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# Woodward-Clyd e Consultant s

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PreTABL E O F CONTENT S P. 3

Chapte r 1 , INTRODUCTION 1. 1 Th e Ambien t Carbo n Monoxid e Problem 1. 2 Organizatio n o f the Repor t Chapte r 2 . HEALT H EFFECT S O F LOW-LEVE L EXPOSUR E TO CO: '

SUMMAR YO F EMPIRICA

L AN D EPIDEMIOLOGICAL FINDING S

2. 3 2. 4 Healt hEffect s o n Cardiovascula r Patient s Healt hEffect s o n Chroni c Obstructiv e Pulmonary Diseas e Patient s Healt hEffect s o n Fetuse s an d Young Childre n Healt hEffect s o n Genera l Populac e 1 1 1 1 1 4 Chapte r 3 . STRUCTUR E O F RIS K ASSESSMEN T MODE L 1 6 3. 1 Overvie wo f the Ris k Assessmen t Mode l 3. 2 Component s o f the Ris k Assessmen t Mode l 1 6 1 7 Chapte r 4 . EXPOSUR E T O CARBO NMONOXID E 2 2 4. 1 Ambien t C O Qualit y 4. 2 Huma n Exposur e t o CO 4. 3 Physiologica l Respons e t o CO 2 2 2 3 2 4 Chapte r 5 . EXPERTS ' RIS K ASSESSMENT S O F HEALT H EFFECT S FROM

LOW-LEVE L EXPOSUR E T O CARBO NMONOXID E 2 7 5. 1 Selectio n o f Healt hExpert s an d InterviewStyl e 5. 2 Th e Healt hEffect s Assessmen t Procedur e 5. 3 Summar

yo f Healt hEffect s an d Ris k Measure s 5. 4 Synopsi s o f the Healt hEffect s Assessment s 2 8 2 9 3 3 3 6 Chapte r 6 . DOSE-RESPONS E RELATIONSHIP S RELATIN GCOH b LEVEL S T O HEALT H EFFECT S 4 6 6. 1 Dose-Respons e Relationship s fo r Majo r Healt hEffect s 6. 2 Dose-Respons e Relationship s fo r Othe r Healt hEffect s 4 8 5 1P. 4

Chapte r 7 . ESTIMATE S O F RIS K 7. 1 Combinatio n o f Exposur e Dat a an d Dose-Exposur e Relationship s 7. 2 Ris k Estimate s fo r Fou r Citie s 7. 3 Analysi s fo r Sensitiv e Group s 7. 4 Analysi s fo r Specia l Exposur e Grou p 7. 5 Ris k Estimate s fo r the U.S . Urba n Populatio n 7. 6 Sensitivit yAnalysi s 

### 5 5
5 5 6 5 6 8 7 0 7 1 7 2 r\

Chapte r 8 . SUMMAR

YAN D DISCUSSION 8. 1 Summaryo f the Analysi s 8. 2 Discussio n o f the Result s 8. 3 Potentia l Refinement s o f the Analysi s 7 4 7 4 7 8 7 9

APPENDI XA . Representativ e interview s wit hexperts . REFERENCE S FIGURE S an

d TABLE S 8 3 9 6 10 2P. 5

: v + Chapte r 1 . INTRODUCTION

I t i s wel l know

n tha t exposur e t o ai r pollutio n can hav e advers e healt heffect s o n some member s o f the public . Recognizing this , Congres s passe d the Clean Ai r Ac t Amendment s o f 197 0 an d 1977 , whic hrequir e the Administrato r o f The Environmenta l Protectio n Agency(EPA ) t o se t primary nationa l ambien t ai r qualit ystandard s t o protec t the publi c healt hwit han adequat e margi n o f safety . However , the problemo f determining an appro priat e standard fo r an yparticula r pollutan t i s difficul t fo r severa l reasons :

