Seekall - Toxicology - Mercury, Rev. A
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SEEKALL: MERCURY, REV. A
http://seekall.wordpress.com/
A Toxicological Overview of:
MERCURY (Hg) Revision A (12/08/2009)
Page 1 of 6
SEEKALL: MERCURY, REV. A
http://seekall.wordpress.com/
Contents: •
Excerpts of Interest from: (A) ENVIRONMENTAL TOXICOLOGY - Second Edition Biological and Health Effects of Pollutants Ming-Ho Yu ISBN: 1-56670-670-X (B) ENCYCLOPEDIA OF TOXICOLOGY FOUR-VOLUME SET -- Volume 2
Page 2 of 6
SEEKALL: MERCURY, REV. A
http://seekall.wordpress.com/
(A) MERCURY 12.4.1 INTRODUCTION • “Hg has no known biological role and, because of its diversity of usage, is an industrial health hazard. It is a bioaccumulative metal that is fat soluble, and has many damaging effects on living organisms.” 12.4.3 SOURCES OF MERCURY POLLUTION • “The majority of Hg comes from anthropogenic sources. Mining, combustion of fossil fuels (Hg content of coal is about 1 ppm), transporting Hg ores, processing pulp and paper, incineration, use of Hg compounds as seed dressings in agriculture, and emissions from smelters are some examples. In addition, Hg waste is produced as a by-product of chlorine manufacturing plants and gold recovery processes, and is found in used batteries and light bulbs.” 12.4.5.3 EFFECTS OF MERCURY ON ANIMALS • “Fish may accumulate Hg in excess of the 0.5 mg/g FDA guideline.” • “Because increased temperature enhances metabolic rate, more Hg is concentrated in the summer than in the winter. The toxicity of Hg and other heavy metals to fish also increases with an increase in temperature.” • “Wild birds concentrate the highest levels of Hg in the kidney and liver, with less in the muscle tissues. … Many species of birds declined, both in numbers and in breeding success…” • “…high accumulation in various organs, such as the brain, is seen in sucklings when compared with adult animals. For example, the absorption rate (as % of oral dose) of 203Hg in one week- old suckling rats was 38.2%, whereas in 18-week-olds on either a milk diet or a standard diet, the rate was 6.7% and 1%, respectively. The neurotoxicity of MeHg varies greatly between animal species. For example, nonhuman primates and cats metabolize MeHg similarly to humans, but rats and mice rapidly metabolize the compound to a less toxic inorganic form.” 12.4.5.4 EFFECTS OF MERCURY ON HUMAN HEALTH • “Coal-fired power plants are the largest source of anthropogenic Hg airborne emissions in the U.S. (40% of total emissions).” • “The critical organ concentration of MeHg may differ for different stages of the human life cycle. The developing fetal and newborn brain may be the most sensitive organ (i.e., critical organ) in terms of human MeHg toxicity. … It was concluded that MeHg had crossed the placenta and that the fetal brain was much more sensitive than the adult brain. … In this outbreak, an infant’s blood Hg level was found to be higher than the mother’s during the first few months of life, supporting the suggestion that the fetal brain is the critical organ in the exposed pregnant female.” • “…Alkylorganic Hg is most likely to accumulate in nervous tissue.” • “Pronounced brain damage occurs in victims of Hg poisoning. The biological half-life of Hg is estimated to be 70 days. The critical daily intake has been estimated to be 300 mg Hg as MeHg for an average 70-kg man. Chronic Hg poisoning may result from exposure to small amounts of Hg over long periods… The victim experiences extreme salivation and thirst, nausea, severe gastrointestinal irritation, and abdominal pain. [colic, anyone?] Loss of fluids and electrolytes occurs.” • “It was reported that she was apparently transferring dimethylmercury in a fume hood when 0.1 to 0.5 ml of the compound spilled on the disposable latex gloves she was wearing and permeated them, quickly seeping into her skin. She became ill a few months later and died of Hg poisoning less than a year after the exposure.” 12.4.6 BIOLOGICAL EFFECTS OF MERCURY • “Mercury, like many other heavy metals, is extremely toxic because as an ion or in certain compounds it is soluble in water. For this reason it is readily absorbed into the body, where it tends to combine with and inhibit the functioning of various enzymes. The ultimate effects of Hg in the body are similar to those of Pb and Cd: inhibition of enzyme activity and cell damage.” • “Inhibits the active transport mechanism, destroys mitochondrial apparatus, causes swelling of cells, leading to lysis, suggested liver dysfunction, decreases DNA content in cells and adversely affects chromosomes and mitosis, leading to mutagenesis…appears to be cytotoxic as it alters the rates of DNA, RNA, and collagen synthesis.”
