Linked Life Data

18049993

Source:http://linkedlifedata.com/resource/pubmed/id/18049993

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2007-11-30
pubmed:abstractText
Dietary exposure to acrylamide is common as a result of its formation during the cooking of carbohydrate foods. This leads to widespread human exposure in adults and children alike. Acrylamide is neurotoxic and is metabolized by cytochrome P-450 (CYP) 2E1 to a mutagenic epoxide, glycidamide. This article describes a modeling framework for assessing acrylamide and glycidamide dosimetry in rats and human adults and children. The challenges in building a physiologically based toxicokinetic (PBTK) model that is compatible with existing rat and human data are described, with an emphasis on calibration against the hemoglobin adduct database. This exploratory PBTK model was adapted to children by incorporating life-stage-specific parameters consistent with children's changing physiology and metabolic capacity for processes involved in acrylamide disposition in terms of CYP2E1, glutathione conjugation, and epoxide hydrolase. Monte Carlo analysis was used to simulate the distribution of internal doses to gain an initial understanding of the range of child/adult differences possible. This analysis suggests modest dosimetry differences between children and adults, with area-under-the-curve (AUC) doses for the 99th percentile child up to fivefold greater than the median adult for both acrylamide and glycidamide. Early life immaturities tended to exert a greater effect on acrylamide than glycidamide dosimetry because immaturities in CYP2E1 and glutathione counteract one another for glycidamide AUC, but both lead to greater acrylamide dose. The analysis points toward glutathione conjugation parameters as being particularly influential and uncertain in early life, making this a key area for future research.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1528-7394
pubmed:author
pubmed:issnType
Print
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2033-55
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18049993-Acrylamide, pubmed-meshheading:18049993-Adolescent, pubmed-meshheading:18049993-Adult, pubmed-meshheading:18049993-Animals, pubmed-meshheading:18049993-Child, pubmed-meshheading:18049993-Child, Preschool, pubmed-meshheading:18049993-Cytochrome P-450 CYP2E1, pubmed-meshheading:18049993-Dose-Response Relationship, Drug, pubmed-meshheading:18049993-Epoxide Hydrolases, pubmed-meshheading:18049993-Epoxy Compounds, pubmed-meshheading:18049993-Food Contamination, pubmed-meshheading:18049993-Glutathione, pubmed-meshheading:18049993-Glutathione Transferase, pubmed-meshheading:18049993-Humans, pubmed-meshheading:18049993-Infant, pubmed-meshheading:18049993-Infant, Newborn, pubmed-meshheading:18049993-Liver, pubmed-meshheading:18049993-Models, Biological, pubmed-meshheading:18049993-Monte Carlo Method, pubmed-meshheading:18049993-Rats
pubmed:year
2007
pubmed:articleTitle
Approaches to acrylamide physiologically based toxicokinetic modeling for exploring child-adult dosimetry differences.
pubmed:affiliation
Clark University, Center for Technology, Environment and Development, Worcester, Massachusetts, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't