Subacute toxicity of methylmercury in the adult cat☆
Abstract
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 for the elimination of mercury from blood was found to be 39 ± 4 days (mean ± SE).
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Cited by (39)
Mercury
2021, Handbook on the Toxicology of Metals: Fifth EditionMercury occurs as elemental mercury and as inorganic and organic compounds (mercury vapor, mercury liquid, mercury salts, short-chain alkylmercury compounds, alkoxyalkylmercury compounds, and phenylmercury compounds), all with different toxicological properties. Total mercury can be analyzed in water, air, and biological material by cold vapor atomic absorption methods and by neutron activation analysis and can be detected down to concentrations of a 10th of a nanogram per gram in biological material. Methylmercury (MeHg) can be detected in biological material at levels of a few nanograms by extraction with benzene after strong acidification with hydrochloric acid, followed by gas chromatographic analysis of MeHg chloride. Other analytical methods for speciating inorganic mercury and several of the organomercurial forms have also been published. These methods include isotope dilution mass spectrometry, time-of-flight mass spectrometry, high-performance liquid chromatography inductively coupled plasma (ICP) mass spectrometry, capillary electrophoresis-ICP, gas chromatography-ICP, and X-ray absorption fine structure spectroscopy.
Mercury is circulated naturally in the biosphere, with 5500 metric tons (t) being released into the atmosphere by degassing from the Earth's crust and the oceans. In addition, 2500 t of mercury are released into the environment each year through human activities such as the combustion of fossil fuels and other industrial releases. Approximately 2000 tons of mercury per year is produced for industrial use, a small part of which is used for synthesizing organic mercury compounds. The world production of mercury for commercial uses has been slowly declining over the past 20 years. There is now a ban on the export of mercury from the European Union and the United States.
In nature, MeHg is produced from inorganic mercury as a consequence of microbial activity. In mammals, oxidative demethylation occurs in vivo to produce inorganic mercury. In fish, most mercury is present as MeHg. Factors determining the MeHg concentration in fish are the mercury content in water and bottom sediments, the pH and redox potential of water, and the species, age, and size of the fish.
The toxic properties of mercury vapor are a consequence of mercury accumulation in the brain causing neurological signs involving an unspecific psychasthenic and vegetative syndrome (micromercurialism). At high exposure levels, mercurial tremor is seen, accompanied by severe behavioral and personality changes, increased excitability, loss of memory, and insomnia. Mercurials may also affect other organ systems, such as the kidney. On a group basis, exposure levels are likely to be reflected by mercury concentrations in the blood and urine. Occupational exposure to mercury concentrations in air of >0.1 mg/m3 may produce mercurialism. Micromercurialism has not been reported at concentrations <0.01 mg/m3. Exposure to mercury vapor inhibits brain development in primates and in humans with certain genotypes. The exact dose–response relationship in humans is not known. Inorganic mercury, but not MeHg, has been found to induce and bind to the low molecular weight metal-binding protein, metallothionein.
The acute and long-term actions of mercuric salts, phenylmercury compounds, and alkoxyalkylmercury compounds are likely to be gastrointestinal disturbance and renal damage appearing as tubular dysfunction, with tubular necrosis in severe cases. The lethal dose in humans is approximately 1 g mercuric salt. The mercury load on the kidney is best determined by analysis of renal biopsy. Mercury concentrations in the kidney of between 10 and 70 mg/kg have been reported in poison cases with renal injury. Levels <3 mg/kg may be found in normal cases. Occasionally, mercuric compounds may cause idiosyncratic skin symptoms, which may develop into severe exfoliative dermatitis or cause glomerular nephritis. Animal and clinical observations have shown that mercuric mercury stimulates and MeHg inhibits the immune system. A specific form of idiosyncrasy, called acrodynia or pink disease, is seen in children. Most cases are associated with mercury exposure in which increased levels of mercury in urine are detected.
