p. 1 

# OAR Box 1112 Prepped by Ryan Dugan



### Document

Number: 

# 33 ) ll-C-3 a Docket Number: 

# A-83-2 2

Printed 4/16/2008 9:12:07

AM Sheet 33 of 97P. 2

PROTOCO LFO RENCODIN GPROBABILIT Y JUDGMENT S ABOU T DOSE-RESPONS E CURVE S FO RLEAD-INDUCE D HEMOGLOBI N DECREMENTSAN D FO RDISCUSSIN G POSSIBL E ADVERS E

HEALT H EFFECT S O FELEVATE D E P 

### 1 . INTRODUCTION 2 . LEAD-INDUCE D HEMOGLOBI NDECREMENT S 2. 1 Definitio n o f

Hemoglobi n Decremen t a s a n Advers e Healt hEffec t 3 . POPULATIO N A T RIS K 4 . EXPOSUR E CONDITION S 5 . PHYSIOLOGICA LCONDITION S 6 . FACTOR S T O CONSIDE R 7 . FACTOR S T O KEE P I N MIND WHE

N MAKIN GPROBABILIT Y JUDGMENT S 7. 1 Sequentia l Consideratio n o f Informatio n 7. 2 Effect s o f

Memor y o n Judgmen t 7. 3 Estimatin g Reliabilit y o f Informatio n 7. 4 Relatio n Betwee n Even t Importanc e an dProbabilit y 7. 5 Estimatio n o f

Probabilitie s 7. 6 Recommendation s 8 . POSSIBL E ADVERS E HEALT H EFFECT S O FELEVATE D ERYTHROCYT E PROTOPORPHYRI N 9 . FINA LPREPARATIO N FO RELICITATIO N O FPROBABILIT Y JUDGMENT S (T o b e provide ddurin g initia l visit )

ersio n 84.9.2 1P. 3

PROTOCO L FO RENCODIN G PROBABILIT Y JUDGMENT S ABOU T DOSE-RESPONS E CURVE S FO RLEAD-INDUCE D HEMOGLOBI N DECREMENT S AN D FO RDISCUSSIN G POSSIBL E ADVERS E

HEALT H EFFECT S O F ELEVATE D EP 1 . INTRODUCTIO N Th e Environmenta l Protectio n Agenc y (EPA ) i s charge db y th e Clea n Ai r Ac t withsettin g an drevisin g Nationa l Ambien t Air Qualit y Standard s (NAAQS ) fo r selecte d pollutants , a t

level s sufficien t

t o protec t

th e publi c healt hwithan adequat e margi n of safety . A s you know , th e scientifi c base s fo r NAAQS ar e presente dan dreviewe din criteri adocuments . I

n suppor t o f th e forthcomin g revisio n of th e lea dNAAQS , EPA ha s jus t prepare dane w .\ir

Qualit y Criteria for

Lead. I t

present s scientifi c evidenc e fro m whic hth e mos t

susceptibl e population s ca n b e determine dan dfro mwhic hvariou s advers e healt heffect s ca n b e identified . Th e criteri adocumen t summarize s an d evaluate s th e availabl e clinical , epidemiological , an danima l o r toxicologica l laborator y evidenc e withregar dt o th e physiologica l an dadvers e healt heffect s of lead , an d therefor e represent s ou r mos t u p t o dat e knowledg e on lea deffects . As on e aspec t

o f th e revie w process , EP A assesse s healt hrisk s by identifyin g th e mos t sensitiv e population s fo r eac hpollutant , an destimatin g probabilisticall y th e number s o

f peopl e i n th e population s wh o ma y suffe r eac ho f variou s well-define d advers e healt heffect s attributabl e t o th e pollutant . I t i s believe dtha t

informatio n abou t th e healt hrisk s associate dwit hvariou s potentia l standard s wil l ai dth e EP A administrato r

i n selectin g tha t

standar dwhich , in hi s judgment , protect s th e publi c healt hwitha

n adequat e margi n o

f safety . Becaus e th e ris k

estimate s tha t

EP A seek s ar e ofte n base di n par t on dose

respons e relationship s an dlea dexposur e estimate s whic har e uncertain , i t i s necessar y t o mak e probabilit y judgment s abou t relevan t

dose-respons e function s base don th e availabl e evidence , an dt o probabilisticall y estimat e lea dexposur e unde r alternativ eP. 4

