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.     

Renal functional correlates of methyl mercury intoxication: interaction with acute mercuric chloride toxicity.

To determine the effect of methyl mercury and its possible interaction with mercuric chloride on renal function, male Sprague-Dawley rats were treated with methyl mercuric chloride (1 mg/kg per day × 20 days ip) and/or mercuric chloride (1 mg/kg ip at Day 20) in a 2 × 2 factorial experimental design. Methyl mercury depressed urine osmolality and N-methylnicotinamide (NMN) uptake by renal cortical slices but did not affect the uptake of p-aminohippurate (PAH), blood urea nitrogen concentration (BUN), urine volume, or body weight. Urinary excretion of the lysosomal enzymes, β-galactosidase and acid phosphatase, appeared to be decreased, but excretion of the brush border enzyme, alkaline phosphatase, was not affected. Mercuric chloride treatment increased enzyme excretion, BUN, and uptake of NMN by renal cortical slices, while it decreased PAH uptake and urine osmolality, BUN concentration was further increased by combined treatment, yielding the only significant treatment interaction between methyl mercury and mercuric chloride. Prostaglandin E₂ synthesis and release by renal medullary tissue in vitro was not depressed by methyl mercuric chloride pretreatment nor was renal ammoniagenesis or gluconeogenesis. The effects of methyl mercury upon lysosomal enzyme excretion and NMN accumulation are suggestive of lysosomal and mitochondrial dysfunction. The failure to detect significant interaction between methyl mercury and mercuric chloride indicates that methyl mercury neither potentiates nor protects against acute mercuric chloride toxicity at this time and dose.     

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.     

Thiol antidote to inorganic mercury toxicity with an uncharacteristic mechanism

alpha-Mercapto-beta-(2-furyl)acrylic acid (MFA) significantly reduced the lethality of mercuric chloride to rats (2.2 mg Hg/kg, ip) when administered (25 mg/kg, po) at 1, 24, 48, and 72 hr. Daily administration of MFA (25 mg/kg, po) significantly reduced the lethality of daily injection of increasing amounts of mercuric chloride (1 mg Hg/kg X 7 days, 2 mg Hg/kg X 7 days, 4 mg Hg/kg X 14 days, ip). Mercury concentration in kidneys of MFA-treated rats was significantly higher than in vehicle-treated controls, whereas concentration in liver was (nonsignificantly) lower. Enhanced mercury deposition in kidney as a manifestation of antidotal effect is not characteristic of thiol chelators used in practice for mercury poisoning.     

The comparative toxicology of ethyl- and methylmercury

Neurotoxicity and renotoxicity were compared in rats given by gastric gavage five daily doses of 8.0 mg Hg/kg methyl- or ethylmercuric chloride or 9.6 mg Hg/kg ethylmercuric chloride. Three or 10 days after the last treatment day rats treated with either 8.0 or 9.6 mg Hg/kg ethylmercury had higher total or organic mercury concentrations in blood and lower concentrations in kidneys and brain than methylmercury-treated rats. In each of these tissues the inorganic mercury concentration was higher after ethyl than after methylmercury.Weight loss relative to the expected body weight and renal damage was higher in ethylmercury-treated rats than in rats given equimolar doses of methylmercury. These effects became more severe when the dose of ethylmercury was increased by 20%. Thus in renotoxicity the renal concentration of inorganic mercury seems to be more important than the concentration of organic or total mercury. In methylmercury-treated rats damage and inorganic mercury deposits were restricted to the P₂ region of the proximal tubules, while in ethylmercury-treated rats the distribution of mercury and damage was more widespread.There was little difference in the neurotoxicities of methylmercury and ethylmercury when effects on the dorsal root ganglia or coordination disorders were compared. Based on both criteria, an equimolar dose of ethylmercury was less neurotoxic than methylmercury, but a 20% increase in the dose of ethylmercury was enough to raise the sum of coordination disorder scores slightly and ganglion damage significantly above those in methylmercury-treated rats.In spite of the higher inorganic mercury concentration in the brain of ethylmercurythan in the brain of methylmercury-treated rats, the granular layer damage in the cerebellum was widespread only in the methylmercury-treated rats. Thus inorganic mercury or dealkylation cannot be responsible for granular layer damage in alkylmercury intoxication. Moreover, histochemistry demonstrated no inorganic mercury deposits in the granular layer.     

