# OAR Box 1126 Prepped by Ollie Stewart



## Document

Number: 

# 7)11-1-12 8 Docket Number: 

# A-83-2 2

Printed 4/18/20089:58:21 AM Sheet 7 of 182 P. 1P. 2

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Clair e B « Ernhar t February , 198 4 Comsies&t

s

WL. Chapte r 1 2 Ai r Qualit yCrifcErSL a fo r Lea d Previou s review s covering variou s pojrtifom s o f thi s materia l hav e bee n provide d t o EPA

o Copie s o f thes e ar e appended * lathe r than repeating portion s o f these , theywil l b e referre d t o b ytlbeir date s an

d pag e number s a s Indicated o Note : Recommende d insert s i n tex t ar e inddaafte d b yunderlines , deletion s b y brackets . Sectio n Pag e Para . Lin e 12.4. 2 4 1 3 14-1 5

12.4. 2 4 1 4 4 up 12.4.2.2. 1 5 2 1 10-1 1

12.4.2.2. 2 5 4 3 1 3

12.4.2.2. 2 5 4 3 1 8

12.4.2.2.2. 1 Recommen d deletio n o f th e Cowa n an d Leviton,198 0 an d Needlema n and Landrigan , 198 1 reference s sinc e theycit e methodologicall y poo r researc ha s example s o f soun d techniques . Chang e multipl e comparison s t o regressio n analysis . Cohe n an d Cohen , 1983 , ne wedition . "I t shoul d als o lead exposure. " Ther e i s no t sufficien t evidenc e t o substantiat e thi s statement . Se e discussio n o f studie s below . ...growin

g evidenc e indicate s tha t moderatel y highlea d exposure s no t leading t o diagnose d [overt ] lead Intoxication... " describe s th e availabl e <2^idenc e mor e accurately . Seve n criteri a wer e liste d o n p . 41 . Inappro
priat e generalizatio n and interpretatio n characterizes-- a numbe r to f th e studies . Failur e t o Isolat e decisio n raaking about , say, - Inclu

sio n o r exclusio n o f subjects , fromknowledg e o f othe r feature s o f th®aSat a ca n lead t o seriou s bias . Se e MyJan . 8 3 review , j>. 7 and Apri l 82 , p . 7 . Th e analyse s o f dat a ar e limite d wit h continuou s variable s truncated . Thi s lead s t o oddities , suc ha s a significan t finding fo r Ful l Scal e I Q bu t no t fo r Verba l o r Performanc e IQ . Cutting variable s Ji n thi s wayca n lead t o

-1

-P. 3

' I fortuitou s results . Perhap s mor e Importantly , covariate s ar e not controlled . Givensmal l effec t sizes , th

e Inclusio

no f th e materna l intelligenc e measur e i nanalyse s might hav e eliminate

dstatistica l significance . Thi s i s t on e o f thos e studie s i nwhichwha t i s no t ••;, * | include di s o f interest . Uhy;dl dth e inve s ti-**"* " gator s no t present results'relatin g th e dentine lea dmeasure s an

dth e outcom

e variables ? Th

e longitudina l dat a se t i s appropriat e for th e purpose . Omission s ca ncove r discrepant findings . 12.4.2.2.2. 1 6 0 2 3 u pJan . 83 , pp . 2-4 . Exampl e o f stretching . 12.4.2.2.2. 1 6 1 2 1 4 Mor e stretching . I nthi s case , there wer e a large number o f tests . 12.4.2.2.2. 1 6 1 3 Perino-Ernhart . See appende dmemorandum . 12.4.2.2.2. 1 6 2 2 Ernhar t et al . See appende dmemorandum . 12.4.2.2.2. 1 6 3 3 1 2 u pTh e consistenc

y foun dma y simply be due to th

e limite dcontro l of confoundin g variable s i n mos t of thes e studies . Sinc e lea dexposur e tends to b

e relate

dt o other factor s tha t ar e relate dt o poo

r outcome , limitation s i nthi s regar dwil l replicat e acros s studie s i na wa y that ca ngiv e th e appearanc e o f consistent , thoug hsmal l effects . Replicatio nexacerbate s thi s kin

do f bias . Wha t i s amazin g i s that there i s s o littl e evidenc e o f effec t for asymptomati c hig

hlevels . 12.4.2.2.2. 1 6 3 3 9 u pThi s i s th

e issu e o f threshold . See Jan . 83 , pp . 9-10 . 12.4.2.2.2. 2 6 6 2 6 u pAnother exampl e o f stretching . On e o f th e really remarkabl e thing s about th e Smithstud

y i s that th

e sampl e siz e i s quit e large , large enoug ht o hav

e th e statistica l powe r necessar y t o detec t ver

y smal l effec t sizes . As stated , p . 67 , a larger proportio no f toothdoner s wer e o f a higher socia l clas s tha nnon-doners . Thi s differenc e i s extremel y smal l an

dreache s statistica l significanc e becaus e o f th e ver y large sampl e size . I t i s a ninterestin

g incidenta l findin

g an ddoe s not reflec t a selectio

nbia s that limit s generalizability . Ther e wer e mor e tha nenoug hworkin

g clas s participant s t

o provid

e adequat e varianc e to detec t a

neffect , giventhere wa s one .

-2 -P. 4

12o4o2o2o2 0 2 6 7 12.4.2.2.2. 2 6 8 12.4.2.2.2. 2 6 8 12.4.2.2.2. 2 6 9 

### 3

2 3 1 1 up 

### 1 8



### 7 12.4.2.2.2. 2 6 7 1 1 0 Hhybrin g I n Yul e and Lansdown , 1983 ? Ther e ar e n o significan t socia l clas s difference s i n tha t study . 12.4.2.2.2. 2 6 7 2 1 9 Th e correlation s o f -0.3 2 an d -0.0 6 di d no t contro l fo r confounding variables . Afte r contro l o f covariates , th e J_ fo r lea d wa s les s tha n LOO . Stretching again . O n Yul e an d Lansdown , se e above . "approache d significance " i s no t acceptable . Stretching again . Se e raySept . 8 2 comments . Th e consisten t patter n observe d ma ywel l b e nothing mor e tha n consistenc yo f covariat e effects . 12.4.2.2.2. 3 7 0 2 1 0 Sept . 8 2 comments . 12.4.2.2.2. 4 7 1 1 4 Thi s stud yi s a s seriousl yflawe d a s other s b y th e same investigator . Sinc e it' s new , I'l l step ou t o f thi s restrictiv e forma t t o writ e a shor t commen t date d Feb . 84 . 12.4.2.2.2. 5 7 1 3 Se e Jan . 83 , p . 6 . 12.4.2.2.2. 5 7 1 4 Se e m ycomment s o n Otto , Feb . 83 . 13.5.2. 2 3 1 3 5 u p I' mno t sur e I' d agre e wit hthi s withou t seeing some statemen t regarding th e fac t tha t effect s a t moderat e levels , sa y3 0 t o 5 0 pg/dl , give n theyhol d up i n adequatel ydesigne d research , mayb e reflecting a n earlie r highe r exposur e level . Se e Jan . 83 , pp . 9-1 0 o n th e issu e o f threshold . 13.5.2. 2 3 3 2 5 Th e Ott o studie s ar e bette r than some i n thi s area , bu t calling them"o f considerabl e importance* 3 i s no t justifie d i n vie wo f th e problem s i n interpreting thei r results . Se e Feb . 83 . 13.5.2. 2 3 3 3 1 2 up Th e onl ystudie s reporte d t o dat e wit h plausibl e dat a o n persistenc e o f effec t ar e thos e o f D e l a Burd e an d associate s an

d myself . A s note d earlier , ther e ar e majo r problem s i n he r studies . W o amoun t o f stretching ca n lead t o a n interpretatio n o f persistenc e o f effec t fromm yearl ylead measure s t o th e late r measure s o f intelligence , behavio r an d othe r variables .

-3

-P. 5

13.5.2.2 . 3 5 2 3 The suggestio ni nthi s paragrap

htha t there I s increasin

g evidenc e o f impaire dneuropsycho logi c functionin

g a t bloo

dlea dlevel s belo

w 3 0 t o 4 0 Vg/d l i s simply no t warranted . Th e recent U.K . studies , an dparticularl y

th e wel l conducte

dM . Smit hresearch , ar e important i n thi s regard . It' s telling , I believe , that th e bette r th

e research , wit hgoo dcontro l o f confoundin

g variables , th

e les s th

e likelihoo

d o f positiv

e findings . 13.7. 3 4 3 Tabl e See Jan . 83 , p.11 . Touar e stil l reportin g figure s i na wa

y tha t al l urba

nchildrenwithi n th e ag e categorie s an dal l potentia l fetuse s o f urba nwomenar e a t ris kfro m lea dexposure .



### -4 -P. 6 /£i2flO-(JV-2i-CL jLfi.ec /. 30

Clair e B . Ernhar t February , 198 4 Comment s o n David , O.J. , Hoffnam D S. , & Grad , G . Penicillamin e i n th e treatmen t o f hyper

activ e childre n wit hmoderatel yelevate d lea d levels . In : Rutter , M. 5 Russel l Jones , L , Eds . Lea d versu s health : Source s and effect s o f lo wleve l lea d exposure . Ne wYork , N.Y. : Riley , 1983 , pp . 297-317 . Thi s i s a stud

yo f 5 4 childre n identifie d a s hyperactiv e withou t identifie d etiolog

yfo r hyperactivit ywh o als o presente d lead level s i n th e rang e o f 2 5 t o 5 5 yg/d l whol e blood . Dat a froma grou p o f 1 4 childre n wit h historie s o f lead poisoning wer e als o reported . Th e grou p o f 5 4 childre n wa s divide d int o thre e group s wit hblinde d administratio n ove r a 1 2 wee k perio d o f (a ) penicillamin e an d a placeb o resembling methylphenidate , (b ) methylphenidat e an

d a placeb o resembling penicillamine , o r (c ) placeboe s fo r bot h drugs . Th e grou p wit hth e historyo f lead poisoning receive d th e penicillamin e an

d th e placeb o fo r methylphenidate . Th e result s wer e interprete d a s indicating tha t treatmen t wit hpenicillamine , whic hreduce d bloo d lead level , als o reduce d teache r rating s o f hyperactivity , paren t rating s o f hyperactivity , score s o n a n impulsive-hyperactiv e scal e an d a conduc t disorde r scal e o f a paren t symptomquestionnair e an d a rating o f a physicia n complete d clinica l globa l impression . Ther e ar e thre e Majo r weaknesse s i n thi s study . Regressio n effects . Th e subject s wer e selecte d o n th e basi s o n extreme score s o n th e instrument s t o b e use d a s outcome measure s o r correlate s o f these . Thi s fit s exactl yth e situatio n i n whic ha regressio n effec t lead s t o th e appearanc e o f a treatmen t effect . (Se e th e classi c Campbell-Stanley monograp ho n quasi-experimenta l design. ) Th e situatio n become s a bi t confusing , however , i n tha t childre n wer e admitte d t o stud yonl yi f th e scor e o n th e TR S hyperactivit yscal e wa s greate r tha n 2.5 , ye t th e mea n baselin e score s o n thi s facto r show n i n Tabl e 3 wer e 2. 2 o r 2.3 . Mayb e anothe r administratio n betwee n selectio n an d star t o f stud

ywa s subjec t t o regressio n effects . A t an

yrate , th e chang e attribute d t o treatmen t i s suspect . Randomassignment . Asid e fromth e historyo f lead poisoning group , assignmen t t o treatmen t wa s describe d a s random , bu t severa l exception s an d variant s confus e th e issue . Some childre n wit hhistorie s o f lead poisoning wer e assigne d non-randoml yt o th e methylphenidat e o r t o the placeb o group . Eigh t childre n treate d i n th e firs t yea r wit hmethylphenidat e o r placeb o wer e late r include d i n th e penicillamin e group . (Apparentl ytheyentere d th e stud ytwice. ) Ther e wa s a "chanc e preponderance " i n th e assignmen t o f childre n t o th e penicillamin e conditio n i n th e firs t two years , leading t o a disproportionat e numbe r i n tha t group . Ther e wa s a highdro p ou t rat e i n th e placeb o group . Betwee n grou p dro p ou t rate s ar e no t othe r wis e mentioned ; differentia l mortalit yma yb e relevant . (Campbell-Stanley. ) Statistic s comparing group s o n baselin e measure s ar e no t provide d bu t w e not e tha t childre n assigne d t o methylphenidat e wer e initiall yhigho n the paren t rating o f hyperactivit y(Tabl e 4 ) an d childre n assigne d t o th e placeb o contro l wer e initiall yrate d lo wo n the physician complete d globa l impressio n scale .P. 7

Comment s o

nDavid , e t al. , 198 3 . 2 Clair e B . Ernhar t Statistica l analysis . Th e appropriat e statistica l analysi s woul db e MANOV A o f repeate

dmeasure s o f al l outcom e measure s considere da s a set . Th

e hypothesi s o f a differentia l penicillamin e effec t woul dthe

nb e teste db y an interactio

neffect . (Thi s coul dhel ptak e car e o f th

e abov e mentione

d proble m wit hstatistica l regressio nsinc e regressio

nshoul db

e similar acros s treatments. ) Givensignificanc e wit hthis , breakout univariat e statistica l test 8 coul db

e justified . Instea dw e see a large number o f t-tests , wit h som e reporte

da s significant a t .10 , one-tail .P. 8 £<2fiO(:7>-2/Zj

Clair e B . Ernhar t February , 198 4 Respons e t o Mem o Date d Novembe r 30 , 198 3 fromLeste r D . Gran t Subject : Corrigend a fo r the Firs t Externa l Revie wDraf t

o f 198 3 Revise d EP ACriteri a Document , Ai r Qualit yCriteri a fo r Lea d Thi s respons e i s mad e t o th e sectio n o n Pag e 3 whic hindicate s a aodificatio n o f Chapte r 12 , p.12-6 2 o f th e draf t o f th e abov e Indexe d document . Thi s modificatio n conclude s "Pending resolutio n o f methodologica l problem s wit hth e Ernhar t dat a se t and/o r publicatio n o f adequat e reanalyses , th e subjec t studie s ar e no t considere d furthe r i n thi s document. " Thi s statemen t implie s tha t I faile d t o conduc t th e reanalyse s suggeste d b yth e Exper t Committe e convene d t o revie wthi s stud yan d on e other . I n fact , al l reanalyse s suggeste d a t th e initia l revie wi n Inarch , 198 3 wer e conducte d an

d furthe r wor k wa s undertake n t o clarif yissue s raise d i n th e cours e o f thes e reanalyses . I di d no t d o on e additiona l analysi s suggeste d b ya Committe e membe r afte r al l othe r analyse s wer e completed . I t i s m y opinion , an

d I wil l discus s thi s agai n i n thi s response , tha t th e suggeste d reanalysi s i s irrelevan t t o th e questio n o f whethe r th e dat a suppor t th e hypothesi s tha t ther e ar e identifiabl e effect s o f lead a t lo wlevel s o f exposure . Fo r th e purpose s o f thi s document , however , th e implicatio n o f failur e t o cooperat e i s les s importan t tha n consideratio n o f th e qualit yo f th e dat a a s theyrelat e t o the question s unde r review . Amanuscrip t i s no wbeing prepare d fo r publicatio n o f th e reanalyse s tha t wer e conducted . Pending completio n o f this , however , a numbe r o f feature s o f th e stud yar e clearl y delineate d i n the material s provide d t o th e Committe e an d ar e relevan t t o th e inference s being drawn i n th e documen t i n preparation . I wil l star t wit ha respons e t o particula r item s o f criticis mpertinen t t o mywor k a s liste d i n Appendi x 12-C , Novembe r 14 , 198 3 version . Item s no t mentione d ar e eithe r no t see n a s area s o f difficult yo r the reviewer s conside r th e difficult yt o b e minor . I t i s importan t t o not e tha t man yo f th e suggestion s fo r correction s o r reanalyse s had bee n mad e earlie r o r had bee n anticipate d i n th e cours e o f m y reanalyse s an

d tha t thes e had bee n Incorporate d int o th e summaryrepor t supplie d i n August , 1983 . I n some section s o f th e revise d Appendi x 12- C i t appear s a s i f th e reviewer s copie d th e Augus t 25 , 198 3 versio n (writte n befor e receip t o f m ysummaryreport ) wit hlittl e o r n o consideratio n o f th e materia l supplie d i n th e summaryrepor t o r i n m yOctobe r 7 , 198 3 mem o i n respons e t o th e firs t version . I n general , I appreciat e th e wor k o f th e Committee , bu t th e failur e t o conside r th e wor k tha t I di d i s disappointing . Thi s wor k wa s conducte d a t th e reques t o f th e Committe e an d wa s quit e pertinen t t o the issue s raised . I ca n understan d th e problem s facing th e member s o f th e Committe e i n th e handling o f th e othe r stud yunde r revie wan

d the pres s o f time fo r th e preparatio n o f a report . Nevertheless , th e conclusion s draw

n wit hrespec t t o m ywor k bespea k a disinteres t i n th e reanlyse s requeste d an d supplied .P. 9

B . 1 , p . 11 , (d) . A s indicate di nth e th e Summar

y Report , p . 4 , ite

m 1 , lea dlevel s for a s man y a s possibl e o f th

e childreni nth

e follow-u

pdat a set wer e corrected . B . 2 . p . 12 , (a) . I agre e that th e Amnion s QuickTes t i s les s vali dtha n shor t form

s o f th e WAIS , howeve r administratio no f eve

na shor t for

m o f th e WAI S woul dhav

e resulte

di nanunacceptabl e an dbiasin

g refusa l rate . The us e o f th

e Q T wa s anappreciabl e improvement i nth e stat e o f th

e ar t for that tim e an dth e us e o f eventhi s vali danindicator o f parent intelligenc e wa s no t see ni nothe r studie s o f thi s topi c unti l som e tim e later . Som

e degre e o f validity

i s indicate

db y it s correlatio

nwit hth

e othe r variable s i nth e study , includin

g th e ver y fac t that stepwis e analyse s gav e i t priority

over al l other measures , includin g parent education . I f it s reliability wa s ver

y low , i t coul dno t hav e functioned , a s i t did , i nrenderin g previousl y significant lea

deffec t analyse s non-signfleant . I f i t ha dbeenmor e valid , th e smal l varianc e associate dwit hlea

dwoul dprobably

hav e beenreduce

deve n further , giventh

e directio

no f effect s i nthi s research . B . 2 . p . 13 , (e) . Th e error s i nth

e Perin o dat a wer e foun

dan d corrected . B . 3 . p . 15 . Th

e comment s made about statistica l analysi s ar e wel l taken . However , th

e requeste

dstatistica l analyse s wit hlea dan dal l availabl e confounder s ha

dbeenmade an

dreported . See Summar y Report , p . 5 , ite

m 2 . B . 3 . p . 16 . Test s o f interactio nwithth

e mos t relevant confounder , parent IQ , ha

dbeenmade . See Summar y Report , p . 5 , ite

m 4 . B . 3 . p . 16 , (a) . Correction s fo r unreliability

wer e no t undertaken , bu t one techniqu

e for copin

g withthi s wa s employe di nthat a composit e inde xof th e lea dmeasure s wa s als o analyzed . See Summar y Report , p . 5 , ite

m 3 . B . 3 . p . 1 6 (c) . Onl y ver y sligh t difference s woul dhav e resulte

dfro m regressin

g th e schoo l age intelligenc e tes t score s o nage , a s oppose

dto th e us e o f extrapolation . W e ha danalyze

dth e preschoo l dat a usin g bot hage regresse

dscore s an

dnorme dscore s an

dfoun dn o differenc e eve

nthoug hth e norm s fo r that age range seeme dinadequate . Earlier i nth e revie w (B . 2 . p . 14 , (d)) , th

e reliability

o f th e scales , eve

nwithinterpolate

dscores , wa s considere

dto b e considerable . B . 3 . p . 1 6 (d) . The fac t that th e outcom

e measure s wer e correlate dwa s considered , first , i nth e us e o f th

e T 2 screenin

g o r omnibu s analyse s fo r th e revie w o f th e ful l dat a set , and , second , i nth e interpretatio

no f th e data . Th e us e o f multivariat e analysi s o f covarianc e woul dhav e require

dcate gorizin g subject s int o group s o nth e basi s o f th

e lea dvariables . B . 3 . p . 1 6 (e) . I certainly agre e that i t i s preferabl e to keepdat a i n a continuou s for

m a s oppose

dto categorizatio

nan dthi s i s par t o f th e reaso n fo r usin g regressio

nanalyses . Wher e th e dat a are categorized , i t i s usuall y fo r th e purpos e o f makin

g result s clearer to persons not accustome dt o thinkin g i nterm

s o f proportion s of variance , etc . B . 3 . p . 1 6 (f) . I wa s not aware that Perin o ha dmor e hig

