that are available at the present time this is not such a small margin that is insurmountable.

I have never seen one case of lead poisoning at the onset in child or adult that has not had at least 0.08. Now this does not mean that all people become ill at this point. The majority do not-only a few. This is the lowest level of susceptibility in my experience.

Senator MUSKIE. Let me ask you this.

Is that kind of magin significant or would it become significant if the concentration of lead in the atmosphere were to double?

Dr. KEHOE. Yes, this margin would be quite adequate for this purpose and we have very good evidence for this. If you double the concentration of lead in this that exists, in the ambient atmosphere to which individuals are exposed, you will get no material change in the concentration of lead in their blood within 2 years' time.

Now you have a long time there before there is any kind of buildup that gives you this much difference. The reason for this is that over the long period of time the most of the lead that is absorbed into the body goes into the skeleton.

Consequently the level of concentration in the blood moves up very slowly. In our experiments over a period of years we have seen that it take 4 to 6 to 8 months to get a significant difference in the concentration of lead in the blood and the excretion of the lead in the urine if the dosage moves up slowly.

Senator MUSKIE. What is the significance from the health standpoint of the concentration of lead in the bone?

Dr. KEHOE. This is not negligible but it is slight as compared, for example, with the concentration of lead in the brain. If you have a concentration of lead in the brain, of the order of magnitude of threetenths of a milligram per hundred grams, this is usually indicative of a situation which is productive of fatal lead intoxication.

The bone has four times this concentration under perfectly normal circumstances and conditions. You have this concentration in your body and I in mine at the present time.

Senator MUSKIE. Dr. Prindle had something to say on this yesterday that I would like to get your reaction to. The only way we can evaluate this testimony is to place it side by side so that we can get the clash.

Dr. KEHOE. I can tell you for the record that you will find very little difference between my views and those of Dr. Prindle. Very little difference with respect to the facts. There will be a little difference with respect to considerations in the future, as is entirely appropriate. Senator MUSKIE. His presentation of the facts and yours at least give the impression of being substantially different.

Dr. KEHOE. But there really is not, sir.

Senator MUSKIE. I guess we will have to read those more closely. Dr. KEHOE. I know Dr. Prindle very well.

Senator MUSKIE. I think the testimony I was referring to was in the Surgeon General's testimony rather than in Dr. Prindle's testi

mony.

Dr. KEHOE. I think I could answer that question, sir, without being presumptuous. What I think we are talking about here are two different things. One of them is the uncertainty with reference to what a material like lead might ultimately do. As against the probabilities, which are based on evidence, as to what it has done in fact.

From the point of view of the Public Health we look with considerable concern on any risk that is applied to the public health. I may say we look with a great deal less concern, and I think unfortunately, on the risk which is assumed by the industrial worker.

Senator MUSKIE. I can't find Dr. Stewart's prepared testimony but I have a discussion that took place between him and me on this question. This is the prepared testimony we have finally found:

Evidence was also presented at the symposium which suggests another important respect in which the effects of lead may be largely overlooked because of limitations in our existing knowledge. This aspect of the problem stems from the fact that some of the lead taken into the human body is stored in the bones. Any of a number of factors-including such physiological stresses as peptic ulcer involving excessive bleeding and such physical trauma as accidents in the home or on the highways-may release lead previously held in storage. In such cases, the released lead may cause greater injury than the event which precipitated its release. Here again, the connection may never be made in the course of routine diagnosis and treatment.

I then asked him this question:

You also say that the bones of the human body tend to store lead?

Dr. STEWART. That is right.

Senator MUSKIE. Is there any doubt on this point?

Dr. STEWART. No, there is no doubt on that.

Senator MUSKIE. If that is the fact, then the amount of exposure which the human can take must be constantly reduced?

Dr. STEWART. Well, the body reaches an equilibrium in the amount it is taking in and the amount that the body is putting out, plus this storage factor. There is no solid evidence that the storage factor, that the storage of lead in the bones is itself harmful. Where I was making inference here is that when that storage is suddenly released because of some other event you suddenly have a lot of lead in the body that is released from the storage in the bones, like a fracture or like a severe bleeding.

Senator MUSKIE. But the release is unpredictable?

Dr. STEWART. That is right, it is unpredictable.

Senator MUSKIE. If it is unpredictable, you have to assume, do you not, that the release will take place?

Dr. STEWART. I think so, given some event and the release of the lead depends on how susceptible this person is to lead intoxication.

How would you react to that point?

