Document gEa2nXyYejNkvKvqwN2r4gaJN

Q INTERNATIONAL. LHAD ZINC RHSBARCH ORGANIZATION 4 B*W 1 I *. * V OMfON <OW OtMCtM : October 10, 19ft * To Maaben of the 1.I.A.-I.I.-Z.B.0. Health and Safety Caaaltteei M>cti 196b nteearch Budget - Proposal* ant Work BtatoMota for Cccaldaratloo at tba 196i Budget Meeting Attached la the 196b Catalog of health aad Safety Beeeerch for your revlev la preparation for the Health and Safety Caoalttee Budget Meetlr* to be held October 2$, ISoJ at the 60 Beat b2nd Street Club, 27 th floor, l.lnnoln Buimint, 60 But b2nd Street, lev York 17, I. T. at 91JO a.a. ThU Material la dealpwd to be need ae a guide la our dlacuaelone aod oootalne beeldee a Hat of lteaa to be dlecueeed, revlev and cooeeata co peat perfonaoce of KM of tba projeete. Plaaae revlev theae ltena carefully aod be prepared to aafce your declelcoe at our Meeting eo that our recoaaaadatlcna ay be ecaplated at that tlae. Ve euggeet that you bring the Catalog to the aeetlot to aerve aa refereooe. Tery truly youre, &>*_ Z? -pty+jC**^ Doo 0. Povlar, Secretary Health aad Safety Ccaalttee royjnd N 205 19 CABllOO or KBUCT AM) SJJTH KEsnuca - lap tU-XUK> nun wo sunat comma X- ntvlcv of txUtlfl* Pro>cti o4 Exutalco Propo U* . Vork SUtaatU XXX. fccUaaloa PrcpoMXs 'v :' :' ? f.'. 'j&iSfe^ssr ` qgVM!,1 '* * <32* N 205.01 .-.I ,.Wv '.J -s. ~r. . ca tj i i 19A Cfttftlof of Bealth aod Safety *eee*rcli-leftd x. Brw or marno mntcra *m> bc t t o k b raorosm IC-73 - guaq Igoeurc to AAleot Air Ccooeotrutlcna of Particulate lead -- fee Kettering Laboratory Vort oo thle project ocntlauae aa planned vtth ft poeelbla future progr** extending over tie next two yeera. tb ttee exteaeioa trtU depend, of oewree, oo Aether eignlficent tod eetlafectory reeulte ere obtained before the tad of ft tvo-yeer term erpoeure. If eetlefactcry and alealfleaat reeulte ere obtained eooner, the vert trill, of couree, be tenlsftted eooner* Budget 35,000 lC-^9 - Qtereeterlrtlee of Atmoerfaeric teed Aeroeole - ftaaford fteaearch laetltute tble project bee euooeeafully collated field eeepHnd proem la Lot Angela# ead 6ea Frmacleoo vltb ea eoctaolfttioa of eAleot eir dete on totftl enotote of lead pine particle alee detendan* tioae. The project bee not bees ewoeeefal la Itft atteerpt to neftewft ead ebftxfteterlfte the varlout coapoudi of lead due to liability to identify eoepouade la the aeal.l particle atree fgtnd la the etaoepberv. the reooameoded exteaelon vill allov the uee of the eea^llac techaiguee already developed la other typee of urban ateoepheraa Acre coal ead oil fuel ere need erteaelvely for beetiae purpoeee. Xt ie prcbable that the dletrlbutioo of lead la theee letter atnoepheree trill be different ee to total ancamt ead particle alee fras that Alch vae found la the California eitiee' aanpling. Budget lUnmanitatlco $22,000 IC-T& - Tbe Teetlae of Oniaoolaed Cogpotpde far Boeetblo tedoorlaologlcal and Antl-iaamerr Timor Activity - fee Worceeter foundation Blaoe Ale le eaaeot tally a long-range nedlcel reeearob project Into uncharted flelde of medicine, for ample, oeooer eod erthrltie. It trould be preevaiptucMa to expect reeulte after c m year of rtudy* plea for next year'* vorX vill be e eontlaufttlon of that Aloh bee already been performed. Budget Beeonmeadetlon jU.JJO ,i HaUi-mtlMAit j * 196b Cataloc of B*altb and S*fty to**aroh ImI n v o f k ar*jp<nrw QLC-12 L**d 8tablUa*d P.V.C. H** (fr*p*rd by tatlooal taoltatioo PoizxVtlcc and TWO Staff) BlC-13 load GIu m for Dlao*rw*r* (Pr*jar*4 by 11283 Staff) OLC-lb 1b* tadloprotactlT* Zff*ct* of Xnortaala Lead (Prepared by tb* ** Tort Kadleal Coll***) CLC-15 Toxicity Study of Xoff**t*d taint Ptla (Prepared by Indurtrlal Blo-T*at laboratorl**, Zoo* cod Industrial Syilan* foundation of Aaarlca, In*. xn prmsiai proposals LC-75 Btaaa Ixpoeure to Ablest Air Ccocantretlno* of tartlonlata L**d| 1b* K*ttrla( libontoy 1C-49 CbarectrUtlo of Ataoajtxrla load Aaxoaolaj Stanford hiiiWt .Xnatltvto LC-76 1b* Tostin* of Orjmnolaad Ccnpound* for PoMlbl* Bndrcertno* logical and Aotl Winry Tuaor Actlrityj 1b* Voro**t*r foundation '1 , ,i ' 'l ^iwriiP^-iih*^iWniilifninth^Tirlr jyg pf<uxcT9 ren ccnorrrcuric* a t t h i UJd> HZA1TH AXD 6ATETT COMmXX 1964 k j p q p MBrm F*o*ct ic-79 Titl* iod Coetrtttor Tuote ____ ____________ mou*t*d An?XWd Toxicity fMtlac For Orgxso-LMd Ccx^ouM* -- Tt> Bio* Loborotorl**, Id o . od loAudrlDl llo^wi IAntcrlM| Iso. $10,000 /#,rw tefttAloa for Jkgalrut IDEAL A /*./ * rV.VKT* M^M' - V-;"1J ^fW4fJ' -U-jU*1 JJ'^?UWP>', ; 4!-" i CsT .1 v4 iwawigE/- ' -i 4 - ^.ts^ ..'*__.; - si ,< w AmJ^5*K- A. 9 n. wonc eTAnMBR ron awarnwurai t o LEO WAITS ABD EJkJTTT COMCTU* 1S64 BUDGET MXTDO Wert Statewst T1U fund. DJU Approvtd Pur Aj.1r.Jt DIC-U LC-12 CLC-IJ tno-is Tb ftfcdloprot*ctlT Eff*eta of InoraMila Ind *10,0* Lm4 SUblllMd P.TX. Pip. Jfi.JOO Lm4 OIu m for Uaacrwi. 25,000 Toxiolty Study of X^Mtrt ftlot Plla 20,000 /*<y /C \~r /vrn /o m `*V~ j r`-^T--1 ( -*,-- i. -- y'-V J2 m a y - . * TOTAL V5.*<v V ' vtg|p IB* PFCP0&HL8 FDR CCH3HKRAT10B AT OB USAS EEU3S AXD auvn COMSB i$St warn MEzruo I Pro>ct Titla and Fund* Oaelaloa J Contractor ____________________ Approved for .5 LC-T5 was Erpoaur* to A*>laot Air Cooeastratlooa of Fartieulata Laad 35*000 jC.mr* LC-69 CUnctorlitlei of AtaaRnrH ImI JUnwlt 22,800 hen LC-76 Cm Taatlag of Oiyaol--d Co^pooala for Poaalbla hterlMlifietl aod Anti* 111 mry fiaor Activity 11,250 //. Vt'O / WML ' <V,vfU mmmrnm&imm *V ;j r . . &>v"- ,' ; ''1 - -V* ) -7 -- 'v; C*- ` . ; ' ' r&w; > ''.J .-** - ! ;/v^;;#s3 ,>a ; ,j j -v ' A BU min a d wtn caHsacmam mooMX OeXdbtX l$6j 1 ?5m Mbaltt*4 Vjri 0. 8. Tyoo aa4 Cams*xv, Ins. 230 P*rt Avmn* Av lark IT, 8. X. -ft ;'f si--Jyvvj^ N 205.02  1/IA.y^^,.. , '-ri*--- -iflL A Btateaant of th* Problem tMlrll]r tb# (robin fHri by LIA la tin fltU of health la Co* of parvmalva leooraoo* (bout occtaupcnry lead toxleolo*y. And thla tfoarano* la oot by (ay a**aa oooflaad to ltlaaraot JouroelUte. Nadir*1. baalth official*, laduatrlal hyjlanlate, municipal baalth board* mod aducatort an almllarly mlalnformad. L*at Booth tb* dtat* of Pannaylvasla Nadloal Aaaoclatlco pifcllahed a place co load potaoolac edilcfc vaa tgrtgloualy inaccurate. 8lac* th*a another atat* n*dlcal (Moclatloo baa picbad up aod reprinted th* aaa* fallaetoua artlcla. Dm currant (Octobar) laau* of Cooaunr Bullatla earrlaa a major acar* faatur* co load pol*cnla(. Tb* UK clipping (arris* annually ralaya aeraral tbceiaand rafarape** to lead, alaoat loarl*bly adraraa, *d rally laaocgrata, for th* seat part thaa* go uoaoavtrad. lo lltaiatura azlata to provide aoy of th* laad public*, lay or prcfaaaleeml, lth a brief attention of facta vblcb that public ahoold know about laad. Tb* affaot of thla f*oarl lfsoraoo* tblle difficult to Judea praclaaly la aoealdarahla. Xt la raflaetad la aoora* of raaaarch profraa* d o * bain* oooduotad vhlob an lataadad to d#l*n laad out of a variety of product# -- (aaoUs*, palota, oara, ccapooant*. xt la raflaetad la raatrlotlva labor la*lltlco. Xt 1* raflaetad la dlaeooatla error aad traataaot la my laduatrlal aoaldvnt*. Xt la finally a kind of Ignorance vhlsh, If sot andntad, aay JeopardU* th* aecaptaoe* of aasy of th* na* compound* aod product* uhlah lead raaaaroh program* ala to brlod oa tha market. .` s^PiSPf^SBI :^-Q*\i:'^':. v^-V^r '.: m---f^n fcl' fe' i 4-r.: "I v- .V h.. +v*....;vy-\>- :; .. . '-....- ^ --^f V ^ J>u?-..v jaaL^, <^,)*etl** 9f UA CfatuoleaUco* frscrM la Haaltb X. to lafora rolavaot public* of tfe* U ' 8. To i la tb* profcu local aa wall M popular 1. Indurtrlal bnUnlata 8. Mwilclpal *ad porornactrtal health official* 3. Medical profMalaa A. Mltoca 9. Umtai 6. Nuteant aod avlcjvM of fin* or proceeds* lead wl M product* Action to Initut* Iced Bealth Bdueatlcn Procren X. Proper* J-A taut* of Xitroturo i*1m up tb# *t*t* of t*dmlc*l kaovlad** ropurdla* lead toadeolocr aol air pollution, tlastla* Un i to tb* b**4 of our tiff(root publl**, 8. Secure tertian circulation for *bow throupb paucity *ed direct anil. 3. Produce * rlee of land Health SevelatVero report la* on n*w dereiopnente tod ro***rob** la X#*d. tbl* would b* Mat to LXA aallia* llat of a*a la jablla b*altb aad hyjleoe, Inductrial hjrglea*, *tc. $ k. Publish * r(ulmr bull (u cooptratios with tbs KvtUrlnc laboratory) sa saootatsd blbllcgrashy oe srtlslM spytsj-iog both btra sad abroad ecootroad with lead a* pifclls basard. J. dutcaots tbs pcMM of r--ponding to editors Sou yob1 lottloo any losocuratt srtlcla* boot lsad. Ibsss would bs tosvtrad with M appropriate eossr lsttsr and ocfgr ot our as* bulletin "fnett nbout Issd for sdltors snd educators.* lbs object at tbit shebangs would sot bs to sntsr Into ccctrotsray with tbs editor but to lafara sod sdaests his so tbst bs trill tab s aors skeptical attltuds toward futurs sssrs storlss shlob asp cross bit desk. .6 Cootlout sad seoslsimts our unset progr-- of ocottet ultb acdlaal sod bssltb sttoo1stloos. ::'r ;V' ' .* ` ;" v:''i-.-'.-Y " -;: a " ; : "v ' ' ' ' t- ; ? 4 r-~x':$X*aJ Coot lrtiato 1. Troparatlsa M production at tour Wl* lnforaotlon tellatln*. 2. Dnrcloptof appropriate --Ulm lift tod proparlaf adtTOnryiti plate*. $6,000 1,900 3. Eotterlac blbUocroptgr prom--. 10,000 k. Mklllsc or land laalto a--alatter (tlx --UlBa projected). 8,000 9. MaUlac tod production noate. 1,000 6. Ptollcltp c o u bmI sad aaalitaiw* la Xacte--tlat too astir* --uslsattcs* ttort. 19,000 T Ccn1n*wip Total piwwfmpmii . luia^wiapoqjiifpa myieBin .*#fesSA'-a "'.S' .".'- . '- '." r..-.., ;.' *, . ! rT .... rfw -^Mt. .*-.. I.W*. >J*'-V TNI vottiiTii roiNoitiQN roi I IMIINIITU I I 0 l 0 ( r tAmmmiury. THE TESTINO OP OROANOLEAD COMPOUNDS FOR POSSIBLE ENDOCRINOI/OOICAI. AND ANTI-MAMMARY TUMOR ACTIVITY 1 PROJECT No. LG-76 Report No. 2 For Period September 1, 1902 to August 31, 1963 Principal Investigator Ralph I. Dorflsan Sponsored by International Lead Zinc Researoh Organisation 292 Madison Avenue New York 17, N. Y. 1 I ]S 205.03 Miiminfpiit ?-fy; TABLE OF COKISnS >xn?>tr. 6 Baale Reaulta Sunmarjr Coopounda Studied Table* 1 through 27 Table 28 Table 29 I `........ Q Table 1 Worcester Foundation for Experimental Biology Shrewsbury, Hassschuso tts ASSAY REPORT r i :: Estrogen Assay - (Subcutaneous Injection) Submitted byi Samples Tested* Test Animal* Vahlclai Procedure* Dr. Henry At Hated House, female, 16-Il-day-old. Sesame oil, 0.1 ml. per Injection. Injected once dally for 3 consecu tive days and autopsy on 4th day. Material Administered 0 Estrone HM) HP-24 HP-25 S55 Total Pose Mo. of Mean Uterine uq. Mice patio t S.g. 0 10 0.8? l 0.045 0.05 10 2.1*7 a 0.260 0.15 10 3.60 t 0.226 0.1*5 10 5-52 a 0.22J 100 7 1.13 * 0.066 100 6 1.57 * 0.060 100 7 1.07 t 0.056 100 7 1.65 i 0.060  '." :"- Cvv..-: - m , .'1 ilisL-i-', r IPSWsg5SS*S '' '.V- \ i j ~ ,,A - * '' ,i Table e Woreel ter foundation for Experimental Biology Shrevsbury, Massachusetts ASSAY REPORT estrogen Aaaay (Subcutaneous Injection) Submitted byi Samples Testedi Test AnInalI Vehlclet Procedure! Dr. Henry As listed House, female, 19-21-day-old sesame oil, 0.1 ml. per injection Injected oncedally for 3 consecutive days and autopsy on 4th day. Material ^d.T)lnlitr4 0 Total Dose bq. 0 Mo. of Mlc 10 Mean Oterlne Ratio t 8.8. 0.91 t 0.056 Estrone o.os 0.1S 0.4S 9 10 10 1.87 0.137 4.6S 1 0.198 S.1S l 0.207 HP-24 100 10 0.86 i 0.032 200 9 0.97 1 0.072 400 10 0.7S 0.049 HP-26 100 200 400 0.96 t 0.047 9 0.87 * 0.031 9 0.90 t 0.033 s' h'-- ; 5 ...:M :-mgm ASSAY REPORT Antl-Estroqan Assay (In)action) Subslttad byi ' Suplas Tsatadi Taat Anlnali Vahlclast Procadurai Mouaa, faaala, lS-51-day-old Estrona, sasaaa oil, 0.1 al. par Injactlon. Taat aatarlal, CMC, 0.1 al. par lnjactloo. Adalnlatar traataents at saparata altas onca dally tor 3 consacutlva days and autopay on 4U* day. TEST MATERIAL Total Doaa Daaiqnatlon 00 00 17-MrtbyleDa<? -30-ol 2000 HP-57 50 3000 Istrona Total Doaa uq. 0 0.1 0.1 0.1 0.1 Mo.of H1C 9 Maan Dtarlna Ratio * .. i.oe t 0.137 9 1.8s t 0.2)6 9 1.51 t 0.1U 9 1.2) t 0.20$ 0 DEAD V*'-' 'H', }` -; - -'.i> ^r'i ' :7 -V !- . -v--.