Threshold of Toxicological Concern (TTC)

These questions were addressed in a recently completed Cefic LRI project. The researchers initially identified 137 non-genotoxic tumorigenic substances whose threshold limits could be derived from studies in the Cancer Potency Database and from peer-reviewed publications. To distinguish the most sensitive point of departure for risk assessment, they plotted the study NOAELs against the effective tumor dose (ETD10) and the benchmark dose level (BMDL10) calculated by model averaging using the Proast software. The comparative analysis of NOAEL/EDT10 and BMDL10 values revealed that bioaccumulating substances and steroids were among the 5 percent most toxic compounds. Exclusion of these compounds led to comparable 5th percentiles for chronic NOAEL/BMDL10 values, whereas the 5th percentile EDT10 value was about three times higher. A statistically significant difference, however, was not detected. These results were evaluated with regard to the current TTC, supporting the application of Cramer Class thresholds to non-genotoxic tumorigenic substances.