Estragole Hazard Identification Executive Summary
Estragole occurs naturally in many culinary herbs, including anise, star anise, basil, bay, tarragon, fennel, and marjoram. Widespread human exposure to estragole occurs through the consumption of these herbs and through the use of the oils derived from them as flavors and fragrances in numerous foods, cosmetics, and other consumer products. Estragole is a constituent of turpentine oil, and indoor air exposure may result from the use of turpentine oil in furniture and other wood treatments. Estragole or its metabolites administered to adult or newborn mice of different strains, through different routes of administration, produced malignant liver tumors. Carcinogenicity of estragole has not been adequately studied in the rat. One subcutaneous injection study of derivatives of estragole in adult male rats did not observe any treatment-related increase in tumors. Regarding other relevant data, estragole produced genotoxic effects in Salmonella typhimurium, yeast, and mammalian cells. Several DNA adducts have been characterized. Further strong supporting evidence of carcinogenicity comes from comparisons of compounds structurally similar to estragole (e.g., safrole, methyleugenol) which produce liver tumors and tumors at other sites in rodents. The mode of action for estragole carcinogenicity has been well characterized and proceeds through a genotoxic mechanism. Estragole is metabolized by the liver to 1'-hydroxyestragole and several epoxide compounds. 1'-Hydroxyestragole is further conjugated with sulfate to form a sulfuric acid ester compound that readily binds to DNA and is responsible for most, if not all, of estragole’s hepatocellular carcinogenicity in mice. Metabolism of estragole through this pathway appears to be quantitatively consistent among humans and rodents.
- Estragole