Chlorophenols metabolism

Fig. 2. Chlorophenol metabolism in rats (scheme proposed by Ahlborg 1977).

Walker N (1973) Metabolism of chlorophenols by Rhodotorula glutinis. Soil Biol Biochem 5 525-530. 

Salicylate is an intermediate in the metabolism of PAHs including naphthalene and phen-anthrene, and its degradation involves oxidation to catechol. The hydroxylase (monooxygenase) has been extensively studied (references in White-Stevens and Kamin 1972) and in the presence of an analog that does not serve as a substrate, NADH is oxidized with the production of H2O2 (White-Stevens and Kamin 1972). This uncoupling is characteristic of flavoenzymes and is exemplified also by the chlorophenol hydroxylase from an Azotobacter sp. that is noted later. 

Spokes JR, N Walker (1974) Chlorophenol and chlorobenzoic acid co-metabolism by different genera of soil hacteria. Arch Microbiol 96 125-134. 

The tolerance of the strains to high concentrations of pentachlorophenol—S. chlorophenolica appears to be less sensitive than M. chlorophenolicus (Miethling and Karlson 1996). This may be attribnted to the ability of the cells to adapt their metabolism to avoid synthesis of toxic concentrations of chlorinated hydroquinones, and is consistent with the low levels of these metabolites measnred in the cytoplasm of cells metabolizing pentachlorophenol (McCarthy et al. 1997). Inocnla have also been immobilized on polyurethane that, in addition, ameliorates the toxicity of chlorophenols (Valo et al. 1990). 

Soil. Ambrosi et al. (1977a) studied the persistence and metabolism of phosalone in both moist and flooded Matapeake loam and Monmouth fine sandy loam. Phosalone rapidly degraded (half-life 3-7 d) but mineralization to carbon dioxide accounted for only 10% of the loss. The primary degradative pathway proceeded by oxidation of phosalone to phosalone oxon. Subsequent cleavage of the 0,0-diethyl methyl phosphorodithioate linkage gave 6-chloro-2-benzoxazolinone. Although 2-amino-5-chlorophenol was not detected in this study, they postulated that the condensation of this compound yielded phenoxazinone. 

Wang et al. (1996) found that a 1 ppm solution of 1,4-dichlorobenzene was taken up by carrots Daucus car Ota, 49%), soybeans Glycine max, 50%), and red goosefoot Chenopodium rubrum, 62%), but not by tomatoes (Lycopersicon esculentum). Only the soybean cell cultures provided evidence of the existence of metabolites of this compound, probably conjugates of chlorophenol. The authors further observed that the uptake, metabolism, and toxicity of 1,4-dichlorobenzene differed among the species tested. 

The absorption of 2,4-dichloro-, 2,4,5-trichloro-, 2,4,6-trichloro-, 2,3,4,5- and 2,3,4,6-tetrachlorophenol is relatively rapid when they are given orally, dermally or by inhalation. Chlorophenols are almost exclusively metabolized to conjugates which are mainly excreted in the urine. Half-lives are from hours to days, the compounds with higher chlorine content having longer half-lives (lARC, 1986). 

The highest concentrations of studied chlorophenols (2,4-, 2,4,6- and 2,3,4,6-) have been found in kidney, liver and spleen and the lowest concentrations in muscle and brain, either after parenteral administration of these chlorophenols themselves or as metabolites of other organochlorine compounds. Over 80% of the dose is excreted in urine and 5-20% in faeces. Metabolism varies somewhat depending on chlorine content the low-chlorine substances tend to be excreted as glucuronide and sulfate conjugates with higher chlorine substitution, excretion of the unchanged substance tends to increase. Formation of chlorinated 1,4-quinones is a minor pathway except for 2,3,5,6-tetrachlorophenol (WHO, 1989). 

Wainstok de Calmanovici, R. San Martin de Viale, L.C. (1980) Effect of chlorophenols on porphyrin metabolism in rats and chick embryo. Int. J. Biochem., 12, 1039-1044... 

In such a case, the organisms have an enzyme capable of oxidizing Q. Only degradation of Q allows the bacteria to obtain carbon and energy sufficient to maintain and multiply the population. Due to imperfect substrate specificity, the same enzymatic reaction takes place with BQ too. Similar co-metabolism by enzymes intended for natural substrates has been reported for many xenobiotic compounds like chlorinated solvents (Semprini, 1997), chlorophenols (Kim and Hao, 1999), and chlorobiphenyls (Kohler et al., 1988). 

Valo, R. (1990). Occurrence and metabolism of chlorophenolic wood preservative in the environment. Ph.D. thesis, University of Helsinki, Helsinki, Finland. 

