Risk assessment of herbal supplements containing ingredients that are genotoxic and carcinogenic

Abstract

Botanicals and botanical preparations including plant food supplements as well as medicinal herbal supplements can contain possible beneficial health compounds, but also ingredients of concern. Compounds that are both genotoxic and carcinogenic have been found in herbal supplements and may raise a safety concern. Genotoxic carcinogens that can be present in botanicals and botanical preprations include especially pyrrolizidine alkaloids (PAs), aristolochic acids (AAs) and alkenylbenzenes (ABs). The present manuscript provides an overview of the levels of these compounds reported to date to be present in herbal supplements with an associated risk assessment. Exposure was estimated based on levels of PAs, AAs and ABs in individual supplements and their proposed uses. In addition a probabilistic exposure assessment was performed based on the distribution of the level of the compounds of concern in the food supplements and of the recommended uses, resulting in 5th to 95th percentile consumer exposure values. To evaluate the risk of these exposures, the margin of exposure (MOE) approach for lifetime exposure was used. To correct exposure estimates for shorter than lifetime exposure, Haber’s rule as a first tier approach was applied. It is concluded that the proposed uses and use levels as well as the presence of AAs, ABs and PAs in food supplements should be carefully monitored to manage potential consumer risks. More information on estimated daily intake resulting from supplement use, as well as consequences of concomitant exposure will further improve the risk evaluation of products containing these compounds of concern.

Keywords:

• herbal supplements
• risk assessment
• safety
• pyrrolizidine alkaloids
• aristolochic acids
• alkenylbenzenes
• margin of exposure (MOE)

Acknowledgements

The authors acknowledge the reviewers and the editor for their time and dedication in reviewing the manuscript. Their comments and suggestions made a valuable contribution to the manuscript. Ivonne Rietjens and Jacques Vervoort would like to acknowlegde former PhD students Suzanne van den Berg, Abdalmajeed M. Alajlouni, Amer J. Al-Malahmeh, Jia Ning, Lu Chen and Rozaini Abdullah and all other (co)authors of several of the papers from which part of the data were collected.

Declaration of interest

The authors report no conflicts of interest. The author’s affiliation are as shown on the cover page. The institutions with which the authors are affiliated are academic institutions and the authors take sole responsibility for the writing and content of the manuscript. None of the authors have been involved in legal or regulatory matters related to the contents of the paper. This manuscript was prepared during the normal course of the authors’ employment using institutional funding, with no external funding used in preparation of the manuscript. During the past 5 years, none of the authors have participated in any legal or regulatory proceedings related to the contents of this manuscript.