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

Abstract

Interactive effects on toxicity and biochemical parameters were studied between 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a 13-week feeding study of female Sprague-Dawley rats. The diets were supplemented with PCB 156 (1.2, 6, or 12 mg/kg), with TCDD (5 micrograms/kg), or with combinations of both compounds. Estimated daily intake of 365 micrograms/kg body wt/day (6 mg/kg diet group) of PCB 156 caused a decrease in body weight gain, thymic atrophy, liver enlargement, a loss in hepatic retinoids, induction of CYP2B activity, and a decrease in plasma thyroxine concentrations. At an estimated daily intake of 81 micrograms PCB 156/kg body wt/day CYP1A1 and CYP1A2 activities were induced. Compared to a simultaneous subchronic feeding study with TCDD a toxic equivalency factor (TEF) between 0.00004 and 0.001 was estimated for PCB 156 with respect to the mentioned effects. Antagonistic effects were found between TCDD and PCB 156 for CYP2B activity and hepatic retinol levels. These effects concurred with a PCB 156 dose-dependent decrease in hepatic TCDD levels. Hepatic PCB 156 levels were found to be increased at the 1.2-mg PCB 156/kg dose group in coadministration with TCDD. In conclusion, at least part of the antagonistic effects between PCB 156 and TCDD observed have a toxico-kinetic base. Furthermore, the magnitude of the antagonistic effects may be neglected in comparison with the uncertainty in the TEF value. Therefore, the interactive effects found between PCB 156 and TCDD may have no implications for the additivity of the TEF concept.

Induction of olfactory mucosal and liver metabolism of lidocaine by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin

“…12]. There is some controversy over compound, gender, age, and strain-related factors associated with CYP2B induction [31,32], but our results, showing increased PROD activity in liver microsomes from TCDDtreated rats, are consistent with previously reported observations [33]. The observation that multiple CYPs are inducible by nasal mucosa has several human health implications.…”

Characterization of Potential Endocrine-Related Health Effects at Low-Dose Levels of Exposure to PCBs

“…At postnatal day 21, there were no observable reductions in plasma T4 levels, indicating that perinatal exposure to PCBs did not cause permanent alterations in thyroid hormone levels in the offspring. Reduced plasma T4 levels were also observed in rat pups born to dams exposed to 4 or 16 mg of 2,3',4,4',5-pentaCB (PCB 118) and 16 or 64 mg of 2,2',4,4',5,5'-hexaCB (PCB 153)/kg/day from gestation day 10 to gestation day 16 (41).…”

“…For example, severely depressed T4 levels (by 60-90%) were observed in fetal and neonatal rats following in utero exposure to 5 or 25 mg of Aroclor 1254/kg from gestation day 10 to gestation day 16 (32), while much higher doses of Aroclor 1254 were needed in adult rats to cause similar changes in plasma T4 levels (36). At postnatal day 21, there were no observable reductions in plasma T4 levels, indicating that perinatal exposure to PCBs did not cause permanent alterations in thyroid hormone levels in the offspring.…”

Differential effects of two lots of aroclor 1254 on enzyme induction, thyroid hormones, and oxidative stress.

“…In the case of synergism, the congeners act via multiple mechanisms to produce a greater than additive effect which the TEQ would thus underpredict. Van Birgelen et al (42) found clear evidence of synergism for increases in both hepatic and urinary porphyrins as well as significant decreases in total T4 (36,43).…”