hlea dcase s early inth e dat a collectio

nperiod . Hi s wif e ha dset u pth e dat a collectio

n

-2 -P.1 0

schedul e and th e numbering scheme . Sinc e h e wa s unawar e o f th e lead level s an d sinc e h e wa s wel l trained , I don' t think th e orde r had a n effect , bu t i t wasn' t ideal . B . 3 . p . 17 , para . 2-3 . Thi s i s a aodifie d versio n o f & mor e detaile d suggestio n mad e i n th e Augus t 25 , 198 3 Appendi x 12-C . I discusse d thi s suggestio n i n m

yOctobe r 7 „ 198 3 respons e an d I d o no t fee l tha t o yrespons e wa s give n reasonabl e consideration . Th e critica l relationshi p i s betwee n earl ylead exposur e and late r intelligence . On e migh t als o as k i f ther e i s a significan t relationshi p betwee n earl ylea d and chang e i n intelligence , particularl yi f ther e i s a significan t lea d effec t o n th e earl yintelligenc e measure . An d on e migh t measur e chang e eithe r a s a simpl e chang e score , a s I di d i n respons e t o Committe e suggestio n (reporte d i n th e SummaryReport , p.5 , item5) , o r b y regressing th e late r intelligenc e measur e o n th e earlier . Ther e i s n o way , however , b ywhic ha correlatio n o f tw o set s o f residua l scores , effectivel yremoving th e varianc e o f th e earl ylead measure , ca n b e considere d t o provid e a tes t o f lead effects . Th e fac t tha t bloo d lead level s decreas e wit h ag e (or , possibly , time ) i s important ; th e effect s o f toxi c exposur e i f any , woul d certainl yb e greate r a t th e highe r leve l an d a t th e earlie r age . Al l th e analysi s suggeste d woul d accomplis hmigh t b e a statemen t tha t th e exten t o f th e dro p i n lead leve l i s greate r fo r thos e childre n wh o sho wsome increas e i n measure d intelligenc e an d tha t ther e i s les s decreas e i n lea d leve l fo r thos e whos e Intelligenc e decreases . O r vic e versa . I though t I had responde d quit e clearl yt o thi s issu e i n th e Oct . 7 , 198 3 respons e t o th e earlie r versio n o f Appendi x 12- C an d I ar a disappointe d tha t th e opinio n o f th e reviewe r i n thi s regard wa s no t clarifie d mor e fully . Ther e i s n o questio n bu t wha t longitudina l analysi s involving chang e ove r time , particularl ychang e i n th e measure d outcome variable , i s important . Thi s i s on e o f th e strength s o f th e study ; unti l th e dat a fromthe prospectiv e studie s ar e available , thi s i s the onl ystudy , asid e fromth e D e l a Burd e reports , t o relat e systematicall ycollecte d earl ylead measure s t o late r intelligenc e measures . Thi s applie s bot ht o th e preschoo l lead measure s an

d t o dentin e lead leve l a s a n indicato r o f earl yexposure . B . 4 . Th e Committe e conclude d tha t th e bloo d lead an d th e psychometri c measure s wer e adequate , bu t tha t confounding measure s ma yno t hav e bee n adequatel ymeasured . Th e measur e o f paren t intelligenc e mus t hav e bee n reasonabl yvali d o r i t woul d no t hav e entere d dat a analysi s a s i t did . Th e inclusio n o f th e educatio n measur e I n dat a analysi s ha d n o effec t o n th e results . Th e dat a o f th e Perin o stud ywer e correcte d an d wer e use d wit hth e 198 1 dat a i n longitudina l analyses . I believ e tha t th e Committe e wa s reeis s i n failing t o conside r the reanalyse s mad e an d th e response s provide d i n th e SummaryReport , th e Respons e t o Appendi x 12- C date d Octobe r 7 , 1983 , an d m y lette r t o Dr . Gran t date d Octobe r 25 , 198 3 whic hwoul d hav e bee n receive d prio r t o th e las t meetin g o f th e Committee . Th e Yamin s dissertatio n wa s include d i n thi s revie wan d reanalyse s wer e mad e o f th e dat a a t th e reques t o f EPA . Thi s stud ywa s no t published ; w e di d no t fee l tha t i t wa s strong enoughfo r publication . I f w e had bee n abl e t o

-3

-P.1 1

correc t th

e bloo dmeasures , i t might hav e beenfeasibl e t o merg e thes e dat a wit hth e Perin o data , a s indicate do np . 3 o f th

e Summar

y Repor t t o increas e th e statistica l power fo r cros s sectiona l analysi s at th e preschoo l age . A s i t happens , i t wa s rather a wast e o f tim e for th

e Committee t o hav

e reviewe

d i t i nsuc

hdetail . Th

e Committee Conclusions , p . 21 , indicat e further that th e materia l provide

di nth e Summar

y Repor t wa s no t integrate dint o th

e preparatio

no f Appendi x12-C . Conclusions . Th

e quality

o f th e dat a an

dth e analyse s conducted , includin g th e reanalyses , i nth e Perino-Ernhar t an dErnhart , e t al. , studie s i s superior t o that o f mos t o f th e studie s treate

dwit hcredibility

i nth e Draf t o f th e Ai r Quality

Criteri a fo

r Lead . Th

e dismissa l o f th

e finding s appear s t o be due t o th

e fac t tha t I challenge dth e procedure s usedi nanothe r stud y whichha s beenvariousl y describe

da s "classic " or "pioneering. " Weaknesse s i nthi s latter study , an dit s spin-offs , hav e beennote

db y other s an

da carefu l revie

w o f tha t wor kwa s i norder . I t appear s a s i f m y workwa s als o subjec t to revie

w i norde r to provid e a nappearanc e o f fairnes s to th e revie w o f th e othe r work . I di dno t objec t sinc e I hav e nothin

g to hid

e an dsinc e I fel t tha t thi s would , indeed , facilitat e th e carefu l revie

w o f th e other work . Reanalyse s wer e suggested . Thes e wer e based , i npart , o nmor e recentl y

publishe

d report s regardin

g problem

s i nth e bloo danalyse s use

di none o f m

y studie s and , i npart , o

nsuggeste

dvariation s i ndat a analysis , a s th e inclusio

no f educatio

na s a covariat e (thoug hI kne w i t woul dcontribut e nothing ) an dth e analysi s o f change scores . Thes e analyse s wer e done . The exclusio

no f th e result s o f m

y workfro

m consideratio

ni nth e Revie w Draf t to impar t anaura o f fairnes s fo r th e exclusio

no f a clearl y

faulte d wor k i s highl y

discriminatory . Mor e important tha ndiscriminatio

nagains t m

y wor k i s th

e exclusio

no f th e finding s o f that workl nth e conclusion s to b

e draw nwit hrespec t t o th e effect s o f lo

w leve l lea

dexposure o

nchildren . Sinc e th

e Committee faile

dto'integrat e reanalyse s int o it s conclusion s an d simply dismisse

dth e studie s a s no t providin g conclusiv

e evidence , i t i s incumbent o

nm e t o integrat e th

e finding s o f thes e studies . Finding s o f th

e Perino-Ernhar t Studies . 1 . A sampl e o f 8 0 urba

ndisadvantage

dblac kchildre

nwit hbloo

dlea d level s rangin

g fro m .0 1 t o .0 7 mg/d l whol e bloo dwa s teste

dwit hth

e McCarth

y Scale s o f Childrens ' Abilities . N o statisticall y

significant relationshi p wa s foun

dbetweenlea

dleve l an

dperformanc e o

nan y scal e o f th

e McCarth

y Scale s whenparent intelligence , birthweight , an dparent educatio

nwer e entere dint o th

e model . Thi s i s i ncontras t to previousl y reporte

d findings . Th

e change i s du

e to a nerror foun

di nth e computatio

no f th e age o f one chil dan

dto th e previou s us e o f anincorrec t terr a fo r degree s o f freedo m i nananalysis . Paragrap h3 , p . 12-6 1 o f th e Revie w Draf t need s correctio

nto accommodat e thes e correcte dfindings . 2 . Wit hthi s sam

e sample , there i s n o significant differenc e betwee n moderat e an

dlo w lea dleve l group s i nth e correlatio

no f parent an

dchil d intelligence . Thi s represent s a correctio no f th e previou s report . Th e

-4 -P.1 2

correctio n i s du e t o the change d intelligenc e tes t scor e fo r th e abov e indicate d child . Paragraph3 , p . 12-6 1 o f th e Revie wDraf t need s correctio n t o accommodat e thes e correcte d findings . 3 . Fiv e year s late r 6 3 o f thes e childre n wer e trace d an d examine d wit h th e McCarth

yScales , th e Bende r Gestal t Test , and severa l exploratory measures . Teache r rating s wer e obtaine d and score s o n reading test s wer e provide d b

yth e schools . Th e dat a o f on e chil d wer e exclude d o n th e basi s o f a dentin e lead leve l consisten t wit hfrank lea d poisoning an d clini c obtaine d environmenta l evidenc e supporting tha t inference . Th e mos t importan t analyse s o f thes e dat a ar e longitudinal , i.e. , determining the possibilit yo f a n effec t o f th e early , preschoo l lead exposur e inde x o n th e late r outcome measures . Thes e ar e particularl y critica l analyse s bot hbecaus e lead level s a t th e preschoo l perio d wer e significantly , an

d appreciably , highe r tha n thos e recorde d fiv e year s late r and becaus e preschoo l childre n ar e considere d t o b e mor e vulnerabl e tha n olde r childre n t o lea d effects . Furthermore , persisten t effect s woul d undoubtedl yb e mor e seriou s tha n concurrent , bu t possibl ytransitor yeffects . Th e preschoo l bloo d lead level s wer e no t significantl yrelate d t o an yo f th e abov e liste d outcome measures , no r wer e theysignificantl yrelate d t o chang e score s compute d fo r th e Genera l Cognitiv e Inde x o r th e Verba l Inde x o f th e McCarth

yScales . (Thes e wer e chose n fo r measuremen t o f chang e sinc e they wer e th e mos t valid , an d probabl yth e mos t Importan t o f th e outcome measures. ) O f particula r importanc e ar e th e measure s o f intelligenc e an d the teache r behavio r rating s sinc e thes e hav e bee n relate d t o lead leve l i n some o f th e methodologicall y-weaker studies . 4 . Anothe r inde x o f earl ylea d exposure , dentin e lead level , wa s avail

abl e fo r 3 3 o f th e childre n (wit hthe outlie r cas e excluded) . Thi s wa s no t significantl yrelate d t o an youtcome measure . 5 . Bloo d sample s had bee n collecte d fo r al l childre n see n a t fiv e yea r follow-up . Technica l problem s i n th e analyse s fo r lead require d correction , bu t th e informatio n require d fo r thi s correctio n (hematocri t level ) wa s availabl e a t the time o f the reanalyse s fo r onl y4 5 o f thes e children . Analyse s o f th e adjuste d schoo l ag e lead leve l an d a lead leve l exposur e construc t (preschoo l lead , schoo l ag e lead , an d fre e erythrocyt e proto
porphyrin ) wer e made , wit hparen t Intelligence , paren t education , an d se x a s covariates . O f th e eightee n analyse s (si x McCarth yScales , Reading Level , and tw o chang e scores ) on e reache d significanc e a t th e .0 5 level . Asingl e devian t cas e mayhav e accounte d fo r thi s on e positiv e finding i n the set . Becaus e lead effect s migh t b e moderate d b ysocia l factors , the Interaction s o f th e stronges t socia l index , paren t intelligence , wit hth e adjuste d bloo d lead valu e an d wit hthe lead construc t inde x wer e analyze d fo r thes e same nin e outcome measures . On e o f th e eightee n analyse s wa s significan t a t th e .0 5 level . Th e interactio n o f paren t intelligenc e an d adjuste d lead leve l wa s significan t fo r the Perceptual-Performanc e Scal e o f th e McCarth

yScales . Thi s occurre d i n th e absenc e o f significan t mai n effect s fo r eithe r variable . Whil e score s wer e negativel yassociate d wit h lea d leve l fo r lo wintelligenc e parent s bu t positivel yassociate d wit hlead

-5

-P.1 3

leve l hig

hintelligenc e parents . Sinc e there i s n o mai neffec t i nthi s crossove r interactio nan dsinc e there i s n

o reasonabl e interpretatio no f beneficia l effect s for hig hintelligenc e parents , i t i s reasonabl e t o infe r tha t thi s i s a chanc e findin g i na nessentiall y

nul l se t o f data . 6 . Considere

daltogether , th

e result s o f thes e studie s len dn o suppor t t o th e hypothesi s o f significant effect s o f lea dexposure i nth

e range examined . O f particular Importanc e i s th e failure t o fin

dan y evidenc e o f an effec t o f th

e earl y exposur e o

nmeasure s made fiv e year s later .



### -6 -P.1 4 

### 'zcffoM'-D-Si-a- •rrfl.d.c./. SO 

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. Metropolita nGenera l Ilosb i i i 4 wa>mttttiMMr.>»o" w MMAMM M 

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. OHI O 4410 9 • 2 10-393-600 0

HENR YE

. MANNIN G PRESIDEN T GLEN N E.POTTE R VIC E PRESIDEN TOPEHATION S Octobe r 25 , 198 3

Dr . Leste r Gran t Unite d State s Environmenta l Protectio n Agenc y Environmenta l Criteri a an d Assessmen t Offic e (MD-52 ) Researc hTriangl e Par k Nort hCarolina , 2771 1 Dea r Les : Volume s I an

d I V o f the Revie wDraf t arrive d today . M yinitia l though t wa s tha t I woul d wai t unti l afte r th e Committe e meeting thi s wee k t o respon d sinc e yo u will , I presume , be revising the relevan t section s accordingly . (Correction s o f th e previousl yreporte d positiv e finding s o f th e Perino

Ernhar t dat a wil l b e mos t necessary. ) However , the presentatio n o f the Committee' s comment s o n 12-6 2 wa s suc htha t I decide d t o mak e th e following point s fo r thei r consideratio n a t th e meeting . I didn' t muc happreciat e the statement s o n 12-6 1 an d 12-6 2 regarding the exclusio n o f paren t educatio n fro mthe dat a analyses . I n bot hpaper s an d i n ora l exchang e wit hHerb o n th e matter , I state d tha t paren t educatio n wa s no t entere d becaus e i t didn' t contribut e significantl yt o th e mode l unde r an y circumstanc e afte r paren t I.Q . wa s entered . Bot hb ystepwis e an

d b ya rationall ybase d hierarchica l model , paren t I.Q . mus t ente r first . Th e enclose d summar

ystatement s fro

mthe analyse s summarize d i n m yAugus t repor t indicat e tha t on e can tak e paren t educatio n an d ente r i t i n an

ywaytha t an

y on e migh t lik e an

d i t wouldn' t mak e a differenc e fo r an yanalysis . Ther e ar e part s o f m

ywor k wit hwhic hon e migh t disagree , bu t the contentio n tha t I failed t o contro l paren t educatio n shoul d no t be on e o f them . Th e Ammon s Q T isn' t great , I know , bu t administratio n o f a WAI S unde r the circumstance s woul d hav e resulte d i n an unacceptabl e an d biasing refusa l rate . Th e us e o f the Q T wa s bette r than no t using anything . Some degre e o f validit yi s indicate d b yit s correlation s wit hth e othe r variable s i n the study , including the ver yfac t tha t stepwis e analyse s gav e i t priorit yi n the selectio n procedure . Th e ter m"questionabl e utility " overstate s it s limitations .P.1 5

I don' t agre e wit hthe statemen t o n 12-59 , lin e 3 , tha t d e l a Burd e an d Choat e conducte d the onl ystud ytha t wa s no t eithe r retrospectiv e o r cross sectional . Give n the problem s tha t I reporte d a s a resul t o f m yreanalyses , the on e ver

yimportan t finding tha t stil l hold s i s tha t ther e wa s n o significan t relatio n betwee n the early , an d appreciabl yhigher , preschoo l lea d level s an

d an youtcome measur e fiv e year s later . Becaus e the earlie r blood lea

d indice s wer e highe r an d becaus e childre n ar e considere d t o b e mor e vulnerabl e a t a younge r age , thes e exposur e dat a ar e particularl yimportant . Sinc e earl ylea

d leve l an

d schoolag e test s wer e no t affecte d b ythe variou s difficultie s note d b ythe Committe e an

d foun d b ym e i n the reanalyses , thi s i s wort h mor e than the rathe r incidenta l indicatio n o n lin e 14 , 12-62 . I f ther e i s an

yrelationshi p o f interes t i n thes e dat a b ynow , i t i s i n th e existenc e o f thi s demonstratio n tha t moderat e level s o f lea d i n th e earl y period di d no t hav e an effec t grea t enoughan d persisten t enought o be detecte d o n an

yo f the measure s use d fiv e year s later ; Ther e is , o f course , a powe r proble mi n making an interpretatio n o f minima l o r n o effect . Wit halpha se t a t .05 , powe r a t .80 , k = 4 (thre e covariate s an d lead) , n = 62 , an d the R 2 = .2 7 fo r GC I 77 , the detectabl e effec t siz e (incremen t i n varianc e associate d wit hlead ) woul d be.128 . I f alpha i s change d t o .01 , i t woul d be .190 . I' mno t sur e ho won e woul d handl e the powe r issu e fo r multipl e non-independen t outcome measure s suc ha s w e hav e i n thi s kin

d o f research . Mayb e Larr yha s some suggestions . Onc e again , I appreciat e the objective an d knowledgeabl e approac htake n b y th e Committe e i n thi s review . Sincerel yyours ,

Clair e B . Ernhar tP.1 6 JZ£- 3
. C. / . 3& 

### February , 198 3

Comment s onElectrophysiolog y an dLea d- Dav e Otto' s wor k Th e T S o r tone-shutte r procedur e i s describe da s followin g a classica l con ditionin g paradigm , bu t th e CRan dth e UCRappea r t o be reverse dindirection . I t i s the nappropriat e t o say tha t "P bexposur e interfere s i nsome wa y wit hcon ditionin g o r learning inchildren? " (Otto , e t al. , 1981 , p . 236) . Thes e dat a ar e base do n3 5 conditionin g trials . Becaus e o f artifacts , thes e wer e no t enoug hdat a t o describ e th e cours e o f conditioning . Usabl e dat a wer e obtaine dfro m 4 1 children , bu t some hada s few

a s 1 0 artifact-fre e trails . Significan t effect s o f leadandlead-by-ag e wer e reporte d(Otto , e t al. , 1981) . Onth e basi s o f th e linea r mode l includin g leadandth e lead-by-ag e interaction , predicte dregressio nline s wer e compute dfo r th e mos t extreme age s an dothe r ag e groups . (Thes e wer e no t empireall y andindependentl y

derive dfro

m th e respectiv e ages. ) Ther e appear s t o be n o significan t P beffec t fo r th e olde r ag e (4 8 - 7 5 months ) group . Thi s wil l be a concer ni f we try t o replicat e a t ag e fou r years . I s ther e an

y reasonabl e explanatio no f ag e interaction ? Th e number s a t th e respec tiv e age s andleadlevel s ar e relativel y low fo r th e interpretation s draw nandth e necessit y

o f a replicatio ni s clear . Th e author s di dreplicat e wit ha sampl e o f 2 8 childre nreevaluate dtw o year s later . (Som

e ha dno t beeninclude dinth e earlie r repor t becasu e o f artifacts , bu t al l hadbloo dleaddat a fro m two year s earlier. ) Bloo dleaddat a droppe da n averag e o f 1 1 pg/dl . Thi s appear s t o be a secula r rathe r tha na developmenta l chang e sinc e i t occurre dfo r olde r a s wel l a s younge r children . Althoug hneithe r ag e block s no r tria l block s correspon dexactly , i t i s possibl e t o conside r par t o f th e result s a s a replication . Thes e ar e tria l block s 1 - 4 0 fo r tw

o ag e groups . Fo r neithe r ag e groupandfo r neithe r PbB l (tw o year s earlier ) no r PbB 2 (current ) indice s wa s th e previou s findin g replicated , ye t Ott o (pape r fo r Rutter-Jone s book , p . 6 ) sai dtha t "th e same linea r relationshi po f SW voltage , ag e andP bwa s observed. " Ther e wa s a significan t P beffec t fo r the late r tiral s (4 1 - 100 ) fo r bot h earl y an dlate r leadindices , bu t th e P bb y ag e interactio nwa s significan t onl y fo r the earlie r P bindex . (Fo r 1 2 o f th e 2 8 childre nth e PbB dat a wer e the same betwee nreplications. ) Interestin g enough , however , th e directio no f th e interactio n wa s reversed . (I nth e Dusseldor f report , scatterplot s wer e mentione dbu t no t provided , s o I' m

lookin g a t extreme-ag e predicte dregressio nlines. ) Now ther e appear s t o be a slight , andprobabl y non-significan t negativ e relatio no f SW 4 1 - 10 0 andPbB l fo r olde r childre nbu t a positiv e an dprobabl y

significan t regressio no f SW 4 1 - 10 0 o

nPbB l fo r younge r children . Thi s i s th e revers e o f wha t ha dpre viousl y bee nreporte dfo r S W 1 - 3 5 an

dPbBl . This , too , i s inconsisten t wit h "th e sam e linea r relationshi po f SW voltage , ag e andP bwa s observed. " Thes e re versal s anddiscrepancie s ar e no t addressed . I f thes e piece s o f wha t appear s t o be a highe r orde r cros s ove r interactio nsituatio n(Pbxag e xtria l block s xrep lication ) ar e meaningful , th e rational e o f thes e reversal s i s no t given . Th e neg ativ e correlatio nbetwee nearl y an dlat e tria l block s make s fo r stil l mor e confusion .P.1 7 

