Document 2zyanQj4yZnap8j0yNEeLyxa

?iOIO CAjLL THOMPSON 2/ 21/ 66 Dear Jim, Concernin'" It . ife.- :.;;'r, paper which was sent you on February it, we have now transcribed this and recoyniziny that the piiobostat sent you was very 'difficult to read, we are now enclosin'/, a carbon of the paper as retyped. Koto that the material in brackets was material that she had crossed out in her original. HILLAND KNOWLTON, INC 150 Fast-l2miStreet New York,N.Y.10017 OXtord 7-5l>00 t 2 i i 3G 'I 4 . .i KE\ 0019182 H/lh/C) v e lecm or^ortuaity to rctvcv vitil yen crtala avoilablo data and errussvurcd, cuestiona in tho study o? load efdect frca tho vicvpoint -- vhich is raino -- el* c, physciea 'iatxccted ia clinical preventivo raedieino in cncrol cr,,d ir the cpccific dIa~r.ostic and thorapoutic problema p e e d by a cinglo pntieni fcscriptioa od ay uca;;o cd toras ln tkis paper v i ba useful. divo veris "tsric C>i vV * lo Iced-causcd cPaspe resultiru" ln no dotoatablo (brrrpa cr ion . ho verde :orm. " "\4-i5<-.*>> !-}J *:*('--" "(cV.*c.. urea that Ubo Icad-preduccd effect cannot bo tolerated cr handled vitheut produci" obnoraal function. ... ..... ....... .... . .... .......... .. It Is necceeasy to eephesisa that no luxrraful oddest od lend la uripno oueept perhaps the motor palsy of tho ucot-uocd eusclo crop?, 3 in tho vrist rep cd a ripht-liandcd printer loose loft; vrist Is uncufcetcd. dais ncu-v./ccificihy of leni iutoricatioa means that identification od lew level derapo requires a eerbirntien od cpidcniolopic evidence, astuto clinical cssorvavren to rale cut other etiolcpies topather triti old orti ixu experimental evidence critically Jelpsd dor consistency and repeatability* Another duhdaaoctal cousiclcx'c.tion that vcih3 heavily in this discussion *r* v*fc\**1*1*" hoed that lead in the body at levels considered drees industrie!, Od*. 'V. e to be harmless can act vith other factors to produce dreco. Id w i n VvV*W .*wW*U ^ otke: biplani and Uvleoedor Hatch In this country havo urced that those rnsyevd''Jno dor establish!:; tolerance diraito, tachlo tho difficult problem of racesarirp tin nuluiplo doctoro that nay influence tho offset cd environmental hrsverds.} KE 0 0 1 9 1 8 3 effects or lead are rmifold. These; of spedcl ic/tercst in vhat X have to present aro as follows: First,--the action or dead in deotroyi ng KBC (red bleed colls) is voli recognised and illustrates tho fro Vandeanentclo Joss to -- the nonspecificity cf such an effect, i.c., the many cruses cf such destruction Further, tho fcosard to the tody of chert supply cf red blood collo if, For cxoaplo, there is chronic bleed loos frees another cause ns is. VJ. V<s Uf ding frac a peptic ulcer illustrates tho problem of rears thorn coo .ctor iiri'luoncind tho pathologic effect. The behavior of lead in follcv;..p leiua to the ehoicica and its r.cbilication thcrofraa by such x l l z o l y events pregnancy end agoing (periods of starvation) is a cocc.id veil established ooihility pertinent to tills discussion. Thirdly, of potential irgorhsaco is .a areirrdLaticn of lead in an organ as it does in the liver and in tho erne of pounds tho CF3 (central nervous oystcit). A fourth biological feet perhaps cf tho greatest significance is tho dareging influence of leal ,certain levels ca grevth and ensyno activity. I quota frees a WIG verhiag per of Lure Friberg as helpful in introducing this subject: /fho question of istneral metabolism is, hcvcver, cf interest (also in other connections the use of radioactive isotopes thus ire-lies that) oven minute amounts; of a metal -- harmless ia itcolf -- :.ay la of essential biological importance\ J w2hs possibility has also been discussed vhetlrer certain motels) in ouch ralnuto amounts es are normally present in the body might contribute to the development cf chronic disease. She reason for tills discussion is the fact that certain essential metals form ccrcpieaos, for cnsmplo iron end cobalt in the porphyrin chelates homo and Vitamin Against tho bach.grouad cf K 0019184 P*. C * V V-^aiUb . M *sJ `M>..--O d* *<. V> W 'Wo, 1* * v * y . .* .- luhj V 1.w. ------O k-0^. , , -...., r-? **-7*v tir*w\A LV4>)v,<Uvivi*}t y,.-.,..w` VvX ** *---W m^ ,.-- *-> - .- *v ";' "7 - *-t .** -1. -'.- > C.kM*r^'" * .-*' " * '* - v-J <" _ t r a t i c n o f c a e s ie t a l vcu Xd t h u s erc-r.ta c. c o a l i t i o n o* d e fi c ie n c y c f a n o t h e r . ? c r caxrfplc,, ca lr elva and xsercu ry vo u ld th en d is p la c e s in e .c v ia s t o t h e i r e o l a t i o n u i i h U ce a d a vh icfc. n cr r o o lly c h e la t e v i t h s i n e . " <71- VV W* lk>vV..