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J^1> « i * TM \ UNITE D STATE S ENVIRONMENTA L PROTECTIO N AGENC Y I ^)/2- " Offic e o f Ai rQualit yPlannin g an d Standard s \ 1t o*- p Researc h Triangl e Park , Nort h Carolin a 2771 1 RECEIVE D ENVIRONMENTA L PROTECTIO N

AGENCY Novembe r1 , 198 4 w. ^ , 

### MO V 

### 0 7 1# U CENTRA L DOCKE T MEMORANDU M SECTIO N SUBJECT : Protoco l fo rEncodin g Judgment s abou t Dose-Respons e

Curve s fo rLead-Induce d Hemoglobi n Increment s an d Fo r Discussin g Possibl e Advers e Healt h Effect s o f Elevate d E P FROM : Joh n H
. Haine s S^^C*** 4 ***-'* *

Ambien t Standar d Branc h (MD-12 ) TO : Docke t A-83-2 2
Th e purpos e o f thi s memorandu mi s t o ente r int o Docke t A-83-22 , a revise d versio n o f th e subjec t protoco l date d Octobe r 17 , 198 4 (cop y attached) . Th e revise d versio n supersede s th e on e previousl yentere d (ite mII-C-3a ) whic h wa s date d Septembe r 21 , 1984 . Th e Octobe r 17 , 198 4 versio n o f th e protoco l incorporate s th e followin g changes : 1 ) On pag e 2 , fift h lin e - th e wor d revisio n ha s bee n change d t o review . 2 ) O n pag e 6 , the sentenc e beginnin g o n th e elevent h lin e ha s bee n change d t o rea d - Considerin g onl ytha t portio n o f E P elevatio n du e t o lead , i n you r judgment , i s th e relationshi p betwee n bloo d lea d an d hemoglobi n differen t a t differen t E P levels ? 3 ) O n pag e 11 , th e las t thre e paragraph s hav e bee n change d t o rea d - I n you rjudgment , i s lead-induce d elevate d EP associate d wit h alteration s i n an yo f th e following , an d i f so , a t wha t leve l o r rang e o f level s o f E P woul d yo u conside rth e effect s t o becom e adverse ? Thes e ar e alteration s in : 1
. Neurochemistr yo rothe rCNS functions , 2
. Live rdetoxificatio n capabilities , o r 3
. Rena l o rendocrin e functio n (i n particular , reduce d biosynthesi s o f 1,25-dihydroxyvitami n D)
.P. 3

I s ther e a relatio n betwee n lea d induce d elevate d E P and anemi a o f an ysor t beyon d tha t whic hca n b e indexe d b yblood-lea d leve l alone ? Doe s elevate d E P sugges t tha t th e individua l i s mor e susceptibl e t o lea d toxicit ydu e t o subsequen t exposures ? Ar e ther e othe r advers e healt h effect s tha t yo u believ e ma yb e associate d wit helevate d EP ? Attachmen tP. 4

PROTOCOL FO

RENCODIN

G PROBABILIT

Y JUDGMENT S ABOUT DOSE-RESPONS E CURVES FORLEAD-INDUCED HEMOGLOBI N DECREMENTS AND FORDISCUSSIN G POSSIBL

E ADVERSE HEALT H EFFECT S OF ELEVATE D E P 

### 1 . INTRODUCTIO

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

Hemoglobi nDecremen t a s a nAdvers e Healt hEffec t 3
. POPULATIO N A T RIS K 4
. EXPOSUR ECONDITION S 5
. PHYSIOLOGICA LCONDITION S 6
. FACTOR S TO CONSIDER 7
. FACTOR S T O KEE PI N MIN D WHE NMAKINGPROBABILITY JUDGMENT S 7. 1 Sequentia l Consideratio n o f Informatio n 7. 2 Effect s o f

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

Probabilitie s 7. 6 Recommendation s 8
. POSSIBL

EADVERS EHEALT H EFFECT S O FELEVATE D ERYTHROCYT E PROTOPORPHYRI N 9
. FINA LPREPARATIO N FO RELICITATIO NO FPROBABILITY JUDGMENT S (T o b e provide ddurin g initia l visit )

