{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:09:36Z","timestamp":1792462176954,"version":"4.5.0"},"reference-count":13,"publisher":"Georg Thieme Verlag KG","issue":"03","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Aim Enflicoxib, a selective COX-2 inhibitor approved for the treatment of\n                    pain and inflammation associated with osteoarthritis in dogs\n                        (Daxocox\u00ae [Ecuphar\/Animalcare Group]) was\n                    assessed for its genotoxic potential in a battery of in vitro and in\n                        vivo genotoxicity assays. These comprised a bacterial reverse mutation\n                    assay (Ames test), an in vitro human lymphocyte chromosome aberration\n                    assay and an in vivo mouse bone marrow micronucleus assay.<\/jats:p><jats:p>\n          Methods Relevant vehicle and positive control cultures and animals were\n                    included in all assays. In the Ames test, enflicoxib was tested at\n                    concentrations of up to 5000\u2009\u03bcg\/plate. Signs of\n                    cytotoxicity were observed at the highest tested concentrations for several of\n                    the bacterial strains, both in absence and presence of S9. In human lymphocytes,\n                    enflicoxib was assessed for the induction of chromosomal aberrations when\n                    exposed at concentrations of up to 62.5 (3\u2009hours) and\n                    29.6\u2009\u00b5g\/mL (20\u2009hours) in the absence of S9, and\n                    up to 66.7\u2009\u00b5g\/mL (3\u2009hours) in presence of S9.\n                    Signs of cell toxicity, evidenced as a decrease in the mitotic index, were\n                    observed at these concentrations. In the mouse micronucleus assay, enflicoxib\n                    dose levels of up to 2000\u2009mg\/kg were administered (single dose)\n                    to male and female animals, and bone marrow samples were taken 24 and\n                    48\u2009hours (high-dose animals only) after administration.<\/jats:p><jats:p>\n          Results Enflicoxib was shown to lack genotoxic activity in the conducted\n                    assays.<\/jats:p><jats:p>\n          Conclusions The administration of enflicoxib as a therapeutic analgesic\n                    agent would not pose a genotoxic risk to animals or humans.<\/jats:p>","DOI":"10.1055\/a-1727-5733","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T23:49:47Z","timestamp":1642549787000},"page":"163-170","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of the Genotoxic Potential of the Selective COX-2\n                    Inhibitor Enflicoxib in a Battery of in vitro and in vivo\n                    Genotoxicity Assays"],"prefix":"10.1055","volume":"72","author":[{"given":"Antonio","family":"Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Welab Barcelona. Barcelona Science Park, C\/Baldiri Reixac 4-8,\n                    Barcelona \u2013 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Homedes","sequence":"additional","affiliation":[{"name":"Ecuphar Veterinaria S.L.U. (Animalcare Group). Avgda. R\u00edo de\n                    Janeiro 60 \u2013 66, planta 13, Barcelona \u2013 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Salichs","sequence":"additional","affiliation":[{"name":"Ecuphar Veterinaria S.L.U. (Animalcare Group). Avgda. R\u00edo de\n                    Janeiro 60 \u2013 66, planta 13, Barcelona \u2013 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1593\/tlo.08160","article-title":"COX-2 inhibition combined with radiation reduces Orthotopic Glioma outgrowthby\n                    targeting the tumor vasculature","volume":"2","author":"M Wagemakers","year":"2009","journal-title":"Transl Oncol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e949","DOI":"10.1002\/vetr.949","article-title":"Efficacy and safety of enflicoxib for treatment of canine osteoarthritis: A\n                    6-week randomised, controlled, blind, multicentre clinical trial","author":"M Salichs","year":"2021","journal-title":"Vet Rec"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/s12917-021-02910-0","article-title":"Long-term safety evaluation of Daxocox\u00ae tablets (enflicoxib) in dogs\n                    after weekly oral administrations for seven months","volume":"17","author":"J Homedes","year":"2021","journal-title":"BMC Vet Res"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/0165-1161(83)90010-9","article-title":"Revised methods for the Salmonella mutagenicity test","volume":"113","author":"D M Maron","year":"1983","journal-title":"Mutat Res"},{"key":"ref11","first-page":"187","volume-title":"Assays for the detection of chemically-induced chromosome damage in cultured\n                    mammalian cells, in: S.Venitt, J.M.Parry (Eds.), Mutagenicity Testing: A\n                    practical approach","author":"B J Dean","year":"1984"},{"key":"ref14","first-page":"141","volume-title":"Analysis of data from in vitro cytogenetic assays, in: Statistical evaluation of\n                    mutagenicity test data, (UKEMS Guidelines subcommittee report, Part III), D.J.\n                    Kirkland","author":"C Richardson","year":"1989"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/0165-1161(75)90058-8","article-title":"The micronucleus test","volume":"31","author":"W Schmid","year":"1975","journal-title":"Mutat Res"},{"key":"ref17","first-page":"L276","article-title":"DIRECTIVE 2010\/63\/EU on the protection of animals used for\n                    scientific purposes","author":"E Parliament","year":"2010","journal-title":"EU Off. 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Res."},{"key":"ref26","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.mrgentox.2006.10.006","article-title":"Report of the IWGT working group on strategy\/interpretation for\n                    regulatory in vivo tests II. Identification of in vivo-only\n                    positive compounds in the bone marrow micronucleus test","volume":"627","author":"D J Tweats","year":"2007","journal-title":"Mutat. Res"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12995","article-title":"Pharmacokinetics of enflicoxib in dogs: Effects of prandial state and repeated\n                    administration","author":"J Homedes","year":"2021","journal-title":"J Vet Pharmacol Ther"}],"container-title":["Drug Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1727-5733.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T23:59:45Z","timestamp":1646697585000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1727-5733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,18]]},"references-count":13,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2022,3,7]]},"published-print":{"date-parts":[[2022,3]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1727-5733","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2194-9379","2194-9387"],"issn-type":[{"value":"2194-9379","type":"print"},{"value":"2194-9387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,18]]}}}