NAAQS . Obtainin g th e healt hris k estimate s the n involve s combinin g dose-respons e an d exposur e probabilit y estimates . Th e proble mo

f estimatin g dose-respons e relationship s i s simila r t o tha t whic h exist s i n clinica l medicin e whe n ther e d o no t exis t dat atha t

bea r precisel y o n th e patient' s problem . I

n tha t cas e i t i s necessar y t o us e scientifi c judgmen t t o extrapolat e fro mth e dat at o mak e abes t decisio n fo r

th e patient . Here , too , i t i s necessar y t o us e scientifi c judgmen t

t o extrapolat e fro mth e availabl e data . Th e extrapolatio n i s no t certai n and , therefore , w e wil l ai dyou t o represen t you r opinio n probabilistically . Furthermore , sinc e th e extrapolatio n depend s on one' s interpretatio n of th e literature , differen t peopl e wil l hav e differen t judgments . Fo r

eac hhealt heffec t

w e inten dt o obtai n th e probabilisti c judgment s o f abou t fiv e expert s t o sampl e th e rang e o f respecte d opinions . Th e mode l fo r estimatin g risk s wil l no t merg e thes e judgment s int o asingl e averag e judgment , bu t

rathe r wil l estimat e th e rang e o f risk s base don th e rang e of judgments . I

f w e a s ris k

analyst s do ou r

jo b properly , the n not

onl y wil l w e b e abl e t o sho w th e EP

A administrato r

th e rang e o

f estimate s base don th e rang e o f judgments , bu t w e wil l als o b e abl e t o sho w som e of th e source s of

th e disagreements . Indeed , asid e benefi t o f thi s exercis e in whic hw e prob e you r knowledg e i

n astructure dmanne r

may b e t o hel p identif

y source s of

greates t disagreement . Base do n th e evidenc e i n th e lea dcriteri adocument , tw o population s hav e bee n identifie da s bein g mos t susceptibl e t o th e effect s o f lea dintoxication . On e i s childre n fro mbirt hthroug hth e sevent hbirthday , an dth e othe r i s pregnan t

women , o r

mor e precisely , th e fetuse s bein g carrie dby th e pregnan t women . A numbe r

of advers e healt h effect s hav e bee n identifie dfo r whic hw e woul dlik e t o estimat e dose-respons e function s includin g th e on e discusse dbelow . 2 . LEAD-INDUCED HEMOGLOBI N DECREMENT S W e woul dlik e t o represen t in probabilisti c formyou r opinio n abou t

th e locatio n an dshap e of

dose-respons e function s fo r certai n wel l define dlevel s o f lead-induce dP. 5

hemoglobi n reductio n in th e populatio n of U.S . childre n fro mconceptio n throug hth e sevent hbirthday . W

e realiz e tha t

availabl e dat ad o no t

full y defin e thes e functions ; i f the y did , the n i t

woul db e unnecessar y t o obtai n you r an dothe r

experts ' opinion s abou t them . Nevertheless , i

f th e population , th e exposur e conditions , an dth e healt heffect s ar e al l precisel y defined , the n suc hfunction s i n fac t exis t an dw e woul dlik e you r bes t judgmen t abou t wha t the y woul dloo k

lik e i f th e dat acoul db e collected . 2. 1 Definitio n o f

Hemoglobi n Decremen ta s a n Advers e Healt h Effec t Ther e ar e difference s o f opinion , of

course , a s t o wha t

degre e of

reductio n i n hemoglobi n leve l constitute s ahealt hrisk . Th e Clea n Ai r Ac t make s i t

clea r tha t EPA shoul dse t

it s standard s t o protec t agains t advers e healt heffects . However , th e reductio n in hemoglobi n leve l considere dt o b e advers e ma y b e differen t

fo r regulator y purpose s tha n fo r

clinica l action . Sinc e i t i s generall y agree dfo r childre n tha t

a hemoglobi n leve l o

f abou t 1 2 gram s pe r

decilite r

i s norma l an dabou t

9 gram s pe r decilite r i s anemic , w e wil l specif y tw o hemoglobi n level s i n tha t interval , namel y 9. 5 an d1 1 gm/dl , an dtrea t eac ha s th e physiologica l effec t fo r purpose s of

specifyin g a dose-respons e function . W e wil l elici t

fro myou probabilit y judgment s abou t th e shap e an dlocatio n o

f th e dose-respons e curv e fo r eac hof th e tw o level s o

f effect s i

n th e sensitiv e population . 3 . POPULATIO

N A T RIS K W e ar e definin g th e mos t susceptibl e grou p a s al l Unite dState s childre n fro m conceptio n throug hthei r sevent hbirthday . However , yo u ma y believ e o