Versio n84.10.1 7P. 5

PROTOCOL FORENCODING PROBABILIT Y JUDGMENT S ABOUT DOSE-RESPONS E CURVE S FO RLEAD-INDUCED HEMOGLOBI N DECREMENTS AN D FORDISCUSSING POSSIBL E ADVERSE HEALT H EFFECT S OF ELEVATE D E P 1 . INTRODUCTION Th e Environmenta l Protectio nAgenc y (EPA ) i s charge db y th e Clea nAi r Ac t wit hsettin g an drevisin g Nationa l Ambien t Ai r 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 hwit ha nadequat e margi n o f safety
. A s yo u know , th e scientifi c base s fo r NAAQ S ar e presente dan dreviewe di n criteri adocuments
. I

n suppor t of th e forthcomin g revie w of th e lea dNAAQS , EP A ha s jus t prepare dane w Air

Quality Criteria for

Lead. I t

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

susceptibl e population s ca nb 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 wit hregar dt o th e physiologica l an dadvers e healt heffect s of lead , an d therefor e represent s ou r mos t up t o dat e knowledg e o nlea deffects
. A s on e aspec t

of th e revie w process , EP A assesse s healt hrisk s b y 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 hof

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 nabou t th e healt hrisk s associate dwit hvariou s potentia l standard s wil l ai dth e EPA administrato r

i n selectin g tha t

standar dwhich , inhi s judgment , protect s th e publi c healt hwit ha 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 nbase dinpar t o n 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 do n th e availabl e evidence , an dt o probabilisticall y estimat e lea dexposur e unde r alternativ eP. 6

NAAQS
. Obtainin g th e healt hris k estimate s the ninvolve s combinin g dose-respons e an d exposur e probabilit y estimates
.

„ Th e proble mof

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
. In 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 nfo 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 ni s no t certai n and , therefore , w e wil l ai dyo u t o represen t you r opinio nprobabilistically
. Furthermore , sinc e th e extrapolatio ndepend s o none' s interpretatio no f 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 nth e probabilisti c judgment s of 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 do nth e rang e o f judgments
. I

f w e a s ris k

analyst s d o ou r

jo b properly , the nno t 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 do nth e rang e o f judgments , bu t w e wil l als o b e abl e t o sho w som e o f th e source s of

th e disagreements
. Indeed , asid e benefi t of thi s exercis e i n whic hw e prob e you r knowledg e inastructure dmanne r ma y b e t o hel p identif

y source s o f

greates t disagreement
. Base do nth 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 of 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 db y th e pregnan t women . A numbe r

o f 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 i nprobabilisti c for myou r opinio nabou t

th e locatio n an dshap e o f

dose-respons e function s fo r certai nwel l define dlevel s of lead-induce dP. 7

hemoglobi nreductio n in th e populatio no f U.S
. childre nfro mconceptio nthroug 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 nyou 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 infac 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 an Advers e Healt h Effec t Ther e ar e difference s of opinion , of

course , a s t o wha t

degre e of

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

clea r tha t EP A 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 ntha t

a hemoglobi nleve 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 nlevel s i ntha 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 o f

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

fro myo u probabilit y judgment s abou t th e shap e an dlocatio n of

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

effect s i nth e sensitiv e population
.
3 . POPULATION 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 nfro m conceptio n throug hthei r sevent hbirthday
. However , yo u ma y believ e o nvariou s ground s tha t younge r an dolde r

childre n i n thi s grou p hav e differen t dose-respons e function s fo r lead-induce dhemoglobi n reduction
. I f so , the nw e wil l elici t you r judgment s separatel y fo r th e ag e group s 0- 3 and 4-6
.P. 8

