Publications : 2017

McMillan DA, Kosemund K, Mahony C, Huber M, Bowtell P. Threshold of toxicological concern (TTC) for botanicals—Data analysis to substantiate and extend the TTC approach to botanicals. In: The Toxicologist: Suppl to Toxicol Sci 156(1), Abstract no. 1831, Society of Toxicology, 2017.


The presence of botanicals in consumer products has become an important consumer criterion for the purchase of specific product cat-egories. Botanicals are complex mixtures of mostly unknown natural chemical constituents and classical toxicological data are often lacking. While some botanicals are used broadly by humans as food, flavors/spices, or medicines, other botanicals are also known to cause various toxic effects. The combination of these uncertainties makes risk assess-ment for botanicals a challenging task. Establishing safe botanical expo-sure levels in the absence of carcinogenicity and genotoxicity data, which address the most sensitive endpoint becomes a critical and often rate limiting step in botanical risk assessment. To support the presence of single chemicals at low exposure levels in consumer products the TTC based approach can be used in absence of full toxicological characteri-zation (Blackburn et al. 2005). This approach can also serve as a basis for deriving exposure limits for botanicals. The TTC decision tree approach starts with the identification and evaluation of possible structural alerts for genotoxicity and high potency carcinogenicity. This step applies an exposure threshold of 0.15µg/person/day (Munro, 1996, Kroes, 2004). We propose to extend the TTC approach to botanicals, relying on this first TTC exposure limit of 0.15µg/day (0.0025 µg/kg bw/day) and adjusting it based on the concentration of natural chemical constituents of concern that are found in plants. An evaluation of over 50 genotoxic/DNA reactive and carcinogenic chemical constituents found in plants has been made and the concentration data from several hundred plant species compiled (over 2300 observations). The distribution of the data was modeled using a variety of statistical techniques with the Weibull model providing the best fit. The concentration probability at the 95th percentile for the concentration of chemical constituents of concern in plants was used to adjust the TTC. When classical toxicological data are lacking, we suggest using 15µg/day (0.25μg/kg bw/day) as a health protective TTC exposure limit for botanicals and their simple extracts.