NR1I3 and neoplasm: We would argue that without a greater understanding of the mechanism of carcinogenicity, current human-relevant model systems, for example using human cell lines, hepatocytes, or chimeric animals transplanted with human hepatocytes, which measure the capacity of a compound to induce DNA synthesis (which in their own right have a number of significant limitations) do not rule out the possibility that a human CAR activator might act as a non-genotoxic tumour-promoting agent in humans.