Safety assessment of vitacoxib: Acute and 90-day sub-chronic oral toxicity studies |
| |
| Affiliation: | 1. Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People''s Republic of China;2. Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People''s Republic of China;3. Key Laboratory of Detection for Veterinary Drug Residue and Illegal Additive, Ministry of Agriculture, Beijing 100193, People''s Republic of China;4. Beijing Orbiepharm Co., Ltd, Beijing 100185, People''s Republic of China;1. Downing College, Cambridge, UK;2. School of Public Health, Imperial College London, London, UK;3. Physiological Laboratory, Rayne Institute, University of Cambridge, St. Thomas'' Hospital, Westminster Bridge Road, London SE1 7EH, UK;1. SafeBridge Consultants, Inc., USA;2. Merck & Co., Inc., USA;3. Ashland, Inc., USA;4. Genentech, Inc., USA;1. Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Kaiyuan Road 190, Guangzhou Science Park, Guangzhou 510530, China;2. The School of Life Sciences, Anhui University, Hefei 230027, China;3. National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA |
| |
| Abstract: | Vitacoxib, is a newly developed coxibs NSAID (selective inhibitors of cyclooxygenase-2). To date, no experimental data have been published concerning its safety for use as an additive in the human diet. In the present study, we assessed the acute and sub-chronic toxicity of vitacoxib administered by gavage. The acute toxicity tests in Sprague Dawley (SD) rats and ICR mice demonstrated that vitacoxib at a dose of 5000 mg/kg BW failed to alter any of the parameters studied. In the 90-day sub-chronic toxicity test, vitacoxib was administered to SD rats at the doses of 0 (control), 5, 10, 20, 30, and 60 mg/kg BW. The results demonstrated that there were no significant differences for most indexes of sub-chronic toxicity throughout the experiment at the dose of 5–20 mg/kg BW, indicating no apparent dose-dependent. However, there were significant histopathology changes in the liver and kidney, and alterations in some biochemical parameters in the 60 mg/kg BW group. Based on these findings, the gavage LD50 was determined to be > 5000 mg/kg in SD rats and ICR mice, and the 90-day gavage no-observed-adverse-effect level (NOAEL) of vitacoxib was considered to be 20 mg/kg BW under the present study conditions. |
| |
| Keywords: | Vitacoxib Coxibs NSAIDs Acute toxicity Subchronic toxicity |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