Mercury distribution in neonatal rat brain after intrauterine methylmercury exposure

Methylmercuric chloride (MMC) was orally administered to pregnant Wistar rats from gestational day 6 (G6) for 5 consecutive days. After delivery, the neonatal rats were decapitated and the cerebrum, cerebellum and hippocampus were excised on postnatal day (PND) 1, 7, 14, 21, 30 to determine total Hg contents and concentrations (six per stage). Both total Hg contents and concentrations in all the three regions increased as exposure dose increased and declined as postnatal time prolonged. Interestingly, differences of total Hg content between cerebrum and hippocampus at each time-point were significant (P<0.05). In the meantime, considering the Hg concentration, while no differences were observed before PND14 (P<0.05) among the three regions, Hg concentration in hippocampus was significantly higher than in cerebrum after that time period (P<0.05). We demonstrated that MeHg could pass through the placental and blood-brain barriers in a dose-dependent manner. Moreover, we found mercury redistribution occurred in offspring brain following the prolongation of postnatal time. The hippocampus was the major target of MeHg accumulation.     

Chronic phenylmercuric acetate toxicity in a horse

Phenylmercuric acetate (PMA) was administered orally to a horse over a period of 27 weeks (190 days) at a dose rate of 0.4 mg Hg/kg per day. The effects produced were consistent with those of chronic inorganic mercury intoxication. The clinical features included masseter muscle atrophy, difficulty in prehension and mastication, malodorous breath, reduced appetite and weight loss, and reflected significant pathological changes involving the buccal, mandibular and dental tissues. Renal dysfunction was evident terminally and there was degeration and necrosis of the proximal tubular epithelium. Necrotic and mineralized foci were found in facial and masticatory msucles, splenic trabecuale and the myocardium. The central nervous system and the intestinal tract were unaffected. The approximate mean plasma inorganic mercury concentration was 500 ng/ml whereas organic mercury levels in blood were much lower. The renal cortex had the highest inorganic mercury content, three times greater than in the liver and cecum, while organic mercury was highest in those tissues and absent from the kidney. The difference in the effects produced in this horse as compared to those in a horse receiving mercuric chloride at the same mercury dose rate, could be attributed to the more rapid and complete absorption of PMA from the gastrointestinal tract.     

Effects of L- or D-cysteine coadministration on short-term distribution of inorganic mercury in the rat

Male Sprague-Dawley rats received iv injections of mercuric chloride alone or in combination with l-cysteine or d-cysteine. Mercury concentrations in kidney, liver, and cerebrum 5 min after injection increased linearly over the dose range of 0.1, 0.5, 1.0, and 2.0 μmol of mercury/kg. Over this dose range, coadministration of l-cysteine or d-cysteine at a 2-to-1 molar ratio relative to mercury increased renal mercury concentrations and reduced mercury accumulation in the liver, cerebrum, and erythrocytes. Renal mercury concentrations were highly correlated with plasma mercury concentrations 5 min after injection and coadministration of l-cysteine or d-cysteine did not alter this relationship. Hepatic and cerebral mercury concentrations were also highly correlated with plasma mercury concentrations but coadministration of either thiol compound altered the relationship between plasma and tissue mercury concentrations. These data suggested that different processes underlie short-term mercury accumulation in different tissues. Investigations of the effects on tissue distribution of various molar ratios of l- or d-cysteine relative to mercury further suggested that direct complexation of mercury by either thiol may be a critical factor in the control of mercury deposition in these tissues.     

