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.     

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     

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.     

Accumulation and tissue distribution of mercury in the guinea pig during subacute administration of methyl mercury

Female guinea pigs were dosed po daily for 71 days with 0.4, 4, 40, or 400 μg Hg/kg given as radiolabeled methyl mercuric chloride. The accumulation of total mercury was followed in 10 tissues at 6 time intervals. After dosing ceased, the decay profiles of mercury were followed for an additional 35 days. The accumulation pattern for mercury was similar for each dose level, and the tissue mercury concentration on day 71 increased in the following order: blood < cerebellum < hypothalamus < calcarine cortex < frontal lobe < occipital lobe < caudate nucleus < muscle < liver < kidney. Mercury accumulation in all tissues, except kidney at the 4-, 40-, and 400-μg/kg dose levels, approached steady-state values in the 35–71 -day dosing period. The accumulation curves could be fitted by an exponential equation incorporating the mercury half-life obtained from the decay profiles. As the dose level increased, tissue mercury concentrations increased to a greater extent than anticipated. Although doses increased 1000-fold from 0.4 to 400 μg Hg/kg, kidney concentrations increased 3300-fold after 71 days of dosing. At this time, inorganic mercury (Hg²⁺) comprised 42% of the total kidney mercury and 5% of the total liver mercury at the 400 μg/kg dose.Clinical signs of methyl mercury intoxication were induced in guinea pigs after dosing daily for 9 days at 5 mg Hg/kg. The activities of 6 enzymes were monitored and cholinesterase (serum), choline acetylase (caudate nucleus) and carboxylesterase (liver) were significantly lower than control values. The total mercury concentration in whole brain was 28 μg/g (wet weight). Animals dosed at 400 μg Hg/kg for 71 days showed no decrease in the activities of the selected enzymes, there was no change in weight gain when compared to the control and there were no signs of methyl mercury toxicity. The highest brain mercury concentration after 71 days dosing was 11 μg/g (wet weight) in the caudate nucleus.     

Effect of Methyl Mercury Exposure on the Uptake of Radiolabeled Inorganic Mercury in the Brain of Rabbits

Exposure to mercuric compounds at high dose levels has previously been shown to alter the integrity and function of the blood-brain barrier in laboratory animals. In the present study, we have investigated the distribution of intravenously administered inorganic ²⁰³Hg in rabbits additionally exposed to MeHg. A single dose of ²⁰³HgCl₂ was administered together with or 5 min. or 24 hr after administration of a single dose (10 or 37.5 μmol/kg b.wt.) of MeHg. In another experiment, ²⁰³HgCl₂ was administered to rabbits subchronically exposed to MeHg (1 μmol/kg b.wt. daily for three weeks) 24 hr after cessation of treatment. The integrity of the blood-brain barrier was assayed by measuring the uptake of ²⁰³Hg in the brain, as the blood-brain barrier usually serves to exclude inorganic Hg from the brain. The concentration of ²⁰³Hg within the brain was similar in all MeHg-treated rabbits, corresponding to 0.02% of the administered dose, and not different from that of control animals. Under these conditions, no obvious damage to the blood-brain barrier by MeHg could be observed.     

Induction by mercury compounds of brain metallothionein in rats: Hg0 exposure induces long-lived brain metallothionein

Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to␣most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 μmol/kg per day × 5 days, p.o.) showed brain Hg levels as high as 18 μg/g with slight neurological signs 10␣days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7–8 μg Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for >2␣weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT. Received: 25 June 1997 / Accepted: 4 November 1997     

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.     

Time-dependent tissue/organ uptake and distribution of 203Hg in mice exposed to multiple sublethal doses of methyl mercury.

Swiss-Webster mice were injected intraperitoneally with one to ten doses (2.5 mg Hg/kg) of ²⁰³Hg-labeled methyl mercury. Doses were administered at 72-hr intervals. Maximal tissue/organ Hg uptake usually occurred 72 hr postinjection and was monitored at 3 and 6 days by gamma scintillation spectrometry. Most tissues/organs required five to six doses to attain maximal Hg concentrations (the carcass required seven doses; hair and fat, eight doses; lens, nine doses). Data for hair were highly variable. Except for hair (which required seven to eight doses), maximal tissue/organ concentration factors (CF) were reached 72 hr after the first dose. Kidney, liver, and hair attained CF values > 1. Except for hair, all CF values decreased with increasing dose number. Initial rates of decrease were much greater for kidney, blood, spleen, muscle, and liver than lens, brain, and fat. Only hair exhibited a significantly higher Hg concentration at 6 days after each dose than at 3 days. With increasing dose number, blood Hg; tissue/organ Hg ratios remained relatively constant for liver, kidney, spleen, and muscle; decreased for lens and brain; and decreased for hair and fat after an initial increase.     