Hazards involved in the long-term intake of food containing MeHg or ethylmercury (EthylHg) and in occupational exposure to MeHg are a result of the efficient absorption (90%) of alkylmercury in humans and the long retention time (half-life of 70 days for MeHg and shorter for EthylHg) leading to accumulation of alkylmercury in the brain. Chronic poisoning results in degeneration and atrophy of the sensory cerebral cortex, paresthesia, ataxia, hearing, and visual impairment, and an increased risk for cardiovascular diseases such as myocardial infarction and stroke. The latter effects are attenuated by the intake of polyunsaturated fatty acids (PUFAs) through fish consumption. Prenatal exposure causes cerebral palsy and, in less severe cases, psychomotor retardation. MeHg concentration in the blood and hair reflects the body burden and the brain concentration of MeHg. Intake resulting in body burdens of <0.5 mg/kg body weight is not likely to give rise to detectable neurological signs in adults. This intake corresponds to blood values of <200 μg/L and mercury levels in the hair of <50 mg/kg. However, this level of MeHg exposure in pregnant women may result in inhibited brain development of the fetus, with psychomotor retardation of the child. This effect also appears to be reduced by the intake of PUFAs through fish consumption. The highest level of MeHg load in pregnant women that is not associated with inhibition of fetal brain development is not known. Recent epidemiological studies have revealed that genetic polymorphisms can modify mercury metabolism and susceptibility to mercury exposure. Specific genotypes have been associated with increased susceptibility to mercury exposure in humans.
Current and historical nephric and hepatic mercury concentrations in terrestrial mammals in Poland and other European countries
2021, Science of the Total EnvironmentCitation Excerpt :In groups CF, THg levels were generally higher in kidneys than livers (except group D, Fig. 2). The dynamics of MeHg accumulation are influenced by many factors, including its amount in the diet, regularity or sporadicity of its supply, the presence of other substances in the diet (e.g. selenium), age, periodic moult, and finally the differentiation and capacity of detoxification mechanisms in marine, semiaquatic and terrestrial species – processes which are not yet fully known (Charbonneau et al., 1974; Chen et al., 1983; Bridges and Zalups, 2010; Roos et al., 2010; Dietz et al., 2011; Scheuhammer et al., 2015; Evans et al., 2016). Taken together, they may be responsible for the observed differences in the proportions of hepatic and nephric THg levels between species and mammalian ecotrophic groups.
The long-term anthropogenic release of mercury (Hg) into the environment has led to contamination of the biosphere, with all forms of Hg showing toxic effects and the ability to accumulate in organisms. Since the 1970s, efforts have been made in Western Europe to reduce Hg emissions and for the economic use of Hg, leading to a reduction in Hg exposure to humans and entire ecosystems. The purpose of this research was to present the total mercury (THg) burden in three mustelids (the piscivorous Eurasian otter and American mink, and the invertebrativorous European badger) inhabiting north-western Poland (mostly floodplains) and other European countries (literature data). Moreover, we wanted to investigate whether reductions in the environmental Hg burden in Europe have resulted in reductions in liver and kidney levels in wild terrestrial mammals (Eurasian otter, wild boar, red deer, roe deer, cervids, leporids, rodents, and ecotrophic groups: piscivorous mustelids, non-mustelids whose diets include aquatic prey, canids and other carnivores, omnivores, herbivores), between samples collected before and after 2000. We revealed significantly higher nephric THg levels in roadkilled than in trapped American minks. As roadkilled piscivorous mustelids from the same floodplain had similar hepatic and nephric THg concentrations, we suggest that the European research on Hg ecotoxicology should more often use alien American mink instead of the protected Eurasian otter. Badgers inhabiting Polish and other European floodplains bioaccumulated higher amounts of THg than those from other areas, and as such, may be recommended as bioindicator of mercury soil contamination. Our analysis of abundant data on mammalian hepatic and nephric THg concentrations (excluding non-piscivores mustelids) showed that in 12 of 21 cases, Hg concentrations had dropped significantly since 2000. This data signals a reduction in Hg contamination in terrestrial mammals, such as the Eurasian otter, and may be reason for cautious optimism.
Neuroprotection elicited by nerve growth factor and brain-derived neurotrophic factor released from astrocytes in response to methylmercury
2015, Environmental Toxicology and PharmacologyCitation Excerpt :Thus, MeHg primarily targets the central nervous system (CNS), and induce abnormal behavior, depending on CNS disruption (Takeuchi, 1982). Furthermore, MeHg elicits sensory and auditory impairment in humans (Uchino et al., 1995), visual disturbance and tremors in monkeys (Charbonneau et al., 1974), and hind limb bending cross in rats (Klein et al., 1972). Some reports have suggested possible mechanisms of MeHg-induced neuronal injury, including disruption of microtubule, and apoptosis induced by reactive oxygen species (Dare et al., 2000).
The protective roles of astrocytes in neurotoxicity induced by environmental chemicals, such as methylmercury (MeHg), are largely unknown. We found that conditioned medium of MeHg-treated astrocytes (MCM) attenuated neuronal cell death induced by MeHg, suggesting that astrocytes-released factors can protect neuronal cells. The increased expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) was observed in MeHg-treated astrocytes. NGF and BDNF were detected in culture media as homodimers, which are able to bind specific tyrosine kinase receptors, tropomyosin related kinase (Trk) A and TrkB, respectively. The TrkA antagonist and TrkB antagonist abolished the protective effects of MCM in neuronal cell death induced by MeHg. Taken together, astrocytes synthesize and release NGF and BDNF in response to MeHg to protect neurons from MeHg toxicity. This study is considered to show a novel defense mechanism against MeHg-induced neurotoxicity.
