It is a precursor in the synthesis of the insecticide synergist piperonyl butoxide, the fragrance piperonal via isosafrole, and the empathogenic/entactogenic substance MDMA.
[8]: 929 By 1884, the German chemist Theodor Poleck (1821–1906) suggested that safrole was a derivative of benzene, to which two oxygen atoms were joined as epoxides (cyclic ethers).
[10]: 40–41 He also noted that shikimol and safrole had the same empirical formula and had other similar properties, and thus he suggested that they were probably identical.
In the United States, commercially available culinary sassafras oil is usually devoid of safrole due to a rule passed by the U.S. FDA in 1960.
The newly formed 1′-hydroxysafrole will undergo a phase II drug metabolism reaction with a sulfotransferase enzyme to create 1′-sulfoxysafrole, which can cause DNA adducts.
The cleavage of the methylenedioxy ring and the metabolism of the allyl group involve hepatic microsomal mixed-function oxidases.
[26] Toxicological studies have shown that safrole is a weak hepatocarcinogen at higher doses in rats and mice.
[26] Metabolic conversion of the allyl group in safrole is able to produce intermediates which are directly capable of binding covalently with DNA and proteins.
[25] In rats, safrole and related compounds produced both benign and malignant tumors after intake through the mouth.
[33] It occurs naturally in a variety of spices, such as cinnamon, nutmeg, and black pepper, and herbs such as basil.
In that role, safrole, like many naturally-occurring compounds, may have a small but measurable ability to induce cancer in rodents.
Despite this, the effects in humans were estimated by the Lawrence Berkeley National Laboratory to be similar to risks posed by breathing indoor air or drinking municipally supplied water.
[34] Besides being a hepatocarcinogen, safrole exhibits further adverse effects in that it will induce the formation of hepatic lipid hydroperoxides.
[35] Safrole is listed as a Table I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.
[36] Due to their role in the manufacture of MDMA, safrole, isosafrole, and piperonal are Category I precursors under regulation no.
The root bark of American sassafras contains a low percentage of steam-volatile oil, which is typically 75% safrole.
[38] Attempts to refine safrole from sassafras bark in mass quantities are generally not economically viable due to low yield and high effort.
[15] Demand for safrole is causing rapid and illicit harvesting of the Cinnamomum parthenoxylon tree in Southeast Asia, in particular the Cardamom Mountains in Cambodia.
[40][41] Sustainable harvesting of safrole is possible from leaves and stems of certain plants, including the roots of camphor seedlings.