{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:14:50Z","timestamp":1786644890525,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["5U44ES024698\u201005"],"award-info":[{"award-number":["5U44ES024698\u201005"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This interlaboratory evaluation of HepaRG CometChip was conducted to assess transferability and reproducibility of this new approach methodology (NAM) across four laboratories. Concentrations inducing up to ~70% relative cytotoxicity were determined by the organizing laboratory, and frozen chemical formulation blocks were sent to each participant. When noncytotoxic, 10\u2009mM was the maximum dose. Cultures were exposed once daily for three consecutive days, and both cytotoxicity assessment, via ATP quantification, and comet analysis, commenced 3\u20134\u2009h after initiation of the final exposure. Positive response was statistical pairwise significance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) with concentration\u2010related increases in %Tail DNA across \u2265\u20092 consecutive exposures. For 8 of 11 compounds, all four labs generated unanimous test results, with four negative compounds (2\u2010acetylaminofluorene [2\u2010AAF], 2,4\u2010dichlorophenol, eugenol and hydroquinone) and four positive compounds (azidothymidine, benzo(a)pyrene [BP], cyclophosphamide [CP], ethyl methanesulfonate).For the remaining chemicals, three of four labs generated negative calls for amitrole, cadmium chloride, and DMBA. In cases where bulky lesions were anticipated, the magnitude of %Tail DNA was low, due to the inherent insensitivity of the alkaline comet assay (not the CometChip per se) to detect bulky adducts repaired by nucleotide excision repair. This is supported by the small magnitude in %Tail DNA induced by BP and CP. Taken together, for all compounds there was majority agreement in CometChip results across participating laboratories supporting that the endpoint is readily transferable to new labs. Overall, this platform is a promising human\u2010relevant NAM, with a physiologically relevant detoxification process that could be incorporated into rodent replacement strategies.\n                  <\/jats:p>","DOI":"10.1002\/em.70037","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T04:25:08Z","timestamp":1764217508000},"page":"478-491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transferability and Reproducibility of the\n                    <scp>HepaRG CometChip<\/scp>\n                    Assay"],"prefix":"10.1002","volume":"66","author":[{"given":"Leslie","family":"Recio","sequence":"first","affiliation":[{"name":"Integrated Laboratory Systems  Research\u202fTriangle\u202fPark North Carolina USA"},{"name":"ScitoVation  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Swartz","sequence":"additional","affiliation":[{"name":"Integrated Laboratory Systems  Research\u202fTriangle\u202fPark North Carolina USA"},{"name":"Inotiv RTP  Morrisville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lincoln","family":"Martin","sequence":"additional","affiliation":[{"name":"Integrated Laboratory Systems  Research\u202fTriangle\u202fPark North Carolina USA"},{"name":"Inotiv RTP  Morrisville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Rottinger","sequence":"additional","affiliation":[{"name":"Proctor &amp; Gamble Co.  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