Dr. KEHOE. I would react very strongly to that, sir, by saying that the thing which is feared here has not been seen to occur. We are again talking about what may occur, and not what has occurred. There is not the slightest evidence.

Senator MUSKIE. Which conclusion would you draw, that it will or will not occur?

Dr. KEHOE. My conclusion is that lead in the concentration that has occurred in your skeleton and mine and in man in generations ahead of us has never been known to produce lead poisoning, unless it becomes highly elevated. We have no evidence that this has ever occurred.

Senator MUSKIE. Why would the Surgeon General raise this point? Dr. KEHOE. Because there is in the literature a series of experimental studies made a number of years ago that indicated that under a variety of conditions lead is readily released from the skeleton. I think, Senator, it has been quite clearly demonstrated that this is not true.

Senator MUSKIE. You are satisfied that this is not true?

Dr. KEHOE. I am quite satisfied that it is not true. In fact, I have never seen any situation of this sort reported that to me was in anyway

plausible except in connection with a disease of the kind that results in the virtual disintegration of the skeleton. Now I have been told by one of my pediatrician friends, in whom I have very considerable confidence, that there is a situation which has occurred occasionally in children. I sought the evidence. I was unable to find it. He was unable to find it. He still believes as he believes and I still believe as I believe. What I am saying is that the fragmentary evidence that is available in this field is much too fragmentary to be trusted. I am sorry that the Surgeon General said this because I have to flatly disagree with him and I don't like to do it.

Senator MUSKIE. You say it is fragmentary, too fragmentary to be trusted.

Dr. KEHOE. Yes, sir.

Senator MUSKIE. Is it too fragmentary to base a disagreement upon?

Dr. KEHOE. In my judgment, no. I am quite sure if the Surgeon General was to read the literature in this field with great care he would change his conclusion.

Senator MUSKIE. Maybe you ought to suggest that to him.

Dr. KEHOE. I have suggested it here. I think this will probably come to his attention.

Senator MUSKIE. Speaking as a Senator now, you can't rely on that. Why don't you proceed, Doctor? I think I have asked all the questions.

Dr. KEHOE. The facts obtained from these experiments and from several field surveys have demonstrated clearly that the quantity of lead which is being absorbed daily by the average adult citizen of the United States who is not subjected to occupational or otherwise unusual types of exposure to lead, is balanced for all practical purposes by the excretion of a corresponding quantity of lead. This balance is achieved within the first several years of childhood (after the varied diet of the adult has been adopted) during which the levels of concentration of lead in the tissues of the newborn infant approach and overtake those of the adult.

The newborn infant has some lead in the tissues. The concentrations are quite low and they do not move upward until later. They don't reach an equilibrium until the child is on a full diet. Much the highest concentration of this lead (of the order of five times that in any other tissue) is found in the skeleton. Moreover, the mass of the skeleton, relative to the other tissues of the body, is such as to reduce the concentration of such a minor constituent as lead, in the other tissues, under ordinary circumstances, to almost negligible proportions. (It is not negligible since it can be measured quantitatively.) Indeed the concentration of lead in the skeleton of the average child or man in the United States who has not been subjected to any unusual exposure to lead, appears to be of the order of 1 to 3 milligrams per 100 grams of fresh, untreated bone, and this, when restated in the gross relationships of the total weight of the lead contained in the skeleton to the total weight of the skeleton, comes to the average value of about 20 parts per million, which is not far from the natural concentration of lead in soil and coal. This gives you some idea of the relationship to the earth in which we live.

So it is that the great proportion of the lead in the body of the ordinary man is sequestered, in some degree, in that part of the body

that is least likely to be affected by it, and is, in addition, in low concentration even there.

The absorption and excretion of lead under "abnormal" conditions of exposure: The foregoing interpretation of the behavior of lead taken into the body from ordinary sources is supported by the facts observed when individuals have been subjected to the absorption of quantities of lead beyond the range of those which are encountered in ordinary life. Under such circumstances, the rate of the excretion of lead in the urine varies primarily with the current rate of the absorption of lead. The concentration of lead in the blood also varies with the rate of the absorption of lead, but is relatively slow in reflecting this rate (unless the latter is very rapid). Instead, it tends to represent the approximate state of the body generally, with reference to its overall burden of lead. Accordingly, if the current rate of the absorption of lead is sufficiently high, as compared to that which characterizes the usual pattern of persons in the general population under ordinary environmental conditions, there is an accumulation of lead in the tissues of the body, including the blood, and the concentration of lead in the blood mounts slowly to a point at which it is indicativeit does not give the absolute numbers, but it is indicative of the approximate quantity of lead accumulated in the entire body.

