Document zzvjn7oaa5wby23L0jezQvYqR

^ - -......... - munttidnA si i mni i i i<iiivrM&si*ti*Miittiiaaiiaito tOHMOl P. PA0TM ChMOTOM 9ptatr 1, 1965 TOt All Hecbera of th LU-UlflO Lead Beelth and Sttrt; Caoaitteo TKMx Doo 0. Fowler SCajKTt 196s Budget Huttos of lead Health ud Safety Coelttee} October 1, 19651 Sixty Ext Clubi Eev Torn City lead Health and Safety Coselttee vlll bold it* 196 Budget Heating at the location pacified above on Friday, October 1, a* preeloualy announced. Project Smart** and Krtenaloo Proposal* to be eon*Id*red at the Meeting re enclosed cr el11 be Issued a* toon aa possible. The oev Project SuMnarle* replace the Catalog* of Research Issued prior to previous budget Meetings. We hope you vlU find thl* nev fonset mo t * convenient for project revlev. please bring the enclosure* to the Meeting. Project or *cal-annual reports are being foreerded to you as soon a* they are received by XLZRO. >fcny bare already been sent, and v* hope to be able to forward Ibe reaalnder In tlae for you to rerlrv thee prior to the Meeting. An Agenda for the Meeting la attached. V* look forward to seeing you on tha 1st. eci Lead Technical Steering Coolttee focli a. Agenda Including lilting of enclosure* b. HZfO Project Smarts* (for all currently active project#, active project* being ceosldered for extension and nev projects being re* OCBBSOded). fe Datet 1966 BUDGET XEZTDO of rax LIA-IUflO LEAD BEAUB AID SAfJTT OOMOTra fridayj October 1, 1965 Tiaej 9t30 a.a. FUet Sixty Mut Club, 60 tut V2 8traet, Nv York City u. APOn* f I. Called To Order z XX. Approval cf Mlautee of Pravioua MtHlif * HI. lead Infonset loo Progrea. IWport aad Budget for I966. ijr- IV. (felted SUtti Public Health Service Syapoelua 00 Total Load Ccataalaatloo of the Envlrooarnt J v. Becent occurreocea In the pmi VI. Other bualaees V- vn. 1966 HZBO BUDGET F" Fund# Proposal or r Project Reoueated Work Statement Tltla and Contractor 1**75 35,000 Yea Hwaa Expoaure to Particulate lead Coopouoda la the Air Ubder Expert* aental Coodltloos; Ublverelty of ClaclaMtl 1 1H-79 Ro m Ro Toxicity Teatlag for Orgaoo*lead Ccapovnde; Ioduatrlal Bto*Teat Lab< oratorlea, lac. aad The Hloe lab* oratorlea, lac. 18*46 Ro m Mo Laed Glatta for DlnMjyaraj Rutgara, Tba State Ublveralty 18-9^ }t,?60.26 Tea Study of the Biological Baal* for lead Intoxlcatlooj Harvard Medical School > :- LR-1CA Ro m Ro Toxicity Study of Instated Paint Ml| Haaletoe Laboratorlee, Inc. -jpvf&rjKmmfyi.ju //' *./r,- N 433.01 i.: 3 "M*i PROJECT HQ. - LB-75 ILZPO PROJECT SLHttKY X*ua Datet Septeober 1, 1965 TTTLE - Buena Exposure to Particulate Laad Coapounde la th Air Under Bcperlnenta.1 Condltlcee PpmOCB IDP/rinCAnoW - LC-75 - H*ea Exposure to Ahbleat Air Concentration* of Particulate lead OCtfTRACTQB - Ublvaraity of Claclmetl, Cincinnati, Ohio c u r c t t t cqrmrr - 1/1/65-12/31/65, 135,000, 1965 Budget CUMULATIVE EXPOGES (to June JO, 1965) $06,000 1966 PPOPOSED OB CONTRACT PRICE $35,000 1966 PROPOSED BUDGET $35,000 1966 AUTBOPgATTCB 1965 A Prior Budgete Ubcoaaltted 1966 Propoeed Budget Ubdetlgnated Research fund 1966 Propoeed or Cootract Price loo* $35,000 Hone m&s h apm AmjCATigq Direct to geaollne additive, and Indirectly to soot other uee* of lead. 0MU-T1VE - Defend gaaollne additive earket. BE3BARCH RgYIPf TI Current 8tatue Eetieeted 00* Half to tvo thlrda work accaopllshed. 2. Projected BeMarch - Ccot leu* a* needed to lnaure thla aarket. 3. Beport* Iued (a) jWn Report* 1 - Huaber of progre*e report* leeued froa 1/1/63 to 8/I9/65, three 2 - Laet report Ho.' 3 - date* of period covered 6/l/6b to 6/1/63 (b) Proyaal -<LH-75)P*CP0SA1. TO EmSATTCRAL LEAD ZIBC CttMETZATIC* P0B TEE C0!msilA.