1 . ther e ar e usuall ysevera l differen t healt heffect s attributabl e t o exposur e t o a pollutant , 2 . ther e ar e man

yexpert s knowledgeabl e abou t the particula r healt h effect s o f a pollutant , perhap s wit hdiffering views , 3 . the bes t availabl e dat a relating exposur e t o healt heffect s ha s numerou s shortcomings : i t i s extrapolate d fro msmal l contro l group s observe d unde r laborator yconditions , inferre d from laboratorystudie s involving animals , o r observe d fromactua l societa l circumstance s (e.g. , during a smo g alert ) wher e numerou s possibl e "extraneous " effect s can no t b e controlled , 4 . ther e i s significan t uncertaint yabou t the relationshi p betwee n propose d standard s an d resulting huma n exposur e sinc e thi s depend s o n factor s sucha s the meteorolog ywhic hdilute s an d distribute s the pollutant s an d activit ypattern s an d location s o f humans ,if' 5 . man

ydifferen t type s o f alternativ e standard s ar e availabl e including combination s whic hlimi t the concentratio n o f the pollutant , specif ythe time perio d ove r whic hconcentratio n i s measured , an

d indicat e the numbe r o f time s the limi t can b e exceede d befor e the standard i s violated , 6 . the nee d t o utiliz e valu e judgment s i n deciding whic hhealt h effect s ar e categorize d a s advers e an d the relativ e importanc e o f the differen t type s o f healt heffects . Th e complexit yo f appraising alternativ e standard s i s clearl ysufficien t t o rul e ou t the possibilit ytha t a reasonabl e selectio n can occu r withou t the insight s tha t can b e provide d b ya thoroughanalysis . I n addition , suc han analysi s can b e usefu l i n documenting an d justifying the appropriatenes s o f the alternativ e chosen . Th e purpos e o f thi s repor t i s t o demonstrat e the developmen t an d pre sentatio n o f an analysi s o f possibl e ambien t ai r qualit ystandard s fo r on e majo r pollutant , carbo n monoxid e (CO) . Th e analysi s i s conducte d t o addres s explicitl ythe si xcomplexitie s inheren t i n suc hstandard-setting problem s an

d t o illustrat e a methodology , no t t o develop an analysi s whic h i s t o b e use d i n standard setting a t thi s time . Specifically , w e develop a ris k assessmen t mode l t o relat e advers e healt heffect s t o alternativ e carbo n monoxid e standards . Th e problemi s decompose d int o manageabl e portions , corresponding t o field s o f expertise . Th e ris k assessmen t involve s a blend o f informatio n gathering an d modeling t o quantif yan d synthesiz e al l the availabl e information , including the professiona l judgment s o f severa l expert s a s wel l a s experimenta l data . Quantitativ e estimate s ar e obtaine d fo r selecte d summarymeasure s o f advers e healt hP. 7

». ^ effects,'and uncertaint yi s recognize d formall yi n term s o f probabilit y distributions .

1. 1 Th e Ambien t Carbo n Monoxid e Problem

Thi s sectio n briefl youtline s the problemaddresse d b yspecifying th e objective s chose n fo r the analysi s an d the alternativ e standard s examined .

Base d o n the availabl e informatio n abou t exposur e t o carbo n monoxide , the majo r healt heffect s appea r t o b e the possibilit yo f increase d angina attack s an

d increase d hear t attack s (i.e. , myocardia l infarction) , some o f whic hmayb e fatal . I n addition , othe r effect s includ e the aggravatio n o f angina , periphera l vascula r diseas e (PVD) , chroni c obstructiv e pulmonary diseas e (COPD) , vigilanc e impairment , an d increase d healt heffect s fo r newborn s whe n mother s wer e exposed . Th e objectiv e fo r the problemwa s t o provid e a ris k assessmen t fo r thes e healt heffect s associate d wit hexposur e t o carbo n monoxide . I n thi s ris k assessment , w e develop quantitativ e estimate s (including probabilities ) o f the occurrenc e o f eac hhealt heffec t fo r eac hpropose d standard .

