Document nNprep5m8G0kLykrY6YQBZgn2

' *4 I L an! maasftopSeisi AmmmmimMwm A N D R E W FLETCH E R .PR E SIO E N T K . C - B R O W N E L L , VICE PRESIDENT vJ . A . M A R T I N O , V I C E P R E S I O E N T M . M Z O L U E R , VICE PRESIO EN T R O B E R T L1NOLEY Z IE G F E L D , SECRETARY-TREASURER 60 EAST 42nd STREET NEW YORK 17.N.Y. July 21st, 1958 MANFRED B O W D 1T C H DIRECTOR O F HEALTH AND SAFETY Robert A. Kehoe, M. D ., Director Kettering Laboratory of Applied Physiology, University of Cincinnati, College of Medicine, Eden Avenue, Cincinnati 1?, C-hio* ' Dear Bob: I need not explain th is delayed word of thanks for your exhaustive and in terestin g le t t e r of July 3rd* I t was in the stack on iry desk when I returned la s t week from a four weeks absence (in the course of which there were relaxing reunions with A lice Hamilton at Washington, Paul at Salt Lake, Red at San Francisco, and Tom at Santa F e), and I only now have had the time to absorb a l l that you have said* I don't know whether you r e c a ll Paul' s famous "Abraham Lincoln story," hairing to do with correct observations and erroneous deductions, but portions of Moeschlin's paper seem the perfect example of th is combination* Even though i t dates back some seven years (a long time for one with my fo rg ettery ), I w ell remember the walnut sh e ll matter* How anyone could confuse the hazard here involved with that alleged to inhere in leaded exhaust gases i s quite beyond me* I have been much in terested to note the increasing conservativism anent EDTA, of which Harriet Hardy's attitu d e i s an outstanding example. My own thinking has under gone a sim ilar rev isio n , so th is su its me fine* You say that you have no knowledge of the Swiss version o f th is product* I have a sin g le amoule, labeled "Calcium Hausmann," and could probably get more from the same source i f i t were wanted. I once asked Hervey Elkins i f he thought an analysis of th is would be p ro fita b le, and he was not en th u siastic. However, i f you think otherwise, I would be glad to see what I can scare up for you. I t i s fortunate that the German for "rat" i s "Ratte". Otherwise, I fear that the Herr Geheimrath (of whose d iv in ity I am w ell aware) might take serious exception to your omission of h is terminal "h". * Knot-ling that i t w ill in te re st them, and fe e lin g sure that you w ill have no objection, I am sending copies of your le t t e r to the Boston pals to whom I am indebted for the Moeschlin manuscript. Robert A. Kehoe, July 2 1 st, 1958 - 2- P* S* By way of c o d ic il, here is a copy of l-beschlin's reply to the le t t e r from Brugsch of i-Jhich I sent you a copy* . m H E 0014 9b9 June 3, 1955 Solothurn, May 2U, 1958 Dear Dr. Brugsch: Many thanks for your le t t e r of Kay 15, 1958 which interested me very much. In answer to your question, I can t e l l you that since iqy publication in the Schweiz. Med. Wschr., August, 195?, four additional cases which termi nated fa ta lly have been reported to me, due to kidney damage in the course of Ca-SDTA treatment a severe nephrosis occurred with fa ta l termination. One case was reported to me from Zagreb, Yugoslavia; one from Germany; and two addi tion al cases from Switzerland. Five cases altogether are known to Suval at Lucerne. I r e a lly b elieve that one has to be very carefu l. We are now carrying on extensive c lin ic a l investigation s which w ill be published la t e r , in which we further experimented with various dosages on a l l sorts of patients with severe Cancers and other d isea ses. I t has become apparent that i f one reduces the dosage to 20 mg./kg body weight, kidney damage i s not observed, as for instance, with a dosage of 1.2 g. d aily for a p atient weighing 60 k g ., when we gave i t for three days and then interposed a treatment free period for three days. Perorally the drug, while le s s e ffe c tiv e , i s better tolerated , and one is .ju stified to in crease the dosage to 30 m g./kg., in other words, again a total of 2g. perorally. I b e lie v e , however, th a t 2 g. intravenous per day i s perhaps somewhat too dan gerous and p articu larly i f U g . i . v . are given as