RESUMO
The urinary metabolites of isosafrole (1,2-methylenedioxy-4-propenylbenzene) and dihydrosafrole (1,2-methylenedioxy-4-propylbenzene) in the rat were identified using gas chromatographic mass spectrometric methods. Additionally, the amounts of the individual metabolites excreted were determined gas chromatographically. Metabolite excretion was 89% (isosafrole) and 97% (dihydrosafrole) of the dose in 72 h. Although isosafrole was metabolized by allylic hydroxylation and via the epoxide-diol pathway, demethylenation leading mainly to 1,2-dihydroxy-4-propenylbenzene was by far the most prominent reaction. This was similarly true with dihydrosafrole which was metabolized mainly to 1,2-dihydroxy-4-(1-propyl) benzene. The total amount of demethylenated metabolites formed were 92% (isosafrole) and 95% (dihydrosafrole) of the identified material.
Assuntos
Dioxóis/metabolismo , Safrol/metabolismo , Animais , Fenômenos Químicos , Química , Cromatografia Gasosa , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Ratos , Ratos Endogâmicos , Safrol/análogos & derivados , Safrol/urinaRESUMO
The metabolic disposition of different doses of [14C] safrole were studied in rat and man. In both species, small amounts of orally administered safrole were absorbed rapidly and then excreted almost entirely within 24 h in the urine. In the rat, when the dose was raised from 0.6 to 750 mg/kg, a marked decrease in the rate of elimination occurred as only 25% of the dose was excreted in the urine in 24 h. Furthermore, at the high dose level, plasma and tissue concentrations of both unchanged safrole and its metabolites remained elevated for 48 h probably indicating impairment of the degradation/excretion pathways. The main urinary metabolite in both species was 1,2-dihydroxy-4-allylbenzene which was excreted in a conjugated form. Small amounts of eugenol or its isomer 1-methoxy-2-hydroxy-4-allylbenzene were also detected in rat and man. 1'-Hydroxysafrole, a proximate carcinogen of safrole, and 3'-hydroxyisosafrole were detected as conjugates in the urine of the rat. However, in these investigations we were unable to demonstrate the presence of the latter metabolites in man.
