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## Document

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# 107)11-1-260
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Sheet 107 of 198P. 2



# G3f x• v^./ " 

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DOCUXZK T REVIEW * FOR M


### fltlt/Draf t Ai rQualit y Criteri afo rLea d (Externa l Revie wDraf t#1 ) aUturn to : Projec tOffice rfo rLea d Environmenta l Criteri aan d Assessmen tOffice , U.S . 2P i MD-S 2 \ Researc h Triangl e Park , N C : ConsBcstcr/Organlzation/Addres s * Herber tL . Needlesran , M.D . Children' s Hospita l o f Pittsburg h 12 5 DeSot o Stree t Pittsburgh , P

A 1521 3 \ Chapte r No./Titl e Chapte r 1 2 and^ Appendi x1 2

RECOMMENDATION S O (1 ) Acceptabl e a s I s D (2 ) Acceptabl e afte r mine r revisio n D (3 1 Aeeeptabi e afta r majo r .•visio n O (« l Ne t aecepubl a I fye u hev * eheci.e * withe r 3 o r 4 . pleas e (pacificall y stat e reasons ) i n th a cemmant t spac e below .

Reviewer' s Signatur e Dat e 

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ORIGINA L FIL E COP Y D O NOT'REMOV E ECAC7TI C 

## uP. 3

ECA O Critique , Needlema n

Genera l Comments : Th e qualit y o f th e documen t varie s widely . Som e chapter s ar e model s o f scholarsi pan dre-flectiv e criticism , whil e other s ar e tendentious , superficia l an dnoncritical . Th e mos t egregiou s error s ar e i nth e mos t critica l chapter . Thi s i s Chapte r 12 , wher e huma nhealt heffect s ar e evaluated . Thi s discussio ninn o wa y come s u pt o th e standar do f th e ethe r chapters . I t i s neithe r fai r no r accurate . I shal l concentrat e o nthi s chapter , becaus e it s conten t i s s o vita l t o th e constructio no f a vali ddocumen t tha t wil l withstan d critica l scrutin y

an deventua l testin g i nth e courts . CHAPTE R1 2 section / pag e / par a / lin e Comment s 12.4.2/12-42/2/1 6 "Som e prospectiv e longitudina l studie s o f th e effect s o f lea do ninfant s an dyoun g childre nar e currentl y

inprogress , bu t th e result s ar e no t ye t available" . Thi s i s incorrect . Ul e hav e reporte dth e result s o f ou r prospectiv e studie s .o f prenata l exposur e a t 2 nationa l scientifi c meeting s (Societ y fo r Pediatri c Research , an d Societ y

fo r Researc hinChil d Development) . Bot h wer e reporte dinearl y 198 3 befor e th e EP A deadline . Bot ho f thes e studie s wer e peer-reviewed , an dth e abstract s wer e publishe d i na referee djournal . Pediatri c Researc h 17:179a , 1983 ; 17:1281a , 1983 . Thes e studie s showe da dose-dependen t relationshi p betwee nlea d inumbilica l cor d bloo d an dmino r congenita l anomalies , an dlate r developmenta l statu s in infants , controllin g fo r relevan t cova r i ate s . The y ar e th e firs t publication s inth e huma n literatur e o nth e subjec t an dshoul d b e cite d here . Th e congenita l anomalie s pape r i s in pness , JAMA . 12.4.2.1.2/12-48 / Th e studie s o f E.Bake r e t a l o nth e psychiatri c symptom s o f lea dworker s a t lo w dose^Act a Psychiatric a Scandinavia , 1982 ) ar e no t mentione d inthi s section . 12.4.2. 2 Thi s sectio ni s inadaequat e i nit s discussio no f th e definitio no f encephalopathy . Olde r definition s o f encephalopath y implie dbrai nedem a an d hemorraoe . Thes e findino s wer e associate dwit h

- 1 - VP. 4

ECA D C r i 1 1 qu e , Needlema n

elevation s o f bloo dlea dlevel s abov e 88ug/dl . I f lea dexposur e a t lowe r dos e result s i ndecrease d cognitiv e o r behaviora l adaptation , th e orga n whic hmediate s thi s deleteriou s chang e mus t "b e th e brain . Th e change s inbrai nanatomy whic h accompan y

thes e alteration s ar e pathological , eve ni f no t accompanie db y change s foun de nligh t microscopy . Moder npathologist s hav e shifte d thei r locu s o f investigatio ndow nfro m change s a t leve l o f ligh t microscop y t o thos e identifiabl e onl y b y electro nmicroscop y o r chemica l techniques . A

moder ntreatmen t o f thi s issu e require s a moder ndefinitio no f encep a 1 op a thy , congruen t wit hth e facts . Al l change s inbrai n functio nnecessaril y impl y

brai ndisorder , an d pathologica l change s of ' th e brai na t an y leve l ar e necessaril y th e groun dsubstanc e o f encephalopathy . 12.4.2.2.2.1/12-60/12 / 2 2 I t i s unscientifi c t o assig na 1 owe r leve l t o th e bloo dlead s inBurde' s stud y sampl e o nth e basi s o f Betts ' pape r fo r thi s reason ! Th e diagnosi s o f lea dline s varie s widel y amon g individual s an d institutions . On e canno t validl y assig na bloo d valu e t o Burde' s subject s withou t comparin g film s fro m bot hsample s t o calibrat e th e relativ e sensitivit y

o f eac hgroup' s diagnosti c criteria . Thi s criticism , i t wil l b e noted , ha s bee n applie db y

author s o f th e draf t documen t t o th e us e o f othe r non-standardize d instrument s i n othe r part s o f th e document . 12.4.2.2.2.1 / 

### 12-62/ 2 Th e revie w

o f Ernhart' s secon dpape r shoul o stat e tha t afte r multivariat e contro l o f covariates , significan t difference s favorin g th e low lea d grou pwer e foun de n4 o f 5 subtest s o f th e McCarth y

Scales . I t i s obligator y tha t th e Criteri a Documen t rende r a veridica l revie w o f th e primar y

papers , an dno t rel y o nth e conclusion s o f th e neurobehaviora l parrel , wh o wer e no t a par t o f th e tota l discussio no f tni s subject . 

### 12.4.2.2.2.1 / 12-64/ 2 / 8 Th e summar yo f th e repor t o f Needlema n e t a l comparin g I Q distribution s i n hig h an d io wlea d group s showe d tha t th e ris k o f havin g a n I Q < 8 8 wa s increase d almos t 4-fol d i n associatio n wit hECA O Critique , Needlema n*

hig htoot hlea dlevels . Thi s shoul db e mentione d inthi s section . Thi s grap hshoul db e publishe d inthi s sec t ion . 12.4.2.2.2.1 / 12-65 / 1/ 4 I nothe r communication s t o EPA/ORD , I hav e demonstrate dtha t th e Neurobehaviora l Pane l appointe dt o revie w m y wor k an dtha t o f Dr . Ernhar t committe da t leas t 1 2 error s o f fac t in thei r evaluatio no f m y studies . Th e directio no f al l o f thes e error s wa s t o weake nth e conclusion s draw nb y

m y studies . Man y o f these s error s persiste dinth e fac e o f repeate dattempt s b y m e t o correc t them . Althoug hmos t o f th e error s whic happeare dinth e Augus t 198 3 draf t o f th e Pane l repor t wer e extirpate di nth e Novembe r 198 3 version , th e conclusion s whic hrelie d o nthes e error s wer e allowe dt o stand . Th e panel s conclusions , whic hwer e no t subjec t t o pee r review , _s±i.nul. d nnl ja_p.p.e.___

c ID lh£ LLII&LI*. j_l__.___i-l . 12.4.2.2.2.1 / 12-65 / 3 / Th e stud y

e f McBrid e e t al<1982 ) employe da s th e principa l outcom e measure , a tes t tha t I ha d show nin197 5 t o b e insensitiv e t o th e effect s o f lo w leve l lea d. exposure : th e Peabod y .Pictur e Vocabular y

