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.     

Mobilization of Methyl Mercury in Vivo and in Vitro using N–acetyl–DL–penicillamine and other Complexing Agents

Abstract The distribution and excretion of mercury was studied in mice given a single intravenous dose of 5 umol/kg of methyl mercuric chloride. Oral treatment with N–acetyl–DL–penicillamine (3 mmol/kg per day) removed more mercury from the brain and from the whole body than the corresponding treatment with other complexing agents, and it was also effective on delayed treatment. Even more mercury was removed into the faeces and the urine, by higher doses of N–acetyl–DL–penicillamine, and 4 days of treatment with 27 mmol/kg per day of this compound did not give rise to any significant toxic symptoms in the mice. In vitro experiments showed that the chemical affinity of N–acetyl–DL–penicillamine for methyl mercury was higher than that of the other thiols tested, except D–penicillamine. In contrast to the latter, N–acetyl–DL–penicillamine easily penetrated the cellular membranes, and therefore rapidly removed a substantial fraction of methyl mercury from the blood cells. It is assumed that N–acetyl–DL–penicillamine can reduce the mercury concentration in brain cells by converting the intracellularly non–diffusible methyl mercury into a freely diffusible complex.     

Effect of amino acids on brain uptake of methyl mercury

To investigate the effect of amino acids on the brain uptake of methyl mercury (MM), methyl mercury chloride (MMC), and some amino acids were injected iv to Wistar strain male rats (190 ± 10 g). One hour after the simultaneous injection of 10 μmol and 100 μmol l-cysteine (l-Cys) to the rat, brain mercury content increased about three times as compared with that after a single injection of MMC alone. This effect of l-Cys was depressed by pre- and post-treatment with l-phenylalanine (l-Phe), but not with l-lysine (l-Lys) or l-glutamic acid (l-Glu). BAL also increased the brain uptake of MM. However, l-Phe did not exert an effect on the increased brain uptake of MM. When 10 μmol MMC was injected to the rat treated with l-Phe or l-isoleucine (l-Ile) (pre-, simultaneous, and post-treatment), brain mercury 2 hr after the injection was lower than that after the single injection of MMC. At that time, there was no significant difference in blood and plasma mercury concentrations between the l-Phe-treated and nontreated rats. Treatment with l-Lys and l-Glu did not affect the brain mercury content after MMC injection. Brain mercury after the injection of 10 μmol MMC increased with time. The rate of increase was lowered by pre-, simultaneous, and post-treatment with l-Phe for 2, 6, 9, and 12 hr. When l-Phe injection was started 12 hr after MMC injection and continued repeatedly for 12 hr, the brain mercury content was low when compared with that after the single injection of MMC. These data demonstrate that the brain uptake of MM is depressed by l-Phe and l-Ile, which are neutral amino acids, and not by l-Lys and l-Glu, which are a basic and an acidic amino acid, respectively.     

Treatment of mercuric chloride poisoning with dimercaptosuccinic acid and diuretics: preliminary studies

The distribution and excretion of mercury were studied in mice given a single injection of HgCl2 with or without chelation treatment. DMS (2,3-dimercaptosuccinic acid) given intravenously (0.5 mmol SH/kg) to mice 24 h after the mercury injection reduced the kidney Hg level significantly, while NAPA (N-acetyl-DL-penicillamine) and BAL (2,3-dimercaptopropanol) did not. The effectivity of DMS to remove Hg from kidneys was comparable to that of BAL-sulph (2,3-dimercaptopropane-1-sulfonate), irrespective of whether these chelating agents were given orally or intravenously. Immediate chelation treatment with DMS or mercaptodextran reduced the renal Hg level to about 50% of control levels, as measured 3 d after the treatment. Combination of DMS with immediate intraperitoneal treatment with spironolactone was even more effective in reducing the renal levels, and acted both by increasing the fecal and urinary excretion. The DMS treatment, as well as DMS + spironolactone in combination, could protect against kidney damage following injection of 30 mumol HgCl2/kg. Such treatment was essentially nontoxic.     

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.     

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.     

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.     

Combined effect of sodium maleate and some thiol compounds on mercury excretion and redistribution in rats

1. (+)-Penicillamine in a dose of 193 μmoles/kg given subcutaneously twice a day on the sixth and seventh days after the administration of 100 μg mercury increased the urinary excretion of rats more than the equimolar dose of N-acetyl-(+)-penicillamine but less than 2,3-dimercaptopropanol 48.3 μmoles/kg.

