Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
1,4-Dioxane is a widely used synthetic industrial chemical and its contamination of drinking water and food is a potential health concern. It induces liver tumors when administered in the drinking water to rats and mice. The purpose of the present study was to determine the mechanisms of hepatocarcinogenicity and quantitatively evaluate the cancer risk of 1,4-dioxane in rats. gpt delta transgenic F344 rats were administered 1,4-dioxane at various doses in the drinking water for 16 weeks. The overall mutation frequency (MF) and A:T to G:C transitions and A:T to T:A transversions in the gpt delta transgene were significantly increased by administration of 5000 ppm 1,4-dioxane. A:T to T:A transversions were also significantly increased by administration of 1000 ppm 1,4-dioxane. Furthermore, the DNA repair enzyme MGMT was significantly induced at 5000 ppm 1,4-dioxane, implying that extensive genetic damage exceeded the repair capacity of the cells in the liver and consequently led to liver carcinogenesis. These findings demonstrate that 1,4-dioxane is a genotoxic hepatocarcinogen and induces hepatocarcinogenesis through a mutagenic mode of action in rats. Because our data indicate that 1,4-dioxane is a genotoxic carcinogen, we also estimated the point of departure of the mutagenicity and carcinogenicity of 1,4-dioxane using the no-observed effect level approach and the Benchmark dose approach to characterize its dose-response relationship at low doses.