Tes t (Needleman , EP A Fina l Repor t 1976) . 12.4.2.2.2.1 / 12-66/ 2 Th e ECA O ha s bee ninconsisten t i nit s applicatio n o f th e groun drule s applie d t o studie s admitte d t o th e Draf t Criteri a Document . Th e Executiv e Summar y

state s tha t th e scientifi c literatur e ha s bee nreviewe du pt o Jun e 1983 . Thi s pape r wa s no t availabl e t o th e scientifi c communit y unti l it s publicatio nunti l Octobe r 1983 . Sufficien t tim e ha s no t bee navailabl e t o evaluat e i t thoroughl y b y th e scientifi c community . A quic k analysi s reveal s tha t th e conclusion s draw nb y th e author s ma y wel l b e incorrect , an dtha t thi s pace r support s th e positio ntha t lea da t low dos e ma y affec t development . Amon g th e criticism s whic h requir e tha t th e paper' s conclusion s b e scepticall y

receive dare : Th e author s use dwhol e toot hlevels , a techniqu e whic hma y lea dt o misc 1 assificatio no f subjects . The y employe da larg e batter y

o f tests , bu t i nreportin g thei r results , onl y

stat e tha t the y wer e ne t significant ; the y d o no t giv e actua l p-values .

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ECA O Critique , Needlema n

( I hav e writte nt o R . Lansdow nan drequeste d them ) Th e difference s betwee ngroup s wa s o f th e sam e orde r o f magnitud e a s thos e reporte db y Needlema ne t al , befor e contro l o f covariates , an dth e reductio nindifference s wa s abou t th e same . Thi s findin g ha s le dMichae l Rutte r t o conclud e tha t th e stud y support s conclusio ntha t lea d a t thes e dose s i s neurotoxic(Rutter , 1981 , 1982) . Ha.cue.a_.l

s aa.ae.f

c i_ & ao l l a aalal-* . aa dha s a o ala.c c l a Ihe . docua_aal« . 12.4.2.2.2.1 / 12-68 / I t i s no t clea r wh y th e documen t conclude s tha t th e differenc e inteacher' s ratin g foun db y Yul e e t a l o nth e Needlema nscal e reflec t attentio n deficit s rathe r tha nconduc t disorder . I t i s tru e tha t th e ratin g an dth e correlated , bu t tha t doe s behaviora l effect s wer e les s studie s o f Attentio nDefici t IQ' s wer e no t mea ntha t th e important . Followu p Disorde r hav e show n tha t increase s i nth e incidenc e o f conduc t disorder s ar e frequentl y associate dwit hthi s syndrome . Yule' s grap ho f teachers ' rating s shoul db e publishe d here . 12.4,2.2.2.1/12-68 / U i nr^kfr'f t *tnrii» s ^r e inadequatel y treate di

n thi s discussion . The y als o suppor t th e lead developmen t relationship . Th e bia s o f th e write r i s apparen t inth e treatmen t o f Winneke' s work . 12.4.2.2.2.1/12-6 9 Th e summar y

paragrap ho nthi s pag e betray s naivet e abou t epidemiologica l studies . N o epidemiologica l stud y i s withou t flaw . No r ca n causalit y

b e demonstrate dempirically - eithe r i n th e fiel do r inth e experimenta l laboratory . I t strain s th e bound s o f critica l thinkin g t o sa y tha t becaus e e f this , n o conclusion s ca nb e draw n abou t th e cause s o f defici t i nrelatio nt o lea d a t lo w dose . Thi s chapte r doe s no t g o thi s far. , bu t b y

it s cautionar y tone , provide s usefu l an d quotabl e materia l to . thos e wh o woul dtak e thi s position . Investigator s inthi s area , an a educate dreader s kno w th e limitation s o f thei r craft , an dd o no t requir e tha t th e limitation s o f thes e studie s b e repeatedl y brough t t o thei r a t ten t i on . 12.4.2.2.2. 5 12/71/ 2

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ECA O Critique , Needlema n

I t i s difficul t t o understan dwh y the stud y

o f Burchfie l e t a l i s dismisse ds o summarily . Th e writer s o f th e chapte r stat e tha t becaus e individua l dentin e l** d level s wer e no t furnished , i t i s impossibl e t o estimat e lead-exposur e level s associate d wit hth e observe d EE Geffects . The y as k mor e fro m th e stud y

tha n i t wa s designe dt o do . Th e stud y wa s designe dt o addres s thi s question : Doe s lea dexposur e belo w tha t whic hproduce s clinica l symptom s produc e electroencephalographi c changes ? Th e medica l I'i teratur e prio r t o thi s publicatio nwa s unifor m inconcludin g tha t EE C change s wer e no t see ni f clinica l encephalopath y wa s no t observed . Thi s pape r i s th e first(an donly)repor t t o disput e thi s statement , an ddeserve s mentio ninthi s context . Inference s ca nreadil y b e mad e abou t th e exposur e level s experience db y subject s in thi s study . Th e expose dgrou pcam e fro m th e highes t decil e fo r dentin e lead , an dtha t thei r mea nbloo dlea dlevel , fou r year s prio r t o havin g thei r EEC' s evaluated , wa s 34 " ug/dl . I ncontras t t o th e intriguin g finding s o f th e Ott o study , whos e clinica l significanc e i s no t clear , th e clinica l relevanc e o f th e change s in. th e Burchfie l stud y ar e obvious . 12.6.1.4 . 12/152/ 3 Th e effect s o f lea d o nth e developin g human . Thi s sectio ncontain s n o mentio no f th e studie s b y Needlema ne t a l dealin g wwhic hsho w tha t increasin g umbilica l cor dbloo dlea dlevel s ar e associate dwit hincrease dris k fo r mino r congenita l malformation s an ddecrease d developmenta l score s o nth e Bayle y ScalesXPe d Res.17:1281a,1983 , Pe d Res.17:179a,1983,an d JAMA . inpress) . I nbot hstudies , contro l o f relevan t covariate s wa s achieved , an dsignifican t lea d effect s o nbirt houtcom e an dsubsequen t developmen t wa s demonstrated . APPENDI X12-C : Genera l Comment s Thi s appendi xappeare dintw o versions , on e issue di nAugust , 1983 , an dth e secon dinNovember,1983 . Th e firs t versio nwa s issue dwit h1 2 rathe r obviou s error s concernin g th e studie s o f m y group . Al l o f thes e wer e biase dt o diminis hth e conclusion s draw nby

m y grou pabou t th e 1ead-neurobehaviora l relationship . Thes e error s wer e committe d eve nthoug hI ha dcorrecte d man y o f them , inwritin g t o th e ECA O director , prio r t o the draft' s

«. •P. 8



### ECA O Critique , Needlema n

i issue
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### a s agreed , receiv e a prepublieati© n draf t 4or peview
. w a s withdraw n whe n I See k str©n g exeeptie n t ©it s orrers s bu t ne t al l © f th ©orrer s wer e eaeised o Man y© f th e conclusion s draw n fro mth e err©r s wer e all©we d t ©-stand . pre vi ©ugl y Thi s draf t many , yhi1 e th ©

member s © f th e pane l ar e unquestionabl yexperience d i n th e field s © f biometries , devel©pmenta l psyehelegy , an d pathelegy , i t i s worth y© f meri t i© n tha t n ©membe r © f th e pane l i n th e relevan t discipline s © f fiel d texieelogy
. Thi s deficienc ybecome s wit hear e th e canon s the yappl yt © th e lea d effect s a t lo wdose . A-fte r

b e encounter d afte r tha t appear s t o hav e experienc e epidemiolog y© r behaviora l apparen t whe n ©n e .examine s enterpris e © f evaluatin g reviewin g th e type s © f findin g whie hcoul d studyin g thi s problem , th e pane l conclude s