^--- >' -- V-C* i la lakk C ' V w W i < A la j^ va-S*|*, -*V# icu a d e n t i n t h a n a t u r a l v e r i l i n v h ic h r.an c v o lv c d , i t vo u ld l o saa'p r is i n i .ad U l n ot p r evo t o p a r t ic ip t e in c c r y o t it io u fo r P o s it io n in a le p c r ir a a t a l o vid cn co tZiat le e d isay in t e r io r o vit ix c e llu la r fr e ce :: s s s tsoleeu lar in e it e l by W esterraa, J eanen e t a l in ca e r t ie lo p u b lish e i uyo 0.30 t h a t lo a d p r od u ce s r lt o c h o x o ir ia l r s o r p h o lccia c ram ees cr.d r ib s o a a e f X<V*< / W w i J ^ * V X k M U v % v v V V l A V > '0 G.. C--- u/vC'- u lp vr n t c l o ld en d n ev d a t a fr e a t t o l i t e r a t u r e en d r y c lis o ic a l c:r p r r icr .o o. l n e r d o r t o p r ese n t ; t h o oo d a t a l o t u s o ^ r co f o r t h o s a a s o n t -t h a t c t u l y o f Is.:. e f fo o t Kr.y t o v s lu a b lo . *on o con c i t o s e n s e i leifzcc.'lu ^ 1C<0 *fV an d a cir .p .lo I r ir p o d o s e ; t h e s e n s ; trno o f i c n i a i n y ;; -- vi<".*i \.U c- a t 3 "u arylliisa can r e s u lt in ebroai' m a t in e d ie c e s "bota b'ccu au to does cau sin g e a s ily d ia gn osis ( cic ) txir ylliisn p oiecn ln p and ile a r d o ses s o le w t l a t n o die<paosablo d ie e a s o i s p r od u ced a t t i e t !? n . / fid s i s o n ly an cacoosle, t u t o t h e r laoebaaiaso o f e .ctlcn s a y co co n s id o r o l. l i l l o t ia r a can be n oth in g d e fin it iva s a id a t .t ills ca cn t, i t vou ld t o id -s in s i f I ce d d id n o t p r o ve to ix u r t ic ip a t a i n e o r p e t i t i o n f o r p o s it io n i n tfE- 0019185 9 8 6 I 0 0 3H oto,.toro jo cocox^AO.t'T poaroirqo tpj. 0 7 tra rucacpoo cpq pcsvrjjctoo 0 0 1:7 s oAirq c.toqrtv3 qnccrj jo xoqcmt t> pw `Z T (9 ^) CT^tn^.tn:oo -q. poonpp-o pc.iTj cor ppoo-mcP opea tpr 0 7 'Zcxkv.x :j, jo ootropTA;j tOTCpnO 0 77 co, trpaop ptra cnq.oj oqp oppanfup /TTOiXiTpaT 00177 pu? vrrpxoq^xcTo 0 70 0 7'.o:p coq. cop-inpUT o,c~TJ pesp 'cppoo ^t ot gt -T ^ co cop jo 1:0 770 1? oqcj. co coppnro eptr tawy: sopapocoo 'oAOftOi: *Tl~Z Tzz *orno,rpnocrai errrern sqo, o poop jo roojjo P7:Tprptui:7TS proojxp n 7.r.o;p-n o tpT.n c.noppcj sn^oj cip; jo copspr.iPco qrotp- ptro pcopq perjontra o:.;?. ifJne.tr.r ro ppso rszaS 0177 tro tj.oojjo 0 5.7 /et. sot&po cnrroj 0 :77 cpppir m p r/c:^. ot copeco ,70 cp.ca oip, op es /Ptocrj, popd!oocro ppenen erp, cOs .pseo a trop o rea c.7c.\cooco paorpoa .Cp popotr can troppot? spqp piro co p rca r*-*-''>,*-+ --XT'* -`V'p'n-'t **--* -nt C'--'vV ^Tlr,^`''V' ihr-oSrA -- /T TV^^T^'!".'>*T*"',;U TV^-T*v''1-* -- f t-'~;~z.TT,y'-Z poop rp rvto.n o:?n itcacn S c e sa cSpop&crnr r o r r o o j o t-crz'oa - ;. -.,,k <** /**** <_s. l.-,, t-- i.}' ".4 <** ** 4 -n ~ V ^ - v ~ *- - ' *;- -' -`i-j--TV* *t*>T*'*vr >,-v> i-v-'J ^'-.*v-i>(<yv,4* {,t-v<"-fcTA Vf*v--..*'r *.r:;. ctp*, n \ r j correi'" q.p r.opppp.po tzp *t x & piro co ro s qcq. j o sppoo cvm"? ;o 1:077.00 cr.opm.'r.T. tro ci;*' prop qnrq. 'cPtrpq, uirvroq s o r.top?roA.tocrj> crrzj 7"'.:o :.rr:ov:.7-i~ "::>o praptro a o a j tp*,c-?. ` ooccpjAO opapr^OAcrococci: c t caopp,, crono i :IC pcop.o p u p Iy H ^ E j o uoprTP-' ijto rrocrj rc-pq/oront) q-iici-qac;" e s~ ^trfr.ojro 'roojjo pcop Sapnirrop "- "PT'- <7no.ir.' C.T7J o-pp e-.? cnc.i2 ps-oocTe 0 7:17. uoirq. cenoepp 0 7 tpron Ju t a ;Ci:".v'::'-t" 0 7 Sitp^.7ojo.t ito sopccorcpio cqiroq-pprori ooppy *.t<i Strr-M.ouop 0 7Popot|-".tca tcpxpuoqoo^pn piro coprprcrcrocpo poaocoptet i'ZO,eoonx-iv. tv no-;;o 0 7 cttropTAO p-rocaprO'Trro quocmo er a c j o pa 7 0 rxa.'0 70 0 /i /'poTJl .PTTeco 14- p*.*' hLw''%i-5. ^ i' V V ? 'v-' 0 ^ <- A. . h i ^ O**' .' i .V. .j*^ v i ^ y V * w w % * > ^ ^ S*'**'*k wr*^ V i vrJ \ W i > v i " y .'. * ^ ""r,.rt -r-r-r<o-A-fpTJ T,'*'-' r^'i'TT^? ^Try-vt ++*),r *r*.**' /*'-'**" .'-:-^T'.' ~r- cnid s t i l l b i r t h i a th e im r i t a l h is t o r y c f m ale lo a d vorhors ( f c r d io ii 5 C, c.--u.*.ayro ayo, Bonau-u oourp ov) * f c m p s m o nest m p ^ r m i ^ ca.-.'.vp -u. <s .Vr.**.*.-** .^.^. *1 ^ 1 ft*.*O*r+V/*-*V^V VfAy-'*V%-.*yy---,.. /^^->\*-Z\'Jy\ ")T.v.#.,^^,,<- .A * .?>** ^^****^ *-.O<A*~*V*~ V ,f com parison v i t h a proup or vorhrxn d if f e r in g from -he* f i r s t ^roup o n ly ** t '* 1*4 .-%'>'* /V1^ r t " *?*' f ' O * *** ^ * ' -. *] - y -".h *. %' .s- u \ < v-fc^ W * 4> L* w V W ww\-- 11 *. *-^,'N-' \ ~ * **"'*\ f \ '~ " ` - " V '. "! " r> t ' " ' "* * } * w s- . -`v * -4 d- % ** w' W ,? *|r* * * w records cf voi-lsaea2 w to lead in %jCJCZZ--Z0 C'.^b. w..,,* W ,. a.,- -- vith the histories of thCSQ vorlcinp in C/<-w- rfr- sterile mrriaces GCitj^i>wUw--m\-+ pdhfVI Utiu a. V/4kW ^!