THE VALUE OF INFORMATION GENERATED BY LONG-TERM TOXICITY STUDIES IN THE DOG FOR THE NONCLINICAL SAFETY ASSESSMENT OF PHARMACEUTICAL COMPOUNDS

Data on 117 pharmaceutical compounds in the CMR toxicology database ha ve been analyzed to determine what new toxicological information was p rovided by the dog in chronic (6 months or longer) toxicity testing. F or more than half of the 117 compounds, all salient effects in the dog were seen for the first time within 3 months. For just under one-thir d of the compounds, any effects that occurred for the first time beyon d 3 months in the dog were also seen in studies in the rat. Only 13 of the 117 compounds showed new and possibly important effects in the ch ronic study. No particular therapeutic class nor any other single circ umstance was implicated in these 13 cases. Types of late-onset finding s in the dog occurring with more than 1 compound included nonspecific effects or hypertrophic/hyperplastic changes. There may be several rea sons, pragmatic as well as scientific, why it can sometimes be desirab le to carry out chronic repeat-dose studies of 6 months or longer in t he dog. However, the results of this retrospective evaluation have dem onstrated that in the large majority of cases analyzed, long-term toxi city studies in the dog provide relatively little qualitatively new to xicological information not already gained from a shortterm (3 month) study in the dog in conjunction with short- and long-term studies in t he rat. (C) 1995 Society of Toxicology.