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Titolo:
Quantitative exposure assessment: application of physiologically-based pharmacokinetic (PBPK) modeling of low-dose, long-term exposures of organic acid toxicant in the brain
Autore:
Kim, CS; Sandberg, JA; Slikker, W; Binienda, Z; Schlosser, PM; Patterson, TA;
Indirizzi:
US FDA, Div Toxicol Res HFS 506, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA US FDA Washington DC USA 20204 fety & Appl Nutr, Washington, DC 20204 USA Natl Ctr Toxicol Res, Div Neurotoxicol HFT 132, Jefferson, AR 72079 USA Natl Ctr Toxicol Res Jefferson AR USA 72079 132, Jefferson, AR 72079 USA Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA Chem Ind Inst Toxicol Res Triangle Pk NC USA 27709 angle Pk, NC 27709 USA
Titolo Testata:
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
fascicolo: 4, volume: 9, anno: 2001,
pagine: 153 - 160
SICI:
1382-6689(200103)9:4<153:QEAAOP>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
RABBIT BRAIN; 2,4-D; RATS; DOSIMETRY;
Keywords:
physiologically-based pharmacokinetic (PBPK) modeling; low-dose; long-term exposures; brain;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
17
Recensione:
Indirizzi per estratti:
Indirizzo: Kim, CS US FDA, Div Toxicol Res HFS 506, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA US FDA Washington DC USA 20204 ppl Nutr, Washington, DC 20204 USA
Citazione:
C.S. Kim et al., "Quantitative exposure assessment: application of physiologically-based pharmacokinetic (PBPK) modeling of low-dose, long-term exposures of organic acid toxicant in the brain", ENV TOX PH, 9(4), 2001, pp. 153-160

Abstract

Our objective was to construct a physiologically-based pharmacokinetic (PBPK) model describing the kinetic behavior of 2,4-dichlorophenoxyacetic acid(2:4-D) on rats after long-term exposures to low doses. Our study demonstrated the model's ability to simulate uptake of 2,4-D in discrete areas of, the rat brain. The model was derived from the generic PBPK model that was first developed for high-dose, single exposures of 2,4-D to rats or rabbits (Kim, C.S., Gargas, M.L., Andersen, M.E., 1994. Pharmacokinetic modeling of2,4-dichlorophenoxyacetic acid (2,4-D) in rats and rabbits brain followingsingle dose administration. Toxicol. Lett. 74, 189-201; Kim, C.S., Slikker, W., Jr., Binienda, 2., Gargas, M.L., Andersen, M.E., 1995. Development ofa physiologically based pharmacokinetic (PBPK) model for 2,4-dichlorophenoxyacetic acid (2,4-D) dosimetry in discrete areas of the brain following a single intraperitoneal or intravenous dose. Neurotox. Teratol. 17, 111-120.), to which a subcutaneous (hypodermal) compartment was incorporated for low-dose, long-term infusion. It consisted of two body compartments, along with compartments for venous and arterial blood, cerebrospinal fluid, brain plasma and six brain regions. Uptake of the toxin was membrane-limited by the blood-brain barrier with clearance from the brain provided by cerebrospinal fluid 'sink' mechanisms. This model predicted profiles of 2,4-D levels in brain and blood over a 28-day period that compared well with concentrations measured in vivo with rats that had been given 2,4-D (1 or 10 mg/kg per day) with [C-14]-2,4-D subcutaneously (s.c.) for 7, 14, or 28 days, respectively. This PBPK model should be an effective tool for evaluating the target tissue doses that may produce the neurotoxicity of organic acid toxicantsafter low-dose, long-term exposures to contaminated foods or the environment. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 10:18:05