/'"S -- -Sp, only it.3 per cent for the non-lead croup; the i>orccataco cf precr.ancle: cndin.3 prematurely or in stillbirth vas 3.2 for the lead croup nr,d 0.2 for the control croup. /The infant mortality rate vas v.2 per coat for the former and 10,2 per cent for the latt-arsy" /hallo there are contradictory reports g o to the dsmaco to mile porn cell a cousins sterility and in trancedttins lend dreenpo to the ictus, the turn is cuito clear on tills element's fcara to the fcronlc reproductive g ;, pnssacc from Cantarov one. "nraor sursarioes the -.reslively cinj7 data on the harmful effect of lead 'to female reproduction: 1 pucto "`die paaoaoo of lead through the placenta into 'die 1.vJw/li. "wlndGliCO* m* hao been demonstrated z-cpoatedly...If born alive,'the child freouently clicrs evidence cf the deleterious effects of lead exerted during the period of Intrauterine development. It is often veal; and vndersiuad, ar.d tlioro is a high incidence cf epilepsy, jsuocular spasms, convulsions, a*a owhor nervous disturbances, idiocy and imfoociliiy (Biondi; Mcillerc; Brendcrpast). /ps3X roported that dentition van delayed in Cc of the offspring of Indian women living in a exciter village^ Iccoruln,;: to KB' 0019187 in Vi 4kV t, ; , .-'w-k U y X 4 4.A V * 'ITO^-Ox1 ?,--4 f*<* ' O V I|A> A y ^ , .f C v P / - * M . * A Sr-i-.w * -Pi .-*- ^ *> peculiar 2 oz*z cC `iUf.*J*.) .t.br, f?S, O'i a*. Ol/"> < .haly or CfOi >LLO1 or both, and tha mortality vao 5G>. A n this instance the possibility of absorption or lead after birth must bo considered, i?ortleularly Ginee significant quantities of lead xxiy bo present in the rather^ **"*1*- i *TA* *ir* *t** *,*,<".*i*? **' ^*1"*+v*r */ . ^ 4* Jw U 'V A W V'trA^ t 4 * 1*) ^ yv?** ^ 4 < U Ui.*.*. K f A K . + X* V ~ C ~ .f i V - * V * * ' ^ AP.-. vi. -* W i ifc4 4 V * M* fc.w. >.-- '* 4 / 4M # d * W t # * V 4 ^ ^ ' *1 Ak'<* 4 4 * V v 4 4 4 W >4 ii v V W | 4 ^ 4 <f4 >/ iy\y A 4.V 4m v Srf v**> --, ^ >,.*-v,^. ,-**`li,-- ^ V>4> 4 k W V 4 * 4 4 > V < 4 V / < i W m O > U V w ^ ^ b i 4 ^ t 1^ . * k O U v > * , v-T-i'**<*; VX.* A A C*. kSO. r - W V > 4 /i X w > . 4 w v < U *^WfcVPiA W * < w V.4 k.X*'0 < 4 w U t ^ . v W i U >4 Phare can bo little doubt that caesura ci ,--r .-. .. v-- '-/'-**--V_i`i* ` -1s > beet vc?oa fertility, the course of pregnancy end the development of 1 . 4 w < U v v<t> # /he heard yesterday of an csoay by S. 0. Oilfillcn entitled ''r.ccuui Culturt and lysponic Load Poiconins" elaborates with fascinating evidence tho author's point that Greece and Peso foil chiefly because of lead in coolest' end in vino, his thesis is that when, about 150 33.C., relaxed rules alleged the vivos to drirh vino they failed to reproduce and the cristoerncy vns decinatcd.7 lids is a coed place to sent!on that root authors vho have vritten on the subject are of tlso opinion that fesxsles /react unfavorably to/ suffer huuv.vful effect at loves' doses of lead than do rales. If tlnis is true, it is b.pcreant noising (unclear tent)... Loll, vnir.~ lead as therapy for uaiiynancy. a W^y >. J U .' -. ... *, r , W..-W x^`-;xril.ee cx;d *' - -v -- S sJ . K f 0019188 v_ states licit vasca are sost.liable to develop poisoning tstvccn the s&cs of lo Y V. -T i", -> >V*"i**t t * M dL * w * * k * k ti i*>- V W s ^ A W ^ O W . * V * <i.h t* 4 4 *. ...\ ^ . W .v . `. + O - *.* L/iivJ 4k S. - * <4 v \S+ *A-*V w A U , v * * i.'M VWli l * 4 V < t 4 . ' . i W l W k U . * 4 *^ * o V colic, luci: observations have loco rode In o:;geriTncntai or therapeutic cltucticnc or In industries vitbnut Industrial hygicno controls. tue value "CO VIo C*ti Ci-*--w rooting of ouch observations is to point cut i-<.'^>,`U wlLvi.*.*Gkt K--\j *.-f IV* . V* U. k# J `' rt,'\/''*^' f*>v** ** *# ? /I ."*V"* * -fl A * S ? x A C C* kk4>.i.* C W A , V > v i / + . J . k.V^.'vi. T /"> Vrf -** *'**"TV** 'f* A /V**"."*. *S ,'<S> * -I i / i v'^-i Vv ,*.*- - '.' v 4 jL v . Uw i*..-. 4 J * >,.k .. U W O j Ah'-r?a:i! y?***/eleni, illuo wiTCwC?S tho critical j.a*cc u*uue le.i.opd o_* ^ irooi asny o m l l coco racy to gunlitativaly like tl'.c scare iuncdicta acute oricct cl o. cinrjlc or lever higher doses received over a shorter period cl tire. Ire second special' group ana tho one shout vhieh rest date, arc cvv.l;.llc in udscuceicn ci lead poisonlnp is that cf tho crcr,rixiz child, oercadinp .lellv- '.;erk on the inriuar.ee of lead cu call-erovth one is struck by tiro w;ry cliuto solutions of lead acetate ha found to retard croerth. In the rnn,,e of 1 to ICO to as little as 1 to 100,000 ail very ycuns tadpoles were hilled, *,.v:croe.s Vioro natura tadpoles survived out suffered retarded grovth in th.a 1 to 100,010 solutions, loll concludes iron: thcco and rany jeoro stailos that I puoto !