Elimination kinetics and toxicity of 2,3,7,8-tetrachlorothianthren, a thio analogue of 2,3,7,8-TCDD.

Abstract:

:In comparison to the polychlorinated dibenzo-p-dioxins (PCDD) informations on their thio analogues the polychlorinated thianthrens (PCTA) are very limited. In this study we investigated the kinetics and toxicity of 2,3,7,8-tetrachlorothianthren (TCTA), the analogue of the most toxic PCDD congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It was found that TCTA is rapidly eliminated in mouse liver homogenate fortified with an NADPH-regenerating system suggesting rapid metabolic degradation by liver monooxygenases. Furthermore, TCTA was rapidly eliminated from mouse liver and whole body. In accordance with this rapid elimination, a weekly dosage of 1mg TCTA per kg body weight (i.p.) over six weeks did not result in weight loss or other signs of overt toxicity in male mice. In rat hepatocytes in primary culture, TCTA was active as inducer of dioxin receptor-regulated cytochrome P4501A1 activity measured as 7-ethoxyresorufin O-deethylase (EROD). The relative inducing potency was about 0.0001 in comparison to TCDD. In spite of this molecular effects, the rapid elimination both in vitro and in vivo argues against a consideration of a TCDD equivalency factor for TCTA.

journal_name

Chemosphere

journal_title

Chemosphere

authors

Weber R,Hagenmaier H,Schrenk D

doi

10.1016/s0045-6535(97)10227-2

subject

Has Abstract

pub_date

1998-05-01 00:00:00

pages

2635-41

issue

12

eissn

0045-6535

issn

1879-1298

pii

S0045653597102272

journal_volume

36

pub_type

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