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Titolo:
Analysis of methylmercury disposition in humans utilizing a PBPK model andanimal pharmacokinetic data
Autore:
Young, JF; Wosilait, WD; Luecke, RH;
Indirizzi:
Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA Natl Ctr Toxicol Res Jefferson AR USA 72079 ment, Jefferson, AR 72079 USA Univ Missouri, Sch Med, Dept Pharmacol, Columbia, MO 65212 USA Univ Missouri Columbia MO USA 65212 ept Pharmacol, Columbia, MO 65212 USA Univ Missouri, Dept Chem Engn, Columbia, MO 65212 USA Univ Missouri Columbia MO USA 65212 ept Chem Engn, Columbia, MO 65212 USA
Titolo Testata:
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A
fascicolo: 1, volume: 63, anno: 2001,
pagine: 19 - 52
SICI:
1528-7394(20010511)63:1<19:AOMDIH>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
METHYL-MERCURY; COMPUTER-MODEL; EXPOSURE; GROWTH; BLOOD; PREGNANCY; FISH; HAIR; MICE; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Young, JF Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA Natl Ctr Toxicol Res 3900 NCTR Rd Jefferson AR USA 72079 079 USA
Citazione:
J.F. Young et al., "Analysis of methylmercury disposition in humans utilizing a PBPK model andanimal pharmacokinetic data", J TOX E H A, 63(1), 2001, pp. 19-52

Abstract

Physiologically based pharmacokinetic (PBPK) models are excellent tools toaid in the extrapolation of animal data to humans. When the late of the chemical is the same among species bring compared, animal data can appropriately be considered as a model for human exposure. For methylmercury exposure, sufficient data exist to allow comparison of numerous mammalian species to humans. PBPK model validation entails obtaining blood and tissue concentrations of the parent chemical and metabolite(s) at various times following a known exposure. From ethical and practical considerations, human tissue concentrations following a known exposure to an environmental toxicant are scarce. While animal-to-human extrapolation demands that sufficient human data exist to validate the model, the validation requirements are less stringent if multiple animal models are utilized within a single model template. A versatile PBPK model was used to analyze the distribution and eliminationof methylmercury and its metabolite, inorganic mercury. Uniquely, the model is formed in a generic way from a single basic template during the initial program compilation. Basic parameters are defined for different PBPK models for mammalian species that span a relatively large range of sizes. In this article, the analyser include 12 species (mouse. hamster, rat, guinea pig, cat rabbit, monkey sheep, pig, gear, cow, and human), Allometric (weight-based) correlations of tissue binding coefficients, metabolism rate constants, and elimination parameters for both methylmercury and inorganic mercury are presented for species for which sufficient data are available. The resulting human model, in accord with the animal models, predicts relatively high inorganic mercury levels in the kidneys long alter the disappearance of methylmercury from the blood.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 23:19:13