°...n e matte r he wearefull ydesigne d an d executed , erosssecti©na l studie s e f relationship s betwee n Pb an d cognitiv e functionin g ar ©no t abl e t ©yiel d definitiv e conclusion s regardin g th e influenc e © f low-leve l Pb exposure s o n huma n cognitiv e functioning..
. A t best , suc hcross-sectiena l studie s ma yyiel d © v suggestiv e o f effect s o f low~l@ve l P b exposure s woul d nee d t o b e confirme d definitiv e researc hdesigns° 0 

### by studie s usin g i dene ©

w hi e h mor e Thi s statement , containe d i n th e introductio n t e th e report , predict s thei r late r judgements
. The yinfe r t h studie s publishe d t o dat e ar e cross-sectional , n o "def i conclusion s ca n b e draw n fro mth e curren t bod yo f se i informatio n e n huma n effect s e f lea d a t lo wdose . Th e woul d hav e i t tha t w ©mus t wait , 6 year s an d 1 7 paper s a f firs t ai r lea d standard , fo r a forwar d stud yt o allo wde f conclusion s t o b e drawn . Sinc e onl yon e forwar d studyv m bee n publishe d t o date , an d sinc e th e pane l an d ECA O h reviewe d it , th ©reade r coul d predic t wit h pane l wil l en d wit ha n equivoca l conclusion , almos t al l panel s o f thi s natur e do . wit h studies
. Thi s typ e o f stereotypi c behavio r earlie r t o man ysuc henvironmenta l questions , accurac yt h The ycon e I u a ca l 1 f o h a s bee n mos t not a c r i t i e i sm s asbestos . .o f studie s o f th e risk s e f exposur e t o teba e panel' s a t a l 1 n i t i ve " e n t i f i c pane l te r th e i n i t i ve i ne)ha s a s no t a t th e de . a s r mor e appl i e d b 1 yin c o an d Epidemiolgist s ar e awar e o f th e limitation s o f thei r craft 0 

### an d th ©inabilit yo f thei r exertion s t o yiel d "definitive " proo f o f th e relationship s unde r study . The yse t mor e realisti c goal s fo r themselves , an d expec t t o ad d incrementa l informatio n t o th e clarificatio n o f th e phenomen a unde r examination
. The yd o no t tax themselve s wit h th e responsibiIt yo f providin g definitiv e conclusion s £.vl

s^a&^ls

abou t th e relationship s the yinvestigate ,

- o - ___U HP. 9

ECA O Critique , Needlema n

bu t hop e t o pain t par t o f a picture , whic hi f consisten t an d coheren t wit hothe r studie s fro m th e fiel dan dlaboratory , permi t judgement s t o b e mad e abou t th e causa l (tha t i s t o say predictabl e an ddependable ) relationship s betwee nth e event s unde r examination . Th e inabilt y o f empirica l studie s t o prov e causa l relationship s wa s clearl y state db y

Hume , and.on e o f th e member s o f th e pan e I(Kupper) , inrecognitio no f this , state s

"Inferrin g tha t a give nfacto r i s a ris k facto r fo r a diseas e i s a v*ry comple xproces s involvin g man y uncertainties . Ther e ar e severa l reason s fo r believin g tha t causa l inferenc e depend s o nmor e tha na singl e tes t o f a hypothesi s base do non e se t o f observations....Final1y , w e canno t dra w a definitiv e conclusio nfro m th e result s o f on e analytica l tes t becaus e o f th e limitation s o f inductio ndiscusse d above. " Despit e this , th e pane l repor t use s thi s acknowledge dlimitatio n t o diminis hth e impac t o f th e tw o studie s the y cite , eac h examine dinisolation . Th e pane l nowher e givr s attentio nt o th e coherenc e an dconsistenc y o f th e recen t studie s o f lea d an d children . I t doe s no t troubl e itsel f t o collat e th e studie s whic hbea r o nthi s point . Th e repor t treat s eac hstud y a s i f i t exist s ina cognitiv e vacuum , and ' ignore s th e similaritie s in differenc e inI Q score s betwee nhig han dlo w lea d group s i n studie s conducte dinthre e differen t countries . The y similarl y ignor e th e intriguin g findin g tha t al l o f thes e studie s sho w th e sam e amoun t o f difference(abou t 4- 6 points ) o nI Q score s befor e controllin g fo r covariates , an dtha t afte r adjusting , th e reductio ni s abou t th e sam e i nal l studies(3- 4 points) . A t n o poin t inthei r critiqu e d o the y recogniz e th e correspondenc e betwee nth e anima l studie s an dth e epidemiologica l investigations . Specifi c comment s o nAppendi x12- C Pag e 7 : Th e documen t doe s no t indicat e tha t Ernhar t neglecte dt o contro l socioeconomi c statu s ineithe r th e firs t investigatio n (197 4 o r th e follow-u p stud y (1981) . Th e onl y commen t o nthi s egregiou s omissio ni s oblique : "I t i s no t know nwhethe r a fine r SE S scal e woul dhav e resulte di ngreate r relation s betwee nSE S an dothe r variable s inth e stud y tha nthos e relate db y Perrin o (1973)' . Th e neurobehaviora l pane l state s that , "Materna l occupatio nwa s recorde dfro m clini c record s employin g a 195 6 censu s classificatio ntha t wa s 4D.ad__j_ij_1.a_l._

_±& J±L11£I:£JL,±12L±£

_ymnr.. g jur-b-a nhl^cksl . temphas i s added ] O ncarefu l reading , th e origina l pape r b y

Perrin o an dErnhar t i s inconflic t wit hthi s statement . I t says: . "The y

[parents ] range dfro m _r_a.aa.QacE. * clecica l wocLfccs * stille daa duask_ille. d wock.ac s l o se.C-__.xoe . wock.e.c s aa dt__e.ii.ace .

- 7 -P.1 0



### SCA O Critique , Needlema n

£.__.e_ip.i-i&lg>
. Eemphasi s added ] Th©superficia l attentio n © f th e pane l t©th e ©missio n by ^orrin ©

an d Ernhar t © f SE S contro l stand s i n distinc t eentras t t © th e eritieism s © f th e wor k o f Needleman, . o t a l . In thes e eritieisms, , th e Needlema n stud yi s faulte d ne t fe r neglectin g t ©e©ntr© l f© r SES , bu S <{"© r usin g parenta l SE S instea d © f parenta l odueati©n

_Sinc e SE S i s a composit e yariabl o eempese d © f odueati© n an d ©eeupatien , th e tw o faeter s ea n b e expecte d t©be = an d are°highl ycorrelated . Th e pane l ratifie s th e PQmeva l ©f a D 

### ©utlie r ° by Ernhar t i

n an unpublishe d study , a s appropriat e methodology . Thi s subjec t wa s remove d fro m

th e analysi s afte r bein g identifie d a s havin g a sever e decreas e i n intelligence
. Thi s retrospectiv e remova l o f subject s doe s ne t withstan d seientifi e scrutiny
. A s X tel d th e working * p<%rty

i n Nort h Carolina , th e hig h dentin e loa d leve l i n th e subjec t exclude d by Ernhar t wa s probabl ycause d by dentina l hypertroph ysecondar yt e th e eari e i n tha t t©eth . I t i s no t legitimat e t o exelud e th e subjeet , wh ©wa s discovere d becaus e th e I Q scor e wa s v<sr-y low , an d the n reconstruc t a reason . Accordin g t e Perrino' s an d Ernhart' s origina l paper , D 

