Pentachlorophenol conjugated

Initially formed polar metabolites such as phenols and amines may be conjugated to water-soluble terminal metabolites that are excreted into the medium and function as an effective mechanism of detoxification. For example, pentachlorophenol and pentachlorothiophenol produced from pentachloronitrobenzene conjugated represented the major metabolites. Although the naphthalene dihydrodiol was the major metabolite produced from naphthalene, the further transformation... 

Stehly, G.R. and W.L. Hayton. 1988. Detection of pentachlorophenol and its glucuronide and sulfate conjugates in fish bile and exposure water. Jour. Environ. Sci. Health B23 355-366. 

Covalent protein adducts of quinones are formed through Mchael-type addihon reachon with protein sulfhydryl groups or glutathione. Metabolic activahon of several toxins (e.g., naphthalene, pentachlorophenol, and benzene) into quinones has been shown to result in protein quinone adducts (Lin et al, 1997 Rappaport et al, 1996 Zheng et al., 1997). Conversion of substituted hydroquinones such as p-aminophenol-hydroquinone and 2-bromo-hydroquinone to their respective glutathione S-conjugates must occur to allow bioactivation into nephrotoxic metabolites (Dekant, 1993). Western blot analysis of proteins from the kidneys of rats treated with 2-bromo-hydroquinone has revealed three distinct protein adducts conjugated to quinone-thioethers (Kleiner et al, 1998). 

Absorption of pentachlorophenol is relatively rapid in all species studied, but elimination differs between species and also between sexes. Metabolism occurs through glucuronic acid conjugation and hydrolytic dechlorination to tetrachlorohydroquinone, which is further conjugated. In contrast to rodents, rhesus monkeys eliminate pentachlorophenol in urine unchanged (lARC, 1991). 

Detailed toxicokinetic studies have been performed in both rats (Yuan et al., 1994) and mice (Reigner et al., 1992), comparing intravenous and gavage (and in rat feed) administration of pentachlorophenol. In mice, after either intravenous or oral administration, tlie elimination half-life was about 5-6 h. Only 8% of the dose (15 mg/kg bw) was excreted unchanged in urine, while 20% was excreted as tetrachlorohydroquinone and its conjugates. Sulfate conjugates represented 90% of the total conjugates of pentachlorophenol and tetrachlorohydroquinone. 

Disposition in the Body. Readily absorbed after ingestion, inhalation or through intact skin. Pentachlorophenol and its oxidised metabolite, tetrachlorohydroquinone, are excreted in the urine in free and conjugated forms, with about 74% of a dose being excreted unchanged in 7 days. About 4% of a dose is eliminated in the faeces. 

Pentachlorobenzene can be absorbed readily through gastrointestinal and respiratory tracts in humans and experimental animals. Chlorobenzenes accumulate primarily in fatty tissues and have been shown to cross the placenta. Pentachlorobenzene is metabolized via cytochrome P450-dependent processes to its major metabolites pentachlorophenol and 2,3,4,6-tetrachlorophenol. Food restriction was reported to increase its metabolism. Metabolites are excreted in the urine as mercapturic acids, glucuronic acid, or sulfate conjugates. Some proportion of the chemical is eliminated unchanged in the feces. 

As shown in Table I, photoreactions of certain halogenated aromatic compounds and conjugated dienes are very rapid with full exposure to solar radiation. Field studies of Crossland and Wolff (10) showed that direct photoreaction of pentachlorophenol was its dominant fate in selected ponds in southern England (Figure 1). 

Glucuronide conjugates of pentachlorobenzene were observed following the initial phenol formation from hexachlorobenzene in rainbow trout (Oncorhynchus mykiss) fry following dietary exposure27. Other metabolites included traces of 2,5-dichloro-, 2,3,6-trichloro- and 2,4,5-trichloro-phenol. The biotransformation of pentachlorophenol... 

Postscript A fatty acid-conjugated pesticide palmitoyl pentachlorophenol was Isolated from human fat and reported In the literature after this manuscript was presented at the 189th National ACS Meeting (31). 

Schuur AG, Bergman A, Brouwer A, et al. 1999. Effects of pentachlorophenol and hydroxylated polychlorinated biphenyls on thyroid hormone conjugation in a rat and a human hepatoma cell line. Toxicol in Vitro 13 417-425. 

Pretreatment of rats with pentachlorophenol, an inhibitor of sulfation and perhaps of other conjugation reactions, led to a marked decrease in the inversion, suggesting that this chiral inversion of stiripentol is at least in part mediated by an enantioselective conjugation mechanism [160]. Further studies examining the influence of the route of administration demonstrated that this inversion phenomenon was not observed when stiripentol was administered intravenously or intraperitoneally (Fig. 17). Finally, in vitro experiments suggest that stiripentol may undergo partial acid-catalyzed racemization in the rat stomach before absorption from the G1 tract [161]. 

Formation of glycoside conjugates does not necessarily represent the termination of a particular herbicide detoxification sequence in plants, and the glycoside conjugates are frequently subjected to further modification. Thus, 25 was acylated to the N-malonylglucoside in tomato plants, as was the )8-D-glucosyl conjugate of pentachlorophenol in suspension cultures of soybean and wheat. 

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