Linked Life Data

2606678

Source:http://linkedlifedata.com/resource/pubmed/id/2606678

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1990-2-16
pubmed:abstractText
The nitrogen-containing polycyclic aromatic hydrocarbon 1-nitropyrene (NP), a bacterial mutagen and mammalian carcinogen, is a ubiquitous environmental pollutant. A physiologically based toxicokinetic model was developed describing the disposition of NP after oral administration (ingestion) or after inhalation. The model incorporated the following compartments: blood, upper respiratory tract, lung, liver, kidney, gastrointestinal (GI) tract, and a general tissue compartment. First-order rate constants for absorption of NP from the GI tract (2 h-1), metabolism by the liver (30 h-1), excretion of metabolites in bile and urine (2 and 4 h-1, respectively), and covalent binding of NP metabolites to tissue macromolecules (0.05, 0.05, 0.1, and 0.001 h-1 for lung, liver, kidney, and general tissue compartment, respectively) determined from model simulations were used to describe absorption, biotransformation, and excretion of NP. Physiological parameters such as alveolar ventilation, cardiac output, blood flow to organs volume, and tissue/blood partition coefficients described movement of NP and metabolites among compartments. Model predictions for concentrations of NP and metabolites in tissues were compared to experimentally determined data obtained in rats after inhalation of NP. Model predictions for concentrations of NP metabolites covalently bound to tissue macromolecules agreed with experimentally determined data in rats. Levels of bound material in lung and liver were about one-tenth that found in kidney. Results indicated that NP movement among tissue compartments could be described to a large extent by blood flow and organ volume alone (e.g., tissue/blood partition coefficients = 1). The use of physiologically realistic parameters will enable scaling of the model developed using animal studies to predict disposition of NP in humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0017-9078
pubmed:author
pubmed:issnType
Print
pubmed:volume
57 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
149-55
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
A physiologically based model of 1-nitropyrene metabolism after inhalation or ingestion.
pubmed:affiliation
Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.