Biologic and toxic effects of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in the guinea pig. Quantitative structure-activity relationships

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-pentachloro-dibenzofuran 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 thein vivo ed₅₀ values for AHH and EROD induction and body weight loss were 2.8 × 10^-10, 9.3 × 10^-11 and 5.6 × 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 viuo -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)].