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SEEKALL: MERCURY, REV. A
•
http://seekall.wordpress.com/
“The MT protein receptor present in kidney tissue tends to bind actively with Hg and may thus exercise a protective effect. When the MT receptors are saturated with Hg, morphologic damage becomes manifest. An adaptive mechanism may also exit; MT content in the kidneys increases with repeated Hg exposure.”
12.4.7 MERCURY AND NUTRITION • “Dietary Se [Selenium] has been shown to exhibit a protective effect against Hg toxicity. Treatment with Se reduced the lethal and neurotoxic effects of MeHg and other Hg compounds. The reason for this protective action is not clear.” • “In addition to Se, vitamin E is also known to protect against the toxic effect of MeHg. However, a much higher concentration of this vitamin is required to provide the same level of protection.” (12.4.7) • “Ascorbic acid added to the diet of chicks was shown to overcome growth depression caused by 500 ppm Hg. … High dietary levels of ascorbic acid might result in increased urinary excretion of cations to balance the excretion of the ascorbate anion and thus increase the rate of excretion of toxic elements.”
ENVIRONMENTAL TOXICOLOGY - Second Edition Biological and Health Effects of Pollutants Ming-Ho Yu ISBN: 1-56670-670-X
==================================================================== === END OF ABOVE SOURCE =========================================== ====================================================================
Page 4 of 6
SEEKALL: MERCURY, REV. A
http://seekall.wordpress.com/
(B) MERCURY USES: • A major issue in recent years has been the presence of mercury in some vaccines, for example, in the vaccine preservative thimerosal – this has led to suspension of some vaccination programs and the development of preservative-free (i.e., mercury-free) vaccines as replacements. • Today, exposure of the general population comes from three major sources: fish consumption, dental amalgams, and vaccines. • Despite the extensive knowledge of the dangers of mercury, it is still misused and mishandled. For example, mercury has been sold in recent years in the United States under the name Azogue in Hispanic botanicas for oral administration to treat constipation, colic, or stomachache, and there have also been cases of mercury poisoning due to the use of a beauty cream, Crema de Belleza–Manning (6–10% w/w mercury), produced in Mexico but ‘commonly used among women of childbearing age’. TOXICOKINETICS: • Inhaled mercury vapor crosses through the alveolar cells readily, is 75% absorbed, and is carried by the red blood cells. Catalase in these cells oxidizes elemental mercury almost at once to the divalent state. Alcohol inhibits the catalase activity; however, in the seconds it takes for a complete blood circulation cycle, a significant amount of free mercury can cross the blood–brain barrier. • It is estimated that humans absorb 10% of ingested elemental mercury; whereas absorption of ingested methylmercury can be as high as 90%. • Inorganic forms of mercury (not organic forms) induce a metallothionein. Inorganic mercury concentrates mainly in the kidney. Organic mercury compounds, being lipid soluble, concentrate in adipose tissue and the brain. Elimination is primarily in the urine and the feces, with small amounts in breath, sweat, and saliva. MECHANISM OF TOXICITY: • Mercury has a great affinity for sulfydryl moieties and, hence, binds and inactivates a variety of enzymes. Methylmercury also initiates lipid peroxidation, which can produce alterations in cell membranes. Mercury damages the microtubules in the brain by reacting with the protein tubilin. ACUTE AND SHORT-TERM TOXICITY (OR EXPOSURE) (Human): • Mercury is an accumulative poison. • Renal failure occurs rapidly and, when patients survive, they must be maintained by dialysis. Regeneration of some kidney cells