Threshold of Toxicological Concern (TTC) for Botanical Extracts (Botanical-TTC) derived from a meta-analysis of repeated-dose toxicity studies. (November 2019)

• Record Type: Journal Article
• Authors: Kawamoto, Taisuke; Fuchs, Anne; Fautz, Rolf; Morita, Osamu
• Is Part Of: Toxicology letters. Volume 316(2019)
• Page Start: 1
• Page End: 9
• Publication Date: 2019-11
• Subjects: AIC Akaike's information criterion -- BIC Bayesian information criterion -- BMD benchmark dose -- BMDL benchmark dose lower confidence limit -- CoC Cohort-of-Concern -- DNEL derived-no-effect-level -- DMEL derived-minimal-effect-level -- LOAEL lowest-observed-adverse-effect-level -- MTD maximum tolerable dose -- NOAEL no-observed-adverse-effect-level -- NOEL no-observed-effect-level -- PoD point-of-departure -- TTC Threshold of Toxicological Concern; Threshold of Toxicological Concern -- TTC -- Botanical-TTC -- Botanical extract -- Mixture; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2019.08.006
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: 213 Point-of-Departures on botanical extracts were collected. Cramer III TTC can be considered as conservative enough for botanical extracts. A novel TTC value of 663 μg/day for botanical extracts is proposed. Abstract: Threshold of Toxicological Concern (TTC) is a promising approach for evaluating the human health risk for systemic toxicity when there is a lack of toxicological information. The threshold for systemic toxicity is reportedly 1800, 540, and 90 μg/day for Cramer I–III chemical structures, according to Munro's structural decision tree, and 0.15 μg/day for genotoxic compounds. However, the concept of TTC has been developed for single substances; therefore, the applicability of TTC for mixtures remains unclear. To expand application of probability approach for mixtures, a validation study using the point of departures (PoDs) derived from mixtures is required. In the present study, we investigated novel TTC of botanical extracts (Botanical-TTC) for cosmetics from a meta-analysis based on the PoDs derived from repeated dose toxicity testing in botanical extracts. Accordingly, 213 PoDs were determined by repeated-dose toxicity studies and divided using a default uncertainty factor of 100 combined with the extrapolation factor of study duration to calculate the derived-no-effect-level (DNEL) and derived-minimal-effect-level (DMEL). The minimum DNEL/DMEL was 1.6-fold higher than the Cramer III TTC. In addition, because human health risk below the 1 st percentile value (663 μg/day) was considered as extremely limited, the exposure level can be proposed as Botanical-TTC.