### -2 - February , 198 3

Th e conclusio ntha t ther e i s a significan t linea r relationshi po f S W voltag e an dPbB withi na rang e o f si xt o 5 5 pg/d l deserve s discussion . Th e firs t study , inwhic hPbB wen t a s lo w a s si xpg/dl , wa s no t replicated . Fo r th e dat a o f th e secondtrai l bloc ko f th e secondstudy , th e confidenc e interval s o f th e projecte d regressio nline s o f th e tw o extreme age s overla ps o completel y inth e are a o f PbB < 3 0 pg/d l tha t ther e ma y actuall y

be littl e o r no effec t i nthi s range . Ott o make s a poin t o f th e linearit y o f th e model , bu t wit hrelativel y fe w subject s andth e for

m o f th e interaction , i t ma y be incorrec t t o say tha t ther e ar e sig nifican t effect s a t th e lowe r endo f th e PbB range . Althoug hOtt o ha s bee ndul y cautiou s i nstatin g tha t thes e measure s hav e no t ye t bee nvalidated , he ha s discusse dhi s result s i nterm s o f harmfulnes s a t lowe r level s o f PbB . Fro

m thes e studie s it' s difficul t t o determin e whic hdirectio no f effect s i s associate dwit hleada t wha t age . Ho w the nca nw e eve nsay wha t direc tiono f S W

effec t i s harmful ? O nth e basi s o f th e Ott o e t al . (1981 ) pape r we woul dassume tha t a negativ e voltag e i s deleterious , a t leas t inearl y trial s fo r childre nbelow ag e 4 year s (wit hlittl e o r n o indicatio nfo r olde r children) . Wit hth e ful l ag e rang e o f th e secondstudy , th e SW

1 - 4 0 i s correlate dnegativel y wit hIQ . Thi s suggest s tha t negativ e voltag e inth e earl y trai l block s i s beneficial . Whateve r i s goin g on , statement s abou t "harm " see m premature . Wha t i s th e basi s fo r th e statemen t tha t SW effects , whic hca ng o i neithe r direction , represen t CN S impairments? " Ott o andhi s associate s ar e t o b e commende dfo r undertakin g a difficul t task . The y ar e mor e knowledgeabl e abou t some aspect s o f researc hdesig ntha nar e some o f th e othe r investigator s workin g inth e leadeffect s topic . Th e us e o f linea r analysi s a s oppose dt o ANOV A indicate s a recognitio no f powe r consideration s an dmodels th e dat a arra y

mor e appropriately . Unfortunately , th e proportio no f varianc e accounte dfo r inth e analyse s i s no t reported . Th e correlatio no f .0 4 betwee nPbB l andSW 4 1 - 10 0 i s ver y

strang e (coul di t be a typo? ) give nth e significan t re gressio no f S W

4 1 - 10 0 o

nPbBl . Thi s se t o f paper s i s confusing . Whe non e add s th e cubi c trendlin e o f EE G spectr a gai ninth e Benignu s report , th e situatio nbecome s eve nstranger . Benignu s e t al . recognize dtha t currentl y obtaine dPbB value s ar e likel y t o be lowe r thanpreviou s pea kvalues . Thi s i s animportan t poin t i nview o f curren t attempt s t o attribut e effect s t o ver y lo w exposur e levels .P.1 8

-,--,,., • /ECAO - <?7> - #/• & ZLfl •£•€./. 3 a Clair e B
. Ernhar t Sept
. 22 , 198 2 Comment s o n Winneke , G. , Hrdina , K.G. , an d Broekhaus , A . Neuropsychologica l studie s i n childre n wit helevate d toot hlead-concentrations . Par t I : pilo t study . Internationa l Archive s o f Occupationa l an d Environmenta l Health(i n press ) Winneke , G. , Kramer , V. , Broekhaus , A. , Ewers , U . , Kujanek , G. , Lechner , H. , an

d Janke , W . Internationa l Archive s o f Occupationa l an d Environmenta l Health(i npress ) I n thes e relate d studies , Winnek e an d hi s co-author s hav e mad e a con certe d effor t t o evaluat e possibl e lea d effect s i n populatio n wit hles s exposur e t o lea

d base d pain t than i s the cas e fo r U.S . children . I n both , th e majo r inde x wa s toot hlead . Some failur e o f concordanc e betwee n sample s i s noted ; thi s i s consisten t wit hthe observation s o f Needleman , e t al . (1979 ) an

d o f Ernhart , e t al . (1981) . Bloo d lea d dat a (but no t EP ) wer e availabl e fo r 8 3 o f th e children . Th e correlatio n o f .4 7 betwee n the two indice s i s consistan t wit hthe correlatio n o f ,4 3 reporte d b yErnhart , e t al . (1981) . I n the firs t study

^ the participatio n rat e wa s highe r fo r control s than fo r the lea

d group ; matching wa s use d fo r contro l o f socia l factors . I n th e secon d stud yth e participatio n rat e wa s unrelate d t o lead ; afte r testing th e relationshi p o f lea d t o a numbe r o f contro l variables , a singl e dichotomou s variable , "socio-hereditarybackgroun d (SHB) " wa s formed . Apositiv e scor e i n thi s wa s obtaine d i f eithe r paren t wa s a n unskille d worke r c r i f the chil d attende d secondar yschool . I n neithe r stud ywer e parenta l intelligenc e o r th e caretaking environmen t measured . Thi s i s a ver yimportan t weaknes s give n the verytenuou s qualityo f the findings . A s note d elsewhere , the directio n o f bia s associate d wit hfailur e t o contro l suc hvariable s i s toward findin

g a n effec t whic hi s no t there .P.1 9

-2

- Th e selectio n o f outcome measure s i s reasonable . I t i s base d o n previou s finding s b yothe r investigator s and , i n th e cas e o f the secon d study , o n the result s o f the first . I thin k tha t Winnek e i s t o b e com mende d fo r restrictin g the outcome measure s t o thos e specifie d b ythe hypotheses ^ (p . 11 , prepublicatio n copy) , bu t I' mno t sur e exactl ywha t
wa s include d i n tabl e 9 whic hi s missing fro mm ycopy . Th e basi c strateg

yo f hierarchica l organizatio n i n th e secon d stud y is , o f course , appealing t o me . However , including the experimenta l reactio n time measur e i n th e Typ e I hypothese s tes t i s stretching thing s a lot , an

d I' mno t a t al l sur e I' d hav e the GF T i n there . (I t woul d hav e bee n good t o se e measure s o f academi c achievemen t there. ) Mor e importantly , an d unfortunately , the strateg yo f hierarchica l organizatio n t o for mset s fo r multivariat e analysi s wa s no t followed . Th e interpretatio n o f the statistica l result s concern s m e greatly . I
can se e a rational e fo r on e taile d tests , thoug hI'v e neve r see n themnote d whe n effect s ar e large . Here , though , w e se e statistica l test s tha t ar e jus t above th

e .0 5 level , on e tai l fo r the GFT , i n bot hstudie s discusse d
a s i f the

ywer e quit e robus t (Lancet , Sept . 4 , 1982 ) withou t recognitio n tha t inclusio n o f another , eve n rathe r weak , contro l variabl e i n th e analysi s woul d was hthemou t completely . Thi s same poin t applie s t o th e reference s t o statistica l test s a s being borderlin e significan t a t p^O.10 , on e tail . Th e reactio n tim

e measur e i s on e o f thos e tha t i s "borderlin e significant " (p<^ . 10 , on e tail) ; i n th e Lance t lette r i t i s identifie d a s being affecte d b y environmenta l lead . I n the secon

d study , whe n behavio r rating questionnaire s wer e discussed , item s wer e summe d int o a singl e scor e a s a "screening step. " I assume d a protectio n procedur e wa s being use d (a s i n Fisher' s "protecte d t" ) t o reduc e( : • - i P.2 0

. -3

- the likelihoo d o f Typ e I error . No t so . Whe n n o significan t lea d effect s wer e found , the scale s wer e stil l opene d u p t o item-by-itemanalyse s an d describe d (Lancet ) a s significan t eve n thoug hvarianc e fo r a singl e item rarel yexceede d 3 % and , onc e again , importan t contro l variable s wer e no t included . Table s an

d graph s fo r result s withou t residualizing fo r the SHB variabl e ar e no t appropriat e a s evidenc e o f a lea d effect . (The

ydo sho w tha t eve n thi s simpl e covariat e reduce s the varianc e tha t migh t b e attribute d t o lea d i n a n analysi s i n whic hi t i s no t incorporated. ) Finally , i n a stud

yi n whic hthe finding s ar e s o minute , mor e attentio n shoul d b e pai d t o studywis e error . Winneke , e t al < (extende d study ) men tione d thi s an

d the lac k o f contro l fo r parenta l I Q an d caretaking environ

ment , ye t the

yinterprete d thei r verymargina l result s a s evidenc e o f th e effect s o f lea

d exposure . Afte r reading thes e papers , I wonde r ho wfar on e ca n stretch ? An

d wha t i s thi s overwhelming nee d t o fin d lea d effect s i n the absenc e o f sufficien t evidence ?P.2 1

January , 198 3 C B . Ernhar t

Comment s Regardin

g Thos e Portion s o f Chapter s 1 2 an d 13 , Draft , Ai r Qualit yDoc
umen t fo r Lea

d Concerne d wit hNeurotoxi c Effect s o n Childre n

INTRODUCTIO

N Th e tas k o f the reviewe r o f thi s topi c wa s difficul t an d th e effor t t o pre sen t a balanced pictur e i s appreciated . Th e following supplement s th e material s previousl ysubmitte d an d I a mre peating particula r point s onl ywhe n the issu e seem s t o m e t o requir e furthe r emphasi s o r expansion . Genera l Comment s I wa s "please

d t o se e the problem s o f statistica l analysis , generalizatio n an d interpretation , an

d the need fo r "blind " examination s adde d t o the lis t o n pag e 12-40 . On e o f m

ygenera l comment s i s tha t I do no t thin k enoug hattentio n i s pai d t o some o f thes e issue s i n th e reviewo f particula r studies , particularl ycontro l o f confounding variable s an d the failur e eithe r t o us e appropriat e multivariat e statistic s o r t o conside r studywis e error . In additio n t o the qualit yo f eachstudy , the reviewe r ha s considere d the consistenc yo f result s acros s studies . A n emphasi s on consistenc yacros s studie s i s important , particularl yi n thi s are a i n whic hresearc hi s very difficul t an

d expensiv e an

d i n whic hobtaine d effect s ar e small . Thre e observation s on thi s topi c o f across-stud yconsistencywil l be discussed , (a ) importan t set s o f dat a o r analyse s have been omitted , (b ) consistencyca n b e consistencyo f bias , an d (c ) th e attemp t t o mak e result s consisten t wit hthe interpretatio n o f a singl e stud yha s lea

d t o "stretching" . Omissio n o f Dat a Set s an d Analyses . Wit ha ver yfewexceptions , the reviewe r ha s include d onl ypublishe d papers . Certainl ysome unpublishe d report s shoul d be allowe d t o fad e rapidl you t o f view . Wit hrespec t t o thi s highl ycontroversia l topic , however , a person who i s strongl ycommitte d t o a give n positio n ma yaccu mulat e dat a o r conduc t analyse s the result s o f whic har e no t consisten t wit h his/he r positio n an d ma ythen fai l o r eve n refus e t o shar e the mwit hothe r sci

entist s reviewing the topic . Thi s i s on e o f the mor e seriou s problem s i n th e researc hprogra mo f Herber t Needleman . Ther e ar e man yquestion s regarding the 197 9 pape r whic hcoul d have bee n averte d b

ymor e complet e presentatio n o f results . Thes e omission s ar e par ticularl yimportan t fo r the across-stud yreviewbecaus e thi s on e relativel ylarg e study , conducte d b

yan assertiv e investigator , appear s t o have been selecte d a s a standard o r referrent , the conclusion s o f whic hmayo r ma yno t b e buttresse d b ythe result s o f othe r reports . Thu s th e failur e t o provid e complet e report s o f stud yfeature s an

d analyse s i s critica l t o the entir e enterpris e covere d in thi s section . Some additiona l analyse s o f th e dat a o f thi s stud ywer e provide d i

n a pape r (Bellinge r an

d Needleman ) tha t Dr . Needleman refuse d t o shar e wit hthe grou p i n Augus t becaus e i t wa s unde r editoria l review . (Th e purpos e o f the priviledge d communicatio n fo r a manuscrip t unde r reviewi s t o preven t prio r stud yan d pub

licatio n b

yanother . Sinc e no on e els e coul d publis hanalyse s o f thi s dat a set , thi s basi s fo r no t sharin g the analyse s i s no t valid. ) Analyse s included in thi sJanuary , 198 3 C B . Ernhar t

repor t ar e importan t t o the question s unde r reivew . Give n tha t i t i s nowi n press , circulatio n t o EP

Aan d directl yconcerne d investigator s prio r t o the workshop migh t hav e bee n helpful . I t i s possibl e tha t feature s I noted therei n tha t ar e contrar yt o the investigator' s positio n wil l have bee n edite d out . Anothe r repor t (1981 ) o f a replicatio n supporte d b yEP A(Contract # 68-02-2217 ) ha s no t been reviewe d i n th e draft . I t ha s no t bee n published , presumabl ybecaus e th e result s wer e no t significant . Th e failur e t o repor t a nonconformatoryrepli

catio n i s an importan t omission . Dr . Needleman objecte d a t the workshop t o the discussio n o f thi s stud yo n the ground s tha t h e hadn' t had time t o revis e fo r pub

lication . Sinc e thi s wa s contracte d b yEPA , shoul d no t th e repor t b e o f suc h a qualit ytha t EP

Aan d the intereste d publi c can utiliz e th e findings ? (Tha t i t i s a disorganize d manuscrip t describing a rathe r poorl ydesigne d stud yi s something o f an insul t t o th e funding agency , bu t that' s anothe r issue. ) Comment s o n th e stud y wil l be provide d below . In the repor t t o EP Ao f tha t replicatio n ther e i s mentio n o f psychologica l tes t dat a collecte d wit htha t sample . Ther e appea r t o be no pub

lishe d report s o f thes e data . Dat a set s o f the siz e generate d i n thes e studie s ar e ver yimportant . I do no t fee l tha t an investigato r ha s the righ t t o concea l result s no r shoul d w e ig

nor e suc hresult s a s ar e publicl yavailabl e bu t whic hwer e no t published . Consistenc yo f Bias . Th e importanc e o f confounding variable s wa s indicate d o n page s 12-43 . Wha t i s no t indicate d i s tha t uncontrolle d confounding variable s i n thi s researc hten d t o bia s i n th e same direction , sinc e othe r ris k condition s ar e usuall ycorrelate d wit hlea d level . Furthermore , som e o f the mor e critica l confounding variables , mor e limited paren t I Q an d les s tha

n optima l caregiving en vironment , ar e no t considere d i n mos t o f the studies. . I t mayno t be fai r t o faul t a n investigato r becaus e the stat e o f th e ar t a t the tim e a stud

ywa s planne d o r othe r practica l consideration s (a s limite d funding ) le d t o non-inclusio n o f some importan t covariate . It' s u p t o us , however , t o be awar e o f the confounding an d t o us e du e cautio n i n the interpretatio n o f results . Eve n whe n a confounding variabl e i s entere d int o statistica l analysis , th e result s i s a n undercorrectio n whic h i s seldomrecognize d b yth e investigato r (Reichardt , 1979) . I t i s crucia l t o recogniz e tha t thi s bia s du e t o confounding i s pervasiv e acros s studie s an d tha t i t shoul d be considere d i n discussing consistencyo f results , particularl ywhe n effect s ar e small . O n pag e 13-4 4 o f the draft , th e smal l siz e o f som e o f the psychologica l effect s wa s mentioned . Smal l effects , i f theyar e tru e effects , may b e quit e important , give n th e incidenc e o f exposur e a t the indicate d levels . T o decreas e the functiona l capacit yo f a larg e numbe r o f individual s t o a n exten t no t considere d t o be devian t i n an individua l i s stil l a ver ylarg e los s t o society . Th e proble mwit hsmal l obtaine d effect s i n researc hi s tha t i t i s ver y hard t o differentiat e lead-relate d effect s fro mth e consequence s o f everything els e tha t i s happenin g t o thes e individual s i n a study . Stretching . Th e reviewe r stated tha t ther e i s on e stud y(Needleman , 1979 ) tha t provide s th

e stronges t evidence , t o date , o f associatio n betwee n lo wleve l lea d exposur e an

d neurotoxi c effects , i.e. , intellectua l an d behaviora l deficit s in children , bu t tha t ther e ar e unanswere d questions . Othe r studie s ar e then cited a s supporting thi s positio n o n the basi s o f partia l replication . Thes e result s ar e describe d a s "striking " (p . 12-84) . In eacho f thes e studie s however , the investigato r ha s stretche d ver yminima l finding s i n a n attemp t t o provid e an in

terpretatio n consisten t wit hthe Needleman position .P.2 3

-3

- January , 198 3 C B . Ernhar t

I n som e instances , th e stretching i s statistical , a s i n referenc e t o trend s (no t significant ) inthe dat a o r i n the us e o f alpha <_ .10 , one-tail , fo r statis

tica l significance . Failur e t o conside r the effect s o f the directio n o f bia s du e t o uncontrolle d confounding variable s characterize s al l o f thes e studies . I n hi s pilo t studie s o f attainmen t an d intelligenc e an

d o f teache r behavio r ratings , Yul e stated ver

yclearl ytha t parenta l intelligenc e an d caretaking environmen t wer e no t considered . Th e behavio r rating s describe d i n the secon d pape r wer e interprete d a s replicating the Needleman results , bu t th e fou r lea d leve l group s di d no t diffe r significantl yon tota l scor e o r on rating s o f hyperactivit yo r impulsivity . (Thes e ar e ofte n incorporate d int o description s o f minima l brai n dysfunction. ) Result s acros s the four lea d leve l group s di d no t followa dose

respons e pattern . N o chil d i n th e highes t lea d grou p wa s hyperactive . Distract

abilit yan

d disorganization , whic hmigh t be considere d significan t i n the Needlema n EP Acontrac t replicatio n wer e no t significan t i n the Yul e e t al . study . Whe n th e numbe r o f significan t items acros s al l scale s (seven ) wa s compare d wit hexpectation s o n the basi s o f chanc e (four) , th e result s ar e prett ythin , ye t Yul e e t al . con sidere d the

ma s bein

g impressive i n thei r similarit yt o thos e o f Needleman . Th e Yule-Lansdow

n wor k nowunde r wayi s bette r designe d an d I hop e tha t the need t o b

e consisten t wit ha stud yconsidere d t o b

e centra l doe s no t influenc e the inference s drawn . Th e nex t instanc e o f stretching i s i n the Winnek e studies . Although Winnek e carefull yqualife d hi s result s i n hi s pape r (th e extende d study) , the need t o stretc h very

margina l finding s wa s apparen t i n a lette r t o Lancet . Hi s lette r an d m yresponse , no t published,hav e bee n supplie d previously . Yul e e t al . an d Winnek e e t al . d

o presen t thei r result s i n sucha wa ytha t on e ca

n separat e result s an d inferenc e an

d the yar e awar e tha t ther e ar e limitation s t o thei r studies . Comment s on the Thatche r paper s have bee n sen t t o EPA . Th e evidenc e o f stretchin

g i s clear . I di d no t respon d t o hi s repl ybecaus e the situatio n seem s fairl yobvious . I did.-writ e t o hi masking i f he coul d provid e a plo t o f intel

ligenc e residualize d o n covariate s agains t the lea d index . ( I ha

d jus t see n m

y outlie r plot. ) H e di d no t reply . On e poin t shoul d be noted : In the JL D pape r h e di d no t indicat e tha t cadniu mwa s a confounding variable. . I n spit e o f notin