Mercury
2015, Handbook on the Toxicology of Metals: Fourth EditionMercury occurs as elemental mercury and as inorganic and organic compounds (mercury vapor, mercury liquid, mercury salts, short-chain alkylmercury compounds, alkoxyalkylmercury compounds, and phenylmercury compounds), all with different toxicological properties. Total mercury can be analyzed in water, air, and biological material by cold vapor atomic absorption methods and by neutron activation analysis, and can be detected down to concentrations of a tenth of a nanogram per gram in biological material. Methylmercury (MeHg) can be detected in biological material at levels of a few nanograms by extraction with benzene after strong acidification with hydrochloric acid, followed by gas chromatographic analysis of MeHg chloride. Other analytical methods for speciating inorganic mercury and several of the organomercurial forms have also been published. These methods include isotope dilution mass spectrometry, time-of-flight mass spectrometry, high performance liquid chromatography inductively coupled (ICP) plasma mass spectrometry, capillary electrophoresis-ICP, gas chromatography-ICP, and X-ray absorption fine structure spectroscopy.
Mercury is circulated naturally in the biosphere, with 30,000-50,000 tons being released into the atmosphere by degassing from the Earth’s crust and the oceans. In addition, 20,000 tons of mercury is released into the environment each year through human activities such as combustion of fossil fuels and other industrial releases. Approximately 2000 tons of mercury per year is produced for industrial use, a small part of which is used for synthesizing organic mercury compounds. The world production of mercury for commercial uses has been slowly declining over the past 20 years. There is now a ban on the export of mercury from the European Union.
In nature, MeHg is produced from inorganic mercury as a consequence of microbial activity. In mammals, oxidative demethylation occurs in vivo to produce inorganic mercury. In fish, most mercury is present as MeHg. Factors determining the MeHg concentration in fish are the mercury content in water and bottom sediments, the pH and redox potential of water, and the species, age, and size of the fish.
The toxic properties of mercury vapor are a consequence of mercury accumulation in the brain causing neurological signs involving an unspecific psychoasthenic and vegetative syndrome (micromercurialism). At high exposure levels, mercurial tremor is seen, accompanied by severe behavioral and personality changes, increased excitability, loss of memory, and insomnia. Mercurials may also affect other organ systems, such as the kidney. On a group basis, exposure levels are likely to be reflected in mercury concentrations in the blood and urine. Occupational exposure to mercury concentrations in air of > 0.1 mg/m3 may produce mercurialism. Micromercurialism has not been reported at concentrations < 0.01 mg/m3. Exposure to mercury vapor inhibits brain development in primates and in humans with certain genotypes. The exact dose-response relationship in humans is not known. Inorganic mercury but not MeHg has been found to induce and bind to the low molecular weight metal-binding protein, metallothionein.
The acute and long-term actions of mercuric salts, phenylmercury compounds, and alkoxyalkylmercury compounds are likely to be gastrointestinal disturbance and renal damage appearing as tubular dysfunction, with tubular necrosis in severe cases. The lethal dose in humans is approximately 1 g mercuric salt. The mercury load on the kidney is best determined by analysis of renal biopsy. Mercury concentrations in the kidney of between 10 and 70 mg/kg have been reported in poison cases with renal injury. Levels < 3 mg/kg may be found in normal cases. Occasionally, mercuric compounds may cause idiosyncratic skin symptoms, which may develop into severe exfoliative dermatitis or cause glomerular nephritis. Animal and clinical observations have shown that mercuric mercury stimulates and MeHg inhibits the immune system. A specific form of idiosyncrasy, called acrodynia or pink disease, is seen in children. Most cases are associated with mercury exposure in which increased levels of mercury in urine are observed.
