{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:34:33Z","timestamp":1778740473247,"version":"3.51.4"},"reference-count":31,"publisher":"SAGE Publications","issue":"3-4","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Altern Lab Anim"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>Collagen vitrigel membranes (CVMs) comprising high-density collagen fibrils equivalent to in vivo connective tissues have been widely used in cell culture applications. A human corneal epithelium (hCE) model was previously developed by the Takezawa group, by culturing HCE-T cells (derived from hCE cells) on a CVM scaffold in a chamber that provided an air\u2013liquid interface culture system. This hCE model was used to establish a new test method, known as the Vitrigel-Eye Irritancy Test (Vitrigel-EIT) method, which can be used to estimate the ocular irritation potential of test chemicals by analysing relative changes in transepithelial electrical resistance (TEER) over time. The current study was conducted in order to assess the reliability and relevance of the Vitrigel-EIT method at three participating laboratories by determining the method\u2019s within-laboratory reproducibility and between-laboratory reproducibility, as well as its capacity for distinguishing non-irritants from irritants in a bottom-up approach. The initial test sample size was found to be too low to evaluate the predictive capacity of the test method, and so it was evaluated with additional in-house data for a total of 93 test chemicals. The results showed 80\u2013100% within-laboratory reproducibility and an excellent between-laboratory reproducibility that met the acceptance criteria of 80%. However, the method\u2019s predictive capacity for distinguishing non-irritants (test chemicals not requiring classification and labelling for eye irritation or serious eye damage, i.e. United Nations Globally Harmonised System of Classification and Labelling of Chemicals (GHS) No Category) from irritants (GHS Categories 1 and 2) in a bottom-up approach was unacceptable because of false negative rates as high as 16.7%. After considerable review of the data with a view to using the method for regulatory purposes, it was determined that a more defined applicability domain, excluding test chemical solutions with a pH of 5 or less and solid test chemicals, improved the false negative rate to 4.2%. These results suggested that, within this carefully defined applicability domain, the Vitrigel-EIT method could be a useful alternative for distinguishing test chemicals that are ocular non-irritants from those that are irritants as part of a bottom-up approach.<\/jats:p>","DOI":"10.1177\/0261192919886665","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T04:59:43Z","timestamp":1576472383000},"page":"140-157","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Multi-laboratory Validation Study of the Vitrigel-Eye Irritancy Test Method as an Alternative to\n                    <i>In Vivo<\/i>\n                    Eye Irritation Testing"],"prefix":"10.1177","volume":"47","author":[{"given":"Hajime","family":"Kojima","sequence":"first","affiliation":[{"name":"Japanese Center for the Validation of Alternative Methods (JaCVAM), National Institute of Health Sciences (NIHS), Kawasaki, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Kanto Chemical Co., Inc., Isehara, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Sozu","sequence":"additional","affiliation":[{"name":"Tokyo University of Science, Katsushika-ku, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Kleinstreuer","sequence":"additional","affiliation":[{"name":"National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)\/Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), Research Triangle Park, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lim","family":"Chae-Hyung","sequence":"additional","affiliation":[{"name":"Korean Center for the Validation of Alternative Methods (KoCVAM), National Institute of Food and Drug Safety Evaluation, Osong-eup, Chungcheongbuk-do, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wannhsin","family":"Chen","sequence":"additional","affiliation":[{"name":"Industrial Technology Research Institute, (ITRI), Hsinchu, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mika","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Hatano Research Institute, Food and Drug Safety Center (FDSC), Hadano, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Bozo Research Center (BRC), Setagaya-ku, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiko","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Daicel Corporation (Daicel), Himeji, Hyogo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiaki","family":"Takezawa","sequence":"additional","affiliation":[{"name":"Institute of Agrobiological Sciences (NIAS), National Agriculture and Food Research Organization (NARO), Tsukuba, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,12,16]]},"reference":[{"key":"bibr1-0261192919886665","doi-asserted-by":"publisher","DOI":"10.3727\/000000004783983882"},{"key":"bibr2-0261192919886665","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.0248"},{"key":"bibr3-0261192919886665","doi-asserted-by":"publisher","DOI":"10.1159\/000101325"},{"key":"bibr4-0261192919886665","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2007.05.033"},{"key":"bibr5-0261192919886665","first-page":"176","volume":"13","author":"Takezawa T","year":"2008","journal-title":"AATEX"},{"key":"bibr6-0261192919886665","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2011.05.021"},{"key":"bibr7-0261192919886665","doi-asserted-by":"publisher","DOI":"10.1159\/000109986"},{"key":"bibr8-0261192919886665","volume-title":"24th European conference on biomaterials","author":"Takezawa T"},{"key":"bibr9-0261192919886665","first-page":"181","volume-title":"24th European conference on biomaterials (Ed. 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