Toxic Potency of 3,3′,4,4′,5-Pentachlorobiphenyl Relative to and in Combination with 2,3,7,8-Tetrachlorodibenzo-p-dioxin in a Subchronic Feeding Study in the Rat

Abstract

Toxic and biochemical potencies of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) were studied relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a 13-week feeding study in female Sprague-Dawley rats. To study possible interactive effects the combinations of both compounds were administered. The diets were supplemented with PCB 126 (7, 50, or 180 μg/kg diet), with TCDD (0.4 or 5 μg/kg diet), or with combinations of both compounds. An estimated daily intake of 0.47 μg PCB 126/kg body weight/day caused thymic atrophy, a dramatic loss in he patic retinoids, and a marked induction in CYP1A1 and CYP1A2 activities. At a daily intake of 3.18 μg PCB 126/kg body weight/day a decrease in body weight gain, liver enlarge ment, and plasma thyroid hormone concentrations occurred. Based on a simultaneous subchronic feeding study with TCDD, a toxic equivalency factor range between 0.01 and 0.1 was estimated for PCB 126 for the mentioned effects. Antagonism was found between TCDD and PCB 126 for hepatic retinol levels and CYP1A2 activity. At the same time, TCDD and PCB 126 liver residue levels were slightly decreased by coadministration. However, these antagonistic effects occurred at maximum induction levels of CYP1A1 and CYP1A2, which are not likely to occur at levels relevant for humans.