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Safety evaluation of certain food additives - ipcs inchem

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384 ALKOXY-SUBSTITUTED ALLYLBENZENES<br />

Table 2. Results <strong>of</strong> studies for acute toxicity <strong>of</strong> methoxy- and methylenedioxysubstituted<br />

allylbenzenes administered orally<br />

No. Flavouring agent Species; sex LD50<br />

(mg/kg bw)<br />

2.2.2 Short-term studies <strong>of</strong> toxicity<br />

The results <strong>of</strong> short-term studies <strong>of</strong> toxicity <strong>of</strong> methoxy-and methylenedioxysubstituted<br />

allylbenzenes are summarized in Table 3.<br />

(a) Nutmeg oil<br />

Reference<br />

1789 Estragole Mouse; NR 1250 Jenner et al. (1964)<br />

1789 Estragole Rat; M, F 1820 Jenner et al. (1964)<br />

1789 Estragole Rat; M, F 1820 Taylor et al. (1964)<br />

1789 Estragole Rat; M 1230 Moreno (1972)<br />

1790 Methyl eugenol Rat; M, F 1560 Jenner et al. (1964)<br />

1790 Methyl eugenol Rat; NR 810 Keating (1972)<br />

1790 Methyl eugenol Rat; NR 1560 Bär & Griepentrog (1967)<br />

1790 Methyl eugenol Rat; M, F 1179 Beroza et al. (1975)<br />

1792 Safrole Mouse; NR 2350 Jenner et al. (1964)<br />

1792 Safrole Rat; M, F 1950 Jenner et al. (1964)<br />

1792 Safrole Rat; NR 1950 Bär & Griepentrog (1967)<br />

1792 Safrole Mouse; M, F 2350 Hagan et al. (1965)<br />

1792 Safrole Rat; M, F 1950 Hagan et al. (1965)<br />

F, female; M, male; NR, not reported.<br />

(i) Rats<br />

Nutmeg oil, composed <strong>of</strong> approximately 7% myristicin, 1.3% safrole and<br />

>80% monoterpene hydrocarbons (- and -pinene and sabinene) (Mills, 1989),<br />

was administered to groups <strong>of</strong> 10 male and 10 female Fischer 344 rats for 28 days.<br />

The test material, which was administered daily at dose levels <strong>of</strong> 0 (control), 20, 100<br />

or 500 mg/kg bw by gavage in corn oil (10 ml/kg), was calculated to provide an intake<br />

<strong>of</strong> 0, 1.6, 8.3 or 41.5 mg alkoxy-substituted allylbenzenes/kg bw and 0, 16, 80 or<br />

400 mg monoterpene hydrocarbons/kg bw. With the exception <strong>of</strong> one accidental<br />

death at the highest dose, all animals survived to the scheduled sacrifice. Weekly<br />

measurements <strong>of</strong> body weights revealed significantly decreased body weights in<br />

males (days 22, 28 and 29) and females (day 29). Body weight gain was significantly<br />

decreased for the 100 and 500 mg/kg bw per day groups <strong>of</strong> both sexes. Clinical<br />

chemistry <strong>evaluation</strong> revealed increased serum phosphate and AST in the highdose<br />

males and increased mean serum creatinine in all treated males. No significant

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