### A 1 I [subjects ] wer e asymptomati c an d ha d n o know n illnes s o r histor yo f condition s associate d wit h intellectua l impairment..iadditional1y , ther e wer e n e record s e f previou s hospitalisation s fo r lea d intoxication. " I t canno t b e considere d scientificall yrigorou s firs t t o se t up criteri a t o tes t a hypothesi s an d then , sem e year s later , whe n th e conclusion s draw n ar e ne t acceptabl e t e th e author , selectivel yremov e a subjee t wh o initiall yme t th e criteria
. Supportin g thi s procedur e doe s no t testif yt o th e panel' s critica l acuity
. Pag e 14 : Th e pane l note s tha t readin g tes t score s wer e obtaine d fro m man ydifferen t tests , bu t conclude s tha t th e combinatio n o f multipl e measure s doe s no t necessaril ycompromis e th e assessmen t o f readin g achievement
. Whil e thi s ma yb t tru e fo r estimatio n o f a n individual' s achievement , i t canno t b e considere d acceptabl e practic e in a researc h effort . Thi s woul d b e on e e f th e firs t time s tha t a researc h desig n woul d permi t th e mergin g o f dat a fro meleven ^ differen t instrument s acros s th e sampl e siz e e f approximatel y80 , withou t establishin g intertes t reliability
. Whe n th e pane l turn s t o th e studie s o f m ygroup , i t appear s tha t a differen t leve l o f critica l stringenc yi s employ^ . I n th e firs t versio n o f th e panel' s report , th e panel , whos e rol e wa s t e asses s th e precisio n an d validit yo f m ywork , committe d a t leas t 1 2 error s o f fac t an d inference
. Thes e wer e calle d t e th e attentio n o f Dr . Gran t an d th e EP Ain a lette r o f Octobe r 9 (enclosed). . I wil l no t repea t th e documentatio n o f thes e error s here . ' Thes e error s wer e i n th e mai n remove d fro mth e secon d

- 8 -P.1 1

ECA O Critique , Needlema n

versio no f th e panel' s report , bu t th e conclusion s whic hwer e derive dfro m

the m wer e allowe dt o stand . Pag e 2 9 Paragrap hD Th e metho do f isolatin g dentin e whic hI personall y develope din Bosto nwa s quit e simple , contrar y t o th e panel' s report . I t involve dth e us e o f a smal l chise l an da coppe r mallet . Th e pane l reiterate s tha t thi s entail s methodologi c •kill . The y g o t o stat e tha t i t appear s tha t a plu s o r minu s 157 . represent s a reasonabl e specifi c estimat e o f th e variabilit y fo r dentin e analysis . Tha t i * correct . I t i s als o correc t tha t a s state do n pag e 38 , "greate r variatio nexist s amon g thos e individual s excluded" . Tha t i s becaus e greate r variatio nwa s precisel y th e reaso nfo r thei r exclusion . Paragrap hE Whil e Shapir o an dco-worker s di drepor t a bette r correlatio no f tooth/lea dcontration s pe r year , wit heithe r bloo do r E P contratiens , th e coefficien t o f determinatio nwa s extremel y small . I nparagrap h3 , pag e 32 , th e tw o error s detecte db y th e pane l i

ncalculatio no f parenta l I Q wer e correcte dan dth e dat a reanalyzed . Thi s i s show nintabl e 1 o f th e appendix . N o differenc e i nth e significanc e e f th e I Q score s wa s found . I n paragrap h4 , th e pane l note da highe r proportio no f discrepancie s betwee nverba l an dperformanc e I Q scores . W e calculate dth e correlatio nbetwee nth e verba l an dperformanc e I Q score s inou r sampl e an dfoun dtha t the y corresponde dquit e closel y t o thos e in th e Wechsle r manual . Pag e 3 3 I ter

nA Th e pane l question s whethe r subject s woul db e reassigne d becaus e o f th e 15 % variabilit y indentin e lea danalyses . I t shoul db e note dtha t th e lb'/, variabilit y i s define da s acceptabl e b y th e Cente r fe r Diseas e Contro l init s qualit y contro l fo r bloo dlead . Ther e i s n o reaso nt o believ e tha t th e variatio n woul db e biase dan di t i s therefor e reasonabl e t o assum e tha t reassignmen t du e t o varianc e indentin e lea dlevel s woul db e rando m an dunbiase dacros s categories . I f anything , thi s varianc e woul d bia s th e stud y l-ouiac

d ±h£ null hxf,n±b££,l&m. Pag e 3 4 Ite m

C Thi s criticis m

simpl y

doe s no t correspon dwit hth e facts . Th e criteri a fo r exclusio nwer e clearl y delineated , an dw e adhere dt o them . I ter nD

- 9 -P.1 2

ECA O Critique , Needlema n

W e hav e reanalyze dth e data , usin g bot hag e norme d score s an d ra w score s an dpresen t the m inth e attache dreport . Ou r conclusion s ar e sustaine db y thi s reanalysis . Ite m F Th e committe e neglecte dt o mentio ntha t 6 5 ou t o f 66 outcom e favore dth e lo w

lea d group , eve ni f no t a t th e leve l o f .85 . Th e possibilit y

o f thi s occurrin g unde r th e nul l hypothesi s i s vanishingl y

small . Thi s findin g wa s reporte dinLancet , Septembe r 11 , 1982 , an dcalle dt o th e committee' s attention . I ter nG Whe nw e di dintroduc e ag e int o th e regressio na s a covariat e an dra w

score s a s a noutcom e variable , th e relationshi pbetwee n lea d an doutcom e wa s no t materiall y altered . Introducin g ag e int o th e regressio nagains t scale dscore s cause da chang e i nth e sig ne f coefficien t o f th e ag e variable . Thi s support s th e assertio ntha t i t i s undesirabl e t o correc t ..fo r ag e twic e a s quote di

nth e panel' s report . Pag e 3 8 Comment s o nth e Burchfie l Stud y Ite m C Th e pane l assert s tha t becaus e ther e i s n o definit e dentin e o r bloo dlea dlevel s reporte dfo r specifi c children , i t i s impossibl e t o determin e wit han y confidenc e th e specifi c lea d exposure . Th e stud y wa s no t designe dt o determin e specifi c lea d exposure . It s goa l wa s t o asses s whethe r "subclinical " lea d exposur e wa s asssociate dwit hchange s i nfunction . A nestimatio n o f th e bloo dlea dlevel s inbot hgroup s i s possible , however . Th e childre ninth e hig hlea dgroup'wer e i nth e 96t hpercentil e fo r lea d i

nSommervill e an dChelse a an dthei r mea nbloo dlea d leve l teste dfou r year s prio r t o toot hsheddin g wa s 3 4 ug/dl . Th e referen t grou pwa s childre ninth e lowes t 16t hpercentil e fo r lead . Thei r mea nbloo d lea dleve l i. n197 4 wa s 24ug/d l . Thi s i s a straightforwar d analysi s o f varianc e desig nwhic hha s bee nuse d fo r decade s incompariso no f dru g effect s an dtoxi c exposure . *.£*g * 3 9 1 ter

nD Th e comment s o f th e pane l o nth e 198 2 Needlema nrepor t ar e incomplete . I t i s worth y o f mentio ntha t th e teacher' s ratin g scal e analysi s inthi s sample , fro m a differen t city,show s a simila r relationshi pbetwee ndentin e lea dan dproportio no f childre nreceivin g negativ e report s o neac hitem . I naddition , step-wis e logisti c regressio ncontrollin g fo r covariate s o f relevanc e indicate s tha t a relationshi p betwee nlea d an d behaviora l dysfunctio nwa s found . Th e reservation s expresse dby '



### - i e 

### -P.1 3

ECA O Critique , Needlema n

th e committe e regardin g th e 198 2 pape r wer e similarl y state din th e error-ridde nearlie r repor t o f th e committee . Whil e th e error s ar e extripated , th e conclusion s remai nth e same . Th e fina l statemen t o f th e committe e tha t th e cumulativ e frequenc y distributio ncurve s i nasymptomati c subject s i s misleadin g i s absolutel y

incorrect . Whil e on e o f th e subject s wit hclinica l lea dpoisonin g di dhav e a hig hIQ , thi s findin g i s irrelevan t t o th e presentatio no f distributio ncurve s inasymptomati c subjects . Thi s study , b y a p.t_____at

l design , exclude dsymptomati c subject s fro m

dat a analysis . Page.4 0 Commen t F I t i s difficul t t o understan dthes e remarks . Th e pane l state s tha t a nanalysi s o f th e relationshi pbetwee nteache r ratin g an d lea d leve l followin g adjustmen t fo r confoundin g variable s wa s no t reported . O nth e contrary , i t wa s reported , an dform s th e majo r burde no f th e repor t t o EPA . I nthi s study , w e reduce dth e outcom e spac e b y cluste r analysi s an dthe nsubmitte dth e cluster s t o logisti c regressio nanalysis , enterin g relevan t covariate s int o th e model . Thi s i s clearl y documente din.-th e repor t t o EPA .

SUMMAR Y I nsummary , thi s appendi xi s remarkabl e inth e unevenes s o f th e criteri a i t applie s t o th e tw o group s o f studies . Althoug hmos t o f th e error s identifie db y m e i

nm y lette r t o th e directo r o f ECA O ar e removed , th e conclusion s draw nar e virtuall y unchanged . W e recentl y

reanalyze dth e dat a inou r stud y accordin g t o th e criticism s o f th e panel , an dpresen t th e result s inth e followin g pages . I t i s apparen t tha t afte r reanalysis , th e relationshi p betwee ndentin e lea d leve l an dneuropsychologi c outcom e (Wechsle r full-scal e an dverba l IQ ) remaine da s reporte dinou r 197 9 paper . Th e outpu t o f thi s pane l wa s foretol dinth e earl y page s o f thei r report . Th e pane l establishe dcriteri a fo r establishin g causalit y

tha t n o singl e epidemiologica l stud y coul dmeet , an d havin g don e this , rejec t a s flawe dth e studie s the y reviewed . Th e pertinen t questio nt o addres s t o thi s panel' s appendi xis : "Wha t evidenc e woul dthe y hav e foun dpersuasiv e tha t lea da t lo w dos e i s neurotoxic? " Th e applicatio no f wrongl y place d epistemologi c criteria , th e numerou s misinterpretation s o f my work , thei r refractorines s t o correction , an dthei r unwillingnes s o r inabilit y

t o vie w

thes e studie s i ncontex t sugges t tha t n o concatenatio n© f studie s woul dhav e altere d thei r preconceptions. .

- 1 1 -P.1 4



### APPENDI Xt o th

e ECA O CRITIQU E B YHERBER T NEEDLEMA N INTRODUCTION : Th e repor t o f th e ECA O pane l o

nneurobehaviora l studie s raise dsome question s abou t the desig nan ddat a analysi s o f the Bosto nstud y o f lo

w leve l lea dexposure<Needlema ne t al,1979) . Tha t repor t wa s issue d i ntw o versions , August,198 3 andNovember , 1983 . Th e criticism s raise dma y be summarize da s follows : 1 . Tha t Fathers ' Educatio nshoul dhav e bee nuse da s a covariat e instea do f Fathers ' SES . 2 . Tha t error s i ncalculatin g Paren t I Q coul dhav e biase dou r results . 3 . Tha t samplin g procedure s coul dhav e introduce dbias , andtha t missin g dat a point s coul dhav e pose da validit y problem . 4 . Tha t criteri a use dt o defin e P bexposur e o r t o exclud e subject s wer e arbitrary , an dtha t differen t result s coul dhav e bee nobtaine db y differen t methods . 5 . Tha t ag e shoul dhav e beeenuse da s a covariat e i n th e analysi s instea do f relyin g o nage-normalize d scores . 6 . Tha t th

e sprea dbetweenVerba l andPerformanc e score s withi n subject s wa s greate r thanexpected . 7 . Tha t th e teacher s ratin g score s canno t be use da s evidenc e fo r a lead-behavio r effec t becaus e covariate s wer e no t controlled . '8.. - Tha t th e us e o f analysi s o f varianc e mode l t o compar e extreme s coul d overemphasiz e the differenc e betwee ngroups , andvitiate s th e utilit y

o f the stud y

t o determin e dose-effec t relationships . 9. . Tha t th

e validit y

o f classificatio no f subject s 'b y dentin e lea d i s questionable . 

### I n j. lette r t o Leste r Grant(Oc t 7,1983) , I responde dt e th e man y error s o f fac t an dinterpretatio ncontaine di nth e firs t draf t o f th

e panel s report(Aug,1983) . Tha t respons e wil l no t b e repeate dhere . Inthi s report , I attempt , t o addres s primaril y thos e question s o f desig nan danalysi s mad e b y th e panel , an

dt o evaluat e thei r impac t o nthe conclusion s m y colleague s andI orew i n197 9 o

nth e effect s o f lea dat 1© w dos e an

dneuropsychologica l functio ni

nchildren . I nthi s presentation , fo r reason s o f econom y o f tim

e andfunds , w e concentrat e o non e outcom e measur e o f majo r importance : th e WISC- RI Q scores . Th e same analysi s coul dbe applie dt e the othe r outcome measure s a s well .

- 1 -P.1 5 1

CRITICIS M

AN D RESPONSE S 1 . Father' s SE S *houl dhav e bee nreplace dwit hfather s s educatio na s a covariate . « W e substitute dfather' s educatio ninth e ANACOU A mode l (Tabl e 1 , Mode l 4). , an dcompare dmea n•cores , an dF ratios . 2 . Mistake s i nparen t I Q calculatio nma y hav e introduce d bia s int o th e analysis . * W e correcte dth e tw o erroneou s paren t I Q scores(ou t o f 15 8 subjects) , an drepeate dth e analysis(Tabl e 1.Mod e 3 . Exclusio no f subject s fo r missin g covariate s coul dhav e biase dth e analysis .

• W e compare doutcom e measure s o nthos e subject s include dan dexclude dbecaus e o f missin g variables , an dteste d significanc e b y

T-tests.(Tabl e 2 ) 4 . Exclusion s o f subject s fo r possibl y confoundin g variables , e.g. , hea dinjury , no t bein g discharge dwit hmother , ma y hav e biase dresults .

« W e regresse ddentin e lea d leve l an dcovariate s v s I Q fo r al l subjects , fo r include dsubjects , an dfo r exclude d subjects , an dexamine dth e coefficient s fo r lea d an dcovariates .

