This paper evaluates use of the Threshold of Toxicological Concern (TTC) approach to assess safety of botanical preparations that may contain potentially genotoxic constituents, based on estimation of the fraction that may be genotoxic. A database of 107 chemical constituents of botanicals was compiled and their potential for genotoxicity evaluated from published data. Forty-three constituents met the criteria for potential genotoxicity. Concentration data on their occurrence in plants provided 2878 data points; the majority were in the low ppm level (range 0.00001-139,965 ppm, by dry weight). Weibull models of the quantitative distribution data were used to calculate 95th percentile values for chemical concentrations, analysing the dataset according to their presence in botanicals (i) as a single chemical, (ii) as two or more chemicals from the same chemical group, or (iii) as two or more chemicals from different chemical groups. The highest 95th percentile concentration value from these analyses was 1.8%. Using the TTC value of 0.15 μg/person per day for potentially genotoxic substances proposed in 2004, this value of 1.8% was used to derive an adjusted TTC value of 10 μg of plant material on a dry weight basis/person per day for assessment of potentially genotoxic substances in botanicals.
Keywords: Botanical extracts; Botanicals; Genotoxicity; TTC; Threshold of toxicological concern.
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Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was funded by The Procter & Gamble Company. The authors declare no conflict of interest other than employment. Catherine Mahony, Phil Bowtell, Stefan Pfuhler, Tingting Zhu, and Donna McMillan are employees of The Procter & Gamble Company. Kirstin Kosemund is a former employee of The Procter & Gamble Company. Susan Barlow received personal fees from The Procter & Gamble Company during the preparation of this manuscript.
Health related guide values for drinking-water since 1993 as guidance to assess presence of new analytes in drinking-water.Int J Hyg Environ Health. 2014 Mar;217(2-3):117-32. doi: 10.1016/j.ijheh.2013.05.001. Epub 2013 Jun 6. Int J Hyg Environ Health. 2014. PMID: 23820379
Threshold of Toxicological Concern (TTC) for Botanical Extracts (Botanical-TTC) derived from a meta-analysis of repeated-dose toxicity studies.Toxicol Lett. 2019 Nov;316:1-9. doi: 10.1016/j.toxlet.2019.08.006. Epub 2019 Aug 12. Toxicol Lett. 2019. PMID: 31415786
Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet.Food Chem Toxicol. 2004 Jan;42(1):65-83. doi: 10.1016/j.fct.2003.08.006. Food Chem Toxicol. 2004. PMID: 14630131 Review.
Testing the thresholds of toxicological concern values using a new database for food-related substances.Toxicol Lett. 2019 Oct 10;314:117-123. doi: 10.1016/j.toxlet.2019.07.019. Epub 2019 Jul 17. Toxicol Lett. 2019. PMID: 31325634
Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation.Crit Rev Toxicol. 2017 Sep;47(8):705-727. doi: 10.1080/10408444.2017.1318822. Epub 2017 May 16. Crit Rev Toxicol. 2017. PMID: 28510487 Review.