Document 4JzDJ6RK0RvEQ8RB62QkR2XXR

OF THE -. .LEAD EmROIS'-ENTAL HEALTH- COtMITTEE . . . OF THE. INTEEITATICIIAL LEAD. ZINC -RESEARCH' ORGANIZATION, INC. . h, - SEPTEMBER 1),, 1970 : In accordance with the notice of June 22, 1970, the 1971.Budget Meeting of the Lead Environmental Health -Committee was convened at 9:30 AM, Mon day, Sept ernher l4, 1970 at the Engineers' Club, 32 West tcth Street, New York, Hew York. R. C. Bell presided and J. F. Cole served as secretary. Those in attendance were: R. C. Bell ( Chairman) K. .Nelson L. Cogen E. Gay R. Semens R. Butler D. Biggs R..Suginoto Ii. Sakurai H. Tachimori J. Calandra J. Darcey D. Bielstein , R. Kubalak J. Sevick F. Werner Cominco, Ltd. American Smelting and Refining, Company Ametalco, Inc. (Representing Tsumeb Corporation, Lt Associated. Octel Company, Ltd. The Broken Hill Associated Smelters Pty., Ltd. E. I. duPont de Nemours & Company E. I. duPont de Nemours & Company Houston Chemical Company Mitsubishi Metal Mining Company, Ltd. . Mitsui Mining and Smelting Company, Ltd. . Nalco Chemical Company . Societe Miniere et Metallurgique de Penarroyr. St., Joe Minerals Corporation St. Joe Minerals Corporation St. Joe Minerals Corporation U. S. Smelting, Mining and Refining Company ASSOCIATE MEMBERS 1J. Pallies R. Rogers S. Hiscock B. Borcina J. Kimberley . Zeek ESB, Inc. Hill and Knowlton, Inc. Lead Development Association Lead Industries Association,, Lead Industries Association C. Tennant Sons & Company . ILZRO Staff D. Carr J. Cole S. Radfcke I. Voting Members The chairmen counted fifteen (l5) voting members. Note- because seven .1 members could not attend the entia e meeting, the total number of Votes registered was not always 15. II. Approval of I-'inv-tes of Previous Meeting The minutes of the Spring Meeting .of the lead .Environmental lea1th Cor held- in St. Louis, Missouri on April. 7, 1970 were I'.nanimousl 7 approved submitted to the.Lead. Environi.ental Health Committee. 2- - III. Election of Chairman for 1976-71 Kr. Bell Pinned the floor ik)r nomination for chaiman of the ILKRO Lead EnvIroh'fental Eiealth Comittee for. 1970-71. Kf. Kelson nominated Kr. E. C.;Bell of Qo&inco.. There being no more-nominations, the floor vas closed and Mr. Bell vac elected unanimously as chairman for 1970-71* . IV-. Budget Action on. 1970 lead Environmental Health Research Projects 1..LK-157 . Health Study of Lead.Eorhers, Tabei'shcv-Cooper Associates, 484,900, (iLZPlO, $42,450, TEL, $42,450). . ,.f Dr. Cole presented the report on the feasibility study and. proposal from : Tabershav-Cooper Associates vhich was presented to the Steering Committee assigned to this project on September 2, 1970. The Steering Committee's recommendation v&s that ILZEO accept the proposal and that work - on the full study beginipnedlately. Dr. Calandra noted that the feasibility . study had taken much longer than vas: originally anticipated and suggested that theire be a performance requirement in such contracts. Dr. Coleagreed that the feasibility study had been delayed arid for. this reason a full, time project vould be assigned to this project by the contractor. Dr. Eadtke noted that a performance clause is included in all ILZEO con tracts. Vote In Eavor . 15' Opposed ; 0 ,. Abstentions 0 1971 Funds Recommended ILZRO T3L $42,450 $42,450 V. Budget Action on 1971 Lead Environr::ental Health Research Projects 1. LH-157 Health Study of Lead Workers, Tabershav-Cooper Associates, $84,925, (ILZR0,:$42,462.50, TEL, $42,462.50). Since this'project will begin immediately it vas required that funds be allocated for the second year of this project vhich will begin in 1971. Dr. Cole pointed out that a proposal for the second year of the study vould be submitted to the Environmental Health Committee for there ap proval before the contract is extended. Vote In Eavor 13 Opposed 0 Abstentions 0 I97I Funds Recommended ILZEO t ot . : $42,462.50 $42,462.50 2. LH-I76 ILZRO/TEL Defense, Atomics International Comnany, $75,000 .