Lipophilic chlorinated hydrocarbon

Both hexachloroethane and its lipophilic metabolites can distribute to body fat. Only hexachloroethane can be used to confirm compound exposure by way of a fat biopsy, since some of its metabolites are also produced from other chlorinated hydrocarbons or are present as contaminants in the environment. Based on one worker occupationally exposed to hexachloroethane, Selden et al. (1993) estimated that the plasma half-life in humans was several days, but less than one week. A clearance half-life in rats of 2.5 days was reported for hexachloroethane absorbed from the diet (Gorzinski et al. 1985). Therefore, similar to measurement of hexachloroethane in blood, urine, and feces, hexachloroethane in body fat is representative of current exposures rather than exposures that occurred weeks or months before testing. 

The quantities of solvents in paints vary with desired characteristics (e.g., drying time desired) and application (building interiors, automotive surfaces, and architectural applications). Other solvents, including chlorinated hydrocarbons and terpenes, for example, are also formulated into paints. Virtually all solvent-based paints contain mixtures of lipophiles and hydrophiles. The exposures of painters to low levels of solvents (sufficiently low enough so that they do not experience acute symptoms at the time of exposure and below the TLVs for the individual solvent molecules) enables one to ascribe neurotoxicological reactions to low level mixture exposures. 

The compounds that have been identified as xenoestrogens vary widely in chemical nature. Many are highly lipophilic and slowly metabolized (TCDD, chlorinated hydrocarbon pesticides). Others are less lipophilic and more labile (phthalates) and some are hydrophilic (methyl paraben, aluminum chloride, and aluminum chlorohydrate). It is known that lipophilic chemicals are more readily absorbed through the skin than hydrophilic chemicals, but as has been pointed out repeatedly in this book, lipophiles facilitate the absorption of hydrophiles and contribute to unexplained mixture effects. Table 22.3 lists some of the known xenoestrogens, types of products they are used in, and their K)w values. 

Reproductive disorders in humans are known to be caused by more than 100 different individual chemicals and are suspected to be caused by some 200 more. Table 23.1 lists some of these compounds and their Kqw values. W As can be seen from this table, many different types of chemicals containing far different functional groups cause reproductive disorders. These include aliphatic and aromatic hydrocarbons, glycol ethers, chlorinated hydrocarbons, pesticides, and heavy metals. Both lipophilic and hydrophilic compounds are contained in the list. Some of the chemicals are rapidly metabolized, whereas others accumulate in adipose tissue and are stored in the body for long periods of time. The mechanisms by which many of these chemicals act remain unknown. 

The hepatotoxicity of 1,1,1-trichloroethane is quite low compared to other chlorinated hydrocarbons, including 1,1,2-trichloroethane. The relatively low toxicity of 1,1,1-trichloroethane may be due to its relatively low metabolism rate, since the more hepatotoxic halocarbons are extensively metabolized. Whether the mild effects of repeated 1,1,1 -trichloroethane exposure are evoked by the parent compound or the limited quantities of metabolites produced is not known, however. The available data indicate that the acute effects on the central nervous and the cardiovascular systems are caused by 1,1,1-trichloroethane and not its metabolites. The interference of 1,1,1-trichloroethane with membrane-mediated processes, due to lipophilicity, may be responsible for the acute effects on these systems several cellular and biochemical processes appear to be affected by... 

Supersolubilisation of NAPL can be achieved by adding lipophilic linkers to the system. Best results for chlorinated hydrocarbons were obtained with both hydrophilic and lipophilic linkers [71]. Lipophilic linkers increase the interaction between surfactant and oil [72], and hydrophilic linkers the interaction between surfactant and water. Systems with Aerosol MA as surfactant, sodium mono- and dimethyl naphthalate as hydrophilic linker, and dodecanol as lipophilic linker display the best performance regarding efficiency, economy and environmental aspects [65]. 

Lipophilic substances with low reactivity may dissolve in the cell membranes and change their physical characteristics. Alcohols, petrol, aromatics, chlorinated hydrocarbons, and many other substances show this kind of toxicity. Other, quite unrelated organic solvents like toluene give very similar toxic effects. Lipophilic substances may have additional mechanisms for their toxicity. Examples are hexane, which is metabolized to 2,5-hexandion, a nerve poison, and methanol, which is very toxic to primates. 

Biotransformation of certain chlorinated hydrocarbon insecticides results in their conversion to metabolites which are less polar than the parent chemical. Heptachlor and aldrin are converted to the more lipophilic compounds heptachlor epoxide and dieldrin, respectively, whereas DDT is converted to DDE. The primary residue of DDT, which persists to the present day in animals and humans after exposure over a decade ago, is DDE. Following biotransformation, these compounds distribute to tissues which are higher in neutral lipid content than are the major organs of metabolism and excretion, the liver and kidney. These lipid-rich tissues are relatively, deficient in the so-called mixed-function oxidase (MFO) enzyme systems necessary for biotransformation of the halogenated hydrocarbons to more polar and thus more easily excreted compounds. As a result, these lipophilic chemicals remain unchanged in adipose tissue with only limited amounts returning to the circulation for possible metabolism and excretion. Paradoxically, aldrin and heptachlor metabolism results in an increased rather than reduced body load. This is opposite of the pattern seen for most other pesticide classes. 

Heavily chlorinated hydrocarbon carcinogens such as dieldrin, DDT, and carbon tetrachloride are not positive in either the Ames test, the E. coli polA test, or yeast mitotic recombination assay. The reason for the lack of positive results for these compounds in all of the microbial assays is not known but may be related to their highly lipophilic nature which may result in their entrapment in microbial cell wall membranes. 

B. Chlorinated Hydrocarbons These agents are persistent—very poorly metabolized— lipophilic chemicals that accumulate in body fat and thus are subject to both bioaccumulation and biomagnification (see Table 57-1). 

Dioxins are a family of the most toxic chlorinated organic compounds known to science, numbering around 75 dioxins and 135 related furans. These can cause cancer and are ECD for humans, even at very low exposure levels, since minute amounts, can bio-accumulate due to their ease of solubility in body fat (dioxins are hydrophobic, water-hating and lipophilic, fat-loving ). Number and position of chlorine atoms in the molecule has a considerable effect on toxicity, and 17 dioxins are classed as highly toxic. These include polychlorinated dioxins (PCDD) and dibenzofurans (PCDF) which are by-products of the chlorine bleaching of paper, the burning of chlorinated hydrocarbons (such as pentachlorophenol, PCB, and PVC) and the incineration of municipal/medical... 

In a study carried out by the U.S. National Toxicology Program, laboratory animals were watered with water containing a mixture of 25 common groundwater contaminants at environmentally relevant levels. The chemicals, which included many lipophiles and hydrophUes, included aromatic hydrocarbons, chlorinated hydrocarbons, and other... 

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