Hazards involved in the long-term intake of food containing MeHg or ethylmercury (EthylHg) and in occupational exposure to MeHg are a result of the efficient absorption (90%) of alkylmercury in humans and the long retention time (half-life of 70 days for MeHg and shorter for EthylHg) leading to accumulation of alkylmercury in the brain. Chronic poisoning results in degeneration and atrophy of the sensory cerebral cortex, paresthesia, ataxia, hearing, and visual impairment, and implies an increased risk for cardiovascular disease such as cardiac infarction and stroke. The latter effects are attenuated by the intake of polyunsaturated fatty acids (PUFAs) through fish consumption. Prenatal exposure causes cerebral palsy and, in less severe cases, psychomotor retardation. MeHg concentration in the blood and hair reflects the body burden and the brain concentration of MeHg. Intake resulting in body burdens of < 0.5 mg/kg body weight is not likely to give rise to detectable neurological signs in adults. This intake corresponds to blood values of < 200 μg/L and mercury levels in the hair of < 50 mg/kg. However, this level of MeHg exposure in pregnant women may result in inhibited brain development of the fetus, with psychomotor retardation of the child. This effect also appears to be reduced by intake of PUFAs through fish consumption. The highest level of MeHg load in pregnant women that is not associated with inhibition of fetal brain development is not known. Recent epidemiological studies have revealed that genetic polymorphisms can modify mercury metabolism and susceptibility to mercury exposure. Specific genotypes have been associated with increased susceptibility to mercury exposure in humans.
A general overview of mercury from a historical perspective has been reviewed by Goldwater (1972). The pharmacology and toxicology of mercury was previously reviewed by Clarkson et al. (1972), the chemistry of mercury in biological systems by Carty and Malone (1979), the toxicology of MeHg by a Swedish Expert Group (1971), and the toxicology and epidemiology of mercury by Friberg and Vostal (1972), the Task Group on Metal Accumulation (1973), the Task Group on Metal Toxicity (1976), and the World Health Organization (WHO (World Health Organization), 1976, WHO, 1980, WHO., 1990, WHO., 1991). The toxicology of mercury has been reviewed in the U.S. Environmental Protection Agency Report to Congress (EPA, 1997), the Agency for Toxic Substances and Disease Registry (ATSDR, 1999), National Academy of Sciences National Research Council (NAS/NRC, 2000), and Institute of Medicine Report on Mercury in Vaccines (IOM, 2004).
Mercury
2014, Handbook on the Toxicology of MetalsMercury occurs as elemental mercury and as inorganic and organic compounds (mercury vapor, mercury liquid, mercury salts, short-chain alkylmercury compounds, alkoxyalkylmercury compounds, and phenylmercury compounds), all with different toxicological properties. Total mercury can be analyzed in water, air, and biological material by cold vapor atomic absorption methods and by neutron activation analysis, and can be detected down to concentrations of a tenth of a nanogram per gram in biological material. Methylmercury (MeHg) can be detected in biological material at levels of a few nanograms by extraction with benzene after strong acidification with hydrochloric acid, followed by gas chromatographic analysis of MeHg chloride. Other analytical methods for speciating inorganic mercury and several of the organomercurial forms have also been published. These methods include isotope dilution mass spectrometry, time-of-flight mass spectrometry, high performance liquid chromatography inductively coupled (ICP) plasma mass spectrometry, capillary electrophoresis-ICP, gas chromatography-ICP, and X-ray absorption fine structure spectroscopy.
Mercury is circulated naturally in the biosphere, with 30,000-50,000 tons being released into the atmosphere by degassing from the Earth’s crust and the oceans. In addition, 20,000 tons of mercury is released into the environment each year through human activities such as combustion of fossil fuels and other industrial releases. Approximately 2000 tons of mercury per year is produced for industrial use, a small part of which is used for synthesizing organic mercury compounds. The world production of mercury for commercial uses has been slowly declining over the past 20 years. There is now a ban on the export of mercury from the European Union.
In nature, MeHg is produced from inorganic mercury as a consequence of microbial activity. In mammals, oxidative demethylation occurs in vivo to produce inorganic mercury. In fish, most mercury is present as MeHg. Factors determining the MeHg concentration in fish are the mercury content in water and bottom sediments, the pH and redox potential of water, and the species, age, and size of the fish.
The toxic properties of mercury vapor are a consequence of mercury accumulation in the brain causing neurological signs involving an unspecific psychoasthenic and vegetative syndrome (micromercurialism). At high exposure levels, mercurial tremor is seen, accompanied by severe behavioral and personality changes, increased excitability, loss of memory, and insomnia. Mercurials may also affect other organ systems, such as the kidney. On a group basis, exposure levels are likely to be reflected in mercury concentrations in the blood and urine. Occupational exposure to mercury concentrations in air of > 0.1 mg/m3 may produce mercurialism. Micromercurialism has not been reported at concentrations < 0.01 mg/m3. Exposure to mercury vapor inhibits brain development in primates and in humans with certain genotypes. The exact dose-response relationship in humans is not known. Inorganic mercury but not MeHg has been found to induce and bind to the low molecular weight metal-binding protein, metallothionein.