(ILZEO, $37,500,. TEL, $37,500 ). Dr. Carr presented a report on his visit to Atomics International Company along with a description of their device for.the removal of lead from, automotive exhaust using a eutectic salt scrubber. Dr. Carr stated that Atomics International had reached the point in the development of this device at vhich funds vere needed from other industries to convince their own management that such a device may have a future market. Dr. Diggs, Mr. Hall and Mr. Gay vere pessimistic about the future of.the device but Mr. Kimberley noted that the. TEL .market van.so important as to varraiit an attempt to bring any possible solution to fruition. Dr. Diggs stated that he;felt that such an expenditure could not be made at this time by DuPont, but that if the device looked more promising in the EPI 000209 future, it nay -warrant. consideration. Mr. Sugimotb commented that he received a report from the National Air Pollution Control -Admin-' istration regarding their support of the initial development phase on this project. Mr. Cuginoto offered-to make this report available to the entire`committee. Mr. Kimberley"recommended that a suati in. the anount of A37,1>00 te^ allocated by ILZRO and that he -would attemot to obtain ,a -notching, s u e from the Lead Industries Association. Vote, In Favor 9 Opposed , ,0 Abstentions 6 1971 Funds HecoEsmended ILZRO ' TEL $37,500 . Hone EK-79 Toxicity Testingof Organolead Corroounds, Various Contractors, $10,000, (lLZE0> $10,000) These funds are used on an as-needed basis for toxicity testing of promising.new organolead compounds, synthesized, under the LC-lS pro gram. Vote In Favor 14 Opposed 0. Abstentions ,1 1971 Funds R&cormince-d. ILZRO TEL $10,000 Hone LII-86 Lead Glazes for Dinnerware, Rutgers Universltv, $25,000, (ILZRO, $2,50C) Dr. Cole explained that this project t o e reinitiated during 1970 because, of. several recent cases of lead intoxication involving poor ly glazed. dimiervare and subsecuent activity by, the U.S. Food and Drug Adirlnistration.. The current program is designed to compare . the A3TM test for the release of lead from glazes with actual use conditions. It"was recommended that this project be continued through 1971 in cooperation with the U.S. Potters Association. Vote In Favor. 15 Ooposec 0 Abstentions .0 1971 Funds Recommended ILZRO TSL $2,500" Hone Study of the Biological Basis for Lead Intoxication, Harvard Medical School, $52,254.00, (ILZRO, $26,127, TEL, $26,127) Dr. Cole noted, that Dr. Vallee had become very interested in the current problems besetting the lead industries regarding d-aminolevulenic' acid dehyarase. It was also noted that Dr. Valles had mode excellent presentations at the LE-lol Lead Symposium held ia Puerto Rico in 1970 and at the April : meeting of the Lead Environ mental Health Committee. Future plans call for ILZRO tojattempt to obtain more public exposure for Dr. Vallee.and his work. Dr. Diggs noted that Dr . Vallee's report tils year was excellent, and urged IJ.ZBO to attempt to have the "prologueof the report pub lished and also to approach Dr.Vall.ee with an aim toward having hill testify before regulatory groups.. .Vote In Favor Opnosed 14 ., . 0.. Abstentions 1: 1971 Funds Decemmended ILZRO ; TEL $26,127 $26,127 111-10:': .Lettering 'Abstracts of Lead Toxicology, University of Cin- cinhati, $0,023.65, (ILZRO, $3,073.05) Epr 000210 k_ ..Although-'the .amount requested for this project has been considerably increased for 1971; hr. Cole recommended that...this service he contihp.ed. l.It. vac pointed, out that the G7500. paid in the past for the total, contract by ILZRO,. LIA and LDA vias not nearly enough to cover the costs, of the University of Cincinnati. Vote In Favor ,ik Opposed 0 ... . Abstentions 0 1971 Funds -Recommended ILSR0 TEL $8,023.05 None 7. ; LEI-llV Effects of Chronic Plumbism on Neurological' Behavior in the RhesusMonkey, Indus trial Bio-test Laboratories., "-55,052.06, (ILZRO, $27,525.03, TBLy $27,526.03) . I)r. Cole pointed opt,that the ILZPU Environmental Health Connittee .had recommended that neurological. testing he continued on the animls vhich had been fed lead on this project for approximately two years. It. vas felt that with suah a unique group of animals we should atteri.pt to obtain as much neurological information as pos sible. It was noted, however, that the contractor had recommended . that"a new set of animals be brought into the study because hase. line!data electroencephalographic data are not available on the ani mals which have been undergoing lead exposure. Er. Calsndra offer ed to see that the full amount of work as outlined in the proposal is carried out if ILZRCwould.fund this project at approximately the sane level as it had been funded in the past. Dr. Calendra. also noted that ILZRO has been paying only half the actual cost of this . research in the past. Vote In Favor Opposed 12 ; . 