n variou s ground s tha t younge r an dolde r

childre n in thi s grou p hav e differen t dose-respons e function s fo r lead-induce dhemoglobi n reduction . I f so , the n w e wil l elici t

you r judgment s separatel y fo r th e ag e group s 0- 3 an d4-6 .P. 6

4 . EXPOSUR

E CONDITION

S W e wil l b e askin g your

judgmen t

abou t populatio n respons e rate s a t variou s blood-lea dlevels . Assum e tha t th e blood-lea dleve l unde r consideratio n fo r

agive n judgmen t i s in equilibriu ma s aresul t o f asufficientl y long-ter mconstan t lea dexposur e withou t gros s excursion s abov e o r belo w th e state dlevel . 5 . PHYSIOLOGICA

L CONDITION

S Becaus e th e effec t

of lea don hemoglobi n leve l depend s on man y parameter s of a person' s system , i t

i s necessar y t o specif y assumption s abou t

thos e parameter s in th e population . Th e effec t o f lea di n th e syste mdepend s on th e person' s nutritiona l an d metaboli c status . Th e incidenc e o f iro n deficienc y i s greate r in childre n tha n i n adults , an dgreate r

ye t in childre n ag e 0- 3 tha n ag e 4-6 , wit hawid e rang e of iro n level s i n childre n u

p t o thei r sevent hbirthday . Assum e tha t th e distributio n o

f iro n level s i s tha t whic hyou believ e i t

actuall y t o b e i n th e ag e group s 0- 3 an d4-6 . Th e effec t of lea dals o depend s on th e level s o

f zinc , copper , vitamin s A , C , D , an dE , calcium , phosphorou s an d magnesium . Assum e i

n al l case s tha t

thes e nutrient s ar e distribute din th e tw o ag e group s a s you believ e the y in fac t are , takin g int o accoun t th e wid e rang e of

diet s an d nutritiona l level s o

f U.S . children . I t i s wel l established , o

f course , tha t

erythrocyt e protoporphyri n (EP ) leve l i s positivel y correlate dwit hblood-lea dlevel . However , th e correlatio n i s no t perfect , an d ther e i s arang e o

f E P value s a t

an y give n bloo dlead . Yo u ma y believ e tha t

th e effec t

of lea dvarie s withE

P level . I

f so , assum e tha t

E P i s distribute da t

eac hblood-lea dleve l a s you believ e i t

i n fac t is . 6 . FACTOR

S T O CONSIDE

R I n orde r t o hel p yo

u brin g t o min dth e relevan t evidenc e s o tha t

yo u may conside r i t systematically , an dals o i n orde r t o hel p u s t o interpre t you r judgments , w e woul dlik eP. 7

t o as k you t o discus s briefl y you r interpretation s of

variou s aspect s o

f th e literature . Firs t of all , coul dyo u tel l u s somethin g abou t how , i n your judgment , lea dan diro n interac t t o reduc e hemoglobi n level s an dsomethin g abou t th e relatio n betwee n iro n an d lea dlevel s in th e body ? Similarly , w e woul db e intereste di n your opinion s abou t

th e sam e question s wit hregar dt o zin c an dlea dan dt o calciu man dlead . I t appear s tha t

lea d affect s hemoglobi n level s throug hthre e somewha t separat e routes : interferenc e wit h hem e synthesis , interferenc e withglobi n synthesis , an ddecrease dlif e expectanc y o

f erythrocytes . Briefly , wha t i s you r interpretatio n o

f th e literatur e on thes e variou s effect s o f lead ? EP leve l increase s wit hiro n deficiency , but i t als o increase s wit hbloo d lea dan di s considere dt o b e aprox y measur e fo r th e amoun t

o f lea drecentl y cumulate d in bod y tissue . Considerin g onl y tha t portio n of