--.v...;-v-t ' * ;1 - o>..;; Table k Worctatar Foundation For Experimental Biology Shrevatxiry, Maaaechuaetta AS8AY UPOKT Anti-Eatro^en Aaaay (Injection) Submitted by iaaplea Taatadi Taat Anlaali Vahiclaai Procedural Kouaa, feaala, 19-?l-dy-old Eatrona, aeaaaa oil, 0.1 al. par Injection. Teat material, CMC, 0.1 al. par injection. Adalnlater treatments at aeperata aitea once dally for 3 conaecutiva days and autopey on 4th day. TSST KATCAXAL Total Done Eatrone Total Doae Mo.of Mean Otarlna 0 00 10 0.67 A 0.054 0 HP-23 0 0.4 9 4.30 1 0.206 1 0.4 10 6.16 A 0.260 HP-24 1 0.4 10 3.47 A 0.123 KF-26 1 0.4 10 4.99 A 0.214 i * * '- - `"'i. .......................................... - ,, 7^i^|yPij))gjTOg|SWElBgWW|l|^^ I--. .-~'V--- "*' ''** *. -'*- -. - - -tr'' Vi'--|-(it-i ---- - Table 5 Worcester Foundation For Experimental Biology Shrewsbury, Massachusetts ASSAY REPORT Anti-Estrogen Assay (Injection) utnltted byi sop la a Tastadi Teat Anlmali Mouse, feaisla, 19-21-day-old s Vehiclesi Estrone, seaana oil, 0.1 Ml. per Injection. Test Mterlal, CMC, 0.1 sd. per injection. Procedural Administer trsaUssnte at separate sites once dally for 1 consecutive days and autopsy on 4th day. TEST MATEEXAL Total Dose Estrone Total Dose Mo.of Mean Uterine 0 0 ar-zj 00 0 0.4 5 0.4 so 0.4 Go 0.4 240 0.4 10 1.10 1 0.064 10 J.6J i 0.16} 10 5.55 a 0.221 10 5.J2 a 0.260 10 5.42 a 0.254 10 5.23 t 0.214 .3 -T o VvV V*VmV.,'-v -- Table 6 ........... -.......... ~ - Morceatar Foundation For Experimental Biology o Shrevabury, Maaaachuaett* ASSAY REPORT Antl-Eatrogen Aaaay (Injection) ubaltted byi Sample* Teatedi Teat An Inali Vahlclaai Procedure! Mouae, female, 19-11-day-old Eatrone, a* a am* oil, 0.1 ml. per Injection. Teat material, CMC, 0.1 ml. per Injection. Admlnlater treatmenta at aeparate eltea once dally for 3 conaecutlve daya and autopey on 4th day. TEST MATERIAL Total Doae Dealqnatlon - P9. . Eatrone Total Doe* pq. 0 00 0 0 0.1 EF 29 BP 29 EF 30 BF 31 50 0.1 500 0.1 50 0.1 500 0.1 50 0.1 500 0.1 50 0.1 500 0.1 Bo.of Kean Uterine Mice _ patio * S.B, 10 1.01 l 0.063 10 5.36 * 0.225 lO 5.H 0.177 10 5.23 t 0.153 10 5.53 * 0.291 AIL DEW 10 5-9* * 0.280 10 6.33 * 0.231 10 5.85 * 0.207 10 5.01 t 0.117 age jpni;m wss^p ^JSpSi a we* Table 7 Worcester Foundation For Experimental Biology Shrewsbury, Massachusetts ASSAY REPORT Chick Androgen Assay Submitted byi Samples Testcdi Test Animali Day-old male white Leghorn Chick Vehlclei CMC, 0.05 ml. abeolute alcohol per Inunction. Procedure! Inurvct once dally for 7 days and autopsy on 8th day. Material Total Dose odyN* ot Mean Comb 0 Testosterone HP-35 0 **7 12 1 51 9 3 *7 10 9 52 10 27 50 9 61 *7 7 & J*9 10 50 9 1200 50 8 0.30 a 0.019 0.33 t 0.025 0.33 t 0.018 0.V[ 1 0.025 0.51 t 0.055 o.ej o.iio 0.27 * 0.019 0.31 t 0.01V 0.28 i 0.019 l \ '' i : * v.j>u.W!ffa i^smn>wuu.gwwwwii nm.n... -r Wtfrge^ *................. Table 8............. Worcester Foundation For Experimental Biology Shrevsbury, Maaaachuaetta ASSAY REPORT Chick Androgen Assay Submitted byt Samples Tsstedi Teat bilaali Day-old aal* white Leghorn Chick Vehicle) CMC, 0.05 aL. absolute alcohol per Inunction. Procedure, Inunct once dally for 7 days and autopsy on Bth day. Material Inunctad 0 Testosterone HP-23 EP-2% BP-25 EP-26 Total Does u<?. 0 2 8 32 300 300 300 300 Ho. of Chicks 9 9 9 9 8 10 10 6 Mean Cash Ratio 1 8.E. O.36 1 0.020 0.k3 a 0.028 0.62 a 0.051 0.80 t 0.076 O.kl a 0.036 0.10 1 0.050 0.16 a 0.0*> 0.*> t 0.029 4 r** **' ;. -.% v * i Worcester Foundation lor Experimental Biology Shrewsbury, Massachusetts Table 9 Assay lUCFOitT Chick antl-Androgen Aaaay Submitted byi Dr. tery Samples Tested* Aa Hated Teat Animali Day-old male white leghorn Chick. Vehicle t Teatoeterone enanthate, aeaame oil, 0.3 ml. Teat material, aeaame oil, 0.03 ml. per inunction. On first day chicks are Injected once with teatoeterone enanthate. Beginning on same day lnunct test material once dally for 7 days and autopsy on 8th day. TEST HATSAIM, Total Dose -Mr 00 0 nej TO5 HK>6 0 3 3 3 Teatoeterone Enanthate Total Dose pq. 0 0.5 0.5 0.5 0.5 BO. of Chlcka 9 12 a a a Body Vt. q- 57 5* to 53 U Mean Comb Batlg i #.*, O.tt t 0.039 1.2! a 0.06! I.M. a o.oaa 1.16 a 0.118 1.38 a o.oej ,,. ............... Worcester Foundation for Experlamntal Biology Shrevsbury, Massachusetts Table 10 ASSAY ASPORT Chick Anti-Androgen Assay Submitted byi Samples Teatedi Teat Anlmali Day-old mela whits Leghorn Chick. Vehlclei Testosterone anaathate, sesame oil, 0.3 al. Test material, aeaene oil, 0.0S al. per Inunction. Procedure! On first day chicks are Injected once with testosterone enanthate. Beginning on sane day launct teat material once dally for 7 days and autopsy on 6th day. TSST MATSRIAL Testosterone Mean Total Knanthate Body Dose Total Dose *o. of Mt. Mean Comb 0 0 0 12 so 0.39 t 0.020 0 0 0.3 11 40 0.79 * 0.077 Ro 2-7239 0.3 1 O.S 0.3 10 31 0.71 0.043 10 56 0.63 * 0.039 HP-1 3 0.3 11 34 0.97 i 0.071 HP-7 3 0.3 12 62 1.09 t 0.055 BP-13 0.3 O.S 1 O.S 2 0.3 3. O.S 12 39 0.91 * 0.066 11 39 0.91 * 0.072 11 61 0.00 * 0.039 11 61 1.01 A 0.060 9 <jii % i Table 11 Woroeater Foundation for Experimental Biology Shrewsbury, Massachusetts s msmtitf1*- f.- * ' Rat Anti-Androgen Assay (Injaction) Subsltted byi Dr. Henry Staples Tested, As listed ' Test Aninali Ret, male, 21-day-old. Vehicles Testosterone, CMC, 0.5 nl. per Injection Test material, CMC, 0.5 *1. per Injection Procedures Castrate 21st - 28th day of life. Beginning on sa day, administer txeataanta at separate sites once daily for 7 days and autopsy on 8th day. =.: -..'..... .-1. ',VS-....-;';?-a.: - .; Jf>: .:r:--`':i *i- -vV TEST MATERIAL Total Dose Designation sag. Testosterone Total Dose Ho.of ag. Rats Mean Body Vt. g. TISSUE RATIO * S. B. SeaInal Prostate Vesicles Levator Anl Testosterone Progesterone ISO 2 10 94 10 90 10 94 0.0710.005 0.1510.011 0.1910.024 0.5510.125 1.2810.076 0.3510.033 1.2710.055 1.2410. 051 0.6310.029 HP-15 75 2 10 95 10 85 1.0610.072 1.2210. 104 0.6810.033 1.5310.068 1.5410. 055 0.8010.039 HP-1 8 79 10 7 6 10 84 1.7610.107 1.6110. 094 0.8210.012 1.6510.136 1.6610. 094 0.8310.039 1.7010.147 1.6710.125 0.8810.029 HP-7 22 2 10 87 9 91 10 95 1.5010.078 1.5510.061 0.8510.034 1.3410.070 1.4010.137 0.7710.040 1.2210.046 1.3910.046 0.7910.015 * WAMPUM*1 ; ' . &> W M C W iW fl' " iiu,l^W ' i'. | i. i[.iii; i; ; i|i i wii. in niii i wi' Boreastar foundation for Exparlaantal Biology Shrewsbury, Massachusetts Tabla 12 ASSAY REPORT i Sutaittad by Sanplas Subnittads Test Anlaalt vahlclai Procedural Houaa Anti-Androgen Aaaay Injaction Mica, Bala, 21-2] days Saiana oil - 0.1 al. par Injection - Testosterone OtC - 0.2 Bl. par lnjactloo - Tast Cenpound Caatratloo - 21-21 days of ago. Xnjactlons started day of surgery and continued oeca dally for 7 days. Autopsy on 8th day. TEST CCHFOOHD Total Total Doss of Doaa Tastoatarooa Bo.of Haan Body Wt. TISSUE RATIO S. E. Saalnal Prostata _______vat Idas *1 0 0 0 7 18 0.10 0.005 0.21 0.039 00 0.8 9 18 0.28 t 0.029 1.08 0.087 1 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 i-: h * HOUt* Antl-Androgan Maty Injactlon i Sutnlttad byi Saaplaa Subatttad. Taat Anlaalt Mica, ult, 21-23 daya - Vahlciai Mi im Oil - 0.1 al. par lnjactloo - Taatoatarcoa CMC - 0.2 al. par lnjactioa - Taat Compound ? Procedural Caatratlon - 21-23 daya of aga. Injactiona atartad day of aurgary and cootlnuad ooca daily for 7 daya. Autopay oo 8th day. TKST CCKPOUHD Naan l Total Total Doaa of Body Doaa Taatoatarona o.of wt. TISffOB RATIO + 8. B. Banin al paalqnatlon 04. WJ. Mica 9- Proatata Vaalclaa f9t---------0------------- 0 0 0 0 U 20 0.05 0.005 0.13 1 0.010 U 17 0.19 * 0.018 0.97 A 0.183 10 0.8 20 0.8 2*0 0.8 12 20 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 xr-zt 5 0.8 AIL DEAD 7"! j 7 '1 P: 7 l: Ii?r' . ^ ^ TV.'-; ... ; "-4- '^sjad^Lv.'- 'li- vy-j a- Mou*a Anti-Androjan Mity laJactton Sutalttad by> Sapla* sutelttadi Teat AnLmalt Vahlclai Procedural Klee, mala, 21-21 day* 5i im oil - 0.1 ml. par Injection - Testosterone CMC - 0.2 ml. par Injection - T**t Compound castration - 21-2] day* of *9*. Injection* atartad day of surgery and continued ooca dally for 7 days. Autopay on 8th day. 3 TXST COMPOUND Total do m Designation 9- 0 Total Do*a of Tastoatarona *>9. 0 No.of Mica 12 Mean Body Wta ? 19 TISSUS RATIO a f. I. Seminal Proatit* Vaalcla* 0.09 * o.ou 0.17 * O.ou 0 0 0.8 12 20 0.20 t 0.022 0.60 * 0.056 Frocaaterooe 20 10 0.8 0.8 12 22 0.15 * 0.012 0.V5 t 0.019 12 21 0.18 * 0.016 0.10 t 0.018 HP-27 BP-28 10 0.8 10 0.8 ALL HMD ALL HMD ; > Muubimp*- v>* i .Vfa.4'- LIA11445 * : # ---------------------------"- Table 13........ .......... ..................... Worcester foundation for Experimental Biology Shrewsbury, Massachusetts ASSAY REPORT Anti-Androgen Assay-Mouse (Injection) Vr'-':: '';:;.%>'';::4-': ^^ '''r;- Teat I Compound Testoa- Mean TISSUE RATIO + S. I. terone Body Material Total Total Mo.of Vt. Seminal Administered dose mg. Dose mg. Kloe e* Prostate Vesloles ! 00 19-Morprogesterone SO 40 HPS3 HP26 40 40 HP2T 40 0 0 SI 0.1310.032 0.2110.026 0.8 9 so 0.1710.014 O.861O.080 0.8 8 so 0.1910.018 I.O51O.O63 0.8 8 24 0.1510.018 0.5U0.046 0.8 6 17 0.2110.027 1.0510.156 0.8 5 15 0.2910.033 1.1610.198 0.8 9 22 0.2210.013 1.0810.104 itt s MW#PfWP Ppmai"e^-y ; *Y*'y, ;v-4 .' . 'v *' ;? Worcester foundation for Experimental Biology Shrewsbury, Massachusetts Table 16 ASSAY REPORT Submitted byi Samples Submitted! Te*t Animal* Vehicles Procedure t Nous* Anti-Androgen Assay Injection Dr. Haloola Henry As Listed Mice, male, 31-3) day* Sesame oil - 0.1 ml., per injection - Testosterone CMC - 0.3 ml. per injection - Test Compound Castration - 31-33 days of age. Injections started day of surgery and continued once dally for 7 days. Autopsy on 8th dsy. TEST CGMPOUMD Total Dose Designation Total Doae of Testosterone sag. Vo.of Hie* Mean Body Kt. g. _ 0 0 AO 16 0 0 0.S 10 19 frasesteroae 20 AO 0.8 0.8 6 19 9 19 HP-27 10 0.8 AO 0.8 SCAD DEAD TISSUE RATIO I. E. Seminal Prostate Veelclea 0.08 S 0.00$ 0.19 s 0.02A 0.19 t 0.019 0.9J * 0.07A 0.2$ * 0.018 0.21 X 0.0)1 0.87 * 0.186 0.7A x 0.038 \ '.V ' >: 1 i .; H 7- . O "* . _ ___ 9 LIA11447 ^j.3* . > # \4 vi. ^ *7'i iWirailwaiiMt^^^aKirrw- `` ,,/ - _ K " ` ` a^fci ___ Worcester foundation for Bxperinental Biology_____ ____ . Shrevsbury, Massachusetts Table 17 ASSAY RBBORT Nous* Anti-Androgen A***y Injection Submitted byl Saatples Subalttedi Teat a 1m1i Procedures Nice, Mis, 21-23 days Sesaaa oil - 0.1 ml. per Injection - Testosterone CMC - 0.2 bl I. per Injection - Test Coapound Castration - 21-23 daye of age. Injections started day of surgery and continued once dally for 7 days. Autopsy on 8th day. Tsrr ccHKxrm Total Do Total Doe* of Testosterone WT. NO. of Naan Body Wt. g. TXSSOX RATIO 1 8. B. SeaInal Prostate Vesicle* i _0 @0 00 0 0.8 7 17 0.02 t 0.010 0.17 0.018 4 17 0.17 t 0.012 1.01 * 0.131 Progesterone 2.3 3 10 0.8 0.8 0.8 9 16 0.10 1 0.022 0.90 * 0.111 9 19 0.11 1 0.016 0.96 * 0.163 8 16 0.09 i 0.013 0.84 1 0.147 HP 32 HP 33 3 3 0.8 0.8 Dead Dead V ~;s. %.Xv Table 18 Worcester Foundation for Experimental Biology Shrevsbury, Massachusetts ASSAY REPOST Parabiosis Assay (Injection) Submitted byi Samples Tested! Test Animals i Vehicle! Procedure! Male and resale rats 21-day-old CMC, 0.2 si. per injection Place a castrated sale (29-31 days of age) in parabiosis with an intact fesale (29-31 days of age). Begin injection of test material on day of surgery and continue once dally for 10 days and autopsy on 11th day. Material Administered 0 Total Dose mg. 0 Testosterone 0.8 [ KP-21 10 lo.of Pairs 5 5 5 Mean Body Vt. g. 101 103 95 MALI - CAITXATI Naan Mean Seminal Mesa Prostate Vesicles Levator Anl Vt. Vt. Vt. mg 1 8.E. mg * S.E. mg * 8.B. 11.5H.080 11.811.021 16.0*2,362 55.1*11.003 12.0117.008 52.4*11.327 26.2*3.989 10.7*1.1^ 11.9*1.509 XXTACT rTXAUt Mean Body Vt. 93 Mean Ovarian Vt. mg * S.B. 124.0*21.834 93 61.5*27.204 85 96.5*27.950 .V'/S, k I Mm Worcester rounds t ion for Experimental Biology Shrewsbury, Kaaaachuaatta Table 19 ASSAY REPORT txpar. Ho. Autopay Datsi Anti-Mammary Tumor Assay Submitted byi Samples Testedi Test Animali Vehlclsi Procedural Dr. Malcolm Henry Sprsgus-Dswlay rat, female, 45 days old on delivery. CMC, 0.5 ml per Injection. Tumor seeds vers transplanted into the rats at 52 days of age. Beginning 5 weeks later, three an1msla having growing tumors were In jected once dally for 14 days. On the 14th day, each rat received $ uc/10 u mole glycine-2-C14 in 0.5 ml 0.9X saline followed by autopsy 24 hours later. Material Administered Total Dose Mean Body MO. of wt. Rats .. g, . HO. of Tumors Mean Tumor wt. rcr. Mean Specific Activity cjn/mq Protein i s E . 0 0 u 233 20 2648 102.3 3.99 2a-Methyl-5o-dehydrotesto- 7.0 iterone HP-28 21.0" 11 7 252 239 20 1990 89.0 2.98(P<0.01) 11 3701 108.2 * 2.88 HP-29 21.0" 10 240 19 2497 117.2 2.68(P<0.01) HP-30 21.0 8 233 14 5438 122.8 1 4.45(P<0.01) HP-31 21.0* 10 220 17 2041 105.7 2.58 " Considerable Inflaiasatlon at site of Injection. + Slight Inflammation at site of Injection. Table eo i Wore# tar foundation for Experimental Biology Shravabury, Maaaachuaatta AS8AY REPORT THYHOLYTIC AMD AMTI-IHrLAMKATORY ASSAY (Injection) 8uhmltt#d byi Snaplaa Teatedi 100-123 9 Taat Anlaali Mala rat *l-*3 day* old at atart. Vahlclai CMC, 0.3 nl. par day by injection. procedural Bllatarally adrenalectcnlae rata oci 23rd-26th day of Ufa and inaart two cotton pallata aubcutanaoualy. I Baginning on aaiaa day, adalnlatar treatment onca dally for 6 conaecutlve daya and autopay on 7th day. Renove granuloeaa (cotton pal lata), weigh, dry for ;; 24 houra at 100C and walgh again. Alao remove and walgh, aftar blotting dry, aach thynua gland. Matarlal Administered 90 Total Doc pq-... Mfta Body Wt. <7. 0 153 THYMUS TEST Mo. of Mean Thynua Bata patio 1 S.E. 7 2.74 1 0.144 AMTX-1BYLAHMATOPY TEST Bo. of Kean Cry Tlaaua Oh#. wt. *. * 8-8. . 8 129.2 1 18.972 Cortlaol 0.3 147 7 2.65 * 0.1B0 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 1 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 BE 33 5 139 7 3.14 1 0.168 8 103.9 1 13.518 % Group# b e 32 - HE 33 - Compound under Skin A A .'.4 Q 1 .^f*l gftfc . a . - v*\ VJfr'' - .. . - 1 'V-.fev * -V'V ' * - C *> $ .r'V* ^;-'-*~.S *.* t*?vV-/- i t': : i uniaMhifiri'iiri Mwhhntri'v' ihrtiftinifrii Worcester foundation for Experimental Biology Shrewsbury, Massachusetts Table 21 ASSAY RETORT THYMOLYTIC AID ATI-IKYI*A>*lATOJtY ASSAY (Inj action) Submitted byi Saeplaa Tea tad i Taat Anlaalt Vehiclei Trodedursi Kale rat 31-2) days old at start. CMC, O.S al. per injection. Bilaterally adrenalectoalae rata oo 23rd-26th day of life and Insert two cotton pellets subcutaneously. Beginning oo sane day, edalalater treatment ooce dally for 6 consecutive days and autopsy on 7th day. Reaova granulosus (cotton pellets), weigh, dry for 34 hours at 100C and weigh again. Also rs w o t s and weigh, after blotting dry,.each thyme gland. Material Total Dose Ko. sight Is TEST ^Mean ttiyaus Awri-nnJustATOoy Ko. of Mean Dry Tissue 0 0 8 67 3.48 t 0.331 8 24.7 * 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 t 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 * 9.874 HT-25 8 DEAD -- ----------------- Kf-26 8 1 75 4.13 t 0.424 3 21.0 t 4.362 8 5 70 3.47 1 0.522 5 17.7 t 2.650 V-vX'V;r) ' * - ' .' - ` -t . LLW ...at , rir-hoe >.- ^ ifc i I i- Tabl 22 Vorpeeter foundation for Sxyerlneatal Biology Ou-cwatury, Haaeachuaetta a S&OT RZFORT TBTMXTTIC AID Ajfn-DOrWdtATORT ASSa T (Icjectloo) :i -'3 0 aihdtM By: Staplea Tceted: 7at AcInal: Vehicle: Procedure: Dr. Hanry HP-13 Mal rat 21-23 day* old at Itart. OC, 0.5 al. par Injection. Bilaterally adreoalactonlae rata oc 23rd~26th day at Ufa and lnaert taro cotton pallrta auhcutaneoaaly. Beginning on ease day, adalnlatar treetnent ooea dally for 6 conaecutlve day* and astopey oo 7th day. Rcaove granuloaaa (cottoo pallrta), weigh, dry Par 2k bourn at 100C and weigh again. Alao ra-ira and weigh, after blotting dry, each thyaua gland. Ihterfal mbUolatered 0 Cortlvol IP-13 total Dm* . Nm Bod/ vt. 0 85 1.0 82 h.O 81 1 72 2 78 ramus teat >9. Of Hma TB/Kia Riti Ratio 1 S. I. 8 3.81 t 0.27% 10 3.0k t 0.129 10 1.52 t 0.136 7 3.65 * 0.268 8 3.81 t 0.255 Ajcn-nfieMurarr fc. Of Mean Dry tlaaue Cbe. . . * S. I. 8 23.5 t 2.600 10 17.6 11.K9 10 12.8 * 1.127 7 16.8 t 1.6k5 8 20.7 i 1.5V r Table 23 Worcester Foundation for Experimental Biology Shrewsbury, Massachusetts ASSAY REPORT THYMOLYTIC AND ANTI-INFLAMMATORY ASSAY (Injection) i Submitted byi Samples Tested: Test Animal: Kale rat 21-23 days old at start. Vehicle: CKT, 0.5 ml. per Injection. procedure: Bilaterally adrenaleotoolse 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. r Remove granulomas (ootton pellets), weigh, dry for 24 hours at 100c and weigh again. Also remove and weigh, after blotting dry, each thymus gland. 0t Total Mean THYMUS TEST ANT I-INFLAMMATORY ; Material Dose Body No.of Kean Thymus No. of Mean Dry Tissue Administered . Vt. Rats Ratio t S.E. Oba. tft. mg. * S. E. * t. 0 0 70 9 4.10 t 0.111 9 29.5 * 4.229 Cortisol 70 9 3.18 t 0.2J3 9 19.3 t 1.700 I- 74 10 2.93 * 0.140 10 19.0 t 1.283 74 9 1.90 * O.I67 9 11.5 * 1.972 HF-13 4 57 8 75 4.63 2.63 t t 0. 0. sa- 5 ' ,2 10.2 t 2.631 18.0 i 0.606 HF-1* 4 61 3 3.82 t 0.250 3 16.3 * 0.836 8 62 2 3.86 t 0.773 2 19.7 t 2.575 ti 'Ll'*-. v_UJ yillj flail'll. 111^.1 M --up'JjT ^.1jfl t I.i'ume ( n me. ---uigvuv/wiy m mh m-w w k h ""I'm i'.ry>,j^pp^|ffy i i i i i Worcester Foundation for Experimental Biology Shrewsbury, Massachusetts Table 24 ASSAY REPORT t I | Submitted byi Samples Submitted! Twat AnInali Vehiclet Procedurei House 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 CHC - 0.2 ml. per injection - Test Compound Castration - 21-23 days of age. Injections started day of surgery and continued once daily for 7 days. Autopsy on 8th day. . 'Jly PLII TEST COMPOUND He an Total Total Dose of Body TISSUE RATIO + 8. X. ; Dose Teatoeterone Ho. of wt. Seminal DesIgnation tnq. roq. Mice g. Proetate Vea Idea * Kbl49(THO) 0 20 0 0.8 6 15 DEAD 0.05 * 0.013 0.20 x 0.033 - 32(7S0) S 82 (TWO) 20 20 0.8 0.8 DiAD DEAD IP 129 (TWO) 20 0.8 9 16 0.17 * 0.021 0.75 * 0.046 Progesterone 2.5 0.8 9 16 0.19 * 0.015 0.93 * 0.060 5 0.8 10 0.8 20 0.8 8 13 0.19 * O.OHi 0.G6 t 0.066 n8 0.20 I 0.017 0.76 0.053 n9 0.14 1 0.015 0.46 X 0.041 f 0 0 0.8 6 15 0.22 x 0.029 1.20 X 0.156 Ilf, ............... ' ' IWll| ' t 'W>IU llil> WJMl TF-was-wiy. msyti' JU^O-VS U. W^WL;'. 'II. ' <s>'<; . t j" r" /'t' v' i Worcester Foundation for Experimental Biology Shrewsbury, Massachusetts Table 25 ASSAY REPORT Submitted byi Ssnples Subaltteds Test Anleali Vehicles Procedures Route Anti-Androgen Assay Injection Mice, malm, 21-23 days Seaesse Oil - 0.1 si. per Injection - Testosterone CMC - 0.2 al. par Injection - Teat Compound Castration - 21-21 days of age. Injections started day of surgery and continued once dally for 7 days. Autopsy on 8th day. TEST CCKPOCSD Total Total Dose of Doss Teatosterooe Designation - fOq. 0 00 Vo.of Mice 6 Maas Body trt. 1. .. 20 TISSUE RATIO * 8. E. . Sesalnal Prostate Vesicles 0.08 l 0.01A 0.25 * 0.021 0 0 0.8 6 21 0.23 * 0.017 0.91 * 0.118 Progesterone 10 0 SC-U6 (TX>) SC-7k (no) 0.1 0.1 0.8 0.8 0.8 0.8 7 19 0.20 t 0.012 0.85 * O.O53 8 19 0.21 t 0.017 0.71 * 0.082 8 19 0.17 * 0.012 O.77 * 0.0k6 8 IS 0.18 1 0.027 0.91 t 0.12k vi-iaa (no) ac-79 (no) MS-22 (no) 0.1 0.1 0.1 0.8 0.6 0.8 6 18 0.21 1 0.02} 0.82 t 0.096 8 18 0.23 * 0.023 I.03 t 0.118 8 18 0.21 * 0.019 0.89 * 0.097 Worcester foundation for Experimental Biology ------ -----------Shrewsbury, Massachusetts ASSAY REPORT Table 26 Estrogen Assay (Subcutaneous Injection) - Submitted byi Samples Testadi Test Anlsali Vehlclei Procedural > - v " ' House, female, 19-11-day-old. Sesame oil, 0.1 ml. per injection. Injected once dally for I Consecotlve days and autopsy on 4th day. NiUrlil &dalnl*trd 0 Estrone x-u no sc-7l ns vi-lea tso ss-79 t s o Hs-22 TSO B>-H9 TSO SIC-0J TSO 81-82 TSO SC-129 ISO Total Dose v<s. 0 HO. Of Hlce 10 Ma id UtrliM RfttlO 8.Be 1.00 t 0.059 0.0$ 0.1 0.2 0.1 10 2.11 t 0.090 10 3.27 0.297 9 1.6$ 1 0.267 0 5.26 * 0.277 100 6 3>1 t 0.375 100 5 0.ej a 0.060 100 6 1.06 1 0.09$ 100 6 0.68 1 0.073 100 6 1.01 t 0.071 100 6 1.13 2 0.066 100 6 0.86 t 0.072 100 6 1.09 * 0.076 100 6 1.02 1 0.060 ______________ __ Table 27 . _________________ Worcester Foundation For Experimental Biology Shrevsbury, Massachusetts ASSAY REPORT Antl-Iatrogen Aaaay (Injection) Submitted byi 8amplea Teetedi Teat Animali Vehlcleai Procedure i -V-'s'- Be, vaa'Aor Want Mouse, female, 19-21-day-old Estrone, aeaaaa oil, 0.1 ad. per Injection. Teat ataterlal, CMC, 0.1 ad. per Injection. Adnlnleter treatments at eeperata eltee once dally for 1 consecutive daya and autopsy on 4th day. TEST MATERIAL Total Dose Deslqnatlon U<I, -0 0 Matrons Total Doaa p j . 0 0 o 0.1 302 (wo) >,;>4**000^ aS3 (no) 1000 0e^ " 0.1 10019 (no) 19 (wo) 1000 ,1000 0.1 0.1 aoK (no) ' 2000 0.1 visa (wo) 3000 0.1 M2 (WO) swi (no) 1000 1000 0.1 0.1 0029 (wo) 1000 0.1 Mo.of Mean Uterine Mice Ratio t S.S. 12 0.97 * 0.068 12 5.75 a 0.208 DEAD DEAD SCAB SCAD 2 J.79 * 0.071 SCAD OCAS SCAD 12 1.59 a 0.210 * - ,*;i ' 'y*. i . a * ''v V "v . ^ . , i.fy BtMKXKY Poaalbla Significant Activities jta<ju 1 rLag Further Confirmation Table WQ Coapouivl BP 32 HP 32 Significant Activity Anti-Inf1--story Activity 21 22 - ** *?* 24 P V- ' ' w. v - I*'* .-? 1 29 HP 22 HP 26 BP 13 HP 14 SX 129 (no) Antl-Xnflanatory Activity vS' , r-y Antl-Infla--atory .* Activity - ' '-.a 'J " .... -::i '* Antl-Arxlrogea -- ,, *. ..............................- , sx-116 (no) Antl-Androgan 26 SX-116 (T>0) UtrcjM . r. \ Code Sk 116 Sk 7* Kb 149 Sk 79 Sk 62 8k 83 fa 22 Ml 488 Sk 129 HP 1 HP 7 HP 13 HP 14 HP 15 HP 21 HP 23 Kf . ' HP 29 HP 26 ; HP 27 HP 28 HP 29 HP 30 HP 31 TABLE 29 COKPOWDS STUDIED Structure Fhenyllead triacetate Dibutyllcad dl acetate Trlethyllead aoetate H( trlbotylplusblylj-laldazole Trlaethyllead acetate Tributyllead acetate Dlethyllead dlacetate V' Trlaethyllead cyanaalde Tetrebutyllead Tetraphenyllead Bla-trlphenyllead eulphlde Thlobenzyltrlphenyllead Thlophenyltriphenyllead Thioacetyltrlphenyllead -'-*1 lead Benzyl Mereaptlde Lead dlthtobenzoate I*** thlophenolate \> xlno aaetate eoaplM`4u&?jil _ TTlphenyllead dlmethylaralnate ' Bla-dlphenylohlorolead ethyl arilnate ^3 PbSCHgCOCCt >,-.-cc. V*.: ' * ' '* fnptml for >mn> OX VrspoMl Bo. M 6J-J1* 'MAwlo j *si;.. v v`" ,, < -f *. iu v*^; mjMt # ic-69 ^ . v.. **vfc** cuNCMimvx of JOdsnocnc w d a s u o o c * , " ~ " * *- " VS*> " , :V.S&Vyfes >jr ZXaor Bdblaoaa - '" 'J ,i'~ .V`` - A'C^tvo" -nVy for '- ' ' '* /: . ">* >` -*? . XttontUcBOl loti tine Brnox* OrtMlaotlc* - 8* IMImi Av o w * t : l TorIt S1T7*, BMo*v TTOorRt .%- : i-f'.'Sf. -v' Bt Cr. Sohrote f. IMtko v `'- '' C,n ''Jjjjm-*V ' `.s^. " ' J < -*^vV^/ -*** - "** ** /- - ' N 205.04 cuMcmxarxca ar a s c bk b o o ttu> a e k b o u 2 mtua ntxaut Objectives lbs Objectives of tbli Hmra moiraa ini 1* To extend tbe exploratoryimjllra of tawjhtto lead aerosols to anrlrooseota **re Maaojtorlo emissions art bo * dcnlnstsd by autoariblla sxbsotta ',, 8. To sxtend tba sis# rena of tho eeryling tyetca for a tlrl# etapUng ported 5. To cheractertaa xon enyistsly tbs nature of tbe ImI Mrnanl ' Bscbrrouni Ptscusslcn Cw propowTnuoofefc progrsa la aa extension of oar study oa "Cbaracteristlne of Ataosjberlo load Aerosols,* SRI Project kill. ibis study haa successfully developed a "TMnt azsd analysis proeadaro vbsre- by tbe alxa dlatrlbutloo of tbe laod aerosol oas be obtained} tba netted baa baas need la exploratory aa^illng of ablest lead aaroaola la eevual plaoaa la tba Baa freoolsco Bay Axaa tod la too fapUt. Cccaldereble effort baa beta axptodtd to detemlae tba lead eapomb iblcb aakeup tba etaoejberto lead aerosol. VbUa tba acnpounde oaaoot yat bo ccapletely delineated, provisional Infonetlon baa been obtained. ,j fna tba ataoajbarla aa^illr^ vhlch baa baas oanrltd eat tbae far* . a typical alxa dlatrlbutloo nl*ht bo ooo hevln* a aaaa aadlaa equivalent dlaaotar of 0.3 e>, .8$$ of tbo ness la pattlolaa ler**r tbaa 1.0p, aod v. 30$ of tbe aassla pemelsslaea tbaa O.lj tba total alaa naa l^t - * `AroaS axtaod trm 0.0$ to 3 a. To obtain a alaa distribution vltb tba tecta* . Billet used to data rtijalrta a aaajllm parted of b to S boon) la aar coa teat period tba alia dlatrtbutlce oaa be detezalned la only a portloa ' ., of tba full ranga tfalcb tba laatnaast cao cover. Biue, any ettcapt to ' daacrlbo tba eoaplata alaa dlatrlbutloo of tbo laod aaroaol requires ltbcr extrepcletln* dlafla text results beyoad tba llalta of tba aaap* ....... Ur< eyetea or otablnlnj tba raaulta of Nitnl text periods lato ooe oversea distribution. Seltbsr prooedura la entirely satisfactory vltb* -f out aara detailed kntxrledye of tba characteristics of aslant aaroaol alto distributions. Bence, aa extension of tba present eeapllrn aetbod ' ris\% to tout a acre eoapleta coraxape of tba full alia distribution of tba ' i, laad aerosol la a locloal acatlnustloa of tba present taaaarcb projpan. ^ Teat data vhlab, la a stadia empH'm period, vouldd>ecrtt aoee nearly tba full alts ten** of tba laad aaroaol la tapeelally Uportaot la devaloplaf aetboda for Interpreting data fren stapler aod note routlna axapHnt techniques. 'A . .* *' -i Iba exploretory lsed aaroaol field stapling to data oaa oarrled out at various looatloaa In California Aurlof tba staaar ct 1$6J. It aeana clear that tba prlnotpel souroe of laad la tbeaa eaaplse me auto* acfcUs exhaust. Urns, tba raaulta are obviously biased toward TO. sffluaata. Cbolat and oc-uortare* barn polatad out a varlaty of aouroea % *Cbolak, JL J. Bcbaver, and T.P. Sterling. Tbe lead ScateM of tbs ataoapbara. f. Air Poll. Coot. Aaaa. (B) 86l (June l$$l). i5 for land ntroaola In vafcaa amt but thay tnpbaalud tht aadmtlan of eonl nod Aunt fret bl^i-latd toll*. City furtbtr ttata that 90$ of thn lttd In oonl vlU bn dlncbtrctd to tht ttnotjhtrt tod that lnmtttd Irrtlt of land In tht ntaotpbtr* Is otrtata clttat durinc thn vtatnr wmj bn Aut to tht taomttd catauttlon of oonl. Atotutt thtrt era uifetn tourott of land in addition to Cm note* Oblit, m Attn tbould bt cttbtrtA an tbt ntturt of tht ttaotphtrl* ttrotol in that* othtr torlracntota. Cm purport of thin ttapltaf vculd bt to axtalnt tht terotol tlu chnnetarlttlca in not nrttn thtrt tht tutOBobUt sty not ntcttttrUy bt tht aajor aouroa of tbt laad atrotol. Pltont Milch vwlA aoct llktly cant vlthln thin- ottacory valid bt tan etctern or sld-vtttaro imt torioc tht vlnttr Mmo oonl nnd futl oil nrt btlnc ttted In rtlttlrtly ltr** tnouatt. Cant tffart tbould tlto bt atdt to Obtain tnturtm nta on bnekcrouod dutt In tent rtaota trnnt. (barn trt nay rtaota arm In California nuitablt for annaransU of natural ntaotjharln Intd acnenntmtlon. IB nddltloo to dbtalnlnf data on lttd ntrotoln in thttt othtr mm, non tttantloo tbould bt fltta to ldentlfyinf tht rtticnn for tnd tht tlnoifletnct at apparent vtrlntlann In lttd ttrotol tint dlttributloot, far nxatplt, durlnc tht flrtt tatgiUnc proerta in ten Auction, it vtt notad thnt tftarnoon tonlyntt thovtd centrally n ntlltr alatd ttrotol thtn aorntac tatta. further ttudltt of atrotol obtrtotartatlon > thoild altntpt to dttaralnt to Mint tztant tueh vnrlntioot raprtaant ml cfcancet In touret obnrnettrlttlen of ntaotjhtrlo yrootttta nod to Mint extant thty l*ht bt dun to randoa nffneta. Cm ntturt of tht lttd ttrotolt It of inttmt btotatt nxponurt to amanita oonetotrntloM ota bt toxin.' fartinIt tun tnd ocnotatrnUna nrt <only tvo fiotort Milob bat* to Ixportaatbaartat on thn tmrlalty tht ttrotol in nay elm altuntian. Dr. Cabot notloot that tnothtr ' 'v faster It tht cbtalcnl eaqeaitlso at tht ntaotibtrta ttrotol.* Beat jtad etapouada nrt Much lttt trahltton than ethart. Oiut, infomticn on tha cbtnlctl ntturt of tba ntaoajbnrfo lnnd atrotol could bnvt taper* . tact appllcatloct to crfmlty problrtt. Cm rtttnroh proem to data bat Included oontldtnhlt effort to Identify tht land ecspomda -*m| up tha atrotol. Qaetroo tod x-ray diffnotloo tnchalquat vara tht principal aathoda uttd, but tbt cxptrintnta van, la ftnarnl, untuootttful. Cm lack of auootta ota bt tracad to tha aaall tint of Boat of tht atrotol partlolat, tht low oeoonotntlon of lttd la tht total taoajbnrla dutt, , anrlma lntarftrnaota fra othtr ataoajbarlo ttrotol attartalt, and-tba land atrosol ltatlf btlnc probably not n ttacit ooapound but * Btaturt of i Bo m abartotorlttiet of tht lttd aaronol, ta : ptrtloultr ltt notability, btvt bttn obtatatd frcattudlat of bulk nntplnt obtained vlth blfb-Tolmt aaapltra. A aorb cartful AtUaattioa of tht thytlonl cbtrnoterlttlct of tbt lttd ttrotol vould provide teat btttt for ttttantlnc tht ntturt of tht ttrotol ta tht tbttso* of dlrtot eo^ouad Identification. . -------- ` " ;tv .!*' ^ *C*boo, I. A. Cm hyctaait ttptota of tht production tnd utf of lend totlknook toapoundt. down. AfQA ^ (7) Jib (duly I96J). . . A A ~ ` g Muttx>8 of teroab Cm pntoMl continuation of ths studies of staoepberlc load will extend sad eoeplsaeot ti prcgrsa thleb la belag occcludedj Much of the methodology hs alxesdy been established. Cm extension of 1m range Milch oan be eorwrwd la a eli*le swgltng period can doubtlessly be done bp operating two Ooets Aerosol Spectrometers la parallel (ooe ualt operating la tbs large alee range, ' tbe other ualt la the mall else recce). A second Aerosol Bpeetroaeter esawt be added to tbe present aobll* ssnpllng system vltbout asking s o bs changes. At present, there Is sot enoutfr power tot a second system. Cm largest ilogls power user la tbe refrigeration systea Milch tbs Aerosol tpecIreneter at a constant tcsvcratui*. Several possible solutions to this problem are (a) Installing speelal refrlgaratloa vltb lower power rsqulrweinta, (b) operating two apeatreasters froa a circle . refrigeration eyatsa sod (a) adding additional imietlig capacity. Tbs final eholoe would depend on ublcfc enbeae ooold be aoet readily adapted to field aarrlsa. Valt, space, eonplarlty, and dependability so* tbs aost isportant criteria. Consideration abould also be glrea to tbs design of a slngla aerosol epeetroaeter with a greater ranee, Cila could be obtained by Increasing tbe else of tbe collector eons end thus providing aa lucraaead path length within tbe unit. * prtfil Friuli In^ltetee that If tbe present cone were Increased froa 8 to lb ca, tbe path length would Increase fra tbe present 14 ca to aore tbaa 100 ca. Ibis would markedly Increels tbs else ranee of tbs ualt. Bomsxwr, wbstbar tbs ela> els large ualt would perform batter than two standard units can only be determined by careful calculation using tbs presently aeallsbls data on tbs lead aaroaol characteristics. . . " A decision cn tbe bast way to expand tbe else rarge CwaJd ba aade early In tbe progiwa because. If at all possible, tbe expended - . sapling systea abould b* used la tbe extended field pregraa which ha* been propoeed. It should also be tested in tbs Ins Angelas area sad tba results ocapared with tests aade la I96J. Cm proposed field progrsa will bs designed to explore lbs sis* distribution as well as ease of tbs jfcysloel and chemical cbaraeterlstleg of etaoepberlo lead asrcsols la areas Miers autcaobllt ejheust way not BaoaaaarUy ba tbs asjor touroa. Sampling abould bs carrlad out la tbs winter or early spring la order to obtain tbs naxlsus influence of apses* besting effluents. It Is planned to carry out this sapling In two cities end to spend about three weeks la each city. In selecting tbe two oltlee, one of tbe chief criteria will be tbe fuel used. Attewpte will be aade to select one city Mmre coal is tbe'aajor fuel sad another where fuel oil predominates. Sample* will slsobs takas la varioue rural areas to determine tba lead carteat of natural dust aerosol*. Cile probably can ba done aost eoowenleatly by earing stopovers In rural areas during tripe between urban sampling locations. Spsclsl trips Vo scat remote California treat would also bs aade. Hiring tbe field work, easplse will be taken end reaer-ved for tbs ocapoucd Identification research. Ilgjb-voluee seal ing will probably -3- ZJSuMb* be tbs basis tsobalgua used. lbs laboratory proem will lDecatlcste cbenotarlstlea such as solubility, nltlng points, vaporisation taaiptrsturwa, ate., of tba lead ocapoua&a found la bulk staples M a Moo of general eharaotarlaatlco. b^uli will b placed tMteatiy on Hu m compounds previously Identified In eutatdblle exhaust. further work o d single partial* identification will not b mlmlirt, but ex ploratory experinenta will bw carried cut on techniques that alit overo o m tba fcxxra difficulties fnelne this typs of analysis. Son analytlel offort sdgbt b directed to segregating tba blgb-volns ample to tbnt sufficient eoneactratlou af tb* lead copBi Is attained for >-ny diffraction. Ibis M snrlebacst night b scoaopllahad directly In tbs sollsetorj additionally, tbsrs any bs naad for selective extraction sod/ or nqontln prooedum In order to provide suitable en^lu for diffraction. 9m tbrss research phases outlined above -- sits range wftloit non-sutendbll* ecvirccnental eeapling, tod eneoud tbsrsatsrisntlon -- OSM bs Integrated Into s 12-acath research proem, lbs following tsntstlws tine-table tor tbs research proem non prsotlesl. risld eeapHi^ Is coal- sod oil-burning srsss should bt esrrlsd out ferine tbs period of ftnusxy Kerch, 196k uslnc tltbtr tbs extended rsnet ayeten If It scold bs sstsfelsd is tin or tbs prsttst unit, tbs sprint ssd earner proem would Include osllbrstlon work, rursl ssd loesl Bey ins sen'll ng, sod about cos wontb of sailing In Los Anetlst nine tbs extendedrange tnlt. 9m ssslytlssl compound ldtntlflestlon proem will continue ss s atssdy effort. *vsi'! M^- tats analysis and report prspsrstlon will soncluds tbs contract. In addition to tbs final report it would aaaa fealxabla to spend scat tint prtparine ooa or two ooaprabenaive technical papers describing tba proem and Its raaulta. tbase eould bs given at tbs sprlne nesting of..a a technical eoalety safe as tba Ansrinan Oeopfcyalcal felon or tbs Anri- > san Chaslrsl Society. Pertinent dlaeuaalon and crltleln durlnc cuoh a tsohnloal presentation oould bt considers* In plaialne tba latter part of tbaasaaroh proem. n netnigd staurxtmm Ibis research, Ilka tba passant proem, will bs carried out lx tba Departsent of Ateoejherlc Scteooee wltb considerable aaalataaos from tbs Analytical Aaeaarob Cepartneat. lbs fkollltlss to bo used will - Inoluds not only tbs spsoUllsad project equipment, but also tbs extsn- slws laboratory faellltlaa of tbs Institute. Those specialisedjtfealU- ties xhlcb are expected to bs used durlnc tba rsttsrcb proem inaliida aerosol eaoarstlne sod analysis eofulpaent, tbs Kltsobl electron nlero- soaps, tod tbs *-rty diffraction equipeeot. Ptrsoansl bs beys been tbs nejor acntrlbutors to tba pmact rtawanh art expected to eoctlnua tbelr aaaoclatlcn wltb tba p--g-- Mr. Slnr Boblneco, project Laadari fir. John S. DeVries, Hunger, Analytics! ferrloaej Dr. T. lop*las, Cbaslat (x-ray dlffiaatlon)) fir. I. Chaikin, Cbaslat (electron alcroeoopy)| Kr. P. L. Ludwig, Meteorologiat (field eaapllng and Mllbrstloo atudlaa). In addition, other Institute staff ambers will bs aonaultsd abac tbelr speciallaed knowledge could bs useful la solving rsaasrab problan that arias. ->V^  m CCRMCTOU. HUIM Suxraatad Wert 8tat taint ft# follovlnf work atatanant 1* augiaatad for tba proponed Saaaaroh Prograb, but tba Znatltuta vould b* happy to dlaoua* any daalrad codification*. 1. Exploratory field railing etudi*# vlll b* rate la amrtroo aot# (Mar# eslaalcoa ara aot naoaaaarlZy Arm1 rated by auto* acfeUa axbauat, and, la particular, eanpUng vlll ba oarrlad cut during tba heating saaaoa la tvo eltUa tfeare ooal aaA oil ara need artaoaltvly and la mm raaota rural area*. * fta alM raaga of tba atiling catted for a given eaapllng lotarral vlll ba extended to aara aaarly cover tba raaga of tba ataoepberla lead aaroaol. flxld aacpltng la loa Angela# vlll ba oaed to Mo* tba appllootloo of tba expanded t technique. 3. Studla* trill ba earrlad out to core ea^lataly ebaxactarla* tba pfcyaloel aal ohwlnal eatura of tba ataoajbarla lead angarii. ; . -. v*.r k. A final report and at laaat ooa taohnloal aelaotlflo paper vlll ba prepared daaerlbtng tba raaaarab raaulta. Ortaolaatlon vlll b* follows. Eatlnatad Tina and Charcte > ` It la aatlelpatad that tba propceeS raaaarab oan ba oeapleted lb a 12-aecth period for aa aatlaatad aoat of |68,b00. Zbla aaount la baaed on tba aaawgtlaa that tba alaa raaga aaa ba extended by adding a aecoed Ooata Aaroaol Spaetrocatar to tba ayataa. Should this not ba tba eaaa, .., tba eoat of tba aoat rieaecable alternative vlll ba dataralaad and if .V *' It aaeaada tba budgatad aaouct, apeelft* autborlsatloo vlll ba obtained .; , prior to any purthaae ooraltaeat. * fta eatlooted ooata lnoluda 11 aaa-aoatba of aaolor ceteorolaglat and aataorologlat tlaa, 0 cuwootbe of aaolor abaciat and obaalat tlaa and 3 aao-cooth# of elarloal and taohalalaa tlaa. Alao lnaludad la tba ? w-'>< tmrhaa* of a aultabla Aaroaol Spaetrocatar. ,, :- " ' " ^ Contract for^ fta leatltut* la a not-for-profit, noa-andovad orgaelMtloa. la vlav of tbl* atatua, tba Znatltuta raguaata that aaob raaaarab alleot aafca aa advaaea dapoalt to eovar vorklng capital requirement* for tba projaat being undertaken. ft* Znatltuta'* lavolalng prooadura 1* d*aerlbad la tba attaebad atandard raaaarab agraaaant. ft* uaual advaooa dapoalt on a project cf tbU alaa ta #U,kOO. If tba raaaarab client trliixi to eliminate pajnent agolnet ptrlodlo lnvoloea, the edteaoe hfMlt m*j bo laamii) to lOOf of outborlied funds. Upon ooepletloc of ft project, any unexpended projeot fundj or* returned to the client. tbli propeeel eoa ba eetebllehed m o project bp otpslaft oad returning two oopUa of the eaoloeed etaaderd iptoutf idiloh or* Incorporated herein oad node o port of tblo propoeel, alone with ft cheek for the adeoaoo peynent. 9m eobetltut^poregrajh 10 oad the added pereertgh 11 la oar preecnt contract with leod laduatrloo JU*ocl*tloof lac. doted 1 Aevuet 1962 or* talte *etlefftcto<7 for laelueloa In thle propceed contract If blind. NrfceaCDBc dotee eoterlnf o period of 12 noetha 000 be laeerted 00 pope 3 of the Stoadord Atreenent fora to eult Internetloool toed tine Peeeoroh Orptalxotloo eectrectla* oad fvmdlnd eebedolea. Acceptance Period lhle propoeol will reoola la effect until 31 Jooiaip 19A. After that dote, we will *ladly eooelder on exteaeico of tine If deelfed. We will be able to effinni wort 1--llitilj after outhorltetlca. Deepectfully nteitted, ' dCfS1.* - lfnodi floor hchlaeoa Xlaar Mblaeoa, Bealor Neteoroloclet ' Department of Ataoepherle Aoloaoee .. Approeedt flcaedj Cborlee J. Cook - Cborlae A. Cook, Blreetor Cbemloel Ibyelaa Mrlaloo < .. ...PiT DtieJ '1 3 e tH* VDROBIIlt KKBUnai 70S BmOMJTflU. BIDLOOT fro>ct # LC-t 6 Sixovobtiry, Ifceeachueotta Beptedar 11, 1963 HBXAJQ 7XMIU Tot International Load Bias Ibeoaroh Orgaolaetlca 292 Mira Avaoua In tort 17, I. t. Title of Beeoarcdu m norm or o k u bo u ad oowoona TOT F0C3DUE ODOCSIRLOGICAL AID An-HM*tM won Acnvar. . General Btatoaentt tar. Maloola C. Hor7 of Betid, Himtwtu, baa (lna and Intend to eontloua to gin ua nrloue crgaaoleed coaporada for tooting. Vo hen oloo received coaporadt flat Frcfeeeor m dor Vast. Vo found ocoo caepounde vltb poeelble l^ortent utllltlee. Vo vth to cootlout then etudlee. Our tooto trill Include alrcfnla activity (oolo aex baneot), eetrogenle activity (feoeli oox bonone). anti* - ootronealc (poeelble actl-tunar activity)' antl-endrcgeala . activity (poeelble trootaaat of proetatle cancer), and aatl-lnflaraatory activity (poaaihla troatoast for rtoraotold arthritic and allergic dlacaaca). Vo ahould alao be pleaeed to etudy rrganoleid crapounda froo other aoureoa. . incaaber 1, 196J to Bonober SO, 19ft. ' 1 Bloaeeay Technician ................................ .... 5,000 Pato, moo aod Cblcka...................................... 3,000 Cocaraabla BuppUee ........... . 1,000 Direct Ceete ...... 4 9,000 lodlroct Coata 25# . . . 2,230 fOZAX. 11.230 m/g lMdi kl|t Z. Pnrfa ' Malik Z. SocfUM N 205.05 L C 75 '..... 3 troromi t o nrowATicBAL izu) tBc m'-'g o^comATioB f o b ra canmromar. "taftrx.a t k s rrART<iy>7 or~*r?sTix as :u l ~fcS>fo>r oT^~rt~h-v.p.t.M c> waLspca or 3 Ca^BrnS5va UioRtecitf, hi -taTfejAicxfcvr or fr.r7i'i?rivt nr.i;rre Jhfo a^tyraAL Elite or tit toLEB? or feaicE5~cTSaTitT,.`Kg!fiy^ 'cicciKjufl-i.'~ai fex Taj kaJi faJooura io joet&t itk ooxarrAivxs i>t txkncvuit it*p* Reference 1* made herein to a proposal sods on October 3, 1962, la rtileh w experiment then underway u described lu torn* detail, as a part of systsettle lnvwettgeticn cf the metabolism of lead la tbe buoen body rtich bad been la progreee sines 1937. since 0ot0ber(1962), tue experiment then referred to bee beeo oagOrted, with reepect to the scheduled exposure of the two ertjecte wlthla the respiratory efceWberv, end the final period ofObservation of the ertjects (for a period, after the teralnetloo of the experimental exposure, sufficient to permit the ellalnation of aoet of the lead that eas absorbed during the experlaental exposure). Cm data obtained la this experlaest to the present tlae beta bees charted axd trill be e^lcyed la the formulation of a progress report covering the details of the work, for preesatatlm to the sponsors of the experimental pragma. Cm following paragraphs ere ooocerned with oootlauatloa of the program through 1964. . While the prior cxjarlseat eas la the stage la which tbs experimental srtjacte acre scheduled within the obeSur, a further expertamt. Involving two new subjects, was deelgned and Initiated. Cm two subjects ware located end engaged after a thorough cllnlonl and physiological survey to eetablleb their suitability for tbs task ahead of tbaa, and the prellalnsry ' obeerwetloos, which are an l^ortant part of any such sxperlaast, were _ Initiated cc March 19th,' 1963.. Tbeee Observations have continued without Interruption to the present tlae, and this Initial parlod, prior to the v>:. C: , experiaestal exposure,: will be terminated cc Septecher 8th, idMa the crucial part of the experiment begins se of 6100 e.a.', Septeeher 9th. Cm second ~ **^6- stags of the experlaest Is scheduled to eontlaoe throughout (sad beyond) . - Eererter 31, 1964, and Is therefore the subject of this proposal.. ' As predicted (third paragzaih 00 page 3 of the proposal of October 3, 1963), tbs successful ccoelueloo of the previous experiment made It aeoeteary, la determining the threshold value (for pthlln safety) of finely divided leed dispersed la the ortlant atmosphere of the casualty, "to establish the order of sagnltude of the Incresee in the concentratloo of leed la the air ts tbs respiratory charter (above that la tbs art lent air), which la required to bring about a barely demonstrable response (la terms of tbs excretory sets sat * tbs ocBOsotretloa la tbe blood), 00 the part of tbs buses subject, to essentially eostlnuoue respiratory exposure to leed.* Vltb this-Ides la Kind, tbe pretest experlmeot has beta designed la the manner described bslov. ,,'*/ Two men la elallar respiretory ehertere will be ertjeetad to parallel experimental eoodltlcne. Crnlr exposure to lead la tbe air will begin at tbe lowest of three projected levsle of eoooentretloc (0.010 ag. par odbla eater), and will recur every other day, for .3 hours per day, over tbs period of about 6} daye (this la tbe approximate length of tlae required Is previous experiments to reach a constant level of lead ta the body of tbs srtjeet, as revvaied by a cocetaot dally output of lead In tbe urine, end a constant soweotrstleo ta the blood),. Cm eoooestretiaa of lead la the air will then be dothled and the ease regimen will continue for aaober 63 days, after rtlofc tbe oooocotretlon will be tripled, during another period of 63 days. N 205.06 ..nfefilfeii. S- Vbo tbla rami of ebMrntlooa baa boec ooaoladad, th a\d>Jeota vlll ooctlnue la tbo mm reglaen, axoapt that uaooatanlnatod elr vlll be circulated throufb tbo eheabere for tbe required mnber of hour* oo tbe alternating day* apent by the *ub>ct4 therein, aad tbla vlll be ocatlaued until any laaroMO that My haw occurred la tb lead la ttaa blood aod urine of tbo otbjeete boo **16*4 to tha Initial lml. (It la anticipated that d o auob loorMaa vlll ba obMnvd la aaaoclatlca vith j hour* ef expoeure, awry otbar day, la tbla loltlal three-etage experlDeot. Dili, bovmr, reaalae to bo ma.) Dependent upon tbo outooM of tbo cbeerotlooo dooorlbod thue far, to lallar aod o u o o o mIv o oorloo of Oboemtlcoo vlll bo aada, la tfclcfc tbo duration of tbo expoeure of tbo oxbjocto oa ovary otbor day vlll bo Imreoeel to 6 btwra aod 9 bouro, xoopoetlvoly.j. . ( . If tbo ootlro oorloo of Oboorvatlooo art required to ooovar tbo prlaary qoertloc, tbla experlaeot probably vlll oxtond cvr tbo period of tvo yeare. It It ootlxaly poMlbla, bouenr, that tbla queotloD cos bo aoovarad aatlafaetorlly la a obortor porlod of tlao. Dot loao, however tbaa a fall year. Bm laoua, la our vlov, auat bo that of providing a definitive aaavor, oa a oond jhyiloloflnal baolo for a otaadard of tbo quality of eriblaat air la tbla regard. tbla etverlnat, aa tbooo vbleb ban preceded It, la tlaoeopoualm aod oootly, but tbla la Dot tbo tint, la vlov of tbo eiivlrq eearneee at tbla foal, to *eut eoraort,* or to aottla for loaa tbaa adequate lafomtlon. It la In tbla oplrlt that tbo oootloulaf atgport for tbla vorfc la ocu^it. tbo budget for tbo continuation of tbla votk vlll tooln oaooottally whanged la 196V, aad la eooaoquooM of tbla altuatloo, tbo opUt botvooo tbo few proooot eponeorlng group# - aoMly Ithyl Corporation, I. I. duPont do 1 Xoaoura aad Coepaoy, tbo 0. I.M1U Boaltb Borvloo aad tbo BrUrootlocal load line Dtoaareb Organlootloo aay nil aad proparly aootlauo at la 1963Bbnld tbaro bo aay altorotloo la tbla arnngoMnf, tbo partloo aonoaraad vlll bo lafocaod prcoptly. dlfuodi Mart A. Keboo Robert A. Xeboa, N. 0., Director Kottarlaf laboratory ftiiftiiiiitjui* -/r.V'i'-O' ,l!*>` 5>' C'* :.?a ^*ii4 . > w i->St, .- -. -; .! f,- * vnwmu. b io -t x o t ia s o mt o r h s , o r . lfllO rrcctage Road Aortbbrook, Illlnnla Telephone CAeetvood 2-J-J- february 19$3 Trojeot nc>u Mr. Poo 0. foultri Project Mnntf bead Industrie# Association 892 )U1k b inow *o lock 17, Sew Tort ' Dear Nr. fcvlen a oertelnly enjoyed your visit lut Friday and look forward to vortob vltb yea la tba future. Considerable thou^t baa baaa given to tba problem of tba toxicity of 1n ( la paint. Va would like to suggest tba following aatbod of ata4y. If you could provide at vltb five powdered pigments containing tbaaa levels of lead, 1, 6, IS, 23 aad 30 par east, wa would conduct 90-day adbaevta oral feeding atudiaa on rata. Va would praataM that tbaaa would bo suitably weatbarad aaeplaa. taeb dlfTarast plgaent would ba fad to rata at diatary lavala of 0.01a ' . 0.0J, 0.20, 1.00 and $.00 par east. Ibeee five aaaplaa would ba fad ccocurrtstly utlilt inf two com control croupa. laob groat would eooalat of tan mala and tan faoala albino rata. Tba followlac paranet an would ba atudlad durlsc tba faadlnf parlodt growth, rwoordad waakir complete blood eounta. Initially and at and 90 day* urinalyses, Initially and at t$ and 90 daya dally observation of all anlaala for reactlooa and mortality At tba and of tba 90-day faadin* period, all anlaala will ba oacropaled. Valuta of tbaaa organa will ba raeordadt llTwr, kidney, baart, gcoeds, aplaan and brain. Tba ratloa of tbaaa organa1 weights to both brain tad body wlfiti will ba determined. All of tbaaa naaauraaant data will bo rejected to aultabla atatlatloal treatment. Tissue aaotlona of twenty different organa will ba prepared for --<trtloo by a pathologist. All control anlaala aad all anlaala froa aaob 9 par cant diatary level will ba eo examined, if unueual blaiopatbologlo ebaagae an noted In earns anlaala froa tba blgbeet feeding level of any pigment, anlaala on tba next loveet level will aleo ba examined. If it la aaoaaaary, anlaala trm all teat lavala will ba anaload. Slnoe you era lntereated in tba poaalbla Interactlea of lead vltb other In gredient* of tba paint* during tba weathering proceee aad tba affect of tbta interacttoe on toxicity, va aball perform acme additional statistical rvaluatlooa on all tba ooabined date. Tble la an attempt to elucidate tba rtetleucelly algnlflsast iffacta of tome of tba varleblee being atudlad. N 205.07 - *7% **"*"; 1 j x d u s ik u l ETonai rouromc* or a md o c a , me. 1 Malloo Inatltvta, WtOO fifth 1*TOJI II Plttabuxyh 13, M. mna # tac-is I Daoaifcar 17, 1962 memo) foa 1 iu x io t t eroons re* v u d mumaa *eaocuruM Introduction Tba pnaast allovabU lanl of load plyot la oartnta paint* baa baao Mtit 4, than on no dot* anllabU to ladloata ifeatbar or cot o fcl*bar lnnl of laad plgnaot la tbaoa potato / bo aasooUtad, for practical purpoooa, vita ao aiyfleaatly (raatar baalth batard thaa tba 1$ Uni. la erdar to Obtola Information oe tbu yatlco, tha lnnatipatloa outllaad baloa baa baao *--t(r--* Bovmr, bafora aattlaf out to daalgs tha lnnatigattce. It la adviaabU to cooaldar It* poaflbU pitfall* oaA to daflaa tba erltarla according to lAloh tba data vlU ba anluatad. IB (anaral, tba plan of tba lanattaatloo 1* to aoa^an tba toodatty of a sins, hlabar lanl of laad pliant la paint vltb tba tonicity lobanat la tba 19 Uni of load plyut. At an Initial ttap, tbl* lnraattjutlon aecordlncly propoaaa to daoooatrata a baraful affaot by faadlnf a toxU amount of tba paint fila from paint oootalnlnc l laad plyot. Tbl* ntada to ba dona In ordar to aatabllob a baaa lint a#*lnat idilch tba banful offaet* of a paint flU oootalnlnc a hlobar parsantafa of laad plyat will ba eoynd. Vbatbar or not tba affacta produoad by tba lncaatloa of a (motor anat of laad plyot (baoauaa of a hiyr paroaotaca of load la tba paint flln) an al(alfloantly Id c raand vould dapaod upon tba Datun of tba affaot *nrvua>4ooa napooaa. if tba mapenaa U ooa-fer-ena, that la* a ttral*>t-Una ntpcoaai tbao for anry alcalficaot lasnaaa la doaa than U a alcnlfleant lnonaaa la affaot. If tbla ba tba eaaa, tbaa any lncnaoa In tba pamantao* of laad plyot la tba paint vould ba aaaocUtad vlth-a aomapoodlof lnonaaa la tba baalth hataid. If, bovmr, tba doaa-affact napooaa 1* a aumd Una vttb tba oaoearlty upvardj tbaa, at a lev doaac* Uni, a alcnifloaot lnonaaa la doaa(a la nfUotad by aa In* l(cIfleant In* anaaa U affaot. Obdar tbaaa alrotnttanoaa, It U only at blab laad.lataba UnU that addad doa*ca nault* la aa aooaUntad lnonaaa of affaot. Aaotbar (u*at loo thlch auat ba aaavand la he* tba tcoda affaota an to ba ataaund. Cot of tba aoat aanaltln aaaaurlnt atlcka, and on* * aooly uaad U tba dataralnatlca of baaltb batard In nav dru(a or food Q addltlna, It tba affaot of tba unknown ebaaleal, vtno addad to tba food of fowl nta, upoo tbalr (rovth eum (tain U valabt). Anotbar aaaaun appllsabU la tbla lnnatlfatlao vould ba tha total aoovnaiUtlon of Uad la a Critical tUaua aa datamlnad by ahanlaal analyala. A third, Uaa aaadtln* aaaaun aly ba tha affaot upoa boo* aarrov fuaottoa. ,~S - i r*1. **V "f **" - N 205.08 Industrial Hygiene foundation of America, las. -a. It la dbrioua that, rather than tha percentage of lead la tha food. It la tha wight of lead absorbed Into tha syataa Wish la the factor determin ing tha development of toxin affacta. In tha caaa of tbs propoeed lnvertlgetlco, tha nagnltude of tha affaot produced by feeding leed-ccctelning paint flla will depend upon a nobber of ooodltlcoai 1. The wlgbt of land ingested e. Tha chemical Datura of tha lead plgaant (thick determines lta solubility and absorbability). 3. Tha physical aod chemical character of tha flla In thlch tha lead plgaant la Incorporated. Thla also influences tha solubility and shsostablllty of As tha lead pl^ssnt. V. Tha finsoss* vith thlch the laad-oontalalsg flla la grand for incorporation In tha anlaal food. Thla baa an lnflutaca on tha aolihlllty of tha aua* paodad lead pliant, and haDCS, lta abacahahlllty. Proposal Tha lnraatlgstlon will, of necessity, oooalat of a preliminary phase for tha determination of tha *baaa Una* followed by tha aaln study. Thla praliainary phase will involve three groups of 1$ young rata each. Oca group, fad a standard basal diet, vlll asm sa cootrol. A second group, fad tha saw diet plus a pre-daterained dosage of paint flla (fratapaint containing 11 lead plgaant) la intended to daaanatrate a Inina! toxic effect. Tha third group of rata trill ha fsd tha sane diet plus tvlos tha -i swart of paint flla fraa paint containing 1$ lead pliant aa tha aaoood group. Tha dosage level of paint flla to be used on tha rata la critical. It trill depend upon the chealcal Datura of tha lead plpMnt, lta solubility, and known toxicity. Tha extent to which tha other ingredients cf tbs paint flla aay modify tha toxicity hatard can only be surmised. Therefore, tha choice of dosags level beccxaee an educated guest and tha possibility of guessing wrong aust be token Into account together with the ecnseqpaaoe* cf guesting wrong) namely, of baring to repast tha atudy. Tha load Industries Association la expected to supply tha paint flla(e) la a fora suitable for incorporation Into the diet food, ground uniformly to a reproducible site. Pertinent Information regarding tha eoapoelticn of the flla netsrial, particularly In regard to tha lead pigment, its eoapoelticn, physical properties, and percentage. Tha dosage 1*Y*1(*) of tha paint fllm(t) to it used in the anlaal feed will be fixed by sgrsspent between the representatives of the Lead Industrie# Association sod tha Investigators. The feeding of the animals will continue for three months. Curing this time, the food consumption (end therefore the lead intake) as well as weekly tody wights will be recorded aod charted. After thla period, the rat* will ha killed with ether and autopsies will be performed. Tbs livers and kldneyi will be weighed aod tha ratios of organ weight/body wight will be determined. Blocks of liver and kidney fran each anlaal will be embedded la paraffin and sections prepared for nlcroeoopla xamioatlon. A chemical analysis of a tissue for lead content will be dene oe each anlaal. umi. iti, un 'nspartewppwiig. .gg... wum*' *r ' ; ' .a o i Industrial Hyglaoa foundation of Aaerioa, loo. -J- Assuming that a nlrlra'l dosage of paint flla fra paint ocrtainInf X< lead plgaent baa baaa found tdilch produce# a aaaaurabla affaet upon tba rata, than aootbar study (tha naia study) can ba begun In Which a grewp of rata la fad a higher (predetermined) percentage of land plgnent contained In tba earn# aaouat of paint film aa la glean tba group la efelcb tba paint fila fra point containing 15 load. Tba latter groqp will term aa tba bane line agalnat ehicb tba cffacta obtained in tba flrat group will ba cccpered. A third group of rata fad only tba baaal dlat will aana aa Dagatlra eootrola. If desired, otbar groupa of rata may ba added, to ba studied slmiltaneously, vlth intakes of ground-up paint file containing larger peroent ga of lead plgaant, differing fra cot aootbar bp a factor of two or acre. SS2S Tba outline of tba lneeetlgatlco la glean In tabular font bale* and tba coat la Indicated, Preliminary Bu m fylth flla froa paint containing 1< lead) "fco.cf Oroup Data Dlat Duration 2*1 1 15 Baaal (control) 3 ~qj 2 15 Baaal plus paint flla (weight to ba agreed upon) 3 *>. > 8/XX) 3 15 Baaal plus tvloe the vel^jt of paint ' 3 ao. j flla aa la Group 2. Oroup Second Ibaae (main etude vlth Increased 4 lead in film) Bo.of Saba Dlat Durstloo a1 1 15 Baaal (control) 3*o.~| 2 15 Baaal plus paint flla (weight to bo 1 agreed upon) 3 ao. > 8,000 J3 15 Baaal plus aaae weight paint flla aa la Group 2 but with x lead la paint. 3 o. b 15 Baaal plua sma weight paint flla aa shoes but with Ti lead la paint. 3ao. 2,500 3 15 Sana aa Oroup V but with tf load la paint. 3 o. 2.500 iw-AWi \.C 79 O PBoroaa k . a XX&JBTKZAl# BIO-TIST USOW>?QR38, DC. 1610 frcctac* Rood Borthbrook, IUlool* YVlnbt** CMatvooi 2-J0J0 --j '4 *1 JUM 12, 196s Kr. tea 0. fovlor Project mt*4T Load ZodurtrlM AMOOlatloa 292 KtdlMO Avraut *ev Tort It. tn York Doer Ooa* V* vlll conduct uaU or*l tad acute percutueou* taxlolty rtudiM u per our proposal of t*bruery 11. 196J. Ox only cheap will be in Ux acute percvteoeoua teat la idtlch t0 rabbita vlll ba uaed at each at 3 doee Imli. Ox <7* irritation tad acute inhalation t4it< ut not of prlae 1>- porttace initially. Oxee Uiti say bdx later If further interact la a particular Propound davelopa. . .... Ox coat for thM ttiti vlll be t27J.00 per arterial if a ainiw of fire aaterlala an evhaitted at the mm tlM. Sincerely four*. 81*zxdj Jo* i. C. CelMdra ' ' Director JOCtptr I ^rtWy * *1 ; .-.vfi-, w?" .* N 205.09 i i. j !. j s DTOUBTKIAL BIO-TOT lABQfiATORUB, DC. lfllO Brootaaa Bod BorthbrooJt, IUiooU Talajfcooa CBaatwood 2-3039 Babniary 11, JSfiJ , Mr. Dou 0. BowUr, Frojaet naptr Lead Induatrita Aaaoclatlca 292 Mira Artout lav York 17# lav York Saar Hr. Bowlart Va art aacloalaf cur prcpoaal for raa^a-finding toxicity taata , oa aatartala la tdilck your aaaoclatloo la lataraatad. Da ooat of Uteaa taata trill ba 1600.00 par aatarlal taatad. If you have any quaatlooa oa tbaaa procaduraa plaaaa do not ' baaltata to call oa. Oiaak you apda for paralttlaf oa to 'jsjc cobalt cur propoaala. `.-135%-*',* Blacaraly# dlfaadi J. C. Calandi* jCCipar J. C. Calaodra Director - ., ., >i : ,1 -ripK" . .^x N 205.1 1'^Tr i>fH lums-mcno t c h c it t ensza I. Panav-rindlaa Acute Oral Toxicity - Albino Pat* A. Acuta Oral Toxicity Albino Bata kaalthy, young albino rata of the Spmgua-Davlay atrain vltb an average body velgat of approximately 100 (ran* an uaad m taat aninala. lb* nta an divided lute (rcup* of four anlaala each for doalng purpoaa*. All aninala uaad an kapt under Observation for fin day* prior to axparlaantal iih , during ttilcb period tbay an cbackad for general jbjalcal vall-balng aad XaapMlty. Tba aninala an housed Individually la stock cage* aad pamltt.d a standard laboratory nt dial* plus aatar ad Ubltta until 16 boon laaadlataly prior to oral Intubation. On the aarnlng of tba flrat taat dap, aftar a l6>bour faat (ante* permitted), tba aalaetad doaa group* of four rata each an latifeatad with previously ealculatad doaaa of tba taat aatarlal. All doaa* an admlnlatand diractly Into tba atoaaeba of tba taat rata ualag a hypodaralc qiU|i agplpptd vltb a ball-polatad Intubating aaadla. Following oral administrationcf tba taat aatarlal, tba rata an nturnad to tbalr atoek cagaa aad Obaamd for tba succeeding lk day*. All algnlfloaat raaetlona aad aortalltla* which occur an racerdad. Particular attaatloa la glvta to tba obaamtloo during tba flnt four boura aftar intubation. . At tba aad of tba obaamtloo period, all data an collected .'iS and tba ncga-fladlng acuta oral aeaa latbal doaa (RPUVn) of tba taat - aatarlal la calculated ualrg tba technique* of Vail**, tbompaco***, aad 'i Tba^aca aad Vail****. $ M -.c y si -:! Rockland Mat Mat, Rockland Parma, lav City, Paw fork. 1 Vail, Carrol S.t Tabla# for Coonnlaot Calculation of tfcdlaa* Xffactlaa Doaa (lDy> or fikn) aad Instruction* la Tbalr Dee. Rloaetrlc*. 