title: Statistical inferences from formaldehyde DNA-protein cross-link data: improving methods for characterization of uncertainty.
abstract: Physiologically based pharmacokinetic (PBPK) modeling has reached considerable sophistication in its application to pharmacological and environmental health problems. Yet, mature methodologies for making statistical inferences have not been routinely incorporated in these applications except in a few data-rich cases. This paper demonstrates how improved statistical inference on estimated model parameters from both frequentist and Bayesian points of view can be routinely carried out. We work with a previously developed PBPK model for the formation and disposition of DNA-protein cross-links formed by inhaled formaldehyde in the nasal lining of rats and rhesus monkeys. We purposefully choose this model because it is based on sparse time-course data.
authors.affiliation: Center for Statistical Research and Methodology, US Census Bureau, Washington, DC 20233, USA. martin.klein@census.gov
authors.forename: Martin D
authors.initials: MD
authors.lastname: Klein
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Sinha
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Subramaniam
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001499:Bayes Theorem; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism*; D005557:Formaldehyde / Q000378:metabolism / Q000493:pharmacokinetics*; D008253:Macaca mulatta; D008954:Models, Biological; D015233:Models, Statistical; D009297:Nasal Mucosa / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D035501:Uncertainty
chemical_list: D003432:Cross-Linking Reagents; D011506:Proteins; D005557:Formaldehyde; D004247:DNA