EP elevatio n du e t o lead , how , i n you r judgment , i s th e blood-lea dhemoglobi n dose-respons e relationshi p affecte dby E P level ? Finally , w e kno w tha t

som e group s of

childre n ar e a t

greate r ris k o f exposur e t o lea ddu e t o thei r

livin g in deterioratin g pre-195 0 housin g o r i n urba n area s withlarg e amount s of

vehicula r

traffic . Thes e childre n woul dten dt o hav e hig hlea dlevels , bu t d o you believ e tha t

ther e ar e als o independen t reason s t o thin k

tha t thei r dose-effec t

curve s wil l b e differen t

fro mchildre n who liv e i n othe r circumstances ? Fo r

example , thes e may b e th e sam e childre n who ten dt o hav e poore r diet s an dles s acces s t o medica l care . Wha t i s you r opinio n regardin g th e possibilit y of acorrelatio n betwee n increase d exposur e an dincrease dsusceptibility ? Ar e ther e othe r factor s t o conside r

i n thinkin g abou t th e dose-respons e function s fo r lead-induce dhemoglobi n decrement s tha t w e shoul ddiscus s now ?

7 . FACTOR S T O KEE PI N MIN D WHE N MAKIN G PROBABILIT Y JUDGMENT S Ther e i s usuall y uncertaint y associate dwit hconclusion s tha t w e dra w fro m research , an dmor e generall y i n ou r everyda y thinking . However , no t everyon e i s awar e o f al l th e source s tha t

shoul dcontribut e t o thei r uncertainty , no r

ar e mos t

peopl eP. 8

familia r withth e proces s o

f actuall y expressin g thei r uncertaint y in probabilisti c terms . Whe n a n exper t i s aske dt o make probabilit y judgment s on sociall y importan t matters , i t i s particularl y importan t tha t h e o r sh e conside r

th e relevan t

evidenc e in asystemati c an deffectiv e manne r

an dprovid e judgment s tha t represen t

hi s o r he r opinion s well . Experimenta l psychologist s an ddecisio n analyst s hav e amasse daconsiderabl e amoun t o f dat aconcernin g th e wa y peopl e forman dexpres s probabilisti c judgments . Th e evidenc e suggest s tha t

whe n considerin g larg e amount s o f comple x information , mos t peopl e emplo y simplifyin g heuristic s an ddemonstrat e certai n systemati c distortion s of thought , i.e. , cognitiv e biases , whic hadversel y affec t thei r judgments . Th e purpos e of thi s sectio n i s t o mak e you awar e o f thes e biase s an dheuristic s s o that , a s muc ha s possible , you ca n avoi dthe mi n makin g probabilit y judgments . W e wil l firs t

revie w th e mos t widesprea dbiase s an dheuristics , an dthe n offe r som e suggestion s t o hel p yo u mitigat e thei r

effects . 7. 1 Sequential Consideratio n o f Informatio n Generally , th e orde r

i n whic hevidenc e i s considere dinfluence s th e fina l judgment , althoug hlogicall y tha t shoul dno t

b e th e case . O

f necessity , piece s of informatio n ar e considere don e b y on e in asequentia l fashion . However , thos e considere dfirs t

an dlas t ten dt o dominat e judgment . I n part , initia l informatio n ha s it s undu e influenc e becaus e i t provide s th e framework whic hsubsequen t

informatio n i s the n tailore dt o fit . Fo r

example , peopl e usuall y searc hfo r evidenc e t o confirm thei r initia l hypotheses ; the y rarel y loo k fo r evidenc e tha t

weigh s against

them . Th e late r

evidenc e ha s it s undu e effec t

simpl y becaus e i t

i s freshe r

i n memory . Relate dt o thes e sequentia l effect s i s th e phenomeno n of anchoring and adjustment. Base don earl y partia l information , on e form s an initia l probabilit y estimat e regardin g th e even t

i n question . Thi s ancho r judgmen t

i s the n adjuste da s subsequen t informatio n i s considered . Unfortunately , suc hadjustment s ten dt o b e to oP. 9
8 conservative . I

n othe r words , to o littl e weigh t i s attache dt o informatio n considere d subsequen t

t o th e formatio n of

th e initia l judgment . 7. 2 Effect s o f

Memor y on Judgmen t I t i s difficul t

fo r mos t peopl e t o conceptualiz e an dmak e judgment s abou t large , abstrac t universe s o r

populations . A natura l tendenc y i s t o recal l specifi c member s an d the n t o conside r

the mrepresentativ e of th e populatio n a s awhole . However , th e specifi c instance s ofte n ar e recalle dprecisel y becaus e the y stan dou t i n som e way , suc ha s bein g familiar , unusual , especiall y concrete , o r o f persona l significance . Unfortunately , th e specifi c characteristic s of thes e singula r

