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Drug Metabolism and Disposition Fast Forward
First published on August 18, 2005; DOI: 10.1124/dmd.105.006189

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Received for publication June 23, 2005.
Revised August 15, 2005.
Accepted for publication August 18, 2005.

THE DECREASE IN LEVEL OF SERUM THYROXINE BY 2,2',4,5,5'-PENTACHLOROBIPHENYL IN RATS AND MICE : NO CORRELATION WITH FORMATION OF METHYLSULFONYL METABOLITES

Yoshihisa Kato 1*, Koichi Haraguchi 2, Tomoaki Yamazaki 1, Ryohei Kimura 1, Nobuyuki Koga 3, Shizuo Yamada 1, masakuni degawa 4

1 University of Shizuoka 2 Daiichi College of Pharmaceutical Sciences 3 Nakamura Gakuen University 4 university of shizuoka

* Address correspondence to: E-mail: kato{at}ys7.u-shizuoka-ken.ac.jp

Abstract

A relationship between formation of methylsulfonyl (MeSO2) metabolites of 2,2',4,5,5'-pentachlorobiphenyl (PentaCB) and decrease in serum thyroxine (T4) level was examined in the rats and mice after a single i.p. injection of PentaCB (342 µmol/kg body weight). In either rats or mice, levels of the 3- and 4-MeSO2 metabolites of PentaCB in the liver and feces increased in a time-dependent fashion up to day 8 after PentaCB-treatment. However, there was a remarked difference between rats and mice in the amount of the metabolites formed, and cumulative amount of the either MeSO2 metabolite for 8 days after PentaCB treatment in the liver was 4-15 times higher in mice than in rats. On the other hand, 40-60% decrease in level of serum total T4 occurred in both rats and mice at day 1 after PentaCB treatment, and the decrease retained up to day 8 after PentaCB treatment. Thus, there was a marked difference between rats and mice in the formation of MeSO2 metabolites from PentaCB, but not significant difference between rats and mice in PentaCB-induced decrease in level of serum total T4, indicating that PentaCB-induced decrease in level of serum total T4 is not necessarily dependent on the MeSO2 metabolites formed.


Key words: polycyclic aromatic hydrocarbons, toxicology




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