those tested in offsetting acute zinc intoxication in mice.     

The whole body retention and tissue distribution of [203Hg]methylmercury in adult cats.

To assess the whole body retention and tissue distribution of methylmercury six adult female random-bred cats were given a single oral dose of 78 μg (55 μCi) of [²⁰³Hg]methylmercury chloride. ²⁰³Hg in the whole body of the cats and in feces and urine were monitored for 156 days. Samples of hair collected throughout the experiment were used to correct the whole body radioactivity measurements for the mercury contained in the hair and to adjust the whole body retention for the amount of mercury contained in the hair. Tissue distribution of ²⁰³Hg was measured 156 days postdosing. The ability of various tissues to concentrate methylmercury was expressed as a concentration factor [CF = (specific activity of a tissue at a time t)/(specific activity of the whole cat at time t)]. The whole body half-period of methylmercury after a single oral dose of [²⁰³Hg]methylmercury to cats was 117.7 ± (SE) 1.4 days including the hair and 76.2 ± 1.6 days excluding the hair. The half-period of appearance of methylmercury in hair, feces and urine were 69 ± 5, 68 ± 5, and 78 ± 4 days, respectively. The percentage of the total dose of methylmercury remaining in the cats after 156 days were 35.9 ± 3.3%. Hair showed the highest CF (30.2 ± 2.6) followed by liver (12.4 ± 1.0), gall-bladder (2.3 ± 0.5), and kidney (2.0 ± 0.1). Muscle, lymph nodes, hide, and adrenal gland had CF values of approximately 1. The CF for various brain areas ranged between 0.48 and 0.60.     

Mercury-selenium interaction: distribution and excretion of 203Hg2+ in rats after simultaneous administration of selenite or selenate

In female rats intravenously injected with 203HgCl2 (0.6 mg Hg2+ per kg body wt.) the effect of intraperitoneal administration of selenite or selenate (0.525 mg Se per kg body wt.) on distribution and excretion of 203Hg was studied. The content of 203Hg was lower in kidney and higher in liver and blood in the groups treated with selenate or selenite when compared with rats which received only mercury. The brain content of 203Hg was significantly increased in rats injected with selenite. Both selenium compounds injected immediately after mercury significantly decreased urinary as well as biliary excretion of 203Hg. A transient increase in the rate of biliary excretion of 203Hg during the first 2 h after administration was observed in rats treated with selenate. This finding seems to support the idea that the reduction of selenate to selenite in the body is not rapid but takes at least several hours.     

The influence of administered mass on the subcellular distribution and binding of mercury in rat liver and kidney

The influence of the administered mass on the tissue and sub-cellular distribution of mercury (Hg) was investigated in rats, using ²⁰³Hg. The fraction of the dose deposited in liver increased threefold over the dose range 0.17–1.65 mg Hg · kg^–1, while the retention in the kidney decreased by a factor of 2. The uptake in other organs, lung, spleen, brain, thymus, salivary glands showed no dose-dependent variation.Subcellular fractionation studies showed a dose-dependent increase in the Hg content of the liver cytosol, with corresponding decreases in the deposition in the lysosomal and nuclei-cell debris fractions. In contrast, no clear changes in the distribution of Hg amongst the subcellular organelles of the kidney were observed.The amount of Hg bound to metallothionein in the liver cytosol rose steeply with increasing dose. However, in the kidney cytosol the mass of Hg bound to metallothionein increased with dose up to 0.55 mg Hg · kg^–1, thereafter remaining approximately constant. These observations suggest that the Hg-binding metallothionein in the kidney was saturated by administered doses greater than 0.55 mg Hg · kg^–1, whereas in liver saturation levels of the metal were not reached even at the highest dose tested, 1.65 mg Hg · kg^–1.