Th e theoretica l reason s fo r .excludin g subject s wit hsuc hris k factor s a s hea dinjur y e r perinata l distres s fro m analysi s ar e sel f evident . Whe nw e cros s tabulate dth e categorie s fo r exclusio nagains t lea d levels , w e foun dn o noteworth y

difference s indistributio no f lea d level s betwee n include dan dexclude dsubjects . Nevertheless , w e examine dth e dose-respons e functio nfo r P ban dIQ , usin g a mode l o f th e f o.l 1 ow i n g form : IO=a*ibX+dPb . + c D

«

_* • • i e I I I'I I wher e Xar e covariate s suc ha s mothers ' IQ , an dD i s a dumm y variabl e tha t tak e o na valu e o f 1 i f exclusionar y an d0 otherwise . W e repeate dthi s analysi s o nth e sam e dat a set , afte r removin g thos e 1 6 case s wh o wer e identifie d a s eithe r havin g ha d lea dintoxication , o r bee nchelated . Thi s wa s don e becaus e o f concern s abou t multico l 1 inearity . Usin g multipl e regressio n analysis , w e teste dth e hypothese s tha t (1 ) th e dcoefficien t maintaine da negativ e sig nwhe nth e previousl y exclude dcase s wer e include dinth e model , an d(2 ) tha t th e exclude dcase s wer e ha-rvd-le

d appropriatel y b y testin g tha t th e coefficient s .wer e negative . 5 . Ag e wa s improperl y controlled . * W e too k bot hra w an d standardize dverba l an dperformanc e I Q scores , an dregresse d them , wit hage , lea dan dcovariates , an dthe ncompare dth e coefficient s fo r ag e an dlea dunde r bot h conditions-unstandardize d an dstandardize d dependen t variables . Th e panel.suggeste d tha t th e prope r specificatio ni nth e I Q . regressio nmode l shoul d hav e th e followin g form :

- 2 -P.1 6

(1 ) (I Q - a « - * « Age) = b• bAg e • d P b

e e i 1 wher e a * - a « Ag e » ag e adjustmen t base dupo nnationa l

9 

### 1 standard s I nth e 197 9 paper , Needlema ne t a l estimate dth e followin g model : (2 ) (I Q - a « - a

6 1 W e agre e tha t equatio n oenera l for m

coul db e

Age ) « * b* d P b 

### e l (2 ) i s a restricte dfor m used . Howeve r w e be i an dtha t a mor e iev e tha t th e fol1ow i n g app l i c.ab

l e specifa t iono f a s equatio n(1 ) th e ag e variabl e i s a s generall y
(3 ) I Q * c • • c Ao e • dP b

0 1 1 wher e c , c , b, b, d= coefficient s t o b e estimated . 6 . Th e difference s betwee nVerba l an dperformanc e I Q score s wa s excessive . * W e measure dth e correlatio n-betwee nverba l an d performanc e IQ , an dcompare dth e result s t o thos e reporte db y th e test' s designe r i nhi s manual . 7 . Th e mean s w e use dt o classif y subjects ' dentin e lea d level s wer e arbitrar y

an dperhap s biased . Th e us e o f ANOV A wa s no t th e appropriat e mode l t o apply . • W e too k al l o £ Ihe . daaiiae . lta d le.i_.els fo r eac ho f th e subject s an dcalculate dth e arithmentic , geometri c means , an dth e media nvalue . Eac hsubjec t the nha da singl e numerica l valu e assigne dt o his/he r lea dlevel . Thes e wer e entere d-int o a multipl e regressio nanalysi s a s independen t variables , an dth e regressio ncoefficient s calculated . RESULT S AN D CONCLUSION S 1 & 2 . ANACOVA , replacin g correcte dparen t I Q inth e model , an d substitution g Fathers'educatio nfo r SE S yielde dpracticall y th e sam e result s (Tabl e 1) . I nthi s table , w e use d2 variable s a s measure s fo r famil y size , numbe r o f pregnancie s an dnumbe r o f liv e births- . W e presen t bot hvariable s fo r information . 3 & 4 . T-test s betwee ninclude dan dexclude dsubject s di dno t sho w significan t difference s (Table2> . Th e dummy variabl e fo r exclusio nha da negativ e sign , supportin g th e validit y o f excludin g thes e subject s o nth e basi s o f theory , an dth e coeficien t fo r P bremaine dpositive , an dth e t valu e larg e whe n th e exclude dsubject s wer e entere dint o th e mode l (Tabl e 3> . Whe n thos e case s wit ha histor y o f lea d toxiciit y wer e excluded , th e dumm y <oef f i c i e nt , -an dth e coefficien t fo r P bbecam e increasingl y negative. , supportin g th e notio no f mu 1 t i co l 1 i nea r i ty-.(Jab l e 4> .P.1 7

5 . Whe nag e wa s entere dint o th e model , th e coefficient s fo r ag e whe nth e dependen t variabl e wa s a standardize dscor e becam e negative . Th e coefficient s fo r P bwhe nag e standardize doutcome s wer e use dwer e simila r t o thos e obtaine dwhe nag e wa s enter dint o regressio nusin g ra w score s (Tabl e 5) . 6 . Th e corrrelatio nbetwee nverba l an dperformanc e I Q inou r sampl e wa s 6.72 , abou t th e sam e a s publishe db y Wechsle r inhi s tes t manual . 7 . I t shoul db e note dtha t th e 197 9 pape r di d contro l fo r covariate s i nth e analysi s o f teachers ' ratings . I n tha t paper , a su m scor e o f th e 1 1 item s wa s constructed . Th e score s o f th e hig han dlo w lead*subject s wer e the nanalyze db y ANACOVA , controllin g fo r 5 covariates , an dsignifican t difference s betwee nexposur e group s wer e foun dafte r controllin g 

### 4or covariates . 8 . Th e criticis m tha t stratificatio no f exposure s int o extreme s shoul db e examine dinth e ligh t o f th e stat e o f knowledg e abou t lea d a t th e tim e tha t th e stud y wa s designed(1973) . A t tha t time , littl e certaint y existe dtha t a neffec t woul db e discovere d a t thes e exposures . Th e mos t efficien t strateg y appeare dt o b e t o compar e th e extrem e groups , and , i f a neffec t wer e discovered , t o loo k a t continuou s distributions . Sinc e n o lead-fre e referen t grou pexisted , w e identifie dindividual s acxros s th e distributio n o f exposures , an dthe nse t ou r referen t a t th e lowes t decile . Stratificatio no f relativel y extrem e exposure s i s th e appropriat e approac ht o explorator y epidemiolog y

wher e on e i s a t temptin g t o determin e whethe r a neffec t exists . Thi s approac hmaximize s th e statistica l powe r fo r a give nsample . Extrem e non-linearit y throug hth e middl e o f a distributio nma y yiel da differen t dose-respons e relationshi p fo r th e bul k o f th e populatio ntha n th e linea r effec t implied . Th e overal l tes t fo r th e presence:o f a neffec t woul d stil l b e statisticall y valid . I nsummary , th e change s mad e inthi s preliminar y reanalysi s o f th e data(correctin g th e tw o paren t IQ's , substitutin g educatio n fo r SES , regressin g fo r ag e v s ra w score , an dcontrollin g fo r exclude dsubject s an dmissin g values) , an dtreatin g lea dleve l a s a continuou s variabl e hav e no t materiall y altere d th e conclusion s draw ni n1979 . Th e relationshi pbetwee nlea da t lo w dos e an d I Q appear s robus t an dconsistent . FINA L NOTE : . Th e printout s fo r th e materia l summarrize d herei n are , o f course , availabl e fo r examinatio ninm y offic e in P i ttsburgh .

Herber t L . Needleman , M.D . Departmen t o f Psychiatr y Children' s Hosp^taa l o f Pittsburg h

- 4 -P.1 8



### VARIABL E DEFINITION S AGEINM O Child' s ag e i nmonths . P A RENT I Q Parent 10 . MOMEDUC H Mother' s educatio nbasedo n Hollingsheadscal e (wit h valu e o f 1 highes t leve l an d valu e o f 6 lowes t level) . MOMEDUC GMother' s education—highes t grade completed . DADSOdC L Father' s socia l positionbase do n Hollingshea d two-facto r inde x (th e lowe r the index , the highe r the socia l position) . DADEDUC H Father' s educatio nbase do nHol lingsheadscal e (wit hvalue o f 1 highes t leve l an

dvalu e o f 6 lowes t level) . DADEDUC GFather' s education—highes t grade completed . MOMAGEBRMother' s ag e inyear s at child' s birth . NUMPRE GNumbe r o f pregnancie s o f mother . NUMLIV E Numbe r o f liv e birth s t o mother. - PBLEV 2 Dumm y variabl e for lea

dlevel : 1 i f hig

hlea dgroup , it otherwise . DUMM YDUMM Yfor exclude d case : 1 i f exclude d I ? otherwis e (Tabl e 2 & 4 ) "RAWVERI Q Verba l I Q - Ra w Scor e RAWPERI Q Performanc e IQ - Ra w Scor e FULSCLI Q Ful l Scal e I Q - Standardize d fo r A= eP.1 9



### VERBALI Q PERI Q

PBMEA N
PBMD N PBGEM N Verba l IQ - Standardizedfo r Age Performanc e IQ - Standardized fo r Ag e Arithmeti c meano f toot hdentine lea dlevels . Media ntoot hdentin e lea dlevel . Geometri c mea no f toothdentine lea dlevels .P.2 0



### Mai neffect : Covariates : Tabl e 1 ANACOV A USINGVARIOU S TERM S P bDentin * (a ) Paren t I Q (b ) Correcte dParen t I Q (c ) Mother' s ag e a t subject' s birt h(d ) Mother' s educatio n(e ) Father' s educatio n(f> Father' s SE S (g ) Numbe r o f liv e birth s <h > Numbe r o f Pregnancie s

MODE L 1 Covariates : FULSCAL E HIG H LO W VERBALI Q HIG H LO U PERFI O HIG H LO W X , F p

(a) , (c) , (d) , (f) f 

### <n > (Origina l model , 1979 )
102.1 0 106.a e 99 . 2 0 104.1 0 104.9 0 108.7 0 4.9 5
4 . 5 8
•2 . B l 0.0 3

0.0 3
0 . 1 0

MODE L 2 Covariates : FULSCAL E HIG H LO W VERBA L IQ HIG H LO W PERFI O HIG H LO W (b) , (c> , (d) , (f) , <h )

102.3 0 4.7 0 106.6 0 99.3 0 4.7 8 103.9 0 104.8 0 2.3 4 108.£ 0 0.0 2
0 . 0 2
0 . 1 2P.2 1



### f-DDE L 3 Covariates : (b) , (c) , <d> , (f> , <g > FULSCAL E HIG H 101.8 0 5.9 2 0.0 £ LO U106.9 0 VERBALI D HIG H 99.0 0 5.4 0 Z. (& £ LO W 104.0 8 PERFI Q HIG H 104.6 0 3.4 0 0.0 7 LO W 108.7 0
MODE L 4 Covariates : <b> , (c) , (d) , (e) , (g ) FULSCAL E HIG H 102.20 . 4.6 3 0.0 2 LO W 106.7 0 VERBALI O HIG H 99.3 0 4.3 0 0.0 4 LO W 102.7 0 PERFI Q HIG H 104.8 0 2.4 2 e . 1 2 LO W 108.5 0
fCDE L 5 Covariates : (b) , (c) , (d) , (e) , (g ) FJL SCAL E HIG H 102.2 0 4.7 3 0.0 4 -O W 106.7 0 

### VZRBALI C HIG H 99.2 0 4.1 2 0.0 4 LO W 102.8 0 HIG H 204.9 0 2.4 0 0.1 2

- LO W 108.5 0

### Tabl e 2 T-TES T O F MEANS : MISSING CASE S VERSU S INCLUDE D CASE S FO R COVARIATE S P.2 2



### RAWVERI Q RAUPERX Q MOMEDUC H N

AN

A DADSOCCL* * -0.0 1 -2.80 * PARENTIQ** * 1.1 9 0.6 5 MOMAGEB R N

AN

A NUMLIV E N

AN

A FULSCLX Q

N A -0.3 9 0.9 S N A N A VERBALI Q

N A 0.9 9 1.2 1 N A N A PERI Q

N A -2 . 00 * 0.4 7 N A N A

N ATo o fe wmissin g case s t o calculat e t-statistic
. * Significan t a t th e .0 5 level . « # Nfo r missin g observation s i s 9 ; fo r non-missing , N=147 . ••* N fo r missin g observation s i s S ; fo r non-missing , N»151 .P.2 3



### Tabl e 3 REGRESSIO NCOEFFICIENT S FDR HIG H AND LOW LEAD SUBJECT S

WIT H TEST S FO R EXCLUSIO NCRITERIA *

- 

### AGEINM O

PARENTI Q

MOMEDUC H

DADSOCC L

MOMAGEB R

NUMLIV E

PBLEV 2

DUMM Y

CONSTAN T N** *
R<2 ) S E F XQVE R

. 689 5 (6.5> * .322 9 (5.11) * -1.675 4 (1.68) *

-. 609 6 (.60 )

. 157 5 (.97 ) -1. 126 7 (1.90) * -2.588 7 (1.50)* * -1.973 3 (.91 ) -22.1 7 18 7

. 2 5 11 . 1 1 12.5 6 IQPE R

.469 6 (2.48) * .5551 .(4.76) •

- . 986 0 (.55 ) -2.351 4 (1.30)* *

. 128 9 (.45 ) -2.590 2 (2.44) * -1.492 7 (.49 ) -7.310 7 (2 . 08) • 17.99 8 18 7
.2 2 19.9 0 8.2 6 FULSCLI Q

.400 6 (5.61) * -1.436 5 (1.31)* * -1.145 3 (1.02 )

. 163 3 (.93 ) -1.837 2 (2.85)*. . -2.836 9 (1.51)* * -3.923 7 (1.82) * 73.707 0 18 7
.2 1 12 . 1 9 12 . 1 5 VERBALI C

.361 2 (4.94) * -1.965 2 (1.75) *

- . 565 2 (.50 )

. 166 2 (.92 ) -1.368 7 (2.08) * -3.214 7 (1.68) * -3 . £27 8 (1.47)* * 72.821 8 18 7

T-" 7 m mm I 

### 12.4 7 10.8 0 PERI Q

.268 9 (4.97) * -.707 2 (.62 ) -1.482 4 (1.28)* *

. 164 6 (.90 ) -2.000 3 (2.99) * -1.7e8 7 (.92 ) -3.B61 C (1.72) * 77.733 2 18 7
.2 7 12.6 8 10.0 2

•• • t statisti c i n parenthese s belo wcoefficien t

* significan t a t tn e .0 5 level , one-taile d tes t ••significan t a t th e .1 0 level , one-taile d tes t •••SAMPL E - Al l hig h &r,c lowlea

d subject s tested .P.2 4



### Tabl e 4 REGRESSIO

N COEFFICIENT S FO RHIG H AND LO

W LEA D SUBJECT S EXCLUDIN

G1 6 CASE S WIT H LEA D INTOXICATIONS * IQVE R XQPE

R FULSCLXQ VERBALXQ PERX Q AGEXNM O

PARENTX Q

MOMEDUC H

DADSOCC L

MOMAGEB R

NUMLIV E

PBLEV 2

DUMM Y

CONSTAN T N** * R(2 ) S E F .822 3

(7.47) * .321 6 (4.67> * -1.941 9 (1.87) * -.312 4 (.30 )

. 173 6 (1.02 ) -1.329 4 (2.16) * -3.981 3 (2.16) * -3.296 4 • (1.43)* * -41.96B 7 17 1
.2 9 10.9 2 14.7 9 .660 3

(3.31) * .582 1 (4.66) * -1.246 2 (.66 ) -1.531 5 (.81 ) .090 4 (.29 ) -3.197 2 (2.89) * -4.334 1 (1.20)* * -11.307 8 (2.71) * .035 1 17 1
.2 7 19.8 2 8.9 6 .404 7