0 ' Abstentions 2 1971 Funds Becamnended ILZRO TEL $12,939 $12,939 : 8. LH-I38 Study of Lead Release From PVC Piping, Rational Lead Company, $10,000, (ILZR0, $10,000) ` The purpose of this study is to obtain National Sanitation Foundation approval for a lead stabilised PVC pipe in potable water. Research is' now .underway at the National Lead Company's Rightstown, New Jer sey laboratories in an attempt to produce a low lead release lead stabilized PVC pipe. Should this work produce a suitable pipe, ILZRO : would support the testing required by the National Sanitation Founda tion. Vote . In Favor 13 Opposed "0 Abstentions 0 1971 Funds RecoFr.ended ILZRO TEL $10,000 None . . LE-152A Blood Lead Analysis Study, Societe de Metailurgique de Pen- arroyc., ITo Funds Requested. ' Mr. .Bareey stated that c request for funds could not be made at this time pending the outcome of preliminary test with the graphite oven. . It was noted that a future request for funds may core to. ILZEG which could he financed from the Undesignated Research Authorization. 'O EPI 00021i -5 lGv LIL-1^23 Blood: Lead Analysis Study,. Environmental Sciences Associates, , :r Inc$24,025, (ILZRO, $12,012,50,TEL, $12,012.50) y Kr. Nelson:pointed out that anodic stripping voltammetry (ASV) is an eliciting new ` de%elopment for the analysis, of lead. However, he .questioned the need for a portable analytical instrument and. stated that the. costa are not likely to be less than with: airesc y existing methods. He suggested that ILZRO. not support this work in view of pur ongoing work pith .LH-152B and federal involvement in an automat- ed ALY system ../,; y : Vote "y In Favor . Opposed 0 12 . 'Abstentions 1a 1971 funds .Beeonnend ec yILZEO TEL None None 11. 1 LH-192 :Information on Lead Environmental Heal th Activities in Europe,. Fowler Davies & Company, $7,000 (ILZRO, $3500, TEL, $3500) .; Dr. Cole recommended that this project be extended through 1971. Dr -Diggs- 'commented that .he would'like to see more emphasis placed yon political occurences in Europe with regard to environmental health activities. Dr. Cole noted that he would inform Mr. Fowler of this . request. Vote In .Favor -Opposed-. 13 0 Astentions 0 1971 Funds Recommended. ILZRO TEL ' $3500 ; $3500 12. LH-159 Study of the Effect of Lead on the Respiratory Activity of Erythropoietic Cello, Ohio State University, $15,c09 (ILZRO, tj,504-,50, TEL, $7,904.50) Dr. Cole noted that this contractor had performed his obligations very well in that the reports, were quite good and on time. -However, he expressed doubt that the research would achieve the desired ob~ jectives. Dr . "Roush.' concurred in this noting that the - contractor had spent a great deal of time in' perfecting methods- which'-.'the cor.:- `' mattee had understood were already perfected. Vote In Favor Onnoscd 0 13. Abstentions v0 1971 Funds Recommended ILZRO TEL None None 13.y LH-lCO Effects of Particle Size on the Absorption of Lead in Hunans, : University of Cincinnati, $c2,366 (ILZRO, 31,183, TEL, 331,183) Dr. Cole . cornented that the lead industries owe Dr. Kehoe,the ..primary _ investigator on this project,' a great- debt for his fine.work over the years. However, with the large expenditure involved in this project and -the.-limited, amount -of useful data which can logically be expected from it, he did not feel that the expenditure would be justified. Ur. Nelson supported this view. Dr. Roush noted that -this.experiment would-provide useful information, but that like other ILZRO Environmental Health projects this information may not have immediate value.- Vote . In Favor 0 Ounosed 6 Abstentions 7 I97I Funds Recommended . ' IllRO ; T1L~ None Norte EPI 000212 . -6- ^ it. - Ul-162.: Human Variations in susceptibility to Lee <3, Clinic a Del Lavoro, University of Ialan,;:!'36,705 (IHZEO, 618,392.50, .TIL, .710,390.50) ;Dr. Cole referred to a letter received just prior to the meeting from Br. Vigliani, explaining that work is now underway on this pro ject. Dr. cole3'explained that a construction strike in Italy had allowed work on a ncu? section of the. 'laboratory causing nearly sir months delay on the project. Dr. Yigliani recuested that a greater sum be allocated for 1971 than for 1970 because of the increased ..expenses caused by inflation and also for the purchase of an anodic .stripping voltarmetry instrument. , The suggestion was made that ILZRO . retain ovnefship to .all such, equipment purchased with IL2T10 funds.. . Dr. .Rafitke agreed that this should be made a.