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Challenges in working towards an internal Threshold of Toxicological Concern (iTTC) for use in the safety assessment of cosmetics: Discussions from the Cosmetics Europe iTTC Working Group workshop

Abstract: 
The Threshold of Toxicological Concern (TTC) is an important risk assessment tool, which has evolved over the last 50 years, and establishes acceptable low-level exposure values to be applied to chemicals with limited toxicological data. The data comprising existing TTC databases are from external exposures, and as such, the corresponding threshold limits are also representative of external exposures. With continued global interest in animal alternative methods for human safety risk assessments, one of the logical next steps in the continued evolution of TTC is to develop this concept further so that it is representative of internal exposures (i.e. a TTC based on plasma concentration). An internal TTC (iTTC) would provide threshold values that could be utilized in exposure-based safety assessments. As part of the Cosmetics Europe (CosEu) Long Range Science Strategy (LRSS) research program, CosEu has initiated a project that is working towards the development of iTTCs that can be used for the human safety assessment. Knowing that the development of an iTTC is an ambitious and broad-spanning topic, CosEu organized a Working Group and workshop to critically evaluate the requirements to establish an iTTC. Outcomes from the workshop included an evaluation on the current state of the science for iTTC, the overall iTTC strategy suggested by CosEu, selection of chemical databases, capture and curation of chemical information, ADME information and repeat dose data, expected challenges, as well as the next steps.