6apt. Tbcnpaco. Vllllaa R.i Uaa of Moving Average* aad Intaipolatloa to Xatlaat* Madlaa-tffectlv* Doaa. Pact, Rev,. Pcrr. 19(7, Tbcapace, Vllllaa A. aad Vail, Carrol S.t On tba Ccoatruotloa of Table* for Moving Avaraa* Interrelation. Bloaatrlca. Mtmb 19J2. N 205.11  XI. Bang*-rinding Acute Psrcut*neou* Toalcltr Albino Babbit* I. Young adult, Be* Zealand (train mal* albino rabbit* an w^lnyad aa t*t an'.msl*. lb# body vaigbt* of the rabbit* u**i rang* from tvo to tbn* kilogram*. A11 rabbit* an oalntalotd under Ob**rvatlca la tb* laboratory for flea day* prior to testing. Curing tb* pn-teet period tb* aolaal* an amalned vitb nspect to tb*lr general btaltb aad (ultablllty a* tart asla*la. lb* rabbit* an bound is (took cage* aad maintained cm tb* ttaadard laboratory rabbit ratloo*, food aod voter an p*raltt*d ad libitum. Twenty-four boon prior to tb* dermal application*, to* back* of tb* rabbit* an ibaved free of balr vltb electria clipper*. Tb* as'aml* an tb*a returned to tblr toek o*c* to avalt teetisg oo tb* follovlng day. lb* 2b-hour veltisg period allowed nectary of tb* atntum cor* arm frca tba disturbance *>lch eccoopesle* tb* clipping proeedun aod also paralt* healIs* of any alcroacople abnolooa possibly produed durla* tb* proc***. Oo tb* testing day, tb* dtraal do** for *acb t*t rabbit 1* Ml|M accurately oo aa analytical balaac*. Application* of tb* t**t oat*rlal an aad* la *olld fora oo tba axpocun *lt* at tb* rabbit*. Ibn* do** lrral* employing four rabbit* *acb an used. After each appllcatlco, tbe exposun site 1* covered by wrapping tb* trunk of tb* vltb oo laperrlou* plastic *b**tlng which 1* eecurely taped In plaoe. Tbl* plaatlc vnp Lceun* latlaat* contact at apldermla and test oaterlal. Ibo teat oaterlal nmala* la contact vltb tbe akin for 2k hour*. Behavioral reaction* an ob**md aod recorded during tb* contact period, after idlcfe tb* pl*tlc (batting la rmovid fra each teat rabbit, lb* ' axpoeun site* an examined far local nactlcn* aad tba anloal* nturoed to tbalr stock cages. At tbl* tine it vlll also be'poeelble to obtain aa estimate of tb# primary akis Irritating propertle* of tb* teet oaterlal*. Obeervetlone for mortality, local reaction*, aad behavioral abnonmlltle* an oaotlautd for a total of lb day* folloviag tb* *kln application. At tb* end of tb* obeervetlon period, *11 data van collected aad tb* range-finding acuta percutaoeou* mean lethal doe* (HTUko) of tb* teet oaterlal la calculated ualsg tb* technique* at Veil**, Ybcrntmco**** end Tbcapeoa aod t*U*"*. Bockland Babbit Bl*t, Bocklaad ran*. Be* City, Bev York dee footnote**, page 1 * See footnote***, peg* 1 ** |h footnote****, peg* 1 J 1 j .. * 3 A .1 -**** Ufa^'rfftMdWuku 3. XXX. Pane*-Finding Acute Inhalation Toxicity - Albino Row Toune, adult albino rate of tlw Sprague -Devley etrein rere eaployed e* tba t*t anlaol*. Pre- and poet-test an end ob*erretlon of tlH r*W or* ***etlally tb* MOM a* that already described for ret* ured la th* rei6-fiodine, oeuW oral toxicity Utt (tre j>. 1). Borerer, anlrel* ured for inhalation exposure vre oot faeted prior to Watlng. Mr* eroup* of four ret* **eh ere utilised Is th* study of tb* teat aterial. tba averse* bod/ relgbt of tb* t**t anlaal* ore appraxlaataly 250 crea*. Tb* Inhalation exposures ore conducted Is o ultlpla Inhalation chaaber deilgoed for alailtaneoua *xpo*ure to otao*{bre soturettd osd fractionally saturated vltb tb* teat reterlal, *. f. 1/2 saturated, 1/b saturated, 1/8 saturated sd 1/1$ saturated *t roan tauperetur* (25^C). It* tret 1* d*elcn*d to run for o four-hour period. At tb* *od of tb* xpo*ur* parlod, tb* rot* are observed for tb* auccredlnc lb d*/a. XT. Baa**-Finding Tre Irrttotlon Tt - Albino Bbblt A croup of fire albino rabbit* ore ured to evaluate tb* / lrrltotlac prop*rtl* of tb* t*t notarial. Touoe adult. Be* Zealand atrola r1-- or* Mleoted for tb* tret. Tb* tret retbod replayed 1* patterned oftr tbot of Dealt* *t ol*. Ciactl/ 5 a* of solid Wat aoWrlol 1* losttiled into tb* cocjunctlval ao of tb* rlit *y* of reeb tret rebblt la a group of fire anlaal*. lb* left / of reeb anlaal rerre* re a oeorlac ecotrol. On*, 2b, bfl, 72, $$ hour*, sad ^ da/* follovloc tb* Initial la*tillation*, tb* corn**, lrla, osd palpebral conjunctiva ore *mls*d individual!/ osd eroded for Irritation and Injur/ according to a ataodard coring systreS. tb* aartaun pcrelbl* *eor* at an/ oo* esaalnatlco and acorlnc period la 110 point* vbleb lndlretre rmn**l Irritation and daoae* to all thre# ocular tlaaure. 2*ro score indicate* no Irritation batrer. After tb* ccopletlan of tb* tret, tb* scores are anal/t*d and a drecrlptlre eye Irritation ratine la a1g>cd to tb* Wat a*trl*l. tb* criteria used for welgcreot of tb* drecrlptlre ratine are tba fr*quncjr, tbs axtret, and tba p*r*lrtoo* of lrrlWtlco or iupi eblch occurred to tba tbrre ocular tlreure. In tb* elarelflcatloo */*ta ured, *p*elal oqbaal* la placed upon Irritation or daaae* to tb* oorore. Corrrepoedlscl/ 1* *tre*s la placed upeo conjunctival and lrldlal affect*. tb* dreerlptlre retIs* assigned are on* of tb* follovlnc, reeb of ^lcb ebarscWrltM a particular level of 0{btbal*lo Irritation and daaaf*i Icn-Irrltatlo* Practically Boo-lrrltatlnc Mlnisally Irritating Mildly Irrltatlne Moderately Irritating Bev*rely Irrltatlne Extrewly Irritating AlMlly 'Method* tor tb* Study of Irrittaattitoono and T_ o_x_i_c_ity o_.f fiiA>*ta_n_c_e* .Ao_oil*^ Topically to tb* BUn *M Hoccue MeatraceDrelt*, John Wooiird Oeoffrey, and Celvery, Herbert 0., J. Ibara. b Exp. lb*r. 02, b, C*cufc*r l?t$. i wgypwfTf FH0T06AL VO. I TIE HOT IABORXTOf.ua SR. Research and Developnant U>99 Folsom Btreat Baa Francisco 3. California June 17, 19fij Mr. Son 0. Fcvler Lead Industrie* Asaoolatlcn 296 Nsdleca Avenue Mv Toi 17 { Star tau It u a gnat pleasure to visit vlth yen laat mk end to rvoev our friendship. Our previous vork la the Air Pollution flail vaa most eojoyebla. X trust that an aay find a flail of Joist affort Is tha aattara of lead as! tha Lead Industries. I haw alvmya admired tha vork of thaaa Industrial aaaoelatlona auch aa API and lead Induatrlaa, aad have fait that they are fIsa examples of tha Aaarlcaa tradition of both ccsqjetltiao and cooperation. Is regard to tha Batter of dewloplag lnfornatloo for the safe kiiin of oev lead product*, our Laboratory vould be aoat happy to vork la this area vlth your group aad vaild be pleased to aaka a proposal for your consideration relative to tha extant of vork *>lcb ahould be done aad tha coats involved. Aa I understand your laendlate problem, there are a tuber of nev lead empounda la varying degress of development ehos, tcxlcltlts are la general unknown. Because of your long experience vlth orgeats leads and kaovledge aa to the much higher toxicity of these ccmpouada aa ccapered vlth different inorganic leads. It does seen appropriate for you to bare determined tha proper order of magnitude of toxicity to that suitable handling precautions aa have been developed for both types of ctaqtouada could be applied. X vould suggest, therefore, that consideration be given to determining toxicity by oral aad percutaneous routes for nil cenpotods, aad that of toxicity follow ing Inhalation by ccapouada which aay have a elgnlfleant vapor pressure. At thin stage only order of nagaltude figures need be obtained, aad ve propose to use our nodlflcatlcn of the standard method of Celcbaaan, la tdklch tha aad LDj q voild be bracketed by adalnletratloo of tbs compounds over a range of doses or concentrations. At such tine as further Infcreation U needed concerning the ccnpouod. Bore precise values ahould be obtained la order to better define the toxicity aad otte r tests vould have to be performed to conform vlth the reqilramsnts of the Basarioue Oubstance Labellag Act. Ve are appending our recommendations for aoecapllahlag this preliminary toxicity evaluation and tha coats relative to these. Ve should like to point out that our laboratory baa bad considerable experience la the - of dangerous and highly toxic compounds, including explosive materials, sad that cur staff, therefore, le Competent to handle compounds of any degree of toxicity end potestlei baiard. N 205.12 4 '^i ] ' *;? :1 ..*---:-s -4 '4| <7| s the Bine laboratorla* Mr. Coo 0. fowler P** Tw o 6/17/63 It 1* aly* acr* convenient and 1* expenalv* to weak with **rl* of confound*, and for that r***oo our laboratory five* * 106 dl*eou>t o b *lx or nor* *aapl*a eubaltted t alngle tla*. V* *r* In politico to *t*rt work oo any toxicity t**t within approxlaately tan day* after receipt of the eoqnwd or notification of It* ahlpntst. V* would he Boat plowed alao to be ccualdcred la connection with other tudl* In Milch your laboratory night nolleIt th* aid of a prof***lonal froup eueh ae our*. Including th* evaluetlco of th* toxicity of palate. Z as looting fonsrd to further pleaeaat aaaoolatlcne. Itry truly your*. Signed! Charley C. H. Blae, M, S., Jh.D. Director The Bln* labor*tori**, lac. f. 1 N.;-. .- A MMMMMMiM 'Ji^uSdi ^a IPfV - 3 f:r :fS ffiSPOSAL fOfi TO MAD DCU3TRIE3 REUTIVI TO PRKJKDUJOf Traticmr SCR3JIM ranters I. yregtetrlc torlcltyi Croupe of tvo ret* (either HZf ICO g3. or nore la >rlgit) are flven eultehle doee lerele vlth an lncrcaent of 1.5 In order to bracket Uu nod U>x o q . Czewletlre nortalltlee in daterained nt 2k, k6 tod l6 hour*. Totnl oont $100.00 n. yercutaneoue tonicltr; Orovpe of tvo rabbita (either aex, 2i 4* or noteIn vL:t) tn (Inn suitable done lerele vlth an lncmaent of 1.5 In order to bracket the LQq and LSvx). Cumulative aortalltlea are determined at 2k, ta and l8 boure. Total coat _ 150.00 m. Vapor Tcrlcltn Croupe of tvo rata (either ear, ICO or aore pu. In velit) are exposed for coaboor to aultable eooeentretleoe vlth anIncment of 1.5 la order to bracket the I3o and LBim. Cumulative aortalltlee are datereined at 2k, CTand lS boure. Total coat 200.00 Coat for all three teete, per eoapoad Coat for tbe ml acreea and percutaaeoua, par ccnpound 100 reduction for alx or Bare ecapouada e\nltted at tbe aaae tine k50.00 ' u 250.00 * --<* !?_ .* * Project f ULC-li W03K OWBCff j um> gmrujm f.v.c. pn*> urrmw-TTca WgTJ polyvinyl chloride pipe le important la today's market and should urae (Tester Importance la the future. Various cascxxx^ls of leed bees been sod ere used successfully ss stabilisers for rigid P.V.C. fomilatloes sod the efficiency, effectiveness sad economy Involved la the use of lead stabilisers la not ea Issue, but Is accepted by nmnufacturars at plastics. What la at Issue is the aaowt of leed uhlch can leech fron piping Mmo It la used for potable ester supplies. Bines the use of rigid P.V.C. p'pe has a food future potential as a replacement for metallic pips. It will be wU for us to measure the leed release or leecbshlllty from the pipe Mmo It la used la standard household water supply systems. Producers of P.V.C. pipe appeer to hesitate to use lead as a stabiliser becsuse of the possibility of such pips beInc Inadvertantly used la a water eupply system. If, however, ws could reessure the plastics industry with ipproprlate measurements at lead leachabUlty (asaiming that tha lead release la low enou>) then sueh producere would feel free to use theaa hltfily desirable lead compounds. ecopt da purpose of this proposedprogram la to obtain lead release data from standard formulations of rigid P.V.C. piping In order to promote tha use of such leed stabinters In the industry. Cm program will be carried cm la two cooeecvtlve phases, the first at Milch will stealns la preliminary fashion vbetber or not excessive anoucts of lead will be released frea standard -3 piping system. If tha lead release is satisfactorily lew than tha second * phase of the program will be carried co Milch will involve obtaining testa and approval at such piping systems for use la potable water supplies. Of oourse, if tha first phase at the pragma shows that ws are not la the rlfit ball park and that lead leaches fits the piping systasM la esceaslva aaotete, we Mil go no further. Bo c bc w c THcrrrvrt Ki&ld vinyl pipe la presently being pradueed la the aaost f about 80,000,000 pounds per year of Milch only 2011 la presently stabHired with leed cavounds. Ve estimate that this provides a market at not mors than 80 tons at lead per year at the present tine. If all of the rigid P.V.C. pipe were etehlllsed with lead compounds, the present market would be att MO tens of leed per year, gcwtvtr, this Is a rapidly expanding market and tha future potential looks good, sueh that la 1967 It la estimated that 100,000,000 pounds of rigid P.V.C. pipe will be produced. Therefore, the present situation Is of ltts Importance to us than tha future and, since It will taka sema time to oarry on a tasting sad approval program, and since the ratultc of the testing and approval program should ha available before the reel aarkat potential tea be realised, it would be Inombent upon us to carry out such a program. N 205.13 MTtOfUL suamt KMldAlIOl TEST3D IASORATOKT, DB. Beedquartera * School of Public Health * Ohlverelty at Michigan Dr. Henry r. Tauten, Prild*at loraoody J-15U Cbarlea A. Pariah, Exec. Director Ext. 2379 Vliter P. Snyder, IlM'jr^rNnnr MB AJfflOR, KTCCTUI A8l0b Auguat 2, 196j Mr. Doo 0. Mir, Project Manager International Lead Else Mlearch Ortaalxatlao 292 Medleoc A\-aue See 101* 17, Sev York 10017 Mi Pintle* Ml**. (Project # OLC-12) Deer Mr. Povlen Tram pour litter of Pulp 30th we here considered the elnlw teetlng that e feel abould he Included end thla Better haa been dlecusied with Doctor McCord and b* eaocure that thla would be a alMaa that ehould be ocoaldered at thla tin. v* would propose, therefore, that the preliminary tooting prey to determine lead leechahUltp be 00 the Collaring baalet 1. Ihat at lent three level* of lead eoooentretee be need la the PVC pipe. 2. That pipe be produced frea at leaat 2 PVC pipe aaoufacturere. ). lb* teat* would be performed oa two type* of water* to be agreed upon before the testing la wodertahea. . ' h. that the lead atehlllier ecapoimda thet are being ueed la ~; Europe be the one eoaaldered la the teat, tbla would aarae that oaa etabllUer would be eooaldared la thla Initial testing proem. If you feel that acre than oaa type of lead cexpound ehould be Included, then thla would double the aaouat of teitln* outlined coder 1 end 2 above. 