2. Sodium maleate in a dose of 156 μmoles/kg given on the sixth and seventh days after the mercury did not influence mercury excretion or redistribution. Sodium maleate in the same dose increased considerably the effect of (+)-penicillamine on the urinary excretion and redistribution of mercury. It increased the effect of N-acetyl-(+)-penicillamine only slightly. There was a tendency to decrease the effect of 2,3-dimercaptopropanol.

3. All the complexing agents decreased the kidney content of mercury and increased the liver and blood concentration of mercury. These changes were highest with 2,3-dimercaptopropanol. The combination of sodium maleate with (+)-pencillamine caused higher mercury excretion and lower kidney content but a smaller increase in the liver and blood mercury contents than 2,3-dimercaptopropanol.

     

The Effect of N–acetyJated DL–penicillamine and DL–homocysteine Thiolactone on the Mercury Distribution in Adult Rats,Rat Foetuses and Macaca Monkeys after Exposure to Methyl Mercuric Chloride

Abstract The distribution and excretion of mercury was studied in pregnant rats, given a single intravenous dose of 2 μmol/kg of CH₃²⁰³HgCl on the 13th day of pregnancy. Oral treatment for one week with N–acetyl–DL–penicillamine (4 mmol/kg per day) increased the mercury excretion in faeces (from 45 to 120 nmol) and urine (from 9 to 160 nmol). Such treatment mobilized mercury from all the organs tested, and the foetal and maternal brain levels of mercury were decreased to 1/5 and 1/3 of the controls, respectively. A four–day period of treatment with N–acetyl–DL–penicillamine started three days after the injection of methyl mercury reduced the foetal and maternal brain levels to 1/2 and 2/3 of the controls, respectively. The rapid removal of metal deposits following treatment with N–acetyl–DL–penicillamine is attributed to a free penetration of the complexing thiol into the tissue cells in question. No signs of toxicity were detected in monkeys given an effective daily dose of the agent (4 mmol/kg) for 6 days. In contrast N–acetyl–DL–homocysteine thiolactone was found to be toxic in the monkeys. In addition, the latter agent was ineffective in increasing the mercury elimination from the brains of monkeys, rats and rat foetuses.     

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.     

Subcutaneous injection of metallic mercury

Deliberate self-injection of metallic mercury into subcutaneous tissue is uncommon. A 41-year-old lady with a history of schizophrenia was admitted to our hospital after deliberate injection of metallic mercury into her right wrist and antecubital fossa. Physical examination was unremarkable except for the injection marks over right antecubital fossa and wrist. The presence of subcutaneous mercury deposits in her right elbow and wrist was confirmed by X-rays and ultrasound scan. Three days later, erythema, swelling, induration and tenderness were seen over the injection sites. At the operation on day 9, mercury streaks were seen within the brachialis muscle belly, surrounded by friable necrotic tissues along the tract. A similar picture was noted in her right wrist. The necrotic tissues and mercury streaks were removed. The patient had been unco-operative and she only received incomplete treatment with dimercaprol and 2,3-dimercaptosuccinic acid. Her total blood mercury level (normal < 50 nmol/L) decreased from 101-151 nmol/L in the first two weeks to 42 nmol/L 3 months later. Her 24-hour urinary mercury excretion (normal < 10 nmol) changed from 55.7-209.5 nmol in the first 7 weeks to 125.4 nmol 3 months later. This case illustrates that soft tissue metallic mercury can produce local necrosis and may allow continuous absorption with persistent elevations in blood and urinary mercury levels. Therefore, early surgical removal of subcutaneous mercury deposits is required to prevent local complications and minimize the risk of systemic absorption and toxicity.     

Effects of carbon monoxide exposure on the distribution of methylmercury in mice

Effects of long-term exposure to sublethal concentration (300-350 ppm) of carbon monoxide (CO) on the distribution of methylmercury (MeHg) in the blood and organs of mice were examined using 6th week-old ICR mice of both sexes. Firstly, female mice were exposed to CO immediately after single ip injection of CH3HgCl (1 mg/kg). At the earliest stage, brain mercury level was higher in CO mice than in control mice, while blood mercury level was lower in CO mice than in control mice. There were indications that compensatory hemoconcentration and resultant increase of mercury levels in the blood, brain and liver occurred in CO mice by the 8th day of CO exposure. Mercury in the blood, brain, liver and kidney decreased more rapidly in CO mice than in control mice for a short period after hemoconcentration had occurred. Secondly, male mice were pre-exposed to CO for 7 days, received single ip injection of CH3HgCl (1 mg/kg) and were re-exposed to CO for an additional 21 days. Hemoconcentration, increased mercury levels in the blood, brain and liver were observed in CO mice. Thirdly, male mice were pre-exposed to CO for 7 days, administered po with CH3HgCl (2 mg/kg) and re-exposed to CO for 24 hr. Mercury levels in the blood, brain and liver but not the kidneys were higher in CO mice than in control mice. The relationships between hemoconcentration and MeHg distribution in vertebrates were discussed.     

