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Previous work has shown that the weight of evidence supports the hypothesis that 1,4-dioxane causes liver tumors in rodents through cytotoxicity and subsequent regenerative hyperplasia. Questions regarding a lack of concordant findings for this mode of action (MOA) in mice have not been resolved, however. In the current work, a reanalysis of data from two chronic mouse cancer bioassays on 1,4-dioxane, one 13-week mouse study, seven rat cancer bioassays, coupled with other data such as 1,4-dioxane's negative mutagenicity, its lack of up-regulated DNA repair, and the appearance of liver tumors with a high background incidence, support the conclusion that rodent liver tumors, including those in mice, are evoked by a regenerative hyperplasia MOA. The initiating event for this MOA is metabolic saturation of 1,4-dioxane. Above metabolic saturation, higher doses of the parent compound cause an ever …