3. lb# coat of conducting the tooting over a alnlaia of a oa* year period on the baale of the outline above would b* 916,300. ,, Ihla would cover the perforate# of all the teeta aa outlined In the above breakdown oa tha baala of ca* lead ecapouad. If you wtah to proceed with the pregrea, we believe that It would b# oeceieery to have tarn further dlaeuaelooa at whloh tlae we could get lata " aore detail regardlr the pacific preoedure*. lour* very truly, Slgnedi Charlei A. Pariah CAP/al Charlea A. Pariah Executive Director N 205.14 loA/ss . Project t tftC-13 vaw atnoMsn l eap ctazw f o b snngvms prnmtTXM la i960 two oaaea of lead polaoalas were reported u lxlas eauaed by the d m of ilwiwn aode by a pottery la California. 6cm fair allllcn pice** of tala vnra bad b*o dlatrlbutod tirou<#iout tba Cblted State* by tbla pottery and tba California Baaltb Dapartornt Undated CO tba return ml ecsflaoaMoo of all of tbla dlaaervara. Cm rvaultlac aooncald lota to tba pottery eauaed It to go out of bualaaaa. Tba 0. S. Potter* Aaaoclatlea raqueated tba Laed Xnduatriee Aaaoclatlon to Join vltb It la aa iBvaatlaatloo of tba load ralaaaa fraa ataodard 0. S. produeta of pottarlaa In varloua parta of tba United State*. Va aooo found that tbera mi Dot even a ataadard aatbod for teatIn* load and baavy natal ralaaaa froa (laxad pottary and tbla baoaa* our flrat order of buelnaaa. Xn a Joint project tba 0. 6. Pcttere Aaaoelatloo and tba Lead Xnduatrla* Aaaoelatloo eoeaced tba Srttarlnc laboratory to develop a teat aatbod and to uee tbla aatbod on rcpraaantatlew produeta to dataialaa lta suitability. Cm teat artbod vaa aueoaaafully drreloped and baa beea accepted by A.S.T.K. aa a tentative taodard. Tbla phaee of tba project bavins beta oaapleted, It now appaara nacaaaary to lnveatlsata otbar factora Milcb have baaa brot^sbt to Ubt by tbc oparntlon at tba Kattarlag Laboratory. Cm Kattarlnc laboratory terta err* run co aaat different typee of slaaea fra aany different aaaufacturera. Since tba reaulta of tba teata were apraad over a retber elda mag* of valuta. It tioaaa of lntereet to aa to inquire ax to tba reaaena for tba varlatlooa. Briefly, vnrlatloaa la lead ralaaaa frea glared dlnaervare appear to be oauaad by !1) slte eaepoaUlao, (2) firing tanparature and oertaln kiln ooodltlcoa, j) coapealtloo of tba blague, (() otbar variable* not adequately coder* atood. load la a ataodard aoaatltuaat of flax* oc^oaltlooa for next of tba pottery dlaaervara aada end told la tbla country cod' , abroad. It la daalnbla tbet flataa contain land for aany taobnlnal cad eecooala reaecoej for lnatanoa, tba plaatla propartlaa ligurtod to tba Slate by It* lead ec^oaltloa allow a wider latitude la fixins tiayiratera and tbla la Important U produetloa pottarlaa. issn Cm purpoae of our propoaad lavaatlgatloa la to Inquire lata tba parawtara that It la naoataary to oootrol la production pottarlaa to aaka uee of lead la a aafe and aoonoala aanaar. Va are here defeodin* a aarkat and alao prcpoalns to axpaad tbla aarkat by ptdilleblof fuldaliaa* 4 v .O' i'. 10A/63 Pro>ct f ULC-1J hlob will allow production potttrtc* to cparato vlth oortalaty la a full vbora up to now than baa boaq a gnat goal of aoplrlcal and guoaroort oporatloo. Bj urlng our ataodard tort awtbod rrfarrad to la tba Introduction, VO win bo abla to lavaatlgato aad to oeuMiato la a iaatltatlva mow for tba uoo of production potUrlo* tho rarloua paraartora tbot ara aoooaoarjr to aoaura a aoothlp oporatlag pottory. peer we gtcunin da arldaaoad bp tba praeodlag dlacuaalcn, tba aoooaaU Juitlflcatlon of thU roooarcb U prlaaxlly dafioilvi. Iron laolatod caoor of dafactlaa glasoa produca adrrrao publicity idiicb 1* banful to tbo load laduati7 la other araaa. It li tborofora laportast to Initioto raooareh tfelch vlll identify tbo raquUltea aoodod to produoa aafa load gloxor and to dotomla* optlaua aaoufacturlag prooeduroe. NarfcrtvlM, tbo total eooouvtloo of load la coraalcr la tbo 0.8.1. via about l,000 tooa la 1962, plua an addltlooal 3,000 too* lapoartod fra Muioo. Vbat percentage of tbla quantity goal Into glaaad diaoanara la not known, although a rough1 aatlaato of 3,000 to 10,000 tooa aoaas raaaoaabla. ' ` *' .. - .- . ' V. ' Y- ./ * g ,v * ' v  sag* Tscctat i ui-ih r bi Tone ystmj. xtuart Plover and firth Avenue Eoepltal# fifth Amu* at OtM Hundred and Sixth Btr*t Rev Tort S$, Rev Turk Department of Pathology laboratory of Ixparlaantal Pathology I JU , 196J 'J 1 frank Priacl, K. D. I Kettering laboratory of Applied Riyalology Unirtratty of Cincinnati Coll*g* of Mtdlnlne -- Idea Amu* Cincinnati 19, Ohio Dear frankj Zbeloaod la th* final protoool of our propoaad aarlao of axparlacnta 00 rata deadened to produce data ocnceralng tho radioprotective affect* of lnorcanlo lead. Incorporated art th* euggeetlcn* of Dr. Donald R. Disc*, the budget 1* for th* work a* outlined and In the arant It la nacaaaary to punu* unexpected raaulta, tupplaaental ftada vlll b* xegueated vlth approprlat* Juetlflcatloo*. "/ If th* protoool 1* accepted, v* would Ilk* to atari work not later than October 1, 1963 If poaalbl*. After January 1, 196k ** will h* aorlng our labor*tortea Into a now reaearch butIdIn* and oev project* aay b* delayed. Cm principal lnreetl. (ator will be the contracting officer for the Inatltutlco. Bine#rely youra, Blsntdt Sarnia Barnard N. Vagner, X. D. frofaaaor and Cbalnaa Dapartaaot of Pathology _ .- SW/aav N 205.16 grreinc a d b i Chanlbal agaota utilized 1b tb* radiation protection of titiuN, organ* and tdmle animal* vary a* to atructure, mod* of action and ipMUl studied. Tract aatal* play B vital role ** Intracellular oo-factor*. Iloo, oobalt, Iron, magnaalia, margenets and ccpper or* aom* of tba metallic loot vltb ettabUabed function* In various aorya* and transport system*.1 lot Mil understood U 1b* Mgh ococstr*tlcm of eadmiia In tb* renal cortex nod tb* relationship of Mlnoliar to muscl* mtabollam. It U ccocalvabl* that In tb* ccnplsx, inttr-relat*d *y*ten* that control call function, radiation laducaa rapid Imitation, formtlcn of fra* radical* and disrupt* molecular apatlal arrangement*. In such altuatlona tb* varloia Mtallla loo* vould undergo severe alteration* In tb*lr aalaoe* b*U*. tb* poulbl* Introduction of appropriate Iona to atatilllta tb* aarly b*ng** produced bp radiation la vorthy of tudy. tbla laboratory ba* tmwuml eatp*t*oea In cytochemistry and hlstochsalitry. In addition, a major group of investigator* ar* studying tba structure and faction of tb* cardlovaacular systen. Tb*** Include: Dr. Sum Schiller Plaid Slocbaalatry Paneerlr tblvarelty of Chlo*go Dr. Villlaa Outataln Blopbyalea B* York University Dr. Mljb fttrabal bp.- fatb. Xnatltut* of Himareh, Ubivaratty of Montimal (Dr. s*ly) Dr. 8. Ncbo* Sxp. Path. Dcwnatat* Nadleal Cantar, I.I. Harold Appleton, IU8 Clinical Hatlonal Inatltut* of Baaltb Cbeniatry Dr. Barnard Vaga*r bp. Patb. Oblvarelty of Washington Porting vitb tbla grtwp on a p*rt>tla* baala la an alaotronle* axptrt and a physicist. tb* tissue* frea tb* animal* In tb* various experimental group* *iU b* prepared by rpeclal tacbnlquas developed fa tbla laboratory to evaluate lntraeallular, extracellular and vascular change>. Yas- cular change* include fixation for observation* of ecnatrlotloa or dilatation. J'* Preliminary *tudl*a aaploylng inorganic, lonlMd lead in tb* intact anLae1 baa indicated that tb* vascular changes ocnaequent to lethal vbols-body X'lrradletlcn nay b* modified, tb* purpose of tbla investigation la to explore In detail tb* following questional 1. Radiation promotion of land ** a function of do**, tin* and s tlaeu* lavala. s. Influesc* of animal aga, aex and diet. J. Kacbanlama of protactlcn at a blatochaslaal, cytological level. . Blood and urln* change* during experiment*. N 205.17 * ! i- Validity ctf Frevloua ObeenratlcM Oroup ZA R>(*a), 00 ag/kg 6 rata too t D Sad soOagAc 6 rata bOO r IC M*)i 00 ag/k( 6 rata boo r ZZ> fb(Ao)j 250 ag/kg 6 rata bOO r n fbCAo)* 50 ag/ks 6 rata bOO r ir **>3 *^3 00 t*/kg 50 a|/kc 6 rata 6 rata boo r boo r FoUi Doaea JO ag/kg/day. X-xnyt 2b hr*. altar laat doaa except Orcupa IC lot IS itan Irradiation Hit adalolatratlcs. Group IB 1* * gbaa treated radiation expoeure control. Vliter rets 100 caa. grpt-HiMirr n moot of Doaa ana t im Oroup A S 6 C 6 D 6 Z 6 ZT 6 1 2 3 b f T 10 lb 1 a 4 m a ' 4 ' 4 m a4 4 4a 4 4 41 a 4 50 ag FB (AC>2 l.f. - So Injection a toorzm Iba experlaeotal A*lien la to relate doaa acbedule aa a fixed variable to tlaa. Za aacta croup of 6 anlaala tbara an 3 aalaa end 3 foatlaa of 100 CM. Initial weight. Vote that Group 2B and Sf vlll raoelee Fb la tbe poet-lrredlatloo period. Ptparlaant in toheaced Mat 8tudy Oroup fcpeat of txperlaeot Z vlth tbe following eaoeptlend III-XA Ad ltbltun diet m*XD Barlcbed protein diet Sj4 Including gs aalno aolda III-I7 Ad lib ZZZ-I9 Xnrlehad Iba 6g rlob talno aolda vlll be adalalatarad by garage aad vlll oemailtute a SJJ loo. la protala 8 over tbe ataodard dally eoneuaptloa of food. `iV-r. ', i t -3- ttrougbout ell experlaente, blood aod urine mo plea vlll bo obtained at judicloua Intervale for tba following dateminet local ms Baaoglobln Baoetoerlt htl^wnl VBC and ilffmstUl JU,I,Ca, eleotroffceragnai >01 qfCTa Load Frotelae Carta Celle, Bp. 0rarity Tleeuea obtained at eutopey vlll include! Brain, Lung*, Boart, Liver, Spleen, Btraarh, Xddaeyr, Adrenal*, Oooede, Ekln, Baa, Bo m Mr o i. la addition to rootIn* atalnlag, mere ladioatad tba follovlng bletccbaaleel raactlcM vllX ba aalfitd. 1. Oxidative aniyaea 2. Bboapbetatee S. Baale protoina . Cooeectlva tleeue polyeeocbarldea lbe experlnente will ba modified during tba couraa of tba imotl* cation at tba dlacratloo of tba laveetigatoee. Prondelng Xaada vlll ba follnmd at no additional expanee. lba experimental.deelga vlll yiald etatletleally algniflcent iafonatioa o&ldi vlll mover fa large part tba original prcblea llotod under title at project. Tba project will require 6-4 acatba for ocapletlco. ccBRiCTttm mu Sonerd M. Vagner, N. B. Ralph 8trebel, fb.B. MUiaa bodall, B-A. - profeeeor and Chairaaa, Bept. at fatboingy (Prlne. laveat.) Aae latent Profaaaor of Kxperlaastel Pathology Cblof, Kiatochealetry laboratory PdCtUTTP IVIIUBH Anlxnl Beeilltlee Blatocbevletry laboratory Cytocbealetry Laboratory Bletopatbology Laboratory X-ray eachin# (rupervoltega available) TxrtmKfsi 1. Iu j mii Bixon, M. and Vabb, t.C., Aeedenlo free* Too., lav Tort, 1956 2. BcbUbert, J.R., Hutb, O.H., Oldfield, J.B. and Revert, L.P.l tzpariaentai Reeulte vltb Beleelta ia White Muaola Blaaaaa of Laafce aod Calve#, Pad. Proe., 20| 689* 1961 3. Vagner, B.N.i Btudlaa of VaaoooMtrlotlcn, Bull. B.T. Aoidaay of MedUlne, >fl| 66, 1962 fc. Van Clttare, It., Wagner, B. H. and Ruahaer, R.t Arobitaotura of 1 BnaU drurlaa during Veeoeonetrletlon, Circ. Baa., IOi 668, 1962. -v 1 ; ' V' _ . .. - -c `Tisw rib i rjfrfi .'jailI V '' } * '-"""'Vj ^rtr'V, i'i -5- " m mxtrm. BtBOP Prlnc lpal lOTtrtlgmtcr - Dr, a. v<a*r Co-Ior*ttpt< - Dr. Raljh stnfeol Tacbclclan, part-tlaa Anlaal Cara-talar, part-tlaa wtrmegff 3.000 8,500 l,kVo CCBSCMABUt SUFP1TB AMsala - Vlatar BU (100) - Aalaal rood, fcaddla* Hlatocbaalcal r*aanta, auppliaa Ilatolocr aqppllaa Blood aad Urlaa taata </inm cruttna X-rajr todmlelaa, part-tlaa aod aaa of *<jul;ant t o t al w h et j o f bbb Otailtaad lOf 9,lk0 Jlk 00 1,000 300 500 800 10,05k TOTAL jmi^'t|yg^!'.^iJ4U|.4ipp -- i ? -r - 'Vs-'"