-part /of all ILZRO. con tracts. The proposal for 1971 will include an investigation of in dividuals: susceptibilities to the effect of lead on d~sminolevulenic acid and d-ar.:inole\aulenic acid dehydrase. . Vote ' .In fETOi Opposed . . ; . ; 77 4- Abstentions 2 1971 Funds Recommended ILZRO: . . TEL 318,392.50 313,332.50 I5. ULE-26 Study of.the Effect of Lead on the Kidney, University of Goteborg, 932,600 (ILZBO, $lo,000, TEL, 6l6,000).' Dr..' Cole noted that the question of the effect of chronic exposure to lead on the kidney was a subject of major concern at the LIi-l6l lead symposium in Puerto Rico. Tile Question of whether chronic ex posure can cause lead nephropathy is one which continues to plague the lead industry and about which little is actually, known. Questions were raised regarding the exposure of the subjects since it was not clear in.the proposal that subjects with low, intermediate and high exposures to lead are to be included in the investigation. It was recommended that subjects with all types of'exposure'be included so that an "effective dosage" could be determined. Further, there was an expression that the amount of money requested was too great for the amount.of work to be accomplished. Also it was recommended that ILZRO retain ownership to any equipment purchased with ILZRO funds. There were three votes taken on this project. The first vote .was on the proposal as written. Vote In Favor Opposed 22 .Abstentions . 9 1971 Finds Recommended ILZRO TEL Hone Hone The second vote was on the proposal as written with the understanding that ILZROMould retain ownership to any equipment purchased. Vote In Favor Opposed 4 5 . . Abstentions ^0 1973. Funds tec crx.ended ILZRO TSL ITone Hone The bhircl vote .was on the motion that the proposal be accepted on the condition that subjects with a graduation of exposures are Included in the Project and that the entire 'project: can be ncconalished for.620,000 .in 1311.5 ; Vote : I:i. j't.vor Of to: cd' 01 Abstentions h 3332 Funds LeeX "ended ILZRO f,L ziOyOoc63.0,000 EPI 000213 -7- 15- ULII-rj .Economic Comparison of Methods Tor Analysis of Lead in' Bloody Enviro;v'cntal Health Laboratories, .$26,000 7(lLZitQ, 726,000) Dh Co] e-recofirrended that this proposal he rejected 'because of the overall demand upon our.available funds. He pointed' out, however, that -the; study;u;as an interesting one and might provide useful infcrirhtionj; hut that its priority must be considered lov. Vote In Favor 0 Op'oosed 13 ;. - Abstentions,.: 0 I97I Funds Recommended ILZRO. , TEL Hone. 7 - Hone l6. TTLHt-SS. An Evaluation of Aromatic and Metallic Substances in Selected ,Urban'^Atmospheres, University of Cincinnati, S93>l4,TlLZR0, $46,920.50, rLL, $1:6, $20.50) / '' ;; \7 ;Dr. Cole recorr.ended that ILSRO support 1/3 of the total cost of this . project with an attempt to obtain; support for the remainder from the . American Petroleum'Institute and, the U.S. Public Health Service. ; ; I'r. Biggs noted that lie could, not support an expenditure for the entire amemnt,. but because of the political benefit which might be gained from suck a project, he recommended that IL2R0 support 1/3 of the total cost of the. program. . ' Vote In Favor ' 10 Opposed 1 Abstentions 2 1971 Funds Kecorrrienclec ILZFO ... TEL $15,6)10.17 $15,640.17 17- ULH-29 Effects of Lead and Insecticides on Avian Reproduction, Cali fornia Fish Si Game Lever foment, $12,23.4.34 (ILZBO, $6,107-17, TEL, $6,107.17) Dr. Cole recommended that the project be rejected since the preliminary ''work submitted by the proposed contractor .seemed to answer the cu.estions posed in the research proposal. Also it was noted that Joint financ ing was not. assured. and that.there had been difficulty in obtaining cooperation. - fron .-the California Fish & Game Department, in an effort for Joint financing. Dr. Diggs noted that he favored assisting state conservation departments with, their problems when they involve lead. Vote In Favor Opposed 1 12 Abstentions 0 .1971 Funds Piecomnended ILZRO . TFT. Hone Hone l8. ULE-30 ' Epidemiological. Study of Effect of Airborne Lead on Heme Synthesis, Ho Contractors yet, $50,000 (ILZRO, 325,000, TEL, $25,000) Dr. Ccle ennclainecl that this project come about because of a suggestion of Dr. John.Goldsmith that such data is needed so'that the effect of ambient exposure to load on delts Arainolevulenic' acid excretion can. be ascertained. The 'Venture'Anelyis presented 'to the committee was paraphrased from a report by a subcommittee appointed by the Lead Liaison Committee to design a protoco], for this work. Lr. Cole er.plaincd the t this project world. not be supported unless it was re- ce: mended By the full Lend Liaison Committee. Vote -m . nvor dOp-o...cd .9 7. h: .V.. fo-.n.L..... 1 ]771 Funds Eccon.v-ended p j..: .'La fid $25,000 $25,000 EPI 000214 9- that each a phenomenon:has been recognized for. years, in the lead . industry and that it resultes from .very high, "body, burdens of lead, in poisoned wbrhers. Chelation therapy removes Only a small por tion of the total body burden, of. lead. After therapy is dlseontinued the body again strives for equilibrium' with respect to lead ane' blood lead concentrations go up and sjmptor.s reoccur. It vad the ; opinion of the "committee , that the research work with baboons d would provide little new "information, regarding lead intoxication. Vote In Favor Opposed 0 ' 11 -Abstentions' 0- 1971;'Funds Recorijsnced ILZRG TEL ITone ' 1 I.'cne 23., 1ULH-33 : Concentretion,of Lead in the Atmosphere and Population in ;vJapan#'-.Keio''University,'.'057^^00 (iLZRO,..