g al l the problem s i n ths e studies , the reviewe r appear s t o be concurring wit hthi s stretching . Fo r example , i n the discussio n o f the extende d Winnek e e t al . study , muc h o f th e nea r significan t ( p < 0.1 0 onertail ) materia l i s listed an d then treate d a s i f relevant ; "...significan t attentiona l deficit s attributabl e t o lea d wer e found,... " whe n effect s a t p < .0 5 (one-tail ) wer e limted t o CF T (like th e Bender-Gestal t Test) . Thes e effect s wer e s o minima l tha t uncontrolle d confounding variable s coul d ver yeasil yaccoun t fo r the effect . (Not e tha t Bender-Gestal t result s ar e no t significan t i n an yothe r study. ) The reviewe r than wen t o n t o tr yt o fin

d a rapprochemen t betwee n the Winnek e an d Needleman results . Th e possibilit ytha t ther e i s n o tru e effec t a t thes e level s doe s no t appea r t o have bee n considered . Th e importanc e o f confounding du e t o caretaking environmen t wa s recognize d b yth e reviewe r i n considering the Mila r e t al . studies . Wh yno t others ? (Note : I appreciat e the effort s mad e b ythe reviewe r bu t I d o no t thin k he gave anywher e nea r enoug hweigh t t o the problem s pervadin

g thes e studies , particularl ythe stud yplace d a t dea

d center. )P.2 4
_4

_January , 198 3 C B . Ernhar t

Wha t i s thi s need.t o stretc ht o ge t result s consisten t wit hthos e o f Needleman ? Th e wor k o f Yul e e t al . an d Winnek e e t al . i s soun d enoug htha t stretching t o ge t a publicatio n shoul d no t be necessary . Bein g aske d t o giv e talks , be a

n exper t witness , appea r on TV , etc . doe s no t see mt o b e reaso n enough . Agoo d par t o f i t mayb e the ide a o f wearing th e whit e ha t (E D Grot h III , EP Atestimony , Apri l 1982 ) an d bein g o n the"environmentalist " sid e o f things . Being concerne d abou t th e environmen t shoul d no t interfer e wit hscientifi c re search , bu t I believ e i t does . Being an environmentalis t make s on e appea r t o b e fo r the littl e gu

y(Lov e Canal , Time s Beach , etc. ) an d permit s making busines s a scapegoa t fo r variou s societa l problems . And , a s Marti n Bax ^ pointe d out , blaming lea

d fo r th e problem s o f childre n make s i t easie r t o ignor e th e mor e immutabl e an

d troublesome condition s whic hw e knowaffec t children , particularl y disadvantage d children . Finally , on e las t facto r whic hm ylea d t o stretching t o drawinference s consisten t wit hthe Needleman positio n i s th e absolutel ybruta l treatmen t on e get s fro mhim.i f on e doe s not . Behavio r Rating s - Th e Needleman Stud y O n pag e 12-6 8 o f th e review , the Needleman behavio r ratin g scal e i s mentioned . I t wa s suggeste d a t the workshop tha t the of t reproduce d graph s fro mth e Needlema n (1979 ) pape r be reproduce d i n th e Ai r Qualit yDocument . I objec t very strenuously . Ther e wa s absolutel yn o contro l fo r confounding variable s i n tha t presentation . M ydat a showe d no hin t o f a n effec t wit hsimila r teache r rating s an d a mor e homo

geneou s population . Mila r e t al. 2 foun d n o evidenc e o f behaviora l effect s o f moderatel yelevate d lea d exposure . A s note d elsewher e in thes e comments , th e dat a o f Yul e e t al. , als o withou t contro l o f confounding , can be considere d a s supportiv e onl yb

ystretching . O f particula r interest , howeve r i s a replicatio n b yNeedleman (Contract # 68-02-2217 , EPA , 1981 ) o f th e teache r ratin g study . Thi s wa s ignore d in th e draf t o f th e Document . Onc e again , th e teache r ratin g dat a wer e obtaine d fo r a larg e numbe r o f schoo l childre n an d she d deciduou s teet hobtaine d fo r a larg e numbe r o f thes e wer e analyse d fo r dentin e lead . Covariat e dat a (called follow

u p data ) wer e obtaine d fo r male s an d psychologica l test s wer e administered . Th e late r dat a ar e no t reporte d her e o r elsewhere . Separat e graphi c presentation s wer e mad e o f the behavio r rating s fo r each . Whil e th e highes t lea d grou p usuall y ha d the highes t prevalenc e o f eac hratin g (excep t fo r hyperactiv e an d impulsive , female ) the dose-respons e pattern wa s no t a s clea r a s i n th e previou s report . Thes e graphicall ypresente d dat a wer e als o no t adjuste d fo r covariates . Cluste r analyse s wer e conducte d bu t the metho d wa s no t specified . Th e firs t cluste r containe d fiv e items , th e secon d an d third , two eac han d other s wer e two singl e ite mclusters . Errors , reflection s o f items , inconsistencie s i n numbers , an

d confusing writing mak e the scal e constructio n procedur e difficul t t o followbu t the resul t appear s t o b e this : 1 . Cluste r 1 . No t persistent , dependent , poo r overal l functioning , les s abl e t o followsimpl e directions , les s abl e t o followsequences . "Followsimpl e directions " wa s droppe d becaus e o f lowfrequencyo f unfavorabl e ratings . (Not e als o tha t i t wa s almos t fla t i n the graphi c presentation. ) T o receiv e a favorabl e scor e on the cluste r a chil d ha d t o be favorabl e on eac hitem ; t o receive a negativ e scor e h e ha d t o be unfavorabl e on each . Al l othe r case s wer e dropped . (Wha t a wast e o f data! )P.2 5

-5

- January , 198 3 C B . Ernhar t

Cluste r 2 . Hyperactive , impulsive . A n unfavorabl e scor e resulte d fro m havin g been rated on eithe r o r bot hscales , a favorabl e scor e resulte d fro m havin g no unfavorabl e rating . No case s wer e droppe d fo r thi s scale . Cluste r 3 . Distractable , disorganized . Fo r thi s scal e a positiv e scor e resulte d fro

mhavin g bot hitems positive ; a negativ e scor e fro mbot hbein

g neg ative . Case s wit hon e positive an d on e negativ e wer e eliminated . Cluster s 4 & 5 . Frustrated , daydreams , wer e singl e items , al l case s included . Covariat e dat a wer e collecte d fo r a portio n o f th e sampl e whic hwa s selecte d t o includ e disproportionat e numbe r o f hyperactiv e male s (an d n o females) . Multipl e logisti c analysi s wa s used i n a mode l whic hfirs t tested th e co variate s (fo r th e case s havin g them ) i

n a stepwis e manne r an d then tested th e effec t o f adding the five level s o f dentin e lea d int o th e model . I n additio n t o th e statistica l test , relative ris k ratio s wer e obtaine d t o determin e the in

crease d ris k o f scorin g positive on the scale , a s describe d above , wit hincreasing level s o f lead . On e on e scale , distracted-disorganized , wa s relate d t o lea d leve l an

d on thi s onl yfo r the highes t lead , >

_18.2 0 ppm , wa s ther e a greate r ris k tha n fo r th e referent , o r lowes t group . Ther e wa s n o evidenc e o f a dose-respons e relationship . Oddl yenough , in thi s same analysi s wit ha p

_valu e lowe r than tha t fo r lead , child

ren in a mi d brithweigh t rang e ( 6 lb , 1 5 o z - 7 lb , 8 oz ) wer e significantl y mor e a t ris k tha

n lowo r hig

hbirthweigh t children . Sinc e thi s i s no t consisten t wit han yreasonabl e interpretatio n o f birthweigh t effects , i t appear s tha t the analysi s i s fault yi n some regard . Considere d altogether , thi s replication , wit hsom e contro l o f confounding variables , faile d t o suppor t conclusion s fro mth e 197 9 study . Whil e the stud y design i f of f i n som e respects , the odditie s shoul d no t have biased agains t getting a

n effect , give n ther e i s one , an d the stud

yshoul d no t b

e ignored . Becaus e the draf t stated ( p 13-42 ) tha t result s o f behavio r rating s ar e "striking an

d consistent " I migh t not e tha t i n a lette r t o the Centra l Docke t Sectio n (A-l30 ) EPA , date d Ma y20 , 1982 , Shapir o an d Marece k reporte d examine r rating s fo r attentio n span shownin g n o systemati c lead effect . Ther e wa s some tendenc ytoward highe r rating s on letharg yan d flattene d emotiona l affec t (both inconsisten t wit hhyperactivit yan d impulsivity ) bu t thes e d o no t appea r t o b e significant . Thes e wer e no t included i n a recen t revisio n o f th e pape r - mayb e they'r e to o unreliabl e t o be o f interest , bu t theyar e contraryt o the consistency the reviewer s see s on thi s issue . "Blindness " i n the Conduc t o f Researc h I wa s gla

d t o se e the nee d fo r "blindness " adde d t o th e lis t o f researc h issues . Mos t investigator s nowrecogniz e the nee d fo r the perso n administering treatment s i n a clinica l tria l o r observing an d codin g result s i n epidemiologica l a s wel l a s clinica l trial s t o be blinded , whe n possible , a s t o the natur e o f the treatment . Th e ide a o f blindnes s i s t o segregat e informatio n suc htha t ther e i s no contaminatio n betwee n cause-sid e an d effect-sid e information . Thi s nee d fo rP.2 6 

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- January , 198 3 C B . Ernhar t

segretatio n o f informatio n applie s t o mor e than th e administratio n o f treatmen t an d the observatio n o f result s an d shoul d appl ywhe n dat a organizatio n an d subjec t exclusio n decision s ar e mad e on eithe r sid e o f th e relationa l barrier . Dat a reductio n i s essentia l whe n ther e ar e a larg e numbe r o f variables . Ofte n eachalon e i s relativel yinsensitive , a s i n th e cas e wit htes t items . Dat a reductio n usuall yconsist s o f summatio n o f items groupe d conceptuall yo r empiricall y o n th e basi s o f facto r analysi s o r a simila r procedure . I t i s essentia l tha t thi s procedur e be don e independentl yo f the dat a t o whic hthes e reduce d variabl e score s wil l b e related . I n th e Burchfie l e t al . stud yth e dat a reductio n wa s deliberatel y conducte d t o includ e onl yitem s tha t differentiate d th e ris k groups . A s I in

dicate d i n a previou s revie wfo r EPA , th e chose n variable s reache d significanc e in the frequencyexpecte d b ychance . Whe n I pointe d thi s ou t i n a lette r t o Lancet , Needleman replie d tha t thi s wa s handle d late r i n th e analysi s b yth e jack-knif e technique . Ther e i s no waytha t the jack-knif e coul d correc t fo r the bia s i n the ite mselectio n procedure . I f thi s ha d been don e a s a procedur e t o develop a n EE G screening tes t fo r lea d leve l (don' t as k m e why ) th e procedur e woul d be appro priat e bu t i t woul d then need t o b e cros s validate d wit ha n independen t sample . A s a tes t o f whethe r ther e ar e electrophysiologica l sequela e o f lowlea d exposur e thi s stud

yi s s o seriousl yflawe d tha t i t shoul d receiv e no^ credibilit yi n th e presen t review . Thi s ver yseriou s problemi s no t note d i n th e presen t draft . Ther e i s n o indication i n the Needleman behavio r ratin g replicatio n stud

y (EP AContract * 68-02-2217 ) tha t th e person s conducting th e unspecifie d cluste r analysi s an

d scal e formatio n wer e unawar e o f th e lead statu s o f th e children . Th e formatio n o f thes e scale s i s no t consisten t wit husua l psychometri c procedure s an d resulte d i n th e exclusio n o f th e dat a o f larg e number s o f children . Unde r the circumstances , the person making the psychometri c decision s shoul d be blinde d re gardin g lea d status . . Whe n th e dat a o f alread yexamine d subject s ar e t o be exclude d fo r cause , the person making the decision s shoul d be blin d t o eithe r the outcome o r the ris k conditio n an

d preferabl yt o both . I hav e previousl ycommente d on th e ver yhig h exclusio n rat e o f the Needleman (1979 ) stud yan d th e very

rea l possibilit yo f bia s i n th e differentia l los s rat e betwee n groups . Willingnes s t D participat e ha s ofte n been relate d t o ris k condition . O f thos e actuall yteste d in th e Needleman stud y 32 % o f thos e wit husabl e dentin e dat a wer e exclude d (secon d stag e exclusion ) fo r no t bein

g discharge d fro

mthe nurserywit hthe mother , possibl e head injury , plumbism , an

d bilingua l home . Frequencie s fo r the specifi c reason s ar e no t given . Alarg e numbe r o f bilingual-home case s have been exclude d a t an earlie r stage . Give n the hig

hrat e o f exclusio n a t th e firs t stage , the 32 % exclusio n rat e o f dat a fo r thes e alread yteste d case s i s extremel yhigh . Theoretically , a t least , thes e exclusion s (aside fro mbilingua l home ) woul d remov e case s tha t jiav e mor e behaviora l problem s o r perfor mmor e poorl ytha

n th e include d cases . Conside r the teache r ratin g data . First , contraryt o a writte n statemen t i n th e pape r an

d i n th e curren t revie wthe tested childre n ( M = '253 ) an d childre n ex clude d a t the firs t stag e ( N= 235 ) di d diffe r o n teache r ratin

g o f Lowoveral l functioning , (x 2 = 4.85 , p < .05) . Thi s i s no t ver ycritical . Wha t doe s ge t un usua l looking i s a contras t o f th e ratin g dat a fo r hyperactivit yan d impulsivit y fo r the hig

hlea d grou p ( n = 5 8 o r 57 ) i n Tabl e 3 an d tha t portio n o f th e distributio nP.2 7

-7

- January , 198 3 C B . Ernhar t

i n Figur e 2 fro

mwhic hthos e case s mus t have been drawn . I f the person making the decision s fo r exclusio n o f th e alread yteste d grou

p wa s no t blin

d t o th e alread ycollecte d dat a (lead , teache r rating s an d othe r data ) a bia s mayhave entered . Analyse s o f the dat a o f the teste d bu t exclude d childre n woul d hel p t o clarif ythe situation . Thes e childre n shoul d b e the same a s o r poore r than the sam e lead-grou

p childre n whos e dat a wer e include d i n th e fina l group s (n s = 10 0 + 58) , Incidenta l Comment s o n Particula r Studie s Comment s o f differen t aspect s o f specifi c studie s have worke d thei r wayint o thi s discours e a t severa l point s an d I'l l no t pul l the mal l togethe r now . ( I hop e tha t prio r comment s stil l stan d an d ar e no t considere d t o be subsume d in this . Ther e isn' t tim e t o red o i t all. ) d e l a Burde ' an

d Choate . Wit hdat a availabl e fro msevera l separate d exam ination s (an

d eve n the infancydata) , s o muchmor e coul d have bee n don e i n thi s analysis . Some contro l o f confounding coul d have bee n used . Variable s coul d have been continuous , no t forced int o nominal , measurement . Multivariat e analysi s coul d have been used . I t i s a sham e no t t o utiliz e preciou s dat a mor e efficiently . I wis h theyha

d given u s dentin e lea d an d outcome measure s jus t a s I wis hNeedleman ha d reporte d hi s blood lea d an d outcome results . (Ther e woul d hav e been some re gressio n effec t i n the latter , bu t i t stil l coul d be helpful. ) Davi d an

d Associates . Se e appende d letter . P i h i an d Parke . Onc e agai n lea d i s confounde d wit hothe r metal s i n hai r analysis . Beatti e an

d Moor e Studies . Thes e studie s ar e interestin g example s o f retro
spective researc husing unusua l indicator s o f feta l exposure . Wha t els e coul d have been relate d t o residenc e i n a n old-plumbing house ? Wha t characteristic s o f the mothe r affec t he r abilit yt o metaboliz e lead ? Excessiv e alcoho l us e and/o r poo r nutritio n (iron balance , calcium , etc. ) ar e possibl e candidates . W e wil l lear n mor e abou t thes e consideration s a s the bette r conducte d o f the prospectiv e stude s star t t o produc e results . Electrophysiologica l Assessments . I d o no t ye t knowal l I wan t t o abou t thi s techniqu e bu t i t doe s no t tak e a specialis t i n the techniqu e t o se e the seriou s design fla

wo f the Burchfie l work . Th e Benignu s an d Ott o studie s appea r t o b e satisfactory , give n the caveat s provide d i n the article s an d b yth e reviewer . Needleman , H.L. , Leviton , A. , Bellinger , P. . Lead-associate d intellectua l deficit . N . Engl . J . Med. , 1982 ; 306 , 367 . A t the workshop Dr . Needleman sai d tha t thi s lette r shoul d b e reviewe d in the Document . Let' s look at-it . Contro l o f confounding variable s wa s ignored , althoug hthes e wer e considere d importan t i n th e 197 9 paper . Aris k rati o (o f I Q <_ 80 ) wa s presente d a s i f lea d wa s th e onl y conditio n systematicall ydifferentiating the groups . Verba l I Q wa s used rathe r than the customar

yan d reliabl e Ful l Scal e IQ . I Q <_ 8 0 wa s selecte d a s a cut-of f score . Thi s i s no t conventiona l fo r menta l retardatio n o r an yothe r usua l division . However , o f the verba l I Q value s unde r 10 0 i n the graphe d data , thi s cut-of f yield s the larges t relative ris k ratio . Th e M . Smit hstud

yi n the U.K . mus t b

e considered . Even i f i t isn' t published , th e strikin

g failur e t o replicat e the Needleman wor k indicate s tha t the inference s draw n ("strikin

g an d consistent" ) need t o b e toned down .P.2 8
-8

- January , 198 3 C B . Ernhar t

Th e statemen t a t the botto mo f page s 12-8 3 t o th e effec t tha t the Needlema n stud y"...can be mos t reasonabl yinterprete d a s clearl ydemonstrating a n associ

ation... " simpl yi s no t reasonable . Th e man yproblem s note d i n variou s review s o f thi s study , hi s refusa l t o shar e wit hothe r scientist s some o f hi s ow n highl y importan t analyses , the very selective metho d o f dat a presentation , an d eve n hi s inabilityt o replicat e hi s result s sugges t tha t building a n interpretatio n o n thi s foundatio n i s highl yrisky . Furthe r comment s ar e provide d i n a lette r publishe d in Contemporar

yPsycholog

y(cop yappended) . Ernhar t Studies . Th e presentatio n o f the mean s i n the summar ytabl e give s th e impressio n o f a n undul ylarg e effect ; thes e wer e no t adjuste d fo r covariates . Fo r th e Reading , Explorator yan d Conner s dat a i t look s a s i f yo u go t th e ns , no t means . Mean s wer e no t published . Pag e 12-67 . Th e statemen t tha t the mea n bloo d lea d leve l fo r m

ymoderatel y elevate d grou

p droppe d fro

m46. 5 t o 32. 4 isn' t quit e right . Th e division s pro vided in Tabl e 1 o f m ypape r wer e don e t o facilitat e th e T ^ analyse s reporte d in Tabl e 3 . Thes e ar e dat a fo r the 6 3 childre n availabl e a t the secon d test . Firs t w e divide d themo

n the preschoo l lea d values , wit hn s o f 4 0 an d 23 . Th e mea n o f 46. 5 correctl yindicate s the preschoo l Pb B valu e fo r th e orignia l moderat e lea d childre n stil l availabl e a t th e followup . Wit hthi s split , w e relate d preschoo l lea d (dichotomized ) t o schoo l ag e outcome s a s show n i n Tabl e 3 . W e coul d no t us e th e same cu t of f fo r th e school-ag e dichotomizatio n becaus e th e highe r lead grou p v/oul d have been quit e smal l an d becaus e vie

woul d have ha

d t o mak e a

n arbitrary decisio n abou t classificatio n fo r value s 31-3 9 (no t presen t i n th e mg/lOOm l unit s o f th e preschoo l lea d analyses) . I f w e ha

d don e wha t th e reviewe r though t w e had , i.e. , retaine d the preschoo l grouping an

d provide d schoo l ag e Pb B mean s fo r thes e group s w e woul d have provide d faultydat a becaus e o f th e inevitabl e regressio n occurring whe n a n arbitraril y divide d grou

p i s examine d on a variabl e correlate d wit hthe variabl e on whic h the divisio n wa s made . Th e significan t decreas e i n varianc e woul d als o exacerbat e the regressio n effect . Adecreas e i n lea d leve l fo r th e initia l hig hlea d grou p woul d have represente d bot hchang e ove r time , a s reporte d fo r the entir e grou p (to p o f p . 915 ) an

d regressio n effects . Th e drop in varianc e wit hdeletio n o f th e outlie r chil d i s t o 2. 6 percen t commo n variance . Th e 4.4 % reporte d (persona l comunications ) wa s based o n re sidua l ization onl yo n paren t IQ . Whe n we ran analyse s t o ascertai n tha t th e sub

scale s variance s als o droppe d w e included sex t o mak e the analyse s paralle l thos e reporte d i n Tabl e 5 o f th e 198 1 paper . Sex wa s no t significantl yrelate d t o GC I bu t i t wa s relate d t o the Moto r Scal e s o w e regresse d al l variable s on sex a s wel l a s paren t I Q i n th e analyses . Th e Perino-Ernhar t tw o correlatio n contras t continue s t o elici t interest . Th e Bellinge r Needleman pape r (198 3 i n press , J . Pediatrics ) shoul d be interesting i n thi s regard . Pag e 12-85 , line 2 . Strik e "mainly" . I gues s the reviewe r ha d onl ythe persona l communication , no t the manuscrip t fo r this .P.2 9

