The cancer threshold of toxicological concern (TTC) as determined by Kroes et al. in 2004 (0.15 µg/day and 1.5 µg/day at risk levels of 1 in 106 or 105, respectively) has been uncritically employed as a key metric in multiple regulatory guidance documents. There are numerous concerns regarding transparency and the highly conservative methodology in relation to its derivation; moreover, no formal confirmation has been undertaken by any regulatory body prior to its adoption. A recent joint report from the European Food Safety Authority and World Health Organization follows this trend, largely replicating previous conclusions and downplaying the need for a re-assessment. This view is challenged by Boobis et al. who confirm concerns regarding lack of transparency and stress that several of the assumptions and approaches used previously have been superseded by advances in knowledge; they recommend as a first step construction of a new dataset derived from the Carcinogenic Potency Database focusing on mutagenic DNA-reactive rodent carcinogens and a critical assessment of the relevance and reliability of carcinogenicity data. This type of approach is supported with two key exceptions: inclusion of data from the ToxTracker assay which provides a direct readout of DNA reactivity, and use of appropriate epidemiological data on acrylamide (AA) to determine a benchmark for human exposure to a typical DNA-reactive rodent carcinogen. It is concluded that a robust re-evaluation using an appropriate dataset and methodology is urgently needed to ensure the integrity of the cancer TTC before it is employed in its present form even more widely.