`the arrest of .prevth in aniisal croanicros is strictly proportional to tlic cecacity for, cr povor of, grarth,'* and ho further writes - quote "load is net only -reach acre tonic to the ycung and prccdolosccnt than to the adult and old thrcu:;;hcut the vertebrate hinpdoa but also that tho effects produced by the rectal are Coueral in the young (Bell calls this soratlc stuntirr*) and local in the achalt." end of cnote. ilicro are a number of studies pursuing tills point. /A study that should be repeated perhaps is that of Calvary who found sicniflcmt retarcaticn of growth of ralo rats at relatively low levels of lead in their diet {3 .53 Pin.)'/ KE 001S189 -3- Cf great importance for this discussion is the mental retardation that follows not only acuto load oncophalopothy "but perenno chronic Ini absorption. Tiere ere cuotrvhicns from the .liseuseion by Byers, a pediatric neurologist at the Lead TTygien? Conference sponsored by the Lead Induetrios rnsooiatisv held .? / H . U "JO^A te* V* a.** ^.,,-vJU^ ^ l^lC * # . "Certainly when children die who have clinical pathological load ' ericeph.edop.athy they die with brain stem compression. They die' vita sieving respiration, pulso rate and blood pressure, anuria, all the usual evidence of increased cranial pressure. I can't believe that this don't in scese way related, to interference with the brain ensyro systems through nessunts of lead which :-.ay net ;; t*. v`.* v - > v . X **'w o i Y u .. >i X i/ ~ a <**> o -U. . 4 4 .ivi L w O .-i ZiiQ of children who had had lead poisoning and had been sent ho:..e frovi/kc 3pitel as cured, who then burned up in r,y neurological clinic beenuso th ey were luicbchaving in one way or another, or not learning in school. One 2-id sot the schoolroom on fire, another nice little girl danced around on the deed;, llano of these children had aouto fulmisating encephalitis. they all hr-d evidence of lead poisoning, like stippled colls, some increase in spinal fluid total protein,- 0 1 symptoms, coproporphyria in the urine. /At that time, ve didn't too;? about the importance of Separating thaw from load. Wo tried, in a desultory way, to separata them. Kaybo va weren't successful about ttot//" , . Tho point I am trying to malic about these children is that though, scone of them, at two or three years, had an acute encephalopathy with their acute intotocation, when they reached six or seven they chewed evidence of brain injury. I thirl; that many children get chronic encephalitis KJ= 0018190 V* -,< %! | m y v e il as acuto. a*--Lin Gl C*tlLO*1 dll<!>'jTOf*uww3 -!.^/ WJLt*w4J O vCi1 *.C*/d.a.igj Lui any acuto len d c u c c it e li t i s . . . . I th ir l; th a t len d done co;;:cthin~ i "-. v - i'n'* *' end uf ruoto Br. Brio, a pedic.tric neurolcgiet, "' VC fk-tv'.Jt'' <<lvu support of oi'ij.c proolci end ero iuclivAias otuay of siblings f lead-poisoned children vith as careful ar* possible; quantitativo essessm u t ; *>al C.jl ..-1 > vO *.lets these children arc c: >>.S\.-7i* V<u. A . ' .X*+.A, ,*>?*. .i . <--.r .<.7 r:pariry; od childhood load p o iso n in g frees urban ccraruuitieo m h o i t c e r i l a *,-a r> known od th e t o t a l nuoiber o f cacca o f a cu ta in tc u ic u h ic n and nothing o f load absorption in quantit i e s th a t m y peso a r ic h to a e r a c i r;ravth. >y C h r istia n o t a l in .C h ic a g o . . They rep' ^<4 ****<" .*.V-S., v *-* * y-.i^ 'P o ^ .in a betw een 19 59->10 6 l , ;:.5 o r b.Y p e r c e n t .coning, end of 5 deaths, 67 or 79 per cen t vero B oston r e p o r t 5 t o 2 5 a c u te ea pOX* j *1* * *.^/.*7*' -7'< *v figures (through the courtesy of Dr. B a o tje r ) -- in this city there ic on encollcnt detection n'osraa -- arc double this nuaeor, reaching over Go in ecr.3 years, i.v--'j.v.;`ent p Burins acuta lead poisoning in childhood thovo is reliable evidence that k id n ey function i s uicturtc-d. H a l e th e blood sugar regains norml, there in readily detected glycoauria, uni renal tubular dcaasgo has boon further demonstrated b y eolncaeiduria end phoaphaturia. In fatal eases acidophilic Inclusion bodies in the k id n ey s are recognised as a pathologic load effect. These f in d in g s r a y arise free; other causes end identification of the lead closure as causative is oaccttoun difficult, While Upper van unable t o c o n f ir a th e findings in hhaesnehusotto, KE 001S191 -- -* C*W'W f - I r\ \ ^ ., , I U v y O m *^. w ' A >. O'* .'.'V* *^H^ ^ O v , t . V . U < . . t l|, r- Wrf. .*. b . M .*. -J i .,,..^ v V '4 > *^ -- .4. 1 ^ c n . * * OS. ^ V,'V-'...' _ ,.;.on. V<i.....Oi ^uOb*PC..wO*<J wiiw C^-XOXC'.Oi* ,,hi'-fUl* V/iilOli Cvi4, U'v .'OCO^.O--OCO. iiO-Lr.^Ov* f- 'v.-d.* wVt* ^ v*0 l#i2Cz*X*> 0-. i^CUwO O *v-t* > > v^<-*.v.-i^O *.. .-- If ua oocsas likely frc;a the accusuluted and ravine; evidence, jra :._csue is uoro vuli^rabla to lead than adult tissue, rieor'seal!-:...' dor;on thru these roqnired to produces diapnasnbl lead poisoaiac In a healthy r.-lnlt r:tb: *>O^. --.