_g

_January , 198 3 C B

. Ernhar t



### Comment s o n Chapte r 1 3 Th e chapte r i s wel l organize d an d wel l writte n b ya reviewer

wh o i s clearl y awar e o f al l issue s involved . Th e presentatio n i s appropriat e t o th e tas k o f providin g a reasonabl yconcis e statemen t o f wha t i s known fo r th e us e o f agenc y decisio n makers . Wit hrespec t t o biologica l effect s (Sectio n 13.5 ) th e Introductio n (pp . 13-3 7 throug h13-39 ) pose s th e issue s i n a logica l an d judiciou s manner . Pag e 13-42 . Fo r th e reason s indicate d elsewher e i n thes e an d previou s comments , reference s t o th e Needlema n (1979 ) requir e eve n furthe r qualificatio n o n th e basi s o f methodologica l problems . Th e paragrap ha t th e botto mo f p . 13-4 2 extend s int o thi s documen t th e stretchin g discusse d earlier . Th e mos t extrem e exampl e o f thi s i s th e discussio n o f attentiona l deficits , indexe d b yratings , a s "strikin g and consistent" . Wha t happen d t o th e Ernhar t e t al . teache r ratings ? Thos e o f others , includin g th e Needlema n EP Asupporte d replicatio n certainl yd o no t con tribut e t o "consistency" . Pag e 13-43 , lin e 9 . Chang e "two " t o "five" . I woul d rewrit e tha t sentence : "Whe n reevaluate d fiv e year s late r menta l retardatio n wa s observe d i n on e chil d whos e blood-P bleve l wa s 6 0 pg/d l an d whos e dentin e lea d leve l wa s consisten t wit hver yexcessiv e lea d exposure . Othe r childre n wh o ha d blood-P blevel s o f 4 0 t o 7 0 pg/d l a s preschooler s showe d n o evidenc e o f persistin g effec t whe n parenta l intelligenc e wa s take n int o account. " Pag e 13-43 . Th e Burchfie l e t al . studyi s s o seriousl yflawe d tha t i s shoul d b e delete d fro m

th e review . Pag e 13-44 , lin e 5 . Whe n referrin g t o smal l effects , i t migh t b e appropriat e t o indicat e tha t th e directio n o f bia s associate d wit hsom e o f th e methodologica l limitation s o f thes e studie s i s towar d findin g o r exaggeratin g smal l effects , i.e. , consistenc yo f bias . Pag e 13-46 , las t paragraph . Th e us e o f "ne wneuropsychologic " finding s t o buttres s th e impetu s towar d revisin g th e blood-P bcriteri a downwar d i s simpl yno t warrante d b

yth e qualit yo f th e findings . Aver yimportan t issue , no t addresse d here , i s th e establishmen t o f a threshol d a t blood-P blevel s curren t a t th e tim e o f th e neuropsychologi c evaluation . Thi s issu e require s elaboration . Threshold . An importan t issu e identifie d i n thi s sectio n i s th e specificatio n o f a threshol d o f effec t fo r cognitiv e defici t an d fo r othe r psychologica l deficits . Hig hleve l lea d exposur e ca n produc e deficit s i n intelligence . ^Deficit s ar e highl yprobabl e i n a chil d presentin g symptoms , particularl yencephalopathy . Furthermore , i t i s quit e possibl e tha t deficit s ca n occu r wit hhig hleve l lea d exposur e whe n ther e ar e lea d relate d symptom s tha t ar e no t diagnose d and , possibly , whe n ther e ar e n o apparen t healt hsymptoms . I f ther e ar e n o deficit s associate d wit hlo wleve l exposure , i t follow s tha t ther e i s som e leve l o f exposur e a t whic ha defici t ma yb e observed . Give n th e variabilit ybetwee n individuals , i t i s no t likel ytha t a fixe d valu e ca n b e determined . Threshold s ma yals o var ybetwee n function s an d ther e certainl yar e variation s i n th e sensitivit yo f assessmen t instruments .P.3 0
-10

- January , 198 3 C B . Ernhar t

Th e autho r o f the draf t appear s t o b e seekin

g a valu e in term s o f bloo d lea d leve l fo r the threshol d fo r intellectua l deficit . Th e merit s o f the specifi c studie s ar e discusse d elsewher e bu t her e I wan t t o poin t ou t a majo r problemi n th e determinatio n o f thi s threshold . Thi s i s the probabl e time spa n betwee n the occurrenc e o f th e ris k facto r (deleteriou s leve l o f lead exposure ) an d measure d deficit . During thi s time period i t i s highl ylikel ytha t th e blood lea d leve l wil l have decrease d whil e th e consequen t damag e persists . Thu s the defici t i s attribute d t o level s o f exposur e whic har e inappropriatel ylow . Th e problemi s particularl yrelevan t i n researc hon the developing child . Th e peak o f exposur e usuall yoccur s during th e earl ypreschoo l year s wit h blood lea

d leve l evidenc e o f th e exposur e decreasing ove r time . However , the mos t sensitiv e indice s o f effec t ar e the mor e vali d test s o f intelligenc e an d achievemen t whic har e no t administere d unti l severa l year s afte r the peak exposure . Thu s i t i s invali d t o infe r tha t the lea d leve l dat a collecte d concurrentl ywit h th e tes t o f effec t ca n identif yth e threshol d o f effect . I f Needleman ha

d relate d hi s blood lea d dat a (abou t ag e 3- 4 years ) t o hi s intelligenc e tes t dat a w e migh t have a bette r ide a o f this . Al l we have i s the mean P b valu e o f 35. 5 fo r 2 3 (40 , no t 15% ) o f the hig htoot hlea

d cases . Ther e ar e two problem s wit husing thi s a s a threshold : (a ) the threshol d leve l fo r the dentin e lea

d ha s no t been published ; i t i s no t approprait e t o le t i t coincid e wit h th e cut-of f fo r inclusion i n the hig hlea d group , an

d (b ) th e hig

hlea d grou p wa s selecte d t o be extreme , henc e blood lea d (correlate d wit hdentin e lea d .4 3 i n m y study ) wil l suffe r regressio n effect s an d be undul ylow . Th e reviewe r recognize d tha t ther e maybe change s i n bloo d lea d value s fro

m the time o f damaging intoxication . Thes e ar e almos t invariabl ychange s downward a s a functio n o f increasin g age . (I f theywer e change s upward fro mminimiall y damaging level s the chil d woul d probabl ybecom e sufficien t symptomati c t o arous e attention. ) Th e effec t o f thi s drop fro mpeak fo r the establishmen t o f a research

determine d threshol d i s no t recognized . Ther e i s anothe r temporall yrelate d design proble mi n the attemp t t o relat e effec t an

d curren t indice s o f exposure . No t onl ydoe s a n index o f exposure , sa y blood lead , decreas e ove r time fro mthe poin t o f peak exposure , i t wil l probabl y decreas e i n a somewha t variabl e wa y(no t constan t fo r al l cases ) a s a function o f continuatio n o f exposure , nutritio n an d othe r idiosyncrati c factors . Thu s the us e o f curren t level s t o estimat e peak o r threshol d level s i s i n erro r bot hi n absolut e leve l and , t o som

e degree , i n relative positioning o f subjects . Thi s latte r problem woul d ten

d t o dilut e a lea

d effect , give n ther e i s one , an d operat e toward a failur e t o fin d a tru e effect . O n th e basi s o f thi s argument , I shoul d have ha d a stron

g relationshi p betwee n m ypreschoo l ag e lea d level s an

d schoo l ag e intelligenc e an d a weake r relationsih p betwee n th e curren t (schoo l age ) bloo d lea d an d intelligence . Suc h wa s no t th e cas e excep t insofa r a s the singl e outlie r can be considere d in

dependentl yo f the whol e sample . Thi s teasin

g apar t o f earl yan d late r correlate s o f effec t badl yneed s mor e dat a an d I thin

k w e have t o reserve decision s on thi s an d on the relate d thres

hol d issu e unti l the result s o f the prospectiv e studie s ar e available . Give n th e limited informatio n no wavailable , th e line : "30-50,cognitiv e (CNS ) deficits,children " shoul d be delete d fro mTabl e 13-1 1 an

d the reason fo r the . deletio n given . The possibilit ytha t the sam e proble

mapplie s in the Ott o an d Benignu s studie s o f electrophysiologica l change s shoul d be considered .P.3 1 

### •11

- January , 198 3 C B . Ernhar t

Pag e 13-5 7 & 13-58 . Tabl e 13-1 3 i s a n exampl e o f How-to-Lie-With-Statistics . Anaiv e reader , lik e a reporter , coul d ver ywel l lif t thes e figure s t o exaggerat e th e exten t o f problem s associate d wit hlea d exposure . Al l thi s i s takin g on e ris k factor , urba n residenc e an d computin g th e numbe r o f urba n residents . Wha t i s no t indicate d i s tha t th e majorit yo f urba n resident s ar e no t a t risk . Ho w abou t computin g th e portio n o f th e populatio n tha t i s blac k an d callin g tha t th e ris k factor ? Concludin g Comment . A t th e workshop , Dr . Piomell i commente d tha t preventiv e medicin e dictate s tha t attentio n b e give n t o condition s tha t ar e precursor s o f poo r health . H e i s right , o f course . Whil e thi s consideratio n migh t b e mentione d i n Chapte r 13 , i t i s importan t tha t w e d o no t us e i t t o distor t th e informatio n provide d i n th e Document . I t i s no t ou r positio n t o mak e policy . I f w e giv e undu e weigh t t o th e result s o f inadequat e studie s o r i f w e attribut e advers e effect s t o undul ylo windicator s o f exposure , w e are , i n effect , inappropriatel yassumin g th e decisio n makin g responsibility . W e canno t assum e a worl d o f infinit e resource s availabl e fo r childre n (an d others) . Ther e ar e cost s whic hwil l obtai n i f w e specif ya n undul ylo wthreshol d for , say , psychologica l sequela e o f exposure . Amon g th e mor e seriou s cost s ma yb e th e diversio n o f resource s fro mth e reall y seriou s problem s o f children . W e mus t als o conside r th e cost s o f furthe r effort s t o remov e lea d fro mth e environmen t i n th e reductio n o f th e benefit s t o societ y o f th e us e o f thi s resource .

Reference s 1 . Bax , M . Editorial . Lea d and imparl*ed abilities . Developmenta l Medicin e an d Chil d Neurology , 1981 , 23^ , 565-566 . 2 . Milar , CR. , Schroeder , S.R. , Mushak , P. , Boone , L . Failur e t o fin d hyper

activit yi n preschoo l childre n wit hmoderatel yelevate d lea d burden . Journa l o f Pediatri c Psychology , 1981 , 6_ , 85-95 .P.3 2

ZHTA.£ d l. 3d Lo wLeve l Lead Exposure : It s Effect s o n Intelligenc e an d Behavio r o f Childre n Clair e B . Ernhart , Ph.D . Thi s pape r i s prepare d a t the reques t o f the Lead Industrie s Association , Inc . a s par t o f the testimon ypresente d t o the Environmenta l Protectio n Agenc y a t hearing s o n Apri l 15-16 , 1982 . Th e topi c o f inquir yi s the desirabilit yo f changing regulation s regarding permitte d level s o f lea d i n gasoline . Th e issu e I a

mdiscussing i s the possibl e effec t o f lowleve l lead exposur e o n th e intelligenc e an d behavio r o f children . Afte r carefu l revie wo f the publishe d studie s o f others , an d m yow n data , I hav e reache d the opinio n tha t i f ther e ar e sucheffects , theyar e minimal . Th e effect s tha t hav e bee n reporte d ar e smal l an

d hav e no t bee n obtaine d consistentl yacros s studies . Mor e importantly , ther e ar e a numbe r o f methodologica l problem s i n thes e studies , including m yown . Thes e can lea d t o biase s o r distortion s i n the findings . Som

e o f thes e biase s ar e one-sided , i.e . theylea d t o finding an effec t whic hmigh t no t be ther e o r t o exaggerating a rea l effect . Whe n ther e i s a tru e effec t whic hi s ver yrobust , w e migh t b e abl e t o ignor e thes e biases . However , whe n a reporte d effec t i s smal l o r i s no t replicate d b yothers , i t i s imperative tha t w e scrutiniz e the design an d procedure s o f the studie s t o identif ysuc hproblems . Th e methodologica l issue s mayb e classifie d int o five categories : 1 . Contro l o f Confounding Variable s 2 . Selectio n an

d Recruitmen t o f Sampl e 3 . Indice s o f Lead Exposur e 4 . Choic e an

d Reporting o f Performanc e Measure s 5 . Study-Wis e Erro r an d Sampl e Siz e Contro l o f Confounding Variable s Contro l o f confounding variable s i s the singl e mos t importan t problemi n thi s are a o f research . Confounding variable s ar e othe r condition s whic hmaybe associate d wit hth

e stud yvaria'ble , i n thi s cas e lead , an d whic hmayinfluenc e the specifie d performanc e variable . Highe r lea d level s ar e ofte n foun d i n childre n whos e parent s hav e lowe r intelligenc e an d les s educatio n an d wh o ar e les s abl e t o provid e a stimulating hom e an d chil d rearing atmosphere . Thes e condition s can an

d do influenc e performanc e measures . Aparticularl yimportan t confounding variabl e i s paren t intelligence . I t ha s lon

g bee n know

n tha t thi s i s the singl e mos t importan t correlat e o f chil d intelligence . Le t u s look a t wha t happen s whe n thi s i s omitte d o r include d i n a stud yo f lea

d effects .P.3 3 Pag e

Percen t o f Varianc e i n Chil d Intelligenc e Accounte d fo r b yLea d Indicato r Withou t an d Wit hContro l o f Paren t Intelligenc e Preschoo l Intelligenc e Measur e Preschoo l Bloo d Lea d Schoo l Ag e Intelligenc e Measur e

Preschoo l Bloo d Lead Schoo l Ag e

Bloo d Lead Schoo l Ag e

Erythrocyt e Protoporphyri n Schoo l Ag e

Dentin e Lea d Withou t Contro l o f Paren t Intelligenc e 10.2* * 6.3 * 17.6* * 8.4 * 3. 1

Wit h Contro l o f Paren t Intelligenc e 1. 2 a * 1. 4 7.7 * 4. 5 0. 0

a Birt hweigh t i s als o controlle d i n thi s figure . * P < .0 5 * * P < .0 1
Th e dat a ar e fro mtw o studie s (1,2 ) i n whic hI have participated . T o simplif ythe table , I a mher e presenting onl ythe result s fo r the Genera l Cognitiv e Inde x o f the McCarth yScales . (Thi s correspond s t o I.Q. ) Th e figure s represen t portio n o f the varianc e i n chil d intelligenc e relate d t o varianc e i n the indicate d lea

d index . Excep t fo r the dentin e lea d results , al l variance s i n whic hparen t intelligenc e i s no t controlle d ar e statisticall ysignificant . Wit h inclusio n o f paren t intelligence , the variance s decreas e dramaticall yan d onl y tw o o f the five barel yreachsimpl e (single-variable ) statistica l significance . I n the larg e majorit yo f studies , paren t intelligenc e i s no t considered . I t i s apparen t tha t thi s confounding variabl e can lea d t o a fals e conclusio n tha t ther e i s an effec t o r the exaggeratio n o f an existing effect . Using a simila r mod e p f analysi s bu t controlling fo r age , se x an d a simpl e index o f socia l class , Yule , Lansdown , e t al . (3 ) reporte d tha t onl y2 1/ 2 t o 4 1/ 2 percen t o f the varianc e i n intelligenc e i s associate d wit hlead . Thi s i s statisticall ysignificant . I wonder , however , i f i t woul d hav e bee n i f paren t I.Q . ha

d bee n include d i n thei r design . Yule , e t al . d o carefull yqualif y thei r result s an

d expres s a concern fo r the appropriat e contro l o f socia l factors . I n thei r ongoing studie s the yar e including intelligenc e tes t dat a fro mbot hthe fathe r an d mothe r a s wel l a s detaile d informatio n o n socia l an d famil yfactors . Theyar e quit e knowledgeabl e abou t methodologica l issue s an d I loo k forward t o reading thei r furthe r reports . I hop e tha t the importanc e o f paren t intelligenc e a s a confounding variabl e wil l be recognize d b yothe r investigators . I n othe r publishe d studie s t o date , onl ythe 197 9 Needleman , e t al . repor t (4 ) include s thi s a s a covariate . A s suggeste d b

yYule , e t al. , paren t intelligenc e i s no t the onl y potentiall yconfounding variabl e i n thes e studies . Fo r example , Mila r an dP.3 4 Pag e
colleague s (5 ) hav e reporte d tha t qualit yo f stimulatio n an d for mo f disciplin e i n the home (Caldwell' s HOME Scal e (6) ) ar e relate d t o lea d exposure . Rutte r (7 ) ha s commente d tha t even wit ha mor e comprehensiv e measuremen t an d contro l o f parenta l characteristics , famil ycircumstances , an d socia l environmen t ther e may stil l remai n a smal l effec t attribute d t o lea d whic hi s actuall ydu e t o socia l o r geneti c factors . Moving awa

yfro msocia l variables , w e fin d anothe r possibl yimportan t confounding variabl e tha t ha s no t bee n mentione d i n an ypublishe d stud

yo f cognitiv e an

d behaviora l effects . Iro n deficienc yi s no t unusua l i n the populatio n o f childre n mos t a t ris k o f lea d exposure , tha t is , the urban inne r cit ychild . Incidentally , according t o on e o f m ycolleague s i n hematology , w e wil l se e a n increase d incidenc e o f iro n deficienc yi n our inner-cit yhospital . Thi s predictio n i s base d upo n reduce d suppor t o f the WI C program . Iro n deficienc yha s bee n show n t o increas e susceptibilit yt o lead . Furthermore , high level s o f lead can lea d t o iro n deficiency- the two condition s ar e no t independent . Osk i an d Honi g (8 ) an

d m ycolleague s a t Cas e Wester n Reserv e University , Lozof f an d Brittenha

m(9) , hav e relate d iro n deficienc yt o developmenta l deficit s i n young children . Iro n deficienc yi n elevate d lea d leve l childre n maywel l be producing effect s sometime s attribute d t o lead . W e ar e no wincluding measure s o f seru mferriti n i n our researc hprotocols . Anothe r aspec t o f the contro l o f confounding variable s ha s no t bee n mentione d i n investigation s othe r than m yown . I t i s wel l know n i n psychometric s tha t the measuremen t o f psychologica l an d socia l factor s include s error . Fo r mos t purposes , i t i s no t biasing o r distorting ; i t merel yincrease s the difficult yo f seeing an effect . Whe n w e us e suc ha measur e a s a contro l variabl e i n analyse s o f covariance , regressio n models , etc . o r eve n i n matching , the correctio n i s no t complete . I n othe r words , whe n w e thin k w e hav e controlle d for , say , paren t I-Q. , w e hav e onl ypartiall ycontrolle d fo r it . Th e directio n o f the bia s i s toward undercorrection . I kno wo f n o effectiv e satistica l solutio n fo r this . Wha t i s importan t i s tha t investigator s be awar e o f thi s whe n the

ymak e interpretation s o f the smal l effect s w e se e i n thes e studies . Summary . (a ) Contro l o f confounding variable s i s probabl ythe singl e mos t importan t problemi n thi s are a o f research . (b ) Majo r factor s tha t coul d be relate d bot ht o lead leve l an d t o chil d performanc e ar e no t include d i n mos t studies : thes e includ e paren t intelligence , a numbe r o f socia l factors , an d possibly , iro n status , (c ) Statistica l technique s use d t o contro l confounding variable s almos t invariabl yundercorrect . (d ) Th e directio n o f bia s i n thi s researc hi s toward findin g a n effec t tha t migh t no t b e ther e o r increasing the apparen t magnitud e o f an actua l effect . Selectio n an

d Recruitmen t o f Sampl e Tw o issue s ar e o f concer n here . Th e firs t i s the choic e o f the sample , the secon d i s differentia l o r biase d los s o f eligibl e cases . Onc e an effec t ha s bee n wel l established , the exten t o f the effec t can be determine d b

yselecting sample s representing the entir e population . Unti l then , i t i s mor e efficien t t o stud ythe populatio n mos t a t ris k fo r th e targe t conditio n - on e i s mor e likel yt o fin d the effect , give n i t exists . Asid e fro m proximit yt o an inadequatel ycontrolle d industria l source , the childre n who ar e mos t ap t t o hav e elevate d lea d level s ar e fro

minner-city , lowsocioeconimi cP.3 5 Pag e

statu s families . I t wa s a sampl e o f disadvantage d urban blac k childre n tha t w e used i n th

e researc hmentione d previously . Selectio n fro

ma mor e restricte d sourc e ha s anothe r advantag e - the sampl e i s mor e homogeneou s an d th e effect s o f socia l facto r confounding ar e lessened . Le t u s conside r a discrepancybetwee n tw o set s o f data . Thes e ar e teache r rating s o f childre n usin g almos t identica l items . Withi n the Needleman , e t al . stud y(4 ) ther e ar e significan t difference s betwee n groups . I n min e (2 ) ther e ar e n o significan t difference s an d the overal l leve l i s les s favorable . Compariso n o f Relationshi p o f Lead Leve l Classification s t o Teache r Rating Item s i n Tw o Studies * Teache r Rating Ite

mErnhart , Needleman ,

e t al . 198 1 e t al . 197 9 Lo wModerat e Lo wHigh Lea d Lead Lea d Lead

Easil yfrustrate d Hyperactiv e Impulsive Distractibl e Daydream s 2 3 2 0 3 7 3 3 1 3 1 9

