Document e1Qm67y7xV6kDMvnZDwpxodg

I) Llj 75 rf<oj'Oj>!.jTO t v t e h n a t k rut uur)_ w it a t k k _ro% t it c o t iTINt a t io n ^ 7 HE \T\ H <> T~?a~M>ASL 1A . .v ; ; '' r~ Gf`_ ^ A HCH t . Of ij .k r>::v. f.;vo ia i-j ^j aV.s j Yj is 7.-5: ib* > : . s r h t mc in S -. .;a i, H/,m.t h oy ~>; cn: j; r. `r >%- : ;c in x c7' TiT. 1?; 1 v>.i.r>it y Of OS TKK tV. Q/-CT HV** f J . - r -:_7 0 J j-i'I i CUIATK LEAD CGMiVi'NUS IN HZ A 1 8 INil.K t X i'L i .* 14. v : A I. CUNMTK^^ I R#f#r*ncs la r&ads herein to our proposal &*<J on October 3, 1962 In vtilch th f* rural cxp*rl**ntal procedure, together vlth ths details of a specific experiment to be carried out In 1963, eere described in aoce detail. A further proposal, in relation to the continuation of tba experimental prog ra through 1964, n ud on Septeeber 4, 1963. Tba present proposal is conea mad eith tba continuation of tha prof ran through tba calendar year 1963. It saaaa uruveceaaary to Include tba substance of aarllar proposals In tha prasant communication* fufflca It to say that a sarlas of Individual axparlnants has baaa designed to alucldats various fsaturas of tha metebolisa of load, aach of which 1. achadulad to axtand ovar a parlod of tonthi or run, according to a p reda t a mlnad achadula, that la aubjact to alt.ratloa tha facta dsvalop. i { i for sows 27 ysara syatswatlc Invsatlgatloni of carafully choaan human aubjacta havo b*n carrlsd out In ordar to (Wltrulna tha court* of .wants (In mataboltc tarwa) aaaoclatad with prolongad axpoaura to laad cowpounda In low (tolarabla) lavala of doiift. During tba firat thlrtaan ysara of tha parlod, tha rwaponaaa of thaaa aubjacta to laad takan by wouth wars datarwlr.ad. Sinew that tlao (bsglnnlng In HM), tha fata of Inhalad, partlculata laad (In Inorganic fora) ha* baan Invsstlgatsd, tha purpoas bslng to datarwlna tha lnfluwnco (1) of ` doiaga (concant rat ton in tha raaplrad air), (2) of tha alia of t ha dtapwrawd parttclaa, (3) of tha apwclflc cowpounda of tha dlaparaad laad, (4) of tha Tha tltla of tha projact ha# ban altarad slightly at this tlaa. In ordar to put it in tomwwhat worn prwclaa tarns. ^.IA 11571 o i i4 1 -a- overall duration of the exposure, end (5) of the intermi ttency of the exposure, versus Its continuity In ties. The orlnglnsl intention ess to proceed with experiments in the sequence Indicated above, Hoeever, after the completion of the initial experiments on dosafe, and the partial Investigation of the Influence of the site of the particles on their fate In the respiratory system, a claaor arose In air* pollution circles for the consideration of a standard for the quality of the ambient air of cities, eith respect to Its lead content, and It *aa believed to be else to revise the experimental schedule and to establish, experimentally, eith ell reasonable speed, the extent of the accumulation of lead In the human body during essentially constant (24 hours per day on 7 days per meek) respiratory axposure, aa contrasted eith the presently known effects of such sxposuro to ths stss experimental conditions during sn eight-hour, five-day schedule simulating that of industrial employment. The first experiment tomard this objective eaa Initiated In January 1959, and aince that tire, five* experimental subjects have been employed productively* in obtaining the necessary Information, Ths experimental procedures and the results obtained up to s certain point in time, have been reported to the sponsors of this experimental program. The full experimental program ess supported Initially end for ten years by Ethyl Corporation alone, dines 1949, part of the coat has been borne by I. duPont de honours end Company. In ths year 1993, as ths result of tho interest of other organisations In the outcome of these experiments, and of desire on the part of the Director of the Kettering Laboratory to spread and thua Au> additional subject, after serving for about months, mas found to be unsatisfactory, and eaa discharged, ehlle another eaa discharged after a very short (10 day)trial period. t I I nn4i)awi  ]>! ' L IA 115 7 2 I1MWS -3- to stablllte the financial aupport of the experimental program over p* rl od of ysara, the financial burdan of thl d=- i 11 d 1 y cot]/ *ork eras shared In substantia Uy equal portion* by four organl is t Ions, nanely Ethyl Corporation, S. I, duPont <S Heaoura and Conpsny, International Lead Zinc Research Organl utlon, and th United States Public Health Service, thereby providing * budget of approximately $100,000 per year. It la the purpoae of thla propoeal to seek the continued aupport of International Lead Zinc