The Effect of 2,3,7,8-Tetrafluorodibenzo-p-dioxin on Pubertal Rats : An Analysis Focusing on the Dioxin-like Acute Toxicity

Hitomi Masaya, Takeda Tomoki, Yamada Hideyuki, Ishii Yuji

doi:10.15017/1809685

It has long been believed that dioxins cause a number of acute toxicity such as body weight loss, hepatotoxicity and immunosuppression due to binding to the aryl hydrocarbon receptor (AHR). To propose provisions for these toxic effects, many researchers have challenged to identify the substances which are antagonistic to the AHR action. As the results, several compounds including polyphenols have been suggested to inhibit activation of AHR to ameliorate dioxin toxicity. However, none of them dramatically show protective effects on the living body. Therefore, developing revolutionary agents targeting the AHR remain to require for protecting our health from dioxin exposure. To address this issue, we newly synthesized 2,3,7,8-tetrafluorodibenzo-p-dioxin (TFDD), the product which chlorine atoms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are replaced with fluorine atoms. Unlike with TCDD, a single oral administration of TFDD (1-1,000 μg/kg) to male pubertal rats hardly altered the hepatic activity of cytochrome P450 1A1 which is induced by AHR activation both one and seven days after treatment. In accordance with this, the suppression of body weight gain, hepatomegaly and thymic atrophy were not observed by TFDD treatment. However, TFDD slightly increased the weights of the lung and spleen, while the heart and kidney weights were slightly decreased by the treatment. These results suggest that an oral administration of TFDD does not have any dioxin-like acute toxicity, although some of tissues are influenced by TFDD at the higher doses.

The Effect of 2,3,7,8-Tetrafluorodibenzo-p-dioxin on Pubertal Rats : An Analysis Focusing on the Dioxin-like Acute Toxicity

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