A Strategy for Developing a Framework of Genotoxicity Assays for Safety Assessment of Botanicals
Author Type(s)
Faculty
Document Type
Abstract
Publication Date
2022
DOI
10.1002/em.22502
Journal Title
Environmental and Molecular Mutagenesis
Department
Pathology, Microbiology and Immunology
Abstract
Botanicals have been used for medicinal purposes for centuries, but safety evaluations of these complex mixtures are often either not available or inadequate. There is an urgent need to define appropriate toxicity evaluations to support their safe use. A cross-sector collaboration is addressing this need through an international group of experts to develop a comprehensive toolkit for generating toxicological profiles of botanicals, including an evaluation of genotoxicity potential. Relying on available in vitro and in silico test methods for evaluating the genotoxicity of chemicals, the experts have developed a tiered, fit-for purpose testing strategy for botanicals that starts with in silico modeling followed by in vitro guideline studies and novel follow-up tests. To evaluate the effectiveness of the proposed testing approach, 13 data-rich botanicals were selected as case studies. Results of our in silico predictive modeling using Leadscope genotoxicity endpoint models indicated that >70% of literature-identified constituents of these 13 botanicals show alerts in at least one of the models. Next, results from in vitro tests, beginning with the Ames and in vitro MN tests, will be compared with the in silico predictions. In an iterative process, the final toolkit and framework for safety testing will be based on the data collected. The goal of this effort is to develop predictive toxicity testing strategies suitable for botanicals that integrate published data with results from in silico and in vitro testing, along with human exposure data, into a robust, comprehensive program providing actionable safety data while minimizing animal testing.
Recommended Citation
Pfuhler, S., Chen, G., Thakkar, Y., Cheairs, T., Eisenbrand, G., MacGregor, J. T., Mei, N., Embry, M., Mitchell, C., Rietjens, I., Smith-Roe, S. L., Stopper, H., Benthem, J., Zeiger, E., & Witt, K. (2022). A Strategy for Developing a Framework of Genotoxicity Assays for Safety Assessment of Botanicals. Environmental and Molecular Mutagenesis, 63, 89. https://doi.org/10.1002/em.22502
