Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in nutmeg-based plant food supplements

Abstract

A risk assessment of nutmeg-based plant food supplements (PFS) containing different alkenylbenzenes was performed based on the alkenylbenzene levels quantified in a series of PFS collected via the online market. The estimated daily intake (EDI) of the alkenylbenzenes amounted to 0.3 to 312 μg kg body weight (bw) for individual alkenylbenzenes, to 1.5 to 631 μg kg bw when adding up the alkenylbenzene levels assuming equal potency, and to 0.4 to 295 μg kg bw when expressed in safrole equivalents using toxic equivalency factors (TEFs). The margin of exposure approach (MOE) was used to evaluate the potential risks. Independent of the method used for the intake estimate, the MOE values obtained were generally lower than 10000 indicating a priority for risk management. When taking into account that PFS may be used for shorter periods of time and using Haber's rule to correct for shorter than lifetime exposure it was shown that limiting exposure to only 1 or 2 weeks would result in MOE values that would be, with the presently determined levels of alkenylbenzenes and proposed uses of the PFS, of low priority for risk management (MOE > 10000). It is concluded that the results of the present paper reveal that nutmeg-based PFS consumption following recommendations for daily intake especially for longer periods of time raise a concern. Copyright © 2017 John Wiley & Sons, Ltd.

A Design of Experiment Approach for Ionic Liquid-Based Extraction of Toxic Components-Minimized Essential Oil from Myristica fragrans Houtt. Fruits †

“…Nutmeg EO shows different percentages of alkenyl benzenes. The Scientific Committee on Food (SCF) regarded safrole, methyleugenole, and estragole as toxic compounds due to their carcinogenic activity [ 26 , 27 , 28 ]; for this reason, any extraction condition that allows a diminished percentage of these compounds in the EO has to be regarded as valuable. On the other hand, there is evidence suggesting that many phenylpropenes are cytotoxic against several cancer cell lines [ 29 ], but most of the reports were not on clinical studies.…”

Safrole-induced expression of proinflammatory responses is associated with phosphorylation of mitogen-activated protein kinase family and the nuclear factor-κB/inhibitor of κB pathway in macrophages

“…Safrole, also called shikimol and Sassafras, is a natural phenylpropanoid compound. Safrole is a colorless oily liquid that can be obtained through natural extraction from Sassafras trees ( Sassafras albidum ) and anise ( Illicium anisatum ), betel ( Piper betle L.), and camphor ( Ocotea pretiosa ) [ 1 2 3 ]. Safrole and its metabolites, including 1-hydroxysafrole, isosafrole, and dihydrosafrole, are carcinogenic and contribute to the development of several cancers, such as oral, esophageal, and hepatocellular cancers [ 4 5 6 7 ].…”

Detoxification of 1,2-dihydroxy- 4-allylbenzene, a major phenolic compound in Piper betle, through glucuronidation using S9 protein of rat liver (Sprague Dawley)

“…Safrole is a bioactive compound in some spices such as nutmeg, mace, cinnamon, star anise, ginger and black pepper (Periasamy et al ., 2016 ;Rocha et al, 2016) and a major compound in sassafras oil (Sasafras albidum). Intake of some food supplements containing those spices raise a health of concern (Al- Malahmeh et al, 2017;Berg et al, 2011). Pure safrole as flavoring agent has already banned by FDA (Food Drug Association) since December 1960 and by EFSA (European Food Safety Authority) food since 2008.…”