Risk and benefit: analysis of herbal products from Indonesia

In Indonesia, the market demand for herbal products keeps growing, and as a result, herbal products increasingly provide economic and perceived clinical benefits. A risk and benefit assessment are crucial to be performed to support the safe use of herbal products although the consumers perceive herbal product as “safe” and “natural” and thus “healthy”. The aim of the PHD thesis was to perform an assessment of potential risks and some benefits of herbal products available in the Indonesian market. The model compounds chosen included especially naturally occurring genotoxic and carcinogenic botanical constituents including alkenylbenzenes (ABs) and pyrrolizidine alkaloids (PAs). Beneficial effects focussed on potential PPARg activation by the carotenoids bixin and crocetin. Existing but also novel testing strategies were used to evaluate the relevance of effects at estimated human intake levels.

Altogether, it can be concluded that the risk assessment using the Margin of Exposure approach combined with Haber’s rule can be used to prioritize risk management actions to prevent the adverse health effects of consuming Indonesian herbal products containing genotoxic carcinogens. In addition, a novel testing strategy, combining in vitro and PBK modeling-facilitated reverse dosimetry was found to facilitate risk and benefit assessment of botanical compounds without the need for animal experiments and/or human intervention studies.

It is important to note that this conclusion holds for herbal products collected by targeted sampling, and not for all herbal products on the Indonesian market. Many aspects, including variability in detected levels of the targeted compounds, variability in recommended daily use mentioned on the label, interindividual variation of exposure among Indonesian people, absence of a generally accepted method to take shorter-than-lifetime exposure into account, the knowledge gaps in modes of action, selection of the best in vitro model for QIVIVE, potential combination effects, the chemical-specific parameters needed for PBK modeling and availability of in vivo studies to validate the predictions should be considered for future research. Seven actions including (1) applying Good Agricultural and Collection Practices (GACP) for farmers, (2) applying good manufacturing practice (GMP) of herbal product and food safety training for manufacturers and producers, (3) development of a toxicity database of medicinal botanicals used in Indonesia, (4) restriction of the exposure to genotoxic carcinogenic compounds by establishing MPLs and refining the label requirements for botanicals and botanical preparations, (5) use of human biomonitoring (HBM) and PBK modeling for a more refined exposure, risk and benefit analysis of Indonesian herbal products, (6) incorporation of Chemical Specific Adjustment Factors (CSAFs) for interspecies and interindividual variation in kinetics within the human population in the risk assessment, and (7) exploring the beneficial effects of botanicals and botanical preparations, were proposed to improve safety and efficacy of botanicals and botanical preparations on the Indonesian market.