- '$28,700, - T2L, $28,700) : Dr. Eadthe explained that the project was '.deeaed to be of great Importance in Japan because of the recent, publicity; given to a finding - by & group of physicians stating that many persons residing near a heavily traveled Intersection, were ill. with lead poisoning. This..group retorted some rather high values for lead in blood; and urine. After .much discussion, concerning the usefulness of the study, hr. Gay suggested that ILZRO supply funds for .carrying out the study but that the Japncese producers provide a fund for the required equipment. Vote In Favor .O' Opposed Abstentions 2 - 1971 Funds Recommended ILZE0 TEL $15,700 . $15,700. 2h. Uadesignatcd Research Authorization, 50,000 (ILZEQ, eft,000, TEL, .,$25,000.) V ' '" Er. Cole pointed cut that the funds authorised under Undesignated Research Authorisation would be used for projects which core vu during the year. Each project, however, will be submitted be the' full Environmental health Committee for c letter ballot. Vote In Favor Opposed 90 , . Abstentions 0 . 1971 Funds E.ecornendod - ILZRO TEL Hone I.rone 25. Dr. Roush presented -.proposal' just received, by him fron the Ethyl. Corporate on to determine if lead methylates in a natural aqueous environment as has been recently found with mercury. Because the committee had such little time to review the proposal. Dr. Cole suggested that, it be circulated to the entire ,committee and. thr t a letter of ballot be taken. If the proposal is accepted the funds will"be ' taken - from' the Unclesignatcd Research Authorization.' VI. Budget Action on 1971 Zinc Environmental Health Research-Projects UZH-l Carcinogenic It,, of Zinc, - University' od Cincinnati, ,'j9,t (ILZRO, $35,000) Dr. Cole explained that this; project vac being presented to-the ' ... lead. Enviromnentu] hen?th Committee because ILZEC does not bug e EPI 000216 a Zinc En-vironnental Iltealth CorniTdttee. Thin "project vcs.-recorarended because, of alleca:tions by Dr. H&lric of ^inland that'low levels of zinc,, such-as foinic in Grinding utter, cause cancer in .laboratory ' animals. Dr. Cole noted that Haline's work had been considered, as poor by a nvaber of rovieveas but the' ket that some evidence exists that zinc nay cause cancer should, be of concern to the zinc, industry. Also since ' it will 'take at Teest ,3 years; to produce date, to either refute .of corroborate Halite, work .should begin soon. It ves the opinion of 'several .members of the canar.it tee .that, such ... poor work, should not /.require. ILZRQ to spend. large /suns' to refute ' it. Also,, epidemiological studies; were suggested to answer Halne1s , claim. Dr. Cole cited LH-lpJ in noting that such studies are very . ., difficult .and very costly. Vote In Favor. Opposed ' 0 8. Abstentions 2: 1971 Funds Recommenced . ILZRO TEL hone . Hone VII. Report on Other ILZRO Environmental Health Programs Because of the late hour and the fact that most other research pro jects hud been discussed during the session this agenda item was cancelled. . VIII.. Adjournment There being no further business to cone before the cdmxiitt.ee, the -meeting yds 'adjourned at 6:00 P.K. Submitted by: J. F. Cole, Sc. D. ._ EPI 000217 ^jji 71-- UNlVERSirA DEGLI STUD! ' ISTITUTL CLINIC! DI PERFEZIONAMENTO CLINIGA DEL LAVORO ''LUIGI DEVOTO" Dir et t o p.e Pr o f . ENRICO C. VICLIANI Dr. Jerome F. Cole Manager, Environmental Health International Lead Zinc Research Organ i sati on, I n c . 