Research Organisation during the year 1943. The Present Experiment The experiment no* In progrexa, ehlch la to be continued Into and probably throughout 1963, haa been deacrlbod In detail In our propoaal dated Septeaber 4, 1963. A change In the procedure area Introduced, boeever, aa deacrlbed In our progreas report of April 19, 1964, In order to take advantage of the reaulta obtained In the early part of the experiment and, hopefully, to expedite the experimental work for the cor.ver.lcr.ee of the sponsors. In vlaoallxlng the loglattca of the experimental dealgn, the sequence of the obaerva11one la outlined briefly herein. Subject M.K. entered upon hie achedule of expoaure to lead In the atmos J phere of the chaaber for the first tine on October T, 1963. He aaa subjected, for 3 hours, to the Inhalation of air containing, approximately, 9 alcrograa* of lead,as the ae*quloxlde,per cubic aster. He folloeed this reglaen on every other day until January 13, hn the length of ttae spent In the chaaber, under the aaaae conditions, saa hours per day on alternate days. (The choice of lengthening the hours Instead of Increasing the concentration of lead as nade for the reason that no deaonetrable effect upon this Subject's output of lss4 t In ths urine (or upon the concentration of lead In hla blood) *aa observed. Ho period of "recovery" as required therefore, and as could proceed to deleralns, experlaeiital ly, vhalhar an effect could be obtained by aterely lengthening ths * Sl'-i-r ' u ; . . a.'yosc.vr.sr.w Xine***-**xg-- . ..... . riii'ii.irT-'jii-n-r-- ............. ................. -im - TM -j T" i L 1*11573 -4 - 3 perltx1 of exposure, this being the primary ltaue of these experiments.) Ths exposure of Subject K.lt. to air containing 9 mlcrograns of lead per cubic meter, for 6 hours per day on every other day, began on January 13 and continued until July If, 1964 by ehlch tine, again, no evidence of an Increase in the excretion of lead In his urine (or blood) had been obtained. (The duration of this phaae of the experiment aa extended, deliberately, beyond our earlier expectations In order to sake sure that any alnute effect could be found through a atallstlcal analysis of the results of an adequate nuaber of observation*,) On July 27, 1964, Subject H.I. m subjected to 9 hours of exposure In the respiratory chamber to the sane conditions that had prevailed previously. He has continued since that time on this schedule. The data will be subjected to statistical analysis ahen a sufficient nuaber ere available. The eecood Subject (S.S.), who had replaced the earlier, unsatisfactory subject, and whoae schedule of otherwise parallel observations waa Initiated tardily and would therefore continue out of atep In tine, entered another respiratory chamber on March 2, 1964, whare h* wa* subjected, for 3 hours per day on every other day, to the Inhalation of air containing 9 alerograms of lead (at aeaquloxlde), He, likewise, failed to ehow any reaponae to the experimental exposure during the period of 24 weeks, and on August 17, 1964, hi* reglnen wa* changed to t hour* per day, on every other day. He continue* *t present on thi* schedule. This experiment, Involving the two subject*, H.K. and S.S., will continue Into the year 196S, and after having gone through the cycle Of 3, , 9 and IS hour* per day on every other day, ovar sufficient periods of time as data rained by the <h i1c <*, each subject sill go on Into a similar cycle, Involving a different (higher) level of lead concentration in the air of tha chamber. y uch tch portion of th cycle of ipour on (h rtiulti of the LIA1157 A ;V -. ... . .u . - J-f VAlirlir.i' rr -5- previous portion, it should t possible to determine, clearly, by the extrapolation of these results to 2< hour* per d*y on 7 days per week, the approximate degree of the physiological tolerance of healthy human aubjcct# to readily abaorbable, particulate lead in the atmosphere. Coapletlon of Preaent Experiment and Dovelopaent of future Program Reaulta wfclch will pereit the termination of the experlssente designed to teet the influence of tine (Intendtlency versus conatancy) upon the metabolism of lead, cay, elth good fortune, be aecured in IMS. (It la likely, boa-ever, that some further time *111 be required for bringing theae observation* to a definitive end. Ko experimental *ork of ainllar leport la In progreaa, so far a* 1* known, and It would be highly undealrable to discontinue the effort to obtain conclusive reaulta.) If this ahould be the case, the next logical step In the prograa, froa the aspect of the practical need for