Humans, alkyl mercurials

Alkyl mercury compounds in the blood stream are found mainly in the blood cehs, and only to a smah extent in the plasma. This is probably the result of the greater stabhity of the alkyl mercuric compounds, as well as their pecuflar solubiUty characteristics. Alkyl mercury compounds affect the central nervous system and accumulate in the brain (17,18). Elimination of alkyl mercury compounds from the body is somewhat slower than that of inorganic mercury compounds and the aryl and alkoxy mercurials. Methylmercury is eliminated from humans at a rate indicating a half-life of 50—60 d (19) inorganic mercurials leave the body according to a half-life pattern of 30—60 d (20). Elimination rates are dependent not only on the nature of the compound but also on the dosage, method of intake, and the rate of intake (21,22). 

Toxicology. Organo (alkyl) mercury compounds cause dysfunction of the central nervous system (CNS) and kidneys and are irritants of the eyes, mucous membranes, and skin methyl mercury causes developmental effects in humans. 

The biological half-life in humans for methyl mercury is about 70 days because elimination is slow, irregular, and individualized, there is a considerable risk of an accumulation of mercury to toxic levels. A precise relationship between atmospheric levels of alkyl mercury and concentrations of mercury in blood or urine has not been shown. Clinical observations indicate that concentrations of 50-100pg mercury/lOOml of whole blood may be associated with symptoms of intoxication concentrations around 10-20pg mercury/ 100 ml are not associated with symptoms. In a study of 20 workers engaged in the manufacture of organic mercurials and exposed for 6 years to mercury concentrations in air between 0.01 and O.lmg/m, there was no evidence of physical impairment or clinical laboratory abnormalities. Low levels of methyl mercury in the blood do not seem to affect the results of behavioral performance tests. ... 

An understanding of the environmental fate of these elements is necessary in the total assessment of associated health risks. Mercury is known to cycle between the geosphere and biosphere (35). Once in the hydrosphere, it can be converted by sediment flora into highly toxic methylmercury whereupon it is incorporated into aquatic life and ultimately accumulates in human food chains (31). Limited bacterial conversion of inorganic to organic mercury has been shown to occur in soil humus (36) and in animal tissue as well (37). There is no evidence that alkylated mercury is generated from coal combustion directly if it did it would probably be dissociated to the elemental form (14). 

Organic Mercury. An autopsy of a man who died after acute high-level exposure to alkyl mercury vapor revealed necrosis of the tubule epithelium, swollen granular protoplasm, and nonstainable nuclei in the kidneys (Hook et al. 1954). No studies were available on renal effects following intermediate or chronic-duration exposure to organic mercury vapors in humans. 

Mercury is unusual in its ability to induce delayed neurological effects. This is especially prevalent with exposure to alkyl mercury compounds. In such cases, the onset of adverse effects may be delayed for months after the initial exposure. The delayed effects of methyl- and dimethylmercury reported in human poisonings are thought, in part, to result from binding to red blood cells, and subsequent slow release. Methylmercury also forms a complex in plasma with the amino acid cysteine, which is structurally similar to the essential amino acid methionine (Aschner and Clarkson 1988). Clarkson (1995) proposed that methylmercury can cross the blood-brain barrier "disguised" as an amino acid via a carrier-mediated system (i.e., transport is not solely the result of methylmercury s lipid solubility). 

Pierce PE, Thompson JF, Likosky WH, et al Alkyl mercury poisoning in humans report of an outbreak. JAMA 220 1439-1442, 1972... 

MeHg" " is distributed throughout the body, and easily penetrates the blood-brain and blood-placental barriers (Clarkson 1993, Hansen et al. 1989, Suzuki et al. 1984). The transport of MeHg" " into tissues is mediated by the formation of a MeHg-cysteine complex (Aschner and Aschner 1990, Tanaka et al. 1991, Kerper et al. 1992). Soon after application, McHg" " is found in the blood, predominantly in the red cells. In humans, the ratio of MeHg in red blood cells to serum is approximately 20 1 (Kershaw et al. 1980). Short-chain alkyl-mercury compounds such as methylmercury or ethylmercury are rather stable in the body, whereas long-chain alkylmercury or arylmercury compounds such as phenylmercury may be metabolized relatively quickly to Hg " " ions (Roberts et al. 1979) and, therefore, show similar behavior to the Hg " " ion (Pfab et al. 

Further studies established that most alkyl mercurials pass through the bile and intestines and are reabsorbed (94). A logarithmic elimination curve which reaches background levels in 40 to 60 days (50) has been found with rats given single doses. Human volunteers excreted half in about 70 days (74, 95). The most active sites for mercury elimination are the kidneys, liver, hair, and feathers (95, 96, 97). In uncontaminated persons the kidneys have 20 times the concentration of the overall body average (95). Higher factors are found in persons exposed... 

In 2006, the speciation of metals and metalloids (As, Bi, Hg, Pb, Sb, Se and Sn) associated with alkyl groups and biomacromolecules in the environment was critically reviewed by Hirner.85 More than 60 species of alkylated metals and metalloids have been found in different ecosystems and terrestrial locations all over the world.85-87 These alkylated metals or metalloids are of interest due to their toxicological properties (e.g. monomethyl mercury, MMHg, which gained worldwide attention during the Minamata tragedy, and are not only known to be produced by microbial methylation within most anaerobic compartments of the environment, but also in the course of enzymatic transformation during human metabolism.85... 

Another major exposure route for humans is via contaminated food. For example, North America s Great Lakes, which are the largest body of freshwater in the world, are polluted with about 362 contaminants that were found in quantifiable amounts in the water, sediment, and biota (IJC 1983 USEPA 1994). The critical pollutants were identified as PCBs, DDT, dieldrin, toxaphene, mirex, methyl mercury, benzofa) pyrene, hexachlorobenzene, polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and alkylated lead. Some of these pollutants biomagnify in the aquatic food chain and can be detected in increased levels in cooked Great Lakes fish. Consequently, the blood serum levels of these chemicals are significantly increased in consumers of contaminated Great Lakes sport fish compared to people who do not eat such fish (Flumphrey 1983 Fiore et al. 1989 Sonzogni et al. 1991). 

In the case of mercury (Fig. 15-8), Wood suggests that reduction of Hg to Hg and alkylation to form methyl- or dimethylmercury can both be viewed as detoxification reactions, because all of the products are volatile and can be lost from the aqueous phase. Organisms can also convert the methylated forms to Hg , which is more volatile and less toxic. However, both the methylated and the reduced forms are more toxic to humans and other mammals than is Hg " ". 

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