Under the conditions of occupational exposure to lead, it has been possible to develop sound criteria for the safety of workmen, individually and collectively, which, when applied scrupulously, result in the elimination of all cases of lead poisoning. Stated in their simplest terms, these criteria define the point in the absorption of lead, as revealed by the general rate of the excretion of lead in the urine, and more precisely by the concentration of lead in the blood, below which, cases of lead poisoning, even of the mildest type, do not occur. The threshold value for the concentration of lead in the urine is approximately 0.15 milligram per liter, while that in the blood is 0.08 milligram per 100 grams of whole blood. Allowance must be made in both instances for the known error of the analytical procedure employed, as well as for the range of the physiological variability of the results, which in the case of the urine is appreciable, but in the case of the blood is minute. Experience has shown, however, that the criteria are reliable, and that men employed in the lead trades remain free of any of the effects of intoxication by lead, so long as they remain within these limits with respect to their absorption of lead. Freedom from intoxication by lead does not mean the mere avoidance of disabling lead poisoning or as it has been spoken of, classical lead intoxication, which is a term that might be used, but also should be defined.

Rather, it means that no symptomatic or objective evidence of intoxication can be detected, as such, by a skillful and experienced physician. It has been suggested that any single numerical limit such as this is most unusual in connection with the toxic action of a chemical agent. To the contrary, it is common, to the point of near regularity, that there should be a minimum toxic, as well as a minimum lethal, dose of a chemical agent. The point here, which has escaped those who have not examined the facts, but have made loose assumptions concerning them, is that the specified limits in the concentration of lead in the urine or blood is not a point above which cases of lead poisoning occur without fail. As a matter of fact, there is no level of lead concentration in the body which means certain lead poisoning,

but it is that point in a range of values below which, regardless of human susceptibility (so far as the present record holds), no case of lead poisoning has been found, in our long experience, to occur. The range of susceptibility, as this term is used in nonspecific medical parlance, extends from this point upward, over a fairly wide range, but not downward. It is wholly in keeping with the variability in the behavior of men, in response to a great variety of stimuli or stresses, that there should be limits within which the response is physiological, and beyond which pathological manifestations occur with increasing frequency and severity.

I would like to point out, as an aside here, that during the entire history of man on this earth he has had lead in his body. He has lead in his food, he has had lead in his drinking water and he has had lead in his body. This is inescapable on this planet. The question is not whether lead per se is dangerous, but whether a certain concentration of lead in his body is dangerous. This is the sole question, physiologically. The applicability of the foregoing criteria of safety from the effects of the absorption of lead, especially that concerned with the concentration of lead in the blood, within the general field of environmental health is, of course, a crucial matter in determining and controlling the risk incurred by our population from the lead in their environment. It is because this is the case, that the matter has been subjected to rigid examination, with the result that, even in the case of infants and very young children, the onset of lead poisoning has not been found to occur in association with levels of lead concentration in the blood under 0.08 milligrams per 100 grams of whole blood, with due regard to an analytical deviation of ±0.01 milligrams per 100 grams, in the case of samples of the usual weight of 10 grams.

The critique which must be applied in the examination of this matter must take into account the nature of lead poisoning, and even more pertinently, at the moment, the opinions of physicians and others concerning its nature those which have been handed down among many generations of both critical and uncritical physicians; those which had a sound basis in clinical and experimental observation and judgment, and those which are little more than "old wives tales." Without bringing all aspects of this subject to definitive resolution, modern physiological and biochemical investigations has exerted a clarifying effect upon the toxicological concept of lead poisoning, including certain of its more subtle or insidious characteristics. At this time, therefore, it is especially futile, other than as a stimulus for further extensions of pharmacodynamic and metabolic investigation in the hands of competent and imaginative physiologists, toxicologists, pathologists, and physicians, to cherish in oneself or others a clairvoyant anticipation of unheralded and disastrous effects of types hitherto unknown among trained observers. Certainly however, the concept of lead poisoning that must be held in mind, now and in the future, must include all disturbances in physiological function and in well-being that can be attributed, on valid present or future evidence, to the effects of lead.

Criteria of public safety with respect to the absorption of lead and methods of identifying a threat to the public: As indicated previously, the opportunities afforded to the average citizen of the United States (who is not subjected to occupational or unusual types of exposure to lead) are concerned with his ingestion (swallowing) and inhalation