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 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.     

Distribution and chemical form of mercury in commercial fish tissues

We analyzed total Hg concentrations in various tissue samples obtained from 7 commercially available fish species. MeHg contents were also estimated for muscle and liver samples by a selective analysis of inorganic Hg. Among the tissues, high Hg accumulations were shown in liver, muscle, heart and spleen throughout all fish species. Carnivorous fish, such as scorpion fish, sea bream and Japanese whiting, tended to show higher Hg accumulations in the muscle, with the highest Hg levels being shown by scorpion fish. Although the liver was expected to show the highest Hg accumulations among tissues throughout all fish species, the highest accumulation in the liver was observed only in scorpion fish. In contrast, the muscle level was significantly higher than the liver in Pacific saury and Japanese whiting. MeHg accumulated in fish is considered to show a sustained increase throughout the life of the fish, due to its long biological half-life. In fact, in the present study, muscle Hg levels in Japanese whiting, Japanese flying fish, and halfbeak showed good correlations with body weights. However, such correlations were not clear in scorpion fish, sea bream, Jack mackerel and Pacific saury. Selective analyses of inorganic Hg levels revealed that most of the Hg (> 95%) in fish muscle existed as MeHg, while the rates of MeHg contents in the liver varied from 56% in scorpion fish to 84% in Jack mackerel. As a result, fish muscle showed the highest MeHg accumulations in all fish species examined. These results suggest that reliable information on total Hg contents in fish muscle might be sufficient to avoid the risk of MeHg exposure caused by eating fish, even when one consumes other tissues such as fish liver.     

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.     

Methyl mercury uptake across bovine brain capillary endothelial cells in vitro: the role of amino acids

Previous studies in the rat in vivo have demonstrated that co-injection of methyl mercury (MeHg) with L-cysteine into the common carotid artery enhances brain Hg levels following a single capillary pass through the CNS vasculature. In order to elucidate the relationship between MeHg transport and the neutral amino acid transport carrier system, regulatory aspects of MeHg transport across the bovine blood-brain barrier were investigated in isolated brain microvessel preparations. Following 1 hour co-incubations of 203Hg-MeHgCl with 0.1 mM L-cysteine at 37 degrees, 203Hg uptake by suspended microvessels was significantly increased (P less than 0.05) compared with controls. This enhanced capillary uptake of 203Hg was abolished by co-incubations of microvessels with 0.1 mM L-cysteine-L-methionine, or 0.1 mM L-cysteine plus AT-125 (alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazolacetic acid), an irreversible inhibitor of gamma-glutamyl-transpeptidase. One hr co-incubations of bovine capillaries with 203Hg-MeHgCl and 0.1 mM D-cysteine at 37 degrees or 0.1 mM L-cysteine at 0 degrees did not increase rat of 203Hg uptake compare with controls. These results indicate that L-cysteine enhances the rate of capillary MeHg uptake. The accumulation of 203Hg in the bovine microvessels appears to be a carrier-mediated process. It is inhibited by L-methionine, a competitive substrate for neutral amino acid transport, and by AT-125. Capillary uptake of 203Hg is stereospecific to the L-enantiomorph of cysteine, suggesting selective uptake of MeHg across the blold-brain barrier. The data emphasize the relationship between the L-enantiomorph neutral amino acid carrier system and MeHg transport across the capillaries.     

Induction by mercury compounds of metallothioneins in mouse tissues: inorganic mercury accumulation is not a dominant factor for metallothionein induction in the liver

Among the naturally occurring three mercury species, metallic mercury (Hg(0)), inorganic mercury (Hg(II)) and methylmercury (MeHg), Hg(II) is well documented to induce metallothionein (MT) in tissues of injected animals. Although Hg(0) and MeHg are considered to be inert in terms of directly inducing MT, MT can be induced by them after in vivo conversion to Hg(II) in an animal body. In the present study we examined accumulations of inorganic mercury and MT inductions in mouse tissues (brain, liver and kidney) up to 72 hr after treatment by one of three mercury compounds of sub-lethal doses. Exposure to mercury compounds caused significant mercury accumulations in mouse tissues examined, except for the Hg(II)-treated mouse brain. Although MeHg caused the highest total mercury accumulation in all tissues among mercury compounds, the rates of inorganic mercury were less than 10% through the experimental period. MT inductions that depended on the inorganic mercury accumulation were observed in kidney and brain. However, MT induction in the liver could not be accounted for by the inorganic mercury accumulation, but by plasma IL6 levels, marked elevation of which was observed in Hg(II) or MeHg-treated mouse. The present study demonstrated that MT was induced in mouse tissues after each of three mercury compounds, Hg(0), Hg(II) and MeHg, but the induction processes were different among tissues. The induction would occur directly through accumulation of inorganic mercury in brain and kidney, whereas the hepatic MT might be induced secondarily through mercury-induced elevation in the plasma cytokines, rather than through mercury accumulation in the tissue.     