292, Madison Avenue New York, N.Y. 10017 U.S.A. 1 bo i as mil an o 28th August, 1970 VIA S. BARN ABA. 8 5V.60.91 - 58.16.10 P rot. 658/ECV/kw J Dear Doctor Cole, Enclosed you will find the scientific and financial programmes for the extension to the research project on "Human Variations in Susceptibility to Lead" for the period from 1st July, 1971, to 30th June, 1972. Of course, in addition to the work planned in the extension, we shad continue the work begun in July 1970 and which might not be completed by June, 1971 . We shall try to put into operation the new method of lead analysis with anodic stripping voltmetry, which you suggested and which seems very promising. I very much hope that our programme will be accepted by ILZRO's Environmental Health Committee. The new floor which has been added to the laboratories of the Clinica del Lavoro is now almost complete and we are now ready to start work on the programme for 1970. As you will see, the financial budget will amount to $30,000 instead of $25,000, but this is due to the rise in all costs which has occurred in Italy in the last few months. In addition to the financial budget, we should like to purchase the MASA 2014 multiple anodic stripping analyzer. From Environmental Sciences Associates brochure we see that the MASA 2014/electronic and cell holder costs $3,950, the .MASA 2014-4/4 cell extension $2,700 and the replacement parts for the cell holder $221.25. Would it be possible to have some assistance from the ILZRO to buy this instrument? We trust that the delay in sending you the programme for 1971 will not cause any inconvenience. The reason for the delay is that we have been extreme!) busy in the past months with a complete renovation of the Clinica del Lavoro, and also I wished to thoroughly discuss with Professor Pernis the lines along which our in vestigation could be carried out in the second year of the research project. With best personal reggrds. Yours sincerely. i PI 000218 : N 11662.01 CL1N1CA DEL LAVORO "LUIGI DEVOTO" Segue Fog/io N. Extension of the Research Project on "Human Variations in Susceptibility to Lead" for the period from 1st July, 1971, to 30th June, 1972. During this period the proposed research will be performed with the main aim of investigating the possible effect of lead on urban populations not professionally exposed to lead. Action of normal urban lead on heme synthesis and life span of red cells A recent report in the literature by Hernberg and Nikkanen (Lancet, i:63, 1970) raises the possibility that lead absorption that may occur under normal urban conditions may be sufficient to inhibit some enzymes involved in heme synthesis like ALA -dehydrogenase. The basis of this assumption rests on an observed inverse cor relation of A LA-dehydrogenase levels and blood lead in a group of individuals not occupationally exposed to lead. i We propose to control this condition on large samples of the urban population in Milan which would also include some individuals such as traffic wardens, etc., who might have been exposed more than the others to the absorption of some lead. The ALA-dehydrogenase activity of erythrocytes will be measured with due attention to the possible criticism of Bonsignore's method, taking into account the modifications of this method that have now been tested in the Institute of Biochemistry of the University of Genoa by Bonsignore and his colleagues. It is foreseen that this methodological work will be completed before July 1971. With regard to the measurement of blood lead, whose accuracy is equally important to obtain a meaningful correlation with the ALA-dehydrogenase levels, particularly at low concentrations of the metal in blood, different methods will be used, including not only a dithizone assay as performed by Hernberg and Nikkanen, but also recent techniques of atomic absorption and, if possible, the electrolysis method. Here again, the time before 1st July, 1971 will be very useful for putting these methods in optimal working conditions. N 1 1662.02 EPI 000219 CLIN1CA DEL LAVORO "LUIGI DEVOTO" S9Sue Fog!(0 N____ 2 If an Inverse correlation between blood lead and A LA-dehydrogenase levels is obtained, then the individuals at the lower right end of the curve (i .e., those with relatively higher blood lead levels and relatively lower ALA-dehydrogenase levels) will be sorted out for further investigation . In these individuals one or more cycles of treatment with EDTA will be per formed in order to see whether there are parallel changes of lead blood levels and ALA-dehydrogenase activity. This will be done with the aim of investigating whether in fact the lowest levels of ALA-dehydrogenase in an urban population are connected with a relatively higher lead intake. Finally, in some volunteer members of this group of individuals, the life span of circulating erythrocytes will be determined with the method of chromium-labelled erythrocytes with the aim of obtaining information on the possibility that in these subjects the apparent inhibition of ALA-dehydrogenase, presumed to be induced by lead, is in fact influencing the erythropoietic system. For this latter purpose we also plan to obtain a complete profile of the different enzymes in erythrocytes of different density (Marks et al., Proc. Natl. Acad. Sci., 50:336, 1963) to get some