Ther e wer e eigh t alternativ e standard s analyze d i n the study . Th e standards , whic hwer e specifie d b ythe EPA , wer e define d i n term s o f thre e parameters : the minimu mallowabl e qualit yo f ai r (i.e. , dail ymaximu m allowabl e pollutio n concentration ) indicate d b ypart s pe r millio n o f C O average d ove r time , the time perio d (i.e. , the averaging time ) ove r whic h thi s leve l mus t b e obtained , an d the expecte d numbe r o f exceedance s allowe d pe r year . Th e eigh t alternative s ar e summarize d i n Tabl e 1.1 . Alternativ e

## J.

1 , the statu s qu o a s o f 1981 , represent s no t jus t a standard , bu t the ^ overal l ai r qualit ysituatio n associate d wit h198 1 standards , regulation s concerning emissio n reductions , enforcemen t programs , an d s o on . 1. 2 Organizatio n o f the Repor t

Thi s repor t i s organize d a s follows . Background informatio n concern ing the healt heffect s o f exposur e t o CO i s summarize d i n Chapte r 2 . Th e overal l structur e o f the ris k assessmen t mode l i s presente d i n Chapte r 3 wit hemphasi s o n the decompositio n o f the problemint o manageabl e componen t models . Chapte r 4 summarize s the exposur e mode l use d t o relat e CO stand

ard s t o actua l person-exposur e measures . Th e gathering o f informatio n abou t advers e healt heffect s an d the choice'o f fina l ris k outpu t measure s i s discusse d i n Chapte r 5 . The dose-respons e curve s relating suc hmeasure s t o the leve l o f exposur e ar e develope d i n Chapte r 6 . Th e ris k estimate s fo r eac hstandard ar e give n i n Chapte r 7 , an d Chapte r 8 contain s a brie f summaryan

d some concluding comments .P. 9

Chapte r 2 . HEALT H EFFECT S O F LOW-LEVE L EXPOSUR E T O CO : SUMMAR YO F EMPIRICAL AN

D EPIDEMIOLOGICAL FINDING S

Th e mechanis mb

ywhic hexposur e t o CO result s i n healt heffect s i s succinctl ydescribe d i n U.S . EPA[1980 ] a s follows :

"EPAinterpret s the existing healt heffect s evidenc e t o indicat e tha t the principa l mechanis mo f C O toxicit yi s throughhypoxemi a (deficien t oxygenatio n o f the blood) . Thi s mechanis msuggest s tha t advers e effect s o n the bod

yresul t fro

mthe strong affinit yo f bloo d hemoglobi n fo r C O (ove r 20 0 time s greate r tha n fo r oxygen) , whic h result s i n the formatio n o f carboxyhemoglobi n (COHb) . Thus , the oxygen-carrying capacit yo f the bloo d i s reduce d sinc e hemoglobi n tha t ha s combine d wit hC O i n thi s manne r i s no t availabl e t o transpor t oxygen ; furthermore , the presenc e o f COH binhibit s the releas e o f oxyge n fromthe remaining hemoglobin . Effect s o n the cardiovascular , centra l nervous , pulmonary , an d othe r system s ar e directl yrelate d t o thi s reductio n i n the abilit yo f the bloo d t o delive r oxyge n t o thes e systems. "

Th e EPACriteri a Documen t fo r Carbo n Monoxid e (EP A[1979] ) provide s a detaile d reviewan

d scientifi c assessmen t o f the effect s o f CO exposur e o n COH bleve l an

d o n health . Th e group s o f individual s tha t appea r mos t sensitive t o C O exposur e ar e cardiovascula r patients , chroni c obstructiv e pulmonarydiseas e patients , an d pregnan t wome n wit hthei r fetuses . Thi s sectio n summarize s empirica l an d epidemiologica l evidenc e o n the effect s o f low-leve l C O exposur e t o member s o f thes e sensitiv e groups , althougheffect s o n individual s no t i n thes e group s ar e als o mentioned . Fo r a muc h

mor e detaile d reviewo f the effect s o f C O exposur e o n COH bleve l (measure d a s the percen t o f concentratio n i n the blood ) an d o n health , se e the Criteri a Documen t (EP A[1979]) . Ashorte r reviewi s provide d b yGoldsmit h an d Landaw[1968] .