9 1 9 3 1 2 5 1 1 2 5 6 1 6 9 2 5 1 4 3 6 1 5 3 4

* Lea d level s a s define d withi n respectiv e studie s

Amajo r differenc e betwee n the studie s wa s tha t the Needleman , e t al . sampl e wa s mor e heterogeneou s wit hrespec t t o socia l factors . Sinc e thes e ar e correlate d wi hlea

d exposure , an

d hav e no t bee n controlle d i n thes e data , i t i s possibl e tha t the

ycaused the appearanc e o f a lea d effect . Aseriou s problemi n som e studie s i s failur e t o recrui t subject s identifie d fo r inclusio n i n a stud yo r attritio n i n longitudina l study . Suc hlos s i s mor e likel yt o occur among familie s wh o ar e sociall yan d economicall ydisadvantaged . Thes e familie s ar e ofte n quit e mobil e an d tracing i s difficult . Parent s ar e ofte n no t motivate d t o bring childre n t o a researc hcenter . Wit hconsiderabl e effor t an

d examinatio n i n home s o r school s on e can keep los s t o a lowlevel . Whe n extensiv e los s occur s i t i s no t randomwit hrespec t t o lea d level . I n th

e Needleman e t al . pape r (4) , the los s rat e du e t o lac k o f interes t an d mobilit y wa s appreciabl yan

d significantl ygreate r fo r the highlea d grou p than fo r th

e lowlea d group . Th e directio n o f bia s associate d wit hextensiv e differentia l los s rat e i s no t alway s eas yt o determine . Sinc e onl yminima l informatio n abou t thes e case s can be obtained , the effec t o f exclusio n i n a give n stud yi s unknown . Ahighe rP.3 6 Pag e

los s rat e i n highe r lea d group s reduce s th e availabl e dat a fo r th e identificatio n o f a n effect , give n i t exists , o r fo r th e identificatio n o f a threshol d level , i f ther e i s one . Summary . (a ) On e i s mor e likel yt o fin d a n effect , give n ther e i s one , by studyin g a populatio n wit h a highe r exposur e level , '(b ) Confoundin g variable s ma yb e les s relevan t i n a mor e homogeneou s population . (c ) Withou t extensiv e effor t t o minimiz e los s rate , los s du e t o lac k o f parenta l interes t wil l b e highe r i n hig h lea d groups . Measuremen t o f Lea d Exposur e Th e mos t frequentl yuse d inde x o f lea d exposur e i s bloo d lea d level . Thi s i s considere d t o b e a rathe r unstabl e index . Systemati c repetitio n o f bloo d lea d measurement ha s no t bee n used . Dentin e lea d fro mshe d deciduou s teet hha s bee n th e inde x i n th e Needleman , e t al . repor t (4) , i n a recen t stud yb yWinnek e an d colleague s (10) , an d i t wa s on e o f severa l indice s i n m ywork . Variabilit y(o r nonconcordance ) withi n an d betwee n teet h fro ma give n chil d i s note d i n al l thre e studies . Arecen t repor t o f a studywit h dog s (11 ) indicate d a discrepanc ybetwee n centra l an d latera l incisors . Thi s descrepanc yincrease d a s dosag e increased . Erythrocyth e protoporphyri n i s a sensitiv e indicato r o f tissu e effec t an d i s no wuse d i n som e screenin g programs . Interestingly , i t als o reflect s iro n deficienc yan d hig h value s requir e furthe r test s t o differentiat e conditions . Th e indice s ar e correlated , bu t th e correlation s w e obtained , whic h ar e show n i n th e table , ar e no t hig henoug hfo r interchangeability . Th e tabl e als o include s preschoo l bloo d lea d value s obtaine d fiv e year s prio r t o th e othe r indices . Althoug h bloo d lea d decrease d significantly , th e betwee n year s correlation s di d no t diffe r muc hfro mth e betwee n indice s correlations .

Means , Standar d Deviations , an d Intercorrelation s o f Lea d Value s Variabl e Descriptiv e Statistics * Intercorrelation s Bloo d Lea d Measure s Pre
schoo l Schoo l FE P Dentin e

Lea d Preschoo l bloo d lea d 32. 5 + 12. 7 School-ag e bloo d lea d 26. 9 + 7. 2 Fre e erythrocyt e pro - 27. 2 + 19. 6 toporphyri n (FEP ) Dentin e 6. 0 + 5. 9 .46 t .46 t .51 t .52 t

• 43 t .66 t

* N= 6 3 excep t fo r dentin e dat a fo r whic hN t P < .0 1 = 3 4P.3 7 Pag e

On e solutio n t o the problemo f choic e o f a n index , give n the instabilit yo f each , i s the us e o f severa l indice s i n a give n study . T o date , thi s approac h ha s been used onl yi n our work . (Needleman , e t al . ha d earlie r (4- 5 year ) blood lea

d value s fo r 8 1 o f thei r children . Theydi d no t repor t the relation s betwee n thes e lea

d level s an

d an youtcome measure s fo r thei r hig han d lowlea

d groups . Thes e dat a coui d have provide d anothe r tes t o f the importan t questio n o f persistenc e o f effect. ) Summary : (a ) Mos t studie s us e a singl e index o f lea d leve l althougheac h ha s som

e degre e o f unreliabilit yan d the intercorrelation s among thes e ar e no t high , (b ) Us e o f severa l indice s i n the sam e stud ywil l resul t i n mor e precis e identificatio n o f lea d effects , i f any . Choic e o f Performanc e Measure s Performanc e measure s selected fo r stud yshoul d mee t two criteria : (a ) the y shoul d be psychometricall ysoun d and , (b ) the

yshoul d be indicator s o f whateve r attribute s on e expect s t o b e affecte d b ylead . Type s o f measur e mayb e hierarchicall yorganize d according t o th e importanc e an

d psychometri c meri t o f availabl e procedures . Som e investigator s hav e reporte d lea d effect s wit hmeasure s tha t ar e no t psychometricall ystandardized . I n fact , fo r some , publishe d procedure s ar e no t available . Whil e the inclusio n o f a fewexperimenta l procedure s i s reasonable , reporting the result s o f thes e i n th e absenc e o f positive finding s wit hmeasure s wit hknow

n characteristic s simpl ycloud s the field . Th e reade r doe s no t kno w jus t wha t i s measured , le t alon e howwel l i t i s measure d o r ho wthe dat a compar e wit hdat a fro

mothe r researc huses . Wit hmeasure s o f unknow n psychometri c characteristics , a stron g possibilit yo f chanc e finding s mus t be entertained . Furthermore , a s discusse d later , ther e ar e problem s tha t ar e no t ususall y recognize d i n having a larg e batter yo f procedures . On e shoul d hav e a strong rational e fo r the inclusio n o f experimenta l procedure s a t the cos t o f standardize d procedures . The mor e importan t measure s includ e intelligence , academi c achievemen t (fo r schoo l ag e children) , behavior , an d perceptual-moto r skills . Thi s orde r reflect s bot havailabilit yo f psychometricall ysoun d measures , and , probably , importanc e fo r the developing child . Mos t investigator s includ e reliabl e an d vali d individuall yadminister d test s o f intelligence . Wher e positive finding s ar e reported , the yar e mos t likel yt o b e obtaine d wit hthes e instruments . Effect s ar e smal l and , a s indicate d above , mos t investigator s fai l t o includ e an yconsideratio n o f parenta l intelligenc e an d hav e onl ylimited informatio n regarding pertinen t socia l factors . I f childre n ar e o f schoo l age , standardize d measure s o f schoo l performanc e ar e indicated . Yule , e t al . (3 ) reporte d significan t effect s o f lea d o n severa l academi c achievemen t tests , bu t onc e agai n thei r stud yi s limite d i n it s contro l o f socia l factor s includin g paren t intelligence . D e l a Burd e an d Choat e (12) , McNeil l an

d Ptasni k (13) , an

d Needleman , e t al . (4 ) have wit hfaile d t o fin d significan t lea d effect s wit hreliabl e standardize d measure s o f academi c achievement . I f lea d ha s an effec t tha t i s mor e tha n minimal , i t shoul d have bee n detecte d wit hthes e measures .P.3 8 Pag e

Behavio r (hyperactivity , shor t attentio n span , impulsiveness , etc. ) can be rated b

yteachers , parents , o r examiners . D e l a Burd e an d Choat e (12 ) reporte d significan t lea

d effect s wit hexamine r rating s bu t di d no t contro l socia l factors . Mila r an d associate s (14 ) repor t n o evidenc e o f lea d effect s o n tw

o paren t ratin

g scale s o f activit yan d on e free-fiel d experimenta l measur e o f gros s activity . Thes e results , considere d wit hthe previousl ymentione d Needleman , e t al . teache r ratings , whic hlac k contro l o f confounding variable s an d our negativ e finding s lea d t o the conclusio n tha t the evidenc e fo r lea d effect s o n behavio r i s quit e tenuous . Ther e i s littl e consistencyi n result s relating lea d t o psychomoto r function . Positiv e finding s wit hthe Bende r Gestal t tes t ar e reporte d b ytwo researc hgroup s (de l a Burd e an d Choat e (12 ) an

d Winnek e e t al . (10) ) bu t four othe r group s faile d t o fin d significan t effects . Positiv e finding s hav e no t bee n obtaine d wit hothe r standardize d procedures . Th e occasiona l significan t finding s reporte d wit hexperimenta l procedure s hav e no t replicate d b yothe r investigators . Summary . (a ) Some performanc e measure s ar e unstandardize d experimenta l procedure s o f unknow n psychometri c quality . Nevertheless , positiv e result s wit h thes e ar e sometime s emphasize d whil e negativ e finding s wit hwel l standardize d procedure s ar e ignored . (b ) Measure s mayreasonabl yb e ordered : intelligence , academi c performance , behaivo r disburbance , an d psychomoto r skills . Positiv e finding s wit hthe bette r standardize d measure s o f intelligenc e an d academi c achievemen t ar e mor e critica l than thos e wit hthe mor e experimenta l behaviora l rating an

d psychomoto r procedure .

Study-Wis e Erro r an d Sampl e Siz e On e migh t thin

k tha t the inclusio n o f a ver ylarg e numbe r o f performanc e measure s improve s a stud ysinc e i t decrease s the liklihoo d tha t something importan t i s overlooked . Som e investigators , however , hav e no t bee n awar e o f th e associate d problems . Whe n ther e ar e a larg e numbe r o f statistica l test s on a se t o f dat a ther e i s a drasticall yincrease d liklihoo d tha t some o f the result s wil l be statisticall ysignifican t i n the absenc e o f a tru e effect . If , fo r instance , on e ha d statistica l analyse s o f fiv e independen t (uncorrelated ) performanc e measure s i n the absenc e o f a tru e effect , the probabilit yo f obtaining a t leas t on e analysi s "significan t a t the .0 5 level " i s .23 , no t .05 . On e coul d reduc e thi s ris k t o .05 , study-wise , b yrequiring an .0 1 leve l fo r the individua l analyses . I f the numbe r o f individua l statistica l analyse s i s increase d to , say , 50 , the probabilit yo f having on e o r mor e individua l analyse s o f independen t variable s reac hthe .0 5 leve l i n the absenc e o f tru e effec t i s .92 . I n orde r t o reacha study-wis e erro r rat e o f .0 5 on e woul d hav e t o ignor e an ystatistica l analysi s fo r whic hthe calculate d probabilit yi s greate r than .001 . Thi s situatio n i s no t farfetched . Th e lead stud ytha t appear s t o hav e the larges t numbe r o f individua l (or univariate ) statistica l test s i s tha t o f Needleman e t al . (4 ) wit ha t leas t 5 2 performanc e measures . B ythes e calculation s onl ytw o statistica l test s i n tha t stud yshoul d be considered . Thes e ar e tw

o tria l block s o f the experimenta l unstandardize d reactio n tim e procedure . Th e above i s somewha t oversimplifie d sinc e the performanc e measure s ar e certainl yno t independent . Failur e t o conside r the intercorrelation s among performanc e measure s can lea d t o distortion s i n the statistica l analyses . Unlik e som

e o f the othe r biase s i n thes e procedures , the direction s o fP.3 9 Pag e 8

distortio n ar e no t alway s predictable . Ther e ar e effective procedure s t o reduc e th e numbe r o f statistica l analyse s i n a larg e dat a set . Thes e inlcud e dat a reductio n technique s an d the us e o f multivariat e statistics . A s a bar e minimum , the investigato r shoul d interpre t ver yconservativel ya ver yfew"statisticall ysignificant " test s i n grou p o f test s o f outcome measures . Thi s cautio n i s no t commo n i n thi s are a o f research , ye t failur e t o conside r th e issu e i s probabl ya s importan t a s inadequat e contro l o f confounding variables . Arelate d technica l issu e i s the relatio n o f sampl e siz e t o the siz e o f the se t o f variables . Areasonabl e rul e o f thum b i s tha t the rati o o f numbe r o f subject s t o numbe r o f variable s shoul d b e abou t 10/1 . Mos t o f u s hav e violate d thi s t o some extent , bu t the mos t flagran t violatio n i s i n the Needlema n e t al . repor t (4 ) wit hit s ver ylarg e numbe r o f variables . Th e problemi s tha t i f the dat a had bee n analyse d b yappropriat e us e o f multivariat e procedures , ther e woul d no t hav e bee n enoug hstatistica l powe r i n the analysi s an d tru e effects , i f any , migh t no t be detected . Th e directio n o f distortio n her e i s no t easil y predicte d bu t statistician s war n tha t distortion s mayb e quit e serious . Summary . A

n investigato r wit ha larg e numbe r o f performanc e measure s mus t carefull yconside r severa l majo r technica l difficulties : (a ) th e univariat e statistic s whic har e mos t frequentl yuse d wil l greatl yincreas e the liklihoo d o f concluding tha t ther e ar e effect s whic har e no t true , (b ) intercorrelation s among performanc e measure s leave one unabl e t o mak e adequat e correction s fo r thes e erro r rate s an d distor t the study-wis e probabilit ysituatio n i n way s tha t can ' t be predicte d and , (c ) i n orde r fo r the appropriat e multivariat e statistica l test s o f a larg e dat a se t t o b e reasonabl ypowerful , a ver ylarg e numbe r o f subject s mus t be enrolled . Implication s Th e methodologica l issue s raise d ar e no t trivial . Wher e a directio n o f bia s can be identified , a s fo r inadequat e contro l o f confounding an d inadequat e handling o f study-wis e error , the directio n i s toward exaggerating an existing effec t o r reporting an effec t whic hi s no t there . Whe n w e considere d al l publishe d studie s an d our ow

n dat a i n ligh t o f thes e issue s w e foun d tha t w e coul d no t suppor t a statemen t tha t lowleve l lea d exposur e influence s the intelligenc e o r behavio r o f children . Infant s a s £ Specia l Grou p Th e conclusion s draw n s o far hav e deal t wit hpreschoo l an d schoo l ag e children . I t ha s bee n suggeste d tha t infant s prio r t o birt han d i n the earl y period o f infancymigh t be particularl yvulnerabl e t o toxi c effect s sinc e thi s i s the time o f maxima l brai n development . The hypothesi s i s being studie d a t severa l centers , includin g ours . Th e prospectiv e stud ydesign appropriat e fo r thi s take s time ; a t the momen t al l I can provid e i s preliminar ydat a reflecting exposur e o f the fetus . Level s o f lea

d i n cor

d blood ar e low . W e collecte d materna l an d cor d blood s fro

ma preliminar

ysampl e o f 6 7 mother-infan t pairs . Thi s i s fro ma populatio n a t ris k fo r hig hlea d values . Th e sampl e i s o f lowsocioeconomi c level . Th e wome n reside , ofte n i n olde r housing , i n the inne r cityare a o f an industria l city . The incidence s o f poo r nutrition , smoking , alcoholism , an d polydrug us e ar e considerabl yhighe r tha n fo r the genera l population . I t i s possibl e tha t wome n occupationall yexpose d o r wh o engag e i n unusua l behavio rP.4 0 Pag e 9

(pic a o f pregnancy , drinking moonshin e liquor , etc. ) wil l hav e highe r lea d values ; asid e fro

maberran t condition s our mean s wil l be abou t a s higha s on e migh t find . Th e mean s ar e abou t 16yg/d l whol e blood fo r bot hmaterna l an d cord samples . Th e highes t cor d lea d leve l wa s 23.9yg/d l whol e blood . Thes e figure s ar e appreciabl ybelowthe lea d level s o f 30-3 5 ug/d l suggeste d i n severa l source s a s being associate d wit hsom e ris k t o th

e fetu s o r newborn . W e hav e no t complete d collecting the dat a t o determin e whethe r ther e ar e cognitive an

d behaviora l effect s associate d wit hthes e levels . M yexpectatio n i s tha t effects , i f any , wit hneonates , wil l b e minima l an d nonpersistent . Thi s expectatio n i s base d i n par t o n the evidenc e availabl e fo r olde r childre n and , i n part , o n experienc e i n infancystudies . Newborn s ar e mor e robus t than i s usuall ythought . I f w e exclud e markedl ydamage d infants , thos e o f u s doing researc h o n infan t development , fin d i t difficul t t o demonstrat e persisting effect s o f neonata l ris k condition s suc ha s anoxi a o r prematurity . I n studie s o f the developmen t o f infant s a t risk , parental , social , home stimulation , an

d nutritio n factor s overwhel mothe r variables . Whe n w e do lead researc hw e ar e tryin g t o detec t a possibl e fain t signa l throug hcontinuing noise . Th e childre n mos t likel yt o be expose d t o lea d ar e thes e mos t likel yt o be poorl ynourished , t o live i n substandard housing , t o hav e a mothe r wh o i s hersel f a child , t o have no visibl e father , t o hav e on e o r bot hparent s activel y abusing drugs , t o witnes s o r be victim s o f stres s an d violence , an

d ar e leas t likel yt o hav e remedia l o r enriching educatio n opportunity.. . W e ar e her e considering the possibilit yo f a jus t noticabl e differenc e associate d wit h lead . Th e rea l concer n shoul d be wit hthe reductio n o f program s t o ameliorat e the rea l problem s o f thes e children . I recentl ywrot e tha t ther e mayb e a ris k o f fran k lea d poisoning i n vulnerabl e childre n an d tha t thi s ris k justifie s limitation s o n lea d i n gasoline . Th e statemen t wa s mad e ou t o f a n interes t i n being ver yconservativ e pending continuing researc hresults . Thre e conditions , whic hI ha d no t completel yreviewed , woul d suppor t thi s conservativ e position . First , ther e mus t be a reasonabl e numbe r o f childre n o f elevate d lead leve l wh o migh t be nea r a threshol d o f effect . Second , thes e childre n woul d no t hav e bee n identifie d b y screening program s wit hthe consequen t remova l o f primar ysource s o f exposure . Third , the increas e i n airborn e lea d associate d wit hchange s i n gasolin e additive s mus t be grea t enoug ht o increas e the lea d leve l i n thes e childre n t o the poin t tha t the

ycros s a threshol d o f effect . Informatio n on thes e condtion s i s beyon

d m yexpertise . I' d lik e t o quot e fro man editoria l b

yMarti n Ba x i n Developmenta l Medicin e an d Chil d Neurology . "I t i s verytemptin g t o accep t som

e physica l aspec t o f the environmen t - b e i t blood lead , food additive s o r to o muc hsuga r - a s the caus e o f children' s problems . B

ydoing so , w e nee d loo k no furthe r a t the chil d an d hi s famil yan

d can avoi d uncovering the uncomfortabl e fac t tha t adult s ar e no t invariabl y sensitiv e t o children' s needs . Thi s o f cours e extend s beyon d meeting thei r simpl e physica l need s t o providing a n environmen t i n whic hcognitiv e an d socia l skill s can develop . Knowing on e s ow n frailties , i t i s unwis e t o poin t the finge r a t anothe r huma n being an d easyt o elec t th

e petro l tanke r a s the sourc e o f al l the mischief. "P.4 1

Reference s 1 . Perino , J . an

d Ernhart , CB . Th e relatio n o f subclinica l lea d leve l t o cognitiv e an d sensorimoto r impairmen t i n blac k preschoolers . Journa l o f Learning Dis

abilities , 1974 , I, 616-620 . 2 . Ernhart , C.B. , Landa , B . an d Schell , N.B . Subclinica l level s o f lea d an d develop

men t defici t - a multivariat e follow-u p reassessment . Pediatrics , 1981 , 67 , 911-919 . 3 . Yule , W. , Lansdown , R. , Millar , I.B . an d Urbanowicz , M . Th e relationshi p betwee n bloo d lea

d concentrations , intelligenc e an d attainmen t i n a schoo l population : Apilo t study . Developmenta l Medicin e an d Chil d Neurology , 1981 , 23 , 567-576 . 4 . Needleman , H.L. , Gunnoe , C , Leviton , A. , Reed , M. , Peresie , H. , Maher , C . an d Barrett , P . Deficit s i n psychologica l an d classroomperformanc e o f childre n wit helevate d dentin e lea d levels . Ne wEnglan d Journa l o f Medicine , 1979 , 300 , 689-695 . 5 . Milar , CR. , Schroeder , P.M. , Dolcourt , J.L . an d Grant , L.D . Contribution s o f the caregiving environmen t t o increase d lead burde n o f children . America n Journa l o f Menta l Deficiency , 1980 , 84 , 339-344 . 6 . Bradley , R . an

d Caldwel l B . Earl yhome environmen t an d change s i n menta l tes t performanc e fro

m6 t o 3 6 months . Developmenta l Psychology , 1976 , ^12 , 93-97 . 7 . Rutter , M . Raise d lea d level s an

d impaire d cognitive/behaviora l functioning : A revie wo f the evidence . Developmenta l Medicin e an d Chil d Neurology , 1980 , _22 , 1-25 . 8 . Oski , F.A . an

d Honig,.A.S . Th e effect s o f therap yo n the developmenta l score s o f iron-deficien t infants . Journa l o f Pediatrics , 1978 , j^2_ , 21-25 . 9 . Lozoff , B. , Brittenham , CM. , Viteri , F.E. , Wolf , A.W . an d Urrutia , J.J . Th e effect s o f short-ter mora l iro n therap

yo n developmenta l deficit s i n iron

deficien t anemi c infants . Journa l o f Pediatrics , 1982 , 100 , 351-357 . 10 . Winneke , G . , Broekhaus , A. , Kramer , U. , Ewers , U. , Kujanek , C , Lechner , H . an d Janke , W . Neuropsychologica l compariso n o f childre n wit hdifferen t tooth-lead levels . Preliminar yreport . Unpublishe d pape r presente d a t th e Internationa l Conferenc e o n Heav

yMetal s i n the Environment . Amsterdam , September , 1981 . 11 . Kaplan , M.L . , Peresie , H.J . an d Jeffcoat , M.K . Th e lea d conten t o f bloo d an d deciduou s teet hi n lead-expose d beagl e pups . I n H.L . Needleman."(Ed.) , Lo w Leve l Lea d Exposure : Th e Clinica l Implication s o f Curren t Research , Ne w York : Raven , 1980 . 12 . D e l a Burd e , B . an d Choate , M.S . Earl yasymptomati c lea d exposur e an

d develop

men t a t schoo l age . Journa l o f Pediatrics , 1975 , 87 , 638-642 .Reference s (continued )

13 . McNeil , J.L . an d Ptasnik , J.S . Epidemiologica l stud yo f a lead contaminate d area . Draf t fina l report , Projec t LH-208 . Internationa l Lea d an d Zin c Researc h Organization , 1975 . 14 .

15 . Milar , C.R. , Schroeder , S.R. , Mushak , P . an d Boone , L . Failur e t o fin d hyper

activit yi n preschoo l childre n wit hmoderatel yelevate d lead burden . Journa l o f Pediatri c Psychology , 1981 , J3 , 85-95 . Bax , M . Editorial . Lea d an d impaire d abilities . Chil d Neurology , 1981 , 23, 565-566 . Developmenta l Medicin e an dP.4 3
jTXfi,&.C.t- 3& 

### Clair e B . Ernhar t Octobe r 7 , 198 3

Respons e t o Appendi x 12- C INDEPENDEN T PEER-REVIE W O F SELECTE D STUDIE S CONCERNIN G NEUROBEHAVIORA L EFFECT S O F LEA D EXPOSURE S I NNOMINALL Y

ASYMPTOMATI C CHILDREN : OFFICIA L REPOR T O F FINDING S AN D RECOMMENDATION S O F A NINTERDISCIPLINAR Y EXPER T REVIE W COMMITTE E

I' d lik e firs t t o commen d th e Committe e fo r th e objectivit yo f it s analyse s an d fo r th e car e wit hwhic hi t reviewe d th e material s provided . I concu r wit h mos t o f wha t i s include d i n th e repor t an d I onl ywis htha t I ha d mor e an d bette r dat a wit hwhic hI coul d answe r mor e definitivel yth e question s pose d b yth e Committee . O n onl yon e suggestion , discusse d below , woul d I disagre e wit hth e recommend

ation s .

Th e introductio n presente d wel l th e mor e critica l o f th e issue s relevan t t o th e desig n o f researc hi n thi s area . Th e weaknesse s o f cross - sectiona l design s ar e wel l stated . Wit hth e completio n o f th e ver yimportan t U.K . studies , w e wil l probabl yse e fewe r cross-sectiona l studies . Meanwhile , w e ar e waitin g fo r th e result s an d dealin g wit h th e difficul t problem s arisin g i n th e conduc t o f th e prospectiv e studies .

Th e balanc e o f thes e comment s deal s wit hth e revie wo f th e studie s b ym

yassociate s an d me . A t th e tim e thi s revie wwa s written , th e Committe e di d no t hav e m yrepor t o f furthe r analyse s o f m ydata . Whil e thes e wer e no t conducte d precisel ya s suggeste d by th e Committe e i n th e repor t a t hand , th e majo r suggestion s wer e implemente d a s wel l a s possibl e an d I fee l tha t furthe r manipulatio n o f th e dat a i s no t warranted . Specifi c Points :

P.15 , firs t paragraph . Al l analyse s o f readin g score s ha d ag e a t tim e o f testin g entere d a s th e firs t covariate . Perhap s regres sin g ra wscore s fo r th e McCarth yscale s o n ag e rathe r tha n usin g extrapolate d o r norme d score s woul d hav e been.better . I' mconcerne d abou t th e regressio n effect s inheren t i n tha t approach . I t seem s highl yunlikel ytha t thi s woul d influenc e th e result s i n any appreciabl e way .

P.15 , las t paragraph . I n th e reanalyse s provide d educatio n wa s force d int o th e covariat e se t althoug hi t wa s no t significantl y relate d t o th e outcom e measur e i n anyanalysi s afte r entr yo f paren t I.Q . I ca n se e th e merit s o f th e backwar d selectio n procedur e i n thi s kin d o f analysis . I n thi s case , I doub t tha t takin g i t bac k ou t woul d hav e mad e anydifference .P.4 4



### P.1 7 (f) . I wa s unawar e tha t Perin o ha d mor e hig hlea d case s earl yi n th e dat a collectio n period . Hi s wif e se t u p th e dat a collectio n schedule . Sinc e h e wa s blinde d an d wel l trained , I don' t thin k th e orde r ha d a n effect , bu t i t wa s no t ideal .

P.18 . I ha d considere d handlin g th e dat a a s a cross-lagge d pane l desig n a s on e wa yo f assessin g th e possiblit ytha t earl y deficit s i n intelligenc e coul d lea d t o highe r level s o f lead . A s noted , th e cros s correlation s wer e lo wan d no t appreciabl ydifferen t fro meac h othe r s o I gav e up tha t approach . I n som e o f m ypresen t work , I' m

developin g causa l model s t o handl e thes e problem s o f longitudina l relationships . I question , however , whethe r ther e i s muc h mor e tha t ca n b e don e i n tha t regar d wit hth e se t o f dat a unde r review . Th e problem s o f measurin g chang e ar e ol d familia r concerns . A simpl e chang e scor e fo r th e intelligenc e measur e wa s adde d t o th e se t o f reanalyse s supplie d i n August . Residual s compute d fro mth e regressio n o f th e late r measur e o n th e earlier , a s suggeste d b yDr . Jones , woul d hav e give n a somewha t differen t resolutio n o f th e problem , bot h numericall yan d i n th e sens e o f wha t th e mode l repre sents . Asid e fro mal l th e problem s involve d i n th e measuremen t o f change , th e ide a o f chang e i n intelligenc e a s a outcom e variabl e relate d t o th e earl yexposur e inde x i s reasonable .

On e ca n als o pu t fort ha rational e fo r chang e i n lea d leve l a s a n outcom e measur e relate d t o earl yintelligence . (Les s intelligen t childre n ma yb e mor e likel yt o b e expose d o r mor e intelligen t childre n t o sta yawa yfro mit. )

I n bot h o f th e abov e design s th e concer n i s wit hth e effec t o f th e earlie r conditio n o n change . Wha t Dr . Jone s suggested , however , i s tha t bot h late r measure s b e regresse d o n th e correspondin g earlie r measures ; thi s essentiall ycancel s eithe r a s a plausibl e etiologica l facto r i n th e model . Th e residualizatio n o f th e lea d measur e i s o f particula r concer n bot h becaus e th e mor e frequentl yhypothesize d directio n o f effec t i s fro mlea d t o defici t an d becaus e lea d leve l droppe d appreciabl yfro mth e preschoo l t o th e schoolag e tim e o f assessment . I f lea d level s i n th e rang e unde r consideratio n d o hav e a n effect , th e earlie r highe r level s ar e o f muc hgreate r concer n tha n th e late r levels . Thi s i s particularl ys o i f ther e i s an y possibilit yo f a threshol d o f effec t withi n thi s range .

Th e availabilit yo f th e earl ylea d measur e i s wha t make s thi s a longitudina l a s oppose d t o a cross-sectiona l stud yan d i t i s important . Wit hth e ful l sampl e o f 6 2 children , th e relativel yhig h preschoo l inde x o f exposur e wa s no t significantl yrelate d t o an y late r outcom e measure .

I objec t t o th e statemen t o n p.18 , 12t hlin e fro mth e bottom : "Thes e simpl e logitudina l analyse s provid e suppor t fo r th e hypothesi s tha t a n increas e i n bloo d P b fro mage s 4- 5 t o 9-1 0 yrs , i s associate d wit h a decreas e i n I Q ... " Whil e mea n I Q change d ver ylittle , mea nP.4 5



### Tea d leve l droppe d appreciabl yan d veryfe wchildre n actuall y increase d i n lea

d level . Th e us e o f residua l score s i n thi s situatio n lead s t o th e anomalou s situatio n i n whic h actua l decrease s i n lea d leve l ar e identifie d a s increase s i n residua l scor e for mbecaus e they d o no t decreas e t o th e exten t predicte d b yth e regression . It' s interesting t o look a t the actua l paire d lea d level s fo r the childre n identifie d b

ysubjec t numbe r i n Figur e 1 . Th e greates t "decrease " i s fo r #5 8 whos e lea

d leve l wa s 1 0 o n bot h time s o f sampling . I n the rang e t o th e righ t o f th e mean , th e same residua l scor e coul d b e obtaine d bot h b

yincreasing o r b

ydecreasing lea

d level , depending o n th e initia l value . Thi s make s sens e fro m wha t w e kno wabou t regres sion , bu t i t i s no t verysensibl e fro m th e perspectiv e o f th e perso n needing t o mak e decision s abou t th e effect s o f lead . Mos t certainl yth e fac t o f th e dro p i n lea d leve l ove r time shoul d b e brough t int o thi s discussion . Th e statemen t quote d abov e ca n easil yb e misconstrue d b yperson s no t familia r wit h thi s fac t an d wit h th e natur e o f regressio n analysis . Wit h lowcros s la

g correlations , it' s hard t o mak e muc hsens e ou t o f th e correlatio n betwee n residuals . I t coul d reflec t anothe r changing conditio n no t include d i n the covariates , or , perhaps , intra-individua l labilit yo r stability . Onc e agai n though , th e mos t importan t problemwit h thi s mode l fo r analysi s o f the dat a i s tha t i t statisticall yextract s th e mos t importan t variable , i.e. , th e preschoo l lea d index .P.4 6
JZp.ts. -t. /.3e> Clair e B . Ernhar t

SUMMAR Y REPORT Reanalysi s o f Dat a o f Thre e Studie s The Effect s o f Lead o n Children 3

I n thi s repor t w e wil l b e referring t o thre e set s o f data . Th e firs t i s the se t reporte d i n the Perino-Ernhar t paper ; the sampl e fo r thi s consiste d o f 8 0 urba n blac k preschoo l ag e children . Th e secon d se t o f data , reporte d i n a dissertatio n b

yYamins , wa s collecte d using 8 0 suburban blac k an d 2 0 subur

ban whit e children . Th e third se t o f dat a resulte d fro ma follow-u

p examinatio n o f 6 3 o f the childre n o f the firs t study .

Variou s reanalyse s o f thes e dat a hav e bee n suggeste d b ydifferen t individuals , including member s o f the Pee r Revie wPane l selecte d b yEP Afo r revie wo f thes e studie s an d thos e o f anothe r investigator . Th e rational e fo r eachfeatur e o f reanalysi s an d the result s obtaine d wil l b e presented . I n al l thre e dat a set s the investigator s had followe d the strateg yo f incorporating int o the statistica l analysi s onl ythos e covariate s whic h sig

nificantl yreduce d the varianc e o f the outcome measur e (in a stepwis e manner ) befor e th

e entr yo f th e lea d variable . Curren t thinking on th e matter-*-' ^ i s tha t thi s i s no t th e mos t appropriat e strategy , tha t covariate s shoul d ente r the mode l o n rationa l o r j a prior i grounds . O n thi s basis , Kupper ^ recommende d tha t paren t education , whic hi s correlate d wit hlea d level , b e entere d int o th e statistica l mode l eve n thoug hi t add s littl e afte r paren t intelligenc e i s entered . Perino-Ernhar t Stud y I n the cours e o f conducting the reanalyse s t o includ e paren t education , we foun d severa l error s i n th e dat a an

d th e previou s analyses . On e child' s ag e wa s incorrec t b

yon e yea r (3 8 month s rathe r than 5 0 months) . Thi s change d hi s Genera l Cognitiv e Index (GCI ) fro m5 0 t o 86 ; othe r score s wer e correspondingl y affected . Anothe r child' s GC I wa s incorrec t b yon e point . Th e degree s o f freedo muse d an

d reporte d i n the test s o f significanc e o f the lea d effec t (regressio n analyses ) shoul d hav e bee n 1 an d 75 , no t 4 an

d 75 . Whe n the dat a wer e corrected , non e o f the analyse s wer e statisticall y significant . Th e result s provide d i n Tabl e 1 ar e fo r the regressio n analyse s o f rawscore s wit hag e a s a firs t covariat e an d fo r norme d scores . Fo r bot h set s o f analyses , the covariate s entere d prio r t o th e lea d dat a wer e paren t IQ , birt hweigh t an d paren t education . W e als o compute d the corresponding analyse s withou t paren t education . Fo r the rawscor e analyses , thi s provide d a correcte d reanalysi s o f the publishe d analyses . Th e result s wit h paren t educatio n omitte d differe d onl yslightl yfro mthos e provide d i n Tabl e 1 . I n othe r words , th

e previousl yreporte d significan t associatio n o f lea d leve l an d McCarth

yScal e GCI , Verba l an d Perceptual-Performanc e Scale s wa s a resul t o f the error s i n th e previou s analyses , no t the exclusio n o f the paren t educa

tion covariate . The assistanc e o f Bet h Landa , Janic e Yamin s an d Abraha

mWol f i n the analyse s o f thes e dat a an

d preparatio n o f thi s repor t i s gratefull yacknowledged .Tabl e 1 Regressio n Analyse s Relatin g Lead Leve l t o McCarth

yScal e Scores , Pre-Schoo l Data , Correcte d 1983 , N= 8 0 Scale s McCarth yScale s o f Children' s Abilit y Ra wScor e Dat a Varianc e Associate d withContro l Variable s Incremen t Associate d wit hLea d Varianc e 

## £ Norme d Score,Dat a Varianc e Associate d wit h Contro l Variable s Incremen t Associate d wit h Lead Varianc e 1 p

_ Gen . Cog . Inde x Verba l Perceptual-Performanc e Quantitativ e Memor y Moto r .8 5 .7 1 .7 5 .7 0 .6 5 .7 7 .00 6 .00 5 .00 8 .00 1 .00 3 .00 0 .1 0

.2 9 .1 3 .5 8 .4 5 .7 4 .3 1

.1 8 .1 6 .1 5 .1 4 .1 3 02 3 01 5 01 7 00 1 01 1 00 1 .1 1

.2 4 .2 2 .7 6 .3 3 .8 2P.4 8

Anothe r frequentl ycited featur e o f the previou s repor t wa s a contras t betwee n the correlatio n o f chil d intelligenc e wit hparen t intel

ligenc e fo r moderat e an d lo wlea d groups . Th e interpretatio n wa s tha t lead exposur e disrupte d the usua l relationshi p o f paren t an d chil d intelligence . Whe n the dat a wer e corrected , the correlatio n fo r the moderat e lea d grou p change d fro

m.1 0 t o .25 . Thi s i s no t significantl ydifferen t ( £ = .17 , two tail ) fro

mth e correlatio n o f .5 3 obtaine d fo r the lo wlea d group . Yamin s Stud

y Yamin s foun

d the dat a workshee t fro mwhic hhe r card s had bee n punched , bu t th

e card s an

d compute r outpu t had apparentl ybee n los t o r dis

carded . W e entere d the dat a fro mthe worksheet s int o our compute r an d rera n he r analyses . Error s whic happea r t o hav e bee n clerica l wer e identifie d i n a matri x o f intercorrelations . Th e correcte d matri x ha s bee n mad e available . W e als o reran an

d confirme d the regressio n analyse s a s provide d i n the dis

sertation . W e the n planne d t o determin e whethe r furthe r correction s i n the dat a wer e indicated .

On e o f the firs t thing s necessar yfo r furthe r analysi s o f th e Yamin s dat a wa s determining the metho d o f bloo d analysis . Bloo d sample s obtaine d b y finger-stic k (micr o technique) , collecte d o n a filte r pape r fro mwhic hpunche d disc s wer e obtaine d an d analyze d b

ythe Delve s cu

p techniqu e £r e subjec t t o error s o f whic hw e had bee n unawar e a t the tim e o f the study . Eve n wit h grea t care , the finger-stic k metho d yield s a highe r (abou t 6 yg/dl ) lea d leve l an

d th e Delve s cu

p metho d overestimate s Nationa l Burea u o f Standard s result s i n thi s genera l rang e b yabou t 1.9 5 yg/d l . Thes e error s woul d relat e t o th e leve l t o whic heffect s ar e attributed ; the ywoul d no t alte r statistica l sig

nificanc e levels . Th e third difficulty , however , require d recomputatio n o f the lea d index . Carter ^ ha s reporte d tha t lowhemoglobi n i s associate d wit h a greate r spread o f bloo d ove r a filte r paper . Wit hthi s greate r diffusion , th e lea d remaining i n the are a assayed b ya punche d dis c i s correspondingl y diminished . Correctio n formula s provide d b yCarte r ar e based on hematocri t pe r cent . Combining thre e source s o f error , the adjustmen t fo r bloo d lead index coul d be determine d b y53. 8 Pb

B (disc ) 7 _

_I t ha

d bee n planne d t o Hematocri t % comput e thi s for al l childre n fo r whomhematocri t dat a wer e available . Appro
priat e correctio n o f the presen t dat a wa s recommende d b yMuscha k . I planne d the n t o analyz e th e Yamin s data , wit hcorrecte d bloo d values , i n conjunctio n wit hthe Perin o dat a i n orde r t o increas e statistica l powe r an

d t o identif ya threshol d o f effec t i f thi s coul d b e observed . Th e difference s betwee n the sample s wer e limited t o a ) yea r o f recruitment , b ) us e o f th

e PPV T a s oppose d t o McCarth yScal e GCI , c ) suburban a s oppose d t o urban residence , an d d ) examiner . Th e sample s di d no t diffe r i n age , paren t intelligence , paren t education , birt hweight , birt horder , o r sex . Th e plan wa s t o contro l suc hdifference s a s wer e presen t b yentering grou

p a s th e firs t covariate . Additionally , the grou p b ylea d leve l interactio n woul d hav e bee n analyze d a s a tes t o f the merge r o f th e tw o samples .P.4 9

Afte r considerabl e effor t i n tracing record s an d contact s wit h person s connecte d wit hthe lea d screening program , Yamin s determine d tha t the punche d dis c techniqu e had indee d bee n the metho d use d wit hhe r subjects . Sh e the n starte d t o inspec t record s i n the archive s o f the Nassa u County Departmen t o f Healt han d foun d that , a t the tim

e o f he r study , hematocri t value s wer e recorde d fo r ver yfewo f he r subjects . Furthermore , thos e fo r whomi t wa s recorde d appeare d t o b e hig hlea d leve l children . I f ther e wer e multipl e lea

d determination s (Yamin s use d mean , highes t an d mos t recen t lea

d level) , hematocri t leve l migh t b e foun d fo r onl yon e o f the bloo d tests . O n th e basi s o f a revie wo f 1 5 cases , w e projecte d tha t w e coul d obtai n usabl e hematocri t dat a fo r the correction s o f the bloo d lea d dat a fo r n o mor e than 1 0 t o 1 2 o f the 8 0 blac k childre n o f he r stud yan d thes e woul d b e almos t exclusivel yhighlea d leve l children . Thi s i s no t sufficien t fo r furthe r analysi s an d w e hav e concluded , quit e regrettably , tha t the Yamin s dat a ar e no t correctabl e an d tha t n o con clusion s can b e draw n fro mhe r study .

