2-Methylfuran toxicity in rats?Role of metabolic activation in vivo

Ravindranath, Vijayalakshmi; McMenamin, Mary G.; Dees, Jane H.; Boyd, Michael R.

doi:10.1016/0041-008x(86)90389-3

Cited by 49 publications

(57 citation statements)

References 12 publications

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“…2-Methylfuran has been found to cause centrilobular necrosis of the liver as well as pulmonary bronchiolar lesions in mice (Franklin and Boyd 1978). It is activated by rat microsomal systems (Ravindranath and Boyd 1985) and metabolites of radiolabeled 2-methylfuran administered intraperitoneally can bind to both DNA and protein (Ravindranath et al 1986;Ravindranath and Boyd 1991). To date, there are no toxicological studies in rodents identifying a no observable adverse effect level (NOAEL) for 2-methylfuran.…”

Section: Introductionmentioning

confidence: 99%

“…Furan and 2-methylfuran were found to be potent hepatotoxins (Wiley et al 1984;Ravindranath et al 1986). Little toxicological information is available for 2-methylfuran where the preferred route of administration was by inhalation (Egle and Gochberg 1979) or intraperitoneal injection.…”

Section: Introductionmentioning

confidence: 99%

“…Little toxicological information is available for 2-methylfuran where the preferred route of administration was by inhalation (Egle and Gochberg 1979) or intraperitoneal injection. Results from inhalation studies of furan, 2-methylfuran, and 3-methylfuran were all found to induce pulmonary toxicity (Ravindranath et al 1986). 2-Methylfuran has been found to cause centrilobular necrosis of the liver as well as pulmonary bronchiolar lesions in mice (Franklin and Boyd 1978).…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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“…The maximal amount of radiolabel was detected in the liver at 8 hours post administration, followed by a steady decline up to 24 hours (Ravindranath et al, 1986).…”

Section: Tissue Distribution Of 50 -200 Mg [mentioning

confidence: 93%

Scientific Opinion on Flavouring Group Evaluation 13, Revision 2 (FGE.13Rev2): Furfuryl and furan derivatives with and without additional side-chain substituents and heteroatoms from chemical group 14

Flavourings¹

2011

EFSA Journal

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The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 27 flavouring substances in the Flavouring Group Evaluation 13, Revision 2, using the Procedure in Commission Regulation (EC) No 1565/2000. Three of the substances [Fl‐no: 13.125, 13.155 and 13.162] were considered to have genotoxic potential. The remaining 24 substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure‐activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that the 24 substances do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Adequate specifications including complete purity criteria and identity for the materials of commerce have been provided for all 24 flavouring substances evaluated through the Procedure.

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“…The importance of the unsaturated furan ring as a prerequisite for toxicity was demonstrated by Wirth et al (1976), who reported that a furosemide analog that had a fully saturated tetrahydrofuran group could not be metabolized to a reactive epoxide and did not become covalently bound to liver microsomes. There is evidence that both 3-methy and 2-methylfuran are also converted by CYP450 metabolism to highly reactive metabolites that are covalently bound to protein (Ravindranath et al 1986;Boyd et al 1978b). Boyd (1980) noted that a number of other furan derivatives, including 1-ipomeanol, 1,4-ipomeanol, ipomeanine, 2-methylfuran, and 2-furamide, as well as furan have been reported to cause pulmonary and/or hepatic necrosis in mice.…”

Section: Toxicology Summarymentioning

confidence: 99%

Proposed Occupational Exposure Limits for Non-Carcinogenic Hanford Waste Tank Vapor Chemicals

Poet¹,

Timchalk²

2006

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2-Methylfuran toxicity in rats?Role of metabolic activation in vivo

Cited by 49 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

Scientific Opinion on Flavouring Group Evaluation 13, Revision 2 (FGE.13Rev2): Furfuryl and furan derivatives with and without additional side-chain substituents and heteroatoms from chemical group 14

Proposed Occupational Exposure Limits for Non-Carcinogenic Hanford Waste Tank Vapor Chemicals

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