{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:50:11Z","timestamp":1785433811164,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Inhalation exposure is the gold standard when assessing pulmonary toxicity. However, it typically requires substantial amounts of test material. Intratracheal instillation is an alternative administration technique, where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea. Instillation requires minimal test material, delivers an exact dose deep into the lung, and is less labor\u2010intensive than inhalation exposures. However, one shortcoming is that the procedure may induce short\u2010term inflammation. To minimize this, we tested different modifications of the technique to identify the potential for refinement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, we tested whether previous findings of increased inflammation could be confirmed. Next, we tested whether instillation with a disposable 1\u2009mL syringe with ball\u2010tipped steel\u2010needle (Disposable\u2010syringe\/steel\u2010needle) induced less inflammation than the use of our standard set\u2010up, a 250\u2009\u03bcL reusable glass syringe with a disposable plastic catheter (Glass\u2010syringe\/plastic\u2010catheter). Finally, we tested if access to pelleted and liquid feed prior to instillation affected inflammation. We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24\u2009h post\u2010exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Vehicle\u2010instilled mice showed a small increase in neutrophil numbers compared to untreated mice. Neutrophil numbers were slightly elevated in the groups instilled with Disposable\u2010syringe\/steel\u2010needle; an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pellets compared to liquid feed. We found no difference between the feed types when using the Glass\u2010syringe\/plastic\u2010catheter combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The Glass\u2010syringe\/plastic\u2010catheter combination induced the least exposure\u2010related inflammation, confirming this as a preferred instillation procedure.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12503","type":"journal-article","created":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T07:04:49Z","timestamp":1735974289000},"page":"378-386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Intratracheal instillation for the testing of pulmonary toxicity in mice\u2014Effects of instillation devices and feed type on inflammation"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1188-445X","authenticated-orcid":false,"given":"Niels","family":"Hadrup","sequence":"first","affiliation":[{"name":"National Research Centre for the Working Environment  Copenhagen Denmark"},{"name":"Research Group for Risk\u2010Benefit, National Food Institute Technical University of Denmark  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Guldbrandsen","sequence":"additional","affiliation":[{"name":"National Research Centre for the Working Environment  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Terrida","sequence":"additional","affiliation":[{"name":"National Research Centre for the Working Environment  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja M. 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