is possible but the damage is usually permanent. CHRONIC TOXICITY (OR EXPOSURE) (Human): • The neurotoxicity of mercury is devastating, especially for the central and peripheral nervous systems of children. Central nervous system defects and erethism as well as arrythmias, cardiomyopathies, and kidney damage have been associated with mercury exposure. The central nervous system symptoms include loss of memory, excitability, fever, and local tremors that can progress to the entire body. Necrotizing bronchitis and pneumonitis from inhalation of mercury vapor can lead to respiratory failure. Mercury is also considered a potent immunostimulant and suppressant, depending on exposure dose and individual susceptibility, producing a number of pathologic sequelae including lymphoproliferation, hypergammaglobulinemia, and total systemic hyper- and hypo-reactivities. Other clinical signs include inflammation of mouth and gums (gingivitis), tremors, loosening of teeth, jerky gait, personality change, depression, irritability, and nervousness. • Other congenital abnormalities con occur with prenatal exposure to methylmercury. A number of brain centers were damaged in the visual cortex and cerebellum. EXPOSURE STANDARDS AND GUIDELINES: • The American Conference of Governmental Industrial Hygienists threshold limit value, 8 h timeweighted average is 0.025 mgm_3 for mercury vapor and inorganic mercury. The (US) National Institute for Occupational Safety and Health Immediately Dangerous to Life or Health value is 10 mgm_3. The US Food and Drug Administration permits zero addition to the 20 ug of mercury contained in the average daily diet. Much of this comes from consumption of fish and seafood.
Page 5 of 6
SEEKALL: MERCURY, REV. A
http://seekall.wordpress.com/
ENCYCLOPEDIA OF TOXICOLOGY, FOUR-VOLUME SET -- VOLUME 3
==================================================================== === END OF ABOVE SOURCE =========================================== ====================================================================
Page 6 of 6
http://seekall.wordpress.com/
A Toxicological Overview of:
MERCURY (Hg) Revision A (12/08/2009)
Page 1 of 6
SEEKALL: MERCURY, REV. A
http://seekall.wordpress.com/
Contents: •
Excerpts of Interest from: (A) ENVIRONMENTAL TOXICOLOGY - Second Edition Biological and Health Effects of Pollutants Ming-Ho Yu ISBN: 1-56670-670-X (B) ENCYCLOPEDIA OF TOXICOLOGY FOUR-VOLUME SET -- Volume 2
Page 2 of 6
SEEKALL: MERCURY, REV. A
http://seekall.wordpress.com/
(A) MERCURY 12.4.1 INTRODUCTION • “Hg has no known biological role and, because of its diversity of usage, is an industrial health hazard. It is a bioaccumulative metal that is fat soluble, and has many damaging effects on living organisms.” 12.4.3 SOURCES OF MERCURY POLLUTION • “The majority of Hg comes from anthropogenic sources. Mining, combustion of fossil fuels (Hg content of coal is about 1 ppm), transporting Hg ores, processing pulp and paper, incineration, use of Hg compounds as seed dressings in agriculture, and emissions from smelters are some examples. In addition, Hg waste is produced as a by-product of chlorine manufacturing plants and gold recovery processes, and is found in used batteries and light bulbs.” 12.4.5.3 EFFECTS OF MERCURY ON ANIMALS • “Fish may accumulate Hg in excess of the 0.5 mg/g FDA guideline.” • “Because increased temperature enhances metabolic rate, more Hg is concentrated in the summer than in the winter. The toxicity of Hg and other heavy metals to fish also increases with an increase in temperature.” • “Wild birds concentrate the highest levels of Hg in the kidney and liver, with less in the muscle tissues. … Many species of birds declined, both in numbers and in breeding success…” • “…high accumulation in various organs, such as the brain, is seen in sucklings when compared with adult animals. For example, the absorption rate (as % of oral dose) of 203Hg