example s ar e the n attributed , ofte n incorrectly , t o al l th e member s of

th e populatio n o

f interest . Moreover , thes e memor y effect s ar e ofte n combine dwit hth e sequentia l phenomen adiscusse dearlier . Fo r example , i

n considerin g th e evidenc e regardin g th e dose-respons e curv e o f aparticula r

pollutant , yo u migh t naturall y firs t

thin k of astud y you o r

apersona l frien drecentl y completed . O r yo u migh t thin k o f astud y you recentl y read , o r on e tha t

wa s unusua l an dtherefor e stand s out . Th e tendenc y migh t the n b e t o trea t

th e recalle dstudie s a s typica l of th e populatio n of

relevan t

research , ignorin g importan t difference s amon g studies . Subsequen t

attempt s t o recal l informatio n coul dresul t in thinkin g primaril y of evidenc e consisten t

wit hth e initia l item s you though t of . 7. 3 Estimatin g Reliabilit y o f Informatio n Peopl e ten dt o overestimat e th e reliabilit y of information , ignorin g factor s suc h a s samplin g erro r

an dimprecisio n of

measurement . Rathe r the y summariz e evidenc e in term s o f simpl e an ddefinit e conclusions , causin g the mt o b e overconfiden t i n thei r judgments . Thi s tendenc y i s stronge r whe n on e ha s aconsiderabl e amoun t o f intellectua l and/o r persona l involvemen t

in aparticula r

field . I

n suc hcases , informatio n i s ofte n interprete di

n awa y whic hi s consisten t

wit hone' s belief s an dexpectations , result s ar e overgeneralized , an dcontradictor y evidenc e i s ignore do r underestimated .P.1 0

7. 4 Relatio n Betwee n Even tImportanc e an d Probability Sometime s th e importanc e o f events , o r

thei r possibl e cost s o r

benefits , influenc e judgment s abou t th e certaint y of

th e event s when , rationally , importanc e shoul dnot

affec t probability . I

n othe r words , one' s attitude s toward s ris k ten dt o affec t one' s abilit y t o mak e accurat e probabilit y judgments . Fo r example , man y physician s ten d t o overestimat e th e probabilit y o f ver y sever e diseases , becaus e the y fee l i t i s importan t t o detec t an dtrea t

them ; an dsimilarly , man y smoker s underestimat e th e probabilit y o f advers e consequence s of smoking , becaus e the y fee l tha t th e odd s do no t

appl y t o themselve s personally . 7. 5 Estimatio n o f

Probabilitie s Anothe r limitatio n i s relate dt o one' s abilit y t o discriminat e betwee n level s of uncertainty , an dt o us e appropriat e criteri ao f discriminatio n fo r

differen t

range s of probability . On e resul t o f thi s fac t

i s tha t peopl e ten dt o estimat e bot hextrem e an d mid-rang e probabilitie s i n th e sam e fashion , usuall y doin g apoo r jo b in th e extremes . I t help s her e t o thin k

i n term s of

odd s a s wel l a s probabilities . Thus , fo r example , changin g aprobabilit y estimat e fro m0.51 0 t o 0.50 1 i s equivalen t t o achang e in odd s fro m1.041: 1 t o 1.004:1 , bu t

achang e fro man estimat e of 0.99 9 t o 0.99 0 change s th e odd s by afacto r o f abou t 10 ? fro m999: 1 t o 99: 1 Th e close r t o th e extreme s (eithe r 0 o r 1 ) tha t on e i s estimatin g probabilities , th e greate r th e impac t

of smal l changes . 7. 6 Recommendation s Althoug hextensiv e an dcarefu l trainin g woul db e necessar y t o eliminat e al l th e problem s mentione dabove , som e relativel y simpl e suggestion s ca n hel p minimiz e them . Mos t importan t

i s t o b e awar e of

one' s natura l cognitiv e biases , an dt o tr y consciousl y t o avoi dthem .P.1 1 1 0 To avoi dsequentia l effects kee p i n min dtha t

th e orde r

i n whic hyou thin k

of informatio n shoul dno t

influenc e you r

fina l judgment . I t

may b e helpfu l t o actuall y not e on pape r th e importan t

fact s you ar e considerin g an dthe n t o reconside r the mi n tw o o r more sequences , checkin g th e consistenc y of you r judgments . Try t o kee p an ope n min d unti l yo u hav e gon e throug hal l th e evidence , an ddon' t le t th e earl y informatio n yo u conside r swa y you mor e tha n i s appropriate . To avoi dadvers e memory effects, defin e variou s classe s o f informatio n tha t