information on the average age of the erythrocyte population in these individuals. If goes without saying that all this work will be performed in addition to ordinary hematological studies, like hemocyfomefry, hemafocrife, study of the size and shape of red blood cells, reticulocyte counts, search for basophilic stippled cells, etc.. In connection with this line of research, which will be mainly epidemiological, another line will be pursued intended to investigate the possibility that ALA-dehydrogenase levels of different individuals may have a different sensitivity to the action of lead. This problem will be approached in the first instance by testing the blood of different normal individuals after addition of lead in vitro . However, we must keep in mind that inhibition of ALA-dehydrogenase by lead In vivo might be a more complex process, as shown by the relative persistence of depressed enzyme levels even a long time after termination of exposure to lead in industrial workers. EPI 000220 CLINiCA DHL LAVORO "LUIGI DEVOTO" Sogi/e Fogiio N,.. . . 3 Recent unpublished work by Bonsignore et al'. has raised the possibility that the action of lead on ALA-dehydrogenase "in vivo" may be partly mediated by the induced synthesis by the metal of a protein inhibitor of the enzyme. This point needs further investigation because if it were substantiated it might be appropriate to try to detect and measure this inhibitor even in persons not industrially exposed to lead, and particularly in that group of normal individuals which we have indicated before as corresponding to those who might have relatively higher levels of lead.in the blood and relatively lower levels of ALA-dehydrogenase,, EF'I 000221 GLIN1CA DEL LAVORO "LUIGI DEVOTO" Soguo Fogfio N.._ Financial Budget for the Extension of the Research Project on "Human Variations in Susceptibility to Lead" for the period from 1st July, 1971, fo 30th June, 1972 Personnel: - One biochemist, 60% of the time - One analytical chemist, 60% of the time - One physician, 60% of the time - One laboratory technician, full time Consultant Services : Supplies: Travel, domestic: Publication costs: Outpatient costs: Total US $ 11 " "" "" 6,000 6,000 6,000 6,000 " " 2,000 " " 2,000 " " 500 11 " 500 " " 1,000 US $ 30,000 Purchase of MASA multiple anodic stripping analyzer Grand Total US $ 6,875 US $ 36,875 N11662.03 EPI 000222 VISIT REPORT By: ; J. F. Cole . Date: September 1, 1570 Location: '-'ThG-.HIne Laboratory Cm Francisco, California Person Visited: Dr. C. K. Line Subject: UIII-52 ; Lysiaskion of Chronic Toxicity.of Triphenyilesd Acetate Although a;-proposal from. Lifestresr.: Laboratories has been, submitted to A. the Lead Environmental Hesltli Committee for support in,1971? I found out suite recently '.that', they have: gone out of business. The proposal w es the best of three received last year when ve: proposed that the wrk.be : financed by the organolead licensees. A proposal was also received from: the Hine Lapoi'atory but was not nearly as comprehensive and much more expensive. . The Hine Laboratory, however, has an excellent reputation in toxicological investigations and it was thought that it right be. valuable to discuss the project with Dr. Line in order to include r.ore work in his proposal and possibly prevail upon him to reduce his price. After discussions I received a verbal commitment from, him to include iinhalation toxicity testing and to reduce the cost of the oral feeding study'. Dr. Hine suggested that we also add lead in tissue determinations to the overall protocol. The. following is a. comparison of the original Hine proposal, the. new one arid the Life.sfeream Laboratory proposal: 90 Day Aerosol Inhalation in Eats 180 Day Oral Feeding in Eats h-5 Day Dermal Toxicity in Rabbits Skin Sensitization in Guinea Figs Repeated Insult Patch Test in Humans Lead Analysis of Tissue Totals Old Hine Hew Hine Lifestrearv Proposal Proposal Proposal Hot Included $10,000 311/000 $18,000 $ .5,000 $9,400 $2, COO $2,0.00 $4,500-"- $ 600 $ 400 $ 400 Hot Included $ 1,000 $ 1,000 Hot Included**:?. 1,200 , Hot Included $20,add $19,500 $22,300 * . Galled 'for'-GO day exposure. ** not included as a specific iter, but included in protocol. Hine had no explanation of why he proposed '318,000 for the ICO day oral feeding study but said that it might have teen mistakenly calculated, on the basis of using dogs. Since Hine has reduced.the cost of his proposal so drastically, it is m:y feeling that we should now give it primary consideration for support in 1971 N11662.04 F - MM+-53 Propor/el To 'he Interridhion;. T head Zinc Research Organization , From . Khio University Tokyo, Japan - ULH-33 Pux'pose' o'* ftrcy: 1,3 - Jixne - IfT'-V: virtually, c.lli Jj-ya-nere-.rievpspor-a reported that- physicians or Kil'x-.