-^37 TKRCUOH TEE YEAR 1966, cr THE PDCAHCIAL SUPPORT 0/ THE PB0CPAH OP RESEARCH OP THE KEITOIBIO LABORATORY, IS THE DEPARIXfJTr OP E37IRCH KUfTAL HEALTH* OP TOE COLLB3E OP KEDICDTE OP THE IFIVEJCmf OP CZHCDCUTI, 0*" TOE PROJECT "HUMAH EXPOSURE TO PARTICULATE LEAD COMKRTIO 15 THE AlB LKDZB EXPERlHnrrAL CCBDiriCHD* ( Officially changed, ae of July 1, 1965, to that above.) (0) Work Otatecent Hoo# pgmripwjfr ppy t t w 1. Pilot Production - Hot applicable 2. Con*user Evaluation - Hot applicable J. Licencing Activltla* - Hot applicable . Patent* - Hot applicable 3. Publication* - Rot applicable (a) ILiHO - Hone (b) Development Aaeooiatioc - Hooe '.j 'V..' '*'* N 433.02 ECCWOGC PtCPfm II Warint Goal* - Maintain world n*rk*t. 2. Appllotloc* and Hart*t Volua* Dm m gMOlla* *ddltlr*. 3- BIm of H*rkt Dfpdlxm - 200,000 too* of l**d la O.8.A. and 51,000 too* la lurop*. Coopt It lr* Thr**t - Ovang* raflaia* t*chalqu* to lininat* l*d additlr**. i - - *r<il V 4 't 1. \ o jte. 0 PBOJKT BO. - LB-79 mao p b o j b c t swwer Xeaua Datei Bepteeber 1, 1965 tTTLS - Toxicity Teating for Orgaao-Laad Ccepouade FRmoua naaTOTCATiai - LC-79 - Toxicity Teetlag for Organo-Laed Caapounde OOgmcTOH - loduatrial Bio-Teat Laboratoriee, Zbs . The Bla* Laboratorlea Id o . CURPJyT OCtmUCT - go contract Deeded. ctKtmrm ccmsa (to j v m j o , 1565) 1,650 19& PBOPQgSD OR OCWTRXCT PRICK - Icoa 1966 PBQPQggP BUPOg 1966 AOT30RIZATICB 196$ b Prior budget* Obcootltted 1966 Proposed Budget Obdaalgnated Beaearch fund 1966 Proposed or Contract Price I 8,350 *5,000 none 25,000 HM&ZT AFPtXCATZCStS - Lubricanta, blocldee, fungicidea, and other* xntlooad for LC-18 aad IC-26. OBJECTIVE - To provide toxic claealflcatloa that vlll aatlafy lagal raqulraaaeta for new aeterlale. MSBkBCB array II Currant Btatua - 8lx ccnpouoda have beta ccaplatad. 2. Projected Raaearch - To teat aa conpounde bacoM available through 790 aad latlck. 3. Beporte Taauad W]Progreaa "Saporta - gcoe (b) Propoeal - too* (c) Work Otataaeot - Icoa pgmoFVKrr vrrpii 1. Pilot Productloo - got applicable 2. Cooavasar Ivaluatlco got applicable 3. Licencing Activities - got applicable k. Patenia . got applicable 5. Publlcatlooe got applicable l:j ILZ.nO - gone D*rlopoent Aaaoc latloo gone ES ftarMt Ooif * Bee LC-18 and LC-26. 2. Application and Market Volnae Bee LC-lfl aod LC-26. 3. PUa of Market Defending See LC-18 and LC-26. b. Coapatltlve threat Bee LC-10 aad LC-28, Pli yW. r- fclfrfeuMill 1ALiUjLpu,.um*11yw** 1wyaya w=u war N 433.03 'iri PBOJBCT WO. - U5-66 ILZflO PBOJBCT StMWff 7TTVS - Lead Olaxea for Dtaaervaxa Xaeue Catet Bepteaber 1, I963 PHXVTQV3 HiarrinCATIOrf - ULC-13 - lead OUmi for ftaoermr* OOlfTRACTOB - Rutgere, The State Qhlvarelty ctmm cornucr - 9/1/65-6/31/66# *7,178, 1965 Budget CTNUIATIVg EEPgfSlS (to Juoe 30, 1965) - | |3j500 1966 ncPOSED o r COTTPACT PRICK - Booa 1966 PROPOSE) BCDOg - Booa 1966 AuraoRrzxnog 1965 fc Prior Budget# Obcomitted 1966 Propoead Budget UndetlgDated Beeearch fuad I966 Propoead or Coctract Price Booa Booa lirfB Booa APPUCATI0B3 - All drilllad couotrlaa uaa (lated dlnaervare. OBJECTIVE - To dafaad pretest aarket aod expand lead uaa by aaauraacaa of aafrty vitb proper ueage. RESEARCH KKVTBf IT Current Statue - Ralf of tba proposed vork la coupletad a* of now. 2. Projected Reaearcb - Concluding yaar of Wo yaar project* 3- Beportaa TItaruroetd (aj Pro^rcat Paport a 1 - Wiener of progreia reporta laauad frea 9/l/6b to 6/1/65, Wo 2 - Laat report Bo. 2 - datea of period ccnrered 3/1/65 to 6/1/65 (b) Propoaal - not applicable (0) Vort Statement - Booa ptvrijopynrr mnu IT Pilot Productloo - Bot applicable 2. Cooaunar Evaluation . Bot applicable J. licentlDg Activities - Bot applicable . Patanta - Bot applicable 9* Publlcatlooa () nZPO - Booa (b) Deyelopoaot Aaaoclatlooa Booa - pxweyce rwcarrrvt 1. Market 0ola - All slated chloa diooervere throughout tba vorld. 