Document N2yGEbjaxV5vxgNOrRanyQDpp

June 9, 1907 Mr. John a. Riga, Chief Bureau of .Ur Sanitation Department of Public Health 2X51 Berkeley Way Berkeley, California 94704 Bear John: Z appreciate very much your having sent me a copy of the report of the Department of Public Health entitled, ''Lead in the Environment and Its Effects on Humans." I have been very busy, as you may well expect, in undertaking to fulfill certain obligations, among them the APSA '`Guide, ' and l have not completed my review of the report. Z shall do so as soon as 1 can find the time. There are, however, certain statements and conceptions in certain of the Sections {Chapters?) which Z have covered that seem to me to be open to comment or criticisms, and X pass some of the latter along at this time for what they may be worth. The principal Section to which I take certain exceptions is VII ~ Health Effects of Atmospheric Lead In California. I would suppose that John Goldsmith is responsible for this Section (and several others), but since no specific author is indicated and the report cam from you, Z direct my reply to you with a carbon copy, for such use as you may think desirable. Z would start out by suggesting that the title of this section Is "loaded," although S would not suppose that this was intended to be. However, since any harmful effects are purely speculative, and the observed effects are in the realm of the physiological differentiation, to some extent, of the behavior of inhaled lead from that of ingested lead, I would regard this title a3 a bit leas than realistic. However, this is of little moment. It is not of small moment, however, that the first statement in A ~ Introduction, is a flat acceptance, as fact, that "lead is thoroughly implicated as a causative agent (without regard to quantify) in - - liver and kidney damage (and in) mental retardation in children. The statements in the literature that these things are true, do not "thoroughly implicate" lead in those natters, and unless one qualifies the statement with the description of the nature of the lesions and the conditions under which they occur, the indication here is that the whole fabric of thiscontroversy has been fully digested and settled. Such is not the case. In the course of an acute intoxication, certainly the liver and kidney show evidence of reversible toxic change, but this is a far cry from the chronic effects that are the burden of the controversy, with particular respect to nephrit I know of no pathogenic process that is regarded more dubiously by more competent clinical and pathological observers than that which relates to the production of chronic nephritis by lead. It is true, without doubt, that children who have survived, after a bout of lead encephalopathy that has resulted in a greatly increased and persistent (for days) intracranial pressure, have suffered gross or focal brain damage and have given evidence thereafter of severe central nervous impairment. However, there is no N13154 t!r. John A. Maga Page j| June 9, 1987 documentary evidence with which 2 a familiar that children who have had the milder forms of load poisoning, including the lesser severe types of encephalopathy and have been found to be mentally retarded, were not mentally retarced before becoming ill from the ingestion of lead. Indeed, there is a distinct impression that the very young children that are afflicted with pica are abnormal mentally. X was inclined, as a pathologist, to the belief that the absorption of lead in the brain, within appropriate limits of concentration, would cause actual cellular carnage. Ko one, however, has succeeded in finding evidence of damage in the brain that can be attributed to the specific effects of lead. It is of interest, in this connection, that the encephalopathy of tetraethyllead poisoning either results fatally or in complete recovery without sequelae. I oo not maintain that, either here or in encephalopathy due to the absorption of inorganic lead, no damage occurs. X say, simply, that as of now there is no such evidence. We are dealing here with a post hoc, ergo propter hoc type of reasoning, both for and against this hypothesis. (Incidentally, Scheper's article in the Archives is cited as an authoritative reference as to the pathologic response to the absorption of tetraethyllead. X can think of no more unreliable source of information. He appeared in this Symposium as an uninvited substitute for John Sapf, and since he came as the spokesman for the Haskell Laboratory, X had to show him and John professional courtesy. The paper he submitted was an atrocious botch, which X had to edit very carefully in order to make it acceptable at all. X did so rather than stage a row in which X would have appeared to be an utter boor*. X am sorry now that X didn't stage the row, and ask John Zapf to have the report prepared by others of his staff, since the article has been cited by several serious investigators, because of its setting. X consider the pathological descriptions which were his primary contribution to this experimental work, to bo essentially worthless. The analytical work, done by others is reliable.) ks to tho influence of lead on the synthesis of hemoglobin, it is hardly proper to refer to this in non"quantitative terms, as though it constituted a function of the absorption of tho usual quantities of load into the body. The evidence is sound, X believe, in indicating that this occurs only when the concentration of lead in tho body is within a certain range. One should qualify the statement by including a clause to this effect. This might be regarded as mi unduly critical attitude on my part, but it is &n astonishing truth that many people who should know better, fail utterly to appreciate the importance of this principle of toxicology. This failure has been noteworthy in the present situation, and therefore it should be combated by suitable care on the part of critical writers. 