previously has been stated by American authors that in certain cases a fa ta l coimplication could occur. I am enclosing below a copy of our therapeutic schemes as worked out by us for the physicians in Switzerland. Ca-Sodlum EDTA (Ca-Tersenate) Ion exchange (1 Ampule Calcium Hausmann fo rte - 2J4 g Versenate - 250 mg. Ca) Dosage: a) i.v * : not mere than 20 mg. Versenate per kg. body w eight.: (for instance,160 kg.' patient - 1.2 a Ampule in /00 com $% Glucose or Laevulose, drop infusion) b) peroral: Adults 2 g. daily permitted Children 30 mg./kg. body weight per day. Duration; Three days therapy, three days interm ission, then repeat according to c lin ic a l picture, in 5-10 Courses. Urine Control: In the presence of 2* albumin, stop immediately! In the presence of p re-existin g renal damage, be ca refu l;1 Onehalf dosage. Looking forward to hearing from you again la te r on, I remain, With best regards, (Signed) S. Kbeschlin KE 0014,960 July 3, 1958 M r. M anfred Bowditch Lead Industries A ssociation 60 E ast 42nd S treet New York 17, New York D ear M anfred: ' ' `............ > I retu rn to you herew ith the typed and the Therm ofax copy of B rugsch's tran slatio n of M oeschlin's paper on lead intoxication. I am grateful to both you and B rugsch fo r your respective contributions to m y inform ation. I was som ewhat fam ilia r with M oeschlin's paper because of a se rie s of discourses sent along to m e by another Sw iss physician, R. F a tz e r, who has needled m e, from tim e to tim e, as the arch-enem y of Sw itzerland in having denied the h a za rd of the d istrib u tio n and use of leaded gasoline. In F a tz e r's eyes the cases d escribed by M oeschlin w ere m ore im portant fo r having proved me wrong about this lead hazard than they w ere fo r th eir dem onstration of the bad effects of calcium v ersenate. Several Swiss physicians, .still under the influence of Z anger, now deceased , who w rote on th is s u b l e t out of no know ledge a t a l l t in 1923,. and was resp o n sib le fo r having leadygasoline banned fro m S w itzerlan d e% fienm e Pan ^Ihs lifted tem p o rarily during the w ar, and then this action was sustained after the w ar, there was a.sto rm of protest from sev eral so u rces. It died down to som e extent, but has p e rsiste d in spots. P ro fe sso r Zanger was regarded as the g reat authority on such hygienic m atters, and as you know,the H e rr G eh eim ratb P ro fesso r speaks with the voice of God and is never wrong. I have visited Sw itzerland th ree tim es to discuss this m atter with the authorities and have been consulted by them h ere, and I talked tw ice with Z anger, who was p rep ared to a lte r his views som ew hat, but not his pronouncem ent. This is a long sto ry into which I cannot go h ere. I can only say that you could have no idea of the em otional content of this battle in c ertain m edical c irc le s in Sw itzerland unless you had been involved in it. Now a s to M oeschlin's c a se s of lead poisoning, I am p rep ared to accep t th e ir validity, but let m e call your attention to the im portant fact that these have nothing to do with the problem of the contam ination of the urban atm osphere with, exhaust gas containing lead. The p ertin en t cases involved exposure to the deposits within the in te rn a l com bustion engine. When these a re rem oved by d ry o r hot m ethods,the lead content of the a ir in the im m ediate vicinity is contam inated with finely divided carbon and finely divided inorganic lead compounds (the c h lo r bromide* sulfate, phosphate and carbonate, usually in variable proportions dependent upon the p recise natureef the:fuel and the fuel additives). I called attention to the problem of the garage m echanic years ago, and within the industry I have done everything I could, when m echanics worked m ore o r less continually a t this job in handling fleets of c a rs , to surround this operation with suitable KC 0014361 \ M r, M anfred Bow ditch - {2) * Ju ly 3, 1958 ' with p recau tio n s. You w ill re m e m b e r, p erh ap s, that/the introduction of an unventilated m achine to b last out the carbon of m otors with nut shell o r other ab rasiv e m a