| Title: | Development and evaluation of a high throughput inhalation model for organic chemicals |
| Author(s): | Linakis MW; Sayre RR; Pearce RG; Sfeir MA; Sipes NS; Pangburn HA; Gearhart JM; Wambaugh JF; |
| Address: | "United States Air Force, 711th Human Performance Wing, Airman Readiness Optimization, Wright-Patterson AFB, Wright-Patterson AFB, OH, 45433, USA. UES, Inc., Dayton, OH, 45432, USA. Oak Ridge Institute for Science and Education, Oak Ridge, TN, 37831, USA. National Center for Computational Toxicology, United States Environmental Protection Agency, Research Triangle Park, NC, 27711, USA. National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27711, USA. United States Air Force, 711th Human Performance Wing, Molecular Bioeffects, Wright-Patterson AFB, Wright-Patterson AFB, OH, 45433, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine, Wright-Patterson AFB, Wright-Patterson AFB, OH, 45433, USA. National Center for Computational Toxicology, United States Environmental Protection Agency, Research Triangle Park, NC, 27711, USA. wambaugh.john@epa.gov" |
| Journal Title: | J Expo Sci Environ Epidemiol |
| DOI: | 10.1038/s41370-020-0238-y |
| ISSN/ISBN: | 1559-064X (Electronic) 1559-0631 (Print) 1559-0631 (Linking) |
| Abstract: | "Currently it is difficult to prospectively estimate human toxicokinetics (particularly for novel chemicals) in a high-throughput manner. The R software package httk has been developed, in part, to address this deficiency, and the aim of this investigation was to develop a generalized inhalation model for httk. The structure of the inhalation model was developed from two previously published physiologically based models from Jongeneelen and Berge (Ann Occup Hyg 55:841-864, 2011) and Clewell et al. (Toxicol Sci 63:160-172, 2001), while calculated physicochemical data was obtained from EPA's CompTox Chemicals Dashboard. In total, 142 exposure scenarios across 41 volatile organic chemicals were modeled and compared to published data. The slope of the regression line of best fit between log-transformed simulated and observed blood and exhaled breath concentrations was 0.46 with an r(2) = 0.45 and a root mean square error (RMSE) of direct comparison between the log-transformed simulated and observed values of 1.11. Approximately 5.1% (n = 108) of the data points analyzed were >2 orders of magnitude different than expected. The volatile organic chemicals examined in this investigation represent small, generally lipophilic molecules. Ultimately this paper details a generalized inhalation component that integrates with the httk physiologically based toxicokinetic model to provide high-throughput estimates of inhalation chemical exposures" |
| Keywords: | "Humans Inhalation Exposure Models, Biological Risk Assessment Toxicokinetics *Volatile Organic Compounds Generic model Inhalation Volatile;" |
| Notes: | "MedlineLinakis, Matthew W Sayre, Risa R Pearce, Robert G Sfeir, Mark A Sipes, Nisha S Pangburn, Heather A Gearhart, Jeffery M Wambaugh, John F eng EPA999999/ImEPA/Intramural EPA/ Research Support, U.S. Gov't, Non-P.H.S. 2020/06/18 J Expo Sci Environ Epidemiol. 2020 Sep; 30(5):866-877. doi: 10.1038/s41370-020-0238-y. Epub 2020 Jun 16" |
