ELIMINATION KINETICS AND TOXICITY OF 2,3,7,8-TETRACHLOROTHIANTHREN, ATHIO ANALOG OF 2,3,7,8-TCDD

In comparison to the polychlorinated dibenzo-p-dioxins (PCDD) informat ions on their thio analogues the polychlorinated thianthrens (PCTA) ar e very limited. In this study we investigated the kinetics and toxicit y of 2,3,7,8-tetrachlorothianthren (TCTA), the analogue of the most to xic PCDD congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It was f ound that TCTA is rapidly eliminated in mouse liver homogenate fortifi ed with an NADPH-regenerating system suggesting rapid metabolic degrad ation by liver monooxygenases. Furthermore, TCTA. was rapidly eliminat ed from mouse liver and whole body. In accordance with this rapid elim ination, a weekly dosage of 1 mg TCTA per kg body weight (i.p.) over s ix weeks did not result in weight loss or other signs of overt toxicit y in male mice. In rat hepatocytes in primary culture, TCTA was active as inducer of dioxin receptor-regulated cytochrome P4501A1 activity m easured as 7-ethoxyresorufin O-deethylase (EROD). The relative inducin g potency was about 0.0001 in comparison to TCDD. In spite of this mol ecular effects, the rapid elimination both in vitro and in vivo argues against a consideration of a TCDD equivalency factor for TCTA. (C) 19 98 Elsevier Science Ltd All rights reserved.