{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T14:12:54Z","timestamp":1781619174779,"version":"3.54.5"},"reference-count":25,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"CounterACT","award":["U01 NS107127 and U01 NS123255"],"award-info":[{"award-number":["U01 NS107127 and U01 NS123255"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Toxicol"],"abstract":"<jats:p>\n                    War and terrorism demonstrate the need for an improved antidote against nerve agents that cause brain damage following inhibition of acetylcholinesterase (AChE). Our laboratories invented substituted phenoxyalkyl pyridinium oxime AChE reactivators (US patent 9,227,937) that demonstrate the ability to cross the blood\u2013brain barrier in\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    rat tests with a sarin surrogate by reducing time to cessation of seizure\u2010like behaviors, glial fibrillary acidic protein levels, and neuropathology, compared to the FDA-approved oxime, 2\u2010pyridine aldoxime methyl chloride (2\u2010PAM). This study investigated the safety profile of novel oximes through evaluation of their cytotoxicity and genotoxicity. Cytotoxicity was evaluated in mouse areolar fibroblasts using a lactate dehydrogenase (LDH) assay and an MTS assay. All novel oximes showed no toxicity in the LDH assay from 1.25\u00a0nM to 5\u00a0mM, whereas 2-PAM did; novel oximes were significantly different from 2-PAM (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; .00001). The MTS assay demonstrated that novel oximes at 2\u00a0\u00b5M to 500\u00a0\u00b5M significantly reduced the metabolic activity of fibroblasts compared to 2-PAM (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = .00001). A modified Ames assay using 5 bacterial strains with and without S9 assessed the genotoxicity of the lead compound, Oxime 20, at concentrations from 100\u00a0\u00b5M to 10\u00a0mM. No concentration, whether with S9 or without, showed any genotoxicity. The LDH and Ames results indicated no cytotoxicity or genotoxicity was caused by the novel oximes.\n                  <\/jats:p>","DOI":"10.1177\/10915818261431761","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T12:24:16Z","timestamp":1781439856000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of the\n                    <i>in vitro<\/i>\n                    Toxicity of Novel Oxime Acetylcholinesterase Reactivators"],"prefix":"10.1177","author":[{"given":"Janice E.","family":"Chambers","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Mississippi State University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"e_1_3_4_2_2","volume-title":"The 13th Element: The Sordid Tale of Murder, Fire, and Phosphorus","author":"Emsley J","year":"2000","unstructured":"Emsley J. 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