(5.53) * -1.847 4 (1.67) * -.526 9 (.48 ) .106 0 (.59 ) - 2 . 024 6 (3 . 16) * -4.928 3 (2.56) * -6.844 3 (2.8) * 75.456 9 17 1
.2 6 11.6 2 14.8 8 .356 3

(4.71) * -2.355 7 (2 . 06> * -.138 4 (.12 ) .112 8 (.60 ) -1.446 1 (2.18) * -5.097 3 (2.56) * -5.883 8 (2.33) * 76.714 1 17 1
.3 1 12.0 0 11 . 8 5 .380 8

(4.89) * -1.009 5 (.86 )

- . 790 0 (.67 )

. 1163 (.60 ) -2.£90 6 (3.36) * -3 . 587 3 (1.75) * -6.246 1 (2.4) * 77.837 4 171 . .2 9

10.7 6

•« • t statisti c i nparenthese s belo w coefficien t V- 'mm •



### . * significan t a t th e .0 5 level , orie-taile d test . ••significan t a

t the .1 0 level , one-taile d test . •••SAMPL E - Al l hig han d lo w subject s excluding thos e wit h history

o f excess " lea

d o r lea

d poisoning .P.2 5



### Tabl e 5 REGRESSIO

N COEFFICIENT S FO R14 2 SUBJECT S INCLUDED I

N TH E ORIGINA

L DAT A ANALYSIS *

AGEINM O

PARENTI Q

MOMEDUC H
• 

### DADSOCC L

* 

### MOMAGEB R

NUMLIV E

PBLEV 2

CONSTAN T N** *
R(2 ) S E F XQVE R .8581 (7.25) * .342 2 (4.41) * -1.277 0 C1.12 )

- . 267 8 (.24 ) -.089 9 (.49 ) -1.216 1 C.B5> * -4.001 0 (1.98) * -48.538 4 14 2
.2 9 10.9 5 14 . 1 4 XQPE R

.743 2 (3.5) *

. 560 0 (4.1) *

. .754 0 (.37 ) -2.623 3 (1.3 ) .0331 ( . 10 ) -2.970 1 (2.5) * -4.718 8 (1.32)* * -6.435 9 14 2
.2 3 19.4 3 7.0 6 FULSCLX Q

. 408 9 (4.95) * -.776 1 (.64 ) -.717 6 (.59 )

. 006 7 (.03 ) -1.932 8 (2.81) * . -5 . 129 0 (2.43) * 73.586 1 14 2
.3 0 11.6 6 11.0 4 VERBALI O

.380 8 (4.46) * -1.513 8 (1.21 ) -.045 9 (.03 ) .011 4 (.05 ) -1.358 9 (1.91) * -5.045 2 (2.31) * 72.452 7 14 2
.2 6 12.0 2 9 . 1 9 PERI Q

1.255 6 (4.10) *

. 160 2 (.13 ) i 

### -1.258 2 (1.07 ) .025 4 (.12 ) 2 . 129 6 (2.95> « -4.099 5 (l.;85) « 79.925 9 14 2

12.2 5 7.7 7

* t statisti c i

nparenthese s belo w coefficien t

* significan t a

t th e .0 5 level , one-taile d tes t ••significan t a

t the .1 0 level , one-taile d tes t •«*SAMPL E - Al l hig han d lo w subject s included i nanalysi s

' • *

### Tabl e 6 REGRESSIO

N COEFFICIENT S WIT H AGE-STANDARDIZE D DEPENDENT VARIABL E AN D AG E INDEPENDENT VARIABL E

AGEXNM O
PARENTI Q
MOMEDUC H
DADSOCC L
MDMAGEBR
NUMLIV E
PBLEV 2
CONSTANT N
R<2 > S E F FULSCLX Q -.166 1 . (1.3)* *

' .412 3 (5.0) *

-. 760 7 (.63 ) -.798 6 (.66 ) -.021 3 ( . 11 ) -1.765 7 (2.53) * -4.582 7 (2.14) * 88.148 2 14 2
.3 0

m. m, . Gtmm 

### 9.7 7 VERBALX Q -.159 4 (1.23 ) .384 1 (4.5) * -1.499 0 (1.20 ) -.123 7 (.1 ) -.015 4 (.08 ) -1 . 198 5 (1.67)* * -4.520 9 (2.04) * 86.427 5 14 2
.2 6 12.0 1 8 . 1 2 PERI Q

-.169 4 (1.28)* * .359 1 (4 . 14) * .176 0 ( . 14 ) ' -1.440 8 (1.14 ) .002 1 0 -1.959 1 . (2.67) * (1.57)* * 94.788 8 14 2

. 2 2

t Z'Z'Z' m 4_ > W — 

### 6 . 9 2



### • significan t a

t the .0 5 level , one-taile dtest , ••significan t a

t th e .1 0 level , one-taile dtest .

### Tabl e 7 REGRESSIO NCOEFFICIENT S WIT H LEA D A S A CONTINUOU S VARIABLE *

AGEXNM O

PARX Q

MOMEDUC H

DADEDUC H .
MOMAGEB R

NUMLIV E

DUMM Y

PBMEA N RAWVERI Q 0.823 6 (8.13) * 0 . 253 5 (4 . 12) * 0.995 0 (1.91) * 0.189 0 (.52 ) 0.128 3 (.81 ) -1.202 0 (2.05) * -3.874 0 (1.87) * -0.165 2 (2.22) * RAWPERI Q

0.768 7 (4.33) * 0. 532 6 (4.94) * -0.215 4 (.24 ) 1.789 0 (2.6) * -0.148 0 (.53 ) -1.535 5 (1.49 ) -7.878 0 (2 . 17) * -0.£23 4 (1.81) * FULSCI Q

0.333 3 (5.28) * 0.6312 (1.18 ) 0.738 1 (1.97.) * 0 . 029 0 ( . 18 ) -1.416 6 (2.36) * -5.612 0 (2.64) * -0.198 0 (2.67) * SCVERI C

0.273 6 (4.06) * 1.035 2 (1.82) * 0.379 2 (.95 ) 0.067 7 (.39 ) -1.222 0 (1.91) * -5.558 0 (2.45) * -0.201 5 (2.55) * SCPERI Q

0.336 6 (5.6) * 0 . 066 7 ( . 12 ) 0 . 989 5 (2.5); * 0.066 3 (.04 ) -1.378 4 (2.18) * -4.368 4 (1.95) * -0.155 7 (1.99) *

* t statisti c i n oarenthese s oelo w coefficient
.
* Significan t a t th e 0.0 5 level , on e taile d test . Samsle i Al l subject s exces t tr.os e wit h P I ur nDieman

d missin g values .

*.-••* .P.2 8



### Tabl e 8 T-TES T OF MEANS : MISSIN GOBSERVATION

CASE S VERSU S N O MISSIN

GOBSERVATIO

N CASE S FO

RMEAN , MEDIAN , GEOMETRI C MEA N LEA D LEVEL S T Statisti c P bDentine PbDentin e PbDentin e Geometri c MeanMedianMean Origina l Mode l (N»156 ) .0 2 * 

### Entir e Sampl e (N»270 ) .6 0 Lo w Lea dGroup(N-133 ) .8 6 Hig hLeadGroup(N*85 ) -.0 7 Unclassifie d Lea

dGrou p (N=53 ) -2.09 ^ -.7 4 -.4 3 . 0 4 . 9 2 . 9 7 

### -..2 8 

### -.0 3

1.5 5 . 8 4 

### 1 . 1 9



### • Significan t a

t th e .0 5 level .