{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:29:48Z","timestamp":1782937788432,"version":"3.54.5"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Charles River Laboratories"},{"name":"MatTek"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In vivo models (mostly rodents) are currently accepted by regulatory authorities for assessing acute inhalation toxicity. Considerable efforts have been made in recent years to evaluate in vitro human airway epithelial models (HAEM) as replacements for in vivo testing. In the current work, an organotypic in vitro rat airway epithelial model (RAEM), rat EpiAirway, was developed and characterized to allow a direct comparison with the available HAEM, human EpiAirway, in order to address potential interspecies variability in responses to harmful agents. The rat and human models were evaluated in 2 independent laboratories with 14 reference chemicals, selected to cover a broad range of chemical structures and reactive groups, as well as known acute animal and human toxicity responses, in 3 replicate rounds of experiments. Toxicity endpoints included changes in tissue viability (MTT assay), epithelial barrier integrity (TEER, transepithelial electrical resistance), and tissue morphology (histopathology). The newly developed rat EpiAirway model produced reproducible results across all replicate experiments in both testing laboratories. Furthermore, a high level of concordance was observed between the RAEM and HAEM toxicity responses (determined by IC25) in both laboratories, with R2=0.78 and 0.88 when analyzed by TEER; and R2=0.92 for both when analyzed by MTT. These results indicate that rat and human airway epithelial tissues respond similarly to acute exposures to chemicals. The new in vitro RAEM will help extrapolate to in vivo rat toxicity responses and support screening as part of a 3Rs program.<\/jats:p>","DOI":"10.1093\/toxsci\/kfad058","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T13:57:04Z","timestamp":1686319024000},"page":"178-190","source":"Crossref","is-referenced-by-count":14,"title":["Evaluation of <i>in vitro<\/i> rat and human airway epithelial models for acute inhalation toxicity testing"],"prefix":"10.1093","volume":"194","author":[{"given":"Joanne","family":"Wallace","sequence":"first","affiliation":[{"name":"Charles River Laboratories Edinburgh Ltd, Elphinstone Research Centre , Tranent, East Lothian EH33 2NE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"George R","family":"Jackson","sequence":"additional","affiliation":[{"name":"MatTek Life Sciences , Ashland, Massachusetts 01721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Kaluzhny","sequence":"additional","affiliation":[{"name":"MatTek Life Sciences , Ashland, Massachusetts 01721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyoum","family":"Ayehunie","sequence":"additional","affiliation":[{"name":"MatTek Life Sciences , Ashland, Massachusetts 01721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison B","family":"Lansley","sequence":"additional","affiliation":[{"name":"Centre for Stress and Age-Related Disease and Biomaterials and Drug Delivery Research and Enterprise Group, School of Applied Sciences, University of Brighton , Brighton BN2 4GJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Roper","sequence":"additional","affiliation":[{"name":"Charles River Laboratories Edinburgh Ltd, Elphinstone Research Centre , Tranent, East Lothian EH33 2NE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J","family":"Hayden","sequence":"additional","affiliation":[{"name":"MatTek Life Sciences , Ashland, Massachusetts 01721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"2023072808463745800_kfad058-B1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3109\/10408447309082020","article-title":"Sensory irritation by airborne chemicals","volume":"2","author":"Alarie","year":"1973","journal-title":"CRC Crit. 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