2* Application# anA >*>rkat Vplunt - Bo data 00 worldwide uaage. 3# Otf of Market >fndlng - 16,000 to 20,000 tone m lead la 0.9Jl. Coppetltlra Threat . Boo-laad cootelning rettrlctloo la arveral countrlta. Threat of gov*rum#Ot L i Wl.UlirJfJji l CTPHiiyi w m ifciitjyBBWM ft** ^ ;> tv. ^ V- 11ZP0 PROJECT StbetAKR Xsaue D>U| September 1, 19^9 FBQJKT WO. - 143-9* TITU - Stud/ of the Biological lull for Lead Intoxication previOCB ILtrffXi'ICATICW - ULC-16 Stud/ of the Biological Beale for Lead Intendcatloo cqrmcrOH - Samrd Hedleel School cpranrr cotmucr - 1/1/65*12/31/65. i3fc.260.26, 1965 Budget ctwuTrvg rxpgces (to June 30, 1965) - ia.570.26 1966 PSOPOSTO OS COffTRACT PKICI i3l.2G0.26 1966 PBQPOSZD BUDGET i3l,2G0.26 1966 *tmCPJ7>TIC 1965 fc Prior Budget* Gbcacaltted 1966 Proposed Budget tJndeelgnated Research fund 1966 Proposed or Contract Price coot i3l,260.26 nco* $3J*,Go.5` MARKET AmjCATIOiO - To U lead nerfeete end usee. OBJECTXVI To provide fundeaentel underetending of the toxic mode of ectloo of lead in biologicel e/etsee. r s p s a r c r wrmw T. durreet Statu* - A etert bee been cede In the derelopoeot of tool* end technique* of Investigation. Application 1* being cede to blood, protein end entyne *y*te*e. 2. Projected Beeeerch - Continue es above. 3. Beport* Xeeued (e) Prcgre.a Reports 1 Burf'er of progress report* l**u*d tram 1/1/65 to 8/l/65 ooe. 2 - Lent report Bo. 1 - date* of period covered 1/1/65 to G/l/65 (t) Propoe*! * I4.9I Propo**! for The Study of The Biological Bee la for 1" PgmOTVWT RTVITM H FTToTTroductloo * Rot applicable 2. Cou*r Kvaluatloo - Rot applicable J. Licensing Activities - Rot applicable . Patent* - Rot applicable 5. PvZlteatton* - Rot applicable (a) ILWC - Iooe (b) Development A**oc let loom - Rone tf* POQHCKIC nrTRTTyi 1. ^rx.t tfTl * Defense of rarleta such ae TIL, paint, can .older, present* 1/ a* 1 led 1/ all* *ttc* of toxlo react loo. Expend lead use Into area*, *ucn ae auto bod/ painting, ubere allegatloca of toxic hatard* altlgate against use. E. i PWTi N 433.04 rt7J0 PROJECT SOMUKY - LH-9* 2. Appllcatlooa ad Htrfcat Volur* . All load u **. 3. 81f of Harfcat Dafeadlag - Applicative to tU laad mitttl. Coapatltlva Itmt - Df*alv agalnat ccccpctltlco and lagal r*trlctloo* 4 > r. E" I ' i i s i mao PROJECT StfrHAW Z**u# D*t*I Beptesfeer 1, 1965 PROJECT WO. - LH-1C* TITU - Toxicity Study of Inserted Point Pita mvHXB IDomnCATXCW - Uta-15 - Toxicity Study of Ingetted Point Pil* CCTTRACTOH Railetoo laboratories, Incorporated cuRKarr carrier - Bern ctJMUUTTvg ncpBraa (to Jvne 30, 1965) - icoe 1965 PHOPOSH) OB CCSTRMT PPICg $9,900 1966 p r o po s e) Btccer - 1966 ATTBOPIZATiai I5C.5 0 Prior Budget# POcemitted 1966 Proposed Budget Obdlgn*ted Reaearcb fund 1966 Propoeed cr Contract Price 9,900 Boo* Son* $37335 HiRXET APPLTCATICB3 - Point pipaent*. oajgrm - To rol*e frao li total load the pr**ent restriction 00 point for Interior u*e. To help create o better cliatie of oplaloo for lead point* in general. r es ear c h revnv 1. Current Statu* - Contract not *lgned. 2. Projected Pe*e*rch - Joint tpcoeorafalp vith national point, Torniah and lacquer Association and advice frao several governeeot agencies. 