Disposition and metabolism of isoeugenol in the male Fischer 344 rat

Badger, Drew A.; Smith, Richard L.; Bao, Jennifer; Kuester, Robert K.; Sipes, I. G.

doi:10.1016/s0278-6915(02)00183-7

Cited by 43 publications

(28 citation statements)

References 14 publications

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“…The phase II conjugation might generally occur much more rapidly than phase I reactions in eugenol metabolism, and this caused three phase I metabolites and their related phase II metabolites not to be found. EQM and its related metabolite glutathione conjugate were not detected in vivo , which was similar to the report for isoeugenol (Badger et al , ). The potential toxicity of eugenol metabolism might compete with the rapid phase II conjugation and this was why the toxicities of eugenol in vitro and AEE in vivo were dose dependent (Lei and Xu, ; Thompson et al , ).…”

Section: Resultsmentioning

confidence: 99%

In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry

Shen

Liu

Yang

et al. 2014

Biomedical Chromatography

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Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with fewer side effects than its precursor, aspirin. Investigation into its metabolic process in target animal species will help to illustrate its mechanism of action and to establish its residual mark compound to formulate its dosage. Six beagle dogs were orally given a dose of 20 mg kg(-1) of AEE and one dog was used to prepare blank liver microsomes. Their liver microsomes were prepared for in vitro study and their plasma and urine were collected for in vivo metabolic analysis using liquid chromatography tandem mass spectrometry. In this study we identified 10 metabolites, M1, M2, M3, M4, M5 in phase I and M6, M7, M8, M9, M10 in phase II. Based on the metabolites of AEE, the pathways of AEE metabolism in dog were demonstrated.

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Section: Resultsmentioning

confidence: 99%

In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry

Shen

Liu

Yang

et al. 2014

Biomedical Chromatography

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“…No parent isoeugenol was detected in the blood at any of the time points analysed (LOD = 0.0009 mg/L). Less than 0.25 % of the radiolabel remained in selected tissues (Badger et al, 2002). Single administration toxicokinetic studies of isoeugenol in male and female rats and mice were conducted via intravenous and oral gavage routes (different oral doses comprised between 17 and 140 mg isoeugenol/kg bw).…”

Section: Safety For the Consumermentioning

confidence: 99%

Scientific Opinion on the safety and efficacy of propenylhydroxybenzenes (chemical group 17) when used as flavourings for all animal species

2012

EFSA Journal

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Isoeugenol is a flavouring compound belonging to chemical group 17, defined as ‘propenylhydroxybenzenes’. The additive is currently authorised for use as flavour in food and is naturally found in various herbs and plants. The use of isoeugenol as a flavour in feed for fish and other aquatic species is contra‐indicated. The range of use levels of 1 to 5 mg/kg feed proposed by the applicant for isoeugenol is safe for all animal species (except fish) with a margin of safety in the range of 1 to 4. Considering the low margin of safety, the simultaneous administration of isoeugenol in feed and water for drinking for poultry should be avoided. The use of isoeugenol as flavour in non‐dairy mammals up to the highest use levels proposed in feed is safe for the consumer. However, the lack of data on metabolism and residues in all other species and categories precludes an assessment of consumer exposure from these sources. No data on the safety for the user was provided. Based on the information available in the literature, the FEEDAP Panel considered isoeugenol as an irritant to the respiratory system, skin and eyes, and as a skin and respiratory sensitiser. The use of the additive in animal nutrition at the levels proposed is expected to be safe for the environment. Since isoeugenol is used in food as flavouring, and its function in feed is essentially the same as that in food, no further demonstration of efficacy is necessary.

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“…After administration by either route, approximately 10 % of the administered dose was excreted in the faeces and < 0.1 % was recovered in expired air. Less than 0.25 % of the radiolabel remained in selected tissues (Badger et al, 2002b). …”

Section: Iii2 Absorption Distribution and Eliminationmentioning

confidence: 99%

“…Isoeugenol, which contains a free phenolic hydroxy group, is also readily conjugated with glucuronic acid and sulphate, and subsequently excreted (Williams, 1959a;Badger et al, 2002b). In male Fischer 344 rats, given [14C] isoeugenol in a single oral dose of 156 mg/kg bw or a single intravenous dose of 15.6 mg, more than 80 % of the administered dose was excreted as the glucuronic acid and sulphate conjugate in the urine within 72 hours.…”

Section: Iii3 Metabolismmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 30, Revision 1 (FGE.30Rev1): 4‐Prop‐1‐enylphenol and 2‐methoxy‐4‐(prop‐1‐enyl)phenyl 3‐methylbutyrate from chemical group 17

Flavourings¹

2011

EFS2

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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 two flavouring substances in the Flavouring Group Evaluation 30, Revision 1, using the Procedure in Commission Regulation (EC) No 1565/2000. None of the substances were considered to have genotoxic potential. The two substances were evaluated through a stepwise approach 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 two substances [FL‐no: 04.097, 09.894] 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. For [FL‐no: 09.894] the composition of the stereoisomeric mixture needs to been specified.

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Disposition and metabolism of isoeugenol in the male Fischer 344 rat

Cited by 43 publications

References 14 publications

In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry

In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry

Scientific Opinion on the safety and efficacy of propenylhydroxybenzenes (chemical group 17) when used as flavourings for all animal species

Scientific Opinion on Flavouring Group Evaluation 30, Revision 1 (FGE.30Rev1): 4‐Prop‐1‐enylphenol and 2‐methoxy‐4‐(prop‐1‐enyl)phenyl 3‐methylbutyrate from chemical group 17

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