Pharmacokinetic and other factors related to mutagenicity testing: quantitative analysis of the testing procedures.

I would like to focus attention first on three major and immediate problem areas inherent in any testing system and then to discuss to a limited extent a major problem, generally not discussed, involved in the elucidation of the meaningfulness of any test system for human health and welfare. The three problem areas I wish to discuss first are: (1) the toxic agent-the suspect compound; (2) the target-the tissue likely to develop the toxic response; and (3) the time factors involved in test systems. There are three questions that must be asked regarding the toxic agent. What chemical is the toxic agent? How much of that agent is present? How long is that agent present? These questions must be asked whether one is doing an experiment on Neurospora, on human cells in vitro, on laboratory animals, individually on man, or on the human population. In more classical terminology, the question of the identity of the agent refers to studies on metabolic alterations of the compounds by cellular activity. The question of amount or concentration of agent is the function of not only the metabolism but also the distribution and the