The Effect of Selenium on the Biliary Excretion and Organ Distribution of Mercury in the Rat after Exposure to Methyl Mercuric Chloride

Abstract The influence of selenium compounds on the biliary excretion and the organ distribution of mercury after injection of methyl mercuric chloride (4 μmol/kg) have been tested. Selenite, seleno-di-N-acetylglycine and seleno-methionine strongly inhibited the biliary excretion of mercury. Selenite even in a molar dose of 1/40 of the methyl mercury dose inhibited the biliary excretion of mercury. The less toxic seleno-di-N-acetylglycine was needed in larger molar doses and did not act as rapidly as selenite. Biliary excreted methyl mercury is known to be partly reabsorbed in the gut. Subsequently a part of it is deposited in the kidneys since drainage of the bile lowered the kidney content of mercury. Rats given selenium compounds in combination with bile drainage showed further reduction of the kidney mercury content than bile duct drainage alone. Thus the demonstrated lowering effect of selenium compounds on the kidney mercury content cannot be completely explained by an inhibition of biliary excretion of mercury. The mercury concentration in the brain was increased by the selenium compounds; the effect being dependent of the selenium dose reaching a maximum at an equimolar selenite - to methyl mercury dose ratio. The mechanisms by which selenium influences the methyl mercury kinetics are discussed.     

Deferoxamine inhibits methyl mercury-induced increases in reactive oxygen species formation in rat brain.

It has been suggested that methyl mercury may express its neurotoxicity by way of iron-mediated oxidative damage. Therefore, the effect of deferoxamine, a potent iron-chelator, on methyl mercury-induced increases in reactive oxygen species formation was studied in rat brain. The generation rate of reactive oxygen species was estimated in crude synaptosomal fractions using the probes 2',7'-dichlorofluorescin diacetate and dihydrorhodamine 123. The formation rate of the fluorescent oxidation products was used as the measure of reactive oxygen species generation. Seven days after a single injection of methyl mercury (5 mg/kg, ip), the formation rate of reactive oxygen species was significantly increased in the cerebellum. Pretreatment with deferoxamine (500 mg/kg, ip) completely prevented the methyl mercury-induced increase in cerebellar reactive oxygen species generation rates. The oxidative consequences of in vitro exposure to methyl mercury (20 microM) were also inhibited by deferoxamine (100 microM). The formation of the iron-saturated complex ferrioxamine was not affected by a 10-fold excess of methylmercuric chloride or mercuric chloride, suggesting that a deferoxamine-mercurial complex does not form. The findings in this study: (1) provide evidence that iron-catalyzed oxygen radical-producing reactions play a role in methyl mercury neurotoxicity, (2) demonstrate the potential of fluorescent probes as a measure of reactive oxygen species formation, and (3) provide support for iron-chelator therapy in protection against xenobiotic-induced oxidative damage.     

The effect of selenium on the biliary excretion and organ distribution of mercury in the rat after exposure to methyl mercuric chloride.

The influence of selenium compounds on the biliary excretion and the organ distribution of mercury after injection of methyl mercuric chloride (4 mumol/kg) have been tested. Selenite, seleno-di-N-acetylglycine and seleno-methionine strongly inhibited the biliary excretion of mercury. Selenite even in a molar dose of 1/40 of the methyl mercury dose inhibited the biliary excretion of mercury. The less toxic seleno-di-N-acetylglycine was needed in larger molar doses and did not act as rapidly as selenite. Biliary excreted methyl mercury is known to be partly reabsorbed in the gut. Subsequently a part of it is deposited in the kidneys since drainage of the bile lowered the kidney content of mercury. Rats given selenium compounds in combination with bile drainage showed further reduction of the kidney mercury content than bile duct drainage alone. Thus the demonstrated lowering effect of selenium compounds on the kidney mercury content cannot be completely explained by an inhibition of biliary excretion of mercury. The mercury concentration in the brain was increased by the selenium compounds; the effect being dependent of the selenium dose reaching a maximum at an equimolar selenite--to methyl mercury dose ratio. The mechanisms by which selenium influences the methyl mercury kinetics are discussed.     

