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Study published on drinking-water exposure to 1,4-dioxane

Drs. Grace ChappellMelissa Heintzand Laurie Haws of ToxStrategies recently published a paper in Current Research in Toxicology, on transcriptomic responses to the chemical 1,4-dioxane. This study, was conducted to gain a better understanding of the underlying molecular mechanisms related to liver tumor development in mice orally exposed to 1,4-dioxane. The work included transcriptomics analyses of liver tissue collected from a 90-day drinkingwater study in female B6D2F1/Crl mice. Overall, global gene expression changes were low, with minimal to no treatment effects at concentrations below 600 ppm. At higher concentrations, genes involved in phase II metabolism and mitotic cell cycle checkpoints were upregulated significantly, with the increase in mitotic signaling most prevalent in the livers of mice exposed to 1,4-dioxane at that concentration for 90 days. There was an overall lack of enrichment of genes related to DNA damage response. The results of the transcriptomics analysis align with, and further support, a threshold-dependent, non-mutagenic, mitogenic mode of action for 1,4-dioxane-induced liver tumors.