Chloroform, biotransformation

Levels of Significant Exposure to Chloroform—Inhalation 2-2 Levels of Significant Exposure to Chloroform—Oral 2-3 Metabolic Pathways of Chloroform Biotransformation... 

Metabolic pathways of chloroform biotransformation are shown in Figure 2-3. Metabolism studies indicated that chloroform was, in part, exhaled from the lungs or was converted by oxidative dehydrochlorination of its carbon-hydrogen bond to form phosgene (Pohl et al. 1981 Stevens and Anders 1981). This reaction was mediated by cytochrome P-450 and was observed in the liver and kidneys (Ade et al. 1994 Branchfiower et al. 1984 Smith et al. 1984). In renal cortex microsomes of... 

Figure 15.2 Proposed mechanism of chloroform biotransformation. (From J. B. Tarloff in An Introduction to Biochemical Toxicology, 3rd ed., E. Hodgson and R. C. Smart eds., Wiley, 2001.)...

Phosgene is widely used as a chemical intermediate. It is used in metallurgy and in the production of pesticides, herbicides, and many other compounds. It is a by-product of chloroform biotransformation and can be generated from some chlorinated hydrocarbon solvents under intense heats. Phosgene has been used as a chemical warfare agent. 

Cianflone DJ, Hewitt WR, Villeneuve DC, et al. 1980. Role of biotransformation, in the alterations of chloroform hepatotoxicity produced by Kepone and mirex. Toxicol Appl Pharmacol 53 140-149. 

Hewitt LA, Caille G, Plaa GL. 1986b. Temporal relationships between biotransformation, detoxication, and chlordecone potentiation of chloroform-induced hepatotoxicity. Can J Physiol Pharmacol 64(4) 477-482. 

Smith JH, Hewitt WR, Hook JB. 1985. Role of intrarenal biotransformation in chloroform-induced nephrotoxicity in rats. Toxicology 79 166-174. 

Testai E, Gramenzi F, Di Marzio S, et al. 1987. Oxidative and reductive biotransformation of chloroform in mouse liver microsomes. Mechanisms and Models in Toxicology Arch Toxicol Suppl 11 42-44. 

Carbon tetrachloride is metabolized by cytochrome P-450 to the reactive metabolites trichloromethyl free radical and trichloromethylperoxy free radical. The trichloromethyl free radical may bind directly to cellular macromolecules such as lipids and proteins, and also to DNA, disrupting cell processes and breaking down membranes. The free radical can take part in anaerobic reactions, subsequently forming such toxic compounds as chloroform, hexachloroethane, and carbon monoxide. Aerobic biotransformation of the... 

See also Acetaminophen Acetylaminofluorene Acetyl-salicylic Acid Aflatoxin Biotransformation Blood Bromo-benzene Carbon Tetrachloride Chloroform Dioxins Distribution Ethanol Excretion Immune System Is-oniazid Lipid Peroxidation Metallothionein Peroxisome Proliferators Tissue Repair. 

Cresteil, T., Beaune, R, Leroux, J. R, Lange, M., Mansuy, D. Biotransformation of chloroform by rat and human liver microsomes in vitro effect on some enzyme activities and mechanism of irreversible binding to macromolecules. Chem. Biol. Interact. 1979, 24, 153-165. 

Chloroform is assumed to be metabolized in either the liver or the kidney, and the rates of biotransformation in these tissue are described by Michaelis-Menten kinetics. Metabolism is implemented in a general manner, with biotransformation possible in any compartment. Biotransformation is limited to the liver and kidney by setting the V ax coefficients for compartments other than the liver and kidney to zero (see Lines 100 and 101 in Code Listing 3, Appendix 43.3). 

A preparative-scale biotransformation of benzosampangine (192 mg) was performed with Cunninghamella blakesleeana ATCC 8688a. This afforded a partially pure metabolite (70.8 mg). This metabolite was further purified by HPLC over a silica gel column, using chloroform-methanol (8 2) mixture as eluent and fractions were collected and combined based on retention time and TLC analysis. This afforded a pure metabolite (BZSAMMl, 6 mg, 2% yield). This yield is not a good representative of the actual conversion of benzosampangine into this metabolite, since rapid... 