3. Report* Iu*d jo) Progr*** Reporta - Boo# (b) Proposal - Bone to be considered.' (c) tfprt Statanent - Bot applicable SEYnarxm wvnv 1. Pilot I'ro-jcticn . Bot applicable 2. Consumer Jfreli*tlco - Bot applicable 3. licensing Actlvltlee - Bot applicable t. Potent* - Bot applicable 3. Publication* . Bot applicable (*) IU-tO - Boo# (t>) Derelojcent Association* Bone ftXMcmc nrrurnvy 1 Hrt n,vti* Prlnaryi interior paint*, vlth estimated potential of 10,000 ton* nee i**4"u*#. Cecondaryi Kl*c*llan*ou* use*, *ucb aa auto body flnl*h*. ? 9. Apr-llcattcna and Hartet Valune * Paint uee 1* lncreas tng with prevent mIi * in *xce* of two billion Roller*`per year. . -' i',. w imo t 1 1,10"H1- -m.Mti.i-*>' *j"^ae*ea>eE#'. N 433.05 3. 8It* of Htrkat Defending - Preaent 0.8. about 50,000 too* par yt*r, A. Ccgpatltlva Threat - All ooo-ltad pl<penta. ExUtIrvg and propoaad le*l raatrlctloo*. A1 4 J .j ; 5 ijgwux..t -.t iw m.ih mw i * *& - *V; \ ,, ~- r.*. r"%v.^*:t.Lr - '-V7%  V---J , PROGRESS REPORT - PROJECT NO. LH-75 INVESTIGATION OF HUMAN EXPOSURE TO PARTICULATE LEAD COMPOUNDS IN THE AIR UNDER EXPERIMENTAL CONDITIONS The work outlined In previous reports of progress, the laet of which wee dated September 10, 1964, has been directed primarily toward the determination of the maximum concentration of ideally respirable (that is, particles of lead too small to be deposited in the upper respiratory tract) inorganic lead in the atmos phere, that can be inhaled continuously throughout a lifetime by normal, healthy persons, without demonstrably progressive accumulation of lead in their bodily tissues. The approach to this problem is patterned on the results of balance - experiments (intake of lead in food and beverages, and output in the feces and ' urine) carried out previously with human subjects under various conditions. In 3 the present experiment, such subjects, after preliminary observation of their lead metabolism under normal conditions, are subjected to the inhalation of air con* taining lead in a known concentration over periods of time sufficient to demon strate the occurrence of non-occurrence of a physiological response in the form of an Increase in the urinary output of lead, (This response can be detected before any other in the intact human organism. ) It is postulated, on good grounds, that the response of human beings to continuous exposure of this type can be determined with approximate accuracy by extrapolation from the results of regular incremental 1 Increases in the duration of Intermittent exposure - that Is, j i hours of exposure per day for a suitable time, followed by i*j J^end 4j< hours of expoaure, for com parable periods of time, will yield a series of points on a cutve which can be !E)M't.4S'' wjtl'.'Pe.'xe'-wwww > i L. N 433.06 I extended to 24 hour* per day, every day. In a continuation of previoua experiment*, Subject* N. K. and S. 5., in essentially parallel experiment*, have been subjected to exposure to lead sesqui- oxide dl*per**d In the air of the two reiplratory chamber* In particle* ranging from 0.01 to 0.18 micron In diameter (mean *lte 0,05 micron) in the concentra tion of approximately 10 microgram* of lead per cubic meter. (After preliminary control observation*, over a period of month* prior to the year 1965), the** subject* were introduced Into the chamber* for 3 hour* on every other day (10.5 V Cj- hour* per week) over the period of 12 week*. Subsequently the duration of the b exposure per day was doubled, trebled, and further multiplied until, at present, s August 18, 1965, one of the subject* (H. K.) 1* spending 63,0 hour* per week, in the chamber, white the other (S.S., who started a bit later) i* spending 52.5 hours per week, both having passed through periods of approximately 16 weeks of exposure for 10. 