Relative potency values derived from hepatic vitamin A reduction in male and female Sprague-Dawley rats following subchronic dietary exposure to individual polychlorinated dibenzo-p-dioxin and dibenzofuran congeners and a mixture thereof

This stud investigated the potency of individual polychlorinated dibenza-p-dioxins (PCDDs) and dibenzofurans (PCDFs) to reduce hepatic vitamin A in the rat. Dose-response relationships were determined following long-term dietary exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran, 1,2,3,4,8-pentachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzofuran, 1,2,3,6,7,8-hexachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzo-p-dioxin octachlorodibenzo-p-dioxin, octachlorodibenzofuran, or mixtures of some of these congeners. The aim was to estimate vitamin A-related relative potency (REP) values for each congener in relation to that of TCDD and to investigate if these values were in accordance with REP values estimated for the subchronic toxicity observed in the same study. An additional aim was to investigate if the effect on hepatic vitamin A levels was additive compared to the effect of the individual congeners. The obtained results demonstrate that hepatic vitamin A reduction occurs as a consequence of long-term low-level exposure to 2,3,7,8-substituted but not to non-2,3,7,8-substituted congeners. Female rats were slightly more responsive to this effect as judged from the lower EC50 values for all the congeners in this sex. The vitamin A-related REP values were similar for female and male rats and were in good agreement with the estimated REP values for subchronic toxicity in the same animals. The vitamin A effect of the individual congeners in the mixture tended to be somewhat less than pure additive for male rats and very close to pure additive for female rats. Ln conclusion, the presented data show that reduction of hepatic vitamin A is a sensitive marker of an altered retinoid homeostasis following long-term low-dose exposure to dioxin-like compounds, which essentially conforms to their assumed additive mechanism of action. (C) 2000 Academic Press.