Reactive Metabolites From the Bioactivation of Toxic Methylfurans

Ravindranath, Vijayalakshmi; Burka, Leo T.; Boyd, Michael R.

doi:10.1126/science.6719117

Cited by 142 publications

(102 citation statements)

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“…The methyl analogs of furan are metabolically activated in a similar fashion as the parent furan, yielding highly reactive, unsaturated dialdehydes (Ravindranath, Burka, and Boyd 1984;Ravindranath and Boyd 1985). Estimates of dietary exposure have been calculated by conducting surveys of furan levels within foods found in Canada .…”

Section: Introductionmentioning

confidence: 99%

A 28-day Gavage Toxicity Study in Male Fischer 344 Rats with 2-methylfuran

et al. 2013

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In most thermally treated products, a series of alkylated furan derivatives have been found, in particular 2-substituted alkylfurans such as 2-methylfuran. These methyl analogs are metabolically activated in a similar fashion as the parent furan, yielding highly reactive unsaturated dialdehydes. There is currently limited toxicological data available for 2-methyl furan exposure by any route that makes conducting a risk assessment difficult. In this pilot study, we report the general toxicology findings affecting tissue morphology, histopathology, clinical biochemistry, and hematology in a 28-day gavage study. The liver was the primary target organ that developed dose-dependent toxicity. Relative liver weights were increased by 42% at 25.0 mg/kg/body weight (bw)/day. Histological changes in the liver were observed at 0.4, 1.5, 3.0, 6.0, 12.0, and 25.0 mg/kg bw/ day. These changes were not accompanied by clinical changes in the serum enzyme markers such as alanine transaminase, alkaline phosphatase, and aspartate transaminase. Clinical biochemistry markers for kidney were altered, but these were not accompanied by histological changes. The prostate was significantly decreased in size at the 25.0 mg/kg bw/day dose of 2-methyfuran. Some hematological parameters were also altered.

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Section: Introductionmentioning

confidence: 99%

A 28-day Gavage Toxicity Study in Male Fischer 344 Rats with 2-methylfuran

et al. 2013

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“…They are frequently observed in the exhaust plumes and nearby environment of combustion sources. Many studies have shown that they are toxic, whether ingested or inhaled, and thus pose a considerable threat to human health (1)(2)(3)(4). The simplest of these compounds (i.e., unsubstituted furan, C 4 H 4 O) is a cyclic, dienic ether with a low molecular weight, high volatility, and high lipophilicity.…”

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confidence: 99%

Formation and emission of large furans and oxygenated hydrocarbons from flames

Johansson

Dillstrom

Monti

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Many oxygenated hydrocarbon species formed during combustion, such as furans, are highly toxic and detrimental to human health and the environment. These species may also increase the hygroscopicity of soot and strongly influence the effects of soot on regional and global climate. However, large furans and associated oxygenated species have not previously been observed in flames, and their formation mechanism and interplay with polycyclic aromatic hydrocarbons (PAHs) are poorly understood. We report on a synergistic computational and experimental effort that elucidates the formation of oxygen-embedded compounds, such as furans and other oxygenated hydrocarbons, during the combustion of hydrocarbon fuels. We used ab initio and probabilistic computational techniques to identify low-barrier reaction mechanisms for the formation of large furans and other oxygenated hydrocarbons. We used vacuum-UV photoionization aerosol mass spectrometry and X-ray photoelectron spectroscopy to confirm these predictions. We show that furans are produced in the high-temperature regions of hydrocarbon flames, where they remarkably survive and become the main functional group of oxygenates that incorporate into incipient soot. In controlled flame studies, we discovered ∼100 oxygenated species previously unaccounted for. We found that large alcohols and enols act as precursors to furans, leading to incorporation of oxygen into the carbon skeletons of PAHs. Our results depart dramatically from the crude chemistry of carbonand oxygen-containing molecules previously considered in hydrocarbon formation and oxidation models and spearhead the emerging understanding of the oxidation chemistry that is critical, for example, to control emissions of toxic and carcinogenic combustion by-products, which also greatly affect global warming.furans | oxygenated hydrocarbons | soot | organic carbon | black carbon

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“…Autoradiography revealed that the covalently bound radioactivity was predominantly associated with Clara cells, and in vitro studies suggested that a cytochrome P-450-dependent monooxygenase was required to activate 4-ipomeanol to a reactive metabolite(s) that bound covalently to macromolecules. While much of the early data suggested that the reactive metabolite of 4-ipomeanol was the furan epoxide, studies with 2-and 3-methylfuran identified the unsaturated aldehydes acetylacrolein and methylbutenedial, respectively, as the principal reactive metabolites (62). Thus, in the absence of further data we cannot yet conclude the nature of the reactive metabolites of 4-ipomeanol.…”

Section: -Lpomeanolmentioning

confidence: 88%

Pulmonary Metabolism of Foreign Compounds: Its Role in Metabolic Activation

Cohen¹

1990

Environmental Health Perspectives

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The lung has the potential of metabolizing many foreign chemicals to a vast array ofmetabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity ofmany pulmonary toxins. Enviroxnmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity.

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Reactive Metabolites From the Bioactivation of Toxic Methylfurans

Cited by 142 publications

References 12 publications

A 28-day Gavage Toxicity Study in Male Fischer 344 Rats with 2-methylfuran

A 28-day Gavage Toxicity Study in Male Fischer 344 Rats with 2-methylfuran

Formation and emission of large furans and oxygenated hydrocarbons from flames

Pulmonary Metabolism of Foreign Compounds: Its Role in Metabolic Activation

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