4 . EXPOSUR

E CONDITIONS W e wil l b e askin g yourjudgmen tabou tpopulatio n respons e rate s a tvariou s blood-lea d levels . Assum e tha tth e blood-lea d leve l underconsideratio n fo ragive n judgmen ti s in equilibrium a s aresul to f asufficientl y long-ter m constan tlea d exposur e withou tgros s excursion s abov e o rbelo wth e state d level .
5 . PHYSIOLOGICA

L CONDITION

S Becaus e th e effec tof

lea d on hemoglobi n leve l depend s on man y parameter s o f

a person' s system , i ti s necessar y t o specif y assumption s abou tthos e parameter s in th e population . The effec to f lea d in th e syste m depend s on th e person' s nutritiona l and metaboli cstatus . The incidenc e o f iro n deficienc y i s greate rin childre n tha n in adults , an d greate rye tin childre n ag e 0- 3 tha n ag e 4-6 , with awid e rang e of iro n level s i n childre n u

p t o thei rsevent h birthday . Assum e tha tth e distributio n of iro n level s i s tha t whic h yo u believ e i tactuall y t o b e in th e ag e group s 0- 3 an d 4-6 . Th e effec to f

lea d als o depend s o n th e level s o f zinc , copper , vitamin s A , C , D , an d E , calcium , phosphorou s and magnesium . Assum e in al l case s tha tthes e nutrient s ar e distributed in th e tw o ag e group s a s yo u believ e the y i n fac tare , takin g int o accoun tth e wid e rang e o f diet s and nutritiona l level s o f

U.S . children . Iti s wel l established , o f course , tha terythrocyt e protoporphyri n (EP) leve l i s positivel y correlate d with blood-lea d level . However , th e correlatio n i s no tperfect , and ther e i s arang e o f

E Pvalue s a tany give n bloo d lead . You ma y believ e tha tth e effec to f lea d varie s with E

Plevel . I

f so , assum e tha tE

Pi s distribute d a teac h blood-lea d leve l a s yo u believ e i ti n fac tis .
6 . FACTORS T O CONSIDER I n orde rt o hel p yo u brin g t o mind th e relevan tevidenc e s o tha tyo u may conside r i tsystematically , an

d als o i n orde rt o hel p us t o interpre tyou rjudgments , w e woul d lik eP. 9 6 

### t o ask yo u t o discus s briefl y you

r interpretation s o

f variou s aspect s o

f th e literature
. Firs t o f all , coul dyou tell , u s somethin g abou t how , in your

judgment , lea dan diro n interac t t o reduc e hemoglobin level s andsomethin g abou t th e relatio n betwee n iro n an d lea dlevel s in th e body ? Similarly , we wouldb e intereste di n your opinion s abou t

th e sam e question s withregar dt o zin c andlea dandt o calciu mandlead
. I t appear s tha t

lea d affect s hemoglobin level s throug hthre e somewha t separat e routes : interferenc e with heme synthesis , interferenc e wit hglobi 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 ? E Pleve l increase s wit

hiro n deficiency , bu t

i t als o increase s wit

hbloo d lea dandi s considere dt o b e aproxy measur e for th e amoun t

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

f E Pelevatio n du e t o lead , inyour judgment , i s th e relationshi p betwee n bloo dlea dan dhemoglobin differen t a t differen t E Plevels ? Finally , we kno

w tha t some group s o

f 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 or in urban area s withlarg e amount s o

f vehicula r traffic
. Thes e childre n wouldten dt o hav e highlea dlevels , bu t do you believ e tha t

ther e ar e als o independen t reason s t o think

tha t thei r dose-effec t

curve s wil l b e differen t

fromchildre n wh

o liv e in othe r

circumstances ? For

example , thes e ma

y b e th e sam e childre n wh o ten dt o hav e poore r

diet s an dles s acces s t o medical care . Wha t i s you r opinio n regardin g th e possibility o f acorrelatio n betwee n increase d exposure andincrease dsusceptibility ? Are ther e othe r factor s t o conside r

in 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 dwithconclusion s tha t we draw fro m research , an dmore generall y in ou r everyday 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 , nor

ar e mos t

peopl eP.1 0

familia r wit hth e proces s o f

actuall y expressin g thei r uncertaint y i nprobabilisti c terms . Whena n exper t

