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The FEMA GRAS Assessment of trans-Anethole Used as a Flavouring Substance

Newberne, P, Smith, R.L, Doull, J, Goodman, J.I, Munro, I.C, Portoghese, P.S, Wagner, B.M, Weil, C.S, Woods, L.A, Adams, T.B, Lucas, C.D, Ford, R.A·1999·Food and Chemical Toxicology
DOI 10.1016/s0278-6915(99)00037-x
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Abstract

This publication is the fourth in a series of safety evaluations performed by the Expert Panel of the Flavour and Extract Manufacturers' Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavouring substances under conditions of intended use. In this review, scientific data relevant to the safety evaluation of trans-anethole (i.e. 4-methoxypropenylbenzene) as a flavouring substance is critically evaluated by the FEMA Expert Panel. The evaluation uses a mechanism-based approach in which production of the hepatotoxic metabolite anethole epoxide (AE) is used to interpret the pathological changes observed in different species and sexes of laboratory rodents in chronic and subchronic dietary studies. Female Sprague Dawley rats metabolize more trans-anethole to AE than mice or humans and, therefore, are the most conservative model for evaluating the potential for AE-induced hepatotoxicity in humans exposed to trans-anethole from use as a flavouring substance. At low levels of exposure, trans-anethole is efficiently detoxicated in rodents and humans primarily by O-demethylation and omega-oxidation, respectively, while epoxidation is only a minor pathway. At high dose levels in rats, particularly females, a metabolic shift occurs resulting in increased epoxidation and formation of AE. Lower activity of the "fast" acting detoxication enzyme epoxide hydrolase in the female is associated with more pronounced hepatot…

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Cited by

Metadata

Authors
Newberne, P., Smith, R. L., Doull, J., Goodman, J. I., Munro, I. C., Portoghese, P. S., Wagner, B. M., Weil, C. S., Woods, L. A., Adams, T. B., Lucas, C. D., & Ford, R. A.
Venue
Food and Chemical Toxicology
Publisher
Elsevier BV
Published
1999-07
Volume
37
Issue
7
Pages
789-811
ISSN
0278-6915
DOI
10.1016/s0278-6915(99)00037-x
Cited by
118
References
0
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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