Absorption, metabolism and excretion of safrole in the rat and man

Joint FAO/WHO Expert Committee on Food Additives (JECFA)

“…Administration of safrole to rats at oral dose levels ranging from 0.9 to 600 mg/kg bw revealed a dose-dependent decrease in O-demethylenated metabolites and an increase in allyl side-chain oxidation products; 1 -hydroxysafrole was formed in rats, but it was not detected in humans administered a dose of 1.66 mg safrole (Benedetti et al, 1977).…”

“…Ninety-eight per cent of the dose was recovered in the urine and faeces after 5 days. The kinetics of elimination of the radioactivity were biphasic, with half-lives of 2.5 and 15 h (Benedetti et al, 1977).…”

“…At the 750 mg/kg bw dose, liver and kidney radioactivity levels remained high up to 48 h, and the tissue to plasma radioactivity ratio and unchanged safrole levels were much greater than recorded at the low dose of 4.2 mg/kg bw. Collection of bile from rats given [1 -14 C]safrole at either 0.8 or 750 mg/kg bw showed that 20% of total radioactivity was eliminated in the bile in 24 h at the low dose and only 3% at the high dose (Benedetti et al, 1977).…”

“…1789) and elemicin (No. 1788)-indicate that this group of substances undergoes rapid and essentially complete absorption following oral intake (Kamienski & Casida, 1970;Fritsch et al, 1975aFritsch et al, , 1975bBenedetti et al, 1977;Sutton et al, 1985;Anthony et al, 1987;Lee et al, 1998). Based on studies in rats and humans, these substances are highly bioavailable following the consumption of spices containing these constituents (Beyer et al, 2006).…”

Determination of Safrole in Ethanol Extract of Nutmeg (Myristica fragrans Houtt) Using Reversed-Phase High Performance Liquid Chromatography

“…Of the three compounds, safrole is the most toxic substance due to its carcinogenic activity (Lestari, 2010;Li & Yang, 2012). Safrole and isosafrole (0.5%) has been shown to increase the occurance rate of malignant tumours in mice (Benedetti, Malnoe, & Broillet, 1977). The major toxicity of safrole is caused by its metabolite character.…”