i s aske dt o mak e probabilit y judgment s o nsociall 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 i nasystemati 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 nanalyst s hav e amasse daconsiderabl e amoun t o f dat aconcernin g th e way peopl e for man 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 nsystemati 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 yo u awar e of thes e biase s an dheuristic s s o that , a s muc ha s possible , yo u 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 noffe r som e suggestion s t o hel p yo u mitigat e thei r

effects
.
7. 1 Sequentia l 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 o f informatio n ar e considere don e b y on e i nasequentia l fashion
. However , thos e considere dfirs t

an dlas t

ten dt o dominat e judgment
. I npart , initia l informatio nha s it s undu e influenc e becaus e i t provide s th e framewor k whic hsubsequen t

informatio ni 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 nmemory . Relate dt o thes e sequentia l effect s i s th e phenomeno nof anchoring and adjustment. Base do n earl y partia l information , on e form s a ninitia l probabilit y estimat e regardin g th e even t

i n question
. Thi s ancho r judgmen t

i s the nadjuste da s subsequen t informatio ni s considered
. Unfortunately , suc hadjustment s ten dt o b e to oP.1 1 8 conservative
. In othe r words , to o littl e weigh t i s attache dt o informatio nconsidere d subsequen t

t o th e formation,o f

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

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

example s ar e the nattributed , ofte nincorrectly , t o al l th e member s of

th e populatio nof

interest
. Moreover , thes e memor y effect s ar e ofte n combine dwit hth e sequentia l phenomen adiscusse dearlier
. Fo r example , in considerin g th e evidenc e regardin g th e dose-respons e curv e of aparticula r

pollutant , yo u migh t naturall y firs t

thin k o f astud y yo u o r

apersona l frien drecentl y completed
. O r yo u migh t

thin k of astud y yo u recentl y read , o r on e tha t

was unusua l an dtherefor e stand s out . Th e tendenc y migh t the nb e t o trea t

th e recalle dstudie s a s typica l o f th e populatio no f

relevan t

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

attempt s t o recal l informatio ncoul dresul t i nthinkin g primaril y o f evidenc e consisten t

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

an dimprecisio n o f

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

field
. I nsuc hcases , informatio ni 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 2

7. 4 Relatio n Betwee n Even tImportanc e and 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 o f

th e event s when , rationally , importanc e shoul dno t

affec t probability
. In 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 of 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 of advers e consequence s o f smoking , becaus e the y fee l tha t th e odd s d o 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 nlevel s o f uncertainty , an dt o us e appropriat e criteri ao f discriminatio nfo r

differen t

range s o f 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 in th e sam e fashion , usuall y doin g apoo r jo b i nth 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 i nodd s fro m1.041: 1 t o 1.004:1, bu t

achang e fro ma n estimat e o f 0.99 9 t o 0.99 0 change s th e odd s b y 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

o f 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 nhel p minimiz e them
. Mos t importan t

i s t o b e awar e o f

one' s natura l cognitiv e biases , an dt o tr y consciousl y t o avoi dthem
.P.1 3
1 0 T o avoi dsequential

effects kee p i nmin dtha t th e orde r

i nwhic hyo u thin k

o f informatio n shoul dno t

influenc e you r

fina l judgment
. I t

ma y b e helpfu l t o actuall y not e o n pape r th e importan t

fact s yo u ar e considerin g an dthe nt o reconside r the mi ntw o o r mor e sequences , checkin g th e consistenc y o f you r judgments
. Tr y t o kee p a nope nmin 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 nyo u conside r swa y yo u mor e tha n i s appropriate
. T o avoi dadvers e memor y effects, defin e variou s classe s of informatio ntha t

yo u dee mrelevant , an dthe nsearc hyou r memor y fo r

example s o f

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 . Make aspecia l attemp t t o conside r conflictin g evidence , an dt o thin k of dat atha t

ma y b e inconsisten t

wit ha particula r

theory
. Also , b e carefu l t o concentrat e o nth e give nprobabilit y judgmen t an d d o no t le t you r ow n value s (ho w yo u woul dmak e th e decisio nyourself ) affec t thos e judgments
. T o accuratel y estimate the reliability of information, pa y attentio nt o suc h matter s a s sampl e siz e an dpowe r of th e statistica l tests . Kee p inmin dtha t dat aar e probabilisti c i n nature , subjec t t o element s o f