Toxicokinetics of methyl mercury in pigs

Toxicokinetics of methyl mercury were studied in pigs after intravenous (i.v.) administration of the compound. The distribution of methyl mercury was slow taking 3–4 days to be completed. Blood elimination half-life was found to be 25 days. The apparent volume of distribution was 9.8 l/kg indicating pronounced tissue accumulation of methyl mercury. Highest mercury levels were found in kidney and liver, with lower contents in muscle and brain and very little in adipose tissue. The results indicate that from organs like liver and kidney methyl mercury is eliminated much more slowly than from the blood. Over a period of 15 days 16% of the dose administered was excreted with faeces and 0.9% in the urine.     

Pharmacodynamics of methyl mercury in the rainbow trout (Salmo gairdneri): tissue uptake, distribution and excretion

The tissue distribution, rate of uptake and concentration of ²⁰³Hg-labeled methylmercury was investigated in 20 different tissues/organs over a period of 100 days following a single intragastric dose of 0.5 mg Hg/kg body weight. Mercury content was analyzed by gamma scintillation spectrometry. After 1 hr, mercury concentration factors >0.1 were detected in the blood, heart, liver, spleen and kidney (a concentration factor (CF) of 1.0 equals mercury concentration in dose). Highest mercury concentrations (CF > 7.0) were observed in the blood (at 7 days) and spleen (at 14 days). After 100 days, the CF of the blood was >2.0 and the CF values of the spleen, kidney and liver were >1.0. Maximum CF values were reached in the skeletal muscle, brain and lens after 34, 56 and >90 days, respectively. Maximum values were reached in most other tissues/organs at approximately 7 days. Skeletal muscle appeared to function as a reservoir for methyl mercury and accumulated 50% of the dose from 34 to 100 days post administration. Methyl mercury accumulation in the brain was limited to 0.1% of the dose. The rate of mercury excretion appeared to be biphasic as a result of a slow elimination from the skeletal muscle relative to the other tissues/organs. Employing both the slow and fast rate, the half-retention time for methyl mercury in rainbow trout was estimated to be >200 days.     

Enhanced elimination of tissue methylmercury in Parachlorella beijerinckii-fed mice

To investigate the influence of Chlorella (Parachlorella beijerinckii) on the excretion and tissue accumulation of methylmercury (MeHg), we orally administered 5 mg/kg of MeHg chloride (4 mg Hg/kg) to female C57BL/6N mice (aged 10 weeks). The mice were housed in metabolism cages to collect urine and feces for 3 weeks with diets containing 0%, 5%, or 10% P. beijerinckii powder (BP) in a basal diet (CE-2). The lowered blood Hg levels in the 5% and 10% BP groups became significant compared to those of the control group (0% BP) as early as day 7. During the 21 days of testing, significant increases in the cumulative Hg eliminations into urine (5% BP) and feces (5% and 10% BP) were found in the BP groups. Twenty-one days after administration, the organ Hg levels in both BP groups tended to decrease compared to that of the control group. The reduction of Hg levels in the kidney and brain were significant, whereas that in the liver was not. Although tissue Hg levels are known to be closely related to glutathione (GSH) metabolism, no difference was found in GSH levels in the blood or organs between the control group and the 10% BP group. These results suggest that continuous BP intake accelerates the excretion of MeHg and subsequently decreases tissue Hg levels in mice, with no alteration of GSH metabolism. We should conduct further research to elucidate details regarding the mechanism of BP-induced enhancement of MeHg excretion.     