5, 21, 31.5 and 42 hour* per week, respectively, while Subject fo N. K. wa* subject to, additionally 52.5 hour* per week for 16 weeks, before under- ? % going the present phase of the experiment. : There ha* been no demonstrable excretory response on the part of either b' ?> r subject to the experimental regimen. That 1* to *ay that the quantity of tead absorbed daily In the lungs of these subject* ha* not been sufficient under the** condition* to be demonstrated in the face of the variability of the urinary excretion of lead from day to day Induced by (he absorption from the alimentary tract. Or to be still more specific, the quantities of lead absorbed from the alimentary tract f. from day to day are so much larger (they esn be expected to be much more variable, aleo) than th* quantities absorbed daily from the lung that ths latter cannot be r detected. -< v i V <9? It it necessary to obtain a response, and In fact to obtain a series of incrtaaing excretory responses, In order to obtain the data for extrapolation from intermittent to continuoue expoiure. Therefore the experiment muit be continued in Increasing increments of severity (concentration of load in air and duration of exposure) until such data have been obtained. One would with to expedite the experimental procedure eo ae to obtain definitive results more promptly and at lesser cost. However, in view of the total tack of experimental precedent, and because of the risk of overshooting the nark (In terms of concentration of lead in air) and thus rendering the subjects unfit for further observations, it seems wise, at this time, to follow the original experimental design during the coming year. If this is done, and U it is necessary, as seems likely, to go beyond the level of 10 micrograms of lead per cubic meter of air in order to obtain an excretory response, the procedure will be that of beginning the new levet of exposure at a point, in terms of concentration and time, which is judged to be equivalent to the next serial increment of Increase in Inten sity. Once a response has then been obtained and stabilised (other data indicate that a plateau of response will have been reached in 16 weeks, at most), the course Is set for the addition of further points in a curve which will yield the approximate value for continuous exposure. There does not appear, at this time, to be a short cut to this result, and in view of the investment of time and money in this experi ment and in the metabolic evidence on which the experiment is foundedf'lt would seem unwise, now, to alter the design. However, at the end of this year (196)), the experimental data will be reviewed critically, at a meant of checking the ex'perlmental design and of affecting such reduction of time, effort and monetary expenditure at may be feasible. Such modification of procedure ae may seem feasible and wise will be communicated to the sponsors for comment and criticism. * - o * to achieve the maximum benefit from the collective critique. Considering the preeent situation of the principal inveetlgator (on leave in the eervice of PanAmerican Health Organliation for the next three month*) a* well aa the preeent stage of the experiment) it is believed that no useful purpose would be served at this time by assembling the data that would merely illustrate the negative results of the experiment as conducted up to this point. It should be emphasised, perhaps, that the very negativity of the results. In relation to the point of significance that remains to be established is an extremely Important finding. C Robert A. Kehos, tV D. Principal Investigator Date: August iS, 1965 HlUti PROPOSAL TO INTERNATIONAL LEAD ZINC ORGANIZATION FOR THE CONTINUATION. THROUGH THE YEAR 1966. OF THE FINANCIAL SUPPORT OF THE