In vivo acute exposure to polychlorinated biphenyls: Effects on free and total thyroxine in rats

Hedge, JM; Devito, MJ; Crofton, KM

HERO ID

1404458

Reference Type

Journal Article

Year

2009

Language

English

PMID

19815845

HERO ID 1404458
In Press No
Year 2009
Title In vivo acute exposure to polychlorinated biphenyls: Effects on free and total thyroxine in rats
Authors Hedge, JM; Devito, MJ; Crofton, KM
Journal International Journal of Toxicology
Volume 28
Issue 5
Page Numbers 382-391
Abstract Hypothyroxinemia in rats has been well documented as a result of exposure to polychlorinated biphenyls (PCBs). Hypothetical mechanisms include induction of hepatic catabolic enzymes and cellular hormone transporters, and/or interference with plasma transport proteins. We hypothesized that if thyroxine displacement from transport proteins by PCBs occurs in vivo, it would result in increased free thyroxine (FT4). This study investigates the effects of a single oral dose of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153 at 60 mg/kg) or 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169 at 1 mg/kg) on rats at 28 or 76 days of age. Total thyroxine (TT4) and FT4 were measured at 0.5, 1, 2, 4, 8, 24, or 48 hours post-dosing. Microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD) activity and uridine diphosphoglucuronosyl transferase (UGT) activity were determined. No significant increase in TT4 or FT4 concentrations was seen at any time point. PCB 153 significantly decreased TT4 and FT4 in young and adult rats, with young rats showing a time-by-treatment interaction from 2 to 48 hours post-dosing in serum FT4. With PCB 169 exposure, young rats showed a decrease in FT4 only, whereas adult rats showed decreases in TT4 only. Hepatic EROD and PROD activities were both dramatically increased following PCB 169 and 153, respectively. Uridine diphosphoglucuronosyl transferase activity was increased only after PCB 169 exposure. These data demonstrate that neither PCB 153 nor PCB169 increased FT4, which supports the conclusion that these PCBs do not displace thyroxine from serum TTR, or if it does occur, there is no subsequent increase in serum FT4 in vivo.
Doi 10.1177/1091581809344631
Pmid 19815845
Wosid WOS:000270635800005
Url http://<Go to ISI>://WOS:000270635800005
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword endocrine disruptors; free thyroxine; polychlorinated biphenyls; thyroid hormones; total thyroxine