However, like TOL, TOM encodes the meta-fission of the resulting catechol (Figure 11.4). Consequently, it is unproductive in the assimilation of chloroaromatics like chlorobenzene and 2-chlorophenol, which are also metabolized to 3-chlorocatechol because of catechol 2,3-dioxygenase inactivation. To avoid a build-up of this product an ortho-cleavage enzyme and downstream enzymes for the complete catabolism of the product were recruited through the introduction of the 2,4-dichlorophenoxyacetic-acid-degradativeplasmid pROlOl (Kaphammer, Kukor Olsen, 1990). 

Relatively stable arene oxides are the expected intermediates in the metabolism of halobenzenes to a variety of products.214 Oxide 107 isomerizes exclusively to 2-chlorophenol, whereas 109 rearranges exclusively to 4-chlorophenol. Both 107 and 109 react with glutathione and are converted to trans-dihydrodiols. 

Lindsay-Smith et al. (1972) reported that the major metabolites of chlorobenzene in the rabbit are p-chlorophenylmercapturic acid and conjugates of 4-chlorocatechol. Other urinary metabolites included quinol, 3- chlorocatechol, and o-and m-chlorophenylmercapturic acids. Oesch et al. (1973) studied the metabolism of chlorobenzene in rats administered chlorobenzene by intraperitoneal injection. Thirty-three percent of the administered dose was excreted in the urine, with p-chlorophenol as the major metabolite. Other metabolites included 4-chlorocatechol, o-chlorophenol, and m- chlorophenol. 

Polychlorinated diphenyl ethers (PCDE) are common impurities in chlorophenol formulations, which were earlier used as fungicides, slimicides, and as wood preservatives. PCDEs are structurally and by physical properties similar to polychlorinated biphenyls (PCB). They have low water solubility and are lipophilic. PCDEs are quite resistant to degradation and are persistent in the environment. In the aquatic environment, PCDEs bioaccumulate. These compounds are found in sediment, mussel, fish, bird, and seal. PCDEs show biomagnification potential, since levels of PCDEs increase in species at higher trophic levels. PCDEs are also detected in human tissue. Despite the persistence and bio accumulation, the significance of PCDEs as environmental contaminants is uncertain. The acute toxicity and Ah-receptor-me-diated (aryl hydrocarbon) activity of PCDEs is low compared to those of polychlorinated di-benzo-p-dioxins (PCDD) and dibenzofurans (PCDF). Due to structural similarity to thyroid hormone, PCDEs could bind to thyroid hormone receptor and alter thyroid function. Furthermore, PCDEs might be metabolized to toxic metabolites. In the environment, it is possible that photolysis converts PCDEs to toxic PCDDs and PCDFs. 

Just as diphenyl ether is metabolized to hydroxydiphenyl ether derivatives [107],PCDEs can be metabolized to hydroxy-PCDEs [18,34].Tulp et al. [18] studied the metabolism of PCDEs in rats and observed that the major metabolic route is hydroxylation, but chlorophenols can also be formed by scission of the ether bond. They detected mono-, di-, and trihydroxy metabolites in rats and... 

Suflita, J.M., Miller, G.D. (1985) Microbial metabolism of chlorophenolic compounds in groundwater aquifers. Environ. Toxicol. Chem. 4, 751-758. 

Chlorophenols block adenosine triphosphate (ATP) production, without blocking the electron transport chain. They inhibit oxidative phosphorylation, which increases basal metabolic rate and increases body temperature. As body temperature rises, heat-dissipating mechanisms are overcome and metabolism is accelerated. Adenosine diphosphate (ADP) and other substrates accumulate, and stimulate the electron transport chain further. This process demands more oxygen in a futile effort to produce ATP. Oxygen demand quickly surpasses oxygen supply and energy reserves of the body become depleted. 

The metabolites of hexachlorobenzene, penta chlorophenol (PCP) and tetrachlorohydroquinone (TCHQ), appear to be capable of altering porphyrin metabolism in in vitro systems containing d-ALA... 

Chlorophenols are a class of pesticide substances, e.g. fungicides, used for wood preservation, in pulp production and other miscellaneous applications. The substances were introduced in the 1930s and have been used in very large amounts. Today, the consumption has decreased and the substances are banned in many countries. The main active substance in chlorophenol products is pentachloro-phenol (PCP Figure 3.10). The substance is moderately lipophilic and persistent, yet readily absorbed and accumulated in biota and expresses a rather high acute toxicity. The metabolism and breakdown of this envirotoxicant in biota and in the environment are rather slow, resulting in successively dechlorinated metabolites. 

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