-.vshf to; Gotti cueut' hozgital,had claimed n: or thread: of herd .poison! n./cn-" .inhabitants;: in hraa. of heavy traffic, in :Tokyo.. Thin iepork cc'vs panic/ar'onp" Ja^P/ne" people iu relation to a ;"Public ; Fviacnce''. 'Howeyc F jater inves thaoioo by a :veil-established and respected institute, tl; 'Occupational ,Service ''outer, 2 ,-cded by Dr. Jr.v.c Jj'boba, refuted the res .rlepqrted, I";, theaGettlovrgnt .Hoc or tai physic lens. nevertheless, the letb report rlich appeared.bin- Japanese- newspapers, covering airiest a fall :r.;:c, liasaieftvfb lastiiiC: irpirpseicii; on' the- Japanese Populace.. Because- of tki -F the ill riotry of Co: ; ercc declared 'thet T3L inuct 1c cougletelj' removed frer 'garc2..h' within. five, years . Ih fact, beginning, in ly'hV the amount of T2L in h sollne. ear- reduced -by ope-ha/.i from the amount uc-ed previously, although aroix tic hydrocarbons were increased. to maintain the octane rating. It would be h-rprising; If the ruling of the I-lnistry, of Commerce vill he .implemented v irr sieh a short period of tine, In this situation, it has beccre post important to elucidate whether or not the lead in the air of Japanese Cities could cause any significant health hazard to rxn. kith regard, to: lead in the ambient air of urban coKvunities in Japan, only s very liisitec number of reports have been published. This proposed study, therefore, aims to clarify /whether or not lead in the , ambient air of areas of heavy traffic-, has any effect on human health inj terms of body burden. General Outline of.methods - In 1905.,' a report entitled., "Survey of Lead in the .Atmosphere of Three Urban C6r.sr.unities-",-/ was- .published., in the U.S.A. Subsequently, a study entitled, "Seven Cities Study", was initiated. In general, 'the -proposed study ..would folio-,? the method used in the "Seven Cities Study". The cities proposed for this study are Tokyo and a Uni.ted area of Yokohama. This proposed inves tigation is much .enaller in scope then the Seven Cities Study of the U.S.A. It .is..proposed that blood sanp2.es. be obtained from the Japanese population of different areas of Tokyo, and also from specific occupational groups, ''such as .workers in road construction companies,' taxi drivers, policemen and so forth. A total cf about 2,000 blood samples for lead .analyses would be col lected .during-,the- -study. Urine -samples' would also be collected' .and .'analyzed for coproporphyria and celta-ci ino levulenie acid. The results,obtained, would be analyzed KtatisticcJly with respect to age distribution, sex, resiFFnee, nisei so forth. Air sampling;--' s te tiens vouicl be-;, selectively - located in Tokyo and Yokohama. At the present r..o: cut eight btrsipns,. routinely operated-'-by the Tokyo Ket .rcpplifccn health Uepar.trerit.,. would 'be -used. In addition, four or five new station:; .would be, er.tcl.-lished for - this study. However , .the a forementlone <2 eight staticssc do not k.-.-y-e nrra"igercente for lead sampling: a total cf> two.1 ve air sampling utnbions for lead are recoxr;ended for the proiionec! study. Hood lead analyzes wo'clc; be- r.\v e by two institutes, the hfdo Univcrr : ty 3choc of hcdiclne uj-icer Profov.- or henaabvro Tzuch.iya, and the O^cu". ; tional He-'-.l-' Center-'; vnqer Pr. Jrlro ihf.ota .''] r: J analyses ,-/ou3d -be r - - -,.d by the N11662.05 EPI 000224 ' ;L ; ' - 2- Yokohorr- I.';, clonal University School of' Engineering, directed by Dr. Yoohita Kobayoshi. ' This is agener:! outline 'ofthe. work proposed. Subsequently, a detailed plan vlll/le prepare! in accordance pith the recommendations/ of the iir.PG Enviv'.;,jaontal health Committee. ' The program can he initiated by 1 November 10t'0, or by 1 January If ;i upon advice of the 1111:0 Stuff. Coat Analysis It is envisioned that' the-/study will be completed one . year after approval c; the proposed'program. 1. Fersonnel Costs Three .full time technicians/1 year Secretary, 1 month m Three Lab. technicians, l.nonth each Total . 2,0 Supplies ; Ecuipm.en.fc $6,000-.00 200.00 1,200.00 v 7/1)0.,./ i Lou temperature asher (?) High'Voiuv.e Sampler (12)' Total 016,000.00 10,000.00 y?6,000.CO 3- Lead sampling and analyses^ Blood (2,000 samples).- \ .Air (600 samples) Coproportihyrin. and^-ALA in urine (2,000 samples) "~" Total " $1^,G0C.C0 2,000.001 8,000.00 02^,000.00-: Grand Total . - - --- itY/;-?" .00 (l ~----- Submitted by Dr, X. Tsuchiya, Keio University, Tokyo, Japan. EFi 000225