{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:56:13Z","timestamp":1790942173342,"version":"4.1.0"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Labcorp","id":[{"id":"https:\/\/ror.org\/03zsdhz84","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nonclinical inhalation studies often rely on systemic biomarkers of exposure and pharmacology for serial evaluations, since local pulmonary effects are generally limited to assessment by terminal procedures. In addition, invasive procedures raise concern with health impact for subsequent inhalation doses and artifacts in tissue histology that could confound interpretation of toxicity. To test a non-terminal lung monitoring technique for use in non-human primate repeat-dose inhalation toxicology studies, bronchoalveolar lavage was performed during the pretest phase (twice), following 7\u2009d of treatment with saline or albuterol, and the day after the final dose. Evaluations included clinical observations and histopathology, as well as differential cell counts and quantification of protein, lactate dehydrogenase, and urea in bronchoalveolar lavage fluid. Animals sufficiently recovered from the procedure were dosed by conscious facemask inhalation several hours later, without incident, and had slightly lower lavage total cell counts. Bronchoalveolar lavage the day before necropsy was associated with mixed cell infiltrates or inflammation in 2 of 8 animals. Total white cell counts in lavage fluid were higher but more variable when collected as a terminal rather than survival procedure, although intra-animal variability between pretest occasions was notable as well. Urea concentration showed greater variability than total protein and lactate dehydrogenase, although values were near the method\u2019s limit of detection. In summary, this study showed that bronchoalveolar lavage can be performed as a serial evaluation in nonclinical studies, without benefit from multiple baseline occasions and with some effect on lung histopathology.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag044","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T11:28:26Z","timestamp":1775561306000},"source":"Crossref","is-referenced-by-count":0,"title":["Repeated bronchoalveolar lavage variability and impact in a 2-week nonclinical toxicology study"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0012-3663","authenticated-orcid":false,"given":"Emily","family":"Hackshaw","sequence":"first","affiliation":[{"name":"Labcorp , Madison, WI 53704,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Nelson","sequence":"additional","affiliation":[{"name":"Labcorp , Madison, WI 53704,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6082-8454","authenticated-orcid":false,"given":"Molly H","family":"Boyle","sequence":"additional","affiliation":[{"name":"Labcorp , Chantilly, VA 20151,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"2026100207212521700_kfag044-B1","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1513\/AnnalsATS.202505-543ST","article-title":"Research priorities for noninvasive sampling of the lower respiratory tract during acute respiratory failure: an official American Thoracic Society Workshop Report","volume":"22","author":"Bain","year":"2025","journal-title":"Ann Am Thorac Soc"},{"key":"2026100207212521700_kfag044-B2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s40635-019-0225-6","article-title":"Regional pulmonary effects of bronchoalveolar lavage procedure determined by electrical impedance tomography","volume":"7","author":"Frerichs","year":"2019","journal-title":"Intensive Care Med Exp"},{"key":"2026100207212521700_kfag044-B3","doi-asserted-by":"publisher","first-page":"6831","DOI":"10.3390\/ijms26146831","article-title":"Cytokine profiles of bronchoalveolar lavage in patients with interstitial lung diseases and non-allergic asthma","volume":"26","author":"Greif Lenar\u010di\u010d","year":"2025","journal-title":"Int J Mol Sci"},{"key":"2026100207212521700_kfag044-B4","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1177\/01926233241309905","article-title":"Scientific and regulatory policy committee points to consider: proposal and recommendations to reduce euthanasia of control nonhuman primates in nonclinical toxicity studies","volume":"53","author":"Guffroy","year":"2025","journal-title":"Toxicol Pathol"},{"key":"2026100207212521700_kfag044-B5","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1007\/s10753-009-9168-5","article-title":"Cellular and molecular characterization of ozone-induced pulmonary inflammation in the cynomolgus monkey","volume":"33","author":"Hicks","year":"2010","journal-title":"Inflammation"},{"key":"2026100207212521700_kfag044-B6","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1517\/14740338.6.2.207","article-title":"Histologically defined biomarkers in toxicology","volume":"6","author":"Kilty","year":"2007","journal-title":"Expert Opin Drug Saf"},{"key":"2026100207212521700_kfag044-B7","doi-asserted-by":"publisher","first-page":"e0282404","DOI":"10.1371\/journal.pone.0282404","article-title":"How important are concurrent vehicle control groups in (sub)chronic non-human primate toxicity studies conducted in pharmaceutical development? 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