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

generalize , fro maparticula r stud y t o asituatio nof 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 o ninformatio n whic hyo u conside r mor e reliable , bu t

d o no t trea t i t a s "absolut e truth. " Kee p i nmin 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 noutcom e influenc e th e poin t

a t whic hactio n i s take nwit 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 nterm s of

th e measur e (probabilit y o r

odds ) wit hwhic hyo u fee l mor e comfortable , bu t sometime s translat e t oP. M
1 1 th e alternativ e scale , o reve n t o measure s o f othe revent s (e.g, , th e probability o f th e even tno thappening) . Whe Restimatin g ver y smal l o rver y larg e likelihoods , i ti s usuall y bes tt o thin kin term s o f odds , whic h ar e unbounded , instea d o f probabilities , whic h ar e bounded . Fo rexample , on e ca n mor e easil y conceptualiz e odd s o f 1:200 tha n a probability o f

.005 .
8 . POSSIBL

E ADVERSE HEALT

H EFFECT S OF ELEVATE D ERYTHROCYTE PROTOPORPHYRI

N (EP) Itseem s wel l establishe d tha tther e i s apositiv e dose-respons e relationshi p betwee n bloo d lea d and EP . Althoug h thi s elevate d E Pca n b e trace d t o hem e synthesi s interference , ther e i s disagreemen ta s t o what , if any advers e healt h effect s ar e associate d wit h lea d induce d elevate d EP . W e woul d lik e t o discus s you rview s o n thi s issu e in oursecon d visi tafte rw e hav e complete d encodin g you rprobabilisti cjudgment s concernin g th e hemoglobi n blood-lea d dose-respons e function . I n you rjudgment , i s lead-induce d elevate d E Passociate d wit h alteration s i n an y o f th e following , an

d i f so , a twhatleve l o rrang e o f level s o f

E Pwoul d yo u conside rth e effect s t o becom e adverse ? Thes e ar e alteration s in : 1 . Neurochemistr y o rothe rCN S functions , 2 . Live rdetoxificatio n capabilities , o r 3 . Renal o rendocrin e functio n (i n particular , reduce d biosynthesi s o f 1,25-dihydroxyvitami n D) . I s ther e arelatio n betwee n lea d induce d elevate d E Pan d anemi ao f

an y sor t beyon d tha twhic h ca n b e indexe d b y blood-lea d leve l alone ? Doe s elevate d E Psugges t tha tth e individual i s mor e susceptibl e t o lea d toxicit y du e t o subsequen texposures ? Ar e ther e othe radvers e healt h effect s tha tyo u believ e ma y b e associate d wit h elevate d EP ?P.1 5
1 2 9 . FINAL PREPARATIO N FORELICITATIO N OF 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 ad o no t determin e th e dose-respons e relationshi p exactly
. Yet , if

w e hav e define dth e dose-respons e curv e precisely , i namathematica l sens e suc harelationshi p doe s exist
. Ou r goa l i s t o hav e yo u represen t probabilisticall y you r ow n uncertaint y abou t th e locatio nan 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 nrespondin 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 nreviewe d i n th e criteri adocument , an dconsul t it , th e literature , o r you r file s a s yo u dee m appropriate
. Th e previou s sectio n suggest s ways 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 noverloa dnaturall y resultin g fro mrapi dconsideratio no f larg e amount s o f comple x evidence
. You ma y fin di t helpfu l t o revie w th e sectio no 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 nb e represente d probabilisticall y i n tw o differen t ways . 1
. Uncertaint y abou t

th e percentag e of

th e define dpopulatio ntha t woul db e affecte db y give nblood-lea dconcentrations ca nb 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 wa y a t atime , focusin g primaril y o nth e firs t one . Fo r thes e purpose s i t

i s helpfu l t o imagin e tha t everyon e i nth e populatio nha s a specifie dblood-lea dleve l tha t ha s becom e stabilize di nth e manne r describe dabov eP.1 6
1 3 unde r Exposur e Conditions. Then , a s aresult , som e percentag e of th e populatio nwil l suffe r th e hemoglobi n response .