Chlorite and chlorate are rapidly absorbed into the plasma and distributed throughout the body, with the highest concentrations in plasma. They are excreted primarily in the urine in the form of chloride, with lesser amounts of chlorite and chlorate. However, the extent to which these are formed as chemical degradation products prior to absorption or as a result of biotransformation was unclear. There was some indication of metabolism to chloroform, but the data were inadequate to evaluate or to use in the safety assessment. 

Weathers, L. J. Parkin, G. F. Metallic Iron-Enhanced Biotransformation of Carbon Tetrachloride and Chloroform Under Methanogenic Conditions. In Bioremediation of Chlorinated Solvents Hinchee, R. E., et al., Eds. Battelle Press Columbus, OH, 1995 pp 117-122. 

Ephedrine is an alkaloid, a sympathomimetic amine with molecular formula Cjo Hi5 NOi, a molecular mass of 165.2, and the stmctural name (IR, 25)-2-methylamino-l-phenylpropan-l-ol. This bitter colorless or white solid-crystal is completely soluble in water, alcohol, chloroform, ether, and glycerol. Ephedrine is also produced by chemical synthesis and there is significant documentation of commercial ephedrine production using microbial biotransformation techniques [42]. Ephedrine has a structure close to methamphetamines, and its stimulant actions are comparable to epinephrine (adrenaline), a hormone produces by the adrenal glands that enhances heart rate and constriction of blood vessels in high-stress situations. Medicinal use of ephedrine began around 3000 B.C with the Chinese from md hudng, but its isolation was first reported in 1855 and its pharmaceutical application started in 1930 [22]. Studies on ephedrine s molecular structure show that two asynunetric carbon atoms are involved in ephedrine s molecular skeleton therefore, four optically active stereoisomers forms naturally occur as follows (IR, 2S)-(—)-ephedrine, (IS, 2R)-(+)-ephedrine, (IR, 2R)-( )-pseudoephedrine, (IS, 2S)-(+)-pseudoephedrine (Fig. 27.2). 

It has recently been found that obligately anaerobic microbial consortia can mineralize many recalcitrant chemicals (toluene, chloroform, benzene, chlorophenols, etc.) that had been considered essentially nonbiodegradable in the absence of oxygen (19, 20, 21). Extensive work at the University of Idaho with obligately anaerobic microbial consortia indicates that these systems are capable of complete biodegradation of nitroaromatic pollutants. Work with 2-.s c-butyl-4,6-dinitrophenol (dinoseb) has shown complete fermentation of this nitroaromatic pollutant in soils by anaerobic consortia without buildup of aromatic biotransformation products (16, 17). Similar results were observed with a variety of nitro-toluenes and munitions residues, including TNT and trimethylenenitramine (RDX) under appropriately controlled conditions (12, 13). In the work with TNT and RDX, hydroxyaro-... 

The effect of moisture content on production of phenylacetyl carbinol by cells immobilized on celite was investigated using hexane as organic solvent (Table 3). Maximum biotransformation activity was observed with a moisture level of 10%, The effect of the solvent type on the rate of production of phenylacetyl carbinol was investigated in two-phase systems containing 10% moisture and related to log P. The results are presented in Table 4. The highest biotransformation activities were observed with hexane and hexa-decane and the lowest with chloroform and toluene. 

Cell surfaces of yeast biocatalyst recovered from biphasic media containing hexane, decane, and toluene after 26 h biotransformation reaction demonstrated no apparent damage (Fig, 2). Meanwhile cell puncturing was observed after shorter biotransformation periods with hydrophilic solvents (having P < 2.0), chloroform, etiiyl acetate, and butyl acetate (Figs. 3-5). Furthermore, cell-damaging solvents, ethyl acetate, butyl acetate, and chloroform resulted in the extraction of phosphohpid from the cell membranes into the... 

Figure 5 Scanning electron micrographs of biocatalyst recovered from two-phase systems containing chloroform at 0 time (left) and after a 2-h biotransformation (right). (From Ref. 73.)...

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