PROGRAM OF RESEARCH OF THE KETTERING LABORATORY. IN THE DEPARTMENT OF ENVIRONMENTAL HEALTH* OF THE COLLEGE OF MEDICINE OF THE UNIVERSITY OF CINCINNATI, ON THE PROJECT "HUMAN EXPOSURE TO PARTICULATE LEAD COMPOUNDS IN THE AIR UNDER EXPERtMENTAL CONDITIONS" On October ), 1962, ths general experimental procedure of this project, together with the details of a epeclflc experiment to be carried out in 196). were described in detail. Further proposals, relating to the continuation of the work, were made on September 4, 196) and on September 10, 1964. The work has gone on in essential accordance with the purposes and procedure described in these proposals, and is to be continued in the year 1966 along similar lines indicated herein. The Immediate goal of the sxperimertal work in 1965 was that of defining, through human experience, the maximum concentration of ideally respirable and absorbable (i.e., pulmonary absorption, exclusively) particulate lead in the ambient atmosphere to which normal, healthy, human subjects might be subjected, con* tlnuously and for indefinitely prolonged periods of time, without incurring the potential risk of a demonstrable degree of accumulation of lead In their bodily tissues. The experimental principle Involved the exposure of two human subjects, In parallel respiratory chambers, to air <ont.>lnlng lead (approximately 10 micro* Ofliclalty changed, as of July I, |9?5, to that above. t .* - v. '"St ; j- ' \: f; N 433.07 gram* of Pb( * toad sesquioxlde, par cubic meter) dispersed in minute particle* (ranging in diameter from le** than 0,01 to 0, 18 micron*, with the mean diameter of 0.05 micron*), on an intermittent schedule of lncreating duration (3 hour* per day every other day for approximately 16 week*, I.*., 10.5 hour* per week; 6 hour* per day every other day for approximately 16 week*, i, *., 21.0 hour* per week; and o on to 31.5, 42.0 hour*, etc. ) until the effect of the expotur* became evident through a (light (ststlstically demonitrable) increaie In the output or con* centratlon of tead in the urine, preiumabty (a* judged by earlier experiment*) without demonitrable increaie in the concentration of lead in the blood, of the ubject*. During 1965, the** observation* have continued a* scheduled, except for nec***ary adaptation of the period* of expoiure to the tolerance of the lubjecte for diiruption* of their daily live*. That is, when the schedule reached the point of requiring the subject* to spend more than 12 hour* per day in the chamber (on alternate day*) it became necessary to shift to daily period* of exposure. Obvious* ly also, the continuation of the famity life of the subject* required,at least, on* day per week of freedom from exposure. The result wa* a new schedule, involving the proper number of hour* of exposure per week subdivided into equivalent period* on *ix of the seven day* of each week. At this time (August 1965), on* of the subject* (N. K. ) i* spending 63 hour* per week in the chamber, while the other ($.S.) (who wa* taken on late a* an experimental subject, a* reported previously) i* spending 52,50 hour* p*r week. Inasmuch a* neither of the** subject* ha* yielded the slightest response to the graduated levels of experimental exposure, the experiment 1* to continue as long as possible at the present level of lesd concentration in air. It I* not anticipated at iV, -v ' - _.* -eu- ' f:.......'. ' ' . -*' ^ygjgra** ip**.