Document rB2xa1ReDqvBr35dyakGYK8eE

June 18, 1958 D r. T. G eorge Bidder U niversity H ospital of C leveland 2065 A dalbert Road C levelan d , Ohio D ear D octor Bidder: I cannot c a ll to m ind a ll of the data obtained in an im al exp erim en ts, but, o ff-h a n d , I do n ot r e m e m b e r an y th a t 'would a n s w e r y o u r p u r p o s e s . I think I can a ssu r e you that you w ill not be able to find any sa tisfa cto ry evidences of a p recise, co rrela tio n betw een the concentration of lead in the blood o f m en and that in th eir brain, excep t under certain v ery lim ited conditions. This does not m ean that th ere is no such a relation sh ip but that i s is an in con stan t on e, dependent upon the tim e fa c to r . It is a ls o n e c e ssa r y ip speaking of such a relationship to confine one's rem arks to in organic com pounds of lead . When tetraeth yl lead is ab sorb ed , for exam ple,, the lead content of the brain m ay becom e v ery high without any appreciable or m easurable elevation of the blood lead. If th ere- w e r e s u ffic ie n t data: i n a strfficient; v a id e ty o f sdtuatioms,. s o m e su ch rela tio n sh ip would he found. In o rd er to ex p lain m y m ean in g, I m u st d e scr ib e the m etab olism of lead in the anim al o r human body, a s it has been pieced togeth er into a fa irly com prehensive pattern through observations m ade at different tim es and under a variety of experim ental and clinical conditions. Under ordinary circu m stan ces lead is absorbed in norm al quantities daily. . Under th ese conditions there is a pattern of distribution of lead in the body w hereby a rela tiv ely high concentration is found in the sk eleton and m uch low er concen trations a re found in the soft tis s u e s , including the b rain . The blood is rela tiv ely high in lead , as com pared with certain other m eta llic elem en ts that p a ss into and through the body regu larly, because it com bines with som ething (probably a com plex organic phosphate) in the ery th ro cy tes, the m ean norm al concentration being about 0. 026 m g. p er 100 gram s of fresh whole blood. The m ean norm al concentration in human liv e r , kidney, spleen, m u scle and brain a re 0. 13, 0. 02?, 0. 030, 0. 010 and 0. 013 m g. per 100 gram s of fresh tissu e, respectively. W h en ev er there is a significant and m aintained in crea se in the absorption of lead - a s, for exam ple, under conditions of occupational exposure, or m ore p articu larly when the individual or group in g ests lead regularly at a higher than norm al le v e l, th ere is a p r o g r e ssiv e in c r ea se in the lead content of the tis s u e s of the body g en era lly . The g r e a te st in c r e a se in concentration is in the sk eleton , but the soft tis s u e s , including the blood, share in the in crea se. D r. X. G eorge B id d er - (Z) - June 18, 1958 T here la som e question about the behavior o f the brain in th is regard, and it is b elieved by m any people, without suitab le evid en ce, that there is a b a rrier which preven ts absorption into the brain u n less the concentration in the blood ex ceed s a certa in undeterm ined le v e l. This view m ay be doubted b e c a u s e of the fa c t that th e b ra in c o n ta in s le a d n o r m a lly . It would ap p ear th at th er e is so m e eq u ilib riu m b etw een b ra in (and oth er organ s) and the circulating m edium , w hereby under any set of conditions there is a pattern o f d is tr ib u tio n . Thus in fata.1 le a d in to x ic a tio n in c h ild r e n (w hich h a s p ro v id ed m o st of the valid data on human b ein gs) we find relation sh ip s of which the follow ing are ty p ica l:. D istribution of lead in fresh tis s u e s in m g. per 100 gram s (Children) D iver 3 .2 7 4. 00 3 .9 1 4 .4 0 2 .96 . ' K id n ey 0 .6 1 0. 88 _ 2 .5 9 1 .7 4 B ra in Q. 35 0 .2 9 0 .5 8 0. 24 0 .4 2 0 .5 0 Fiat Bone 1 3 .0 10.65 26. 80 1 7 .0 0 17.90 - T h ese c a se s have the advantage, from th e asp ect of lead m etab olism , that the duration o f expo su re ,to lead, has b een r e la tiv e ly b r ie f and fa ir ly continuous, a s com pared with adult c a se s in which the exp osu re is lik ely to have been both prolonged and interm ittent. The tim e factor can disturb the relationships greatly for a num ber,of rea so n s. - It is d ifficu lt to be su re o f the con cen tration s of lead in the blood a t the tim e of death. I know it is greatly elevated in a ll of th ese in sta n ces, but actual data w ere not alw ays available in our early c a se m a teria l, and the later findings a re com plicated sqm ewhat by the therapeutic m easu res that have been taken. I fe e l reasonably sure that I have sa tisfa cto ry data in the file s , but I have not had tim e la t e ly to pu t th em to g e th e r and stu d y them * In th e gtroup o f c a s e s above, without taking tim e to go back to the reco rd s, the concentrations in the blood probably ranged from 0 .1 6 or 0. 20 m g. per 100 gram s to valu es as high a s 0. 40 or perhaps even 0 .6 0 m g. per 100 gram s. This is sufficient to show the trend o f ev en ts, and I doubt v ery m uch if anything b etter than th is g ro ss relationship can be established. Data on adult tis s u e s, gen erally speaking, in relation to inorganic lead, are not available and aae not lik ely to be, for the reason that fatal lead poisoning is a rare occu rren ce in the adult, and for the additional reason that,necropsy m aterial from person s who have worked at a lead trade until death (from a variety of ca u ses) has overtaken them , is hard to obtain. I have been on the lo ck -o u t for such m a teria l fo r y ea rs with but little su c c e ss (for the reason I D T. G eorge B id d er - {3) - June 18, 1958 I tru st that the inform ation which I have given you w ill be of som e in terest to you. Co rdially your s , RAK ef Robert A . Kehoa, M .B . P. S. I take satisfaction in your rem arks about the article on Lead in T ice's sy stem of m ed icin e d esp ite the fact that m y contribution to it was (so far as the w riting is concerned) very sm a ll. I induced Jim Hughes to prepare the a r tic le and I made only a few su g g estio n s. It has m y approval, of co u rse, but the work was h is. R. A. K. KG' 0019310