in one week- old suckling rats was 38.2%, whereas in 18-week-olds on either a milk diet or a standard diet, the rate was 6.7% and 1%, respectively. The neurotoxicity of MeHg varies greatly between animal species. For example, nonhuman primates and cats metabolize MeHg similarly to humans, but rats and mice rapidly metabolize the compound to a less toxic inorganic form.” 12.4.5.4 EFFECTS OF MERCURY ON HUMAN HEALTH • “Coal-fired power plants are the largest source of anthropogenic Hg airborne emissions in the U.S. (40% of total emissions).” • “The critical organ concentration of MeHg may differ for different stages of the human life cycle. The developing fetal and newborn brain may be the most sensitive organ (i.e., critical organ) in terms of human MeHg toxicity. … It was concluded that MeHg had crossed the placenta and that the fetal brain was much more sensitive than the adult brain. … In this outbreak, an infant’s blood Hg level was found to be higher than the mother’s during the first few months of life, supporting the suggestion that the fetal brain is the critical organ in the exposed pregnant female.” • “…Alkylorganic Hg is most likely to accumulate in nervous tissue.” • “Pronounced brain damage occurs in victims of Hg poisoning. The biological half-life of Hg is estimated to be 70 days. The critical daily intake has been estimated to be 300 mg Hg as MeHg for an average 70-kg man. Chronic Hg poisoning may result from exposure to small amounts of Hg over long periods… The victim experiences extreme salivation and thirst, nausea, severe gastrointestinal irritation, and abdominal pain. [colic, anyone?] Loss of fluids and electrolytes occurs.” • “It was reported that she was apparently transferring dimethylmercury in a fume hood when 0.1 to 0.5 ml of the compound spilled on the disposable latex gloves she was wearing and permeated them, quickly seeping into her skin. She became ill a few months later and died of Hg poisoning less than a year after the exposure.” 12.4.6 BIOLOGICAL EFFECTS OF MERCURY • “Mercury, like many other heavy metals, is extremely toxic because as an ion or in certain compounds it is soluble in water. For this reason it is readily absorbed into the body, where it tends to combine with and inhibit the functioning of various enzymes. The ultimate effects of Hg in the body are similar to those of Pb and Cd: inhibition of enzyme activity and cell damage.” • “Inhibits the active transport mechanism, destroys mitochondrial apparatus, causes swelling of cells, leading to lysis, suggested liver dysfunction, decreases DNA content in cells and adversely affects chromosomes and mitosis, leading to mutagenesis…appears to be cytotoxic as it alters the rates of DNA, RNA, and collagen synthesis.”
Page 3 of 6
SEEKALL: MERCURY, REV. A
•
http://seekall.wordpress.com/
“The MT protein receptor present in kidney tissue tends to bind actively with Hg and may thus exercise a protective effect. When the MT receptors are saturated with Hg, morphologic damage becomes manifest. An adaptive mechanism may also exit; MT content in the kidneys increases with repeated Hg exposure.”
12.4.7 MERCURY AND NUTRITION • “Dietary Se [Selenium] has been shown to exhibit a protective effect against Hg toxicity. Treatment with Se reduced the lethal and neurotoxic effects of MeHg and other Hg compounds. The reason for this protective action is not clear.” • “In addition to Se, vitamin E is also known to protect against the toxic effect of MeHg. However, a much higher concentration of this vitamin is required to provide the same level of protection.” (12.4.7) • “Ascorbic acid added to the diet of chicks was shown to overcome growth depression caused by 500 ppm Hg. … High dietary levels of ascorbic acid might result in increased urinary excretion of cations to balance the excretion of the ascorbate anion and thus increase the rate of excretion of toxic elements.”
