Estragole (methyl chavicol)

Classified as a potential genotoxic carcinogen at high doses by EFSA. Risk is dose-dependent and primarily relevant to concentrated essential oil preparations, not culinary herb use. Chemotype selection is critical for medicinal use.

Antispasmodic effects of estragole have been confirmed in ex vivo guinea pig ileum preparations (IC50 ~40 µM) and rat uterine strip preparations, with smooth muscle relaxation comparable to papaverine at higher doses. Local anesthetic activity was confirmed in rat sciatic nerve block models at 50 mM concentrations. The carcinogenicity risk of dietary estragole was comprehensively evaluated by EFSA (2001, reaffirmed 2012): the margin of exposure (MOE) for dietary intake through food flavorings was calculated at >10,000, generally considered acceptable risk; MOE for supplement-dose concentrated estragole was substantially lower (~1,000), warranting regulatory restriction of non-food applications. No clinical trials specifically targeting estragole-mediated antispasmodic or anesthetic activity in humans have been conducted.