* i-*- w'.J--W l>* *4^<-V-sCOJ ij i*0**.0Ob>iAtb.C Z.J *t'_, ' J^ . .... id childhood no that shirts la pi;, variation in intestinal acidity nr nlhali....;., x.iiich nsy dissolve injected lead r.oan that absorption, distribution and stern.-. of lend are not as veil ova; "! - ' t v ^ *T i WV A I n A t mm i*. C .C.J.V ^ -I. m*.'_ . 1 . 'v s P w G onor.rss of lead peso i-entcr _...-. .or..."U w-d.c4,urs m and e a 1; bone, ^ V '* * -'-, ,* \ / * * > )' t " ,1 K r>K^.4.V^r V 'w . *' .<. ' v ^ l C i ^ v > > --. ..'........o>..i.o.c.^"'owm.Wwd* a.<*xi i'd.vSv^>e0. ^uo>i ^fi.0 .a. ......o c.o w . ? li.o o* *..* *_r .. iv.tcsricaticn if lead invested or inhaled ic added at a tizse 0* a*0 -*_*d Oj. leas. free; bone {?). Bocauso cf the daaiisaaco of ;iy clinical cscpcricnce, X liivc- been Intorestsl in censidorina x.imt effect lead absorption vithout datectilolc cvidor.ce of poisoning rdii.t bd.ve in tlie cedical events of an oth.en/iso healtiiy individual, lire dic..yec;sis of lead darape is not ulvayo easy to saai;o because of tlio aoncpcdficity of cyvitcrs, oi.yeo, laboratory findings, cc^alae that aiyot ell be related to otlior otiolcylos. Bren this U n a of thinking 2 conelalo trait an apparently veil lead vorker ccratitutcs a third cpecial pcoup for tha purpcao of this session. DD rr.. IhTkCUe*h<toWeW-'Ms^ olepint studio: .-re finidr:scntni to tha points X ralso. *,;ith ex*, ^measur.eU>dU> quantity of Icea stored in dole ton raid liver, vith lesser recounts in ether ports of his body, cnch a., individual is in scene jeopardy, a point Dr. IC reads yesterday, cad ray not be abi '->. iV - A'w * 7t--M v / A M s,*,-^X *?.a*,V>c-m\*>* 7>fX *wW vU'~<Aw * --*--^* *-*-`,t-^.... / ,-.. >* r-o - *,* trcullo than a verier without < > . . , ? v -v> O/ C aW a * V V<*l V . \ a 4,* " cal event c.*acbW A V - J i^ W a I O W O w M s a 'v -, * * od :.-.c uncr M a care, rollarne reported the nceoclcldn. values c. i'-.a,-!- 11 ') ^ * V V < t o w ~ A f K-- W WsCoa tveon 9e and 23*1 ; x V.** * r Vii:acr m m g rancia! free 0.12 ui^-A I CIO ../~. '+ 4.**A W ATv.-, -%^-vr/vf--- .** TV* r r **,,, *,**& ?.v* r**.**.n. -VT*,.. . N ^ X t . L's a -- wl .-- . t * < X * X .. * Sir . L>4 * W u \A*-.a ..,-!..-O.-j.-.--0'--, *Vt-Vw'~~s-`\v\'~ A'A i*'\*,% * >*y*" '**/*>><'*** "" "**-7*1 T f; .^ i . k iV - i'U v .''. V / V -"- W****.a X v V * S V < '.A `- J ~ *W*. A S A . ^ ^ M W l a V s l X i > V ) W U V ^ 'A W '**-.-*- / ., ^ * aJ*a -- --*-..1-t ^ y~iy<~-j -r^ ;.v W U W V l w i i : , V W V . . a W . ' . *j' x+1 D uTVwC i Idea. iic^2y TT-V?Sv.- A-. i */J -!> ^ <xr: > *--4(*' V'.V.-HC" /- v - ^ -- -s\ % * - w --- - C ~ V ,,-.A / r..-:J. acv;.n2 t;:xc pcrica on zo o.0* 2*3 inrir^ry lorul c ;:uv/;:.:.c `:i v.xu .COJU0u. 01*0 o *. *XvJ' Js_. .,,.,,-y*,.. ..A.A-v>* IT"? -rt rs-.-r-.**/>"?*? *? /'*"'," A * *v * * V i i v . ' n V ^ v . J * v .'a^ S a 'w ./ `a v * % a . w V i V -~ -,r ** w -- . -.w - > > '.;| ' / I | / V 1|,* * \ .S . A N... . .V.A. . V . ^ a ^ J? }- a- A -* *.! *tm * W - a 4 4-** v *h. v O O # v A.--^-vS'o.^r^4 a-.-T* ' -\4 *- 0 ^ * . W %/ U< > O d * A W U C * U ` OwiX X*wX0. r nta cl load in pans by M o n e y than in talnl cl leevr^*-* n f VTa. * *>.HA 4^*'.`,-.4 /* i* V \ - <V W * \tJ <V. .% *' I t 'iA--** 4-- iii'jWW'WAVApI a a X v^ WV**'** ^ 4 ^->^r4.rvA>W>X V > - W P V v - ' I V 1C, V l p i l U*--U.*X '.O " W P l(W* V <1* > * * ! W X 0 * w ,'<V'*`a w U iV W M a J. W V M . t V a t i ^ " X W i v ' * W C a . X X - s a a ^ a W aX S.!. i > y i ^ .need end the reticulocyte count elevated oi^sstins accelerated red eel traction (unclear tret}... /Althouc^ those non res not ill cueh Iced err-tien uvoana toMc land effect.. tty clinical ironbecy hoc cere true in oral caeca in say cun oryoxicnccJ In soy clinical cnpcricnco tlic fcllou- cue- Caeca of ycytic leer, not held related to veri ".rith lead, iroved *v-O ... -- .i. V V l O A +L ~ +jL *m m '\ * J ** OXCw~U. vtC #^4* * - 4 4 *.**d .Li ."* -- W .-- C. - Vh^d. * '- W'* 1*.V i" **.* '*.'* - . :*. ! - .-s"| 4N " *' ~ t **>+ W * ** w ' W M t '*.[.%' " /*.*% I ,*/* * "->. ^ * V ^ V > W ^ ' v , U V* - W ** *> * * \ ,-- . , .*-- ' - fi' 'r "N '' '* M ..**..<,**. W V . W `-W V -- ^-*N* jO C w ^ U 'w J .'-* r-i-C \JV*.W'--' C*- Cd. U'w't.uC U-'*-.,, _,V*v' .no *u a k-* vvl***^-n en ry arder : .wvo ,.i3*x xic.ccd.cxi *c.c>c o dcxactra 't o ureo V - t A - w W -- O v W * 1 .a end CjiniW0<> C.w'- v.v*fs. ^ \.j* Ci;vi ci* u .xlly i**.*''**''***`.T^ "TIi`f1 ^* -^v --*'V*fcfSi a/n-u-n "**v ?-1 '?'* <" 1-,\!*"; W . W 1 i W-fc- M W . V ^ w U j | * X v J . * W W v M <** *. N ,^ m- * W 1 ,k*.L . 1 t>. V Vy * .' *)W * W...>wOw fcw'vCoa O'^ii-O vi-*/ W .-.' .f -r ,-, #.*^ -*^ T V4 -*****-W v*Sr*W *i,', !1 1 ,- a .n u.;: eoay e t th e le v e a t end ed l*,<*^n L.`*l*'U W '* 1 -k/-- 't -^ V ii probloas, actin^ alone or uitli ci amento ,,.d V.!, iA.*'* o C 4J,..; ; . - v ^ .*. ,y\ .j * 1 .*. W-.*. v~>- l o . w** i^ * / i* ? j-^ ^ v \ ^ " *> > 'f t * A 1* * \ - - j * t ..#*. i* ' * .4 ** t-h-;/jL.s * * c ^j, w j . w v U-**v.* . h a i m 0 --- u O w w j .v ^ U < m * *-+-.%j .*. > , -# aa_'.voprieViio p o in t a t v ie a CO tacl-clo th e ov er p rca o n t vwi0** . ej r*<'1 ^ X ;to n n i a h o ip r u i i n Cantaro'7 ano 1* .S VS -< ** "* t , d * - y v y w V *-. T ' *> 1 - *h ^ 'wv< LO d i n . t * th o cena i' th o s ta tc n c n ta oro c o n tV o v o ro la l; Quc-tC "hlthou^h a nni.l r r ly irido diX reronco i n in d i.v id u a l e un caroto In unil'o m crcups cd eacporiroatnl cciir.isls, it is y c r k n ; tari, ss pointcd cut ty I-linot, tifer io a cenaleicnt quantitative rclc-tionship botueen th siaouat ex' load and the latansity e" ita c'ii'ect upon single tissucs, cuci* a bocd celle, uscio, ateotinn etrita, etc., no cucia vcriability of responso bolng cbncrvcd as cecina won te intact orgaalsa is exposed to Icn-d. /.a ciao succosto, tho individuai diitt'crcnca in otaspcctibility to load poiconins io tlicrodcro 2>robnbly duo lar^oly to variationo ivi lactoro which inTlucnco tho c-csunt et Icad to vltLch tho tlcnuca aro c;;pcccd rathox* then to variatiosan in j<g 001S194 -13- the doprco of resistance of the tissues* Thaoo include factors influencing cboorptioa, storace, rrobilination and excretion (lot, alcolici, constipation, malnutrition, acuta and chronic infections, trau.ru, renal, vascular, and haptic disease, vitamin deficiencies, crups, cucii as iodides, end acid-fcrating substances and ell:alleo). Thus, acuta symptom of plurfoisa nay follow injury (Slrofflobothari), pneumonia or influenza (Chic), clccholisrc (Oliver ** V.-"' ' V T 'y i * i renal disease (Edsall; Oliver), etc. As stated by Aub and his asnceic.tcc, Imunity is always rclativo and nay be broken c o m by covered 'actors which influence tea eenaral nliysic.nl condition. Then, too, local tissue dur.upo m y render those tissues more susceptible to the tonic action of lead, 0 .3 ., renal, vascular, or hepatic disease and ar.euda (komxlopoietic arenas)." End cf quote / i l i a use of chelating agents in the diagnosis o f chronic le a d p o is e nine has brought to the attention of those interested the fact th a t h e a lth y you:*c a d u lts in cities not exposed to lead at their jobs excrete 0 . 5 rnppn/X* of lo a d after a ulnplo dosa of Calia SD'fA of 3 - 5 intravenously. Reported b lo o d lends iz n / In clu d ed in possible lead rich to the healthy U.8. m l c in a Pb usinq; in d u s tr y ue have learned that cigarette cmofccrs have a slightly higher blood le a d than do non cigarette nnohers. In addition, if he drinks beer ho vlll ta k e in . 1 apa Pb/Li of bur -- if vino from .0 3 to .S o u p s P b /Li -- a p r c b lc a nora serious for European b o m vorhers than xaoofc U.S. workers. Eot/ever .thsso p o in ts e r e pressed to urea that t e e problem of control of dijr.10.plu3 lead exposure bo considered not as tliat of ono isolated source but r a tlie r a s e r i e s i n view of the widespread presence of Zb in nature and its ubiquitous, tint is vanted is to consider the total Pb dose the body is expected to handle ^Xru H 001S195 -i'-f" fhiic the raaiberc a ? individuals H w m to to suffering vith suet disease . .. . .. great, assccssant of the effect of snail Ci o of lead on pntoiute vita cc.rtr.ln diseases underlines tho necessity of evaluating the interaction of lord of brother disease entity with a quite (?) separate etiology. For cecnrylc, I have chosen 2 diseases First -- because Iced destroys red blood cello it Imo occurred to esq that patients with sickle cell trait (thought to ho yoootic- inhoritanee duo to inrtberleso years of closure to the malaria ginoinedua} right net to more vulnerable to load. I have seen one such ease hut vac net able to nuke certsin of the quantity of Job related lead and hence ...(unclear tent) certain of lend as the reason for tho aarhcdly decreased red blood call count. In Juno l$ C k 2 veil studied eases voro reported -- two Kudnuosa verkers vith sickle call trait suffered severe honolytic anemia as a direct result of lend exposure. fuch a lead deserves further study. Cirrhosis of the liver both free: excess alcohol intalce and disturbance in iron excretion is the second disease. ntudiC3 of the natal content of such livers chrr an excess of lead over that found in livers not so effected, butt ot al have studied this problem and*report that one third of alcoholics vith cirrhosis store iron and present a ratal pattern oirailnr to that in haecohrcxotosio. T:.icy speculate as follows, quota "Does lead, in response to iron otixrage, have an insidious and latent offset on hepatic colls, affecting their ability to excreta iron?" It'd of quote. Since