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.
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.
Van Birgelen
A P
AP
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Van der Kolk
J
J
Fase
K M
KM
Bol
I
I
Poiger
H
H
Van den Berg
M
M
Brouwer
A
A
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D005260:Female; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000097:blood; D014801:Vitamin A / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D013963:Thyroid Hormones; D014801:Vitamin A; C087667:2,3,3',4,4',5-hexachlorobiphenyl; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls