Document nma0y97bg0goY5G9Y7JwjQY1X

Q INTERNATIONAL. LEAD ZINC RESEARCH ORGANIZATION i 1 M*e*o* mew *r. n * o mo n m nw ,1 1 I3 5 i ' '4 1 * .^4 f 5 I October 10, 1963 To Motor* of tb* L.I Jk.-I.L.Z.B.O. Baaltb aod Safety Caaolttaat Afejactt l?Sb Baaaarch Budget - Fropoaal* an* Work Btataraot* for Cooaldaratloo <t tb* 19A Budget Mortise Attached 1* tb* I96L Catalog of Health tad Safety Baaaareh for four reriev la preparation for tb* Baaltb and Safety Ccnaltta# Budget Meeting to b* bald October 25, ISbJ at tba 60 Baat AZod Street Club, 27tb floor, Maeola Building, 60 Sot 42nd Btraat, Sav fork 17, B. T. at JiJO a.a. Bit aatarlal 1* daalgnad to ba uaad a* a guld* la our dlaeuaalooa aod contain* baaldaa a Hat of ltaaa to ba dlacuaaad, rvrt.au and coeuaot* co paat parforaaac* of con* of tb* project*. Blaa** rvrtau tbaa* ltec* carefully aod ba praparad to aak* your daeltlco* at our aaatiag *0 that our raooaaendatlcn* nay b* acaplatad at that tin*. V* auggeat that you bring tba Catalog to tb* aaatiag to bare* aa refaraao*. Yery truly your*, MTiod So*. 27 Boo 0. fouler, Sacratary laaltb aod Bafaty Coaalttaa IS 205 19 cmiflo or k b u c t a u d s t o t KEsnuca - lap ux-nzx nun wo sunat comma X- Btrl*v of XxUUiic Pro>cti o4 Exutalco Propo H. . Vork SUtaatU HI. feuaaloa PrcpeMls r;; * ^ , C*Wlo of BMXth *ad 6*mjr H#*ftrcb-iMd a X. CTW Of gCISTPP HCJICTfl AHP PCTBOIQB VKffOOAXM Pf-75 *|g*B tootur* to Aa&lfrpt Air CcooogtrotUni of EtrtlegUf lead -- Ibc E-ottcrlr.,^Tchoratory V' Voffe CD thle project ocotlauae ee planned *tth ft poeelble future pror*a extending over the next two year*. Ibe tlae axteaeloa *111 depend, of oouree, oe Whether elfulfieeat end eetlefectory reeulta ere obtained before the cad of tvo-yeer ten expoeur*. If ftttftfaetcx7 and algolfleaat reeulte ftre obtained eocner, the work trill, of ctwree, be tenlseted ftoooer. ..4 Budget Bee Mentation |3$,000 U-& - Qiaraetortotlco of Ateoerfaertc lead Aeroeole - gtaaford fteeearch Inetltute .2 Thle project bee euooeeefully ocaplated ft field rafting progjan la Loe Aagelee ftad 6ea fraacleco vltb aa eocwilatloa of adsleot air data oo total eaounte of lead pine particle alee detendaa* tlooe. The project baa not bees eueoeeeful la lte attaft to aeeeuxa aad ebazaeterlae the varloua eofotmde of lead due to Inability to Identify acryounda la the eeel.l particle elaee foud la the atnoepbere. the nooaeeoded exteaaloo vlll alio* the uee of the e^llnf tecbalguea already Oereloped la other typee of urban etaoe;Dereft taiere coal aad oil fuel are seed axteoelvely for beating purpoaae. ' It 1* probable that the dletrlbutloo of lead la theee letter ataoepfaerea *111 be different ae to total aeount aad particle alee froa that ehlch a vaa found la the California eltlea' aaapliag. Budget lUniMandrUco j?,flCO IC-76 - The Teetlae of Onieoolead Cogpotpde for foeitble todoorlnological and Antl-Hmearr Tioor Activity - Pie Worceeter Foundation dlaoe thle le eeeenttally a long-range aedlcal reeeerob project lato uncharted fieIda of aedlclne, for exanple, oaooer and erthritle. It vculd be preevreptucMa to expect reeulte after one year of ftudy. The plaa for next yuar'a *nt vlll be a aeotlauatlea of that thlob baa already baas performed. Budget Keeoneadatloa |U,S30 -,`"W t ' '. ' > *1 *' *v. 1 ft. ti&fctj* './> `i * -... v:^ !1 . :i 196b Cctcloc of B*cltb cod S*f*ty to**croh - ImI n v o f k ar*jp<nrw QLC-12 L*d 8tcblUc*d P.V.C. Ply* (Pr*p*rd by Actional Scoltatloo tawdctlon ml HER) Staff) dC-13 load GIu m for Dlao*rmr* (Prepared by IXZK) Staff) OLC-lb 1b* tadloprotactlv* Zff*ct* of Xnortcala lead (Prepared by th* Jfev Tork Nadleal Coll***) ,- CLC-15 Toxicity Study of Xoff**t*d taint Ptla (Prepared by Indurtrlal Bio-T*t laborctorl**, Zoo* cod Industrial Syilaa* foundation of Aacrica, In*. xn PTOtsiai proposals LC-75 taw Ixpoaure to Aslant Air Concentration* of tartlonlct* Zaadj 1b* Kcttarlnf laboratoqr IC-69 Cb*netrljtle* of Ataocjbcrln load A*xo*olC) Stanford fcniwt . . Institute .... v. ..... .... ... . LC-76 1b* Tastln* of Orgcnolaad Cc*$ouDd* for taMlbl* Indrocrlao* lo*leal cod Antl-Nanayy Tucor Activity; 1b* Voro**t*r foundation y *, ''- -. ". . > x <' .. ` - f ' - :x o ..$ ' * - ij %zW* 'M - -a 7* JSffL pj j x c t 9 rea ccnorrrcuric* at t h i LEAD HEALTH AXD fiATETT CCNCBTXS 1964 Kcoxr MBrm Jfrojtct 10-79 Titl* iod CoetrMtor Tuodi ____ ____________ m9u*t*d Apprwtd Toxicity TtlOf For Orgju-L4 Co^ouM* -Tfco Iloo LDborotorlD*, Id o . lod iDdurtrlol Bio-Tort labontorlM, Id o . $10,000 teAiiloa ^or kgxlDJt TOCU, A /t.rrt *'Y O/Vrt WWPUFppgl 1W w w w h -- s^g^Pr: ii.i-><;>- A* f rr-i & n. wonc eTAnMBR ron ccnstrsMrtai a t t o LEO HIAIffH ABD 8APETT COMCTU* 1S64 BUDGET MXTDO Wert Statewst T1U fund. DJU Approvtd Pur Aj.1r.Jt ULC-U LC-12 CLC-IJ mc*is B* Ite&loproUctlT. Eff*eta of InoraMila Ind *10,0* Lm4 SUblllMd P.TX. Pip. Jfi.JOO Lm4 OIu m for Uaacrwi. 25,000 Toxiolty Study of X^Mtrt ftlot Plla 20,000 /*<y /t\~r* /vrn /o m `*V~ J rr`-^T--1 '.'. -Tlf i - . > TOTAL V5.*<v fefek JYr.\-*--: V ' iiujwnvi'iii^pwajp^gi ^gTjWft BWJfl'MgBW!J''ll'1 Vfg|p WB til namioa p r o p c b a ib f o r coHsnsmnoa a t o b u a s e e a it h a x d BArerr c mo r b l$St HXDB MEZrUO Pro>et Situ toi Cootrkctor IMnda _____________ ftauert*d AppPOTad DteUlon for Agalnat LC-T5 LC-69 LC-76 tag frpoaura to A*>laot Air CoBcaotntlooa of FutleuUM LmI Cbaractariatic* of Ataitfurte ImI Aaroaolj S TMtlac of Orgaol--i Co^pooada for Po mlbla *a4ocrlDOlo*loal ud AntiMw; Iiaor Actlritjr 35*000 22,800 11,250 //. V\'o v-" / SWAL :' ' " .-...................... . i- I'Ipfe ,:M - t-a "V, Sci 5 &.v J ^ " * *:-/ ` IL ' s?r '^V.-j -^W A BU min us worm ooMcnc*mB ncaun r`^\ .'"V ' - * Octcbvr l$6j Mbaltt*4 Vjri 0. 8. Tyvoo ul C<*s*njr, Id o . 230 P*rt Avmn* XV lark IT, 8. X. [?< ' ; **? N 205.02 k-A Btatcacut af tht Problan Baaloally the problca fte*d by UK la tin fie14 of health 1* ow of ptrvaalvw lfooraooe (bout cccteatpcrary lead toxloolocr- And till* lewranoe la oot by aay acani oonflaad to Itinerant journalist#. Medical health officials, Industrial ' hygienists, aunlelpal health beard# and (due*tort art eld larly alalnfoiatd. Laat Booth tba Btate of Pannaylvanla Madloal Association pifcllchad a place on lead poisoning ldiloh was egraglouely Inaccurate. Since thaa aaothar atata ndlcal aaaociatloa bat pleiad up (ad reprinted tba aaaa fallaetoua article. Dm eurrtat (Ootobar) laaua of Cotnatf Bulletin etrrlta a aajor acara faatura on lead poisoning. Tba UK clipping nemos amually relay* several thousand rafaraaeaa to load, alaoet Invariably adverae, anxrally laaoeurata. for tha seat part thaaa (o unanswered. lo literature aslata to provide any of tba leed publics, lay or professional, vlth a brlaf atanatlon of faota which that public Aould know about load. Tba affaot of thla general laaortooa vblle difficult to Judge prcItaly la oonaldanbla. Xt la raflaotad la aeons - of research progress d o * balog oonduotad vdxleh an Intended ' to deal^i lead out of a variety of product# -- gasoline, paints, oare, ecqeorati. Xt la raflaotad la raatrlatlva labor legislation. Xt la rfleeted la dlagnoetle error aad traetaant la aaay laduatrlaX aoaldaota. Xt la finally a kind of Ignorance vhloh, If sot eteCxted, nay Jeopardise tba aeceptanee of aaay of tba new oo^ouads aad product# which Xaad rcoearoh progress ala to brlnf oa tba nartat. -V Mrtawffl&afev'l'nifrfT - rprrijTTt^tTfSftr.; mi.i ,t ntn A: ^fW^giHg^vri -- i ZA.%< j J *> 1 - 3 <^$actl of Lu C^nwnlrMlcM fr*m la Banltfc 1. to lafcn nlmot public* of tfeo facta of lMd tolMloar, 8. To oouctr*ct nl11 rg >ttwniU Is tbn profOMlaoal * noil M popular pr*M. Milan for tba frcgraa ' ' I. Xaluatrlal togtanlato 8* Mulclpal tad *nanantal banlth official* ' 3. Madlonl profaMlan %. allton J. Uwtei 6. Naan*earat nod anployiaa of flnw or procMala* lal nod M product# Action to Inltlntn Land hritli Mueatlcn Procna ' 1. Pnpnn 3-t ultt of liter*tun inning op tbn otntn of tMlulul taovMfi rtfutlai land toadoolo*? not air pollution, fluting tbu to tbn b m4 of our Ulfmat pObllff. 8. Seovra atlna circulation for itxm throat piAUnlt? and Alnct anti. 3. froduen n narln of tend Unit* evalnttora reportla* ea an Aartlopnact* nod riMWcM la l#nl. Tblf would to Mat to LXA anlllag lUt of am la plllt bnnlth aal hyjlao*, lalvwtrlnl tjrglaoa, etc. i*.. ' . - k. Fvfcllah ca a r>|ulir bull (u eoopentlca ultb the KvtUrlnc laboratory) aa aaooteted blbllofrejfcy ot artlelee appearlaf both ban tal abroad concerned ulth lead a* pifclla huu4. J. Autcaate the pcMN at mpoodui to *41ton Ao n publication carry Inaccurate utlilM boot lead. Ibeee would be um4 with *m 4 appropriate eonr letter id oopy at our m bulletin *facta about lead - for edltora and educetore.* The object at thli aham would not be to eater Into ccatimi) with tba editor but to lafaru end educate bin *0 that be elll taka a non skeptical attitude toeard future eoere etorlee ablcb Mgr aroae hie desk. 6. Contlma and accelerate cur cunant ptuayaa at ecotect vltb aedlcal eod health aeeoelatlcoe. `i -j m 0 * l .5 '1 i j j Co* ** >* 1. Prajarntloa nod production at tear tents ltfonttin bulletins. $6,000 2. Dnalsplaf appropriate ! lln| Hat and preparing adfrrnnnngmiti platen. 1,500 3. btUtlH bibliography progrno. 10,000 k, telling at land Inaltt Vanalatter (la nalllnga projected). 8,000 9. tel Una te production aonte. 1,000 6. Nbllclty c o u b mI aad aaalntaiwa la tetnartlt| tte astir* or--intentloon ttort. 19,000 T. Ccntlagnasp Total ,9.000 f,$66 'v.V'v:.v < .-'a-' - -;. r:^ r v:;r/?- y3.-v , \. , '"Avv'ict-.--"-/ -* - --f * i tflafaiiirfii i f~ii iii i i ---^--^, TNI VOICEITII lOINOItlON fOI IIMIINIITIt IIOIOIT THE TESTING OP OROANOLEAD COMPOUNDS FOR POSSIBLE ENDOCRINOI/OOICAI. AND ANTI-MAMMARY TUMOR ACTIVITY PROJECT No. LC-76 Report No. 2 For Period September 1, 1902 to August 31, 1963 Principal Investigator Ralph I. Dorfman Sponsored by International Lead Zinc Research Organisation 292 Madison Avenue New York 17, N. Y. 1 I ]S 205.03 I "d. fg TABLE OP CONTENTS Baalc Result* SUBwarjr Compounds Studied Table* 1 through 27 Table 28 Table 29 4 J *........ Q . Table 1 Worcester Foundation for Experimental Biology Shrewsbury, Massachusetts ASSAY REPORT r 4 i Eatrogen Aaaay -(Subcutaneous Injection) Submitted byi Saeplea Tea tedi Teat Anlmali Vehiclei Procedure! Dr. Henry As listed Mouse, female, 19-31-day-old. Sesame oil, 0.1 ml. par Injection. Injected once dally for 3 conaecutlve days and autopsy on 4th day. Total Material Dose Vo. of Mean Uterine ^A5lrlatered_______j[j_2_;___JJilce____^tlo__i;ii 0 0 10 0.8? A 0.045 Estrone HP-83 HP-at HP-25 mm2 0.0$ 0.15 0.45 100 100 100 100 10 2.47 A 0.220 10 3.80 t 0.228 10 5.52 t 0.223 7 1.13 * 0.068 6 1.57 * 0.020 7 1.07 * 0.058 7 1.25 t 0.030 1 ` 0 Table C Wo reel ter foundation for Experimental Biology ' Shrevsbury, Massachusetts ASSAY REPORT I Estrogen Assay (Subcutanaoua Injection) Sub It tad by i Sample# Testedi Tat Animali Vehiclei Procedural Dr. Henry As listed House, female, 19-21-day-old sesame oil, 0.1 ml. per injection Injected once daily for 1 consecutive days and autopsy on 4th day. Total Material Dose dmlnlstejred__ Mo.of Mean Otarlne ( 0 0 10 0.91 t 0.056 I Estrone O.OS 0.1S 0.4S 9 10 10 1.87 0.137 4.6$ 1 0.198 S.1S 1 0.207 - *> `j HP-24 100 10 0.86 t 0.012 200 9 0.97 1 0.072 s 400 10 0.75 0.049 .. tj HP-26 100 200 400 0.96 t 0.047 9 0.87 0.011 9 0.90 i 0.011 Tabla 3 ....... Norcaatar Foundation For Expariaantal Biology 9 Shravabury, ASSAY REPORT r: 3 Antl-Etrogn Assay (In.) action) iutaitUd by 1 Stop la a Taatadi Taat Anlaali Vahlclaai Frocadurai ' Mouaa, faaala, IB-21-day-old Estrona, aaaaiaa oil, 0.1 1. par Injactlon. Taat aatarlal, CMC, 0.1 atl. par lnjactloo. Administer traataenta at aaparata altaa onca dally for 3 conaacutlva daya and autopay on 4Ut day. TEST MATERIAL Total Doaa P4#ign*cion ____SL-_ 00 Eatrona Total Doaa ___ 0 Mo.of 9 Maaa Ptarlna * *f i.oe t 0.137 0 0 0.1 9 1.85 0.23$ 17-Hrthylcca-^* -30-01 000 KP-27 50 3000 0.1 9 1.511 O.lll 0.1 9 1.23 1 0.205 0.1 0 OKU) I *1 Rr ft-- Tab la 4 ............... Worcbatar foundation for Experimental Biology Bhravabury, Maaaachuaatta AS8AY REPORT Antl-Eatro</en Aasay (Injactlon) Submitted by 8 ample a Teatedi Teat AnlMli Vahlclaai frocadurat No u h , (mla, 19-21-day-old Eetrona, aeaaaa oil, 0.1 al. par Injactlon. Taat material, CMC, 0.1 al. par Injactlon. Adalnlater traataanta at aaparata altaa onca dally for 3 conaacutlva days and autopay on 4th day. TSST MATERIAL Total Doaa Eatrona Total Doaa Mo.of Maan Oterlne 0 00 10 0.67 1 0.034 0 0 0.4 9 4.30 1 0.306 HP-23 HP-24 Kf-26 1 0.4 10 6.16 A 0.360 1 0.4 10 3.47 * 0.133 1 0.4 10 4.99 1 0.314 .w f t  ^.*--^--...-.. ...-.1....,I--. ''** *. -'*- - - - -tr'' Vi'--rnt-i ------ - j ' i^ ................... Table 5 Worcester Foundation For Experimental Biology Shrevsbury, Massachusetts ASSAY REPORT Antl-Sstrogen Aaaay (Injection) utnltted byi amp la a Teetedi Teat Animali Vehiclesi Procedural Mouse, female, 19-21-day-old Estrone, sesame oil, 0.1 Ml. per Injection. Test material, CMC, 0.1 ad. per Injection. Administer treatments at separate sites once dally for 1 consecutive days and autopsy on 4th day. TEST MATERIAL Total Dose Designation pq... _ Estrone Total Dose pg. 0 00 0 0 0.4 ar-zj 5 0.4 SO 0.4 Go 0.4 240 0.4 MO.Of Mice 10 10 10 10 10 10 Mean Uterine patio * 8.8, 1.10 1 0.064 J.6J i 0.16} 5.55 a 0.221 5.J2 a 0.260 5.42 a 0.254 5.23 t 0.214 -T o V-*'- -- Table 6 ........... -.......... ~ ~ Worcester Foundation For Experimental Biology o Shrewsbury, Massachusetts ASSAY REPORT I1 Anti-Eatroven Assay (Injection) : Subalttad byi ` Samples Teatedi . Test Anlmali House, Female, 19-11-day-old Vehicles! . Estrone, sesame oil, 0.1 ml. per . Injection. Teat material, CMC, 0.1 ml. j per Injection. | Procedure! Administer treatments at eeperate aitea Jonce dally for 1 consecutive days and autopsy on 4th day. TEST MATERIAL Total Dose Estrone Total Dose Ho.of Kean Uterine 0 0 0 10 1.01 l 0.063 0 0 0.1 10 5-36 * 0.225 HP 2d HP 29 HP 30 HP 31 50 0.1 10 5.U 0.177 500 0.1 10 5.28 t 0.156 50 0.1 10 5.58 t 0.291 500 0.1 AIL teu> 50 0.1 10 5.91 * 0.280 500 0.1 10 6.33 * 0.23! 50 0.1 10 5.85 * 0.207 500 0.1 10 5.01 t 0.117 1wwip^ *wy,w i^i^lPLiji^Aiiwwfflww "^lyj1 if^.-wpfgB mim^'1 ""-- : ^ . ut Ai:y J'-^Ailfer.- * .1 3 ' \ \ Table 7 Worcester Foundation For Experimental Biology Shrewsbury, Massachusetts ASSAY REPORT Chick Androgen Assay Submitted byi Samples Testedi Test Animali Day-old stale white Leghorn Chick Vehiclei CMC, 0.05 ml. absolute alcohol per Inunction. Procedure! Xnunct once dally for 7 days and autopsy on 8th day. Material 0 Testosterone HP-35 Total Mean Dose Body**0. -i ....n0 *7 12 l 51 9 3 *7 10 9 52 10 27 50 9 ex *7 7 30 J*9 10 600 50 9 1200 50 8 Mean Conb 0.30 * 0.019 0.33 * 0.025 0.33 l 0.018 O.Vf t 0.025 0.51 t 0.055 o.ej o.iio 0.27 * 0.019 0.31 t 0.01a 0.28 i 0.019 I, > *5 .& h- ti~wr,:ir!,Sf.>n i'-L\ >*r.nniiiii*iW Httfljit' ' ' *................. Table 8............. - - - Morcaater Foundation For experimental Biology Shrewsbury, Maaaachuaetta ASSAY REPORT Chick Androgen Aaaay Subaltted byr Samples Taatadi Taat AnlJaali Day-old Ml# white Leghorn Chick Vahlclai CMC, 0.05 nl. abaoluta alcohol par Inunction. Procadurai Inunct once dally for 7 daya and autopay on 8th day. Matarlal Inunctod 0 Teatoateraae HP-23 HP-21 BP-25 EP-26 Total Doaa uq. 0 2 8 32 300 300 300 300 Mo. of Chlcka 9 9 9 9 8 10 10 6 Maan Comb Ratio * 8.B. 0.36 1 0.020 0.3 1 0.028 0.62 t 0.051 0.80 t 0.076 0.11 t 0.036 o.io 1 0.050 0.16 a o.do 0.10 i 0.029 ...Nx>.V . % Wore**tor Foundation for Experimental Biology Shrewsbury, Massachusetts Table 9 ASSAY AtPORT Chick Anti-Androgen Aaeay Submitted byi Dr. Bactry Samples Tested) Aa Slated Teat Animali Day-old male wtiite leghorn Chick. Vehicle i Teatoeterone enanthate, sesame oil, 0.3 al. Teat material, aeaaaa oil, 0.0S al. per I 1 inunction. Procedurei On first day chicks are injected once with testosterone enanthate. Beginning oo ease day inunct teat material once dally for 7 days and autopsy on 8th day. TtST KATtAIM, Total Doae Teatoeterone Enanthate Total Doae ' Bo. of Mean Body Vt. Naan Coab 0 0 irej IR3 EFSt6 00 0 0.5 3 0.5 3 0.5 3 0.5 9 57 0M * 0.039 U 5* 1.2k t 0.00k a (o l.kl a o.oaa a 53 i.w * o.uo a 1.3a * 0.001 Worceater Foundation for Experloiental Biology flhrevabury, Maaaachuaetta ........... -v Table 10 AB8AY REPORT Chick Anti-Androgen Aaaay lutalttad byi . aaplea Tea ted i Teat Anlmali Day-old aale white leghorn Chick. Vehiclei Teatoaterone enanthate, aeaajaa oil, 0.3 al. Teat Material, eeaaiae oil, 0.0S al. per Inunction. Procedure On flrat day chlcka are Injected once with tea toeterone enanthate. Beginning on sane day lnunct teat Material once dally for 7 daya and autopay on 8th day. TSST MATERIAL Teatoaterone Hean Total Enanthate Body Doee Total Doee *o. of Kt. Mean Coab pealgnatlon____P3_._________ Bli_________ ghlcka___ _______ Ratio t 0 0 0 12 so 0.39 0.020 0 0 0.3 11 48 0.79 t 0.077 RO 2-7239 0.3 1 O.S 0.3 10 31 0.71 0.043 10 56 0.63 0.039 r KP-1 3 0.3 11 34 0.97 t 0.071 HP-7 HR-13 3 0.3 0.3 O.S 1 O.S 2 0.3 3. O.S 12 62 1.09 t 0.033 12 39 0.91 * 0.066 11 39 0.91 * 0.072 11 61 0.88 t 0.039 11 61 1.01 * 0.060 ^ o ^i^-aftvAAS^^^av-^y^y-W 2;..-.-.;. Table 11 Woroester Foundation for Experimental Biology Shrewsbury, Haaaaohusetta Rat Anti-Androgen Assay (Injection) Submitted byi Dr. Henry Stales Testedt As listed ' '` ' Test Anlnali Ret, male, 21-day-old. Vehicles Testosterone, CMC, 0.5 ml. per Injection Test material, CMC, 0.5 ml. per Injection Procedures Castrate 21st - 28th day of life. Beginning on sa day, administer-treatments at separate sites once dally for 7 days and autopsy on 8th day. Tl*A>i TEST MATERIAL Total Dose Designation mg. 00 Testosterone Progesterone ISO HP-15 75 2 HP-1 4 -8 2 HP-7 2 Tto#t*roo* Total Dose o.of mg. lUtS M*aa Body V. . TISSUE RATIO * 8. 8. Prostate Seminal Vesicles Levator Anl 0 10 94 0.0710.005 0.1510.011 0.1910.024 2 10 90 0.5510.125 1.2810.076 0.3510.033 2 10 94 1.2710.055 1.2410.051 0.6310.029 2 10 95 1.0610.072 1.2210.104 0.6810.033 2 10 85 1.5)10.068 1.5410.055 0.8010.039 i . ` 2 8 79 1.7610.107 1.6310.094 0.8210.032 " O-VVv . r 1 >pS9J*![S 2 10 76 1.6510.136 1.6610.094 0.8310.039 2 10 84 1.7010.147 1.6710.125 0.8810.029 1` 2 10 87 1.5010.078 1.5510.081 0.8510.034 2 91 1.3410.070 1.4010.137 0.7710.040 2 10 95 1.2210.046 1.3910.046 0.7910.015 0 ' v' ''&*)% Worcester foundation for Experimental Biology Shrevsbury, Massachusetts Tabla 12 ASSAY REPORT r -vw Submitted by Samples Suknlttedi Test Animals vahlclai Procedural Houaa Anti-Androgen Aaaay InJaction Klee, Mia, 21-2] days Sesame Oil - 0.1 al. par Injection - Testosterone OtC - 0.2 al. par Injection - Tast Compound Castration - 21-21 days of ago. Injections started day of surgery and continued once dally for 7 days. Autopsy on 8th day. -v-:y TEST CCHFOtMD Total Doaa Total Dose of Testosterone Bo.of ice Naa Body Wt. TISSUE RATIO S. E. Sea Inal Prostate_______ yes teles *1 0 0 0 7 18 O o 0.005 0.21 0.039 1 a 0 0 0.8 9 18 0.28 t 0.029 1.08 0.087 Progesterone 20 0.8 9 17 0.26 0.019 0.65 * 0.052 HP-31 HP-30 5 0.8 15 0.8 5 0.8 15 0.8 ALL DEAD ALL DEAD ALL DEAD ALL DEAD h is \~rv- . *- 'J HOUt* Xntl-Androgan Aaaay Injactlon i Sutnlttad byi Sanplaa Subnlttadi Ttit Anlaalt Mica, ult, 21-23 daya Vahlclat Miwi Oil - 0.1 ml. par lnjactioo - Taatoatarcoa CMC - 0.2 al. par lnjactioa - Taat Compound ? Procedural Caatratlca - 21-23 daya of aga. Injactiona atartad day of aurgary and cootlauad ooca dally for 7 daya. Autopay oo 8th day. TEST CCKPOUHD Naan l Total Total Doaa of Body Doaa Taatoatarona o.of wt. TISSUE RATIO + 8. B. Santa al paalqnatlon 04. og. Mica g. Proatata Vaalclaa 00 90 0 0 U so 0.05 i 0.005 0.13 0.010 U 17 0.19 i 0.018 0.97 a 0.183 Artifvvtcroo* 10 20 2*0 0.8 0.8 0.8 12 so 0.17 * 0.009 0.70 t 0.095 12 20 0.17 * 0.012 0.51 t 0.171 9 18 0.18 * 0.013 0.56 * 0.052 se-zt 5 0.8 AIL DEAD ' 3 *: r? l: r H-JUlUigy .LI- -v* a Cf: <, wr;- ftps .V'-'` :v'.' *'> }.'" V :. i e Morcasbar Foundation for Ixparlaantal Biology Shrawabury, Maaaachusatta Tablt lb ASSAY REPOKY - - Sutnlttad by Saplas Sutnlttadi Tast Anlaals Vahlclst Procedural Mouaa Antl-Androgan Assay Injsctloa Hies, ula, 21-2] days Saaaaa Oil - 0.1 nl. par Injsctloa - Tastoatarcoa CMC - 0.2 al. par Injsctloa - Tast Conpound castration - 21-2] days of age. InjactIona atartad day of surgery and contlnoad ooca dally for 7 days. Autopsy on 8th day. I , j' ... . iniipinii in TEST COMPOUND Total Total Doss of ix># Tastoatarons Designation a>g. _ > No.Of Mica Ha an Body 1ft a g. TISSUE RATIO a 8. B. Ssalnal Prostata Vaalclsa \ 00 12 19 0.09 * 0.011 0.17 a 0.0U m 0 0 0.8 12 20 0.20 S 0.022 0.80 s 0.058 rr^ntfrom 20 10 0.8 0.8 12 22 o.i; t 0.012 o.l; t 0.019 12 21 0.18 * 0.018 0.10 * 0.018 HP-27 HP-28 10 0.8 10 0.8 ALL OKAS ALL MAD v*,* ,7 >1 "*r -ih h ?1 sy_ Worcester Foundation for Experimental Biology # - Shrewsbury, Massachusetts ASSAY REPORT Anti-Androgen Assay-Mouse (Injection) Material Administered 0 Teat Compound Total dose mg. 0 19-Morprogesterone SO 40 HPS3 HP26 40 40 HP2T 40 Testos terone Total Dose mg. Mo.of Kloe Kean Body vt. e* 0 0 SI 0.8 9 so 0.8 8 so 0.8 8 24 0.8 6 17 0.8 5 15 0.8 9 22 TISSUE RATIO m 3. I. Prostate Seminal Vesloles 0.13*0.032 0.2110.026 0.1710.014 O.861O.060 0.1910.018 1.0510.063 I 0.1510.018 0.5U0.046 0.2110.027 1.0510.156 0.2910.033 1.1610.198 0.2210.013 1.0810.104 i ^jBegewyMM-pi * k ./ . i . ` ' :,- k*-:_ House Anti-Androgen Assay Injection Gutaaltted byi Saaples Submitted! Dr. Halcola Henry Aa Listed Teat Animals Nice, aale, 31-21 days Vehicles seaame oil - 0.1 sal, per injection - Testosterone i Procedure t CMC - 0.2 ml. per injection - Teat Compound Castration - 21-23 days of age. Injections started day of surgery and continued once dally for 7 days. J Autopsy on 8th day. i TEST COMPOUND Total Dose Designation q. Total Doae of Testosterone mg. >o.of Hlce Mean Body Kt. 9- _ e 0 0 10 16 TISSU* RATIO f. I. Seminal ' Prostate Vesicles 0.08 * 0.00$ 0.19 * o.ce% 0 0 0.S 10 19 0.19 t 0.019 0.93 * 0.07% Pros*stereos 20 %0 0.8 0.8 6 19 0.25 * 0.018 0.87 * 0.186 9 19 0.21 t 0.031 0.7% a 0.038 HP-27 10 0.8 10 0.8 SCAD OCAS ^ - - Wore#a ter foundation for Sxperlmontal Biology Shrevabury, Kaaaachuaatta Table 17 ASSAY REPORT No q m Anti-Androgen Aaaay Injection Submitted byl tamplea Submittedi ' Teat Anleali Procedural Klee, male, 21-21 days Seaama Oil - 0.1 ad. per injection - Teatoeterone CMC - 0.2 ad. per Injection - Teat Ccmpound Caa tration - 21-23 daya of age. injectiona a tartad day of aurgery and continued once dally for 7 daya. Antcpey on 8th day. TEST COtPOOBD Total Doee Total Doee of T*ttot*rom M. Vo* of MlC _0 5o 00 0 0.8 7 4 rogeaterone 2.S S 10 0.8 0.8 0.8 9 9 8 HP 32 HP 33 s s 0.8 0.8 Dead Dead Naan Body Wt. 17 17 16 19 16 TIS3UX RATIO 2 8. B. Seminal Proetate Vealclea 1 j 0.02 t 0.010 0.17 0.018 P? 0.17 * 0.012 1.01 t 0.151 ; 0.10 t 0.022 0.11 1 0.016 0.09 t 0.015 0.90 * 0.111 I 0.96 0.163 0.84 t 0.147 8 \!V -y Worcester foundation for Experimental Biology Shrewsbury, Massachusetts 1 A ASSAY REPOKT Parabiosis Assay (Injection) Suinlttad byt Samples Testsdj Test Antreatsi Vahlclst Procedural Kale and fsaala rats 21-day-old CMC, 0.2 al. par injactlon Placa a castratad reals (29-31 days of aga) la parabiosis with an Intact faaala (29-31 days of aga). Bagln Injection of tast reatsrlal on day of surgery and continue ones daily for 10 days and autopsy on 11th day. Kata rial Adrelnleterad 0 Total Dose . pq. 0 Teatostarona 0.8 [ KP-21 10 lo.of Pairs 5 5 5 Kaan Body Vt. Q, 101 MALI - CAITXATK Naan Kaan Sam Inal Mean Prostata Vesicles Levator Anl Vt. Vt. vt. mg 1 S.S. mg l 8.E. no 1 6.B. 11.5*1.080 ll.8tl.021 16.012.362 103 55.1*11.003 95 12.0117.008 52.4111.327 26.213.98? 10.7H.144 ll.9il.508 ZXTACr PZKAL* Mean Body Vt. g. 93 Kaan Ovarian Vt. mg 1 S,B. . . 124.0121.884 93 61.5127.204 85 96.5127.950 m i-v'v.V-. .a *./sT iV.^, Worcester round!tion for Experimental Biology Shrevsbury, Massachusetts Table 19 ASSAY REPORT Kxpar. Bo. Autopay Dates * 4 4 Anti-Mammary Tumor Assay Subalttad byi Samples Testedi Test Animals Vehicles Procadurai Dr. Malcolm Henry Sprague-Dewlay rat, female, 45 days old on delivery. CMC, O.S ml per injection. Tumor seeds were transplanted Into the rats at 52 days of age. Beginning 5 weeks later, those animals having growing tumors were in jected once dally for 14 days. On the 14th day, each rat received 5 uc/10 u mole glycine-2-c14 in O.S ml 0.9X saline followed by autopsy 24 hours later. Material Administered Total Dose mo. Mo. of Rats Mean Body Wt. g, VO. of Tumor# Mean Tumor wt. mg. Mean Specific Activity crci/ma Protein * S.E. 0 0 11 233 20 2648 102.3 * 3.99 2a-Methyl-5o-dehydrotsa to- 7.0 sterone________________ HP-28 21.0** 11 7 252 239 20 1990 89.0 2.98(P<0.01) 11 3701 108.2 6 2.88 HP-29 21.0** 10 240 19 2497 117.2 1 2.68(P<0.01) HP-30 21.0 233 14 5438 122.8 1 4.45(P<0.01) HP-31 21.0* 10 220 17 2041 105.7 * 2.58 * Considerable lnfleimaatlon at site of injection. + Slight inflammation at site of injection. i ............ Table 60 ........... Korea a tar Foundation for Experimental Biology Shravabury, Maaaachuaatta AS8AY REEORT THYHOLYTIC AMD AHTI-IHrLAMMATORY ASSAY (Injection) 8uhmltted byi Snapla a Teatad 100-123 g Taat Anlaali Mala rat *l-*3 day* old at atart. Vahlclai CMC, 0.3 ad. par day by Injection. procedural Bllatarally adrenalectcnlae rata oci 23rd-26th day of Ufa and inaart two cotton pallata aubcutanaoualy. I Baginning on aame day, adalnlatar treatment ooca dally for 6 conaecutlve daya and autopay on 7th day. fc: Remove granuloma* (cotton pallata), weigh, dry for 24 houra at 100C and walgh again. Alao remove and walgh, aftar blotting dry, aach thynua gland. Hatarlal Administered Total Doc .. Ha an Body Ht. g. THYMUS TEST Ho. of he an Thynua Rata Ratio 1 S.E. ANTI-INFLAMMATORY TEST Ho. of Mean Cry Tlaaua 0b* Wt. mu. t 8.R. 0 0 153 7 2.74 1 0.144 8 129.2 1 18.972 Cortlaol 0.3 147 7 2.65 1 o.ieo 1.0 152 8 2.41 t 0.147 4 2.0 150 e 2.52 0.111 4.0 155 B 1.30 1 0.092 HE 32 3 137 4 3.71 t 0.269 8 121.9 t 12.827 8 163.2 23.409 8 96.6 t 3.863 8 73.1 * 8.914 4 104.2 1 9.354 HE 33 5 139 7 3.14 1 0.168 8 103.9 t 13.518 p Oroupa HE 32 ~ HE 33 - Compound undar Skin 3 4 -i  'V-~:v * T. Up--,'fid .rlV*' v--.*'\S *.* .*\-\\-ti i : : i 1> iliiMhfir 'lti Tl'Ti ^-.e-.---e^-*w , Worcester foundation for Experimental Biology Shrewsbury, Massachusetts Table 21 ASSAY RSfOJCT THYMOLYTIC AID ASTl-IXfLAMiATOXY ASSAY (Injection) Sub*Ittad by i Samples Tea ted i Taat Anlaalt Vahiclai frodedurei Mala rat 31-2) days old at start. CMC, O.S al. par injection. Bilaterally adranalactoalaa rata oo 23rd-26th day of Ufa and Insert two cotton pallets subcutaneously. Beginning oo sane day, adalalater treatment one* dally for 6 consecutive days and autopsy oo 7th day. Raaova granulosus (cotton pellets), weigh, dry for 74 hours at 100C and weigh again. Also rssora and weigyhii,f after bDliootting dry,.each thyme gland, Matarlal Meaqjfa lght Total THYMUS t e s t Doaa vo. of /mMeian Thyms Awri-nnjustAToiQr So. of Mean Dry Tissue Rats W Rat 0 0 67 3.48 at 0.331 8 24.7 t 2.230 Cortisol O.S 11 75 3.43 * 0.177 1.5 12 75 3.08 0.118 4.5 12 72 1.35 t 0.107 11 12 12 17.4 * 1.389 17.7 t 1.539 15.3 t 1.212 HP-23 8 5 80 3.79 t 0.337 S 17.6 t 2.132 Hf-24 8 4 80 4.28 t 0.728 4 22.8 t 9.874 HT-25 8 DEAD -- ----------------- Hf-26 8 1 75 4.13 at 0.424 3 21.0 * 4.362 8 5 70 3.47 1 0.522 5 17.7 2.650 **-m*m rTm -t t '<U* *^Ttt >*'> ' . : ' ' v - vi - !- ' I' Tati* 22 Vorpeater foundation for Eaperlaental Biology (hrcvatury, H>aa*chu*etta a S3aY REPORT t b t mx t t ic a id /om-iwwATarr a s s at (Icjectloo) i 0 i SulaltM By: Staple* Tceted: Tnt Anlnal: Vehicle: ftocetoe: Dr. Henry - HP-13 Mil* rat 21-23 day* old at atari. DC, 0.5 al. par Injection. Bllatarally adreoalactoala* rata 00 23rd~2tith day of Ilf* aod laaart two cotton pallet* eubcutaneonaly. Beginning 00 aaa* day, adalnlater treeteent ooe* dally for 6 conaecvtlve day* aod astopay 00 7th day. Bo o t * graauloaa* (cottoo pallet*), weigh, dry far 2H hour* at 100C and v*lgh again. Alao mm aod weigh, after blottl^ dry, each thyao* gland. Ifcterlal Atelolatered 0 Cortlvol ip-13 total Doee ag. Mean Body Vt. 0 85 1.0 82 1.0 81 1 72 2 78 TH94U3 TEST Bo. of Hean Thjwoe Bat* Ratio 1 S. B. 8 3.81 t 0.27% 10 3.0% t 0.129 10 1.52 t 0.136 7 3.65 * 0.268 8 3.81 t 0.253 AlTI-IBPWdUiarr fc. of Mean Dry tl**u* Ob*. Yt* ag. t S. Z. 8 23.5 * 2.600 10 17.6 11.K9 10 12.8 * 1.127 7 16.8 t 1.615 8 20.7 i 1.515 i i 7 Table 23 Worcester Foundation for Experimental Biology o Shrewsbury, Massachusetts ASSAY REPORT THYMOLYTIC AND ANTI-INFLAMMATORY ASSAY Submitted by: Samples Testedi Teat Animal: Vehicle: Procedure: Kale rat 21-23 daya old at start. CHC, 0.5 ml. per Injection. Bilaterally adrenaleotomlse rats on 23rd-26th day of life and Insert two cotton pellets subcutaneously. Beginning on same day, administer treatment once dally for 6 consecutive days and autopsy on 7th day. Remove granulomas (ootton pellets), weigh, dry for 24 hours at 100c and weigh again. Also remove and weigh, after blotting dry, each thymus gland. , A Total " Material Dose Administered mg. Mean Body Vt. THYMUS TEST ANTI-INFLAMMATORY No.of Mean Thymus No. of Mean Dry Tlsaue Rats Ratio t S.E. Oba. Vt. mg. t S. E. 0 Cortisol HP-13 HP-14 0 0.5 1.5 4.5 4 8 4 8 70 9 70 9 74 10 74 9 57 5 75 2 61 3 62 2 4.10 1 0.111 9 3.18 t 0.253 2.93 * 0.140 1.90 * O.167 9 10 9 4,65 t 0.694,,,_ 5 2.63 t 0.704 ' ,2 3.82 t 0.250 3.86 t 0.773 3 2 29.5 * 4.229 19.3 t 1.700 19.0 t 1.288 11.5 * 1.972 10.2 t 2.631 18.0 t 0.606 16.3 * 0.836 19.7 * 2.575 0 'i iif'*' "' y HHTliiyumv (il ll. "In' 'aii'ii.iifnaf ""I'm nrffuj^piwpffy i ii i Worcester Foundation for Experimental Biology Shrewsbury! Massachusetts Table* 24 ASSAY REPORT t l | Submitted byi Samples Submittedi Twat AnInali Vehiclei Procedures Mouse Anti-Androgen Assay Injection Dr. 0. M. can der Want, T.N.O. (Lead Compounds) As listed Mice, male, 21-23 days Sesame oil - 0.1 ml. per injection - Testosterone CMC - 0.2 ml. per injection - Teat Compound Castration - 21-23 days of age. Injections started day of surgery and continued once daily for 7 days. Autopsy on 8th day. t TEST COMPOUND Mean : Total Total Dose of Body TISSUE RATIO + 8. X. Dose Testosterone Ho.of Wt. Seminal Designation mg. mg. Mice g. Proetate Veslcles , 10 0 0 6 15 0.05 * 0.013 0.20 1 0.033 JO>l49(THO) 20 0.8 DEAD - 32(7S0) S 82 (TWO) S*129(TN0) 20 20 20 0.8 0.8 0.8 DiJU) DEAD 9 16 0.17 * o.cei 0.75 * 0.046 froeesterone 0 2.5 5 10 20 0 0.8 0.8 0.8 0.8 0.8 9 16 0.19 * 0.015 0.93 * 0.060 8 13 0.19 * 0.014 0.G6 t 0.066 8 n 0.20 I 0.017 0.76 0.053 9 n 0.14 1 0.015 0.46 X 0.041 6 15 0.22 x 0.009 1.20 X 0.156 n^Tnnrf-'- - ' *; ' a iiii,.-eA.arr.,. % i mm!&EXAL *. "*rr v.'f 'rr.r-rrtfy.ygta1 <s5fei'K5VvS Worcester Foundation for experimental Biology Shrewsbury, Massachusetts Table 25 ASSAY REPORT Submitted byi Samples Submittedi Test Animali Vehicle Procedure Mouce Anti-Androgen Assay Injection ' . - Mice, male, 31-23 days Sesame Oil - 0.1 si. per Injection - Testosterone CMC - 0.3 ad. par Injection - Teat Compound Castration - 31-31 days of age. Injections started day of surgery and continued once dally for 7 days. Autopsy on 8th day. TEST CCKPOOB) Total Total Dose of Do Teatosterooe >l<rnat Ion eg. __ TKJ. 000 Vo.of Mic 6 Mesa Body Kt. g._ so 0 0 o.a 8 si progesterone 8-116 (TX>) 8-7*i (ISO) 10 so 0.1 0.1 0.8 0.8 0.8 0.8 7 19 8 19 8 19 8 18 vi-Ida (no) a-79 (TWO) W-22 (nn) 0.1 0.1 0.1 0.8 0.8 0.8 6 18 8 18 8 18 TISSUE RATIO + 8. B. . Seminal Prostate Vesicles 0.08 1 0.01A 0.2} t 0.021 O.S3 * 0.017 0.91 * 0.118 0.20 t 0.012 0.21 * 0.017 0.17 * 0.012 0.18 * 0.027 0.21 1 0.02} 0.23 * 0.023 0.21 * 0.019 0.65 * O.O53 0.71 S 0.082 0.77 t 0.0k6 0.91 t 0.12k 0.82 t 0.096 1.03 t 0.118 0.89 i 0.097 i: Worcester foundation for Experimental Biology ------ -- 8hrev*lxiry, Massachusetts ASSAY REPORT Table 26 Estrogen Aaaay (Subcutaneous injection) - " Submitted byi Samples Tsstedi Test Anlsali Vehlclei Procedure! '" Mouse,female, 19-21-day-old. Sesame oil, 0.1 Bl. per Injection. Injected once dally for 1 consecu tive days and autopsy on 4th day.. Material Administered 0 Estrone *-u6 no ac-7* no V1A88 no ac-79 no Ms-22 no cb-iig no *-0) no oc-62 no *-129 no Total Does vq. 0 Vo. of Mice 10 Main ut*rln Ratio t 8.K. 1.00 s 0.059 0.0$ 0.1 0.2 O.k 10 2.11 t 0.090 10 3.27 0.297 9 4.6$ 1 0.267 8 5.26 * 0.277 100 6 3.W t 0.375 100 5 0.87 t 0.060 100 6 1.06 t 0.09$ 100 6 0.88 1 0.073 100 6 1.01 t 0.071 100 6 1.13 * 0.068 100 6 0.86 t 0.072 100 6 1.09 * 0.076 100 6 1.02 1 0.000 ______________ Table 27 . _________________ Worcester Foundation For Experimental Biology Shrevsbury, Massachusetts ASSAY REPORT Antl-Istrogen Aaaay (Injection) Submitted byi 8 amplea Teatedt Test Animali Vehiclesi Procedural -V-V- He, van'Aor Want - , Mouse, female, 19-21-day-oid Estrone, seaaaa oil, 0.1 ad. per Injection. Test material, CMC, 0.1 ad. per Injection. Admlnleter treatments at separate sites once dally for ] consecutive days and autopsy on 4th day. TEST MATERIAL Total Doss Designation p i. Vo 0 Estrone Total Dose PC. 0 .0 o 0.1 302 (wo) >,;>4**000^ i/V.Oefc " * aS3 (no) 1000 0.1 10019 (no) 79 (no) 1000 ,1000 0.1 0.1 aoK (wo) ' 2000 0.1 v is a (no) 3000 0.1 M2 (WO) SKI* (WO) 1000 0.1 1000 0.1 0029 (WO) 1000 0.1 Mo.of Mean Uterine Mice Ratio t S.S, 12 0.97 * 0.068 12 5.75 t 0.208 DEAD KAO , BEAD SCAD 2 J.79 * 0.071 SCAD KAO . , : .. SCAD . 12 1.59 a 0.210 '. . .: . . a _ i 'y*. '' *. .. ^ , i.fy V- ."i WMKMY PoasUbla Significant Activities Requiring rurther Confiraatloa Table WO 30 ... expound ar 32 ttf 33 Significant Actlaltv Anti-Inf1--story Activity 21 22 a " ` fa V' 29 HR 23 Kf 26 If 13 H 14 Antl-infl amatory ' Activity ' - - ,;?*' Antl-Infla--atory .* Activity - ` \ ' ' ., - SK 129 M J' ' Anti-Androgen ~ . * . ................. - sx-116 (no) Antl-Androgan r' 26 sx-116 (no) Xatrogan.................... ' * TABLE 29 Code COHPOUXDS STUDIED Structure Sk 116 Sk 7* Xb 19 Sk 79 Sk 62 Sk 83 ' Ha 22 VW1 488 Sk 129 V. . ' ' > Phenyllead triacetate ' Dibutyllcad dlecetate Trlethyllead eoetate H( trlbutylpluBblyl)>taldacole Trlaethyllead acetate Tributyllead acetate Dlethylleed dlecetate - Trlaethyllead cyanaside '' ' ? Tetrebutyllead , jV. - Tetrephenyllead . Bla-triphenyllead sulphide 1 Thlobenzyltrlphenyllead Thlophenyltriphenyllead -- Thloaoetyltrlphenyllead lead Benzyl Mereaptlde Lead dlthlobenzoate v, , > v 1**0 thlophenolate v* eWW - aino acetate eoaplex Trlphenyllead dlmethylaralnate , t Bla-dlphenylohlorolead sethyl aralnate ^3 FbSCHgCOCEt .-(n3 fb.* 1 i HP 29 HP 30 jo';*^ HP 31 ' ($)3 PM (t)s *> - S 9V : OO '.V$fv:vr & D0IXM1 HA* CtllfonU N 205.04 ''? ''Vn ^S||gQ|-`'' ' for lead aaroaola la intan ana* but tbay aapbaalsad tba odtKWtlan ef coal aad teat frea hlgi-laad aoila. 9>ay further abate that 90> of tba laad la coal *111 ba dlacbarpad to tba ataoaifaara and tbat lairiMil la**la of laad la tba atacwpban la oartala eltlaa durlac tba vlatar ay ba Aua to tba laoraaaad coabuatlon cf ooal. Baoauaa tbara art urban aouroaa ef laad la addition to tba auto* ' Ob11a, Btm data abould ba gatbcnd oo tba Datura cf tba ataoajbarla aaroaol la tbaaa otbar aorlrooaaota. To* purpoae of thla aiwpllac would ' ba to axmlaa tba aeroaol alia chanetarlatlca la h m ana* tbara tba autOBoblla any act aaceeaarlly ba tba anjor aouro* of, tba laad aaroaol* Place# Milch would aoat likely eona vltbla tbla- natatory would ba mm aaatern or ald-wiatara araaa tarla* tba vlatar M>ea ooal aad fuel oil wara being **4 la relatively large aaouot*. Bo m affort abould alao ba aad* to obtain naaturwirta ou background teat la acna roaota araaa. __ . . .,9wra an aaoy naote ar^aa la California aultable for Maurnint.* of - natural atooejbaric lead concentration. . .- ' IB addition to obtaining data ea laad aaroaola la tbaaa otbar araaa, aoat attaotloo abould ba given to Identifying tba naaeoa for aad tba algalflcanee of apparent variation# la laad aaroaol ala* diatri- butlooa. Tor ana;la, durlac tba flrat aa^illng progyaa la tea datalaa, It waa aotad that aftaxnoou analyse# aboaad generally a -- Har alaad : aaroaol than Burning teata. further atudlaa cf aareiol ebanctarlrtle* teoild attain to determine to tbat aztant aueb varlatlooa rupmaaet rwal change* la source characteristic# of *tw>epberia prooeeeea and to ` tbat extant they night ba dua to raadea affaeta. . tba aatura of tba laad aaroaola la of Intaraat baoauaa expoaun " to aaoaaelv* ococantratloM oao ba torlo. fartlcla alia aad ocnoeotntlcn ., .,^*rafOoly two factor* wblob ban an liportant.bearing on tba tcxlalty at ' " tba aaroaol la any given altuattco. Br, Kabo* atotlana tbat aootbar v * ` factor la tba obaolcal ccagoaltlon of tba ataotibarlo aaroaol.* Bo m . ' laad expound* an nuch laaa trotblaaeaa tbaa otbar*. Qua, lnforaatlcn ,. on tba chaateal aatura of tbo etaoejberlolead aaroaol eeuld bava lapor* tact application# to ccasualty problem#. Tba raaaareh progna to data ' baa Included ooaaldanbl* affort to Identify tba laad eaqovad* asking . up tba aaroaol. Hadron and x-ray diffractloo techniques wan tba principal aethod* uaad, but tba axparlaaata wan, la ftatral, aosuoeaaaful. . . - lba lack of auooaaa oaa ba traced to tba wal l ala* ef Boat of tba aaroaol partial**, tba lew concentration ef laad la tba total ataoepherla teat, , . - aarlooa lntarfaranoaa frea otbar ataoattwrlo aaroaol net*rial*, and Aba , laad aaroaol ltaalf balac probably not a alacla ooapound but a aonplaa '> . alrtun of aeopeuada. Bco* aharacterlatle# of tba lead aaroaeljula y. ;j . particular lta aolublllty, bava baas obtained frea atudlaa ef bulk ' **B>1*# obtalnad with hldb-voliw* aaaplara. A non cartful dallaaatloa of tba tbyaloal cbermcteriatlca of tba laad aaroaol would provide aaa* baaaa for aatlaatlec tba aatura of tba aaroaol la tba abaanoa of direct ea^ound ldaatlfleatlea. .. _ ' taboo, p, A. Iba hygienic aapaota of tba production aad uaa of laad aotiknook o<Mpouod. Joure. drat (7) J14 (July 196)). . . Method of teawb Cm pivpoHl Kotlauatloo of tbo etudleo of ataoepberlo load Kill extend end eoeplamect *m progrea xhlch la belac oceoludedj Much of the methodology bee already boon eetaollebed. ' Cm exteoelao of ilu iu| Mjloh oaa bo eonred la elacla easing period caa doUbtleaaly bo dona bp operating too Oooto Aeroeol Spectrometer* la parallel (oat unit operatise la tbo large oUo range, ' tbo other unit la the nail olio race*). A oaooort Aoroool SpeotrcaMtor canryrt bo oddad to tbo praeeot noblle oanpl <ng eyetan vltbout aoklae oon change#. At proaoat, tboza la aot anough power for a append epitea. Cm large*! alDAlo power uaer la tbo rofrlforatlaa ayetea Milch aalntalao tbo Aoroool Spectrcneter at a ocnetaat toaperatuxa. Several poaolblo eolutleoa to tbla problem are (a) lnetalllng opoolal refrigeration vltb lower power regilreaiota, (b) operatise two epectrcnetero fra a alacle . refrieuatlon ayetea and () adding additional (nuatlai capacity. Cm flsal choice would depend 00 Mileh inhoaa ooold bo aoot readily adapted to field eetrice. Vlit, apace, ccoplaxlty, oad dependability axo tba aoot leportant criteria, Ccaalderatloa Mrould also bo (lees to tbo deelgn of a elacla aeroeol epectroaeter with e greeter range, Cila could bo Obtalaod bjr lnexaealng tbo olu of tbo collector coco oad tbua prorldlsc aa lucreeeed path length vlthls the unit. An esalyilo cf tbo proooat daolga indlnotoa that If the prooent c o m wore Increased fra 8 to lb ea, tba path leoctb wcttld laeroaoo fra tbo pxeaeot bb ca to aoxa tboa 100 ea. lhle would aarfeedly lacreeee tbo alie rose* of tbo ualt. Bowraar, Wbetbar tba ala> Clo large ualt would perform bettor tboa two etaadord unite eon only bo determined by careful calculation uolnc tbo pro#aptly available date on tba load aoroool characteristic#........... ,, u r, 'V'v'Vi.- -V*St -4^:' ' `ifew " ' " A doclalon ca tbo boot waqr to expand tbo olio range Cwald bo '* ' Bade early la tbo proem bocouae. If at all poeolble, tba expanded - ooapUsg oyoten obould bo uood la tbo oxtondod field progioa wblcfa bao - boon proposed. It ehculd aloo bo tooted la tbo loo Aagcloo area and tbo rooulto ocegared vltb toot* aade la 156]. _ - tbo propoaod field proem will bo dealgned to explore the alw distribution oo well 00 ana of the jbysloal and rtioalnal charactertotloa of ataoepborla load aoroeola la arooo Miere autcaoblle obauet aay aot asoassarlly be the aajor source. SoapUr* should be cerrlad out la tbo viator or early spring la order to Obtain tbo aarlauo lafluraoo of epaoe* beating offluent#. It la planned to carry out tbla online la two cities end to spend about throe weeks in tech clty. Io selecting the two oltlee, o m of tbo chief criteria will bo the fuel need. Atteapto will bo aado to eelect eaa city Mmre coal 1* tbe'aajor fuel aad another Miere fuel oil predcalsatoa. Seaplee will alao bo talas la tarlouo rural arooo to determine tbo load ccmtect of natural duet aoroeola. Cila probably con bo dcoo aoot Choreslastly by aallne atopovoro la rural areae durloe trlpo botwoaa urban tpUsg locstlcno. Special trlpo to ocwo raoto California area* would aloo bo aado. Curing the field work, eaaiplea will be taken and reeorred for ' tbo ooepouad identification reoeerch. Ilgh-voluae peopling will probably be tbo boela technique need. the laboratory proem will laweotlcpta chornnterlftlei ouob no eolUblllty, aeltlnc point*, vaporixetlcu tcaperutuno, etc., of the lead oexpounde fousd la bulk eaopleo M a NMD* of eharaaterltetlco. fejbaelo vlll b placed tmtiotty OB tlio** ccaceunde prerlouoly Identified in outondbllo exhauet. Purtbor work on olncle particle Identification will not b el iiliil, but ex ploratory experlnente vlll bw carried cut co technique* that alit orer- ooa* th# known dlfflcultlo* fnclne thi* type of onalyol*. Son onelytl- el offart Bight b# directed to o*er*e*tlnf tbo hlgh-volra* oenpl* no tbnt Bufflnlant ooooootretloo at tho land oaponli la attained for x-ray diffraction. lhi* load onrlcbacst Bight b oooaopllehod directly la tba collector} additionally, thar* any bo nood for oolactlr* extraction nod/ or *7*por*tlTe prooodtao* In ordor to provide oultoblo iflu for diffraction. . -- tbo tbroo reMarch phone* outllaod obowu -- (loo rone* orteaolog, non-mtqedbllo oowlraaontol ooapUng, tod oriipound ohoractorlintlca -- 00 bo Intocrutod Into a 12-aaoth roooorcb proem* 9m followlod tentative tlaa-tebl* for tbo roooorcb procraB lino prootleol. Plaid eo^iHi^ In cool- and oil-burning orooo ohould bo eorrlad out during tbo period of Jonunry Hatch, 196k uolne oltbor tbo extended roof* ayotoa If It eculd bo taooMlad la tlao or tbo proMet unit, tbo opring and aaMr proem would lnslodo ooUbrctloa work, rural and local Bay In* ooipllni, and about oom aaatb of Mailing In Loo Aneoloo uolne tbo extoodedronge . tnlt. tbo onalytloal ccapouod ldoatlflcotloa proem vlll oootlnao no a otoody offart. t/ v Data onolyolo and report preparation vlll ococludo tbo oooftioet. In oddltloa to tbo final rvport It would oeeo daalxablo to opoad aeat tlno preparing ona or two coegroheoelvo tocbnloal paper* deocrlblnf tbo pro*iao cod It* reoulto. tbaa* could bo given at tbo oprlng oaetlne of a teobnlcal eoalety ouch ao tbo doorman OoopOyolool OBIaa or tbo Haiti. oon Omo Ic q I Society. Pertinent dlacuoiloo ond crltlclea durloc ouch a technical prooeetotlaa oould bo oooaldered la yt--<-g tbo latter port : of tboMooarch proem. - . . n OBtiiuri qnupzcAtsas tblo roooorcb, like tbo prooont proem, will bo carried out la ' tbo Sopartaaat of Atooopfcorle Sctoaoeo wltb cooelderablo aeeletaoo# tram tbo Analytical Been*tub Dopartoent. 1b# facllltleo to bo uood Mil Include not only tbo opoolallMd project opdirnt, but aloo tbo exten- olro laboratory faellltloo of tbo Inotltuto. Thoa# opeojailood jfao111ttoo vbleb are expected to be uotd durloc tbo reeoaroh prograBInclude aoroool conoratloe and onalytli equipment, tbo tltachl alootroo Bleroaoopo, and tbo x-ray diffractloo oqulpeoat. Ptraooool who have boon tbo leejor oootrlbuton to tbo proooBt raowanb are expected to eoctlnue their ooooolatloa with tbo proemi Kr. kloor Boblneoo, Project Leader) Dr. John S. CoVrloo, Nuegar, Analytical Sorrlooaj Dr. T. lopkloo, Cbaalot (x-ray dlffmtloa)) Sr. S. Cbalkla, Cbooltt (alootroo Bloro*oopy)| Kr. P. L. Ludvle, Meteoroloelet (field ooapllnc and eallbration otudlee). In oddltloa, other Inotltuto otoff Bohan will bo eonoultod when their epoolollxod knowlode* oould bo uooful la eolTlnc roooarab probloao that orloo. % 4 - *F'r5S5:',*I* irliiMi to ollalaoto pennant **lr*t ptrlodlo leveloat, the edvoaoe hfMlt a/ bo laamii) to lOOJt of eutborlied fund*. Upon ooopletloc of ft . project, eejr uacxpcnded projeot fuado or* returned to the client. tbli propeeel eoa ba ootoMLlohod m o project bp otpslaft oad rebaralaf too oopl* of the eaoloeed rtoaderd ipHiatf tdiloh or* laeorporoted herein oad node o port at tblo propoeel, elect vltb ft cheek fer tbo advaooa payaont. - . 9m oobotltut^porocrojti 10 oad tbo oddod peracrogfc 11 la ear priooot eoBtnct vltb load laduotrloo Aeeoolatloo, lac. doted 1 Aa^uot 1962 or* tPlto ootlofoetot7 for laeluoloo la tblo prepceod contract If blind. P*rfc**am dotoo ooverlnf o period of 12 ftootho 00a bo laaertod ' 00 poet 3 of tbo Stoadord Acreeoeat fora to cult Isteroetleeel load Zlas Doecoreb Orpoalxotloo ocotroctlaf oad funding tebodoloo. ' Acceptance Period 9ilo propoool vill reoola la effect oatU 31 jaaar7 19A. After that dote, vo vlll gladly eoooldor oa ektenclca of tlae If doolfod. Wo *111 bo able to offinni vert 1--llitilj after outborlootlaa* .' * Aeepectfully odbdttod, ' . . . Signed* Klaar kcfelaeca , ,;S > Uaer noblaooa, Beeler Wrt*orelolt Depertaeat of Ataoepberto Soloaoeo . Approeedt liaedi Cborleo J. Cook - Cborlee J. Cook, Blraetor ftwlnl Ibyelaa Divioloo - !>/- ^ .f* t ;V--` ^ *v; c*?.V*^** N*J^Vri\*ifji1 r m v o b c w iw f n h d a t x o i j o * cmaKtm b b h j o o t Ft eject # Ifi-T* --j 9 ttirevabury, tfceaacfcuectta eptader 11, 1963 Bsmxi nonuL Tot tKUrottloool Lead Lias Btaearch Orycliatlca 292 Madlaon Avenue e* Tort IT, I. T. / Tltl* of ftaaaarcht OH CTSTOO Of OKVWOUAS OOM'OOTS F03 FOGS1312 DDOCSIRLOGICAL AID Mni-NMMAia OMM ACTIVZn. . Gq mt o I Btatoaeatt tar. Maloola C. Bear? of Betid, Ifcesachuaetta, baa flma and lcteode to eontltua to give at verloua crpaolMd caapo'mda for testing. Va hen also received coapomda flat Frcfaeeor na dar Vast. Va fotmd Kai cotpousda vitb possible l^ortaat utilities. Va vlsb to continue these atudlaa. Our taata vill Include androgenic activity (aela sex banoot), estrogenic activity (faaale sex borne). anti* estrogenic (poaalbla antl>tuaor activity), actl-endrcgenla activity (poaalbla traataaat of proatatlc cancer), aad aatl-lBflaaatory activity (poaalbla traataaat for tbetawtold arthritis and allergic disrates). . V ;;v"'Va should alao be plaaaad to1 study rrgsnclesd caapounda froa otbar aoureaa. '' . IVcsaber 1, 1963 to Bonder. 30, i$Sk. ' ' \-*f 1 Bloestay Technician . ...............................( 3,000 Data, Klee aad Cblcka. 3,000 Conatasbla Buppllee ........... . 1,000 Direct Coata ...... 4 9,000 Xadlract Coata 85# ... . 8,250 . ^ , " . TOTAL ^ ' 11,230 - . "W* : / ' SigseAi Daljfe Z. SartaM ' . " ' *ai* X. .; v. -A-- s'fv- BUCOOR aOMLUa, Ib.D., Be.D. OKKOKT FDIOB, 60.D. Min X. DORFMUl.fb.D. Esaeutln Director ftteeersh Director Dlractcr of laboratories " N 205.05 LC 75 3 moram, t o jmrFxmaw. it j & tnc ma'-n tm'JizATioB f o b rax cuw aiuancw. "tafcxa TKs TfAft I9&*. 6?f5f yiitw:UL`6\5%>r cT^-iOw^M c> KraiAftH oP 3 CrfeTf3x) Uijosfccny. hi r/iiT'jAjcxa'C or h::n:rTr,t nr.ifrrE Axb a^t^SQ. HUIaa or ri't coLS:si or kaxcKFcT^alS^TrctTy^ cig:xK:;m.'"ai fej HcjKT. Two) fajpoir-a fe AttH&t Atft cotguryglaa 6? PAKncuula it*Dr inference 1* made herein to a proposal atda oo October 3 1962# ta rtloh aa experlxient than underway *aa described lu e<nta detail# aa a part of a syvtsaatla Investtgetlco of the metabolism of load la the Inaaa body rtlch bad baao la progress sloes 1937. Since 0ot0bor(1962), tuo experiment then rafarrad to baa baao oaa>latad# with raapact to the scheduled axpoaura of tba two srtjecia vlthla tha respiratory charters, aad tha final period cfdbaerratloo of tba ertjecta (for a period, after tha termination of tha experimental axpoaura# aufflolaat to perslt tha elimination of aoat of the lead that waa absorbed during the axparlaantal axpoaura). Tba data obtained la thla experiment to tha psweact ' tlaa bate bean chartednd will ba alloyed la tba fonuletloa of a progress report covering tba datalla of tba work# for praeantatlm to tba apoaacaa of tba axparlaantal progrm. tba following peragrapbs are aooearnad with oootlauatloe of tba progra* through 196b. . While tba prior axjarlaaut waa la tba stage la which tba axparlaantal artjecte ware acbedultd within tba chamber# a further expertnent. Involving two new subjects, waa designed and Initiated, tba two Mbjeata ware * , located and engaged after a thorough clinical and phyalologlnal eurywy to eatahllah their suitability for tba teat ahead of then# and tha preliminary ' observations, rtlch are an l^ortant part of any euch experlmant,were Initiated 00 March 19th# 1963.. Theca dbaervatlone hava continued without ' Interruptloo to the ptaeent tlaa# and thla Initial parted# prior to tha ... axparlaantal expoeura,will be teralaated co deptenfcer 8th# rtaa tha crucial part of tha axparlaaet baglna aa of 6100 a.a., September 9th. tha aaeond : staga of tha experiment la aebadulad to eontlnua throughout (cad beyond) . ..T tanadar 31# 196b, and la tharafora the subject of thla propoeal.. ' ... Aa pradletad (third paragraph on page 3 of tba propoeal of October 3# 193)> tha aueoasaful conclusion of tha prtwloue axparlaant nada It naoeaaary# la determining tha thraabold value (for prtllo aafaty) of finely divided lead dleperaed la tha artiest atmosphere of tha coaaualty, *to aatabllah tha order of aagnltude of tha lneraaaa In tha aooeantratloo of lead In tha air ts tba raaplratory chafer (above that la tha art lent air)# rtloh la required to bring about a baraly demonstrable reepooea (la tana of tha aasratory rata and tha concentration In tha blood)# 00 tha part of tha buaan subject# to aeaentlally aootlnuoua raaplratory axpoaura to lead.* With this-Idea la Bind# tha precast experiment baa bean dealgned la the manner described below. . _., ` : . Two men la etaller raaplratory chartera will ba ertjeoted to parallel experimental aoodltleoe. Their axpoaura to lead In tha air will begin at tha lowest of three projected lavele of eoooentratloo (0.010 ag. par odbla meter), and will recur every other day, for .3 hours par day, over tha period of about 6) daye (thla la tha approximate length of tlaa required la previous experiments to reach a ecoetent level of Lead ta tha body of tba artjeet, aa revealed by a eooataet dally output of lead la tba urine# and a constant ocsKcetntloo la the blood). . . ' The eoooentratloo of lead la the air will then ba dortled and tha Sana regimen will eontlnua tor aaober 83 days, after rtleh tha eoooeotretlea will ba tripled, during soother period of 63 days. . N 205.06 mrnm '' V :s 4 i-j'*' ,..' '.*.; DCXOTRIAl BIO-TtOT IAS0RATGHH8, OR. lfllO frontage Road kortbbrook, Illlnni* 7tl*(bco* CAattvood 2-3*3- Mnujr k, 1963 Project rne-y Mr. Poo 0. foultri Project Mtragar lead Industrie* Aaaoelatlan 292 >*<U*oo Avaou* *#w lock 17, Saw Tort .... . -, - , - : B**r Nr. IMtrt # oartalnly enjoyed four vlxlt l**t frldiy and look forward to waiting with )n la tba future. , Considerable thought baa baaa (Ivan to tba problaa of tba toxicity of 1*1 la paint. Wa would Ilk* to aufgaat tba following attbod of atud/. If you could frorlda at vltb fir* powdered plgnaot* coot*inlng tbcaa level* of load, 1, 6, IS, 23 aad 30 par east, wa would cooduct 90-day aUbaeota oral feeding atudiae 00 rat*. V* would praam* that tb*a* would ba ault- bly waatbarad taspla*. . tech different plgaent would ba fad to rat* at dietary laawla of .Cl* ' v. 0.03, 0.20, 1.00 aad 3.00 par cant. Tbaa* flv* aaapla* would be fad concurrently utilising two erram control (roupa. Xaob groat would eootlat of tan ail* and tan final* albino rata. 1b* following par*attar* would ba atudlad during tba feeding period] growth, recorded weekly caqilrt* blood count*. Initially and at kj and'90 day* urlnalytat, initially and at kj and 90 day* dally ofcear-ration of all anlaala for reaction* and Mortality At tb* and of tba 90-day feeding period, all anlaala will b* nacropalad. Weight* of tbaa* organ* will ba recordedi Hear, kidney, heart, gcoada, aplaea aod brain. The ratio* of thee* organa' weight* to both brain aad body valuta will ba drtaralaad. All of tbaa* aeaeuraaent data will ba *\A>J*ct*d to aultabla atatlatlcal treatment. Ilaau* aectlcna of twenty different organ* will b# prtpertd for amnia*tloo by a patbologltt. All control anlaala aad all anlaala froa aaob 9 per cent dietary level will ba to tmnlaad. If uautrnl bltiopatbologla abangtt are noted In tea* anlaala froa tb* hlgbttt feeding level of any plgeeot, anlaala on tbt next lowttt level will alto ba axaalaad. If it 1* aaoaatary, anlaala fna all t**t levala will ba axaalnad. . Slnoe you ir* lnteratted la tb* pottlbl* Interaction of lead vltb Otbtr la* gradient* of tb* paint* during tb* vw*tiering proa*** aad tb* effect of Utla Interaction 00 toxicity, wa *ball parfora taa* additional etatlatlaal evaluation* on all tba ooablnad data. Tbla la an attanpt to elucidate tb* atetlttlcelly tlgnlfleast affect* of ton* cf tb* variable* being atudiad. N 205.07 ,K~ iTriwwtft1 -----------w Kr. Don 0. Forfar -2- February k, l$6j Tbo analysis of rariaaoo coot eaplatad vlll bo Ki up la this aaaMn of Varlanoo Ttrlablas ptr of m*6tm For Coat Load la Kjamta Dietary Ievrl of Flypasts , Bo* . : ' Interact loop . For Coot toad * Httaqr Loral of flpunt For Coat Load * Bos Dietary Loral of Fl^wat * Bo* ~ For Coot Load a Dietary Loral of Flynect s Bos } k 9 1 80 k 9 80 Bata (trror) kSO ~5W It la obvious that tbo aala varleblee Hated obcre will bo statistically icolflcaot, but It la tbe Interaction* la vhlcb re are Interested. Ho plaa to abject aaasuravrct* Cn four of tbo parameters to thla partlaular Analysis of Ttrlance, ausolyi body velrtt (ala, bsanclotla ooocaotimtloo, llran tody veigfat ratio aad kldaeyr body velybt ratio. If paraaotora other than tboao abov up aa olsalflcaat la our pro1 laicary statistical oraluatlooo, ra vlll sdtstltuto tboao raluoo. Va vlll ropoct tbo feedln* study on a particular pipart ladlrldaally. A rurpleaoctary ropoct vlll bo vrlttoa far tbo additional statistical , aoalysoa oo tbo pooled dcta. Cm cost of this duty vlll bo $20,000. For your Infovation, vs aro eocloslc* a copy of our ullaot Hat. ' Thank you for glrln* a tbo opportunity to dlaeuaa tbaoo etudlo* with r- Sincerely, Blfntdt J, C. Oalaodra fOCiJp tcoleeuro J. C. Calaadra Dlreotor - 2 .1 x x c u s t k u l ETOuai rousnmai or a mo o c a , no, Mellon Institute, 1*00 fifth Avenue nonet # vic-ij Pittsburgh 1J, Fa. btonbw 17, 1962 WCOTCTB FOR tuxa.gr eruona rod XJULD BEU3TRIXS ASSOCIATE* Introduction Sac present allombla level of load pi^snt to eartaln points baa been set at 1$. there ora no data available to Indicate ifestber or act a higher Ural of load plgnent la these potato ay bs assoolstsd, for practical purpoaaa. Vita DO significantly greatar btalth batard than tba 1$ level. la order to Obtain lafonaatlan oe this question, tba towUfftlca outlined bolos baa baao dsslgnsd. Bewever, before setting out to dealgo tba lavestlgstlee, It la adviaabla to consider lta possible pltfalla aad to daflaa tba criteria aocordlog to ldtlch tbe data vill ba evaluated. , la general, tba plaa of tba lavaatlgatloo la to eoa^ara tba tcadelty of a gives, higher level of lead pigment la palat vltb tba todalty loberent la tbe 1) level of lead plpmt. Aa aa laltlel atap, tbla lavaatlgatloo accordingly proposes to deaoeetrata a baraful affect bp feeding a toxic aaouat of tba palat file frea palat oootalalag It lead pigeeut. This aeada to bo done la order to eetabUab a base llae against sdilcb tba baraful effecte of a palat flla oootalalag a higher percentage of lead pigsant will be colored. Vbatber or act tbe effects produoed bp tbe lageettoa of a greater aaoiat of lead plgaest (because of a tiller peroeotage of lead la tba palat flla) are elgalfloaatlp Increased vould depend upon tba nature of tba effect>versu*-does response. U tbe response la ooa-for*coa, tbet la, a etrulgit-llDs retponeei then for every slgalfloaat 1aerease la does there le a significant laoroses la effect. It this be tbe ease, then any Increase la tbe percentage of lead plgaent la tbs palat vould ba associated vltb- a eorreepoadlag Incresee la tbs health hetard. It, bovever, tbs doss-effect response Is a curved line vltb tbe eoneavltp upward) then, at a lov doaagt level, a ilgnlfloent increase la dosage Is reflected by aa Insignificant la* crease la affect. Obder these slroinetenoss, it is only at high lead.lataba levels that added dosage results la aa aoeslanted Increase of offset. ft Another guest loo vbleb auet be ansvered Is bov tbs toxls sffssts are to be assured. One of tbe soet sensitive asasurlng sticks, and Son* jr only used la tba deteralaatlca of health batard la nev drugs or food additives, Is the affect of the unknown ohaalsal, when added to the food of )mng rets, upoa their grovth curve (gala la vetght). Another aeasura epplieable la this Investigation vould be the total eosvaailatloo of load la a 1 critical tissue as Acte ruined by ahsaleel analysis. A third, less sensitive, asaeure algbt be the affect upon boos aarrov fuostton. '*%r N 205.08 t .Ifadaftfial Hyglea* fouDdcttco of Aatrlc*, Id a -8* It 1* Obvious that, rstber than tha percentage of laad la tha food. It la tha weight of load absorbed Into tha system >fcleh la the factor datarain ing tha development of toxin affacta. In tha caaa of tha proposed Investigation, tha aagnltuda of tha affact produced by feeding laad-ocotainlng paint flla vlU dapasd upon a ntebar of occdltlcoai } 1. Ha weight of land lngaatad S. Tha chaalnal Datura of tha laad pigsact (thick dataralnaa lta solubility and ahaortalillty). s 3. Tha physical and chaalnal character of tha flla ' In tdiioh tha laad plgaent la Incorporated. Thla alto influence* tha aolublllty and abacntablllty of tha laad pigment. V. He flDaoaaa vith thlch tha laad-ocotalalBg flla la grand for Incorporation In tha animal food. His baa an influence on tha aolihlllty of tha tul- paodad laad pliant, and hanot, lta absorbability. rropoaal . Ha lnreatlgstlon will, of nacaaalty, oooalat of a pralialnary phaaa for tha dataralnatlon of tha *baaa line" followed by tha aaln atudy. Hla pralialnary phaaa will Involve three groupe of 1$ young rata each. Ona group, fad a standard baaal diet, will aarva aa control. * aacood group, fad tha aaat diet plua a pra-datarained doeage of paint flla (fraapalnt containing in laad plgaecrt) la Intended to daaanatrate a nlntaal toxin affact. Ha third group of rata will ba fad tha aaaa diet plus tvloa tha S amceait of paint flla fraa paint containing lj laad pipant aa tha aacood group. Ha dosage level of paint flla to ba used on tha rata la critical. It will depend upon tha chemical nature of tha laad plpeeut. It* solubility, and known toxicity. He extent to which the other Ingredient# of the paint flla aay aodlfy the toxicity batard can only ba auralaed. Therefore, tha choice of doaags level beccxae* an educated guess and tha poaalbUlty f guaaalng wrong Bust ba token into account together with the oensequanoaa cf guaaalng wrong; namely, of having to repeat tha study. 1 a Ha laad Znduatrlas Association la axpactad to simply tha paint fUa(a) la a fora suitable for lnoorporatlco Into tha dlat food, ground uniformly to a raproduelbla alia. Pertinent lnfonaatloo regarding tha aonpoaltlon of tha flla notarial, particularly In regard to the laad pigment, lta ccapoaltlco, physical propartlaa, and percentage. Ha dosage lava1(e) of the paint flla(*) to Is used In tha anlaal feed vUl ba fixed by sgri awl between tha representatives of tha laad Xnduatrlaa Association and tha investigators. * Ha feeding at tha aalaals will nootlnut for three Booths. Curing this time, tha food cowaptioo (sod thsrsfors tbs laad intake) as wall as weekly body weights will ba recorded and charted. After thla period, tha rats will ba killed with ether and autopsies will ba performed. Ha livers and kidneys will ba weighed and tha ratio# of organ weight/body Might will ba daterained. Blocks of liver and kidney froa each anlaal will ba eabedded la paraffin and section* prepared for alcroaoopla examination. A chemical analyala of a tissue for laad ocotant will ba done on each anlaal. pnn i'M-  ^<1 1 ' -V ` *JL O-r-W.-C* `-- S^" ` "' %*> ' Xa5utrll Hygiene foundation of Amerioa, loo. Aaaualng that a Minimal doaaga of paint film frca paint occtaln* Inf 14 laad plgaant baa baas fount tdilcb producer a maaaurabla affaet upon tba rata, than aoothar atudy (tha aaln atudy) can ba begun In Mblob a group of rata la fat a higher (predetermined) percentage of lead pigment eontalnat In tba aame amount of paint flla aa la glean tba group la ehlch tba paint film from point containing 14 land. Tba lattar group vlll aarea aa tba beaa llna agalnat etlch tba affacta obtalnat In tba flrat group vlll be cccpaj-ed. A third group of rata fad only tba baaal dlat will aarea aa Dagatlra ooert.rola. If dealred, other groupa of rata may ba added, to ba atudlcd almiltanaoualy, vltb Intalea of ground-up paint film containing larger paroantagaa of lead plgaant, differing frca cot another by a factor of two or more. SS2S I- Tba outline of tba invertlgntlcc la glean la tabular font bale* and tba coat la Indicated. "v "ko.cf Oroup Data Dlat 1 15 Baaal (control) Duration 3 o."| 2*1 8 *3 15 Baaal plua paint film (valght to ba agraad upon) 15 Baaal plua tvloa tba vel^jt of paint ' film aa la Oroup 8. )** / 8/0 3I Oroup 1 8 Sacood Ibaaa fala atudy vltb lnereared 4 lead in film) Bo.of Sate Dlat Duration a1 15 Baaal (control) 15 Baaal pint paint film (valght to b agraad upon) 3 ao.~] 1 3 mo. > 8,000 3 15 Baaal plua aaaa valght paint film aa 3 ao-_j la Oroup 8 but vltb x laad la paint. b 15 Baaal plua rat valght paint film aa aboea but vltb 1% laad In paint. 3ao. 2,500 3 15 Sana aa Oroup b but vltb tf laad la paint. 3 M> 2.500 O ~ mf s~- ' SI? ; XKD'JBTKIAL BIO-TIST USOW>?OR38, DC. ; l6lO frootac* RoaA Borttbrook, 111laol* ; ?*l*pboo* Ca*too4 8*3030 .$ JUM 18, 1963 Mr, Coo 0. forlar Project lku(ir Load ladurtrlat Aaaoolatlea 292 Kadlaco Arrau* Rev Tort It, In Tort ^ ' C**r Coot ' V* will conduct acuta oral and tout* parcutaacou* toxloltj atudlaa 4* pr our propoaal at r*bru*z7 11, 1963 Do color chan** will b* la tlx aeuU parcvtaoaou* tot la iftlch two rabbit* will b* uaad t web at 3 doa* 1*V*1*. lb* *7* Irritation and acuta Inhalation taata *r oot of prla* 1- portaaca laltlallor. Tfccaa tnti so/ bedeo* latar it further Interact la a particular ecopouod develop*. lb* coat for tb** tnti vlll bt it7J.00 par wUrlal it a BlalM at fir* wtarlala an \**lttd at tb* taw tlaa. J Sincerely your*, 81*a*di Jo* J. C. Calaoflra ' ' Director , '. JOCipar . ." M 205.09 -i i. !. - IT f r. DTOUBTKIAL BIO-TOT lABQfiATORUB, DR. lfllO Fronts** Road lorthbrook, Illinois Tslajfcoo* CB*trood 2-3030 Ttbrutry ix, j s 6j " , , Mr. Dou 0. ForUr, Project Mumr Lm4 Industri** Assoclatloa 292 Mdisce Arrau* lav Tork 17, 9n Tort ' .: Star Mr. FOvlcrt V* in cacloalsf our proposal for rsa**-flalae toxicity t*ta 00 HttrUli Is blcta your association 1* isttmM. Du oo*t of Umm t**t* win b* 1600.00 per satarial taatad. If you her* any <yi**tloo* os tbas* procadun* pitas* do sot bssltata to cell us. dank you teals for permitting a* to -&xc Mbalt our proposal*. .: v;`- . 81nc*r*ly, ' . \`.r' ' j . . 81*o*di J. C. Calaodi* . JCCipar ' BmX. . J. C. Ctlsodra Wrrator '. - -- , ;,v : ; .1 : ,, . 1 -ti0: , ' v." ' N 205.1 aou Rwus-rnrono icxicirr enona I. A*na*-Pindlna Acuta Oral Toxicity - Albino Pata A. Acuta Oral Toxicity AlhlnoPata fe*elthp, jroun* albino rat* of th# Spra^u# -Davlep train with ea average bodp wl^at of epproxlaattlp 100 (ran* era uead m teat aaiaala. The rata are 41 rid,d Into group# of tour Mini* each for doelr^ purpoaae. All aolaala uaed art kapt under dbearvmtlce for flva dspe prior to axparlaaotal uaa, faring vdilcb period thap art checked for general jfcpalcal well-being and tKKgeaeltp. The Mlnels ara hou*ed Individually to atook cage# and paraltt.d a standard laboratory rat dial* plua water ad Ubltta until l boon laaedlatelp prior to oral Intubation. Oo the anralng of tha flrtt taat dap, aftar a 16-bour faat (water paralttad), tha aalaetad doaa group# of four rata aach ara lntihetad with prvvlouslp ealculatad doaaa of tha taat aatarlal. All doaat ara administered dlractl/ Into tha atoaacha of tha taat rata using a hppodaralo qrU|i equipped with a ball-polatad Intubating aaadla. Following oral adalnlatratlco cf tha taat aatarlal, tha rata art rrturnad to thalr atoek cage* aad obaarrad for tha eucceedlag lk dape. All significant raactlona and aortalltlaa which occur ara racerdad. Particular attaatloo la (Iran to tha observation during tha float four hours aftar Intubation. . At tha aad of tha Observation parted, all data ara eollaetad and tha rangs-fladlag acuta oral aeaa lathal doaa (Kn&n) of tha taat aatarlal la calculated using tha technique* of Vail**, Tboapeoo***, tad Tbc*goo and Wall****, Rockland Jfct Slat, Rockland Paraa, Raw Cltp, Raw Tork. ** Vail, Carrol S.j Tablee for Convenient Calculation of tMlaa* Zffsctlv* Doaa (lDy> or Bm) aad Instructions la Thalr tha. Rlonetrlc*. Sept. 1JJ8. *** Tbonpeco, Vllllaa R.i tha of Moving Average* aad Interpolation to Xatlaata Median-Iffectlr Doaa. Pact Pay.. Row. l$kj. **** Thoapaoo, Vllllaa R. aad Vail, Carrol S.t On tha Coaatruotloa of Table* for Moving Average Interpolation, Bloaetrlcs. Mtruh N 205.11  .wm : mm -mM, '..ysaa!!?.: . *fits - *. * ;fb "I ,*'j ;m ` 'I t "a \ 'V "if *v? f'r' '' nTflC?v i 5V f.if ' v . If-*' fS8i. t ,A I r. .Sr-ftS. *..., Ji iMitiidtfimM pi. iiiiijLifi isSrti, il I I I ill i t- Sfl rissjHi i?!IEi|fh mm*Hs illiil Zs*ss fii ili1t! IitfliPiliIilti 5i?is ;h*m iiiiii . Toung, adult albloo rat* of 10* Sprague-Davley strain war* aaplcyvd >, a* tb* t*t enlaale. Pra- aod poat-teat care and observation of tba** j rata era aaasotlelly to* mo m aa that already described for rat* used . lo tb* range-finding acuta oral toxicity teat (sea p. 1). However, aniset* t used for inhalation exposure vare not feeted prior to testing. five group* of four rat* each are utilised in tb* study of tb* teat aterial, tb* average body valgbt of tb* teat aolaala ara approxlfflately 250 grans. tb* lobalatloo cxposura* era conducted la a oultlpla Inhalation chsaber dstlgaed for sioiltaneou* axpoaura to ataoaibra saturated and fractionally aeturated vltb the teat aeterlel, e. g. 1/2 maturated, 1/b maturated, 1/8 saturated and l/l aeturated et tvm tsnpareturs (2$%). Xbe teat la designed to run for a four-dour period. At tb* end of tb* txpoeur* period, tb* rate are observed for tb* succeeding lb day*. IT. Banes-rindIce Iva Irritation Teat - Albino Babbit* A group of flea albino rabbit* ara used to evaluate tb* eye Irritating properties of tb* teat aaterlal. Toung adult, lev Iceland atrela an Inala art selected for tb* teat. Tb* teat natbod aaplcgnsd la patterned after tbet of Bralt* et al*. Zxactly 50 ag of eolld teat aaterlal la Instilled Into tb* conjunctival sac of tb* rtgit *y* of each test rabbit la a group of five aolaala. Die left aye of eaeb aaisal serve* a* a scoring central. One, 2%, W, 72, $5 hour*, aad 7 days following tb* Initial Instlllatlone, tba cornea, lrla, and palpebral conjunctiva era exsalnad Individually aad graded for Irritation aad Injury according to a standard scoring aystea*, tb* sarlisja possible *cor* at any on* examination and scoring period la . 110 point* vblcb Indicates taxlaal Irritation and daaag* to all three ocular tissue*. Zero score lndlcstes no irritation &at*v*r. After tb* ccapiat ion of tb* test, tb* aeons are analysed and a descriptive ay* Irritation rating la assigned to the teat aaterlal. lb* criteria used for ssslgmsnl of tb* descriptive rating are tb* fnguaacy, tbs extent, aad tba persistence of Irritation or damg* vblcb occurred to tb* this* ocular tissues, la tb* classification systsa used, special asqbaala la placed upon Irritation or daaag* to tb* cornea. Correspondingly lea* *traaa la placed upon conjunctival and lrldlal offacta. lb* descriptive rating assigned are cos of tb* follovlng, each of vblcb ebarsctsrlts* a particular level of oibtbalalo Irritation aod danagsr Boo-lrrltatlng Fractloally Rco-lrrltatlng Mlnlaally Irritating Mildly Irritating Moderately Irritating Bevarsly Irritating Extras*ly Irritating * aMethods tor tb* Study 0?*irritation and toxlclt y of instances AppITlliS Topically to tb* Bkln and Mucous Msabranss", Dr*ilU, John Woodard Osoffray, sod Calvary, Herbert 0., J. tbara. k Exp Tbar. ,'l,D*catf>*r 1946. ,< v .an LC 79 ........................ ............... F5WPC6AL BO. 1 \* Ta Bin lABORATORIEd SBC. Research *04 Development 1099 Folara Btreet Baa Francleeo 3, California Jane 17, 1S6J Mr. Son 0. fowler Lead Industries Association 29S Madison Avenue Bev forte 17 Saar Scot It aa a gnat pleasure to visit with you laat mk end to renew oar friendship. Our previous work la tha Air Mintloo flail was moat enjoyable. X truat that v* may find a flail of Joist affort la tha aattars of load and tha Lead laduatrlaa. I have always admixed tha work of thaaa laduatrial aaaoelatlooa auch aa API aad Lead laduatrlaa, aad hare fait that they are flaa steeples of tha Aaarleaa tradltloo of both ccsqsetltiao aad cooperation. Is reierd to tha aattar of developing Inforaatloo for tha aafa 0f 0aw laad products, our Laboratory would be aoat happy to work la this area with your group aad valid be pleased to aaka a proposal for your consideration relative to tha extant of work Milch should be done aad tha coats involved. Aa I understand your laemdlste problem, there are a maker of new laad cragwunda la varying degrees of development shoe* tcxlcltlea are la general unknown. Because of your long experience with ergiale leads and knowledge aa to tha auch higher toxicity of thaaa ccapouada aa ccapered with different Inorganic leads, it dost aaaa appropriate for you to bare deterelaed tha 9a.;. : proper order of aagnltude of toxicity ao that suitable precautions aa have bean developed for both types of ermpaunde could be applied. I would suggest, therefore, that consideration be given to dataraining toxicity by oral aad percutaneous routes for all cenpasde, aad that of toxicity follow ing inhalation by compounds which aay have a significant vapor pressure. At this stags only order of negnltude figures need be obtained, aad we propose to use our aodlflcatlcn of the standard method of Delchaaam, la Milch tha U\> aad LDiq q world be bracketed by edalnlstnt loo of tbs compounds over a range of doaee or concentrations. At such tine as further Information La needed concerning tha ccapcuod, norm precise values should be obtained la order to batter define tha toxicity aad otls r teats would have to be performed to conform with tha retirements of the Basardoua Substance Labeling Act. :3 Ve are appending our reecmaeodatlocs for aoecapllahlag this preliminary u toxicity evaluation aad tha coats relative to these. Ve should Hke to i point art that our Laboratory baa bad considerable experience la tha of dangerous and highly toxic compounds, Including explosive sateriels, aad that our staff, therefore, la ecarpeted to handle compounds of any degree of toxicity sod potential baierd. ~*yt...i--. 'j -.. 7. - ~ ' '.WSIWi^S V" ` * V. --v-wu N 205.12 Hm Bin* Xaboratorlea Mr. Coo 0. fowler j Pag* Tw o 6/17/63 ' It 1 altsyi sere cecwenleiit end 1* *xp*n*iw* to weak with *rl* of eaapound*, and for that reaaao our Laboratory (lTtl e 106 dl*cout o b (Lx or norv Maple* aubalttad *t (Ingle tlse. V* (r* In politico to *t*rt work oc any toxicity te*t within *pproxlMtly ten day* . .j after receipt of the eamgomi or Dotlflcatloa of It* ahlpnaot. "1 V* would b* Boat pl****d alao to b* ccnaldared In ooonactloo with other (tudla* la Milch your laboratory slgit aollclt th* aid of a prof***loeal group *uch a* oura, Including th* evaluation of th* toxicity of palnta. Z as looting fonsrd to further plaaaaat aaaoolatloB*. `t Wary truly your*. '^i Signed! Charley C. H. Una, K. S., Jb.D. Director * Th* Bin* Labor*torlee, Inc. -i ' .' 3' j... . % *' -: liHs . ~ L :\ rnmmm&m X, yragtatrtc toxlcltyi Group* of tvo ret* (altber Hi, ICO g=t. or oort la >rjgit) ar# clrro aultabl* Io n level* vlth *a lacrneest of 1.5 la order to brocket LCx aod Ii>xon> emulative aortalltle* ar* Oet*rained at 2k, k8 tad l0 hour*. Total coat . $100.00 XX. Percotaneoue Kmleltn Oroup* of tvo rabbit* (altber ii o, 2$ 4* or aorelo val^it) art *lr*n tultabla do** l*v*l* vlth an lnereaent of 1.5 lo order to _. ' 1 bracket the aod IKTM. Cuauletlv* aortalltlaa art determined at 2k, to aod l8 hour*. Total coat 150.00 XIX. Vapor Tmrleltn Group* of tvo rat* (either aex, IDO or aor* c>i la velit) art axpoaed for CO* hoar to aultable concentration* vlth aalacraaaot of 1.5 la order to bracket the L3q aod 10ioo> CuaulatlT* aortalltle* ar* datendned at 2k, to aad l8 hour*. Total eoat . ' 200.00 Coat for all three t**t, par eoapoiad Coat for the oral *creea aod percutaneoua, par ecapowd ' 10$ reductlaa for six or aor* ecapound* aidedtted at the aaaa tlaa k50.00 ' ' 250.00 ' ' -4y' * yjr v 7*,: 1 ' 1. ---~.-i iirftni*d<ip>'itfir iwii-igiAattf^* iniiidk.&>au`*-jW~v>*~ -r-.-r1- .* * 7/12/fiJ Project / ULC-li wow oimxEff ir u ) Baiorjp f.v.c. m% urrmnuLTiea RlfiliS polyvinyl chloride pip* 1* Important la today'* market *od should urjM great*r Importance la ths futur*. Various eanpcxssSa of l**d hsv* boss sod *r* u**d successfully as stabiliser* for rigid P.V.C. fomilatloes sod tbs efficiency, effectiveness sad ecoocay Involved la tbs v m of load stab 111s t * 1* not aa Issue, but 1* acc*ptsd by nanufsctumr* of plastic*. Vbat la at lssus Is tbs anoint of lssd Milch eao lsseb froa piping Mmo It 1* ussd for potsbla ester supplies. Sines tbs us* of rigid P.V.C. p.'p* baa a good futur* potential as a replacement for astallle pip*, It *111 b* eall for u* to nsasurs tbs lssd rslssss or lsacbablllty fro* tbs pips MMn It 1* ussd la ataadard household saur supply lytta*. Producers of P.V.C. pip* appear to hsdtato to uss load as ttsbllUr bscsuss of ths possibility of such pips b*la( laad**rtstly ussd la a vstar supply systsa. If, ho****r, VS could rssssurs tbs plsatlcs Industry vlth appropriate measurement* of laad teachability (eaawlcg that tbs lssd r*lease la lew eaou) than tueh producers would fssl frss to u*s tbsss hltfily dsslrsbla laad oospound*. ` 8C0P Cm purpose of this proposedjrojraa la to Obtain laad release data froa standard formulations of rigid P.V.C. piping In order to proaota tba use of rich Iced stab inters In tbs industry. Cm program will be carried ca la two . consecutive phases, the first of Milch will twin* la pro 11 ml nary faahloa vbstbsr or not axcssalvt anoucta of laad vlll b* released froa ataadard ' " piping systems. If the lssd release Is satisfactorily low than tbs second ' . jhss* of the pragma vlll be carried 00 Milch will Involve obtaining testa aad approval of such piping eyttaaa for us* la potable voter supplies. Of ooures. If the first [has* of the program show* that v* are not la the rltfit hall park and that lead leeches frea the piping ayatesM la excessive anoint*, **<11 go no further. pooBowc mcernre klgld vinyl pip* la presently being produced la the anoint of about 80,000,000 pounds per year of Milch only 20 la presently stabilised vlth lead caxpouads. w* estimate that this provides a Market of not more than 80 tons of lead per year at ths present tins. If all of ths rigid P.V.C. pip* vers stabilised vlth lssd caxpouads, the present market would be about *00 tea* of lead per ytsr. lowtvtr, this la a rapidly expanding market and the future potential looks good, tueh that la 1967 It la satlaated that 100,000,000 pounds of rigid P.V.C. pipe vlll bo produced. Tbsreform, the present situation Is of Its* importance to us than the futur* and, since It vlll take seas time to carry 00 a tasting aad approval prograa, and alone the results of tbs testing and approval pragma should bt available before the real market potential sea be realised, it would he Inombent upon u* to carry out auoh a prograa. N 205.13 .* * MTtofui sumrioi roucaiiai t e s t no ia b o r a t o r t , no. Beedguartere School of Public Health University at )Cohltn* 1 2 3 Dr. Henry T. Yeugben, President Cbarlae A. Parish, Exec. Director Welter T. Baritr, Seo'y-Treaaurwr lomiody J-15U Ext. 2379 MB ARBOR, XXCEXOAI hOlOh August 2, 1S6J Mr. Deo 0. fowler, Project Manager International Lead tine Research Organisation 292 Msdlace A\ -cue See York 7, Sev York 10017 Mi Plastics NlM. (Project f OLC-12) Deer Mr. Powlen Proa your litter of July 30th *0 here considered the testing that re feel ebould he Included end thla aetter hea been discussed with Doctor McCord end be eaocure that thla would be a rlilaa that abould be ocoaldered at thla tlaa. Ve would propose, therefore, that the preliminary testing prey to determine lead leecbablllty be 00 the following baalet , 1. that at leant three lirela of lead concentrates be need la the PVC pipe. - 2. That pipe be produced frea at leant 2 FVC pipe asaufseturere. 3. The teete would be parforaed oa two typee of water* to be agreed upoa before the tenting la undertaken. ' b. That the lead eteblllier ecapoimds thet are being ueed la ': " Europe be the ante eoaaldered la the teet. Thla would . aaeraa that oaa atabllUer would be oooeldered la thla Initial testing progxwe. If you feel that acre than coa - : type of lead cawpcuod ehould be Included, thee thla would double the ancunt of testing outlined coder 1 and 2 above. . 3. the coat of conducting the teetlag errer a ainioo of a oaa year period oa the baele of the outline ahowe would be |l,J00. Thla would cover the perforaenee of all the teete ae outlined la the above breakdown oa tba baa la of oaa lead compound. it you wlah to proceed with the progreo, we believe that it would be necessary to have aowe further dlaeuaelooa at whloh tine we could get into ore detail regarding the specific preoeduree. loure very truly, Slgnedi Charles A. Parish . CAP/al Charles A. Parish Executive Director N 205.14 n la i960 two oaaea of laad polaoalng vet* reported being oauaed by the d m of 41meware soda by a pottery la California. gem fair sllllca piece* of tala vara bad baao dlatribvtad tlrojout tba Cbltad Etaiaa by tbla pottery and tba California Bealtb Dapnrtnnnt Instated CO tba return ant ccsflaoat loo of all of tbla dlnaaxvar*. Tba resulting aooQcala : lota to tba pottery caused It to go out of business. Tba 0. 