of lead compounds which occur in his general environment. The total quantity of lead that may be absorbed from these combined sources constitutes the total threat, if any, of the environment, with respect to lead. However, since these sources differ in their means and ease of penetration into the body, and, to some slight extent at least, in their effect upon the distribution and handling of lead in the body, they must be examined separately as to their quantitative significance. Accordingly, the limit of safety, with respect to the absorption of lead from the one, that is, in the air, must be established while the other is being held constant, that is, in the food, and vice versa. This has been done, up to a point, in experiments in the Kettering Laboratory.

(a) The upper safe limit of the daily intake of absorbable lead into the alimentary tract.

In one set of experiments, each of a series of human subjects, after a period of observation of his daily intake of lead in food and beverages, and his daily output of lead in the feces and urine (under basic conditions with respect to the inhalation of lead from day to day), was given a measured quantity of lead per day, one-third of it with each meal, in simulation of his ingestion of food contaminated with lead. These experiments have been described in some detail. In brief, however, they have set up a criterion for human safety, and have reported the results that meet this criterion. It was evident that, under the conditions of these experiments (in which about the same quantity of lead, the sum of that in the food and beverages and that administered, was ingested each day, for all practical purposes), each individual, to whom a sufficient quantity of lead was administered daily, gave evidence of the absorption of lead, in proportion to the dose administered, and excreted lead in his urine at a steadily increasing rate during the entire period of the administration (for somewhat more than 4 years in one experiment). He also developed an increase in the concentration of lead in his blood, at a substantially uniform yearly rate, and accumulated lead in his body (the cumulative difference between intake and output) at a uniform yearly rate. No such effect was observed, however, in the subject to whom the least dose, in addition to that in his diet, was administered in three doses, each of which was 0.1 milligram.

In this instance, there was a very slight increase of borderline statistical significance in the output of lead in the urine, no increase in the concentration of lead in the blood, and evidence (of borderline statistical significance) of the accumulation of 12 milligrams of lead in his body in the course of 1.5 years. This is believed to be as near the vanishing point of a positive response as one is likely to obtain in an experiment of this type. In consequence, it is probable that a young, healthy adult-I am not talking about the total population, but about a young healthy adult-can ingest, regularly, throughout his life, an average quantity of lead of the order of 0.5 milligram per day, without any risk of accumulating a significant quantity of lead, so long as there is no persistent and significant increase in the intake of lead from the atmosphere. I might say, incidentally, this is not a wild guess. There is evidence at the present time from the literature and from the observations of Williams (Monier Williams in England) that this is about the level at which England is taking in lead daily in food and beverages. This may be a mistake because the information is indirect rather than direct.

(b) The upper safe limit of the concentration of lead in the ambient atmosphere.

The experimental approach to the determination of the safe limit for the inhalation of lead from the general atmosphere differs from that concerned with the ingestion of lead in food and beverages, the reason being that the quantity of lead which is taken into the body with the air breathed, as indicated previously, cannot be determined directly, but is subject to calculation from the concentration in the air and the volume of air breathed during a specified period of time. A number of variables are involved in this calculation, so that it can be carried out with a reasonable degree of accuracy only under well controlled conditions, with respect to the measurements of the lead in the air and of the volume of the respired air. Then too, the quantity of lead absorbed in the respiratory tract and lung varies with the rate and depth of the respiration, as well as its volume, and, to an even greater extent, with the dimensions, shape and solubility of the particles of lead-bearing material that is being inhaled. The most satisfactory physiological criterion, with respect to the significance of the absorption of lead in the respiratory apparatus, lies, therefore, in the response that is afforded by the change in the content of lead in the urine and blood. However, while analyses of the urine and, more effectively, the blood, provide definitive evidence of the safety or the potential risk of the individual (and of groups of individuals) at the time of the analyses, they cannot yield information on which to predict the probable extent of the absorption that will occur ultimately, when lead is being absorbed into the body at a constant, significant rate.

As, for example, an individual in the ambient atmosphere who breathes this atmosphere 7 days a week and on indefinitely. This is a different matter. This is a difference, and it is a fundamental physiological difference, between respiratory exposure to lead according to the normal occupational schedule, now standardized, generally, in the United States at 40 hours per week, and that associated with lead in the atmosphere of the community, which, although somewhat variable, from place to place and time to time, is continuous throughout the day and week. In the occupational situation, (and as simulated by our experiments in which men were subjected to the inhalation of a known compound of lead in a known state of subdivision in the air-nearly ideal for both retention in the lungs and for absorption-for approximately 40 hours per week), the output of lead in the urine and its concentration in the blood increase for some months until they reach a plateau the height of which is determined, under uniform conditions, by the concentration of lead in the air. Afterward, it remains essentially unchanged, on the average, so long as the occupational (or experimental) exposure continues unchanged. This plateau is an expression of an equilibrium between the absorption and excretion of lead, which is achieved by reaching a balance between the periods of exposure, when absorption is greater than excretion, and those of exposure, when the excretion is greater than the absortpion.

There is no opportunity for the achievement of such a balance when the rate of absorption is sustained, as in our experiments during which lead was administered by mouth in three doses through the day, and as it must be when lead-bearing air, within appropriate limits of concentration, is being breathed throughout the 24 hours of the days. These facts make it necessary to approach the criterion of the safety

of the public, in relation to lead in the ambient atmosphere, on a difference principle than that of the safety of employees in the leadusing industries. It is also necessary to employ a different method of observation from that concerned with the ingestion of lead, although the same principle applies, that of establishing the largest daily dosage of lead derived from the air which, when combined with that derived from food and beverages, will be insufficient to result in a measurable (or significant) accumulation of lead in the body in the course of a lifetime.

We are talking here not about the accumulation up to the point of toxicity. We are talking about whether there is or is not accumulation. The latter is the criterion.

Experiments have been carried out in the Kettering Laboratory for 3 of the past 5 years, by which the methodology of the approach to this problem has been worked out. During the past 2 years, two men have been under observation, in accordance with these methods, while they have been subjected to respiratory exposure to air containing a low, uniform concentration of lead (Pb) on an increasing schedule of hours per day during successive periods of 16 weeks. At the conclusion of this experiment, in early July of 1966-one of the men has completed the experiment, but the other has not-they will have spent almost half of their time in such an atmosphere for 16 weeks. No definitive response to such exposure has been observed, up to the present time, in the form of a significant increase in the output of lead in the urine or in the concentration of lead in the blood. Accordingly, in an experiment yet to be performed, the concentration of lead in the respiratory chamber must be increased, and the observations repeated. From all of these data-those available and those to be obtained soon-it will be possible to arrive at a standard concentration of lead in the air as a physiological criterion of public safety, in which a prudent margin against chance may be incorporated. Needless to say, the validity of this criterion should be put to practical test well before the public shall have been subjected to the projected level of exposure, by means of periodic surveys such as that recently made, in which the reaction of the public to an existing exposure of lesser magnitude can be determined.

Certain basic conclusions: From the consideration of the observed facts and the physiological principles developed in the foregoing statement, it would appear that there is no reasonable basis for anxiety concerning any potential threat that is offered to the public from the lead in the ambient atmosphere in the United States.

Moreover, the means now available for the appraisal of the severity of this type of exposure to lead, and of its hygienic significance, would appear to provide ample safeguards in the future, provided such means are employed skillfully and critically, and frequently.

Senator MUSKIE. Doctor, I would like to read from a couple of statements that were made at the symposium on lead held by the Public Health Service last December.

Dr. Heiman said something that I think might be helpful to us to place some of the points you made this morning in the perspective that you would approve as well as the committee. [Reading:]

The first thing I would like to point out is that there has been no evidence that has ever come to my attention, including at this meeting, that a little lead is good for you. I say this because I believe there are some persons who imply

that this is so because of some of the statements which they made. The second point I would like to make is that it is extremely unusual in medical research that there is only one small group in one place in the country in which research in the specific area of knowledge is exclusively done. There needs to be repetition and extension of the fine work which has been done at the Kettering Laboratory with regard to the metabolism and the balanced experiments which have been done on lead. It needs to be repeated in many other places and be extended. There needs to be in my opinion an extension and improvement of the work which was done by the Public Health Service in its tri-city study of lead body burden of people in communities. There needs to be a carefull study of the figures I have given as the safe ones at which lead toxicity will not probably occur. I say specifically.

It is our experience in medicine that to use a single figure on the safe one beyond which poisoning will probably occur and below which poisoning will not occur is a most unusual kind of situation in public health and in medicine. believe there needs to be careful study of the figures which I used.

Would you want to react to that, Doctor?

