Phenolics conjugated metabolites

Although mammals all metabolize phenol to the same metabolites, the amounts of each metabolite vary between species. For example, in the old world monkeys and prosimians, sulfation is the major phenol conjugation pathway, while in the new world monkeys, glucuronidation predominates (Mehta et al. 

Disposition in the Body. Rapidly absorbed from the gastrointestinal tract and readily penetrates the skin. It is metabolised by conjugation to yield phenyl glucuronide and phenyl sulphate small amounts are oxidised to catechol and quinol which are also conjugated. Oxidation of these metabolites to quinones may tint the urine green. Acid-labile phenol conjugates are present endogenously in serum at concentrations of about 0.1 pg/ml. Phenol is a metabolite of benzene. 

Kurihara, U. Urinary metabolites from gamma- and beta-BHC in the mouse Chloro-phenol conjugates. 3rd Intemat. S)mip. Chem. Toxicol. Aspects of Environ. Qual., Tokyo, Japan (19-22 Nov. 1973). 

One of the compoimds commonly determined as its Phase 1 metabolite is benzene, whieh is metabolized to phenol in the body (see Chapter 23, Section 23.13 and Figure 23.16). The phenol metabolic product of benzene is measured in urine, usually by gas chromatography. The urine sample is treated with perchlorie aeid to hydrolyze phenol conjugates and the phenol is extracted into diisopropyl ether for ehromatographic analysis. Two other metabolic products of benzene, trans,trans-mueonie aeid and S-phenyl mercapturic acid, are now commonly measured as more-speeifie biomarkers of benzene exposure. 

In terrestrial animals, the excreted products of PAHs are mainly conjugates formed from oxidative metabolites. These include glutathione conjugates of epoxides, and sulfate and glucuronide conjugates of phenols and diols. 

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... 

Reactive Metabolites of PAHs. A wide variety of products have been identified as metabolites of PAHs. These include phenols, quinones, trans-dihydrodiols, epoxides and a variety of conjugates of these compounds. Simple epoxides, especially those of the K-region, were initially favored as being the active metabolites responsible for the covalent binding of PAH to DNA. Little direct experimental support exists for this idea (62.63,64) except in microsomal incubations using preparation in which oxidations at the K-region are favored (65,66). Evidence has been presented that a 9-hydroxyB[a]P 4,5-oxide may account for some of the adducts observed in vivo (67.68) although these products have never been fully characterized. 

Carbofuran in animals may also be hydrolyzed to produce carbofuran-7-phenol. Hydrolysis of the 3-hydroxyderivative leads to formation of 3-hydrocarbofuran-7-phenol. Other degradation products include /V-hydroxymethyl carbofuran and, as in plants, 3-hydroxy- and 3-ketoderivatives. All of these compounds may become conjugated and excreted by animals in urine and, presumably, bile (Metcalf et al. 1968 Finlayson et al. 1979). At least 10 metabolites of carbofuran are known at present their interrelations are shown in detail by Menzie (1978). 

Many drugs and metabolites are metabolized by conjugation with sulfate or glucuronic acid as described in Chapter 7. Sulfate conjugates can be hydrolyzed back to the alcohol or phenol. Glucuronide conjugates can involve a wider variety of functional groups and... 

The present paper deals with a relation between toxicity and accumulation of chlorophenols in goldfish, Carassius auratus, PCP metabolites and their amounts excreted by the three major routes (branchial, renal and biliary) in the fish, and also with effects of pre-exposure to PCP on PCP-tolerance and on sulfate conjugation with phenol by the liver soluble fraction of the fish. 

Four principal metabolites have been identified in mammals two phenol and two hydroquinone conjugates (of sulfate and glucuronide) (Capel et al. 1972 Kenyon et al. 1995 Wheldrake et al. 1978). 

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