The acute and long-term actions of mercuric salts, phenylmercury compounds, and alkoxyalkylmercury compounds are likely to be gastrointestinal disturbance and renal damage appearing as tubular dysfunction, with tubular necrosis in severe cases. The lethal dose in humans is approximately 1 g mercuric salt. The mercury load on the kidney is best determined by analysis of renal biopsy. Mercury concentrations in the kidney of between 10 and 70 mg/kg have been reported in poison cases with renal injury. Levels < 3 mg/kg may be found in normal cases. Occasionally, mercuric compounds may cause idiosyncratic skin symptoms, which may develop into severe exfoliative dermatitis or cause glomerular nephritis. Animal and clinical observations have shown that mercuric mercury stimulates and MeHg inhibits the immune system. A specific form of idiosyncrasy, called acrodynia or pink disease, is seen in children. Most cases are associated with mercury exposure in which increased levels of mercury in urine are observed.
Hazards involved in the long-term intake of food containing MeHg or ethylmercury (EthylHg) and in occupational exposure to MeHg are a result of the efficient absorption (90%) of alkylmercury in humans and the long retention time (half-life of 70 days for MeHg and shorter for EthylHg) leading to accumulation of alkylmercury in the brain. Chronic poisoning results in degeneration and atrophy of the sensory cerebral cortex, paresthesia, ataxia, hearing, and visual impairment, and implies an increased risk for cardiovascular disease such as cardiac infarction and stroke. The latter effects are attenuated by the intake of polyunsaturated fatty acids (PUFAs) through fish consumption. Prenatal exposure causes cerebral palsy and, in less severe cases, psychomotor retardation. MeHg concentration in the blood and hair reflects the body burden and the brain concentration of MeHg. Intake resulting in body burdens of < 0.5 mg/kg body weight is not likely to give rise to detectable neurological signs in adults. This intake corresponds to blood values of < 200 μg/L and mercury levels in the hair of < 50 mg/kg. However, this level of MeHg exposure in pregnant women may result in inhibited brain development of the fetus, with psychomotor retardation of the child. This effect also appears to be reduced by intake of PUFAs through fish consumption. The highest level of MeHg load in pregnant women that is not associated with inhibition of fetal brain development is not known. Recent epidemiological studies have revealed that genetic polymorphisms can modify mercury metabolism and susceptibility to mercury exposure. Specific genotypes have been associated with increased susceptibility to mercury exposure in humans.
A general overview of mercury from a historical perspective has been reviewed by Goldwater (1972). The pharmacology and toxicology of mercury was previously reviewed by Clarkson et al. (1972), the chemistry of mercury in biological systems by Carty and Malone (1979), the toxicology of MeHg by a Swedish Expert Group (1971), and the toxicology and epidemiology of mercury by Friberg and Vostal (1972), the Task Group on Metal Accumulation (1973), the Task Group on Metal Toxicity (1976), and the World Health Organization (WHO (World Health Organization), 1976, WHO, 1980, WHO., 1990, WHO., 1991). The toxicology of mercury has been reviewed in the U.S. Environmental Protection Agency Report to Congress (EPA, 1997), the Agency for Toxic Substances and Disease Registry (ATSDR, 1999), National Academy of Sciences National Research Council (NAS/NRC, 2000), and Institute of Medicine Report on Mercury in Vaccines (IOM, 2004).
The toxicology of mercury and its compounds
2014, Perspectives in MedicineDieser Artikel gibt einen konzentrierten Überblick über die Toxikologie von anorganischem Quecksilber zusammen mit einer umfassenden Übersicht über die Neurotoxikologie von Methylquecksilber. Die Probleme bei der Verwendung von anorganischem Quecksilber in Dentalamalgam werden sowohl im Hinblick auf eine berufsbedingte Exposition als auch bezüglich der möglichen gesundheitlichen Belastung von Patienten behandelt. Ebenso werden die zwei „ungelösten Rätsel” der Neurotoxizität von Methylquecksilber besprochen: die zelluläre Selektivität und das verzögerte Einsetzen der Symptome. Die für diese Aspekte relevante Literatur wird diskutiert, und es wird eine Reihe von Vorschlägen gemacht, wie diese Beobachtungen erklärt werden können.
- ☆
Presented in part at the Eleventh Annual Meeting of the Society of Toxicology, March, 1972, Williamsburg, Virginia.
- 2
Fisheries Research Board of Canada, Freshwater Institute, Environment Canada, Winnipeg, Manitoba.
- 3
Fisheries Research Board, Halifax, Nova Scotia.