te ria l, th ere was a se rie s of cases of lead poisoning, which led to a new design of the equipm ent with suitable ventilation. When a m echanic does th is jo b o c c a sio n a lly by o rd in a ry m e a n s, he n e v e r g e ts in t >tro u b le , but if th e c irc u m s ta n c e s a r e such th a t he in c u rs d aily e x p o su re to- lea d f o r so m e hours in this w ork, cases of poisoning o ccur. This can be prevented, and in general it has been prevented in the establishm ents where fleets of cars a re dealt with. I call your attention also to the fact, which we pointed out y ears ago, that the garage m echanic sustains other types of exposure to lead in relatively sm all q u an tities, g en erally . Ko does a bit of soldering; he rem oves paint (the u n d er coats of which a re high in th e ir lead content) from cars, and repaints them from tim e to tim e ; he sm ooths fe n d e rs and c a r b o d ies w ith m o lten lead allo y by g rinding th< cooled m etal to a nice even surface; he handles and som etim es rep airs storage b atteries. These things, in the average rep air garage .result in som e absorption of lead, and undoubtedly, the exhaust gas in the re p a ir garage is often high in concentration. . Th total effect is to differentiate garage m echanics, as a class, from the handlers and Users of leaded gasoline, by reason of a barely significant in crease in the m ean level of th e ir U rinary lead excretion, and by a somewhat le ss pronounced in c re a se in the lead concntrtion in th e ir blood (the u rin a ry v alu e is about 0, 05 m g , p e r l it e r in c o m p a riso n w ith about 0 ,0 3 m g. p e r lit e r fo r o rd in ary p erso n s with no occupational lead exposure; the blood value, barely significant statistically and only so because of the large num ber of observations, is about 0.038 a s differentiated from the norm al level which is slightly under 0 .0 3 m g, p e r 100 g ram s). And yet the g arag e m echanic r a r e ly re a c h e s the lev el of dangerous lead absorption and alm o st n ev er has lead poisoning. With the exception of the ra re m an of this type whose reg u lar job involves 3ome special type of exposure to lead, the garage m echanic is not involved in a lead hazard in his occupation, because m ost of Ms jobs do not resu lt in any significant exposure. . ' :, . ' .' I shall not go into the quantitative asp ects of the exposure of the urban population, and some of its special groups, such as parking garage attendants and traffic policem en, to lead from the exhausts of autom obiles. This is a very long story, on which, as you know, we have worked fo r m any y e a rs. Suffice it to say that this problem , for a num ber of good quantitative reasons, is of g reater im portance in the USA th an e lse w h e re ; th a t we have in v e stig a te d it e x te n siv ely fro m th e two a sp e c ts of (1) the lead content of the a tm o sp h e re , and (2) the evidences of lead absorption on the p a rt of exposed p erso n s; th at we have good, sound data on both sid es, and in addition we have studied and a re continuing to study the fate of inhaled lead (as we did ingested lead, e a rlie r) so as to establish physiological standards of safety. K 0014962 M r. M anfred Bowditch - (3) - July 3, 1968 The foregoing m atters will not be news to you, except perhaps as to th e ir scope, but I speak of them to set the record straight. Our friends in Sw itzer land, including M oeschlin, a re talking about lead exposure in non- quantitativ e te rm s, and a re discussing the lead m etabolism in tlje te rm s of the early nineteen tw enties. I su sp ect that M oeschlin is a fajtly good clinician. He m ay even be a brilliant one, but like m ost European doctors, he m ixes observation with in terp retatio n to the point w here it is difficult to differentiate one from the other, and while he does not confuse the issu es com pletely, he talks about exposure to tetraeth y l lead in connection with the work of a garage m echanic, apparently without recognizing that the overwhelm ing proportion of the lead with which these m en a re concerned in a m otor is only an inorganic, therm al decom position product of