Journal Article

Thresholds of Carcinogenicity of Flavors

William J. Waddell

in Toxicological Sciences

Volume 68, issue 2, pages 275-279
Published in print August 2002 | ISSN: 1096-6080
Published online August 2002 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/68.2.275
Thresholds of Carcinogenicity of Flavors

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Fifteen compounds approved by the FEMA (Flavor and Extract Manufacturers Association) expert panel as GRAS (Generally Recognized As Safe) and structurally related compounds have been reported to be carcinogenic in rodent studies. The dose response of the 15 compounds in these studies was scrutinized by attempting to plot the percentage of animals with tumors against the dose of the compound on a logarithmic scale in molecules of compound per kg per day (the Rozman scale). Four compounds had either no or an inverse dose response: benzaldehyde, furfural, 3,4-dihydroxycoumarin, and γ-buterolactone. Three had a response at one dose only: anethole, estragole (2 studies), and isophorone. Obviously, a dose-response curve could not be generated for these 7 compounds. Four compounds had an increasing response at two doses (benzyl acetate, cinnamyl anthranilate, ethyl acrylate, and estragole); three compounds had increasing responses at three doses (citral, 2,4-hexadienal, and pyridine); one compound had increasing responses at four doses (methyl eugenol). The three compounds with three doses fit a linear plot with a correlation coefficient of at least 0.9; the four doses in male rats of methyl eugenol fit a linear plot with a correlation coefficient of 0.999983. The intercept at zero percentage tumors of these linear fits was at least several orders of magnitude greater than the estimated daily dose of these flavoring agents to individuals in the United States. This is interpreted to indicate that these flavoring agents have a clear threshold for carcinogenicity in animals that is well above the levels currently approved for use in foods; consequently, these animal studies should not be a cause for concern for carcinogenicity of these compounds in humans. Rather, the animal studies should be viewed as providing evidence for the safety of these compounds at current levels of human exposure.

Keywords: threshold; carcinogenicity; flavors; foods; FEMA; GRAS; methyleugenol

Journal Article.  2884 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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