Our experience indicates that extrapolation of doses from the maximum tolerated doses (MTD) derived from 4-week dose range finding (DRF) studies conducted in CByB6F1 may overpredict tolerability and undermine utility of the high-dose groups in 26-week carcinogenicity studies conducted in Tg.rasH2. In the 26-week carcinogenicity studies conducted in Tg.rasH2 mice, we analyzed the initial body weights, food consumption (FC), terminal body weights, body weight gain (BWG), mortality, and tumor incidence for vehicle and test article-treated dose groups for 26 studies conducted from 2014 to 2018. Although not statistically significant compared to the control dose group, the % BWG decreased in male mice of mid- and high-dose groups by >10%, whereas in females there were no differences. The mortality increased in a statistically significant manner for medium and high doses of males. In female mice, the mortality increased in the high-dose group but not in a statistically significant manner. When the cause of death (COD) was analyzed in all dose groups of both sexes, the COD due to tumors was highest in the control groups, whereas it was lowest in high-dose groups of both sexes. At the same time, the COD due to undetermined causes, which is possible indication of test article-induced toxicity, was highest in high-dose groups of both sexes. These findings together indicate that MTD derived from earlier DRF studies was exceeded when applied to 26-week carcinogenicity studies and did not serve any purpose in the outcome of these studies.