Whole-body retention of mercury and selenium and histopathological and morphological studies of kidneys and liver of rats exposed repeatedly to mercuric chloride and sodium selenite

Distribution and retention of mercury and selenium was studied in rats exposed repeatedly to HgCl₂ injections (0.5 mg Hg/kg to the tail vein every other day) and intragastrically to Na₂SeO₃ (0.5 mg Se/kg every day), applying combined and separate administration of these metals for 2 weeks. Whole-body retention of mercury in the presence of selenium was augmented by 20% and that of selenium in the presence of mercury by 4% with respect to the administered dose. Combined administration of mercuric chloride and sodium selenite brought about damage to the epithelial cells of renal proximal convolutions and formation of protein casts in their lumen. These changes had the same pattern as those induced by administration of mercuric chloride alone, but the intensity was lower. Submicroscopic studies revealed that repeated combined administration of sodium selenite and mercuric chloride did not completely abolish the mercury-induced mitochondrial swelling and contributed to chromatin destruction in the hepatocyte nuclei.This work was supported by the Section of Medical Sciences of the Polish Academy of Sciences (Agreement 537/VI)     

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.     

Effect of interaction between 65Zn,mercury and selenium in rats (retention,metallothionein, endogenous copper)

Interaction of zinc with mercuric chloride and sodium selenite was studied in the rat at the organ and subcellular levels (liver and kidneys). Zinc chloride was administered subcutaneously at dose of 5 mg Zn/kg, mercury chloride into the tail vein at a dose of 0.5 mg Hg/kg (both metals every other day during 2 weeks) and sodium selenite intragastrically, at doses of 0.1 mg Se/kg, every day. Zinc retention in the rat did not exceed 20% and was unchanged in the presence of mercury. An interaction effect was reflected by an increased whole-body retention of zinc by selenium, mercury, and selenium. In the presence of selenium no peak of metallothionein-like proteins stimulated by zinc or mercury was found in the soluble fraction of the kidneys. The metallothionein level did not differ from that typical for control group animals, too. A significant increase in the level of endogenous copper was found only in the kidneys of rats exposed to zinc in the presence of mercury and selenium.     

Protective Effects of Ca2+ Channel Blockers against Methyl Mercury Toxicity

Abstract: The protective effects of Ca²⁺ channel blockers against the toxicity of methyl mercury were examined by both in vivo and in vitro experiments. In the in vivo study we first examined the effects of the Ca²⁺ channel blockers (20 mg/ kg/day), flunarizine, nifedipine, nicardipine, and verapamil against the toxic level of methyl mercury treatment (5 mg/kg/ day of methyl mercuric chloride for 12 consecutive days). However, there was a difference in potency of the effects among the reagents. All the Ca²⁺ channel blockers prevented a decrease in body weight and/or the appearance of the symptoms of neurological disorders in the rats treated with methyl mercury. In the next experiment, we examined flunarizine at different levels of supplementation (1,25 and 50 mg/kg/day). Flunarizine in a dose-dependent manner prevented a decrease in body weight, appearance of the symptoms of neurological disorder and mortality in the rats treated with methyl mercury. Flunarizine treatment (25 mg/kg/day) for the first 5 days did not affect mercury distribution among the tissues, suggesting that the mechanism of protection against methyl mercury-induced toxicity may be attributed to its own pharmacological effect. In the in vitro study we examined the effect of flunarizine (0, 0.5, 5 and 50 μM) using primary cultures of cerebellar granular cells in 96-well culture plates. Viable cell numbers were estimated 1 and 3 days after treatment with methyl mercury. The estimated 50% lethal concentration (LC50) of methyl mercury was higher in plates treated with 5 and 50 uM of flunarizine both on days 1 and 3, indicating that flunarizine protected the primary cultured cerebellar granular cells against the toxicity of methyl mercury. As such, Ca²⁺ channel blockers protected against the toxicity of methyl mercury both in vivo and in vitro, suggesting that Ca²⁺ plays an important role in the mechanisms of methyl mercury toxicity.     

