Biomaterial Database

The questionable value of long-term animal toxicity studies: a regulatory dilemma. 1986

C E Lumley, and S R Walker

Recommendations for the minimum period of repeated dose administration to animals to support marketing authorization of pharmaceuticals vary from 6 months in the EEC to 18 months in Canada. The value of studies lasting longer than 6 months has not, however, been established. In order to enable retrospective analyses to be carried out, the Centre for Medicines Research has established a toxicology databank containing comprehensive data from repeated dose animal safety evaluation studies on 124 compounds, provided by 21 pharmaceutical companies in Europe (Lumley and Walker 1985a). There are 214 case studies (1 compound tested in 1 species for 1 or more time periods), and in 100 of these tests lasted for longer than 6 months. In 88 long-term studies comparable short-term data are available and these have been analysed to determine what new findings, if any, became apparent after 6 months. The data do not support the need for animal toxicity studies of longer than 6 months, apart from those designed to investigate carcinogenicity. Safety evaluation studies should be of value in predicting adverse drug reactions for man. Unless it can be established that these longer-term studies more accurately define potential target organ effects, the scientific rationale for conventional long-term studies must be questioned.

UI	MeSH Term	Description	Entries
D007256	Information Systems	Integrated set of files, procedures, and equipment for the storage, manipulation, and retrieval of information.	Ancillary Information Systems,Emergency Care Information Systems,Information Retrieval Systems,Perinatal Information System,Ancillary Information System,Information Retrieval System,Information System,Information System, Ancillary,Information System, Perinatal,Perinatal Information Systems,Systems, Information Retrieval
D004353	Drug Evaluation, Preclinical	Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.	Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D005060	Europe	The continent north of AFRICA, west of ASIA and east of the ATLANTIC OCEAN.	Northern Europe,Southern Europe,Western Europe
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D064420	Drug-Related Side Effects and Adverse Reactions	Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.	Drug-Related Side Effects and Adverse Reaction,Adverse Drug Event,Adverse Drug Reaction,Drug Side Effects,Drug Toxicity,Side Effects of Drugs,Toxicity, Drug,Adverse Drug Events,Adverse Drug Reactions,Drug Event, Adverse,Drug Events, Adverse,Drug Reaction, Adverse,Drug Reactions, Adverse,Drug Related Side Effects and Adverse Reaction,Drug Related Side Effects and Adverse Reactions,Drug Side Effect,Drug Toxicities,Effects, Drug Side,Reactions, Adverse Drug,Side Effect, Drug,Side Effects, Drug,Toxicities, Drug