4 statements Justifying the third paragraph of the Introduction can bo found in the literature, as can very many another that is dubious. X have never found the slightest evidence that this is true, except under circumstances in which workmen have been removed from their primary job involving excessive exposure to lead (whether ill or not), and moved into, or returned bad: into, a position involving "less or little" exposure, after having suffered a bout of intoxication. Statements of this type have been made loosely in considerable profusion, by investigators who do not have the detailed information about the activities of the person or persons involved. It Is rare, in our experience, that the concentration of lead in the soft tissues and in the blood (and bane marrow) remains at a sufficient level to give rise to abnormalities in the porphyrin metabolism after the lapse of 12 to 13 months. The concentration in H 0012445 iar Joh n A . Sloga Page 3 Juoe 9* 1967 the hose, in particular in the dense structure of the shafts of long bones* remains elevated for a long time, because* no doubt, of the very slight vascularity of these structures. But there ia no evidence that any type of disease (other than gross osteoporosis) or metabolic disturbance exercises any Important influence on the rate of loss of lead therefrom. After the initial period of relatively rapid loss* over the period of a few or'any months* dependent on the body burden and the time involved in acquiring it* the curve tapers off to an almost level line above and nearly parallel with the base line. Perhaps the most serious error in the report* from the aspect of inadvertent misquotation (the reference is to the Harben Lectures) is found in the last paragraph of the Introduction (page 19)* in which is tho statement that ''less than 0.03 milligram of lead per 100 grams of blood* and - - - less than 0.13 milligram per liter (ia the urine), axe considered to b within 'normal* limits.^'* I cannot understand how this statement can have been drawn from the Harben Lectures* in which the "normal" ranges in tho blood and urine are defined with care, as is also the abnormal range that is unassociated with illness of any type. Tiie threshold value above which* in our experience* ail deviations from normal health and well being occur* is also stated precisely, this does not mean* of course, that the mere exceeding of this threshold results in illness or biochemical abnormality (although the latter is found to bo tho cage not infrequently). Bather it only means that no sign of illness has boon found below this level, I cannot accept the parenthetical remark "(even though blood and urine aaiao-levuliaic acid levels may be high)." 2 do not believe this is true* for while our experience with this phenomenon ia not early so extensive as that with tJie porphyrias, ms have not seen such findings except in association with values at or above the threshold of danger ia the blood. It may be that these phonoaena continue for a time after tlx blood level decreases* following the cessation of exposure. I cannot bo sure of this, one way or the other* since we have not followed tho amino~1vulinic acid long enough to cover the possibilities to my satisfaction. So shall continue* however, to investigate this raatter. But my point is, that I would not make such a statement* even parenthetically. And in order to make my position quite clear, let me say that if this were true and it could fee ascribed reasonably to the effects of lead, I would be entirely willing to regard it not as the forerunner of lead intoxication but as intoxication. The interference with a recognizably significant physiological function in my book* is intoxication* whether temporary or* so to upeak, prodromal. So far as I can see* the establishment of a threshold value for lead in the blood (for physiological reasons* I do not consider the rate of the urinary excretion of lead to be anything like as precise as the concentration of lead in the blood), to which there is no exception* is a very crucial matter* since the blood, as a tissue which participates in the distinct patters of the distribution of lead in the body* provides an excellent indication of the content of lead in the other soft tissues within reasonable limits of variability* and thereby permits one to estimate* with fair accuracy^ the quantity of potentially "effective" lead in the body. 2 should point out right here that the statement on tho next page (page 20, paragraph 2), that "blood - - ~ levels alone are not adequate criteria on which to base Judgments of health effects in adults* and certainly not for children," is indeed a bold statement* in view of the evidence. Certainly the blood level does not signify injury or illness* but rather the danger of illness. It is clear here* however, that the latter is what is meant. It should be so stated* as by changing to some such clause as the following* - "judgments as to the likelihood of the onset of illness." It should have been M r. Joh n A , Maga Page 4 une 9 , 1967 qualified, at least, by indicating that not all persons agree on this matter. The discussion of this matter, in the report, as well as the discussion of the "susceptibilit; of children" in relation to the concentration of lead in the blood, is not a wellbalanced presentation of the issues. It is much too decisive and, so to speak "authoritative." It is based on acceptance of bits and pieces of data, and an insufficiently critical consideration of clinical and analytical procedures, rather than careful weighing of the evidence obtained in prolonged investigations, (z do not expect your people to take the publications of the fettering Laboratory as the gospel, but X do have some right to expect that they be given appropriate weight in matters of this type. Zt is to bo remembered that one point after another which has issued out of this source for the past thirty-odd years, has been confirmed subsequently, the reason being that we have never published prematurely or without making a clear differentiation between established fact and opinion. After a wealth of experience with lead poisoning in adults and infants, before and since the development and application of methods of analysis of high accuracy (so that comparable and precis results could be obtained over the period of years since about 1038), I have stated that we have not seen a case of lead poisoning in adults or infants, in our practice as a group, and in Cincinnati Hospitals, in which the concentration of lead in the blood, at the onset of illness, m s less than Q.08 mg. per 1QQ grama. (We have given a satisfactory rang to this same situation in the urine, but for various physiological reasons this must remain as a range, rather than a point.) I don't think this statement should bo ignored in this discussion, for it represents the longest and almost certainly the most precise critique of this matter that is available. If and when we find exceptions to this, w shall bo the first to publish them, but I shall continue to maintain that the "exceptions" found elsewhere must bo examined critically, on analytical grounds, and on the further crucial issue of whether the blood was obtained and analysed at the right time or at some time appreciably later than the onset of the illness. I might continue ay critique of the report, with reference to various statements that relate to the physiological facts and their interpretation, through th several other sub-sections. Z do not wish to do this, sine by so doing I would convey the idea, which is not intended, that t consider the report to be more than slightly misleading. Actually, I recognize that a great deal of effort and concern for th truth has gone into the preparation of this part of th report. It is not surprising, nor in any sense reprehensible, that certain points which I consider to be crucial, scientifically and hygienically, have escaped th reviewer, or have been looked at with less concern or with a different view;>oint. Another example of this is the statement on page 21, paragraph 2, that, "nevertheless, the evidence suggests that when there is increased respiratory exposure over sufficiently long periods, there is increased lead storage." This is simply untrue.* and it is a most unfortunate statement. On awiy suspect that this is true - namely, that under the conditions of intermittent exposure to lead, such as during the simulation of th duration of the ordinary occupational exposure, some increment of that absorbed flnos its way into the skeleton, when the metabolic processes ara alow, and that this does not get out of the skeleton and the body within the same general period of time, but the experimental evidence gives no clue to such an occurrence. On the other hand, when the exposure is continuous, and sufficient in quantity, there 13 direct and valid evidence of accumulation of lead in the body. It is in matters of this sort, which from the physiological (and also practical) point of view are vital to our understanding of the behavior of lead, * as it has been stated, ^^~ A,i&r. John SSaga }?ag0 3 Ju ne 9 , 1.967 that the data have not been eKaiained with sufficient care, and utateraents have boon jjjad somewhat loosely. In other words, there has not been a clear distinction between the presentation of the facts derived from the data, and their interpretation into opinion. One cannot properly object to the opinions, whether he agrees or disagrees, but he must object to the distortion, so to speak, although unwitting, of the facts supported by data. The other features of this same situation is the critical acceptance or rejection of data. One recogniisess, of course, that it is virtually impossible to do this accurately without direct and precise Inside information. I shall not continue the detailed critique which 2 began, since, I believe, I have illustrated my attitude sufficiently, this is a difficult pathway to tread without appearing to be unduly opinionated and carpingly critical. 1 seem to have gained something of a reputation of the latter type in certain circles recently, and it is not of tho type that I would choose to cultivate. Consequently, it is time for me to get back to my own contributions to the literature of this field, and to the balance and care that are required to have them stand the test of time. I a indeed impressed with tho necessity of assembling, studying, appraising anti publishing a much greater volume and variety of information than has yet boon done. Bineroly yours, Br'dS:wp Robert *i. Kehoe, M.D. Professor Emeritus of Occupational jaediclnc