Extrapolation of animal data

The outcome of low-dose extrapolation is the resulting lifetime cancer risk associated with estimated exposure for a particular population. A wide range of models have been developed for low-dose extrapolation of animal data to calculate a tolerable intake for an acceptable risk, often set at one extra cancer per million exposed persons (see Section 6.2.4 for acceptable risk). 

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

The extrapolation of animal data to predict pharmacokinetic parameters by allo-metric scaling is an often-used tool in drug development, with multiple approaches available at variable success rates [99-101]. In the most frequently used approach, pharmacokinetic parameters between different species are related via body weight using a power function ... 

Porter, G. A., and Bennett, W. M. 1989. Drug-induced renal effects of cyclosporine, aminoglycoside antibiotics and lithium Extrapolation of animal data to man. In Nephrotoxicity Extrapolation from in vitro to in vivo, and animals to man, ed. Bach, P. H. and Lock, E. A., 147-170. New York, London Plenum Press. 

Porter GA. Extrapolation of animal data to man the concordance between toxicity screening and clincial consequence. In Nephrotoxicity in the experimental and clinical situation Part 2. Martinus Nijhoff Publishers. 1987. 

Scott L (1996). Extrapolation of animal data to man issues for consideration. In Proceedings of the CB Medical Treatment Symposium, Vol. 2, p. 86. Spiez, Switzerland. 

As detailed, the overall carcinogenic process is complex and Involves a series of steps comparislng two distinct sequences. Basically, the process is similar in experimental animals and in humans. In fact, several chemical carcinogens have been shown to exert similar effects, such as the type of DNA adduct and type of neoplasm, in both animals and humans. Nevertheless, there are definite quantitative differences between species of animals and between experimental animals and humans. These differences make simplistic mathematical extrapolation of animal data to potential human effects a non-scientific enterprise (35). 

Taking various factors into consideration, it is probably impractical and not realistic to make risk estimations from the carcinogenicity data on rodents given a single carcinogen. However, for a simple extrapolation of animal data for risk estimation, TDjq values, which are the doses needed to develop cancers in 50% of animals fed on carcinogens [IQ, Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, AaC, and MeAaC] for their fife time, have been calculated based on mouse experiments... 

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. 

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