8* Pottara Association requested tba la4 Imluatriaa Association to jda vltb It la aa Investigation of tba load ralaaaa freu ataodard U. 8. products of pottarlaa In varloua parte of tba United Stctaa. Va aooo found that there nu not even a ataodard aatbod far tasting load and baavy natal ralaaaa froa glared pottary and tbla bacaaa our flrat order of bualnaaa. In a Joint project tba 0. 6. Pcttara Aaaoelatloo and tba Laad Industrie* Aaaoelatloo engaged tba lettering laboratory to develop a taat aatbod and to uaa tbla aatbod o d representative produeta to datatalna lta suitability. : Tba taat aatbod uaa aueoaaafully drralopad and baa baaa aooaptad by A.8.T.K. aa a tentative ataodard. Tbla pbaaa of tba proJact having baao completed, It now appaarc nacaaaary to Investigate otbar factor* filth baaa baaa brought to ll>t by tba oparatloo at tba Kettering laboratory. Tba Kettering laboratory tarta vara run 00 may dlffarant typaa of |1u m frm aaay dlffarant aanufacturwr*. 81nea tba raaulta of tba taata vara apraad over a ratbar wlda rang* at valuta, It baeaaa of . lntaraat to ua to inquire aa to tba reasons for tba variations. Briefly, '' variations In laad ralaaaa frea glased Alnaervarn appaar to be Mured by (l) |lm ccapotltloo, (2) firing tenparature and certain kiln conditions* (3) eoapceltleo of tba bisque, (() otbar variables not adequately Udder* stood. _ ' . '.......... Laad 1* a ataodard aoaatltuwnt of (ltu ooupoeltlooa for oat of tba pottery dlanerwara Mde aod cold Is tbla country and' , abroad. Xt la desirable that (lata* centals laad for May teohnlnal and ceoanla rtaeeoej for lnataooa, tba plaetlo propartlea la^artad to tba (Ib m by lta lead ecavoaltlca allow a wider latitude la fixing tea**rater* and tbla la InpcrUot la production pottarlaa. ' . tssa . ' . lb* purpose of ear proposed lnractlgatloa la 14 Inquire Into tba panaatare that it la neeeteary to oontrol Is production pottarlaa to sake uaa of laad la a aafa and aaononla uacnar. Va an bar* defending a sartat and ala* proponing to expand tbla aarkat by polishing guldallsaa N 205.15 loA/65 . Pr>ot f QLC*VS -* ahlob trill allow production pottarlaa to operate vlth oartalaty la a (1U vbara up to no* tbtro bu btan a gnat Aral of aaplrieal and fuaaaaork operation. >7 oalag our ataadard tart rttkoi nfiml to la tba Introduction, *a vtll ba abla to lavaatlgata aad to aaimarmta la a uaatltatlva narmar for tba u*a of production pottarlaa tha varloua paranrtara that an aaoaaaary to aaaura a rnoothly operating pottery. gxr Ktc tacgrrxvi JU tridrneed bp tba preceding dlecuaalcn, tba ecoocnlo Juatlfleetlco of thle ratearch la primarily drfan*Ire. Iran Isolated caaaa of drfrctlre glura product advene publicity idilch la banful to tba laad laduati7 la other araaa. It la tbarafora Important to laltlata raaaareh tfelch vlll Identify tba ra^ulaltaa aaadad to produoa aafa laad gluts and to detemlae optlaua aaoufacturlag prooeduree. Hartatvlaa, tba total ccoemption of laad la earaalca la tba 0.8-1. wee about 16,000 tool la 1962, plua aa additional 5,000 tooa laportad fra Muioo. Vbat percentage of tbla quantity goat lato glaaed dlanemare la not known, although a rougbl aatlaata of 3,000 to 10,000 tooa aaaaa neeonable. - <- a .-- - ,, .... . f.sX.;. ; \ ; - ' > fr*. "pi.- ! taw* FBOJKT / ULC-H r b i Tone va.ms. j o l l h j r flowr and firth Avcira Bo*;dtal* fifth Amu* at OtM Bundrad and Sixth Btr**t 1 *av Tort 9, B*v Turk Dapartaant of fatholoty :( Laboratory of Ixporlaantal Batholocy f- Ly\ July 15, ljfij Blank Priacl, At. Battering Laboratory of AppUad Riyalolncy Ublvaralty of Cincinnati Collag* of Madlcln* -- Idan Amua Claolnaatl 19, Ohio - Daar Frank] . Zbeloaad la th* final protoool of our propound aarloo of axpnrlnenta on rata daalsnad to produc* Bata ooocarnlnd th* rmdloprotactir* affect* of lnorcanla Land. Iboorporatad ar* th* *ug**tlco* of Dr. Donald R. Disc*, th# budget 1* for tha work aa outllnad and In tha *v*nt It 1* nactaaaxy to punu* unaxpactad naulta, aupplaaantal ftad* vlll b recreated vlth appropriat* . Juat Lflcatloo*. . .............. . If tha protoool la aceaptad, vt would Ilk* to atart work not latar than Octob*r 1, 1963 If poaalbla. Aftar January 1, 1961 w* will h* aorlng our labor*torlaa Into a naw raaaarch building and nav project* say h* dalayad. lb* prlnolpal lnr**tl C*tor will b* th* eontractirs officer for tha lnetltutlco. Blnoaraly your*, ;- Signed! Barnla . ' Barnard N. Vagner, X. D. _.. rrofaaaor and Chalraan Dapartaant of Pathology N 205.16 , <1 Title of Project: rsx /wuptoncnvi mvm or immutt LEU) gprcrnc a d c i Oitolcal agent* utlllxed 1b tb* radiation protection at tleauaa, organ* *o1 tool* anInal* vary a* to itructure, node of action and apeclat atudled. Trut octal* play a vital role a* lutraoallular oo-factor*. Zlno, oobelt, iron, oajpaalia, oergtncM and copper are aata of tba ortalile loo* vith *tab11abed function# in varloua enxyne and tramport lyitttl.1 lot veil understood la tb* Mgh ooDCtntration of eadalia In tb* ranal cortex and tb* rtlatlcnahlp of Mlanlm2 to nuacl* netabollaa. It la conceivable that la tha cooplax, Inter-related ayataa* that control call function, radiation ladueaa rapid lanlxatloo, foraetlon of free radtcala and dlarupt* nolacular apatlal arxeuigeacst*. In tuch altuatlooa tha varloua atalllo looa vould undergo aevara alteration* la thalr valaoca abella. B>* poaalbla Introduction of appropriate Iona to atablllta tha early change* produced by radiation la worthy of atady. Ihla laboratory baa an muaual tmpeteoe* In eytoohanlatry nal blatoeh*alati7. In addition, a aajor croup of lnvaatlgatcr* am atudylng tha structure and function of tha cardiovascular ayeten. Zbaaa Include: Weld Pbracrly Dr. Sara Bchlllar Blocbaaiatry Odnnltjr of Chicago Dr. Vllllaa Outataln Blophyalea Bev York OBlvanlty Hr. Btlph Strebal bp.- rath. Xnatltuta of Hi>earch, Cblrerelty of Montreal (Dr. Be lye) Dr. 8. Mabo* bp. fath. Dovnatata Medical Center, I.I. Harold Appleton, ics, Clinical Batlooal Inatltute of Health Cbenlatxy Dr. Barnard Vipar bp. Doth. Dblverelty of Washington Wotting vith thla prop on a part-tin* baala la an electronic! expert cod a pfcyelalat. The tlxruee fron tha anlnala la tha varloua axperlaastal group* Vlll be prepared by apeclal technique* developed fa tble laboratory to araluate Intracellular, extracellular and vaeoular change*. Taacular change* Include fixation for abaemtlona of eonatrletlon or dilatation, a* Pr*Uxlnary atudlea anploylng Inorganic, 1coiled lead la the Intact anlaal ha* indicated that the vaeoular ohaege* oonaaquant to lethal tool*-body X-lrradlatloo nay be aodlfled. The purpoaa of thla inveetlgatten la to explore In detail tha following queatlonai 1. Mediation projection of lead aa a function of Ac**, tlae and tlaau* level*, !. Influenc* of anlaal age, *ex and diet. J. Mecbanlana of protection at a hlatochaaloal, cytological laval. . Blood and urlna change* during *xp*rla*ata. N 205.17 -JIT!-' II 'f*'VcifinW nil fhtl.' ft'VliilK W'nilili? Ill ntitf I 4* lB2S Ea.n^.i Vtll&lty of Prtrlout Obaanrttloo* Oroup U *>(*), 800 ag/kg 6 rata *00 r D StCl soOagAc 6 rata *00 r IC M*)a 800 ag/kg 6 rata *00 r ID *>C*>a 850 ag/kg 6 rata *00 r n fbCAo)* 850 ag/kg 6 rata *00 r * . if AdJOj 800 m/fcg 6 rata *00 r 10 Adj 850 ag/kg 6 rata *00 r Sotai Doatt 50 ag/kg/day. X-nyi 8* hrt. altar loot doaa uxcrpt Group* IC tod II than Irradiation pracadca aalt adalolatratlna. Group IB la a abaa trtatad radiation axpotura control. Vlatar rata 100 c m. rrrnoKXT n Iffact of Doaa and Tim EH2______ 1______ 8 3 *5 T 10 1* 81 Oroup tl 1 2B 6 > SC 6 2D 6 Zz 6 tr 6 4 4 | mm 4 ' 4' a 4 aa 4 4 II - 4 4 aa 4 ft 4 44 44 a 4 50 ag n (*C>2 l.P. Bo lajaetlcn *00 r Iiv Tha axparlaratal do Ian la to ralata doaa acbedula at a flaad aarlablt to tint. Xa **05 croup of 6 anlaala tbara on 3 aalaa aad 3 fanala* of 100 CM. Initial might. Sota that Group 2B and 2f will rwalw Fb la tha pout-irradiation p*rlod. Eqarlaant m fchaaeud DUt Study fcpaat of Bxjarlatnt I with tha following axouptlona Oroup III-XA Ad llbltw dial Ill'll) III-I7 III-IO Borlcbadprotala dlat 255 Including CS anloo as Ida Ad lib Snrlebad Iho AS riot (also told* will ha adulnlatarad by furaga tad will aonutltutu a 855 loo. la prottla t owtr tht atandard dally n mu win Im of food. * \ .. -I . ... . 7 1 . * -* *. . *.* -ti - i 'f \ ..... j g* ::~yj P ' i i\ 4 Throughout all axperlamta, blood and urlaa maplaa vlll be obtain*! at Judlcloua iatarrele for tbe follavlo dateralaatlooai BtOOP Baaoglobls Baoatoerlt Perijbarel VBC and differential B*,E,Ca, electrophercgreer M >01 OTI I*ad Protelaa : Casts Call*, 8p. 0rarity Tl**o*a obtained at autopsy vlll lncludei Brain, B*art, Llrar, Spleen, Btenacb, Kidney*, Adranala, Cooada, Skis, Baa, Boo* Mkrrcv. la addltloo to raitlaa atalalas, edtert lndloatad tba follovlig blatocbaalcal nactlee* Vlll b* analysed. . 1. Oxidative itiiJMi S. fbospbstaaea 2. Baale protein* . Connective tissue polyaeocbarlde* . tbs experlnetrta vlll b* nodlfled during tb* court* of tba lnvaetisatlos at tba discretion of tb* investigator*. Fmlibv load* vlll b followed at d o additional njataa. Tba axperlneatal.datlga vlll Jiald statistically elenifltant laforoatloo vhlcfc vlll asavtr la Ians* cart tb* original prcfelea llat*d under tltla of project. 1b* project vlll require 6-8 aentba for ocnplrtlcn. cowacotm m Bernard M. Vainer, M. 8. - Professor and Cbalraan, Bept. of Pathology (Brine. laveat.) Balpb 8trebel, fb.B. Aaalataat Professor of trptrlanUl Pathology Ml Mao Bedell, B.A. Cblaf, Klatorbaadatry laboratory rdCXLTTTP AVlIUBtl Anlaal facllltlaa Blatocbeelttry laboratory Cytoebenlatry laboratory Blatopathology Laboratory X-ray aecbina (supervoltaga avallabla) ' . mopcBi 1. Ebtywsi Blxoo, M. and Vabb, I.C., Aeadanlo free* Ine., lev Tort, 1936 S. BcbUbert, J.B., Muth, O.B., Oldfield, J.S. and haert, L.7.1 Brpertaental Beaulta vltb Balaelra la Vblta Btuaola Blaeaaa of Laaba and Calvaa, Ted. free., SOi 689, I96I ). Vainer, B.N.i Btudlea of VaaooonatrlatloB, Bull. >.T, Aotdeay of Heduiaa, >61 66, 1?6J 1. Vaa elite re, B., Varner, B. *. and Buahner, B.i Architecture of Basil Arterle* during Vaeoconetrietloo, Clrc. Bee., IOi 668, 1962. 'T dhm yaii>4'ppuut*p^^ j '1 <gy v-  . .--a- '-..^r..'...j..ww.^.... >. .- .. to 4fai Jk. J. Tu Clttar*, B., Vaguer, B.M. ai Ruahnar, B.i fcrUrlsl Valla Aurlnj Vaaoeccetrlctlco, Cor t Veae, liH, 1962 (tart Is Buaelas) 6. V*gn*r, B.M.t Aleirtlao Maaaae of Kink, Artbrltla eo4 RmmUh , Aaeuat, 1963 :v- *5* 9 maowm B 1O1 M--ST Principal Xorartlgator - Sr. B. Vacaar _____ _ Co-Imraatlgator Dr. Ralph Btrtbal 3,000 yachnlolaa, jart-tlaa ' S,JOO Anlaal Car*-taker, part-tla* x,L*J EE35SE .. COBOHABUt sawm AMaala - Vlrtar Bata (100) - Aalaal rood, baddlng Hlatoebaalcal raa^asta, auppliaa Blatolocr auppllaa Blood aad Orina taata vhuM ravens (<1-''t''.;. : , i.i;-. X-rajr technician, part-tin* aodtie* of f^uljaant ' IDEAL DIRECT lUtlBiBI , ... $9,lA0 JIB 800 1,000 yx> jog ..v:'v\' J00 $10,051 IDEAL