- Now , i norde r

fo r u s t o determin e you r

uncertaint y abou t

th e percentage s of

th e populatio n tha t

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

introduc e a definition
. Le t

C b e th e give n blood-lea dconcentratio ni nquestion
. Definition : R(C ) i s th e percentag e of th e populatio nfo r

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

woul dsho w arespons e i f th e entir e populatio n ha dblood-lea dlevel s of 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 nC i s uncertain , an dw e woul dlik e t o obtai n probabilit y judgment s fro myo u 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 of R(C ) b y specifyin g aparticula r percentag e an dhavin g yo u conside r ho w likel y i t

i s tha t R(C ) i s les s tha ntha t value
. T o hel p yo u 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 o f

blu e an dorange . W e ca nrea do nth e bac k o f th e whee l th e percentag e of

th e whee l tha t

i s eac hcolor
. I

nmakin g you r

judgment s yo u 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 o f it s stoppin g wit hth e pointe r o n 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 nC , 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 yo u ar e t o conside r carefull y th e question: D o yo u conside r

i t mor e probabl e tha t

th e tru e populatio nrespons 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 nblu e ,(on arando m spin) ? You 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 nr ;P.1 7
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 wit h th e pointe r

i n blue ; I

" (3 ) Yo

u canno t judg e eithe r

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

concentratio nC 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)
. i Othe r whee l setting s wil l hav e alarg e enoug hrelativ e are aof blu e tha t

yo u 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 hyo u 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 hyo u ar e mos t

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

th e procedure
. Thi s wil l continu e fo r th e give nC 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 o f you r uncertaint y abou t

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

of value s of

C
. I t frequentl y happen s tha t a nexpert' s judgment s alte r somewha t

ove r th e cours e o f 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 yo u fo r you r consideratio nan dcomparison
. A t thes e time s yo u ma y wis ht o chang e som e o f th e judgment s yo u gav e earlier
. W e shoul demphasiz e tha t th e judgment s w e ar e askin g yo u t o mak e ar e no t simpl e ones , no r

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

considere djudgmen t i nligh t

o f th e availabl e relevan t scientifi c data , Therefore , pleas e reflec t o n 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 yo u wis ha s yo u formulat e you r judgments *P.1 8 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 nca nals o b e expresse din term s o f th e blood-lea dconcentratio nnecessar y t o produc e th e effec t i nagive n percentag e of

th e populatio n r , i

f th e entir e populatio nha dth e sam e blood-lea d concentration , stabilize da s th e resul t o f exposur e inth e manne r discusse dearlier
. Mor e 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

i n Rpercen t

of th e population
. Th e valu e of

C(R ) i s uncertai nfo r agive nR , an dw e wan t t o obtai nyou 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 yo u t o conside r

how likel y i t

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

yo u th e question: D o yo u conside r

i t mor e likel y tha t

th e tru e concentratio nC(R ) i s les s tha nc , o r tha t th e whee l woul dsto p wit hth e pointe r o nblu e (o narando mspin) ? Yo u ca ngiv e on e o f

thre e responses : (1 ) You judg e i t

mor e probabl e tha t

C(R ) i s les s tha nc ; (2 ) You judg e i t

mor e probabl e tha t

th e whee l woul dsto p wit hth e pointe r inblue ; (3 ) Yo u canno t

judg e eithe r

even t a s mor e probabl e tha nth e other
. Afte r determinin g th e whee l settin g a t whic hyo u 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 . A s before , fo r eac hRw e wil l elici t

you r comparativ e judgment s fo r variou s value s o f

c .