Discussion Study of Lead Levels in Experimental Animals Emil A. Pfitzer University of Cincinnati, Kettering Laboratory, Cincinnati, Ohio 45219
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t is, indeed, fortunate that it has been possible to obtain concentrations of lead and other metals in the tissues of experimental animals exposed to air from a large U.S. city for approximately 4 years. The unique aspects of this study include these two features: (1) the long-term exposure of four years-few studies, if any, have included exposures beyond 2 years; and (2) the exposure to the identical air to which man has been exposed-most other studies have utilized either a relatively pure lead compound, or auto exhaust, with and without irradiation. The authors have made it clear that this study on lead levels has been added to a research project which was primarily designed to investigate other factors. Thus, it is no direct criticism of the experimental design to note that the greatest loss from this study, in my opinion, is the absence of information which would demonstrate whether or not the concentration of lead in bone was approaching a steady state by the end of 4 years. It is regrettable that a study unique in its length does not provide data which would indicate the attainment of a potential steady state-that information which uniquely requires such a long-term exposure. It is relevant to enumerate some of the pieces of missing information which might be desirable for maximum utilization and interpretation of the data. Many of these items are probably available, although unreported, and others might be estimated or obtained by secondhand methods. The items include: the age and weight of the animals at the initiation of the study; the weight of the animals at the end of the study; measurement of weights of organs and tissues for purposes of estimation of the total content of lead in the body; the sex of the animals from which tissue was analyzed for lead; the source and quantity of bone analyzed for lead; relationship between particle size, concentration and diurnal pattern of lead in the particulate matter breathed by the animals; concentration of lead in blood of the animals; and concentration of lead in the bones of the animals at the initiation of the study. One is tempted, when discussing a research paper, to take liberties with the author’s data and, by making assumptions, attempt to interpret to a greater degree than the authors have done. Time does not permit such liberties, if one would do full justice to such efforts, and I will limit myself to one such observation. The authors have noted that Schroeder and Tipton estimated that 17.6% of the total lead absorbed by an adult man could come from breathing air containing 1 pg. lead per m.3. They have also calculated that guinea pigs and rabbits could receive 13 and 23%, respectively, of their absorbed dose from air containing 2.5 pg. lead per m.3. It is of interest to calculate that the relative increase of the concentration of lead in bone, presumably attributable to lead in air, is 12 and 36%, respectively, for guinea pigs and rabbits. It would be of considerable additional interest to estimate how much of this absorbed dose was actually retained by the animals over the 4-year exposure period. The finding of this study was that the concentration of lead
in bones of animals was visibly elevated due to the intake of lead in air. The term “visibly elevated” is used because, I believe, there should have been no question that elevation would occur. The question at issue was, “Is the elevation of sufficient magnitude to be detectable by the methodology utilized?” The answer was affirmative and, I believe, valid. The conclusion to the study has been interpreted in this manner for a specific reason, and I would maintain that it is not a semantic issue. There appear to be some individuals who have concern for the setting of an air quality standard for lead and who take great stock in the ability to show no visible uptake due to a given exposure. To be sure, it may be comforting, and is indeed relevant to know that uptake under certain conditions is negligible for practical purposes. However, experience in the field of setting standards is replete with examples that show that researchers find increasingly more sensitive methods and that they suggest more subtle criteria, so that what was “negligible for practical purposes” yesterday, today is measurable and requires decisions about its significance. If our logic for setting standards is simply the visible detection of uptake, we are tying ourselves to a system which will inevitably, and with the arbitrary success of research analysts, carry standards to ever lower and lower levels. It may confidently be anticipated, for example, that animals exposed for 10 years to a concentration lower than 2.5 F g . of lead per m.3 will show increased levels of lead in bone attributable to such exposure. Thus, the basic discussion of this research should not deal with whether or not the findings are applicable to man or the setting of standards. They are certainly applicable in that they provide one landmark of quantitation based on animal models, for an understanding of the relationship between lead in air and lead in the body. The utility of the findings for setting of standards must await definition of the criteria upon which a standard will be based. This decision has not been brought into proper focus. Should the criteria be: illness based upon colic and anemia, biochemical changes as measured by urinary coproporphyrin and delta-aminolevulinic acid, concentrations of lead in blood, urine or bone, excretion rates of lead, or estimates of body burden of lead. Should the criterion simply be, as some have indicated, progressively cleaner air for its own sake. These possible criteria do not all have direct interrelationships and our discussions about setting standards will remain confused until we consistently and deliberately state our criterion when we interpret data relevant to a standard. The decisions about criteria bring us face to face with the questions which have long plagued researchers in the field of safety evaluation. Can you have measurable changes within the “normal” range? When are measurable changes desirable homeostatic responses? When are measurable changes permissible and when are they adverse effects? The questions have not as yet been completely resolved for the safety evaluation of lead, but recent progress has been both encouraging and stimulating. Volume 4, Number 4, April 1970 339
