Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344 rats.

Autor: Qian G; Department of Environmental Health Science, the University of Georgia, Athens, GA 30602, USA., Tang L, Wang F, Guo X, Massey ME, Williams JH, Phillips TD, Wang JS
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2013 Jan 07; Vol. 303, pp. 147-51. Date of Electronic Publication: 2012 Nov 09.
DOI: 10.1016/j.tox.2012.10.020
Abstrakt: Aflatoxin B(1)-lysine adduct (AFB-Lys) is a reliable biomarker for aflatoxin exposure; however, a systematic toxicokinetic evaluation has not been reported. In this study, male F344 rats were orally exposed to single, or repeated, doses of AFB(1) and the toxicokinetics of serum AFB-Lys that followed treatments were investigated. A single-dose of AFB(1) increased serum AFB-Lys levels rapidly peaking at 4h, followed by first-order elimination, through which the half-life was estimated to be 2.31 days. A physiologically based pharmacokinetic model showed that approximately 3.00-3.90% and 1.12-1.98% of the administered AFB(1) doses were converted to serum AFB-Lys adducts at 2h and 24h post treatment, respectively. Repeated AFB(1) exposure at 5-25 μg/kg body weight linearly increased serum AFB-Lys levels for 5 weeks in animals, resulting in a 1-1.5 times higher AFB-Lys level overall. This indicates the potential of this adduct as a reliable biomarker for repeated low dose exposure. Higher dose exposure at 75 μg/kg increased the level of AFB-Lys to a maximum at 2 weeks, followed by a gradual decrease to near plateau level up to 5 weeks. In conclusion, this study systematically evaluated the toxicokinetics of serum AFB-Lys adduct in F344 rats using a physiologically based pharmacokinetic model and robust statistical modeling analysis and provided a firm and clear understanding of the toxicokinetics of this biomarker.
(Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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