Metabolic Studies of Environmental Effects

Perhaps some of the comments already made here about developing a theoretical basis for predictive purposes were in disagreement because opportunities vary greatly with the model under discussion. Certainly the general lesson of molecular biology and biochemistry in the last two decades has been surprisingly opposite to that of toxicology in that metabolic pathways are remarkably similar in range, not merely from mouse to man but even from bacteria to man. It is at times hard to accept the claim that animal models are not too useful for studying teratogenesis. Some principles that have been reviewed today are worth summarizing, because if one thinks of certain parameters, such as the final toxic substance (frequently a metabolite of the original pollutant) there is probably not much difference among various species or organisms. At least so it seems from study of enzyme systems. If one considers simpler situations, such as mercury pollution, he can realize the validity of this concept. THREE PARAMETERS OF TOXICITY One could possibly look at the situation as follows: at various stages of the developmental process, starting from the fertilized ovum and progressing to the mature organism or even the aged organism, there are enzymological differences which have become of interest in developmental biology. In particular, in pediatrics we know about programmed processes that go forward inevitably, and others which are subject to control by hormonal influences, by administration of certain substances, or by induction. In the interpretation of any kind of toxic effect, we must consider if our developmental parameter will or will not be toxic at certain stages of development, as I will ifiustrate later.