" i Th e Follow-U

p Stud y Th e re-evaluatio n o f 6 3 o f the childre n see n a t the firs t (Perino

Ernhart ) stud

ywa s o f particula r interes t becaus e i t provided'th e mos t systemati c attempt , befor e th e onse t o f the prospectiv e studies , t o relat e earl yo r preschoo l lea d exposur e t o later , schoo l age , outcome measures . Onl yMcCarth

yScal e Score s an

d Reading Leve l dat a wer e include d i n th e presen t reanalyses . Othe r outcome measure s (includin g the Bende r Gestal t Tes t data ) reporte d i n th e publishe d paper , yielde d result s whic hshowed n o possibilit yo f statistica l significanc e unde r an yfor mo f dat a manipulation . Som e o f th e additiona l procedure s correc t our dat a an d metho d o f analysi s t o resolv e problem s whic hwer e unknow n t o u s a t th

e tim e o f th e pre viousl ypublishe d analyses . Other s ar e conducte d i n respons e t o variou s sug gestions . B

yvirtu e o f th

e shee r numbe r o f analyse s (albei t nonindependent) , the possibilit yo f identifying significan t effect s i s increase d an d thi s wil ? be considere d i n th e summar

yo f the findings . 1 . Th e capillar

ybloo d sample s had bee n analyze d b yth e punche d dis c techniqu e a s describe d above . Hematocri t dat a wer e availabl e i n our file s fo r onl y4 6 o f the children , including one late r exclude d a s an outlier . I n some case s th

e bloo d sample s had bee n hemolyse d an d hematocrit s coul d no t be deter

mine d an

d i n other s the dat a wer e no t recorde d on the forms supplie d u s b ythe Ne wYor k Cit yDepartmen t o f Health . (W e had ho t requeste d the informatio n a t tha t time. ) Effort s t o obtai n thes e dat a for thos e childre n fo r whomi t wa s missing wer e no t successfu l sinc e the informatio n wa s no t retaine d i n the archiva l records . Th e 1 7 childre n withou t hematocri t dat a wer e no t significantl y differen t fro

mthe remaining childre n on th e preschoo l bloo d lea d dat a ( t = .13) . We di d no t tes t difference s on othe r variables , bu t al l looked trivial , a s woul d be expected .2 . Paren t educatio n wa s forced int o al l statistica l model s a s wer e

paren t I Q an

d sex . I n general , onl yparen t I Q mad e appreciabl e contribution s t o th e varianc e o f the McCarth yScales . 3 . Th e intercorrelation s o f lea d exposur e indicator s wer e onl y moderate . Thi s reflect s th e wel l know

n fac t tha t indicator s fluctuat e ove r tim e an d tha t eac hi s relate d i n a differen t wa yt o bod

ylea d burden . I t ha s bee n suggested 8 tha t combining indicator s int o a singl e construc t inde x woul d provid e a mor e vali d measur e o f exposure .

Alea d construc t inde x wa s generate d b yConverting the preschoo l ag e bloo d lea

d level , the schoo l ag e bloo d lea d leve l (adjusted fo r hematocri t percent) , an

d the erythrocyt e protoporphyri n level s t o z-score s an d summing these . Dentin e lead wa s no t include d becaus e th e sampl e siz e woul d hav e bee n deplete d stil l further . Furthermore , asid e fro mthe singl e outlie r cas e describe d below , dentin e lea d i s no t eve n marginall yassociate d wit hthe outcome measures . Wha t w e ar e tryin g t o do her e i s t o verydeliberatel ydevis e a lea d inde x whic hi s mor e likel ythan the individua l scale s t o b e relate d t o th e outcome measures . Thi s construc t scale , then , wa s relate d t o schoo l ag e outcome measure s i n the same manne r a s the independen t preschoo l an d schoo l ag e indices . 4 . Developmentalist s ar e awar e o f interaction s o f healt hris k factor s an d socia l ris k factors . Fo r example , th e effec t o f preter

mdeliveryi s greate r i n childre n o f lowe r socioeconomi c statu s than fo r childre n wit ha mor e enriche d Q environment . Following thi s directio n o f thought , i t ha s bee n suggeste d .that the effect s o f lea

d exposur e woul d b e greate r fo r childre n whos e parent s ar e o f lowe r intelligence . Thi s can b e tested i n an analysi s o f the interactio n o f paren t intelligenc e an d lea d level . The possibilit yo f such a n interactio n wa s tested b ygenerating tw

o variable s whic hwer e th e product s o f schoo l ag e lea d leve l (adjusted ) an d paren t intelligenc e an

d als o lea

d construc t an

d paren t intelligence . Eac ho f thes e wa s tested i n th

e regressio n model s afte r the varianc e associate d wit hparen t intel

ligenc e an

d th e respectiv e lea

d inde x wer e partialled . 5 . Althoughpreschoo l bloo d lea d leve l wa s no t significantl yrelate d t o late r intelligenc e measures , i t wa s suggeste d tha t i t i s stil l possibl e tha t i t wa s related t o chang e scores . I n othe r words , lea d leve l migh t b e relate d t o the amoun t an

d directio n o f chang e i n scores . O n thi s basi s Jones^ O sug gested analysi s o f chang e score s fo r the childre n see n i n th e firs t preschoo l stud yan d th e follow-u

p study . A s a tes t o f thi s possibility , chang e score s fo r the tw o mos t likel y outcome variables , Genera l Cognitiv e Index an d Verba l Index , wer e compute d t o for madditiona l outcome variables . 6 . Th e possibilit yo f a threshol d o f effec t i s suggeste d b ythe dat a o f severa l studies , mos t notabl yi n reanalyses ^ o f the dat a o f one o f the mor eP.5 1

widel ycite d studies . I n reviewing ou r data , w e note d tha t on e child , JT , wa s markedl ydifferen t i n man yrespect s an

d probabl yshoul d hav e bee n identifie d a s having excessiv e lea d exposure . Asummar yo f wha t i s know

n abou t hi mwil l be presente d below . Hi s dat a wer e delete d fro mal l analyse s reporte d herei n excep t the analyse s o f the preschoo l result s reporte d above (Tabl e 1) . Results , Follow-u

p Stud yReanalyse s Whe n w e compute d the z-score s fo r FE P fo r the computatio n o f th e lea d construc t scor e w e note d tha t on e othe r child , WJ , had a z-scor e o f 5.1 6 (ow n dat a include d i n computations) . He r FE P wa s a highl ydevian t 13 0 ug/d l whol e blood . I n additio n t o a preschoo l bloo d lea d leve l o f .0 5 mg/dl , our record s indicat e thre e schoo l ag e lea d leve l analyses . Th e firs t wa s take n shortl y afte r th

e psychometri c testing (June 1977) . Th e lea d leve l wa s 3 5 ug/dl ; the sampl e wa s to o smal l t o d o the FE P analysis . Th e secon d sample , take n t o ge t the FEP , wa s als o a microsample . I t wa s obtaine d si x month s late r (Januar y 1978) . Th e lead leve l wa s 4 0 y g (4 1 adjusted ) an

d the FE P wa s 13 0 yg . Thes e wer e the dat a recorde d fo r analysis . Becaus e o f the elevation , a venou s sampl e wa s obtaine d (March1978 ) an d th e analysi s yielde d 2 8 y g o f lead , 6 9 y

g FE P an d 44 % hematocrit . I n August , 1978 , an evaluatio n for possibl e anemi a yielde d seru miro n o f 8 1 an

d a TIB C o f 296 . Thes e ar e describe d a s normal . Th e reaso n fo r the highl ydevian t FE P i s no t known , bu t an inaccuracyi n analysi s i s plausible . A t th

e sam e time , us e o f the surel ymor e accurat e valu e o f 6 9 obtaine d wit hth

e venous " sampl e woul d no t b e appropriate . Ove r th e five yea r perio d o f the stud

yhe r Gen . Cog . Inde x scor e change d fro m5 0 t o 70 ; th

e Verba l Scor e change d fro

m2 2 t o 21 . I n the analyse s tha t follow , result s fo r th e adjuste d lea

d dat a ar e presente d wit han d withou t he r data . He r dat a wer e exclude d fro

mthe analyse s o f construc t scores , whic hincorporate d FE P an d fro mthe interactio n tests . A s see n i n Tabl e 2 , preschoo l lea d leve l remaine d unrelate d t o an y outcome measur e collecte d five year s later . Referenc e t o Table s 2 an d 3 indicate s tha t onl ytwo analyse s yielde d result s significan t a t th e .0 5 leve l an d non e a t th

e .0 1 level . Le t u s look firs t a t the interactio n o f lea d (adjusted ) an

d paren t intelligenc e o n Perceptual-Performanc e score s (Tabl e 3) . Lead (adjusted ) wa s no t a significan t mai n sourc e i n thi s analysi s (Tabl e 2) . Th e interactio n wa s o f a crossove r for mwit ha wid e discrepancy associate d wit hparen t I Q a t th e highe r en

d o f the lea

d distribution . Further

more , score s wer e negativel yassociate d wit hlea d fo r lo

wintelligenc e parents , a s predicted ; bu t positivel yassociate d wit hlea d fo r hig

hintelligenc e parents . Th e slopes , i n opposit e directions , wer e almos t equal , for + 1 S D paren t intel

ligence . Sinc e ther e i s n o reasonabl e interpretatio n for a beneficia l effec t o f lea d fo r highe r intelligenc e parent s an d sinc e the mai n effec t o f lea d di d no t approac hsignificance , it' s reasonabl e t o infe r tha t thi s i s a/-chance finding .

Th e on e othe r significan t statistica l tes t wa s fo r lea d (adjusted ) . an d Verba l Scal e whe n the chil d wit h elevate d FE P wa s include d i n th e sample . Ther e ar e no t sufficien t ground s t o sa ytha t she wa s impaired a s a resul t o f lea d exposur e and/o r iro n deficiency . I f th e sampl e siz e wer e large r she migh t wel l be par t o f a smal l grou p o f childre n a t the uppe r en d o f the distributio n whos e dat a woul d sugges t a threshol d o f effect .Tabl e 2 Th e Associatio n o f Preschoo l Lead an d Schoo l Ag e Lead (Adjusted ) o n Majo r Outcome Variable s

Outcom e Variabl e Preschoo l Lead Leve l

Contro l Varianc e Incremen t

Associate d wit h Lead 

### £ Schoo l Ag e Lead (Adjusted ) Wit h c Devian t Cas e
Contro l Varianc e Incremen t

Associate d wit hLead 

### £ Withou t Devian t Cas e
Contro l Varianc e Incremen t

Associate d wit h Lead 

### £ McCarth yScal e Gen . Cog . Inde x Verba l Perceptual-Performanc e Quantitativ e Memory Moto r Reading Leve l Chang e i n Gen . Cog . Inde x Chang e i n Verba l Inde x 2 7 2 6 1 2 0 7 1 4 1 6 2 7 0 5 0 6 .00 0

.02 9 .00 5 .02 7 .02 9 .01 2 .02 3 .02 6 • .00 7 .8 8

.1 3 .5 9 .2 0 .1 6 .3 7 .1 9 .2 1 .5 3 .2 9

.3 0 .0 9 .1 1 .1 6 .3 1 .2 5 .1 1 .0 7 .03 0

.06 6 .00 4 .00 3 .01 5 .00 2 .00 2 .01 0 .03 6 .2 0

.04 7 .6 6 .7 0 .4 0 .•7 7 .7 4 .5 1 .2 2 .2 7

.2 8 .1 1 .1 1 .1 4 .2 9 .2 4 .1 6 .0 7 .02 5

.05 2 .01 0 .00 4 .01 0 .00 3 .00 1 .02 4 .03 5 .2 4

.0 9 .5 1 .6 7 .4 9 .6 9 .8 5 .2 8 .2 3

Th e ag e a t whic hth e reading tes t wa s give n wa s entere d a s th e firs t covariate .

, N= 6 2 fo r McCarth yScal e Variables , 5 9 fo r Reading Level .
C N= 4 5 fo r McCarth yScal e VariabJ.es , 4 3 fo r Reading Level . • N= 4 4 fo r McCarth

yScal e Variables , 4 2 fo r Reading Level .Tabi c 3 The Associationof Lea dConstruc t Score s an dInteraction s of Len dIndice s an

d Parent Intelligenc e WithMa.lo r Outcom

e Variable s

Outcom e Variabl e Contro l Varianc e Lea d b

Construc t Incremen t Associate d wit hLen d £ Interactio n Lea d(Adjusted ) by Paren t Intelligenc e Variance , Prio r Variable s Includin g Lea d Incremen t Associate d witi i Interactio n £ Interactio n Lea dConstruc t by Paren t Intelligenc e Variance , Prio r Variable s Includin g Lea d Incremen t Associate d wit hInteractio n -

£ McCarth y Scal e Cen . Cog . Inde

x Verba l Perceptual-Performanc e Quantitativ

e Memor y Moto r Readin g Leve l Chang e i

nGen . Cog . Inde

x Chang e i

nVerba l Inde

x 2 7

2 8 1 1 1 1 I A 2 9 2 4 1 6 0 7 .02 1

.05 0 .00 2 .00 4 .01 6 .00 0 .00 4 .00 9 .04 1 .2 9

.1 0 .7 6 .6 7 .3 9 .8 8 .6 5 .5 2 .1 9 .3 0

.3 3 .1 2 .1 2 .1 5

. .3 0 .2 5 .1 8 .1 0 00 5 00 0 09 9 00 7 00 6 04 5 01 0 00 5 01 5 .5 9

.9 2 .03 5 .5 8 .6 1 .1 2 .5 1 .6 4 .4 3 .2 9

.3 3

- -1 1 .1 2 .1 6 .2 9 .2 5 .1 8 .1 1 .00 0 .00 0 .05 7 .02 4 .00 4 .02 7 .02 2 .00 5 .00 8 .9 9

.9 6 .1 2 .3 1 .6 7 .2 3 .3 2 .6 4 .5 6

The ag e a t whichth e readin

g tes t wa s givenwa s entereda s th e firs t covariate . N = 4 4 for McCarth

y Scal e Variables , 4 2 fo r Readin

g Level .

W .P.5 4

+,• I t . I

\

A s the

yno wstand , th

e dat a d o no t suppor t an inferenc e o f lea d effects . I f ther e ar e suc heffect s i n th e rang e o f exposur e sample d her e the yar e small . A t the sam e time , th

e statistica l powe r o f thes e analyse s i s low , particularl ysinc e the sampl e wa s depleted . Thu s th e inferenc e b f n o effec t i s no t justified . I t woul d be possible , I suppose , t o derive othe r indice s o r way s o f analyzing thes e dat a i n the hop e o f findin g positiv e results , bu t I doub t they' d b e an ymor e successful . I continu e t o believ e tha t i f ther e ar e effect s a t th

e lo wo r moderat e rang e here , o r i n othe r wel l designed , appropriatel yconducted , studie s the yar e smal l indeed . « Th e possibilit yo f an effec t i n highe r leve l childre n whos e care taker s d o no t identif yand/o r see k treatmen t remains . Earlie r I indicate d tha t th e dat a o f on e chil d had bee n exclude d fromal l analyse s save thos e o f the preschoo l outcome data . Th e evidenc e suggesting the possibilit yo f menta l retardatio n secondar yt o elevate d lead exposur e wa s submitte d i n a memo date d Jun e 6 , 1983 . T o summarize : Bloo d lead s range d fro m3 1 t o 6 0 ug/d l a t variou s time s o f sampling , wit hthe highes t occurring a t a preschoo l evaluation . FE P value s wer e moderatel yelevated . Mos t critically , the dentin e lea d leve l o f 107.3 5 wa s highl yabnormal . Fro mthe time o f preschoo l testing , th e intel

ligenc e tes t scor e (McCarth yGCI ) droppe d fro

m8 0 t o 48 . A t the tim e o f th e preschoo l evaluation , record s fro mthe N.Y.C . Lead Poisoning Contro l Progra m indicate d pic a an

d the presenc e o f excessiv e level s o f lea d i n th e home . Th e famil yrefuse d correction . Th e parent s wer e directe d t o take th e chil d fo r medica l attentio n bu t apparentl ydi d no t comply . Th e famil ystil l lived a t thi s residenc e a t ou r reevaluatio n five year s later .

Thi s tragi c cas e i s consisten t wit han interpretatio n o f marke d lea d effect s a t moderatel yhighlevel s i n a chil d wit hpic a an d wit hpreschoo l exposur e ove r a perio d o f time . Th e inclusio n o f hi s dat a i n analyse s o f low leve l lea

d effect s i s no t warrante d an d hi s dat a wer e delete d fro manalyse s o f the schoo l ag e outcome measures .

I n conclusion , thes e set s o f dat a d o no t suppor t a n inferenc e o f low leve l lea

d effects . Unfortunately , the rathe r lowstatistica l powe r prevent s a definitiv e conclusio n o f n o effect . I jus t wis hi t wer e possibl e t o replicat e thi s basi c stud

ywit ha large r sample , wit h mor e sophisticate d researc h method s an d wit h carefull yconducte d analyse s o f venou s bloo d collecte d specificall y fo r research .( ' •

1 . Kleinbaum , D.G. , Kupper , L.L. , & Morgenstern , H . Epidemiologi c Research . Behmont , Calif : Lifetime Learning , 1982 . 2 . Cohe n & Cohen , P . Applie d Multipl e Regression/Correlatio n Analysi s fo r the Behaviora l Sciences . Hillsdale : Lawrenc e Erlbau mAssociates , 1975 . 3 . Kupper , L.L . Persona l Communication . (Pee r Revie wGroup ) Marc h17 , 1983 . .4 . Mahaffey , K.R. , Annest , J.L. , Roberts , J. , Murphy , R.S . Nationa l estimate s o f blood lea

d level : Unite d State s 1976-1980 . Ne wEnglan d Journa l o f Medicine , 1982 , 307 , 573-579 . 5 . Boone , D.J. , Hearn , T. , & Lewis , S . Compariso n o f interlaborator yresult s fo r bloo d lea

d wit hresult s fro

ma definitiv e method . Clinica l Chemistry , 1979 , 2i » 389-393 . 6 . Carter , G.F . Th e pape r punche d dis c techniqu e fo r lea d i n bloo d sample s wit habnorma l haemoglobi n values . Britis hJourna l o f Industria l Medicine , 1978 , J3 5 235-240 . 7 . Muschek , P . Persona l Communicatio n (Pee r Revie wGroup ) Marc h17 , 1983 . 8 . Cohen , J . Th e Needlema n an d Ernhar t studie s o n behaviora l effect s o f subclinica l lea

d fro mthe perspectiv e o f quantitativ e methodology . ILZRO , 1983 . 9 . Pearson , D.T . & Dietrich , K.N . Unpublishe d manuscript , 1983 . 10 . Jones , L.V . Persona l Communicatio n (Pee r Revie wGroup ) Marc h17 , 1983 . 11 . Bellinger , D . & Needleman , H.L . Lead an d the relationshi p betwee n materna l an d chil d intelligence . Journa l o f Pediatrics , 1983 , 10 2 523-527 . V ,\, . * *. \