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Safety evaluation of certain food additives - ipcs inchem

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SUBSTANCES STRUCTURALLY RELATED TO MENTHOL (addendum) 591<br />

Table 5. Studies <strong>of</strong> genotoxicity with substances structurally related to<br />

menthol used as flavouring agents<br />

No. Flavouring<br />

agent<br />

In vitro<br />

1853 2-(l-Menthoxy)ethanol<br />

1853 2-(l-Menthoxy)ethanol<br />

1855 l-Menthyl<br />

(R,S)-3hydroxybutyrate<br />

1855 l-Menthyl<br />

(R,S)-3hydroxybutyrate<br />

End-point Test object Concentration Results References<br />

Reverse<br />

mutation<br />

Reverse<br />

mutation<br />

Reverse<br />

mutation<br />

Reverse<br />

mutation<br />

a Modified preincubation method.<br />

b With and without metabolic activation.<br />

3. REFERENCES<br />

S. typhimurium<br />

TA98, TA100,<br />

TA1535 and<br />

TA1537<br />

E. coli<br />

WP2uvrA<br />

S. typhimurium<br />

TA98, TA100,<br />

TA1535,<br />

TA1537 and<br />

TA1538<br />

E. coli<br />

WP2uvrA<br />

Up to<br />

313 μg/plate<br />

Up to<br />

313 μg/plate<br />

78, 156, 312,<br />

625, 1250,<br />

2500 or<br />

10 000<br />

μg/plate<br />

78, 156, 312,<br />

625, 1250,<br />

2500 or<br />

10 000<br />

μg/plate<br />

Negative a,b Sasaki<br />

(2003)<br />

Negative a,b Sasaki<br />

(2003)<br />

Negative a,b Morimoto<br />

(2005)<br />

Negative a,b Morimoto<br />

(2005)<br />

Anders, M.W. (1989) Biotransformation and bioactivation <strong>of</strong> xenobiotics by the kidney. In:<br />

Hutson, D.H., Caldwell, J. & Paulson, G.D., eds. Intermediary xenobiotic metabolism in<br />

animals. New York, NY, USA, Taylor and Francis, pp. 81–97.<br />

Atzl, G., Bertel, M., Daxenbichler, G. & Gleispach, H. (1972) Determination <strong>of</strong> etheral oils from<br />

the urine by gas–liquid chromatography. Chromatographia, 5, 250–255.<br />

Bucher, J.R., Huff, J. & Kluwe, W.M. (1986) Toxicology and carcinogenesis studies <strong>of</strong><br />

isophorone in F344 rats and B6C3F1 mice. Toxicology, 39, 207–219.<br />

Cramer, G.M., Ford, R.A. & Hall, R.L. (1978) Estimation <strong>of</strong> toxic hazard—a decision tree<br />

approach. Food Cosmet. Toxicol., 16, 255–276.<br />

Edwards, K.B., Kirkby, W.W. & Gellatly, J.B.M. (1977a) Biological safety <strong>evaluation</strong> <strong>of</strong> menthyl<br />

pyrrolidone carboxylate (CF 76). Part 1. Acute and subacute oral toxicity (3 weeks) to<br />

Colworth Wistar rats. Private communication to the Flavor and Extract Manufacturers<br />

Association, Washington, DC, USA. Submitted to WHO by the International Organization<br />

<strong>of</strong> the Flavour Industry, Brussels, Belgium.<br />

Edwards, K.B., Kirkby, W.W. & Gellatly, J.B.M. (1977b) Biological safety <strong>evaluation</strong> <strong>of</strong> menthyl<br />

pyrrolidone carboxylate (CF 76). Part 2. Subacute oral toxicity (13 weeks) to Colworth<br />

Wistar rats. Private communication to the Flavor and Extract Manufacturers Association,<br />

Washington, DC, USA. Submitted to WHO by the International Organization <strong>of</strong> the Flavour<br />

Industry, Brussels, Belgium.

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