2,3-Dimercapto-1-propanol does not alter the porphobilinogen synthase inhibition but decreases the mercury content in liver and kidney of suckling rats exposed to HgCl2

Heavy metals have received great attention as environmental pollutants mainly because once introduced in the biological cycle they are incorporated in the food chain. Especially the mercury toxicity due to a diversity of effects caused by different chemical species should be emphasized. Heavy metal intoxication has been treated with chelating agents such as 2,3-dimercapto-1-propanol (BAL). However, the efficacy of this treatment is questionable due to the lack of specific effect on the toxic metal. The present study examined the effects of HgCl2 exposure (five doses of 5.0 mg/kg between ages 8 to 12 days) on physiological parameters, on porphobilinogen synthase activity, and on mercury content in liver, kidneys and brain from suckling rats. The effect of BAL (one dose of 12.5-75 mg/kg) applied 24 hr after mercury intoxication on these parameters was also investigated. The results demonstrate that HgCl2 intoxication induced a decrease of corporal weight gain as well as brain weight and an increase in renal weight. The inhibition of porphobilinogen synthase from liver and kidney, is still significant and was not modified by subsequent BAL treatment. However, BAL altered two effects induced by mercury: increase in death percentage and decrease in mercury contents in liver and kidney. The increase of mortality induced by mercury was not promoted by metal redistribution to brain nor by the increase of porphobilinogen synthase inhibition induced by metal. More investigations are necessary to determine if the different effects of BAL on intoxication by metals are possibly related to other tissues and/or if the probable metal-chelating complex formed is more toxic than the metal itself.     

Influence of 2,3-dimercaptopropane-1-sulfonate and dimercaptosuccinic acid on the mobilization of mercury from tissues of rats pretreated with mercuric chloride, phenylmercury acetate or mercury vapors

The efficiency of the sodium salt of 2,3-dimercaptopropanesulfonic acid (DMPS) and meso-dimercaptosuccinic acid (DMSA) to mobilize mercury from tissues has been assessed in rats pretreated with different doses of HgCl2, phenylmercury acetate or exposed to different concentrations of mercury vapors. These pretreatments increase the mercury concentration in the kidney and to a lower extent in the liver. Only exposure to metallic mercury vapor leads to mercury accumulation in the brain. Both chelators mobilize mercury stored in the kidney and the amount of metal excreted in urine following a single administration of DMSA is a good indicator of the renal burden of mercury. The rate of removal is greater after DMPS administration than after DMSA but repeated administration of either agents eventually leads to the same total amount of mercury mobilized from the kidney. The loss of mercury from the liver can be slightly accelerated by repeated administration of the chelators. However, the chelators are inefficient in removing mercury from the brain.     

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.     

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.     

Thimerosal distribution and metabolism in neonatal mice: comparison with methyl mercury

Thimerosal, which releases the ethyl mercury radical as the active species, has been used as a preservative in many currently marketed vaccines throughout the world. Because of concerns that its toxicity could be similar to that of methyl mercury, it is no longer incorporated in many vaccines in the United States. There are reasons to believe, however, that the disposition and toxicity of ethyl mercury compounds, including thimerosal, may differ substantially from those of the methyl form. The current study sought to compare, in neonatal mice, the tissue concentrations, disposition and metabolism of thimerosal with that of methyl mercury. ICR mice were given single intramuscular injections of thimerosal or methyl mercury (1.4 mg Hg kg(-1)) on postnatal day 10 (PND 10). Tissue samples were collected daily on PND 11-14. Most analysed tissues demonstrated different patterns of tissue distribution and a different rate of mercury decomposition. The mean organic mercury in the brain and kidneys was significantly lower in mice treated with thimerosal than in the methyl mercury-treated group. In the brain, thimerosal-exposed mice showed a steady decrease of organic mercury levels following the initial peak, whereas in the methyl mercury-exposed mice, concentrations peaked on day 2 after exposure. In the kidneys, thimerosal-exposed mice retained significantly higher inorganic mercury levels than methyl mercury-treated mice. In the liver both organic and inorganic mercury concentrations were significantly higher in thimerosal-exposed mice than in the methyl mercury group. Ethyl mercury was incorporated into growing hair in a similar manner to methyl mercury. The data showing significant kinetic differences in tissue distribution and metabolism of mercury species challenge the assumption that ethyl mercury is toxicologically identical to methyl mercury.