Extrapolation of Animal Data to Humans

Extrapolation of pharmacokinetic data from animals to humans is not without limitations and should be done carefully, keeping in mind the assumptions that are necessary for such extrapolation. It is important to select an appropriate in vitro or animal model that has relevance to humans. Extrapolation of animal data to humans is not likely to be successful in instances when the pharmacokinetics (absorption or disposition) is species-dependent, when active processes are involved, when drug action (either beneficial or adverse effects) is due to a poorly understood mechanism, or when species dependent mechanisms of tolerance or enzyme induction are present." -" ... 

Better understanding of the extrapolation of animal data to humans, making human dose projections more reliable and reducing risk upon entry into clinical development. 

These effects are difficult to evaluate through biological modeling, and those models that are adequate are very complex. In addition, data from short-term experiments cannot be used for prediction of damage. The extrapolation of animal data to human health is a complicated process. Because of these factors, collection of data on potential delayed pesticide effects has been slow, and interpreting the data has been difficult. 

The iCp and percentage absorbed values presented in the literature for various substances have been generated from both in vivo and in vitro studies using a wide range of experimental techniques. Studies on human subjects are costly, experimental conditions are more difficult to control and ethical constraints may rule out testing of toxic compounds. If percutaneous data are obtained using animal studies, this presents a number of difficulties associated with the extrapolation of animal data to humans, e.g. animal species variation, different sites of application, differences between shaved versus unshaved skin and differences in skin metabolism. 

The LD50 and LC50 are least relevant for humcins, because we do not want to have lethal amounts of chemicals in the environment. Such studies are typically used to establish a ceiling for doses in further experiments, which cu e necessary to identify the critical dose-response relationship for each chemical. If possible, we want to keep the chemical at concentrations below threshold levels. Therefore, the NOAEL is usually the most relevant endpoint for extrapolation of animal data to humans. 

Species The test species, whether animal or human, are identified in this column. Chapter 2, "Relevance to Public Health," covers the relevance of animal data to human toxicity and Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent human doses to derive an MRL. 

Schlenker RA. 1988. Skeletal Pb retention following Ra injection Extrapolation of animal data to adult humans. Health Phys 54 383-396. 

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