Chloroform metabolites

A recent in vitro study of mice hepatic microsomes indicated that a reductive pathway may also play an important role in chloroform hepatotoxicity (Testai et al. 1990). It was demonstrated that radical chloroform metabolites bind to macromolecules (proteins, lipids) and the process can be inhibited by reduced GSH. 

The metabolic pathways of chloroform metabolites are well understood. It appears that both the mode of oral administration and the vehicle affect metabolism. Additional data investigating the mode and vehicle of administration would be useful in order to understand the role of these factors in the mechanism of chloroform s toxicity. The co-administration of other compounds (e.g., ethanol) has been shown to alter chloroform metabolism and toxicity. Further investigations of the hazards associated with exposure to complex mixtures containing chloroform would be useful. 

L. Fabrizi, G.W. Taylor, B. Canas, A.R. Boobis and J. Edwards, Adduction of the chloroform metabolite phosgene to lysine residues of human histone H2B, Chem. Res. Toxicol., 16, 266-275 (2003). 

The body is able to rid itself of carcinogenic chloroform metabolites more efficiently at very low doses than it can at very high doses. 

Fabrizi L, Taylor GW, Edwards RJ, Boobis AR. Adducts of the chloroform metabolite phosgene. Adv Exp Med Biol, 2001 500 129-132. 

Diaz Gomez MI and Castro JA (1980). Covalent binding of chloroform metabolites to nuclear proteins - no evidence for binding to nucleic acids. Cancer Lett, 9,213-218. 

Fabrizi L, Taylor GW, Edwards RJ et al. (2001). Adducts of the chloroform metabolite phosgene. In Biological Reactive Intermediates VI (Dansette PM, Snyder R, Delaforge M, eds), pp. 129-132. New York, NY, USA and Amsterdam, The Netherlands Kluwer Academic/Plenum Publishers. 

P. Husek, P. Matucha, P. Simek, Smooth Esterification of Di and Tricarboxylic Acids with Methyl and Ethyl Chloroformates in Gas Chromatographic Profiling of Urinary Acidic Metabolites, Chromatographia, 58, 623 630 (2003). 

Pillai, C.G.P., J.D. Weete, and D.E. Davis. 1977. Metabolism of atrazine by Spartina altemiflora. I. Chloroform-soluble metabolites. Jour. Agric. Food Chem. 25 852-855. 

The 3,7-dicarboxylic acid metabolite was also measured fluorimetrically by extraction with ethyl acetate chloroform 1 1 at pH=l and re-extraction into aqueous solution. The fluorescence was determined at 350/435 nm there was no cross interference with the nalidixic acid determination.(8)... 

Pohl, L.R., Branchflower, R.V., Highet, R.J., et al. 1981. The formation of diglutathionyl dithiocarbonate as a metabolite of chloroform, bromotrichloromethane, and carbon tetrachloride. Drug. Metab. Dispos. 9 334—338. 

FIGURE 4.18 Structures of the CYP2E1 substrates, chloroform, butadiene, and N,N-dimethylnitrosoamine, and their chemically reactive and toxic metabolites. 

Cow feces (di sulfoton and 5 metabolites as total residue) Extraction with chloroform concentration then oxidation with m-chioroperbenzoi c acid clean-up by column chromatography GC/FPD 1ng/kga 74 Bowman and Beroza 1969... 

Water was sampled at given intervals and thoroughly extracted with equal volumes of chloroform. The chloroform extract was concentrated under nitrogen at 25°C and then developed by TLC. Several metabolites were extracted from the gel with acetone for gas chromatographic-mass spectral characterization. 

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