Metabolism and effects of hexachlorobenzene on hepatic microsomal enzymes in the rat

Mehendale, Harihara M.; Fields, Minerva.; Matthews, H. B.

doi:10.1021/jf60198a042

Cited by 99 publications

(25 citation statements)

References 15 publications

(20 reference statements)

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“…Because several of these metabolites are produced by an N1H shift mechanism (12), the oxide must be formed initially at a carbon atom already containing a chlorine atom (32). Reductive dechlorination(s) fol lowed by arene oxide formation (37,67) is also a possible reaction.…”

Section: Discussionmentioning

confidence: 99%

“…The formation of arene oxide intermediates at halo genated positions has been demonstrated to occur in the metabolism of several chlorinated benzenes (32,35,37) and mono- (72) and hexachlorinated (Matthews, manuscript in pre paration) biphenyls. Alternatively, reductive dechlorination(s) followed by arene oxide for mation is a possibility, since a NADPH-and 0 2-requiring microsomal system has been des cribed for hexachlorobenzene metabolism (37). Using highly radioactive TCDD, we show in this report that TCDD metabolism occurs via the cytochrome P-450-mediated monooxygenase system.…”

mentioning

confidence: 99%

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2,3,7,8-Tetrachlorodibenzo-p-Dioxin: Covalent Binding of Reactive Metabolic Intermediates Principally to Protein in vitro

Guenthner¹,

Fysh²,

Nebert³

1979

Pharmacology

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is metabolized by the mouse liver cytochrome P-450-mediated monooxygenase system to reactive intermediates which bind ‘cova-lently’ to cellular macromolecules. Although very difficult to quantitate, the presumably covalent binding to microsomal protein occurs between 120 and 2,640 times more readily than binding to deproteinized DNA in the in vitro reaction. Because of the extremely high rate of binding to protein rather than to DNA, it is visualized that TCDD metabolites may be so reactive that they bind in or near the P-450-active site where the TCDD is monooxygenated. This extreme reactivity may preclude the formation of detectable quantities of phenols, dihydrodiols, or conjugated products. The rate of TCDD metabolism is estimated to be between 9,000 and 36,000 times lower than the rate of P-450-mediated benzo[a]pyrene metabolism. To our knowledge, this is the first demonstration that TCDD is metabolized in any organism. There remains the possibility, however unlikely, that this covalently-bound radioactivity represents metabolites of contaminants -present in the radiolabeled TCDD sample in very minute amounts – rather than metabolites of tritiated TCDD itself. The possible relationship between P450-mediated metabolism of this environmental contaminant and its extreme toxicity or teratogenicity is discussed.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

2,3,7,8-Tetrachlorodibenzo-p-Dioxin: Covalent Binding of Reactive Metabolic Intermediates Principally to Protein in vitro

Guenthner¹,

Fysh²,

Nebert³

1979

Pharmacology

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“…During seven days following a single dose of 14 C-HCB to adult male rats (5 mg/kg b.w. per day, administered by oral intubation in arachis oil), approximately 16 % of the dose was excreted in the faeces and less than 1 % in urine (Mehendale et al, 1975). In a study performed in rats dosed intragastrically with 14 C-HCB, Ingebrigtsen et al (1981) showed that less than 4 % dose was recovered in the bile of bileduct-cannulated animals.…”

Section: Excretionmentioning

confidence: 99%

“…Other studies in rodents identified pentachlorobenzene, pentachlorophenol, pentachlorothiophenol, tetrachlorohydroquinone, tetrachlorobenzene, tetrachlorobenzene-1,4-diol, and 2,4,5-trichlorophenol as major urinary metabolites following oral HCB exposure (Koss et al, 1978;Mehendale et al, 1975;Rizzardini and Smith, 1982;Rozman et al, 1978).…”

Section: Metabolismmentioning

confidence: 99%

“…When HCB is administered in an oil vehicle, approximately 80 % of the dose (between 5 and 180 mg/kg b.w. per day) is absorbed (Albro and Thomas, 1974;Koss and Koransky, 1975;Mehendale et al, 1975;Ingebrigtsen et al, 1981;Ingebrigtsen and Nafstad, 1983). The absorption is limited (2 -20 %, depending on the dose) when HCB is administered as an aqueous suspension, or in a solid crystalline form (Iatropoulos, 1975;Koss and Koransky, 1975).…”

Section: Absorptionmentioning

confidence: 99%

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Opinion of the Scientific Panel on contaminants in the food chain [CONTAM] related to Hexachlorobenzene as undesirable substance in animal feed

2006

EFSA Journal

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Insecticides, Organochlorines

Plimmer¹,

Gammon²

2002

Encyclopedia of Agrochemicals

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Few chlorinated organic insecticides remain in use in North America and Europe. Several have been classified as Persistent Organic Pollutants and proscribed globally. However, their considerable benefits to humanity in the past should not be overlooked nor should the lessons that were learned during the period when they were applied to control disease vectors and agricultural pests throughout the world. Organochlorine compounds were not only used as pesticides, but they also had many industrial uses. Chlorinated organic compounds were also byproducts of a number of chemical manufacturing processes, and as a result of the careless disposal and handling of wastes, quantities were applied into the environment.

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Metabolism and effects of hexachlorobenzene on hepatic microsomal enzymes in the rat

Cited by 99 publications

References 15 publications

2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin: Covalent Binding of Reactive Metabolic Intermediates Principally to Protein <i>in vitro</i>

2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin: Covalent Binding of Reactive Metabolic Intermediates Principally to Protein <i>in vitro</i>

Opinion of the Scientific Panel on contaminants in the food chain [CONTAM] related to Hexachlorobenzene as undesirable substance in animal feed

Insecticides, Organochlorines

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