I

Dr. KEHOE. Yes. I believe first of all that the observations outside of those of the balance experiments-this balance work has not been done by anybody else up to the present time. It may be that some of it should be repeated for the sake of confirmation. It will be confirmed, I can assure you. It may be that these experiments should be done in somewhat the same manner. I should argue against that. I should argue against that because, first of all, these are very expensive experiments and they should not be carried out recklessly without regard to the money that it takes to obtain this kind of information. The methods that have been used in our observation, which to me are crucial in this whole situation, are being used at the present time on a worldwide basis. They have been used now over a period of years and there is simply no question, I think-perhaps I am prejudiced, but I think there is no question in the minds of a very considerable body of experienced people in industrial hygiene that these results are valid. They have been checked by experts in other countries. There is a report that is given here after a translation that has been obtained, that was reported here, that was obtained by our Swiss colleagues a matter of a few years ago who have used substantially the same methods, who have followed out comprehensive observations, I mean with respect to the field surveys, and have come out with precisely the same results.

Now Heiman is right with respect to the need for confirmation of experiments that are crucial. The methods that have been used in these experiments that have been checked by British investigators, by Swiss investigators, by a number of others, as being the crucial points in the determination of whether the information that had been obtained in our observations was correct. This means only one aspect that is left open and that is whether I, myself, and my investigators in the Kettering Lab are clever enough to be dishonest about this and get away with it. Frankly, I don't think we have that kind of clever

ness.

Senator MUSKIE. I don't think that question is involved.
Dr. KEHOE. It is theoretically, sir.

Senator MUSKIE. The only question involved is the interpretation you place upon it. I will be frank to say that it is unusual for me-I am not a scientific man-to find such certainty in the field of scientific inquiry in a subject such as this. The questions so far as we are concerned are: first, what are the effects, or do we know enough about

them, of low-level subtotal exposure to lead in the atmosphere and, secondly, how will the present answer to that question be affected as the number of automobiles in this country and the consumption of gasoline with lead content increases in the future? These are the two questions we are concerned about. On the question of the subclinical effects, Dr. Hardy, who testified earlier this morning, had this to say in the symposium. [Reading:]

I have to protest briefly that there is evidence of lead related damage not identifiable as classic lead poisoning. I have listed the following: Lane's Studies on Mortality of Lead Workers. Henderson's Australian Work on the Relationship Between Lead and Renal Disease. Doctor Jensen's work and, more modestly, mine, on the assymptomatic lead workers difficulty with his hemalogical abnormalities, and then the large body of work on children without identifiable lead poisoning who through well documented evidence have experienced harmful lead effects either in-I am sure I am not pronouncing these medical terms correctly-hematological abnormalities or mental retardation. Dr. Hardy apparently, and I might ask her to comment on this this morning, says that there is evidence of subclinical effects that she feels are of concern as relates to health. You apparently have less doubt on that point.

Dr. KEHOE. No, I don't, because I know that there are residual effects of exposure of a significant degree of severity. What we are talking about here is not the residual effects of one-time serious exposures which do exist, but the effects of a situation in which we are at a very low level of intake, which has never historically been known to result in a single case of illness in child or adult. This is the difference.

We are not talking here about the residual effects of a one-time intoxication. We are talking about whether signs of intoxication come into existence under the conditions that exist in the community at the present time. I submit to you, sir, that there is not the slightest evidence that that is the case in medical literature or in case material. Senator MUSKIE. We are talking about a condition here

Dr. KEHOE. We are talking about a condition which may occur. Senator MUSKIE. We are talking about something physically that is occurring that may be producing a different situation. We talk about growing concentrations of lead in the atmosphere and what that may produce. This is a kind of low-level, long-term exposure that we have not had in the same degree in the past, that we will have in an increasing degree in the future given a continuation of the present methods of transportation by automobiles and the present use of gasoline for fuel.

Dr. KEHOE. Let me put it this way. We have had experience with the situation that exists at the present time, with respect to the level of lead absorption in the American population. We have had experience with this over a period of 30 years or so during which we have been looking for effects in the general population and have failed to find them.

Now, this does not tell us one thing about what will happen 5 years, 10 years, 15 years from now if, as and when the concentration of lead in the atmosphere goes above a point with which we have had previous experience.

Senator MUSKIE. That is bound to happen, is it not?

Dr. KEHOE. What I am prepared to say at this point is that this is something which, just like the food of the country and the beverages