yo u deemrelevant , an dthe n searc hyou r memor y fo r

example s of

each . Don' t

restric t you r thinkin g onl y t o item s tha t stan dou t

fo r specifi c reasons . Mak e aspecia l attemp t

t o conside r conflictin g evidence , an dt o thin k of dat atha t

may b e inconsisten t

wit ha particula r

theory . Also , b e carefu l t o concentrat e on th e give n probabilit y judgmen t an d d o not le t you r ow n value s (ho

w you woul dmak e th e decisio n yourself ) affec t thos e judgments . T o accuratel y estimate the reliability of information, pay attentio n t o suc h matter s a s sampl e siz e an dpowe r o f th e statistica l tests . Kee p i n mindtha t

dat aar e probabilisti c in nature , subjec t t o element s o

f rando merror , imprecis e measurements , an dsubjectiv e evaluatio n an dinterpretation . I n addition , th e furthe r on e mus t extrapolate , o r

generalize , fro maparticula r stud y t o asituatio n of interest , th e les s reliabl e i s th e conclusio n an dth e les s certaint y shoul db e attribute dt o it . Rel y mor e heavil y on informatio n whic hyou conside r mor e reliable , bu t

do no t trea t i t a s "absolut e truth. " Kee p i n min dtha t the importance of

an event or an outcome should

not influence its judged

probability. I t

i s rationa l t o le t

th e costlines s o r

severit y o

f a n outcom e influenc e th e poin t

a t whic hactio n i s take n wit hrespec t t o it , bu t

no t th e judgmen t

tha t i s mad e abou t

th e outcome' s likelihood . Finally , i n makin g probabilit y judgments , thin k primaril y i n term s o

f th e measur e (probabilit y o r

odds ) wit hwhic hyou fee l mor e comfortable , bu t sometime s translat e t oP.1 2
1 1 th e alternativ e scale , o r eve n t o measure s o f othe r event s (e.g, , th e probabilit y o f th e even t no t happening) . Whe n estimatin g ver y smal l o r ver y larg e likelihoods , i t i s usuall y bes t t o thin k

i n term s o f

odds , whic har e unbounded , instea do f probabilities , whic h ar e bounded . Fo r

example , on e ca n mor e easil y conceptualiz e odd s o f 1:20 0 tha n a probabilit y o f

.005 . 8 . POSSIBL E ADVERS E HEALT H EFFECT S O F ELEVATE D ERYTHROCYT E PROTOPORPHYRI N (EP ) I t seem s wel l establishe dtha t ther e i s apositiv e dose-respons e relationshi p betwee n bloo dlea dan dEP . Althoug hthi s elevate dE P ca n b e trace dt o hem e synthesi s interference , ther e i s disagreemen t a s t o what , if

an y advers e healt heffect s ar e associate dwit hlea dinduce delevate dEP . W e woul dlik e t o discus s you r view s o n thi s issu e i n ou r

secon dvisi t

afte r w e hav e complete dencodin g you r probabilisti c judgment s concernin g th e hemoglobi n blood-lea ddose-respons e function . I n you r judgment , i s lea dinduce delevate dE P associate dwit halteration s i n neura l tissu e o r

wit hcentra l nervou s syste mdysfunctio n eithe r directl y o r

indirectly ? I

f so , a t wha t E P leve l o r

rang e o f

level s woul dyo u conside r suc heffect s t o becom e adverse ? I s ther e arelatio n betwee n lea dinduce delevate dE P an danemi ao f an y sor t beyon dtha t

whic hca n b e indexe db y blood-lea dleve l alone ? Doe s elevate dE P interfer e wit hlive r o r rena l function ? I

f so , a t wha t rang e o f E P level s woul dyo u conside r suc heffect s t o becom e adverse ? Ar e ther e othe r advers e healt heffect s tha t

yo u believ e ma y b e associate dwit helevate dEP ?P.1 3
1 2 9 . FINA L PREPARATIO N FO RELICITATIO N O F PROBABILIT Y JUDGMENT S Th e shap e an dlocatio n of th e dose-respons e curv e a s w e define di t abov e i s uncertain , becaus e th e existin g dat ado not determin e th e dose-respons e relationshi p exactly . Yet , i

