While the term “Threshold of Toxicological Concern” is broadly used across sectors, its formal purpose, definition, and implementation is not identical. The TTC may be used for screening and risk-based prioritization for environmental chemicals or exposure-based waiving of cosmetic and food-related substances. However, in the pharmaceutical sector, the TTC is specifically applied to known or putative mutagenic drug impurities at a level below which the compound is anticipated to pose a negligible risk of carcinogenicity (1 x 10^-5) for all patient populations and routes of exposure as described in ICH M7 guidance. Practical considerations for implementing ICH M7, including methodological approaches and global regulatory acceptance, will be discussed for pharmaceuticals administered over varying durations and at different stages of drug development. The historical basis of the TTC described in ICH M7, less-than-lifetime considerations, and efforts to further refine this value will also be presented. To further contextualize similarities and differences in the implementation of the pharmaceutical impurity-specific TTC relative to other TTC applications across sectors, this presentation will provide a high-level overview of key distinctions in TTC use for pharmaceuticals versus other contexts, using case studies to illustrate how sector-specific considerations shape its application.