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If one considers that the ultimate effect is manifested as an all-or-none response, or a quantal response such as death, and that a minimal concentration produces no effect, then there must be a range of concentrations of the chemical that will give a graded effect somewhere between the two extremes. The experimental determination of this range of doses is the basis of the dose–response relationship. Toxicity studies provide systematic ways to measure the adverse effects of compounds, and to understand the relationship between a dose and the route of exposure and metabolism is vital. Toxicity testing must inevitably be performed largely on laboratory animals. It is advisable to use at least two phytogenetically different species for this purpose. Rats and dogs are most commonly used, but particular effects may have to be examined on a wider variety of animals, including nonhuman primates. Although the reactions of animal models are often surprisingly similar to those exhibited by humans, it is known that some substances (e.g., amphetamines) are metabolized along different routes in humans and dogs. Thus, a toxicant may not reproduce in humans the effects recorded in the animal species, and when assessing the potentiality of a new food substance care has to be taken to not assume too close a parallelism between the reactions of the two species. Toxicity testing, no matter how carefully performed, cannot be expected to reveal all the potential adverse effects. Apart from the difficulty of predicting the responses of humans from the results of animal experiments, some toxic effects appear in only a minority of subjects. For example, antibiotics are among the safest of drugs; however, rarely, penicillin administration initiates a fatal anaphylactic reaction. The purpose of toxicity tests is to make a realistic assessment of the potential hazards in relation to the benefits likely to follow after use of the compound. In the final analysis, it is impossible to make this assessment with any assurance until the substance has been in actual use for many years.
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