Befor e proceeding , i t i s importan t t o mentio n tha t the grou p wit hthe highes t level s o f COH bi n the bloo d i s smokers . Th e level s cause d b ysmok

in g generall yexcee d thos e resulting fro mexposur e t o ai r pollution . Thus , the contributio n o f ai r pollutio n to COH blevel s i n a smoke r i s usuall y muc hles s than the contributio n attributabl e t o smoking . Becaus e o f thi s circumstanc e an

d the fac t tha t smoking i s a voluntaryactivity , the EPA directe d tha t thi s stud yno t addres s CO-relate d healt heffect s fo r smokers . Th e healt heffect s o f concer n relat e t o low-leve l C O exposur e du e t o ai r pollution .

2. 1 Healt hEffect s o n Cardiovascula r Patient s

U.S . EPA[1979 ] reviewthe effect s o f CO o n cardiovascula r patients . Majo r healt heffect s includ e aggravatio n o f angina pectori s an d periphera l vascula r disease , an d possibl e increase d mortalit yfromhear t attack s (i.e. , myocardia l infarction) . Angin a pectori s i s a cardiovascula r diseas e i n whic hmil d exercis e o r excitemen t produce s symptom s o f pressur e an d pai n i n the ches t becaus e o f insufficien t oxyge n suppl yt o the hear t muscle . Availabl e healt heffect s dat a indicat e tha t person s wit hangina an d othe r type s o f coronaryhear t diseas e probabl yincur the greates t ris k fro m low-leve l ambien t exposure s t o CO . Angin a patient s wh o hav e bee n expose dP.1 1

t o lowlevel s o f CO whil e resting hav e subsequentl yexhibited , during exercise , reduce d time t o onse t o f angin a an d increase d duratio n o f angina attacks . Aggravatio n o f angina ma yb e the firs t i n a serie s o f progressivel y mor e seriou s symptom s tha t accompan ycardiovascula r disease . Coronary insufficienc yi s a mor e seriou s symptomtha t occur s a t greate r level s o f oxyge n deprivation . Th e mos t seriou s symptomi n thi s serie s i s myocardia l infarctio n (i.e. , a hear t attack) , whic hmayresul t i n longe r an d mor e intens e pai n an

d irreversibl e hear t damag e o r possibl ydeath . Categorize d a s periphera l vascula r diseas e ar e a numbe r o f differen t diseases , the majo r typ e being arteriosclerosis . Low-leve l CO exposur e aggravate s periphera l vascula r diseas e b ydecreasing the time t o onse t o f pain . Thes e effect s ar e discusse d i n U.S . EPA[1980] . Aggravatio n o f Angin a Pectoris . Severa l experiment s hav e expose d individ

ual s t o CO . Arono w[1981] , Arono wan d Isbel l [1973] , an d Anderso n e t al . [1973 ] directl yexpose d subject s t o CO i n laboratorysettings . Arono w [1978 ] pu t subject s i n ventilate d o r unventilate d room s fille d wit htobacc o smok e containing CO an d othe r pollutants . Finally , Arono we t al . [1972 ] had subject s breath e ai r whil e riding i n a n ope n ca r o n Lo s Angele s free

ways . Thes e experiment s hav e show n tha t angina pectori s patients , upo n exposur e t o CO , experienc e a decreas e i n the amoun t o f time the yar e abl e t o exercis e befor e the onse t o f angina l pain . Th e degre e o f time-reductio n unti l onse t o f angina i s positivel yrelate d t o the COH blevel .. < Th e dat a fo r the subject s i n the abov e experiment s ar e summarize d i n Tabl e 2.1 . Excluding Aronow' s [1978 ] tobacc o smok e study , thes e dat a ar e plotte d i n Figur e 2.1 . Using linea r regression , the best-fitting repre sentatio n o f the percen t decreas e i n tim e unti l angina l pai n (PDEC ) a s a functio n o f the COH bconcentratio n i s PDE C = 2.5 6 + 4.6 3 (COHb ) fo r COH blevel s ranging from1. 3 t o 8 percent . Thus , fo r eac hpercentag e increas e i n the COH blevel , the tim

e unti l onse t o f pai n decrease s an averag e o f 4.6 3 percent . Not e tha t ther e i s considerabl e deviatio n among individua l patient s fro mthi s model , a s evidence d b ythe dat a point s i n Figur e 2.1 . Thi s regressio n lin e wa s fitte d b yus . The valu e o f the 2 correlatio n coefficien t ( R) wa s 0.16 6 - undoubtedl ya lowvalue . Subsequently , w e d o no t us e thi s relationshi p i n ou r ris k assessment . Aggravatio n o f Periphera l Vascula r Disease . Arono we t al . [1974 ] studie d the effec t o f C O exposur e o n me n wit hintermitten t claudicatio n o f the cal f o r thig hdu e t o occlusiv e arteria l disease . Afte r CO exposure , the mea n COH bleve l wa s 2.7 7 percen t an d ther e wa s a 1 7 percen t decreas e i n time unti l exercise-induce d onse t o f pain . Studie s relating othe r COH blevel s t o decrease d time unti l pai n hav e no t bee n reported .

Increase d Ris k o f Deat hb yMyocardia l Infarction . Epidemiologica l studie s sugges t tha t ther e mayb e an increase d ris k o f deat hb ymyocardia l infarc

tio n (MI ) a s the C O i n ambien t ai r i s increased . I n a stud yb yKur t e t al . [1978 , 1979 ] i n Denver , a positiv e relationshi p wa s observe d betwee n the ambien t C O level s an d the numbe r o f respiratoryan d cardiovascula r com plaints . Th e specifi c healt heffec t whic hha s bee n reporte d i s decrease dP.1 3

exercis e performance . Cohe n e t al . [1969 ] foun d a significantl yhighe r fatalit yrat e among hospita l admission s fo r myocardia l infarction s i n "more-polluted " Lo s Angele s areas . Thi s associatio n onl yhel d fo r the 1 3 week s during 195 8 whic hhad the highes t overal l weekl ymea n CO pollutio n level s i n the rang e 7.7-1 4 ppm . Fo r the less-pollute d week s o f tha t year , the fatalit yrate s wer e simila r i n bot hthe "more-polluted " an d "less

polluted " areas . Astud yi n Baltimor e (Kulle r e t al . [1975] ) a t lowe r ambien t CO level s di d no t detec t an increase d mortalit yrate . Radfor d [1975 ] foun

d M I patients ' diagnose s t o b e consisten t wit hthe effect s o f C O o n the myocardium , thoug hth e effect s coul d no t definitel yb e attribute d t o C O exposure .

I n suppor t o f Cohe n e t al. , Hexte r an d Goldsmit h[1971 ] buil t a mul

tipl e linea r regressio n mode l whic hrelate d dail ymortalit yi n 1962-196 5 fo r Lo s Angele s Count yt o the logarith mo f the dail ymea n C O concentratio n an d othe r independen t variable s including temperatur e an d da yo f yea r t o adjus t fo r cyclica l variations . Th e resul t indicate d

(Tota l deaths/day ) = (al l othe r factors ) + 24.9 4 log(CO) , wher e C O i s measure d i n part s pe r million . Not e tha t whe n the C O leve l change s fro

m7. 3 ppmt o 20. 2 ppm , ther e i s an increas e o f 24.9 4 (log 20.2

- log 7.3 ) = 1 1 i n tota l death s pe r day . Using thi s model , ther e woul d b e an estimate d 1 1 mor e deaths/dayi f the C O leve l change d fro mthe minimu

m observe d leve l o f 7. 3 dail ymea n pp mt o the maximu

mo f 20. 2 dail ymea n ppm .

1 02. 2 Healt hEffect s o n Chroni c Obstructiv e PulmonaryDiseas e Patient s *

Ther e i s littl e informatio n availabl e o n the effect s o f CO o n chroni c obstructiv e pulmonarydiseas e patients . Arono we t al . [1977 ] conducte d a n experimen t i n whic hchroni c obstructiv e pulmonarydiseas e patient s wer e expose d t o CO . The.mea n COH bleve l afte r C O exposur e wa s 4.0 8 percent . Compare d t o befor e exposur e ther e wa s a 3 3 percen t reductio n i n time unti l marke d exercise-induce d dyspne a afte r C O exposure . Th e author s indicate d tha t the

ybeliev e thi s significan t reductio n i n exercis e performanc e i s du e t o cardiovascula r limitations .

