title: The necessary minimal duration of final long-term toxicologic tests of drugs.
abstract: The optimal, and thus mandatory duration of final, long-term toxicologic tests of drugs in animals prior to marketing for use in human beings remains controversial. Some regulatory authorities contend that exposure for 6 or 12 months is adequate. However, the Bureau of Human Prescription Drugs of the Health Protection Branch of Health and Welfare Canada has evaluated a number of confidential reports from manufacturers in which significant, non-neoplastic, pathologic changes occurred only after exposure of animals for more than 1 year. Fifteen examples from these files and the literature are described. These studies support the current Canadian guidelines' requirement for the duration of final long-term toxicologic tests of drugs to be at least 18 months.
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D006224:Cricetinae; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004935:Esophageal Diseases / Q000139:chemically induced; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D051379:Mice; D004364:Pharmaceutical Preparations / Q000378:metabolism; D051381:Rats; D012164:Retinal Diseases / Q000139:chemically induced; D013997:Time Factors; D014116:Toxicology / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations