Document x1Bm7p4kex81OoMNbeZmDx9rE

? *oto CAiLL THOMPSON 2/21/66 Dear Jira, Concernin'" hr. ife.- :.;; 'r, paper which was sent you on February l'*-, we have now transcribed this and recoynisiny that the photostat sent you was very 'difficult to read, we are now enclosing a carbon of the paper as retyped. Koto that the material in brackets was material that she had crossed out in her original. HILL AND KNOWLTON. INC 150 Fast *42ml Street New York, N. Y. 10017 OXtord 7-5l>00 K\ 0019182 **-./ .LV/ KSJ velecuo opportunity to review vitli you certain available data and uiucnsvc-rcd questions in tho study of load effect free tho viewpoint -- vbich la niao -- cf a physician 'interacted in clinical preventive aedieino in po:unul crl 1::. tee specific diagnostic end therapeutic problems posed by a cinplc patient, description of ay usspc of teres in this paper will bo useful, live words "tonic effect" connote load-caused cheapo resulting in no dotcatciblo densipo or ixnnt. v.aea etet tie lead-pceducod effect cannot bo tolerated cr handled without pcc-duoin." abnormal function. It is necessary to copiesisa that no harmful effect of lead ia unique . . .... %* -t * .. '.- '-> ..y V/ **,-. - -. ^.ts<* . * - U*l*f >** v`k-,*v T ^ 0<a> * .* >--"1 ... dUl--W V-JpV^ .*-- .*. /v e~ ^ .,-, -.. *>.t ^ <!-> .* U drop cf a ripht-luxndod painter d.ose left wrist is trwffcctcd. dais acr-c^ccificity of lucl intori cation tceans that identification of lev level daunqo requires a ecnbinaticii of cpidcaiolopic evidence, astute clinical cbservavlcn to rale cut other ctiolcpiea topother with old and new e:pcrincntal evidence critically judped for consistency and repeatability. Another fundamental cousidC`ro.tion that vciphs heavily in this uiccunoioa is the liheliheed that lead in the body at levels considered frees Industried, ouparicnce to be harsaleps can act with other factors to inroduco dresape. If win be true* in Jwiping vfcat essouat of load is hornless for an individual cr a population, etas insults rndural cr ssxrrrxdo crash bo assessed, (diehard Pell in dnpland and divccdoro Hatch In this country havo urged that those rospc:r;iblo for establishing tolerancc-limito, techie tho difficult problem of vccuurirp the uululqlo factors that nay influence tho effect cf enviromvntal honoris.} K 0019183 N22205.01 -2- JL effects of lead ere manifold. These of special interest vhat X have to present are as follows: First,the action or lead in destroying RBC I HeedS--------- colls) is veil recognised and illustrates too fro fuuHcvsntals Just lv..,,a to -- the nonspecific!ty cf such an effect, i.c., the sonny erases cl oh destruction. Further, the fcseurd to the tody of chert supply cl re- bleed lie if, for cvcrplo, there is chronic bleed loss frees another corse ex: is. trv.ct bleeding from a peptic ulcer illustrates the prcblcn of mere than ere stop iHiuencing the pathologic effect. The bchavicr of lead in foHerlep leiusj to the ehoXetea and its ncbili cation therofTaa by such liholy cvor.tr; pregnancy turd ageing (periods of starvation) is a cceoad veil cotuhlichud soihility pcrtir.ent to t'llo discussion. Thirdly, cf x>otential irgortvr.co is ition of lead in an ergon ca it does in the liver and in tie * c* >o dwvfc dv- pounds the CTT3 (central nervous oystese)* A fourth biological feet perhaps cf the greatest significance is the damging influence of leal certain levels ca growth and cnoyao activity. X quote from a V,";:o vending per of Lure Friberg as helpful in introducing 'this subject: /the question of sslcoral jsctabdlicra is, hcvever, cf interest (also in other connections the use of radilcactlvo isotopes thus implies tlr.t) ever, minute emouats of a Kotal -- harmless in itself -- ;.ny be of essential biological irpcrtoocQjJ "The possibility has also teen discussed vhether certain motels in ouch alnufco.cnouiJto os euro normally present in the body Eight contribute to the development of chrenic disease. Tho reason for thlo discussion is the fact that certain essential metals fora ccr.ple::es, for evsnpio iron end cobalt in the porphyria chelates horn Clllxi, v JL Z? *CO01 OXlTlrU. c~' Kg' 001S184 < " r~~ '--* V > V>*h J\ *' '*. * fl r v' MNJ > V WaU "I --. * ^*, M ,. **mf Vj ,> .* *f ,-- **i ^.-4 s/ \ %* OC^ ^ * w.i.bXlL. T*V.% >.-< --t*. k- -i. V4.X 4 01 *^C>-L v3 fc* *-- w- ->4 , tr^wicn c &g vciLQ tl;ca crcc.ta c. ccr-iii:lc:i oiT .doricicacy c;C ^r.cttvGr# ?or cixr^lo^ e;^I r-crcury vould then <lic;:)lr..co nine cvi:^j to their elioiatios. iriLth H^zr.&z vhich ncrrrrxHy cliolrrio vith r/.U:c:*4* f*7 '~* i*7A-a'-. -%. ^*?wP>vxcl LSm rt ** '"k * ^6*0* rC*k.4-rfw*" /OW>*^JOk j*.O>*-'Xl x<*./0A. *.w**.m*a<m*?LJ*1L/?*C*j vv mwf+i<*y--Gr% A-^m..vm ^i^ v_ .*, V# V. VAj abundant in the natural vcrld in vhich son evolved, it vovtld be oinprisinj; end did not prev to dorticipc.to in ccxspotition for position in a H:C-o-iaontal evidence that lead iscy interfere with cellular nrnscssos uoleeulor is cited by Westerner., Jensen et al in an article published ays eye that lead produces rdtocherdried aoiniiolcsio cram-- so end ribso a a. C.0 snecual yu a..- >j ...inw 4. *u.*v*e co Ox-^er as a ui.oro o_* ..y cm :t cf old end now data Press tlio literature end ry cliisicol ceryoricnoo. -r to present thooo data let us ogre for the latent-that ctudy of lerrc offset ccy to valuable. * *oao con cite sensal leu.':cc.rl Ut'O'po k .>o4 Ginc;ie laargo dose; the sens is true of icnininy rediatico.. VU C< to clonents Issrylliisa can result in chronic lcn^ lastiiic diseas e tsv'fi frera cute dose causing easily diagnosis (cic) `bcryliairi poiscnlnp end iltei e doses so lew tliat no diasnoseblo dicoaso is produced at the tdrn. Ihlz is only an cascade, Isut other laochaaicaa of t>IW U4.0.4 co conesocreu.. lizila thsra can bo nothiac definitiva said at .tills ncaeut, it vould bo ylisins if Iced did not prove to participate in competition for position in KG' 0019185 *vNi<*r-->y* r* ? r*.^ ^ ** 'l-Vfvv* rs-."' * f *v ' ,-. U*iiK*.a -- *vh (4. ' * t--*'* iy X <h >*y v<*.cifci, > <. * '*' -- c Jv-.* vO - "}** "' "T ?* X t"% "* < **><*? (* <***< "*%*' >"V - >% >- -- *n -** *? V> *"V> -> * <r ? > '-:* "J -. ... *_/ - -- - ^ UaV S* 4 v *t *u*W i*V V VAi JL j^J* Vk t4* *- Im V J* *fc \j* *** * *> W Uv. c^lv-1, it is iiholy *'?> *% 4tU>W Wv.'wii ^ *? J-v~ 4 v^-i* a. ,j .. . '**.'' / <. . .a. y *.T *. -- f- - .-** i - >c. .v **-'*-'** o T v*k*" '**--* * >' - ,* --o v* v C*>w , v# < *w * w y w "1 ?* " *-f* " f** f .*> * * ,* *f ,'x ,*.''*# *yt4u Wjk^".*., u >*vv< t* vjv4 * w aU*. -> w ^^ 0` ' - t ,'{**,-,.-* - * -.' * k-4 _'-'.* i. W-^-y*s# a,*-? **'S^*|~* /^.VA*yi "t J-**'-* VA ,-. -ky./-x "J J? /. f"S (?1 ^V^P. V v'! "** I*. .'-> t*. j >* * * *-? > *1 Mki 7 till J*.4^. >W. fc-> iW.VO tiiJk ^UVklC/44^1* ~ _'** - * / 'Eoi'i'cvin.s Dt, Alica ISisailtcn'r; 'c::prcssica in rcforriiic to r.-*ccc-ny :,s :'.:rinw^ X voat to uiocusa tlxca tliLu ooccxal c-.'ot;p ca ti:a i*irct ;;roic? ~xroolo to dccxx^in" lead cTfoct. Fclloyias is a pertinent quotation -ror-i ly3t ccitioa of Xrt--trlnl border-,lo^r: I quota "XLxro is iuccntrovcrtiolo cvidonca, toth from onirrl c;:pcri:r.ai;ct cuxi from otoorvatious ca hvtsan toinpo, that lead lino or* injuricuo aetion on m Ctx-w colls of loth sexes end that in addition it pastes from the viaier-.-! W>> W Wk>Jk V/AWW UUiM MA la/S>k,i WS><V/'*t*k l MS< 4>k ^ '^ y s/ -- -/ vt "'* .... ............* ',--* . > r*.1* I V>< UU'iXW.i W4W<VlwU/ trenea vho veri in load inCustrius^ each ,. % >rs ,s .x a*. ^ ,-v, j>*^ ^'WV'vAy t''*-*!. O'vi **--.W* Sh Umw r-,*v *> ^ T i* , ^ * .^. , ....a ^ diCW'kl u4i -i^-C<A. __' ^ f. . *> tioa aad tide action was noted hy t;cdicc-d ooservors r.-o; L- 0--.. tiro, Z:o usually accepted theory as to the cola of action is that land hills tlia fetus either 'ey its effect on the earns cell or through the mternal tlood and that cjypuloioa of t!ie fetus follous uit'a cr vitl:out u directly otlsailatias effect of lead on the uterir.o r.usculx;turs. Halt loll, however, coaclirlcs from ills ctudioa on the action of lead on raUionant colls, that lead first injuries the chorionic epithelium and thtus indiroctly injuries the fotiu; end deeds to its cccpulsloa, Evidence of the injury to the rale cores--coll veu first c.dd\:ced ty Constantin Paul (ho3) in l3m0, and a nusaber of X'reneh authors have since confirmed his statement on to the abnormal prevalence of abortion HE 0019186 l stillbirth in the marital history cf male load vorhors (fardioii can: '-yro eyo, BonoUi. owurg j..yj * Pumps mo reuse u :' ~a'w-^ ctr^-y .a. * -- b J <s t~*-.<*.!. ^ VA V%* t-*--. A - '<*/ J-A 4 Vi-^ ^ yj *<-.-% * -`- ! -* /V~^ '-V*,-0 ? .-..* 1\*/- *>/Vii.Wii>VW .4. 4* .* vWt *>>i ``Pm.-- cc . .-<v .- r*4 VA A J ;yi.:A s<ou*ii %/J. <S >--*A*V "'"V /' "** --'. %.> /' -*>- ^ --* -- * Vi '* " * *' .* ' ` V*/* * *V\ } **l Oa *p * **...-^ *.4 C.j u 4-* *- ^ ---* u> <.j`*` '*Ji~ 1 ***,*,-<*^ ,-, ^*>4 /*\-*^ /*V *'r`V'"'.0 ' *** ^ **-. *! -.-"..h *.'4**w WW4V>4^ W-4. W VV M.\_i*44 v-|.--*> . <k^4k*4M(^ W h-- ^' * .4 "!* " ?> t '*" ' "* -' * } W' A*4 .?.|r*.j cords cf voi-lsaca, exceed to lead in Japanese storage-bahtcry plants, th -the histories of these vorhing in non-load occupations. "she orilo smrriaces constituted 2*>.7 per cent for the lead group, and on.ly lJr.S per cent for the non-lead croup; the percentage of pregnancies ending prematurely or in stillbirth vas 3.2 for the lead croup curl 0.2 for the control croup, /the infant mortality rate vas v.2 per cent for the former and 19* per cent for tl:e lattorry" /bh.ilo there are contradictory reports as to the damage to mile gem celli in causing sterility and in transmitting lead drcr.ee to the fetus, the nature is cvdte clear on tins element's harm to the fcrsalo reproductive ernj 1 passage from Cantarov and Iruaper sumar.lscs the ^/d-.a-esoively couvincinj7 data on the harmful effect of lead 'to female reproduction: 1 proto "`1:0 passage of lead through the placenta into the fetal tissues... less been demonstrated repeatedly...If born alive,' the child frequently cr.crs evidence cf the deleterious effects of lead escorted during the period of intrauterine development. It is often veal; and usdersitad, and"there is & high incidence cf epilepsy, muscular opassss, convulsions, a.iU o uhor nervous diotui'bar.ccs, idiocy and imbecility (Biondi; Mcillesc; It'endergast). /p&l roported tluxt dentition van delayed in QOfj of the offspring of Indian vesaon living in a cnolter village/7 According to KB' 0018187 .k U y X*4 .* V It *-Oi **, v C*-- X ^ W-.--0 Cv'vT/'* -- ** Sr-i-'.W * ^ *> '*. ^-*.^4* V4. W M .4. .tA4jk *M *4 44aXC4 COli s-~4AV Cv ^ V 4.*A -*. '.**..* W-W icacrcecphaly, vith a sqmre-chcpcd bend vhich developed olculy; this ccr/iiticn vao not seccripsniad by imbecility. About 7-ip of a group of 7? ouch children in thin village hod oithcr rancrccophaly or conanuLsiono or both, and tso mortality vao 50o. /in this instance the possibility of abaoyption of lend after birth aunt bo considered, porticulnrly since significant quantities of lead r.y bo present in the nsthor;o ** " *1 * - i "T'f" ** v t i**? i'' *4*j U'v a W V`t.4*^ t 4 * *'*- , "}*) *fV-* M-v v **.'*.^~` hOUi*4*<w v *aa..w v--a-y ^ V-* v**'^ ip.-* pi. # W l/*ww. i ifc44 V* 4/4m # d Wt.* V *.*4^.0P. Ik.'. 44 * v v4 44 W >4 V v v w| ^ 4^4<Mf4 iy\y d 4. vb* vS. v^> ^^ m* k.w. >. .*<4*^v. l^w*Lt-W <+ V4> 4lMiU<k44 4>W<4V'<W d-O.U t 1^. ^UV> * Va ,* a +* ** C kSO. ^ '--a.v W V'./A Xwi.4V'.m 4<.W^V^WW *<--v.^. w >k> wb** m'vWiVAt Esoro can bo little doubt tlrvt caesura ci ,--r .* foot vc?oa fertility, tho ccuroo of propnancy end the dovolcpa;oj'.t of t4<> . W ( W # /po heard yeoterdey of an cnocy by S. 0. Cill'iHan entitled ''horan Cu -L U ^ bysfonic Load Poisoning" elaborates wi'th faccinatinp evidence the author r.t tlsat Grooco and Peso foil chiefly because of lead in coohery and in id thesis is th.at when, about 150 33.C., relaxed rules alleged tiio ;.rives to orr nh *,,f.ne they failed to reproduce and the aristocracy xras decinatcd.7 d/ds is a coed place to seat!on that root authors vho 3-ave rritten on subject are of the opinion that fexales ./react unfavorably to/ suffer :.vful effect at lerrer doses of lead than do sales. If this is true, it is orient r.ve'uinp (unclear tent)... Loll, usir.~ lead as therapy for ualipnc arts fao cd-ainuo tcede dose given intravenously as 1;0 ngn. of lead for ales and lit r.pn, for calcs. Oliver, a great student of lead poisoning. Kf 0019188 v_ otacos tl~t vovcan cars nest liable to develop poisoning botveea the ages of lo sad 23 years, earlier than is ran and after shorter exposure. 'fall studied *-. * . ...< *W !> >>. Sf b*Vk~ *P**. W*-4 UW. OtiL 4h- S.-*<4 v W i.. -.*^1 a J> .<*.! ^4 i,Wva*^* i. 4 ^ vv<f4 U> wk U U* 4*1. * * *4 V> 4."^. ,^,4 W 4. 4* V-. w -W w L>4t V*Vwi ^4 >-.>'*-VX * -i. 4 >* '--'* V * w'v4. 'W"^; *./** *^ colic. Inch observations have teen undo in c::periTsantai or therapeutic citunticns cr in industries vitknut industrial hygiene controls, due value to us at chin meeting of ouch observations is to point cue vkut lead isay do at love where its effect can to identified. Let re repent, experience with har::,f.:l ~cta ws*V*,..V. ~-s*t i--.4-^4. j/ivyo 1.ceil^ -kl.mue^ejs too critacni , ac c vmu decayd oe. -<-w> j frsr.i nnuy oue.ll doses say be qualitatively like the scare irradiate acute effect of a single or fever higher doses received over a shorter period cf tire. due second special' group ana the one about which asst data are c\u-.l;..Llc in discussion of Iced poisoning is that of the craving child. rereading field v, verb on the influence of lend cu cell-growth one is struck by the very dilute solutions of lead acetate ha found to retard growth. In the ran,,a of 1 to ICO to as little as 1 to 100,000 all very young tadpoles were hilled, whereas aero nature tadpoles survived but suffered retarded grovth in the 1 to 100,010 solutions. hell concludes from thee and many jeoro stulles that 31 quote "the arrest of growth in andsal organ! eras is strictly proportional to the capacity for, cr fever of, growth," and ho frerther writes - quota "lend is net only -retch acre tcscic to the young and prcadoiosccnt than to the adult and old throughout the vertebrate l-ingdcn but also that the effects produced by the rectal arc funeral in the young (Bell colls this serotic stuntirr-) and local in the adult." cud of quote, Shore arc a number of studies pursuing this point, fK study that should be repeated perhaps is that of Calvcry who four,! significant retardation of grovth of ralo rats at relatively low levels of lead in their diet {3 .53 pga.)'/ KZ 001S189 -0- Cf crest importance for this discussion is tho iscntnl retardation that follows not only acute load oncophslopoihy but perhaps chronic lend absorption. here arc cuotahiona from the discussion 'ey slycra, a pediatric ncurrolofist at the Lead TTyyicne Conference sponsored by the Lead Industrion osculation held `'Certainly when children die who have clinical pathological load ancepkelopnthy they die with brain stem compression. They die' vita Gloria a roepiration,, pulse rate and blood pressure, anuria, all the usual evidence of increeccd cranial pressure. I can't believe that thin don't in sense way related, to interference r-* <-.- *> 1v*K *'*- **.> ** * rv^ *1'~`r'y^ i **'a - - *- -- - *- ; *. Y .* !>-.*. v x 'm wJ^. vuw ^/...\^ ** L# JL \ >,,,*j mw -v '1* V J L ** i * ic ... 4 a themselves be impressive... .1 criminally mat interested in lend buenvao the of children who had had lead poisoaius and had been coat her,.a frovn/ho jpitxl an cured, who than turned up in rr,y ncurolo-pical clinic hccaueo they vero misbehaving in one way or another, or not learning in school. Cue hid cot the schoolroom on fire, another nice little ylrl danced around on the deed;. IJono of those children had acute fulminating encephalitis. They all hood evidence of lead poisonlns, li'to stippled colls, some increase in spinel fluid total protein, 01 syraptaos, ccprcporphyrisc in the urine. /At that time, ve didn't know about the importance of Separating them frees load, y tried, in a desultory way, to separata them, ilaybo ve weren't successful about tirdn/ lie point X am trying to make' about these children is that though none of them, at two ox* three years, had an acute encephalopathy with thoir acute into:hLcation, when they reached six or seven they showed evidence of brain injury. I thirl: that many children cot chronic encephalitis HE 0019190 n_ iron loud, os veil a03s acute. `nils group of children det-riorateo grwlvxoLly vritiiuut over having luxe. any acuta lead cnceidolitis... .2' thinh that lead dots concthing J. eat. ' end of rusto If. fata, a pediatric nein\>Xcgiet, end I have Just begun c dive-year c w.-.y j-.** w *. iv.e.n. support o* vhxc ^ec-'O^c i and cere inej-ed.g."ig nveay 0^ exxoney,* cf lead-poisoned children vith as careful an possible queuvtitabivo ossetor-ent of the Iced to ahich theso children ore cup-coed. Variation In diagnosis and regarding of childhood load poisoning frees i:roan ccarruuitios insho it ccrdda that little in kaovn of the total number of cacao of acuta intculcaticn and nothing of load absorption in <ruatitics that aay t>o:;o a rich to ucirrl rpx-vih. fere Itnovlcdso is provided by Cirri ctian ot al in.Chicago. . Ebay report that of 9,b>g canoe of accidental childhood poisoning betveen 19?P-lpol, hip or h.7 per ecu rare eases of ecuto lead poxconing, and of the 5 deaths, 67 or 7p per cent voro due to load. Colleagues in Boston report 5 to 25 acute cates per poor; Baltimore figures (tlvrouyh the courtesy of Hr. Baotjer) -- in this city there is on cneollont doto a tion program -- arc double this number, reaching over &> in cone years, averaging 57* During acute lead poisoning la childhood tfcoro is reliable evidence that hiducy function is disturbed, thilo the blood super remains normal, there is readily detected glycosuria, and renal tubular dqaaco hen boon further demonstrated by rainoaciduria end phoaphatxnria. In fatal cases acidophilic inclusion 'bodies in the hidaeys arc recognised as a potholcglc load effect. These findings :ray ariso from other causes end identification of the lead caesura no causative is caeetinus difficult, Vhila Upper van unable to confira the findings in hnesnehusotto, HB 0018191 *i - CiWw --.vir'wi V.irf** ** *.P. I* -- .4.0 -* '`'Vi.* ****** O*.*'-*.# 0^i.1,C,^...^-*.- V,,'V-'.1 "'< >* V * ^-' L i V.' V'* v 0*- "<>* i'X V*h i.* wJ wL vf ' vJ --4. i. .... w< i *JC<W^V>J WiiU ^'~<OsW* ** .* *. -> ..'-d. ,./.J........ .e. y. Civvw.*^^ .> t.^.^C.Uwi-OICiJOCC'Cv i:U.Lj~i.. d 0 i frj~*-\j wVi^ Jfci * wCOl(,i**l#WU ^ j.O .**1- *^' S. W-vf *l#'w'Afc.'*2/r V*>>^ d.ef bsiS C/.Xm> 0-fc useful.]? Xf ua oocas likely froia the accusuluted and proving cvidcr.co, ...r.. /.. ..ranue is uoro vul&ars&la to leal than adult tissue, far scalier dor;on t'.:c: these required to produce diagnocnifUs lead poisoning la a healthy nb.dt re .1c .... va\Xi bhdr -- w a.l *w <XA i> * x.ti i 4v^i>.00-*> Cv.b u_0 lij w >_. ......................- ? .. *. -.*. e, .. * *u',, ?.. ^ j * s**,*'~ / \ >-.*. uv OUlX d.4-* v '* *. . r -. * Vut* Xvw>C/ri * * v *' s'* * ' 'i A. Lj U>c.*---d- '- ^ r .. J. u. ^ .>., . . chick cry dissolve ingested lead r.oun that absorption, vlistrituliou and stere,-. > of io-d ea-c; not aa veil coveraod in later lire -- added rc-n.toao that ceallcr c-eor.'tt cl* lead pose greater riots in children. Crovi::^ done la ltd 11. > a.d ........ r'ii ...j . w.a.e4.ti.3 en aiil oUw *..re eone^ vr^.'**ee^ec^.*.;a.e i...eDeiXt..^ a....... ..re w.'wrl 3ed.Ovwi^.e.. --...... ,.s^... .....' a. i*..i. ^u vr.e r.e ^,i.^ c^o . ww. . l<.o a.'... _ e .',,. dv.tcericaticn ii lead injected or in'i-.aled ic added at a tine O* tj i-wh-etiil * *o-' Oj . lean drer done {?). Bocaueo cf the daainaaco oB ;^y clinical c:cpce*icnce,, X Irive been Interceded in considering vlmt effect lead absorption vitliout datectrn;lc evidence of poioorina rd'p.t have in the cedical events of an otlier^/iso hoaltiiy indivldtnl. dice dic..pn:;oIa cf Iced dr ::-;te is not ulvayo cany to saai;o because of tlio noncpccifioity of c;r.ptcr.a# oivpcs, laboratory findinge^ ccQuelac that olgat all be related to other otlolcciee. Proa tills line of thinking 2 coaelude tiiat an apporcntly veil lead worker ccnatitutcc a third cpecicd ^pcoup for the purpeae of this session. Dr. ICehoe'e ole pent .studies rc fundresentni to Idle points X raise. '.'1th cn turceasured quantity of Iced stored in ckelcton and livor> vlth lecccr cscounts In ether parts of his body, cue's a., individual is in cccno jeopardy, a point Dr. K node yes and my not b-o ride KE" 0019192 '' ' ? {-.n Ss'Jm 'w* V ' C* -s v y. * t*v- ^ A. ,y^ f.* -`, f-s , A " '' ''* \ <"*' r-^ ' *, * * \i* * V/ w* fc# V i'*`w4 A V * - * ^U* * *. v^jf - u:;;:v:. w-- w L*.O* i>Vm W Wwt/fUu^ wUwti V 14*h '**. *.# w -- e* * ./ V A cc f*"V.`>J; *? *: ` * * '." /**'*- >--. *tn-" .--'* V-f . > "T^ -sT r-1 "? *%"% * > ,, .. -. *, V-- -- ., fc. - j afc- 'jio1-- av*-^ V' -5*' V* V .' C' f ' V >w .^.W *-..> W- -Wa* W^..* *io* z.3--l ^ co i^oGVOwU c.*Tiil, X3*7 v.** *Tr V-i..W.ri, J.4-- lead in wXua vaa net very v-^-- *^-V ^ uc;-v i w'- -~*. /*, cn ~..-.v.>..'.7A*-* - r**' '' *1 ,v^ -- '* ' rt'T* TV* few ^ *^uV** V>"*"W V'iJmw h -- -/ W>4 ?-* vv- p*r,**? T-"f-"^ *T*,*> * f',`j r* IW 0 lr<w^>Uo Wu ^v^nsi W****-*4^ 1 *1 -Vk; ^c-ri *? *-> . jL.aaw-i-j-i^Vw .4 rs* **~n ****:* vv.*!-**v-'v,f ? v *''*'*' ' r- * -> "i u>Ww^.w.^,v i^v..uU'.-4.y ^ M. + i * .'. O u < W' at * 7--, *V-, v-' *' >. v? a^AJl X hy ,,Na<. ^ . r.a-.*, .7 .- *? .-. s VJ. M.CJ */ U^4 ***** C.---*- W jv *-,/ ai. * fc'Vwm','^ **> *t /-, - /T .'S ^ .*-^ < TT-V? *'\ /* *'? j- ! > n oiaS*-, aV-i. S-^> M> W.VV* Vai>i^ v<>, ^ V-V* ezryecv.-rc iz; en eno ren^o ci o.x; r``/N Jtf* VV * y'w' ***V^J,44*# -^ ^ V.a..-.*.-* *i*`',,<i*.1. < / :'-<> ^ *-- ."* V <-- - V' -a l i| 1 U4 ^-W j A UahA^vsA A m W*<4 # W to o.O. S;o vt-i^-ry --c;:w^O';:l.c:i _erica ca tu-i. cccr>aicr3 cr mc c c c j u > ccr:c:; 1r.,.Nlv>fa * ^*/*'.*''' *J /'''* ".a? *f. *) ,*X f** V*-* >> >, V-i" VA at.w>V<V ~ , r *** - - -' r\--t'`* -* W.^M -' |y' ^Vi VVv m** ** ^ *.'***<^y .'S ^ > tf 'y '..- ' *! w'"\ *C *5 r" S'"r r'^*". !r Vvs> w*A wtaC'-* ^ A* V'. vWO C:^.t ouch data roiloct a 2-criaful burden o* lead io ca^'crted *07 C;a ze..a.ver re'^A7*v o -l >*> Wdj -*m jjawabi Via ^ al. A-+-WoO taiwi V'.a'.A^*. L -- > -'-.>.X*W-W',-'. '< .! :unt3 cd lead in pans by biopsy t2ian in urlnl cf It >-H ^ *1 .`t * fS i <. V. .% * '*' *->.*>, * < VWMa +J \ * / ...... .- *---,^ . 1117 W W;A.tf-a-. ^ * (^-,4 f. *>lp VlV-^avS^ P ? V'~ ^ ' <*.''<*- f , . a* V-MW > S> Vw,,-4-- V w*<V<V/lA p>-W V-* <W M vd*. 0MI.I O W V -l# *.*'^ Wja * *WT*-- ailfcaW A^v- --vAla * *-*w ^ Ja* i V** M Vn*.-.i> A >a 'lyt S-a.* yi^ luccd and t!i reticulocyte count elevated oi^estins oceolerntcd red cell jtructicn (unclear te:ct}... /(Mdiouc^ these nea ire not ill cuer. Iced :crpticn :rccao toidc lead effect.. Hy clinical prophecy hca ccas true in coral caoeo in ny on*n cupcrlcnco^J In r.y clinical cnpcrienco tiie follotrinp ia ->,7 <rv `d Cacco of peptic ulcer, not held related to verb ndth lord, proved KE 0019193 . ' ' wO. V J ^ k--CiTvw.^*J * V-iv^JOii W*W +**J* *-wli r>...-- %m mim'mm *m m`.m~ ~ * '- . ' - . j ,a 1 '*!,% " . \ ^ ,*/* ,* '*>.% \ . ** *"> ' fT ' f "S ` * mm **** .* w V-'.i.1-- Mb * >4 WV*. W ^ V.i>V< k/'w'tv .*. < Uw j m * <*# WV.V..** Ww V>' "* * N w '.. -V .* mmm W VUTQC^C 'yW.^yC^ 3.^ id. C '*J V"Ia.',.'Id 0 ki i.,1* tT^ J *U. t* if. '**.'..* ^ -.,/' _. vd.v< '-- * ,,.* *4 . mm 'mm mi* . v* \ X *<* wC ** "** O' k* Cl.> ^ km+ VV*4*<%>-` SpA. KM ^ *U* V V^' 'mm -* l-.. W *'V/ Am-lrn v ""* S. v--vi mtrn'mr V 0.4--^ ai. lUvoii 1*>+ WkvO C-- w V i* 0 ^<n> 1 ,Q k.*. -- W M w vV t-' . , - ^,` W -w/ On-*** (j. O. .*, m. * * * Ol it* WJ V O OtX-fcOOv C^J* XX* H.fcCfa *1 *i iiOlO. C V* U 0<i> Wa > ^ Vi `vVJ*mm} &ooo vjfxxi^j Oi-. cij cc* 0.0*0 . oiio 0*101. wt, o. c 'Oc..-j Lo ^ ....o..o_u,b ^y'* cicculr-i'd lc\v:d c.b:;or^ion cufricisnt to rc-lues horoj,IoVi:i l:i a I;o*LT&?*y :,vtic OOX OiOC i'XCtlC'ilX'-wO ': otrJ*lttCLJ x^iLoio . U W. **.W^-* ' * * -.** ' rs*m \ ''' ^ *' , - * f I '*'\*t ;v* . - .,I'>1,*'*<>,*,'1 f **-. <~ *1 ? .-' t ' l . / ^ mm. m.m-rnmmim^, .m. \ mm -wOV ^WV4a '*`w'*^'J Vj.^i.4 -VX-^ <4,*i>ww f Y4 . v >. ,...;. . , , ' V- . V*.< * V W _^V,-.-V4. K.-J.-m i*. %,A.*^` vii/ ola.'vi mCw CiJU O*.^'-* C*im ^ ^m'm. ;mm m . C' L* V V - i ;ii ^'o'olosw, acting aloaa or vith otlior iiar^i'rd ojonto vhooo s;:;:...r.^io..v; C*^ ; - - V ^ ` -4. ,< y\ | * ^ r^l ^ 44. A / y*^ 14 . 4^ 4'j '> > 4f 4 * 4*/ i 1 * Jm V~<-- v*iVv> <H-*4*k.-4. w* )/i C-U 4/Jk. s^i* w iWw*4VAVV<Mi Hi ^ l * - - - 4* O'* -- U 4 .*, #*. ,* * * .4 ** rt ,. UW<<VIV*# 4 m-*-.-mmJ U. .> _____ o;^_'..-ooric.^o r,oiat at vhiolx be tackles the over precoat \\\rxatier* in iadivih;~.l ron.vvxoo to lead esepcaara. X X*oad a holpikil pocc;op;o in Cantcrov and Ireerpcr -- of tho n catCTuer.ta arc coatVovoroial: Qi "Although a ninilnrly trldo diXPcronco in individual cuaccitibillty czrLots in uniform croups cX e:cporirontai cnilr.ials, it is iipcrtanu that, as pointed cut by PJLaot, tlxcrc is a consistent quaati titive rclevticnsi-iip between the sajouat ex' load and the intensity cP its expect upon single tissues, such as blood colls, rauscle, intestinal strips, etc., m ouch variability of response being observed as occurs when the intact organisa is exposed to leoH. /.a oho auescsto, the individual difi'crcnca in cuspoctibility to load poicordng ic therefore probably due largely to variations in factors which influence the amount cf lead to which the tienuoo are exposed rather than to variations in g 0019194 influenciu h absorption, otorches, r^bilicaticn and excretion (diet, alcohol, ccaitipation, malnutrition, acuta oriel chronic infections, imum, renal, vascular, and haptic disease, vitamin deficiencies, dries, such os iodides, end acid-fcrating substances and alkalies) gmptorcs of1 plur.bisu may follow injury ^ fcf -i vti. 4. MbV W l> .-.! y ^ influenua (Chic), alcoholism (Oliver; r.^^,,1 V-i*\ : (Rdaall; diver), etc. As stated by AySo GXld ;Jo associates, immunity is always relatives and my he broken down by several factors which influence tlxo epncral physical condition. Ikon, too, local tissue &sm~o my render those tissues acre susceptible to the tonic action of lead, e.., renal, vascular, or hepatic disease and anemia (koraxtopoietic creons)." End of quote /ike use of chelating agents in the diagnosis of chronic load poisenirq s brought to the attention of those interested the fact that healthy young ults in cities not exposed to lead at their jobs excrete 0.5 uqu/b of load ter a singlo dosa of Cal'Ia SD'fA of 3 - 5 si intravenously. Reported blood ads ir.7 Included in possible lead risk to the healthy U.S. mile in a Pb using dustry we have learned that cigarette smokers have a slightly higher blood ad than do non cigarette rxcokcrs. In addition, if ha drinks beer he will lie in .1 ryu Fb/Li of bur -- if vino from .03 to .Go apa Ib/ld -- a problem ra serious for European bom workers than raoofc U.S. workers. However thssa into ere pressed to urea that the problem of control of thauaging lead pesure bo considered not as tliat of ono isolated source but rather a series view of tire widespread presence of To in nature and its ubiquitous, tint wanted is to consider the total To doso the body is expected to handle HEt-hc-rt irreversible desaga. 0019195 0/I,r- fhile the raaiberc a? individuals known to to suffering vith suet disease Krj y.^- o --*w^ og o Z'zonw of ^.iio g xfocis oi 0wi**3^X Ct CJ of lend on patoinhs with certain diseases underlines tiro necessity of evaluating the Interaction of Iced of axother diocese entity with a quite (?) separate etiology. ?o:: cucer-plc, I hove chosen 2 diseases. First -- because lend destroys red blood ceils it lies occurred to zsa that patients with sickle cell trait (thought to to gesstic- inkoritaxice duo to numberless' years of closure to the caildria yitminodue) eight net to more vulnerable to load. I have seen one such coco but vac net able to nuke cert sin of the quantity of Job related lead and hence ...(unclear text) certain of lend as the reason for the markedly decreased red blood cell count* In lino l^Ck 2 veil studied coses wore reported -- two Sudanese verkers vith sickle cell trait suffered severe ke-.calytic anemia as a direct result of Iced exposure. Such a lead deserves further study. Cirrhosis of the liver both from excess alcohol intake and disturbance in iron excretion is the second disease. ntudiC3 of the metal content of such livers show an excess of lead over that found in livers not so effected, butt ot al have studied this problem and* report tint one third of alcoholics with cirrhosis store iron and present a metal pattern oimilsr to limit in hancohrcrrrtosio. Ihoy opcculoto as follows, quota "Does lead. In response to iron storage, have an insidious and latent effect on hepatic colls, affecting their ability to excreta iron?" Fad of quote. Since alcoholic cirrhosis is not a rare disease, the influence of snail .doses of lead acting In combination with iron or another rectal deserves further study. Finally, is .cro any evidence that lead accumulation influences life e:qpcctation or is responsible for an excess mortality of diseases encountered in adult life? Cantarow and Uruxper havo collected hureon data end C-.vj^o^r vChi. H 0019196 -15 cnir,al evidence up to 1^44 tod while tha /interpretation/ conclusions of available ctudles varies, it does appear that lead accumulates with ago. Hero recently Tipton, Schroedor and Balcssa have shown that lead in hmein tissues increases with advancing years. Schroc&er hac shewn that in a corefully controlled lood-froo envireuxant, udeo and rats fed lead accumulate the ratal. In addition, life epaa 'was shortened when tha lead in 'tho ourll cuinial tissues vaa in tho concentration range currently found in hutans. Cueh caeorvatioa; might bo repeated and extended. Turning to knowledge of htssan disease, the occurrence of uegl-uxscicrosis rotated to lead is important. Tho Austi'alian work O** Ii.O!idersoa (1955-1957) is inpressiva. Ho delineated a distinctive clinico;^tkologic renal entity in which incroano in lead in bone and/or history of childhood..lead poisesing ws documented. Older literature is pro and con the point that leal cavcoc renal disease, but the majority of investigators believe that cither r.n acute episode of .lead poisoning followed by froedca from work exposure to lead os* repeated lover level exposures way bo responsible for nephrosclerosis. Host *- cc^vincix^ lo tho vorlc of Ixmo and hie colleagues to niruiy of you, vI*0^p0^rVC-CL s.it oilO Syrpsosiua on lend held in Cincinnati in I9S3 and ct the International Congress in Madrid that cane year. Briefly, tho Manchester group presents data to show that lead workers have cca excess lacrtality frora renal (license and cerebrovascular diocese and at an earlier ago than do other wales in the United Kingdexn. Lane mhos in hie veil-chosen words the points X raised earlier, ragarJJ.ni the hasard to tho health and longevity of the workers who absorbs lead but is r.ot ill; The nan who ia a "bit below par,v who !na boccrxs slowly end insidiously poisoned with lead but shows none of theso acute nonilfcstatlons, rarely goes to his doctor. Does thin tsattcr? This slightly poisoned nan io  li able year after yoor to carry on with his work. There is apparently little wrong with hla. Ho complains of nothing end ho continue:; to do his Job. I aaiitoln that It docs natter* that a substantial proportion of these nan arc being daniacod* end that fresa thin group com these* who, later on, chov evidence of this dnciago and in com casco die before they should. I believe that from this croup cam those cocos of chronic noplxritis due to lead* as well t\a a number of casco of cerebral fcemrrhago. Lot no pull together this review. Kanspccificity of sign and cyrptoco, delayed diacnosablo danaco because of the body*a incredible nereis of safety, action of acre than one insult acting like lead or with lead rai re sophisticated attention to the potential effect of let/ doses of lead -- in much the cam manor as low levels of ionising radiation have been otuclicd cinco th use of atomic energy for military purposes in 1945. Cement; I have reviewed several groups designated cs special for the purposes of this meeting* let tee end with what I with O ti,t this mating see ns needed change in concepts. There toot to a departure in thinking from the present U.3. attitude that prevention of occupational disease io the only requirement of those responsible* fertile use of ouch tonic agents as lead. Prevention of diagnoc&blc Fb polo ir; healthy mlo workers Is important but not enough in. over society. There is a wealth of knowledge of the biologic effects of Fo and its compounds at hand. t'itli the exception of FXury'a reports that small amounts of Fb promote growth in plants and lower form of animal life* all data point to Fo effect as hoawful..,.. The body's ability to repair cUusago* Its incredibly large reserve* the non-specif of its' responses help explain the fact that the questions raised by Professor Patterson in hio recent controversial article were not raised earlier. U0018198 17- Vhat action can reosona'bly lx? proposed? Veil designed prospective studios cf ouch special populations as I ha-vn. briefly described here should help establish hcv long and at what low levels can those in such identified croups tolerate the extra burden of Fo in air, water, coil, food -- very different free* quantities of Fb that on average healthy 70 IdLlo `ran can handle. Cell culture studies with isotopes cf lead or stable lead compounds co they occur in 20th century urban air should Give those in authority a feeling for how mtch toxic Pfa effect specific croons can tolerate without neasurablQ dcarge leading to less of function. Bolder attempts to study the effect of multiple factors acting with Fb on an organ or system must bo node. For c:am$?l, the effect on iron defficicnt younc animals and adult' animals with a source of chronic blood loss given varying mounts of lord g-*'* ca.iu xi^h*. cn some o-. the clinical points X have *alo nCyOXXOicO C* r.TM - * 1s ^ f^Uv.'.d.vCI wvtVd t-h =e*>s--e cf Byers, frith and our study at F.T.7. among others, relating mental retardation and psychic distrubanccs in children with" neat'arable excess load stores both with and without overt Pb polo will be heedful. Certainly the sad populations of hospitals for retarded children provide an opportunity to assess the quantity of stored lead with accurate data on lead intalte. 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 the amount of Fu in air, coil, and votevj Finally, X want to quote from Bradford Hill's Presidential Address at the recent founding of the Section of Occupational Kediclne of the Rcynl feeiety. The Title of His address was The Environment and Disease} Association or Causation. X quote K- 00191.99 --13*. "Gur observations reveal an association between tvo variables, perfectly clcar-cut and baycod what wa would care to attribute to the play of clianeo. What aspects of that association should wo especially consider before deciding that the most likely interpretation of it is causation?" Prof. Hill then discusses the following aspects - strength of association, consistency, specificity, tha temporal relationship of the association, uocoresponoo curve, plausibility from tho biological standpoint, coherence with generally known foots, experimental evidence, end Judgement by analogy (using rubella experience to suggest one could agree that another viral disease in pregnancy night be harmful). /hill then discusses tests of significance and I quota briefly from there paragraphs: "Between tha two world worn thero vm a strong case for emphasising S to tho clinician and other research workers tho importance) 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 while the treatment of choice was deduced from a difference between tvo bodfuls of patients and might easily have no true meaning. It was therefore a useful corrective for statisticians to stress, and to teach the need for, tests of significance. I 'wonder whether tho pendulum has not swung too far -- not only with tho attentive pupils but even with the statisticians themselves. To decline to draw conclusions without standard errors can surely bo Just as silly? fortunately I believe vd have not yet cone so far as our friends in tho U.G.A. whore, I ca told, coma editors of Journals will return an article i because tests of significance have not boon applied.// KB 0019200 19' Professor Hill ado his address vith a section ntitlod The Cnee for Action: ''Finally, in panning from association to causation I believe in 'real life' v shall haw to consider vhnt flow from that decision. On scientific grotsndo v should do no ouch thing. Tho evidence is there to he judged on Its mcrit3 and the judgment (in that cense) Ghould he utterly Independent of what hangs upon It - or who hangs because of it* But in another and nor practical sons vo cay surely ask vhat is involved In our decision. Cn fair evidence vo might toko action on vhat appears to ho an occupational hazard, c.g., vo night change from a probably carcinogenic oil to a non-carcinogenic oil in a limited environment and without too much Injustice if vo are wrong. But vo should need very strong evidence before vo made people bum a fuel in their homes that they do net liko or stop smoking the cigarettes and eating the fats and sugar that they do like. Xn asking for wry strong evidence I would, however, repeat emphatically that this does not imply crossing every 1V. and overdo vith every critic, before ve act. All scientific vork is incomplete - vkethor it bo observational or experimental. All scientific vork is liable to bo upset or modified by advancing knowledge. That dooennot confer upon us a freedom to ignore tho knovlodga vo already have, or to postpone tho action that it appears to demand at a given time." X cannot Improve on those quotations os satisfying support of my own viov of cur obligation in tho prevention of man-made lead damage, and I look forward to our afternoon session on Control of Load Pollution. ; ._ KB 0019201 . ' i' ' ' .