Document 0q75KJVvo9Zj821DYZ912meXO

July 22, 1904 Dr. John H. Ludwig, Chairsan Storking Group on Jm && Coatalautlcm Department of ik?altk, Education ami Welfare iiotert a. Tuft Sanitary ijegiaesrins Center -SQ/G Columbia `arkway Cincinnati, Ohio (43230) Door John; Z hast to discuss Dr. Oolasuith's editorial suggestion with Mss and you, before it ia too late <1 aa leaving for ay vacation on July 31 to he gone until deptaadier 2). 1 doing so Z a not to retain what has bee written, without change, but rather to avoid peculation and controversy in a ,.art of tiw? report which should be, so far os possible, a simple sutemttt of the facte. With wioruncu to Jams' aossasut about the fata of the load alkyls in the body, and the possibility (which is not that, but ia rather a certainty) that their .:jtouoiisu in the body and their distribution in the tissues differ fro that of the inorganic coapomwis of lead, 1 have this to say. While a great deal 1* known about the initial and ultimate distribution of the alkyl load ceopovnds in the tissue, it is irrelevant to this discussion. While we have left .the Quantitative repre sentation of tha alkyls in the a&bl&nt air soajewhat open to Question, wu have shown, by ite acta in this report, that tae Qyantitles are saIX to the point of practical insignificance as a factor in the exposure to lead to bleb ti general .population ia subjected. There Is, therefore, no virtue, in raising this issue 1 this report, beyond the treatment that has been given to it,and certainly it would be a source of ambiguity in the discussion on page SO la order to aphasias the foregoing point still further, let w ay that the _aat five iitMjja of John's statement in the second 'paragraph of hi letter should be deleted in any case,for they suggest that there la little or no information on the .cants raised. 11m facts a w otherwise* A fair sixed copulation of aen have been unpaged in the manufacture of tetraethyllead for many years (tetrowethyllead for only a lew years, relativey), Ho sroup of ssea in the lead trades has been investigated o thoroughly as this.,. The following facts have been established beyond the slightest doubt. The response on the part of the urine to the absorption of tetraethyllead is prompt and clearly indicative of the rate and extent- of such absorption. This 1st, in fact, the as by which hygienic control d freed from lead intoxication have been maintained. (Sows of the evidence has been published, but it.has been too voluminous to present in brief articles. I have tees gathering the data for a stonograph on the entire situation.) The lead content of the blood, in association with the absorption of tetraethyllead, on the other hand, is valueless in determining the rate and extent of the absorption. Even in fatal tetraethyllead ..oiaonlng, the concentration of lead in the blood remains within normal limits, at a fix* when the urine aay contain 1 to 3 tsg. of lead per liter. I have avoided the discussion of the miters in the part of this report which 1 sutmttted originally, for such editorial change as might he desirable, not because there is not much useful information, but, ratter, if I aay repeat, because it is KE" 0004705 r. John Luvtwig - (2) - July 22, 1B&4 irrelevant. The third paragraph of Dr. Goldsmith's letter, la y opinion, makes no useful contribution to the discussion. It would, indeed, be advantageous to have or ana better information than is now available cm the 'body burden'* oi lead under Varying coQoitloAs, and to have some feasible neons of obtainintf such information from the intact (living) organism. This we arts attenptlng to do, with true precision, but we have not achieved this objective an yet, and I see no advantage, at this point, or in this report, of dlacussiOK it in relation to the rgost difficult phase of the problem - namely, the oinor variation that occur aiaong persona in the "normal" group. Ute know full well the general facta in this matter, ffhat we do not know are the nuebera - the quantitative relationship in precise mathematical terms. We shall never obtain the by wishing for the. Thanu general facts are 'these: (1) The oouy D-annii increases with every crease in the current level of the abwortlon 4>i iua. That 1, there is an equilibrated relationship between the intake, the output aitu tiie retention of load in the body. In the simpiost terms, tin body buroen x* *o* wnen tiw current rat of intake is low; it is relatively high when the current rut of intake AS relatively high. . <2 ) The cost cius which wo have to tin qisantitativ# relationship in ttm intact .nusun bony is toe concentration of lead in one of the tissues (which ere in equilibrium wits each other) namely, the blood. The catiuoatital expression of this relationship, considering the variable rate of the metabolism of lead in the several tissues, especially in the skeleton, cannot be stated at present. believe it will be -ossiblo, 3oaa, fo ;.