alcoholic cirrhosis is not a reuse disease, tho influence of snail .doses of lead acting in combination vith iron or another metal deserves further study. Finally, is .cro any evidence that lead accumulation influences life expectation or is responsible for an recess mortality of diseases encountered in adult life? Contarow and 2ruxpor havo collected human data end U 0019196 -15 era,cal evidence np to end while tho fetcr^rotaticn/ conclusions of available studies varies, it deea appear that lead accumulates with age. . Hero recently Tipton, Schroedor and Balcssa havo shown that lead in h e n a tissues increases with advancing years. Schrocder has'shewn that in a carefully controlled lood-iroo envireuxent, adco and rata foci lead occuuulato the ratal. In addition, life cyan was shortened when tho lead in tho ctrll caicisl tissues vao in tho concentration rang currently found in Ivar-ana. Cueh observations might bo repeated and extended. Turning to knowledge of h u m n licence, tho occurrence of nop:re:;elcrooio related to lead is important. Tho Australian vorlc of Jlondersoa (l955~lyp7) in irprcooivo. Ho delineated a distinctive cliuicopathaloclc renal entity in which increaso in lead in bone and/or hifltory of childlxood..lead poisoning v-os documented. Older literature is pro and con the point that lead camoc rural disease, but tho majority of investigators believe that cither r.n acute episode of .lead poisoning followed by freedom fre:a verb exposure to lead or repeated lover level exposures nay bo responsible for nephrosclerosis. Host * *- convincing lo tho vorlc of Lana and hi colleaguca Xzncvn to ninny of you, vi*o^po^rvc-cL v-t onto Syrpsosiua on lend, held in Cincinnati in lc>3 end ct the International Congress in Madrid that caao year. Briefly, the* Manchester croup presents data to show that lead workers have an excess mortality from renal (license end cerebrovascular disecso and at an earlier ago than do cover cades in tho United Kingdom. - Lons m h o s in hie veil-chosen words tho points X raised earlier, regarding the hnuard to tho health and longevity of tho vorkorr who absorbs lead but Is not ill; Cue nan who is a "bit below par,v who lias boccrxs slowly end insidiously poisoned with lead but shows none of those acute manifestations, rarely goes to his doctor. Does this natter? This slightly poisoned nan io -16- ablo year after year to carry on with hia verb. lucre is apparently little wrong with hla. Ho complains of nothing and ho continues to do his Job. I aaitaln that it docs sbtter, that a substantial proportion of these ren aro being darnaged, and that freen thin croup ease those who, Inter on, chow evidence of this dnrsago uad In c o m eases die before they should. I believe that from this croup c a m those canon of chronic nopxrtis due to lead, as well va a nusber of eases of celebrai fcemrrbaco. Lot r.o pull together this review. Kanspscificity of sign and cycpteci, delayed diacnosablo fianaco because of the body*a incredible uorgin of safety, action of nore than one insult active like lead or with lead reaui.fe'" sophisticated attention to the potential effect of lew doses of lead -- in r.ue'i the can manner as low levels of ionising radiation have been otudlod cinee -ifa? use of atoraic energy for military purposes in 19^5 1 -----* * bw..w.iv I have reviewed several groups designated cs special for tho purpose: of this meting* lot tea end with what I with O C;.t this ccoting so ,*: . V li needed change in concepts. There Eust bo a departure in thinldng frea the present U.3. attitude taut prevention of occupational disease io tho only requirement of those responsible fertile use of ouch tonic agent as lead. Prevention of diagnocablc Fo polo in healthy tsalo workers is important but not enough in our society. There is a wealth of knowledge of the biologic effects of X*b and its ccnpoundo at hand. t'itla tho exception of SjUiry's reports that oaall ejaounts of Pb proenoto growth in plants and lower f o r m of nnlrc.1 life, all data point to Fo effect an harmful..,.. The body's ability to repair cUunagOj Its incrodibUy large reserve, the non-specificitj of its'responses help explain tho fact that tho questions raised by Professor 17- h'hat action can reasonably lx? proposed? Veil designed prospective studios cf ouch special populations ns I hava. briefly described here should help establish hcv lor and at what low lvale can those in such identified groups tolerate the extra burden of Fo In air, water, coil, food -- very different fren quantities of Fb that an average healthy 70 IdLlo `ran can handle. Cell cultura studies with isotopes cf lead or stable lead compounds co they occur in 20th ccntvtry urban air should give those in authority a fooling for how rcuch