tetraethyl lead. The evaporationcf gasoline spilled o r leaked on a hot engine is alm o st negligible, while the tetraeth y l lead which e s c a p e s fro m th e ''b r e a th e r , " a s w ell a s the c a rb u re tio n sy s te m , is of such little m om ent as to be h ard to detect. The lead deposits within the engine, on the other hand, dependent upon th e ir total quantity and the tim e at which they a re being rem oved, m ay contain gram s of lead along with m ore gram s of caked carbon. It is this failure to explore the facts and the glib theorization about the so u rces of lead exposure without having the facts, that fru stra te m e. We a re all guilty of this to som e extent in the p ractice of clinical m edicine, but one would su sp ect that we could le a rn its p e rils , and be cautious in o u r w riting. The clinical descriptions given by M oeschlin are not those of tetraethyl lead poisoning, and it is apparent that he has never had experience with tetraeth y l lead poisoning. If his analytical findings a re to be tru sted , these a re sufficient to prove this point, since the concentration of lead in the blood in tetraeth y l lead poisoning is never in creased m ore than slightly, w hereas in his cases the blood levels w ere in the range associated with the absorption of dangerous quantities of inorganic lead. Now as to the significance of the outcom e of th ese c ase s in rela tio n to the use of calcium v ersen ate, I am not in position to question M oeschlin's conclusions. Two of the cases seem to m e to point to the c o rre ctn e ss of his interpretation. Two points, how ever, need to be m ade. The m ost im portant of these relates to the dosage of the agent, which by our standards was high. I believe I would be m uch m o re cautious in my u se of it. It has been dem onstrated that low dosages will accom plish much of the desired purpose, and m oreover, we, here, have had no trouble a t all since the f ir s t two serio u s cases (children in v ery bad condition) appeared to respond badly to this therapy. The o th er point re la te s to the p rep aratio n used (the calcium sa lt along) with which I have had no experience. It m ay be ju st as good as the disodium calcium p rep aratio n . Xhave no good reaso n to doubt the satisfacto ry quality of the Swiss p rep aratio n but, on the o ther hand, I have no knowledge of it. In any case, M oeschlin has gone to the extrem e, I think, in denouncing the use M r, M anfred Bow ditch - (4) - Ju ly 3 1958 of versene altogether. That it should be used with care* and that its use had b est be avoided, in c e rta in cases*- seem s/ reasonable. C ertainly A m erican experience as thus fa r rep o rted , does not su p p o rt'th is opinion.. You will . recognise,T believe, that I have not been one of the great enthusiasts for this form of therapy, largely because it accom plishes but little m ore than seem s to be accom plished by nature in a little longer tim e. I believe it to be advantageous in the:treatm ent of the often disastrous lead intoxication of early childhood, which i s .really its crucial: te s t.. T here is , how ever, no evidence that it saves lives. It appearaito shorten the illness,and so is advantageous, e sp e c ia lly , sin c e i t se e m s n o t, of-,it s e lf, to b e d a n g ero u s when u se d w ith a p p ro p r ia te .c a u tio n .. - . . , .... . : - . . . T here is one other asp ect of this m atter: which l am su re you would expect me to m ention nam ely, the relationship of.theee observations to the indiscrim inate use of dis odium -calcium versenate in lead poisoning and in the hastening of the lead excretion of persons whose, exposure to lead m ay be potentially o r actually dangerous . Since this .is being done in this country with little o r no m edical su p e rv isio n , it se e m s lik e ly th a t we a r e indulging in :a d a n g e ro u s, a s w ell a s a foolish and im m oral, practice. . : . ; I th in k I have sp e n t enough of m y day on th e s e c o m m e n ts, .and I! d b e tte r g et to work elsew here. hope they convey my views reasonably well. .; . Sincerely yours, . RAK e f . . : .. . Eobert A . Kehoe, M, D. i 1 . , r) ' . ^ .. K f 0014384