Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5859510 | Toxicology | 2013 | 5 Pages |
Abstract
Aflatoxin B1-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 AFB1 and the toxicokinetics of serum AFB-Lys that followed treatments were investigated. A single-dose of AFB1 increased serum AFB-Lys levels rapidly peaking at 4 h, 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 AFB1 doses were converted to serum AFB-Lys adducts at 2 h and 24 h post treatment, respectively. Repeated AFB1 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.
Keywords
Related Topics
Life Sciences
Environmental Science
Health, Toxicology and Mutagenesis
Authors
Guoqing Qian, Lili Tang, Franklin Wang, Xia Guo, Michael E. Massey, Jonathan H. Williams, Timothy D. Phillips, Jia-Sheng Wang,