-ufe this relationship into a mathematical form which will give reasonably uucquiitn expression to tin principal relationship, i.o., that which exists between ism blood and the skeleton (this la the important one quantitatively, for the reason tii.it under any set of circumstances involving inorganic load, from about 90 to about J3 per cent of the lead in tiu body is found in tb skeleton}. If, therefore, we can iau an indirect means of getting at the lead content of the skeleton, ws shall know, for ail practical purposes, the "body burden'' of load. How, I iubmit that no useful purpose will be served by including this discussion ia this report, and for this reason X left it out of ssy assignment. I regrot that X rust also object to the next paragraph of the letter. What John says here is definitely untrue. Xfc is only when the exposure to lead ia intermittent and at ihu name ties abnormal (as in occupational exposure to lead) that a now level of equilibrated "steady state" is reached. If the exposure is significantly above the usual or normal environmental level and is maintained constant, accumulation of lead in the body occurs at & constant rate which ia detersiiaod by the extent of the ueparture from tit usual (normal) levil It is possible that a new level of the "houy burden" is reached ultimately, but there is no evidence, as yet, that this occurs. The presumption is that the body burden continues to increase. This is, reciseiy the problem of lead In food and drink and in the ambient air. These represent continuous (albeit somewhat variable) exposure, and, as such, they have to bo a ,-raised against a lifetime (the human lifetime) with respect to their potenti alities for harm. John's comments with raapect to the section on lead Intoxication seea to ao to Dr* Jo h n iMKtWig - ( 3 ) - Ju l y S3 , 1904 d a t u m the issue of what is lead Intoxication. Wo arc not talking about exposure or ta criteria of exposure or absorption, but about clinical picabla. What has bean s & U on this tiubjeat is just about as si&l& ana factual as it can bo made. Obviously, there is much ore to bo saia, but a onagrapb would be required to say it* In sy book, the uscretion of prophyrins significantly in excess of the n o m i rang, when it results trota the Intervention of lead in the a t m U u s of hemoglobin, is lend intoxication. I nave never seen any evidence of an increase in the excretion of porphyrins in relation to the absorption of load, until a critical degree (range) of absorption is reached. I cannot be that certain about the juvenile loras of erythrocytes, since they represent a noa-speclfic response to a variety of stimuli (to a such roster decree than that of the porphyria nctaboiiso), but the fact xwataiw that they arc, in fact, important phonosenn in the clinical manifestations of lead intoxication. I offer no objection to the alteration of Table Vl-C-i end Vf-C-3 as proposed by Dr* Goldsmith. X do not agree that the la* two eolusBHt in these tables tend to confuse the facts, but they do not contribute anything that is not evident otherwise, and that is enough fur m * If I u&y susuaari**,in one brief ctatotaeat,ail that X have said above in detail, I recognise that the dlacosaion in C. Sil'octs of lead on Sim is brief, and that there are any points that have been omitted, >iml aar.y mure that could bo discussed at length* Zt was jay purpose to state the facts in the briefest, simplest and least arguable tenor. This, X thought, was necessary, and Z have not changed *y view. If the eot&senia of Sr. Goibessith are injected into this discussion, a great deal uaru will have to be aid, us I believe my letter will indicate. I would consider the enlargement of this report, to this extent, to bo wholly unjustified, Sincerely your, ihiSjvr cc - John It, Goldsmith, M*D, Jo lia isaga Robe rt ilo rto a , M.X). Sobert A * Schoe, H *lt * Handwritten note to Dr. Goldsmith - John: I'm sorry to have to differ with you so nearly completely, but I do consider it necessary to do so. I was very careful in my write up of the matters you .criticize not to say anything that was not fully documented. There is no point, so far as I can see, in talking about the desirability of knowing more about the body burden, or the method of securing this information. The latter is not so simple as you suppose You can indeed analyse bodies, but how can you determine the factors which have influenced the quantities found? Because of this difficulty which is virtually insurmountable, we have resorted to dynamic balance experiments to obtain the answer. RAK