Wasma Alhusainy

Chemical analysis of estragole in fennel based teas and associated safety assessment using the Margin of Exposure (MOE) approach.

This study describes the analysis of estragole in dry fennel preparations and in infusions prepared from them and an associated safety assessment. A wide range of estragole levels of 0.15-13.3mg/g dry fennel preparation was found. The estragole content in infusions was considerably lower ranging between 0.4 and 133.4μg/25mL infusion prepared from 1g dry material. Infusions prepared from whole fennel fruits contained about 3-fold less estragole compared to infusions prepared from fine cut fennel material. Safety assessment was performed using the Margin of Exposure (MOE) approach comparing available tumour data to the estimated daily estragole intakes from the consumption of 1-3 cups fennel tea. MOEs obtained for adults generally point at a low priority for risk management, especially when one cup of fennel tea is used daily during lifetime. MOEs for use of fennel teas by children were generally <10,000 indicating a priority for risk management. However, limiting such uses to 1-2weeks, MOEs might be 3 orders of a magnitude higher and there would be no priority for risk management. These results indicate a low priority for risk management actions for use of fennel teas especially for short-term uses proposed for the symptomatic treatment of digestive disorders.

In vivo validation and physiologically based biokinetic modeling of the inhibition of SULT‐mediated estragole DNA adduct formation in the liver of male Sprague‐Dawley rats by the basil flavonoid nevadensin

SCOPE The present work investigates whether the previous observation that the basil flavonoid nevadensin is able to inhibit sulfotransferase (SULT)-mediated estragole DNA adduct formation in primary rat hepatocytes could be validated in vivo. METHODS AND RESULTS Estragole and nevadensin were co-administered orally to Sprague-Dawley rats, at a ratio reflecting their presence in basil. Moreover, previously developed physiologically based biokinetic (PBBK) models to study this inhibition in rat and in human liver were refined by including a submodel describing nevadensin kinetics. Nevadensin resulted in a significant 36% reduction in the levels of estragole DNA adducts formed in the liver of rats. The refined PBBK model predicts the formation of estragole DNA adducts in the liver of rat with less than twofold difference compared to in vivo data and suggests more potent inhibition in the liver of human compared to rat due to less efficient metabolism of nevadensin in human liver and intestine. CONCLUSION Given the role of the SULT-mediated DNA adduct formation in the hepatocarcinogenicity of estragole, the results of the present study suggest that the likelihood of bioactivation and subsequent adverse effects in rodent bioassays may be lower when estragole is dosed with nevadensin compared to dosing of pure estragole.

Progenitor-derived hepatocyte-like (B-13/H) cells metabolise 1′-hydroxyestragole to a genotoxic species via a SULT2B1-dependent mechanism

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