Biologic and toxic effects of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in the guinea pig. Quantitative structure-activity relationships.
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abstract
The dose-response effects of 2,3,7,8-tetrachorodibenzo-p-dioxin, 1,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,4,7,8-pentachlorodibenzo-p-dioxin, 2,3,4,7,8-, 1,2,3,7,9-, and 2,3,4,7,9-pentachlorodibenzofuran on body weight loss and hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction were determined in the immature male guinea pig. The ED50 values for each compound were measured for the three in vivo responses. The quantitative structure-activity relationships clearly illustrated that the most toxic congeners were substituted in the lateral 2, 3, 7 and 8 positions, and removal of a lateral chlorine group substantially reduced the potency of the resulting compound. The most toxic congener in this series was 2,3,7,8-tetrachlorodibenzo-p-dioxin in which the in vivo ED50 values for AHH and EROD induction and body weight loss were 2.8 X 10(-10), 9.3 X 10(-11) and 5.6 X 10(-9) mol/kg. The structure-activity relationships observed in this study were comparable to those previously reported in rats and rat hepatoma H-4-II E cells in culture. Moreover, there was an excellent linear correlation between in vivo -log ED50 values for body weight loss, AHH and EROD induction and the corresponding in vitro -log EC50 data for AHH induction in rat hepatoma cells [S. Safe, Chemosphere 16, 791 (1987)].
