Lipid-soluble inorganic compounds

Ionic Material. The kinetics of sorption-desorption processes of the ionic compound with the solid substrates under a variety of environmental conditions should be determined to arrive at the equilibrium concentration of the ionic compound in the free form. Complex/chelate formation of the ionic compound with the anions (organic and inorganic), micro-, and macrosolutes should be investigated to determine the extent of alteration in speciation and their behavior in water. Chelate formation with ligands containing donor atoms such as N, S, and Se, or even Cl in some cases (HgCl2) can modify the hydrophilic ionic compound into a strong lipid-soluble covalent compound. 

Nervous System. The nervous system is also a common target of toxic metals particularly, organic metal compounds (see Chapter 16). For example, methylmercury, because it is lipid soluble, readily crosses the blood-brain barrier and enters the nervous system. By contrast, inorganic mercury compounds, which are more water soluble, are less likely to enter the nervous system and are primarily nephrotoxicants. Likewise organic lead compounds are mainly neurotoxicants, whereas the first site of inorganic lead is enzyme inhibition (e.g., enzymes involved in heme synthesis). 

Ingestion. Minor Hg° absorption, except where mucous membranes are breached. Some absorption of soluble inorganic Hg(II). Rapid and easy absorption of organic Hg compounds due to high solubility in lipids. 

It has also been shown that arsenic is incorporated into marine and freshwater organisms in the form of both water-soluble and lipid-soluble compounds. Recent studies have shown the presence of arsenite [As(III)], arsenate [As(V)], methylarsonic acid, dimethylarsinic acid and arsenobetaine (AB). Methylated arsenicals also appear in the urine and plasma of mammals, including man, by biotransformation of inorganic arsenic compounds. Several methods have been devised to characterize these arsenicals. 

The main interest in methylation is the change in properties resulting from the attachment of methyl groups to the inorganic elements or compounds. Lipid solubility, volatility and persistence of metals in biological systems may be increased in the methyl... 

Serfontein and Mekel found that a survey of the literature on bismuth toxicity in man in relation to blood-level data shows the necessity of distinguishing between lipid-soluble and water-soluble organic complexes of bismuth on the one hand, and the simple inorganic salts of bismuth on the other. A characteristic feature of the former, illustrated by the water-soluble bismuth complex triglycollamate, is the high bismuth levels and the nephrotoxic properties of the compound in man. Bismuth absorption after administration of the simple inorganic salts of bismuth is postulated to occur in the form of ionic bismuth. 

Mercury will cross the placental barrier. In mammalian tissue, organic mercury, especially alkyl mercury, is converted to inorganic forms but not vice versa. 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. 

Nickel toxicity induced by parenteral administration of water-soluble, inorganic nickel compounds to rats induces peroxidative degradation of membrane lipids, as evidenced by increased concentrations of thiobarbitu-ric acid chromogens in liver, kidney, lung, spleen, and thymus increased concentrations of conjugated dienes in hepatic microsomal lipids and increased exhalation of ethane and ethylene (Donskoy et al. 1986, Kasprzak etal. 1986, Knight etal. 1986,... 

Organomercurials - particularly the alkyl- and arylmercury compounds - are more active as bactericides or fungicides than the inorganic salts. Phenylmercury acetate prevents the growth of a variety of fungi in vitro at concentrations of approximately 0.125 mg L whereas ethylmercury salts are active at 0.05 mg In contrast, mercuric acetate or chloride are active at 1.0 mg L . The difference may partly be attributed to lipid solubility, where penetra-... 

Tetraethyl lead and tetramethyl lead are lipid-soluble compounds that are absorbed readily from the skin, GI tract, and lungs. The toxicity of tetraethyl lead is believed to be due to its metabolic conversion to triethyl lead and inorganic lead. The major symptoms of intoxication with tetraethyl lead are referable to the CNS insomnia, nightmares, anorexia, nausea and vomiting, diarrhea, headache, muscular weakness, and emotional instability. Subjective CNS symptoms such as... 

The quantitative differences in toxicity between inorganic and alkylated mercury thus seem to be mediated by different bio-availability and pharmaco-kinetics. As already mentioned, inorganic mercury compounds are not as readily absorbed as organic mercury compounds, and the organic compounds have, like metallic mercury, a greater affinity to the brain than the inorganic compounds, due to their lipid-solubility. 

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