ABSTRACT
Although not all differences seen in the responses of animals and/or humans to chemical toxicants are due to differences in the routes and rates of metabolism of the administered chemical, it is a general principle that if differences are found then the first hypothesis should be that this is so. The enhancement of computational power in the past thirty or so years has enabled complex differential equations to be solved and account taken that some of the systems may be saturated with substrate, i.e. be operating at their maximum rate. Thus the delivery of the dose of active intoxicant to the target in particular cells will depend on a variety of constants some of which will be determined by Michaelis-Menton principles, e.g. Km, Vmax, KAff and k (rate constants) of the various systems involved. Compartmental pharmacokinetic (PK) models have been useful in determining the consequences of tissue dosimetry. However, the use of such PK models beyond the immediate test situation is limited and the compartments are derived from the data and are in essence mathematical concepts.
