Linked Life Data

10416263

Source:http://linkedlifedata.com/resource/pubmed/id/10416263

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-10-13
pubmed:abstractText
Di(2-ethylhexyl) phthalate (DEHP), a commercially important plasticizer, induces testicular toxicity in laboratory animals at high doses. After oral exposure, most of the DEHP is rapidly metabolized in the gut to mono(2-ethylhexyl) phthalate (MEHP), which is the active metabolite for induction of testicular toxicity. To quantify the testes dose of MEHP with various routes of exposure and dose levels, we developed a physiologically based pharmacokinetic (PBPK) model for DEHP and MEHP in rats. Tissue:blood partition coefficients for DEHP were estimated from the n-octanol: water partition coefficient, while partition coefficients for MEHP were determined experimentally using a vial equilibration technique. All other parameters were either found in the literature or estimated from blood or tissue levels following oral or intravenous exposure to DEHP or MEHP. A flow-limited model failed to adequately simulate the available data. Alternative plausible mechanisms were explored, including diffusion-limited membrane transport, enterohepatic circulation, and MEHP ionization (pH-trapping model). In the pH-trapping model, only nonionized MEHP is free to become partitioned into the tissues, where it is equilibrated and trapped as ionized MEHP until it is deionized and released. All three alternative models significantly improved predictions of DEHP and MEHP blood concentrations over the flow-limited model predictions. The pH-trapping model gave the best predictions with the largest value of the log likelihood function. Predicted MEHP blood and testes concentrations were compared to measured concentrations in juvenile rats to validate the pH-trapping model. Thus, MEHP ionization may be an important mechanism of MEHP blood and testes disposition in rats.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
172-85
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Quantitative evaluation of alternative mechanisms of blood and testes disposition of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate in rats.
pubmed:affiliation
Department of Statistics, North Carolina State University, Raleigh 27695, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.