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.
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 micrograms/kg diet), with TCDD (0.4 or 5 micrograms/kg diet), or with combinations of both compounds. An estimated daily intake of 0.47 micrograms PCB 126/kg body weight/day caused thymic atrophy, a dramatic loss in hepatic retinoids, and a marked induction in CYP1A1 and CYP1A2 activities. At a daily intake of 3.18 micrograms PCB 126/kg body weight/day a decrease in body weight gain, liver enlargement, 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.
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
Brouwer
A
A
Van den Berg
M
M
D000083:Acetanilides / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004350:Drug Residues; D004435:Eating / Q000187:drug effects; D004790:Enzyme Induction; D005260:Female; D006900:Hydroxylation; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000096:biosynthesis; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000097:blood; D014801:Vitamin A / Q000378:metabolism
D000083:Acetanilides; D000072317:Polychlorinated Dibenzodioxins; D013963:Thyroid Hormones; D014801:Vitamin A; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C023035:3,4,5,3',4'-pentachlorobiphenyl