Linked Life Data

11006361

Source:http://linkedlifedata.com/resource/pubmed/id/11006361

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-10-30
pubmed:abstractText
The available inhalation toxicity information for acrylic acid (AA) suggests that lesions to the nasal cavity, specifically olfactory degeneration, are the most sensitive end point for developing a reference concentration (RfC). Advances in physiologically based pharmacokinetic (PBPK) modeling, specifically the incorporation of computational fluid dynamic (CFD) models, now make it possible to estimate the flux of inhaled chemicals within the nasal cavity of experimental species, specifically rats. The focus of this investigation was to apply an existing CFD-PBPK hybrid model in the estimation of an RfC to determine the impact of incorporation of this new modeling technique into the risk assessment process. Information provided in the literature on the toxicity and mode of action for AA was used to determine the risk assessment approach. A comparison of the approach used for the current U.S. Environmental Protection Agency (U.S. EPA) RfC with the approach using the CFD-PBPK hybrid model was also conducted. The application of the CFD-PBPK hybrid model in a risk assessment for AA resulted in an RfC of 79 ppb, assuming a minute ventilation of 13.8 l/min (20 m(3)/day) in humans. This value differs substantially from the RfC of 0.37 ppb estimated for AA by the U.S. EPA before the PBPK modeling advances became available. The difference in these two RfCs arises from many factors, with the main difference being the species selected (mouse vs. rat). The choice to conduct the evaluation using the rat was based on the availability of dosimetry data in this species. Once these data are available in the mouse, an assessment should be conducted using this information. Additional differences included the methods used for estimating the target tissue concentration, the uncertainty factors (UFs) applied, and the application of duration and uncertainty adjustments to the internal target tissue dose rather than the external exposure concentration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
312-25
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Application of a hybrid CFD-PBPK nasal dosimetry model in an inhalation risk assessment: an example with acrylic acid.
pubmed:affiliation
Colorado State University, CETT, Foothills Campus, Fort Collins, Colorado 80523, USA.
pubmed:publicationType
Journal Article, Comparative Study