f w e hav e define dth e dose-respons e curv e precisely , in amathematica l sens e suc harelationshi p doe s exist . Our goa l i s t o hav e you represen t probabilisticall y you r own uncertaint y abou t th e locatio n an dshap e o f thi s mathematicall y existen t function , base do n you r expertis e an dth e availabl e knowledge . I n respondin g t o th e question s w e wil l as k

you , pleas e thin k

carefull y abou t

th e relevan t

informatio n reviewe d in th e criteri adocument , an dconsul t it , th e literature , o r you r file s a s you dee m appropriate . Th e previou s sectio n suggest s way s t o thin k abou t th e relevan t

data . Th e purpos e o f tha t sectio n i s t o hel p minimiz e th e biasin g effect s tha t frequentl y accompan y th e informatio n overloa dnaturall y resultin g fro mrapi dconsideratio n of larg e amount s of comple x evidence . Yo

u ma y fin di t helpfu l t o revie w th e sectio n o r rais e question s abou t th e point s mad e i

n i t befor e w e begin . Uncertaint y abou t

ados e respons e relationshi p ca n b e represente d probabilisticall y in tw o differen t ways . 1 . Uncertaint y abou t

th e percentag e o

f th e define dpopulatio n tha t woul db e affecte db y give n blood-lead concentrations ca n b e represente dprobabilistically . 2 . Uncertaint y abou t

th e blood-lea dconcentration s tha t woul db e require dt o affec t

agiven percentage of

the defined

population ca n b e represente dprobabilistically . W e wil l concentrat e o n on e way a t atime , focusin g primaril y on th e firs t one . Fo r thes e purpose s i t

i s helpfu l t o imagin e tha t everyon e in th e populatio n ha s a specifie dblood-lea dleve l tha t ha s becom e stabilize di n th e manne r

describe dabov eP. M 1 3 unde r Exposure Conditions. Then , a s aresult , som e percentag e o f th e populatio n wil l suffer'th e hemoglobi n response . Now , i n orde r fo r u s t o determin e you r

uncertaint y abou t

th e percentage s o

f th e populatio n tha t

woul db e affecte db y given blood lead levels we mus t

introduc e a definition . Le t

C b e th e give n blood-lea dconcentratio n in question . Definition : R(C ) i s th e percentag e of th e populatio n fo r

whic hablood-lea dleve l of C woul dcaus e th e define dhemoglobi n healt heffect . Thus , R(C ) i s precisel y th e percen t of th e populatio n tha t

woul dsho w arespons e i f th e entir e populatio n ha dblood-lea dlevel s o f C unde r th e condition s define dabove . R(C ) i s usuall y calle dth e populatio n respons e rate . Th e valu e o

f R(C ) fo r

agive n C i s uncertain , an dw e woul dlik e t o obtai n probabilit y judgment s fro myou abou t it s possibl e values . W e wil l elici t

you r judgment s abou t th e possibl e value s o

f R(C ) by specifyin g aparticula r percentag e an dhavin g you conside r ho w likel y i t

i s tha t R(C ) i s les s tha n tha t value . T o hel p you mak e you r probabilit y judgments , w e wil l mak e us e of adevic e calle daprobabilit y wheel , whic hha s adjustabl e sector s of

blu e an dorange . W e ca n rea don th e bac k o f th e whee l th e percentag e o

f th e whee l tha t

i s eac hcolor . I

n makin g you r

judgment s you ar e t o imagin e tha t th e whee l i s aperfectl y fai r rando mdevice , an dtha t therefor e th e probabilit y of it s stoppin g wit hth e pointe r on blu e i s exactl y represente db y th e relativ e are atha t i s blue . W e wil l the n procee da s follows . Fo r eac hbloo dlea dconcentratio n C , w e wil l specif y aparticula r

percen t r , an dals o se t

th e probabilit y whee l t o hav e aspecifi c relativ e are ao

f blue . The n you ar e t o conside r carefull y th e question: D o you conside r

i t mor e probabl e tha t

th e tru e populatio n respons e rat e R(C ) i s les s tha n r

or tha t th e whee l woul dsto p wit hth e pointe r o n blu e (on arando m spin) ? Yo u ca n giv e on e o

f thre e responses : (1 ) Yo u judg e i t t o b e mor e probabl e tha t R(C ) i s les s tha n r ;P.1 5
1 4 (2) Yo u judg e i t

