BSC Newsletter - December 2021
The Botanical Safety Consortium (BSC) was officially convened in November 2019 as the result of a Memorandum of Understanding (MOU) between the US Food and Drug Administration (FDA), the National Institute of Health’s National Institute of Environmental Health Sciences (NIEHS), and the non-profit Health and Environmental Sciences Institute (HESI). The BSC is a multi-partite, multi-stakeholder, international effort that brings together key scientific experts to enhance the botanical safety toolkit and bring clarity to botanical dietary ingredient assessments. It was formed to provide a sound scientific basis for integrating existing botanical safety and toxicity information with the latest toxicological tools.
The objectives of the BSC are:
- To engage with a broad group of global stakeholders to leverage the best scientific safety approaches;
- To establish the appropriate levels of chemical characterization for complex botanical;
- To identify pragmatic, fit-for-purpose new approach methodologies to evaluate botanical safety;
- To evaluate the application of these tools via comparison to the currently available safety information;
- And to integrate these tools and approaches into a framework that can facilitate robust evaluation of botanicals.
As we enter 2022, we want to thank all our stakeholders for their hard work on the Botanical Safety Consortium! We’ve come a long way since officially launching in 2020. This past year working group members and the steering committee have worked to:
- Source 13 botanicals for our initial case studies
- Generate chemical analysis data on Ashwagandha Root Extract
- Select toxicity screening assays and begin to design experiments
- Design and conduct 13 literature reviews on pilot botanicals
- Perform in silico analyses using botanical constituents
- Expand our membership by adding 4 companies and 2 public sector organizations
- Present at 7 meetings and conferences
- Hold our Annual Meeting in June 2021 with +150 participants
Save the date for the following BSC events in 2022
7-10 March 2022 - 88th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology. The Botanical Safety Consortium´s strategy to enhance the botanical safety toolkit presented by Steering Committee Member Dr. Olaf Kelber.
27–31 March 2022 - 61st Society of Toxicology (SOT)
- Application of in silico and in vitro approaches for evaluating developmental and reproductive toxicity in botanical products
- In silico prediction of botanical constituent’s metabolites
- A strategy for developing a framework of genotoxicity assays for safety assessment for botanicals
- Physiologically based pharmacokinetic (PBPK) simulations and modeling of botanical constituents
28-30 March 2022 - 20th Annual Oxford ICSB. Botanical Safety Consortium Session. Date TBD.
28-31 August 2022 - 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA) in Thessaloniki, Greece. Botanical Safety Consortium Symposium Sunday 28 August.
In addition to the BSC's focus to evaluate the suitability of assays for botanicals as complex mixtures, we have started a collaboration with the University of Malawi’s College of Pharmacy on two projects related to botanicals.
Herbal Drug Interaction Survey: Traditional and Complementary Medicine (TCM) is commonly used among Malawian citizens due to its accessibility and affordability. With an increasing prevalence of non-communicable diseases (NCDs), TCM and conventional medications are more frequently being used concurrently to treat chronic diseases like hypertension and diabetes. This has increased the risk for harmful herb-drug interactions (HDI) to occur. However, there have been limited studies and research to evaluate potential TCM and conventional entities that could contribute to HDIs. The primary objective of this study is to investigate potential herb-drug interactions and adverse reactions associated with concurrent use of conventional and herbal medicines among NCD patients at a clinic in Malawi. This cross-sectional survey took place at Queen Elizabeth Central Hospital’s NCD outpatient clinics from June 2021 to October 2021. Data analyses and a subsequent manuscript will take place in 2022.
Chemical Analysis of Aristolochia hockii: Throughout the world, people are using traditional medicine to meet their primary health care needs. In Malawi, Aristolochia hockii was reported to be sold by 47% of traders. However, even with its high usage there is little to no information on the constituents of Aristolochia hockii. Moreover, other species of Aristolochia contain aristolochic acids which are known to induce genotoxicity and nephrotoxicity in humans. The Malawi College of Medicine College of Pharmacy, HESI, and the Botanical Safety Consortium are collaborating to chemically characterize Aristolochia hockii. All experimental work will take place in Malawi at the College of Pharmacy and the Malawi Bureau of Standards. The collection of plant materials has begun in late 2021 and analyses will begin in 2022 with an expected publication next year.
Below are the toxicity screening assays or models we plan to test in 2022 for their suitability for botanicals as complex mixtures. Please note this is a draft and not a final list. Additional new approach methodology assays can be considered. Select assays can be multiplexed and run together. Details on protocols and results from all will be reported and made public. Each group is also investigating appropriate in silico tools on botanical constituents.
- Ames test
- In vitro micronucleus test
Developmental and Reproductive Toxicity
- Transcriptomics in human cell lines*
- Zebrafish embryos*
- C. Elegans*
- devTOX quickPredict assay
- Transcriptomics in human cell lines*
- ATP depletion
- ROS glo assay
- LDH release
- Cytotoxic Reactive Metabolites
- Zebrafish embryos*
- C. Elegans*
- Multi electrode arrays in neuronal cells
- Cell Viability
- Multi electrode arrays in cardiomyocyte cells
- Voltage sensitive dyes
- Transient Calcium measurements
- Direct Contractility
- GastroPlus Modeling
- Multicompartmental in vitro system
*will provide information for other endpoints
The Botanical Safety Consortium: A public-private partnership to enhance the botanical safety toolkit
Mitchell CA, Dever JT, Gafner S, Griffiths JC, Marsman DS, Rider C, Welch C, Embry MR
Botanical dietary supplement and herbal medicine use is increasing both in the United States and worldwide. Products made from botanicals can be variable in chemical composition, with many aspects affecting their quantitative and qualitative chemical content and unknown impacts on potential toxicity profiles. Many regulatory structures do not currently require toxicity data and only require evidence of harm to induce regulatory action post-market. This can lead to potentially unsafe products for consumers. Because of their inherent complexity, botanicals are difficult to characterize and assess for toxicity and/or efficacy. Currently, it is not known what new methodologies used for single-chemical toxicity testing can be applied for botanicals as complex mixtures. Testing botanicals for toxicity can lead to safer products.
The Botanical Safety Consortium (BSC) was formed to provide a forum for global scientists from government, academia, consumer health groups, industry, and non-profit organizations to work collaboratively to generate a sound scientific basis for integrating existing safety data and the latest in silico and in vitro toxicology tools to evaluate the safety of botanicals. Understanding the safety of botanicals is a critical public health need. BSC is uniquely structured with multidisciplinary and international scientific engagement to support the design and implementation of a novel safety toolkit for botanical screening. This commentary describes the mission and objectives of the Botanical Safety Consortium (BSC).
Full text Online: https://www.sciencedirect.com/science/article/abs/pii/S0273230021002312
Authentication and constituent identification and quantification of Ashwagandha root extract. Authors TBD – Chemical Analysis Working Group. In preparation
- The consortium was officially convened in November 2019 as the result of a Memorandum of Understanding (MOU) between the FDA, NIEHS, and HESI. This multi-partite, multi-stakeholder, international effort brings together key scientific experts to enhance the botanical safety toolkit and bring clarity to botanical dietary ingredient assessments.
- The consortium was highlighted in the 2021 US FDA report titled "Advancing New Alternative Methodologies at FDA" which described progress the FDA has made in integrating alternative approaches into regulatory programs.
- The consortium applied for two Alan and Helene Goldberg In Vitro Toxicology Grants from Johns Hopkins University’s Center for Alternatives to Animal Testing. If awarded, these funds will be used evaluate assays for botanical suitability related to the developmental & reproductive toxicity and the neurotoxicity working groups.