Role of chronic toxicology studies in revealing new toxicities英文电子书.pdf

Regulatory Toxicology and Pharmacology 82 (2016) 94e98 Contents lists available at ScienceDirect Regulatory Toxicology and Pharmacology journal homepage: /locate/yrtph Role of chronic toxicology studies in revealing new toxicities Alema Galijatovic-Idrizbegovic a, *, Judith E. Miller a, Wendy D. Cornell b, James A. Butler c, Gordon K. Wollenberg a, Frank D. Sistare a, Joseph J. DeGeorge a a Merck and Co., Inc., West Point, PA, USA b Merck and Co., Inc., Rahway, NJ, USA c Linguamatics Solutions, USA a r t i c l e i n f o a b s t r a c t Article history: Chronic (3 months) preclinical toxicology studies are conducted to support the safe conduct of clinical Received 14 October 2016 trials exceeding 3 months in duration. We have conducted a review of 32 chronic toxicology studies in Accepted 17 October 2016 non-rodents (22 studies in dogs and 10 in non-human primates) and 27 chronic toxicology studies in rats Available online 18 October 2016 dosed with Merck compounds to determine the frequency at which additional target organ toxicities are observed in chronic toxicology studies as compared to subchronic studies of 3 months in duration. Our Keywords: review shows that majority of the findings are observed in the subchronic studies since additional target Toxicology studies organs were not observed in 24 chronic non rodent studies and in 21 chronic rodent studies. However, 6 Chronic Preclinical species