Effects of coadministered low-molecular-weight thiol compounds on short-term distribution of methyl mercury in the rat

Following iv administration to the rat, methyl mercury was rapidly deposited in the liver, kidneys, and cerebrum. Methyl mercury concentrations in cerebrum 5 min after injection were about equal to the levels attained at 60 min post-treatment. At 5 min after dosing, concentrations of methyl mercury in plasma and tissues were directly proportional to the dose level of methyl mercury. Coadministration of equimolar amounts of l-cysteine increased short-term accumulation of methyl mercury in liver, kidneys, and cerebrum while reducing the levels of methyl mercury in plasma from those found after administration of methyl mercury alone. Equimolar doses of d-cysteine or d-penicillamine lowered plasma methyl mercury levels below those produced by injection of methyl mercury alone, but coadministered N-acetyl-l-cysteine or l-penicillamine did not. Each of these low-molecular-weight thiol compounds given in combination with methyl mercury increased deposition of methyl mercury in liver and kidneys. In addition, l-penicillamine also increased accumulation of methyl mercury in the cerebrum. These results suggest a critical role of plasma methyl mercury levels in the control of short-term methyl mercury distribution. Modification of the distribution pattern by coadministered low-molecular-weight thiol compounds further suggests that methyl mercury-thiol complexes may play a role in the tissue deposition process.     

Subacute toxicity of methylmercury in the adult cat

A dose of 0.25 mg Hg/kg/day was administered po to 2 groups of cats for 12–14 weeks, either as pure methylmercuric chloride or as methylmercury-contaminated fish. A control group received a diet containing uncontaminated fish. Clinical signs of methylmercury intoxication consisting of ataxia, intention tremor and impaired righting reflex and convulsions developed between 55 and 96 days in both treated groups, at which time the total dose received was between 14 and 24 mg Hg/kg. Tissue mercury content was similar in both groups of treated animals, as were the pathologic changes. Lesions were found in the cerebellar vermis and the cerebral cortex. The changes consisted of loss of nerve cells with replacement by reactive and fibrillary gliosis. Chromosome studies of terminal bone marrow samples showed no abnormalities.A separate group of 8 cats received a single oral dose of ²⁰³H-labelled methylmercuric chloride, and the blood mercury concentration was measured weekly. The $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ for the elimination of mercury from blood was found to be 39 ± 4 days (mean ± SE).     

Renal accumulation and intrarenal distribution of inorganic mercury in the rabbit: effect of unilateral nephrectomy and dose of mercuric chloride

The effects of unilateral nephrectomy and dose of mercuric chloride on the short-term renal accumulation and intrarenal distribution of inorganic mercury were studied in the rabbit. The renal accumulation of inorganic mercury, on a per gram basis, was increased in uninephrectomized (NPX) rabbits compared with that in sham-operated (SO) rabbits 24 h after the animals received either a nontoxic 2.0 mumol/kg or nephrotoxic 4.0 mumol/kg dose of mercuric chloride. In the NPX rabbits given the 2.0 mumol/kg dose of mercuric chloride, the increased accumulation of inorganic mercury was due to increased accumulation of mercury in the outer stripe of the outer medulla. In the NPX rabbits given the 4.0 mumol/kg dose of mercuric chloride, the increased renal accumulation of mercury appeared to be due to increased accumulation of mercury in both the renal cortex and outer stripe of the outer medulla. Interestingly, no differences in the renal accumulation of inorganic mercury were found between NPX and SO rabbits given a low nontoxic 0.5 mumol/kg dose of mercuric chloride. As the dose of mercuric chloride was increased from 0.5 to 4.0 mumol/kg, the percent of the administered dose of mercury that accumulated in each gram of renal tissue decreased substantially. The findings in the present study indicate that the renal accumulation of inorganic mercury increases after unilateral nephrectomy when certain nontoxic and nephrotoxic doses of mercuric chloride are administered. In addition, they indicate that the percent of the administered dose of mercury that accumulates in the renal tissue of both NPX and SO rabbits decreases as the dose of mercuric chloride is increased.     

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.     

