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In support of this goal, computational fluid-particle dynamics models were developed to estimate site-specific deposition of inhaled aerosols containing the fungicide, chlorothalonil, in the rat and human for comparisons to prior rat inhalation studies and new human in vitro studies. Under bioassay conditions, the deposition was predicted to be greatest at the front of the rat nose followed by the anterior transitional epithelium and larynx corresponding to regions most sensitive to local contact irritation and cytotoxicity. For humans, simulations of aerosol deposition covering potential occupational or residential exposures (1\u201350\u2009\u00b5m diameter) were conducted using nasal and oral breathing. Aerosols in the 1\u20135\u2009\u00b5m range readily penetrated the deep region of the human lung following both oral and nasal breathing. Under actual use conditions (aerosol formulations &amp;gt;10\u2009\u00b5m), the majority of deposited doses were in the upper conducting airways. Beyond the nose or mouth, the greatest deposition in the pharynx, larynx, trachea, and bronchi was predicted for aerosols in the 10\u201320\u2009\u00b5m size range. Only small amounts of aerosols &amp;gt;20\u2009\u00b5m penetrated past the pharyngeal region. Using the ICRP clearance model, local retained tissue dose metrics including maximal concentrations and areas under the curve were calculated for each airway region following repeated occupational exposures. These results are directly comparable with benchmark doses from in vitro toxicity studies in human cells leading to estimated human equivalent concentrations that reduce the reliance on animals for risk assessments.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab062","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T17:01:20Z","timestamp":1622566880000},"page":"243-259","source":"Crossref","is-referenced-by-count":34,"title":["New Approach Methodology for Assessing Inhalation Risks of a Contact Respiratory Cytotoxicant: Computational Fluid Dynamics-Based Aerosol Dosimetry Modeling for Cross-Species and In Vitro Comparisons"],"prefix":"10.1093","volume":"182","author":[{"given":"Richard A","family":"Corley","sequence":"first","affiliation":[{"name":"Pacific Northwest National Laboratory, Richland, Washington 99352, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P","family":"Kuprat","sequence":"additional","affiliation":[{"name":"Pacific Northwest National Laboratory, Richland, Washington 99352, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah R","family":"Suffield","sequence":"additional","affiliation":[{"name":"Pacific Northwest National Laboratory, Richland, Washington 99352, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senthil","family":"Kabilan","sequence":"additional","affiliation":[{"name":"Pacific Northwest National Laboratory, Richland, Washington 99352, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M","family":"Hinderliter","sequence":"additional","affiliation":[{"name":"Syngenta Crop Protection, Greensboro, North Carolina 27409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Yugulis","sequence":"additional","affiliation":[{"name":"Battelle Memorial Institute, Columbus, Ohio 43201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4949-1037","authenticated-orcid":false,"given":"Tharacad S","family":"Ramanarayanan","sequence":"additional","affiliation":[{"name":"Syngenta Crop Protection, Greensboro, North Carolina 27409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"key":"2021080320324694800_kfab062-B1","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1080\/08958370802207318","article-title":"Association of inhalation toxicologists (AIT) working party recommendations for standard delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals","volume":"20","author":"Alexander","year":"2008","journal-title":"Inhal. 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