Extrapolation of animal toxicity data to man. 1988

F Vocci, and T Farber
Environmental Protection Agency, Office of Pesticides Program, Washington, DC 20460.

Laboratory animals are used as models for humans in toxicity studies. This use is based on the assumption that extrapolation of biological data from animals to humans is valid. Three methods of extrapolation are considered: the use of body mass equivalence, caloric scaling across species, and the use of the surface area equivalence. Allometry, defined as the study of size and its consequences, is considered. There is still controversy whether there is an allometric relationship for energy metabolism. Allometry offers, among others, the concept that not all of the mass of the animal is equally involved in metabolism. In recent years the principles of pharmacokinetics have been applied to interspecies scaling; pharmacokinetic short-term studies can be used to determine whether allometric scaling is justified. Considerations, however, should be given to (pharmacokinetic) differences in the same species and to species variability. It would be useful to develop a set of criteria for deciding when the pharmacokinetic model is needed and when simpler models will suffice.

UI MeSH Term Description Entries
D010599 Pharmacokinetics Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology. ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000280 Administration, Inhalation The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract. Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
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
D013045 Species Specificity The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species. Species Specificities,Specificities, Species,Specificity, Species
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

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