Protective effect of vitamin E against mercuric chloride reproductive toxicity in male mice

Mercury intoxication has been associated with male reproductive toxicity in experimental animals and mercury may have the potential to produce adverse effects on fertility in men. Vitamin E may protect against toxic effects of mercury in the liver and other tissues. To investigate the protective role of vitamin E against mercuric chloride toxicity for the testis, epididymis, and vas deferens of adult male mice, animals were treated with either mercuric chloride 1.25 mg/kg/day, vitamin E 2 mg/kg/kg, or a combination of the two treatments. Control animals were treated with water. Treatments were administered by daily gavage for 45 days. An additional group of animals treated with mercuric chloride were permitted to recover for 45 days after mercuric chloride treatments. Parameters studied included serum testosterone, epididymal sperm count, motility, and morphology, epididymal and vas deferens adenosine triphosphatase (ATPase), phosphorylase, sialic acid, glycogen and protein, testicular succinate dehydrogenase (SDH), phosphatases, cholesterol, ascorbic acid, and glutathione. Fertility was evaluated by sperm positive vaginal smears after overnight cohabitation with a female. Mercuric chloride produced a reduction in epididymal sperm count, sperm motility, and sperm viability, and there were no sperm-positive smears in this group. Biochemical tests from the male reproductive organs were also altered by mercuric chloride treatment. Coadministration of vitamin E with mercuric chloride prevented the changes in sperm and biochemical parameters and was associated with control rates of sperm positive smears after cohabitation. Animals given vitamin E with mercuric chloride also had lower concentrations of mercury in the testis, epididimyis, and vas deferens. Permitting animals to recover for 45 days after mercuric chloride treatment resulted in partial recovery of sperm and biochemical parameters. Vitamin E cotreatment has a protective role against mercury-induced male reproductive toxicity.     

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 of endosulfan in plasma and brain after repeated oral administration to rats

Rats were fed endosulfan (5 or 10 mg/kg) containing alpha- and beta-isomers in the ratio of 2:1, daily for 15 days. The distribution pattern of endosulfan, its isomers and metabolite, endosulfan sulfate, was estimated in the plasma and brain of the rats. On day 16, the alpha-isomer in rats receiving 5 mg/kg was highest in the cerebrum (3.76 microgram/g) followed by the remaining part of the brain (2.66 microgram/g), and the cerebellum (2.04 microgram/g). The concentration of the beta-isomer was 0.06 microgram/g in the cerebrum and 0.02 microgram/g in the cerebellum; no beta-isomer was detected in the remaining part of the brain. The plasma concentration of alpha- and beta-isomers was 2.26 and 0.46 microgram/ml, respectively. No metabolite other than endosulfan sulfate was detected in plasma. No significant changes in brain tissue were observed in any of the groups under treatment. On day 30 (15 days after the last treatment), the concentration in plasma declined more rapidly than that in the brain tissue. At a higher dose (10 mg/kg), the distribution pattern of isomers and its metabolite, endosulfan sulfate, followed almost the same trend except that the concentration was higher than in rats receiving lower doses.     

Treatment of methyl mercury poisoning in mice with 2,3-dimercaptosuccinic acid and other complexing thiols

Treatment with 2,3-dimercaptosuccinic acid was more effective than N-acetyl-DL-penicillamine and monomercaptosuccinic acid in mobilizing mercury from mice after the injection of methyl mercuric chloride. Dimercaptosuccinic acid treatment started 4 days after the mercury injection and given for 8 days at a dose of 1 mmol SH/kg per day removed more than 2/3 of the mercury in the brain, while acetylpenicillamine and mercaptosuccinate correspondingly removed less than 1/2 of the brain deposits. Neither treatment with 2,3-dimercaptorropano-1-sulphonate nor with a new thiolated resin, mercaptostarch, mobilized significant amounts of mercury from the brain. Since the toxicity of dimercaptosuccinate seems to be almost as low as that of D-penicillamine this dithiol may provide a potentially useful agent in clinical poisoning due to methyl mercury.