Metabolism of isosafrole and dihydrosafrole in the rat

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.