title: Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344 rats.
abstract: 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.
authors.affiliation: Department of Environmental Health Science, the University of Georgia, Athens, GA 30602, USA.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Qian
authors.forename: Lili
authors.initials: L
authors.lastname: Tang
authors.forename: Franklin
authors.initials: F
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Guo
authors.forename: Michael E
authors.initials: ME
authors.lastname: Massey
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Williams
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Phillips
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Wang
mesh_terms: D016604:Aflatoxin B1 / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D008239:Lysine / Q000097:blood*; D008297:Male; D008954:Models, Biological; D015233:Models, Statistical; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D015415:Biomarkers; C066451:aflatoxin B1-lysine adduct; D016604:Aflatoxin B1; D008239:Lysine