Sex and strain differences of susceptibility to methylmercury toxicity in mice

Excretion and organ distribution of mercury and susceptibility to methylmercury (MeHg) toxicity were compared between strains and sexes after successive oral administration of MeHg chloride (5 mg/kg per day) using BALB/cA (C) and C57BL/6N (B6) mice. Every mouse died several days after initiation of toxic symptoms, and significant strain and sex differences were found with regard to length of survival. C mice of both sexes died earlier than B6 mice. B6 males survived much longer (greater than 6 weeks) than B6 females (3 weeks), whereas C males died earlier than C females. B6 male mice showed remarkably higher urinary Hg excretion and lower Hg levels in the brain, liver, kidney and blood than the other 3 groups. With daily MeHg administration, the Hg levels in all tissues except the kidney showed linear increase until the manifestation of toxic symptoms. Mercury accumulation in the kidney, the tissue with the greatest uptake of Hg in the mice examined herein, was biphasic: accumulation was rapid for 7-10 days after which the rate of increase was greatly reduced until death. It is suggested that conditions resulting in saturation of the rate of kidney Hg uptake might cause inhibition of urinary Hg excretion via some disturbance of renal function. Subsequently, Hg accumulation would be accelerated in various tissues, including the brain, leading to manifestation of toxic symptoms.     

Partitioning and kinetics of methylmercury among organs in captive mink (Neovison vison): A stable isotope tracer study

Despite the importance of methylmercury (MeHg) as a neurotoxin, we have relatively few good data on partitioning and kinetics of MeHg among organs, particularly across the blood–brain barrier, for mammals that consume large quantities of fish. The objective of this study was to determine the partition coefficients between blood and brain, liver and kidney and fur for MeHg under steady-state conditions and to measure the half-lives for MeHg in these organs. Captive mink (Neovison vison) were fed a diet enriched with two stable isotopes of Hg, Me¹⁹⁹Hg and Me²⁰¹Hg for a period of 60 days. After a period of 10 days the diet was changed to contain only Me²⁰¹Hg so that, between days 10 and 60, we were able to measure both uptake and elimination rates from blood, brain, liver kidney and fur. Liver and kidney response was very rapid, closely following changes in blood concentrations but there was a small lag time between peak blood concentrations and peak brain concentrations. Half-lives for MeHg were 15.4, 10.2 and 13.4 days for brain, liver and kidney, respectively. There was no measurable conversion of the MeHg to inorganic Hg (IHg) in the brain over the 60 day period, unlike in liver and kidney.     

Disposition of inhaled mercury vapor in pregnant rats: maternal toxicity and effects on developmental outcome.

The disposition and toxicity of inhaled elemental mercury (Hg0) vapor for pregnant Long-Evans rats, and potential adverse effects on reproductive outcome were investigated. Rats were exposed to 0, 1, 2, 4, or 8 mg Hg0/m(3) for 2 h/day from gestation day (GD) 6 through GD 15. Maternal toxicity occurred primarily in rats exposed to 4 and 8 mg/m(3) and was manifested as a concentration-related decrease in body weight gain and mild nephrotoxicity. Control rats gained about 13% of their initial body weight during the 10-day exposure. Rats exposed to 4 mg/m(3) Hg0 gained about 7% less than controls, and rats exposed to 8 mg/m(3) Hg0 lost about 17% of their initial body weight during the 10-day exposure period. Maternal kidney weights were significantly increased in the 4 and 8 mg/m(3) concentration groups, and urinalysis revealed increased levels of protein and alkaline phosphatase activity in urine of all Hg0-exposed rats. Dams exposed to 8 mg/m(3) were euthanized in moribund condition on postnatal day (PND) 1. There was no histopathological evidence of toxicity in maternal lung, liver, or kidney of exposed rats at GD 6, GD 15, or PND 1. The incidence of resorptions was significantly increased, litter size and PND 1 neonatal body weights were significantly decreased only in the 8-mg/m(3) group. Total Hg concentrations in maternal tissues increased with increasing number of exposure days and concentration. In general, approximately 70% of Hg was eliminated from maternal tissues during the week following the last exposure (GD 15 to PND 1). Elimination of Hg from maternal brain and kidney was slower than in other tissues, possibly due to higher levels of metallothionein. Total Hg concentrations in fetal tissues increased with increasing number of exposure days and concentration, demonstrating that a significant amount of Hg crossed the placenta. One week after the last exposure, significant amounts of Hg were still present in brain, liver, and kidney of PND 1 neonates. Metallothionein levels in neonatal tissues were not significantly increased by exposure to 4 mg/m(3) Hg0. The total amount of Hg in neonatal brain (ng/brain) continued to increase after termination of inhalation exposure, suggesting a redistribution of Hg from the dam to neonatal brain. These data demonstrate that inhaled Hg0 vapor is distributed to all maternal and fetal tissues in a dose-dependent manner. Adverse effects of Hg on developmental outcome occurred only at a concentration that caused maternal toxicity.