Metabolic fate and disposition of [14C]hydroquinone given orally to Sprague-Dawley rats

DiVincenzo, G.D.; Hamilton, M.L.; Reynolds, R.C.; Ziegler, Donald A.

doi:10.1016/0300-483x(84)90012-x

Cited by 37 publications

(11 citation statements)

References 5 publications

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“…Following single or multiple oral doses of up to 350 mg/kg HQ in experimental animals, approximately 90% of administered dose is recovered in the urine as one of these conjugates (2-to-1 glucuronide/sulfate ratio). [47][48][49]51 Similar values are seen after i.t. administration.…”

Section: Toxicokinetics Of Hqsupporting

confidence: 87%

“…Numerous reports indicate that HQ is well absorbed by the oral route. Single oral doses of up to 350 mg/kg were >90% absorbed in CD and F344 rats, with peak blood levels occurring within <1 h. [47][48][49][50][51] Similar findings were reported with oral exposure of rats to developer solution containing 3% HQ. 52 Rapid and substantial oral absorption in humans ingesting foods containing mg levels of HQ has been demonstrated.…”

Section: Toxicokinetics Of Hqsupporting

confidence: 79%

“…81 Semiquinone radicals can also combine to regenerate HQ and BQ by means of disproportionation. Brunmark and Cadenas proposed 48 an alternative mechanism of redox cycling, in which P450-mediated oxidation of HQ accompanied by GSH addition would form benzenetriol-SG, a derivative more likely to participate in cycling than HQ itself.…”

Section: Macromolecular Binding and Redox Reactionsmentioning

confidence: 98%

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The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

DeCaprio¹

1999

Critical Reviews in Toxicology

174

128

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Hydroquinone (HQ) is a high-volume commodity chemical used as a reducing agent, antioxidant, polymerization inhibitor, and chemical intermediate. It is also used in over-the-counter (OTC) drugs as an ingredient in skin lighteners and is a natural ingredient in many plant-derived products, including vegetables, fruits, grains, coffee, tea, beer, and wine. While there are few reports of adverse health effects associated with the production and use of HQ, a great deal of research has been conducted with HQ because it is a metabolite of benzene. Physicochemical differences between HQ and benzene play a significant role in altering the pharmacokinetics of directly administered when compared with benzene-derived HQ. HQ is only weakly positive in in vivo chromosomal assays when expected human exposure routes are used. Chromosomal effects are increased significantly when parenteral or in vitro assays are used. In cancer bioassays, HQ has reproducibly produced renal adenomas in male F344 rats. The mechanism of tumorigenesis is unclear but probably involves a species-, strain-, and sex-specific interaction between renal tubule toxicity and an interaction with the chronic progressive nephropathy that is characteristic of aged male rats. Mouse liver tumors (adenomas) and mononuclear cell leukemia (female F344 rat) have also been reported following HQ exposure, but their significance is uncertain. Various tumor initiation/promotion assays with HQ have shown generally negative results. Epidemiological studies with HQ have demonstrated lower death rates and reduced cancer rates in production workers when compared with both general and employed referent populations. Parenteral administration of HQ is associated with changes in several hematopoietic and immunologic endpoints. This toxicity is more severe when combined with parenteral administration of phenol. It is likely that oxidation of HQ within the bone marrow compartment to the semiquinone or p-benzoquinone (BQ), followed by covalent macromolecular binding, is critical to these effects. Bone marrow and hematologic effects are generally not characteristic of HQ exposures in animal studies employing routes of exposure other than parenteral. Myelotoxicity is also not associated with human exposure to HQ. These differences are likely due to significant route-dependent toxicokinetic factors. Fetotoxicity (growth retardation) accompanies repeated administration of HQ at maternally toxic dose levels in animal studies. HQ exposure has not been associated with other reproductive and developmental effects using current USEPA test guidelines. The skin pigment lightening properties of HQ appear to be due to inhibition of melanocyte tyrosinase. Adverse effects associated with OTC use of HQ in FDA-regulated products have been limited to a small number of cases of exogenous ochronosis, although higher incidences of this syndrome have been reported with inappropriate use of unregulated OTC products containing higher HQ concentrations. The most serious human health effect related to HQ is p...

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Section: Toxicokinetics Of Hqsupporting

confidence: 87%

Section: Toxicokinetics Of Hqsupporting

confidence: 79%

Section: Macromolecular Binding and Redox Reactionsmentioning

confidence: 98%

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The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

DeCaprio¹

1999

Critical Reviews in Toxicology

174

128

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“…Nevertheless, the rate of formation in rat hepatocyte incubations was probably too low to allow a clear separation and identification of this compound. No evidence was obtained for the formation of HQ disulfate in accordance with a report by Divincenzo et al (28).…”

Section: Discussionsupporting

confidence: 84%

Phase II metabolism of benzene.

Schrenk

Orzechowski

Schwarz

et al. 1996

Environ Health Perspect

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The hepatic metabolism of benzene is thought to be a prerequisite for its bony marrow toxicity. However, the complete pattern of benzene metabolites formed in the liver and their role in bone marrow toxicity are not fully understood. Therefore, benzene metabolism was studied in isolated rodent hepatocytes. Rat hepatocytes released benzene-1,2-dihydrodiol, hydroquinone (HQ), catechol (CT), phenol (PH), trans-trans-muconic acid, and a number of phase II metabolites such as PH sulfate and PH glucuronide. Pretreatment of animals with 3-methylcholantrene (3-MC) markedly increased PH glucuronide formation while PH sulfate formation was decreased. Likewise, V79 cells transfected with the 3-MC-inducible rat UGT1.6 cDNA showed a considerable rate of PH and HQ glucuronidation. In addition to inducing glucuronidation of phenols, 3-MC treatment (reported to protect rats from the myelotoxicity of benzene) resulted in a decrease of hepatic CYP2E1. In contrast, pretreatment of rats with the CYP2E1-inducer isopropanol strongly enhanced benzene metabolism and the formation of phenolic metabolites. Mouse hepatocytes formed much higher amounts of HQ than rat hepatocytes and considerable amounts of 1,2,4-trihydroxybenzene (THB) sulfate and HQ sulfate. In conclusion, the protective effect of 3-MC in rats is probably due to a shift from the labile PH sulfate to the more stable PH glucuronide, and to a decrease in hepatic CYP2E1. The higher susceptibility of mice toward benzene may be related to the high rate of formation of the myelotoxic metabolite HQ and the semistable phase II metabolites HQ sulfate and THB sulfate.ImagesFigure 4.

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“…Estudos realizados em animais de laboratórios têm demonstrado que quando a hidroquinona é administrada por via oral pode ser excretada no ar expirado 0,4%; urina 91,9% e nas fezes 3,8%. Na urina excretada, 25 a 42% está sob a forma de monosulfato e 56 a 66% sob a forma de monoglucuronato (DIVINCENZO, et al, 1984).…”

Section: • Metabolismounclassified

Desenvolvimento de metodologias analíticas para determinação de hidroquinona em cosméticos e medicamentos

García¹

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Metabolic fate and disposition of [14C]hydroquinone given orally to Sprague-Dawley rats

Cited by 37 publications

References 5 publications

The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

Phase II metabolism of benzene.

Desenvolvimento de metodologias analíticas para determinação de hidroquinona em cosméticos e medicamentos

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