- preaent that It can go for beyond 12 hour* per d*y on 6 day* per week, with due regard for the comfort and convenience of the aubjecte, If then no reaponae ahail have been obtained, the concentration of lead in the chamber will be lncreaaed by a email Increment, and the Incremental increaaea in the duration of expoaure will be reacheduled, beginning at a level of Inteneity (time x concentration) that will not duplicate that of previoue atepa. It will be neceaaary, obvioualy, to obtain a reaponae, and auch reaponae muat be graduated from the leaat demonatrable inteneity through at leaat three levela in exceea of the minimum. In order to provide data for extrapolation to the effecta of. continuoua expoaure (24 houra per day on 7 daya per week). Accordingly, the experiment may be expected to continue through the entire year 1966. It la conceivable that the experimental regimen can be modified ao aa to ahorten the time required to obtain definitive reaulta. The meana of ao doing are under conaideration at preaent, and the entire eituation will be explored critically at the end of thia calendar year. There ia aome rlak, however, in any radical alteration of the original deaign of the experiment, in that too aharpan increaae in the expoaure may yield an exceaaive reaponae, and threaten, thereby, the further uaefulneaa of the aubjecta. It waa for thia reaeon that the initial level of the con centration of lead in the chamber waa eet at 10 mlcrograma per cubic meter - a level which could be counted on (from Indirect but eatirfactory evidence) Jo yield negative reaulta at firat, with the poeaibLlity that there might be a poattlve reaponae aa the time factor progreaaed toward continuity. With the preaent facta and anticipation a in mind, the coat of the expert.. mental program in 1966 la expected to be almilar to that of 1964, Some economy rmy be affected, alnce it eerma unneceaaary, in future experimenta, to analyae /- -w- -- duplicate aamplea of the food of the aubject*. (The correlation between the lead in the food, day by day, with that in the fecea, day by day, ia ao aatlafactory aa to enable the former item* of data to be eliminated, apparently without introducing an error that ia greater than the aamptlng error, Further atatiatical work will be neceaaary to aubetantlate the facta in thia regard with certainty, and thia feature of the dealgn will be examined critically at the end of the current year (1965). Only one other iaaue ariaea at thia time in the budgetary conaiderationa. The propoaal to the Public Health Service, involving their further participation in the aupport of thia project, haa been approved in principle, but la dependent upon the availability of funda through Congreaaional appropriation. It ia expected that the funda will be made available, but ahould thia not be the caae, it will be necea* aary either to eubmlt a eupplementary propoaal to the other eponaora of the program, or to curtail the work. The following budget la recommended for 1966, on the baala of the expen* dituree made ia 1 964, and of thoae made to date in 1965; For peraonnet and aervicea (direct and indirect coata) For apecial reagenta, aupptlee, allowancca for food, etc. Overhead (proportional ahare of coat of operating the Laboratory) $ 75,000.00 5,000.00 JO. 000. 00 Total $110,000.00 On the aeeumption that funda wilt be available from previoua aourcea for the aupport of thia work, the coata would be allocated in round number*, aa follow*; Ethyl Corporation E, I. du Pont da Nemour* and Company International Lead 7.Inc Reaearch Organiaation U, S. Public Health Service 115, 000, 00 lb, 009.00 >6,000.00 14, 000, 00 Total $109,000.00 Whit* the roughly eatlmated budget and the equally roughly eettmated sH ,- f ' . . -V '.Ce*-X3*** 4 expenditures are not Identical, there ie little reaeon to doubt that the expenditure can be held within the estimate.