ENVIRONMENTAL TOXICOLOGY - Second Edition Biological and Health Effects of Pollutants Ming-Ho Yu ISBN: 1-56670-670-X
==================================================================== === END OF ABOVE SOURCE =========================================== ====================================================================
Page 4 of 6
SEEKALL: MERCURY, REV. A
http://seekall.wordpress.com/
(B) MERCURY USES: • A major issue in recent years has been the presence of mercury in some vaccines, for example, in the vaccine preservative thimerosal – this has led to suspension of some vaccination programs and the development of preservative-free (i.e., mercury-free) vaccines as replacements. • Today, exposure of the general population comes from three major sources: fish consumption, dental amalgams, and vaccines. • Despite the extensive knowledge of the dangers of mercury, it is still misused and mishandled. For example, mercury has been sold in recent years in the United States under the name Azogue in Hispanic botanicas for oral administration to treat constipation, colic, or stomachache, and there have also been cases of mercury poisoning due to the use of a beauty cream, Crema de Belleza–Manning (6–10% w/w mercury), produced in Mexico but ‘commonly used among women of childbearing age’. TOXICOKINETICS: • Inhaled mercury vapor crosses through the alveolar cells readily, is 75% absorbed, and is carried by the red blood cells. Catalase in these cells oxidizes elemental mercury almost at once to the divalent state. Alcohol inhibits the catalase activity; however, in the seconds it takes for a complete blood circulation cycle, a significant amount of free mercury can cross the blood–brain barrier. • It is estimated that humans absorb 10% of ingested elemental mercury; whereas absorption of ingested methylmercury can be as high as 90%. • Inorganic forms of mercury (not organic forms) induce a metallothionein. Inorganic mercury concentrates mainly in the kidney. Organic mercury compounds, being lipid soluble, concentrate in adipose tissue and the brain. Elimination is primarily in the urine and the feces, with small amounts in breath, sweat, and saliva. MECHANISM OF TOXICITY: • Mercury has a great affinity for sulfydryl moieties and, hence, binds and inactivates a variety of enzymes. Methylmercury also initiates lipid peroxidation, which can produce alterations in cell membranes. Mercury damages the microtubules in the brain by reacting with the protein tubilin. ACUTE AND SHORT-TERM TOXICITY (OR EXPOSURE) (Human): • Mercury is an accumulative poison. • Renal failure occurs rapidly and, when patients survive, they must be maintained by dialysis. Regeneration of some kidney cells is possible but the damage is usually permanent. CHRONIC TOXICITY (OR EXPOSURE) (Human): • The neurotoxicity of mercury is devastating, especially for the central and peripheral nervous systems of children. Central nervous system defects and erethism as well as arrythmias, cardiomyopathies, and kidney damage have been associated with mercury exposure. The central nervous system symptoms include loss of memory, excitability, fever, and local tremors that can progress to the entire body. Necrotizing bronchitis and pneumonitis from inhalation of mercury vapor can lead to respiratory failure. Mercury is also considered a potent immunostimulant and suppressant, depending on exposure dose and individual susceptibility, producing a number of pathologic sequelae including lymphoproliferation, hypergammaglobulinemia, and total systemic hyper- and hypo-reactivities. Other clinical signs include inflammation of mouth and gums (gingivitis), tremors, loosening of teeth, jerky gait, personality change, depression, irritability, and nervousness. • Other congenital abnormalities con occur with prenatal exposure to methylmercury. A number of brain centers were damaged in the visual cortex and cerebellum. EXPOSURE STANDARDS AND GUIDELINES: • The American Conference of Governmental Industrial Hygienists threshold limit value, 8 h timeweighted average is 0.025 mgm_3 for mercury vapor and inorganic mercury. The (US) National Institute for Occupational Safety and Health Immediately Dangerous to Life or Health value is 10 mgm_3. The US Food and Drug Administration permits zero addition to the 20 ug of mercury contained in the average daily diet. Much of this comes from consumption of fish and seafood.
Page 5 of 6
SEEKALL: MERCURY, REV. A
http://seekall.wordpress.com/
ENCYCLOPEDIA OF TOXICOLOGY, FOUR-VOLUME SET -- VOLUME 3
==================================================================== === END OF ABOVE SOURCE =========================================== ====================================================================
Page 6 of 6
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