Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate in rats and mice

Yuan, Joan; Goehl, Thomas J.; Abdo, Kamal M.; Clark, James; Espinosa, Olga; Buggé, Christopher J.L.; Garcia, Dava J.

doi:10.1016/0278-6915(94)00123-6

Cited by 36 publications

(13 citation statements)

References 14 publications

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“…Other possible explanation for the diŠerence in genotoxicity between by feeding administation and gavage administration might be possible. Although it is remained for further studies whether gavage-administered kojic acid saturate metabolic/detoxiˆcation pathway of kojic acid, gavage-administered kojic acid may tend to saturate metabolic/detoxiˆcation pathway of kojic acid, like as Yuan et al (22) showed in their study with benzyl acetate, which might result in gavage-administered kojic acid tended to be more genotoxic. When kojic acid was given to mice in the diet, its genotoxicity tended to decrease as an administration period became long with the exception for its genotoxicity in the liver.…”

Section: Discussionmentioning

confidence: 99%

In vivo Genotoxic Potential of Kojic Acid in Rodent Multiple Organs Detected by the Comet Assay

Kawaguchi

Nakamura

Honda

et al. 2008

Genes and Environment

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Kojic acid has been used for skin whitening as a cosmetic agent. Kojic acid is believed to be hepatocarcinogenic in mice. We conducted the comet assay in mouse and rat multiple organs to evaluate its in vivo genotoxic potential. Kojic acid induced dose-dependent DNA damage in ddY mouse stomach and liver and in Wistar rat stomach, liver, lung, and bone marrow after a single gavage administration at ≦1000 mg/kg. Its hepatic genotoxicity detected by the comet assay seems to contradict to absence of its hepatic tumor initiating activity revealed by the two-step carcinogenesis studies with mice and rats. However, considering the possibility that the sensitivity of the two-step carcinogenesis studies performed are not high enough to detect weak initiating activity of a chemical, it would be premature to conclude that its hepatic genotoxicity contradicts to the absence of initiating activity. In mice fed a diet containing 3% kojic acid for up to 10 days, DNA migration increased in the stomach after feeding for 2 days but it did not increased after feeding for 1 day and ≧4 days. In the colon, DNA migration after feeding of 3% kojic acid for 2 days was higher than the control values, but this increase was not statistically signiˆcant. In the stomach and colon, any statistically signiˆcant increases in DNA migration were not observed after feeding of 1.5% kojic acid. In the liver, DNA migration increased with feeding period and the increases after feeding of 3% and 1.5% kojic acid for ≧4 days and 6 days, respectively, were statistically signiˆcant. Our present results suggested good correlation between hepatocarcinogenicity of kojic acid and increasing tendency of its hepatic genotoxicity with dosing period when it is given to mice continuously in the diet.

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Section: Discussionmentioning

confidence: 99%

In vivo Genotoxic Potential of Kojic Acid in Rodent Multiple Organs Detected by the Comet Assay

Kawaguchi

Nakamura

Honda

et al. 2008

Genes and Environment

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“…Hydrolysis was partially inhibited by the esterase inhibitor sodium fluoride, which suggests that plasma esterases contribute to the rapid EFSA Journal 2012;10(12):2994 hydrolysis. When benzyl acetate was administered to rats and mice in gavage and dosed feed studies, benzyl acetate was not detected in any plasma samples collected (Yuan et al, 1995).…”

Section: Supporting Substances From Subgroupmentioning

confidence: 99%

“…Such conditions appear to have occurred after a bolus gavage dose of benzyl acetate to result in a brief peak in the plasma concentration of benzoic acid. When benzyl acetate was administered to rats and mice in dosed feed, it appears that the CoA conjugation pathway was never saturated and plasma concentration of benzoic acid remained low (Yuan et al, 1995). EFSA Journal 2012;10(12):2994…”

Section: Following Oral Administration Of 375 Mg [mentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 20, Revision 4 (FGE.20Rev4): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

Publication¹

2012

EFS2

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[FL no: 09.858]. None of the substances were considered to have genotoxic potential. The 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 all the 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 45 candidate substances. Twenty-five flavouring substances in the present group have been reported to occur naturally in a wide range of food items.In its evaluation, the Panel as a default used the "Maximised Survey-derived Daily Intake" (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavour Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a "modified Theoretical Added Maximum Daily Intake" (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels.According to the default MSDI approach, the 41 flavouring substances allocated to structural class I have intakes in Europe from 0.001 to 610 microgram/capita/day, which are below the threshold of concern value for structural class I (1800 microgram/person/day). The four substances in structural class II 05.066, 05.221 and 06.104] have estimated intakes of 0.011, 1.2, 0.61 and 100 microgram/capita/day, respectively. These intakes are below the threshold values of 540 microgram/person/day for structural class II.

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“…Hydrolysis was partially inhibited by the esterase inhibitor sodium fluoride, which suggests that plasma esterases contribute to the rapid hydrolysis. When benzyl acetate was administered to rats and mice in gavage and dosed feed studies, benzyl acetate was not detected in any plasma samples collected (Yuan et al, 1995).…”

Section: Supporting Substances From Subgroupmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 20, Revision 2 (FGE.20Rev2): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

Flavourings¹

2010

EFSA Journal

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Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate in rats and mice

Cited by 36 publications

References 14 publications

In vivo Genotoxic Potential of Kojic Acid in Rodent Multiple Organs Detected by the Comet Assay

In vivo Genotoxic Potential of Kojic Acid in Rodent Multiple Organs Detected by the Comet Assay

Scientific Opinion on Flavouring Group Evaluation 20, Revision 4 (FGE.20Rev4): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

Scientific Opinion on Flavouring Group Evaluation 20, Revision 2 (FGE.20Rev2): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

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