Appropriate Animal Study for Extrapolation to Humans

Identification of Appropriate Animal Study for Extrapolation to Humans 

The first step in adjnsting the resnlts of animal toxicology stndies for hnmans is selecting the animal stndy (or stndies) that will provide the raw data. We learned in 

Differences in physiology, especially in enzyme activity, account for a significant amount of this variability. For example, the chemical 6-propylthiopurine, a drug used to treat hyperthyroidism, is metabolized through a specific pathway in the mouse to a potent carcinogen. However, humans metabolize the chemical differently, and the metabolic products (known as metabolites) do not cause cancer. In this case, using the mouse data to set safe levels in humans would greatly overestimate the toxicity of the chemical to humans. 

For other chemicals, the opposite can be true. For example, the chemical 2-acetyl-aminofluorene (2-AAF), which is used in liver toxicology research, is activated by the P-450 enzyme system in the liver to a carcinogen in humans but not in guinea pigs because we metabolize the chemical differently than do guinea pigs. 

Similarly for wildlife species, differences in physiology have dramatic effects in toxic sensitivity. For example, although peregrine falcons are very sensitive to the eggshell thinning effects of DDT (chapter 2), other species of birds are not impacted. For example, this effect has not been observed in game birds (e.g., chickens, turkeys, quail, pheasants). In many instances, these differences are based on differences in the type, speed, and end products of metabolism across species. 

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When selecting an appropriate animal study for extrapolation to humans, the type of toxic effect measured is an important consideration. There are generally three types of toxic endpoints evaluated in laboratory animals ... 

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