toxic Fb effect specific croons can tolerate without rsoasurablQ awage leading to less of function. Bolder attenpto to study the effect of multiple factors acting with Fb on an organ or system must bo roda. For example, the effect on iron efficient young animals end adult anmalo with a source of chronic blood loss given varying amounts of lord right cant light cn some of the clinical points I have made, ittension cf studies such as these cf Byers, Smith and our study at 14.1.7. among others, relating mental retardation and psychic distruboncco in children with" ness'arabio excess load, stores both with and without overt Fb polo will be helpful. Certainly the sad populations of hospitals for retarded children provide an opportunity to assess tho quantity of stored lead with accurate data, on lead intslto. As ability to study genetic defects increase such mentally retarded children can bo studied with a view to seeing what, if any role, can be assigned to the insult of man-made lead stores. /ethers will discuss measures to reduce tho amount of Fb in air, coil, and voter j Finally, I want to quote from Bradford Hill's Presidential Address at tho recent founding of the Section of Occupational Kcdiclno of the Keys.! Cceicty. The Title of His address was The Environment and Disease} Association or Causation. 1 quote . , K\ 0019199 ; --13-- "Gur observations reveal an association between two variables, perfectly clear-cut an! baycad what va would core to attribute to the play of cliance. What aspects of that association should vo especially consider before deciding that the most likely interpretation of it is causation?" Prof. Kill then discusses the following aspects - strength of association, consistency, specificity, the temporal relationship of the association, dosc- rosponoo curve, plausibility from tho biological standpoint, coherence with , generally known facts, experimental evidence, end Judgement by analogy (vising rubella experience to suggest one could agree that another viral disease in pregnancy night be hamful). /hill then discusses testa of significance and I quote briefly from these paragraphs: "Between the two world wars thero v m a strong case for emphasising S to tho clinician and other research workers tho ltsporfcevaco of not overlooking the offocts of the play of chance upon their data. Perhaps too often generalities wore baaed upon two men and a laboratory dog vhilo tho treatment of choice was deduced from a difference between two bodfuls of patients and might easily have no true meaning. It was therefore a useful corrective for statisticians to stress, and to teach tho need for, tests of significance. I 'wonder whether tho pendulum has not swung too far -- not only with tho attentive pupils but even with tho statisticians themaolvoo. To decline to draw conclusions vitheui standard errors can surely bo Just as silly? fortunately I boliova ve have not yet cone so far as our friends in tho U.G.A. whore, I era told, cocci editors of Journals will return an article ,. i because tests of significance have not been applied.//  19- Professor Hill ends his address with a section entitled The Cnee for Action: ''Finally, in panning from association to c(mention I tolleve in 'real life' wo shall h a w to consider vhnt flown from that decision. On scientific grounds we should do no ouch thing. Tha evidence is there to ho judged on its r<crit3 and the judgment (in that cense) Ghould ho utterly Independent of vhat hango upon It - or who hangs hacausa of it* But in another and more practical sense vo may surely ask vhat is involved in our decision. On fair evidonco ve (sight take action on vhat appears to ho an occupational knoard, c.g*, vo night change from a probably carcinogenic oil to a non-carcinogenic oil in a limited environment and without tco nruch injustice if wo ore wrong. But we should need very strong evidence before wo nado people b u m a fuel in their homes that they do net liko or atop rooking the cigarettes and eating the fats and sugar that they do like. In asking for w r y strong evidence I would, however, repeat emphatically that this does not imply crossing every *t*. end swords with every critic, before we act. ' . All scientific work is incomplete - whether it bo observational cr experimental. All scientific vork is liable to be upset or modified by advancing knowledge. That doo ermot confer upon us a freedom to ignore the knowledge wo already have, or to postpone the action that it appears to demand at a given time." . . ' I cannot Improve on these quotations as satisfying support of my own view of cur obligation in the prevention of man-made lead damage, and I look forward to our afternoon session on Control of load. Pollution.- ; K f 0 0 19 2 0 i . . . ; -