t o b e mor e probabl e tha t th e whee l woul dsto p with th e pointe r

i n blue ; (3 ) Yo u canno t judg e eithe r

even t a s mor e probabl e tha n th e other . Fo r aparticula r

concentratio n C an dpercen t r , som e whee l setting s wil l hav e a smal l enoug hrelativ e are aof blu e tha t

yo u wil l fee l confiden t makin g respons e (1) . Othe r whee l setting s wil l hav e alarg e enoug hrelativ e are ao f blu e tha t

you wil l fee l confiden t makin g respons e (2) . Th e intermediat e setting s wil l b e mor e difficul t t o judge . However , w e wil l manipulat e th e whee l setting s t o fin dth e on e fo r whic hyou fee l mos t comfortabl e makin g respons e (3) . Onc e w e hav e determine dth e poin t a t whic hyou ar e mos t

comfortabl e wit h respons e (3) , an dstil l focusin g o n th e give n bloo dlea dC , w e wil l specif y anew percen t r' , an drepea t

th e procedure . Thi s wil l continu e fo r th e give n C unti l w e hav e specifie d variou s percents . The n w e wil l hav e elicite don e o f th e probabilisti c representation s of you r uncertaint y abou t

th e dose-respons e relationshi p w e need . W e wil l obtai n th e nex t probabilisti c representatio n by specifyin g anew C an dcontinuin g a s before . W e wil l d o thi s fo r anumbe r

o f value s o f C . It frequentl y happen s tha t an expert' s judgment s alte r somewha t

ove r th e cours e of asessio n suc ha s this , a s h e o r sh e consider s th e evidenc e fro mvariou s perspective s an dthink s abou t

th e variou s response s calle dfor . Hence , w e wil l grap hyou r response s and , a t appropriat e times , sho w the mt o you fo r you r consideratio n an dcomparison . A t thes e time s you ma

y wis ht o chang e som e o f th e judgment s you gav e earlier . W e shoul demphasiz e tha t th e judgment s w e ar e askin g you t o mak e ar e no t simpl e ones , no r

o f cours e ar e ther e know n correc t answers . Rather , w e wan t you r bes t an dmos t

considere djudgmen t

in ligh t

of th e availabl e relevan t scientifi c data , Therefore , pleas e reflec t on th e availabl e dat acarefully , feelin g fre e t o consul t th e lea d criteri adocumen t

o r othe r source s a s you wis ha s you formulat e you r judgments .P.1 6 1 5 (Encod e judgment s fo r

a t leas t tw o concentration s of

on e dose-respons e function , the n continu e wit hinstructions. ) Recal l tha t

uncertaint y abou t

th e dose-respons e functio n ca n als o b e expresse din term s of th e blood-lea dconcentratio n necessar y t o produc e th e effec t i n agive n percentag e o

f th e populatio n r , i

f th e entir e populatio n ha dth e sam e blood-lea d concentration , stabilize da s th e resul t of exposur e i n th e manne r discusse dearlier . More specifically , proceedin g a s before , le t u s introduc e adefinition : Definition : C(R) i s th e blood-lea dleve l tha t woul dcaus e th e define dhemoglobi n healt heffec t

in Rpercen t

o f th e population . Th e valu e of

C(R) i s uncertai n fo r agive n R , an dwe wan t t o obtai n you r judgment s abou t

it s possibl e values . Analogousl y t o wha t w e hav e alread y done , fo r a give n Rw e wil l specif

y concentration s c an das k you t o conside r

ho w likel y i t

i s tha t th e tru e C(R) i s les s tha n th e specifie dc . Mor e specifically , utilizin g th e whee l a s before , w e wil l as k

yo u th e question: Do yo u conside r

i t more likel y tha t

th e tru e concentratio n C(R) i s les s tha n c , or tha t th e whee l woul dsto p wit hth e pointe r o n blu e (o n arando mspin) ? Yo u ca n giv e on e o

f thre e responses : (1 ) Yo u judg e i t mor e probabl e tha t

C(R) i s les s tha n c ; (2 ) Yo u judg e i t

mor e probabl e tha t

th e whee l woul dsto p wit hth e pointe r i n blue ; (3 ) Yo u canno t judg e eithe r

even t a s mor e probabl e tha n th e other . Afte r determinin g th e whee l settin g a t whic hyou fee l mos t

comfortabl e wit h respons e (3) , w e wil l specif y ane w c an drepea t

th e process . As before , fo r eac hRw e wil l elici t you r comparativ e judgment s fo r variou s value s of

c .