Document dyE10qyxD1zLYJ7EjypkDQ39

July 5, 1955 Dr. Thomas L. ShipmaiHealth Division X.eader Los Alamos Scientific Laboratory P. O, Box 1663 Los Alamos, New Mexico Deal' Tom: Thanks for your letter of the 24th and for the further information on the type of renal damage that is associated with tie administration of suit able quantities of HDTA over sufficient periods of time. The cellular changes described would seem to me to be quite capable o induction by the removal of -minute, amounts of mineral substances from the cells, and I assume that some such, thing does occur to some degree. Whatever the process may bo,the observation is an interesting one. In tuo matter of the retention of lead under a variety of conditions, and the total quantities which, are associated with signs and symptoms of intoxication, we know a fair amount from both direct and indirect evidence. Some of this is in the literature and some {much in fact) is not. We have quite a number of fairly comprehensive data on necropsy material, especially on the tissues of children fatally poisoned by inorganic lead compounds; we have all that would be desired in fatal cases of tetraetnyl lead poisoning in adults, and some (but only a scattering) on cases of inorganic lead poisoning in adults. The indirect information, obtained, in metabolic experiments is extensive. From these combined sources, estimates could be made that are fairly realistic. There are, however, two jokers in tie situation, and one of these cannot be solved by the use of radioactive tracers. The one lies in the initial or normal or, if you wise, incidental, lead content of the tissues (principally -the skeleton) of the child or the adult at the time one begins to make observations. The error of the estimation here is of the same order of magnitude (proportionally) aa that of estimating the content of. the individual who has been subjected to unusual exposure and is ill. Tie other joker is the factor of time. The amount retained without symptoms or danger of symptoms varies with the rate at which the absorption and retention occurs. One can introduce a relatively small quantity quickly and induce illness, but much larger quantities can be introduced slowly, and relatively large quantities retained, without illness. The explanations for tnese differences lie in at least two major phenomena, whatever may be their mechanisms: 0008601 N9759 Dr. Thomas L. Shipman - {2) - July 5, 1955 (1) .Lead is removed from the plasma of the blood almost quantitatively by the erythrocyte, thereby lowering the concentration (presumably the effective concentration) in other soft tie sixes, at least temporarily; {?,} Lead is removed from the soft tissues of the body generally by the skeleton, this bein ' a sort of second-stage and slower operation than that of the erythrocytes. The lead taken into the skeleton moves slowly in some manner from a part of the skeleton from which it is readily lost to a part from which its escape is retarded (never stopped), or perhaps this is a matter of its being changed slowly into a less labile form of compound or structure, in any case, the matter of potential toxicity is a matter of the type of distribution in t ie body (includin'.: the skeleton) or c- composition within the body (including the skeleton), as well as of quantity or, as you opsak of it, of body burden. The skeleton is sc lar'e, and t o relatively inactive (in t'e metabolic, sense) that the total quantity of lead held in it in relatively inactive form may be quite variable from individual to individual, within certain limits. This is not true to any thin like t'- a evtt at it war; believed to be by Aub and ids associates, since inre is no sue tying as roallv inert stored lead. T.;.ere is always a rave of excretion v io - is determined in the final, sense by toe body burden, but tye time factor involved in the s torare necessitates the introduction . a moving variable into tne equation by which one would calculate t .e burden from t-.ia rate of excretion. I feel sure that a careful study of tne available data would provide us with a suitable equation, but this has not beer; done au yet. I cope to rave a chance to do it, wifi the help of a mathematician, in the not to-.-, distant future. To give you some idea of the extent of t.-e variability I mi, .at mention a few fi-ures from memory. A child exposed to lead from only normal sources will have the concentration of about 1 milligram per 100 grains cf free': bone. A healthy child may nave a concentration of from ) to 1 or 1 milligrams of lead per 100 "mmv of fresh bone, this oom . from 75 to JO per cent of t-o lead in the body. A fatally poisoned cisito may uave from 10 to 40 milligrams per 100 grams of fresh bone, this again constituting 75 per cent or more of the lead in the body; or a child fatally .poisoned by the ingestion of lead over tye period of a few days may ha.v<y s or 4 milligrams of lead per 100 crams of fresh bona, and 50 per cent or less of t.:-e lead ii tua body in the skeleton. All of this concerns itself with inorganic lead. Despite tuese vari ables, however, giver; a fairly constant set of conditions in an. industrial environment, r. definite period of exoosure, the data on the blood and urine of the individual from time to time over the period or an appreciable part of it, and t -e weiw.it and height of the individual, the quantity of lead in the body can bo estimated with reasonable accuracy, on the background of our industrial and metabolic (experimental) experience. It is quite certain that tee meta bolism of lead in the human orranis m is c naracterized by a remarkable degree KJ 0008602 Dr. Thomas L. Shipman - ( :) - July 5, 1955 of stability. The mechanisms,therefore, are subject to but little interruption and variation, and if and when we Suave a bit more information on these mecaanisms, the problem of determining the burden will be very simple. Tr e entire rem e of actual quantities of which I*ve been speaking above (in t-'o entire human body of the adult) extends from 2 39 milligrams or so, in tue normal person, to 300 milligrams in the entirely healthy person who has taken in somewu?.t more than the usual (unavoidable) quantity of lead in bis food and drink, up to 2500 or perhaps as much, as 3000 milligrams in some of fens more "heavily leaded" persons. Fatal poisonin'- may result when tnere are quantities of 1000 milligrams or less in tee body, but considerably ? renter quantities (two or three times) may be* found when the build-up is sue icnfcly aracuai, I doubt if ft ever goes much above f:~e outside figure cf 3000 milliqravue, but one r.n. d devise conditions, perhaps, in W ish it would. I'll .navo to look over the data to see if I am correct in thin, but I ar. not far cii. ho .much for this business, V'hic; 1 did rt intend to pursue -when I started tais. Sincere!'.' your . , KAA ei C. C.: Mr. ivi&rj.red Bowditca Robert A. Ide'-oe, M. D. HE 0008G03 #'