information, would seen to be that of A Investigating the rule of the chemical and physical characteristic* of specific compounds of lead dispersed In air upon the absorption, excretion end retention of lead In the body. (The sulfide, the sulfates and the silicate* are of apeclal Interest In this connection.) Preliminary work In preparetlon for the Initiation of these experiment* can be made prior to the terelnatlon of the preaent cycle of experlnent*. There need be no lose of ties, therefore, in the progress of the ork, provided soee of the sponsor* agree to "the next etep," end nak* financial provision for auch an eatension of the work, A detailed (supplementary) proposal *111 be mad* at the proper time, veil In advance of the termination of the preaent experiment, *o a* to anabl* the developmental *ork (working out the method of obtaining and maintaining appropriate experimental conditions within tbs respiratory chamber*) to be done. ye?* W'iM-'E1.*1 W* LIA11575 l financial Conalderat lorn and Budget /or 1963 Sine* the experlr-ental program, n outlined above, haa had much the atce technical methodology for a number of year*, tt nay be aaeuieed that the coat of the conduct of the work will change little. However,certain new factora enter upon the ecene within the year 1643, and all of the aponaora ahould be aware of thee. Tlrat, there will be a new Director of the Kettering Laboratory within the year, and elnce thla experimental program haa boen developed and aupervlaed la detail by the preaent Director, reaponalblllty for lta guidance will have to be put la other banda. It haa been regarded aaunwiae to do thle la advance of the appolnteent of a nee Director, becauae of the need to fit thle prograe Into the atruclure and objective# of the nee reglaxe. Every effort will be eade by the preaent Director to enaure lta continuation In an affective eanner, but there may be ebangee In direction or eephaale. Second, the preaent grant of the Public Health Service will reach lta termination In Auguat 1963. There la reaaon to believe that It wl 11 be extended, but there la no guarantee, and here again, the eltuatlon will newd to be examined by the Individual aponaora. If the progrea la to be maintained. Aalde from theee mattere, which, admittedly, are crucial, but are not likely to be difficult of aolutlon (the day to day work la In good hand#, and no fundamentally different Idea# or procedural will have to be applied or developed to carry It on, along presently productive llnea), (There are ample opport unit lee for the development of nee Ideae, new technique! and new'objective#, but the work of paat yeare haa aerved to poxe certain apeclflc qoeetlona to be anawered and, at the aame time, haa provided metbode whereby theee anewer* can be obtained. The continuation of the prugran le In Jeopardy, therefore, only becauae of financial uncertain! lea. tt la to be hoped thet thla uncertainty will not prove to be aerloua, i i '; .^'ggg'wwgxs LIA11576 -eaa.-aC.ikJ.v--,..":- y^-nfeutt-ii- -7 - since, Jn our view, the questions at Imix are not only answerable, but also are la need of anawre.) On the Uili of the expenditures accounted for thus far In 1061, and of those anticipated during lha remainder of 1064, and on the assumption that > additional developmental eork ahould ba dona In 1966 (to provide tha Mini of dispersing o m of tha lnaolubla compounds of lead, aa partlclaa of uni for* at*e, In tha air of resplratory chaalar, In a known, atabla and uniform concant rat Ion), tha following budget for 1963 ia recommended. It lncludaa certain modest but aaaantlal locraaaaa In salaries, wages and othar alrcellaneoua coats. Personnel Reagents, (laaiaara, allowances to subjects for food, ate. Overhead (all othar coats prorated to aalarlaa) $ 63,000 7,300 43,000 Total $107,300 On the aiauapilon that private funds *111 b* forthcoming in tha aaae aMount a aa In previous years, and that public funds aay not be available after the termination of the present (rant, It aa/ be preused that tha financial outlook In 1963 *111 ba as folloess Itbyl Corporation I. I. dupunt da kaaoura and Company International Laad Zinc Research Organisation V.*. Public Health Sarvica - AP 00220 $ 23,000 23,000 33,000 17,300 Total $102,300 Such funding of tha project null ba inns $3,000 last than tha estimated requirements. Provision for this shortage could ba made Individually or Jointly, prior to January 1963, by tha private sponsors, or 11 may be postponed In favor of reviewing tha situation within the year 1963. Datat September 10, 1964 Hotter t A. fcshoe, N Tb, Director, Kettering Laboratory