NDLI: Human biofluid concentrations of mono(2-ethylhexyl)phthalate extrapolated from pharmacokinetics in chimeric mice with humanized liver administered with di(2-ethylhexyl)phthalate and physiologically based pharmacokinetic modeling.

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Human biofluid concentrations of mono(2-ethylhexyl)phthalate extrapolated from pharmacokinetics in chimeric mice with humanized liver administered with di(2-ethylhexyl)phthalate and physiologically based pharmacokinetic modeling.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Adachi, Koichiro Suemizu, Hiroshi Murayama, Norie Shimizu, Makiko Yamazaki, Hiroshi
Description	Country affiliation: Japan Author Affiliation: Adachi K ( Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.); Suemizu H ( Central Institute for Experimental Animals, Kawasaki-ku, Kawasaki 210-0821, Japan.); Murayama N ( Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.); Shimizu M ( Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.); Yamazaki H ( Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan. Electronic address: hyamazak@ac.shoyaku.ac.jp.)
Abstract	Di(2-ethylhexyl)phthalate (DEHP) is a reproductive toxicant in male rodents. The aim of the current study was to extrapolate the pharmacokinetics and toxicokinetics of mono(2-ethylhexyl)phthalate (MEHP, a primary metabolite of DEHP) in humans by using data from oral administration of DEHP to chimeric mice transplanted with human hepatocytes. MEHP and its glucuronide were detected in plasma from control mice and chimeric mice after single oral doses of 250mg DEHP/kg body weight. Biphasic plasma concentration-time curves of MEHP and its glucuronide were seen only in control mice. MEHP and its glucuronide were extensively excreted in urine within 24h in mice with humanized liver. In contrast, fecal excretion levels of MEHP glucuronide were high in control mice compared with those with humanized liver. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated urine MEHP concentrations in humans were consistent with reported concentrations. This research illustrates how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of pharmacokinetics or toxicokinetics of the primary or secondary metabolites of DEHP.
File Format	HTM / HTML
ISSN	13826689
Issue Number	3
Volume Number	39
e-ISSN	18727077
Journal	Environmental Toxicology and Pharmacology
Language	English
Publisher	Elsevier
Publisher Date	2015-05-01
Publisher Place	Netherlands
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Environmental Health Discipline Pharmacology Diethylhexyl Phthalate Analogs & Derivatives Administration & Dosage Liver Metabolism Administration, Oral Animals Pharmacokinetics Urine Feces Chemistry Humans Liver Transplantation Mice Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology Pharmacology

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