2. 3 Healt hEffect s o n Fetuse s an d Young Childre n

U.S . EPA[1979 , 1980 ] an d the Surgeo n General' s 197 9 repor t o n "Smoking an

d Health " an

d the 198 0 repor t o n the "Healt hConsequence s o f Smoking fo r Women " summarize d the effect s o f CO-containing tobacc o smok e o n fetuse s an

d young children . Long o [1977 ] reviewe d studie s o f the effect s o f CO o n pregnan t animal s an d humans . Majo r healt heffect s includ e increase d perinata l mortality , increase d congenita l abnormalities , an d below-norma l birt hweights .

Increase d Perinata l Mortality . I n a laboratoryexperiment , Astru p e t al . [1972 ] observe d increase d neonata l mortalit yrate s among pregnan t rabbit s expose d t o moderat e amount s o f CO . Obviou s ethica l consideration s mak e i t impossibl e t o conduc t a simila r experimen t fo r huma n females . However , epidemiologica l studie s o f pregnan t wome n wh o voluntaril yexpos e themselve s t o C O i n tobacc o smok e hav e bee n conducted . ThoughC O i s combine d wit h

1 1P.1 5

othe r substance s i n tobacc o smoke , the experimenta l mammalia n studie s strongl ysugges t tha t the CO i n smok e is , a t leas t i n part , responsibl e fo r the infants ' deleteriou s healt heffects .

The perinata l (i.e. , lat e feta l an d earl yneonatal ) mortalit yrat e ha s bee n show

n t o increas e a s the numbe r o f cigarette s smoke d dail yincreases . Meye r e t al . [1976 ] repor t Ontari o (Canada ) perinata l mortalit yrate s (afte r adjusting fo r othe r factors ) fo r nonsmokers , dail ysmoker s o f les s than a pack , an

d fo r smoker s o f a pac k o r mor e a day . Ligh t smokers ' (dailysmoker s o f les s than a pack ) babie s had a 2 0 percen t greate r chanc e o f death . Heav

ysmoking led t o a 3 5 percen t greate r chanc e o f deat h among the heav

ysmokers ' babies . Meye r e t al . [1975 ] describe d the simila r result s o f a collaborativ e perinata l stud yfo r twelv e Unite d State s center s fo r blac k an

d whit e women . Finally , Rantakalli o [1969 ] reporte d perinata l mortalit yrate s fo r smoking an d nonsmoking mother s i n Nort hFinland . Eac h stud yuse d differen t definition s fo r ligh t an d heav ysmokers , s o onl yan approximat e compariso n o f the observed'mortalit yrate s i s possibl e a s show n i n Figur e 2.2 . Thoughthes e studie s linked materna l smoking leve l t o the perinata l mortalit yrate , the ydi d no t identif ythe materna l COH blevel s correspond

in g t o variou s smoking level s o r mortalit yrates . According t o Longo' s [1977 ] review , the COH bconcentratio n i n norma l nonsmoking pregnan t wome n i s usall y0. 5 t o 1. 0 percent . Smoking mothers ' COH blevel s a t tim

e o f birt hhav e range d fro m2 t o 1 4 percent , thoughthes e mayb e lowe r than the averag e COH

bduring the pregnancy . Haddo n e t al . [1961 ] observe d a mea n COH bleve l o f 6. 2 percen t whe n a t leas t on e cigarett e wa s smoke d withi n an

1 2P.1 6

hou r o f delivery . Whe n a t leas t on e cigarett e wa s smoke d 1 t o 2 4 hour s prio r t o delivery , a mea n COH bo f 3. 6 percen t wa s observed .

Increase d Congenita l Abnormalities . I n laboratoryexperiments , upo n mater na l CO exposure , mic e an d rabbit s develope d mino r skeleta l alteration s (Schwet z e t al . [1975]) , an d rabbit s had lim

bdeformitie s (Astru p e t al . [1972]) . Huma n smoking studie s sugges t tha t thes e CO-relate d healt h effect s i n animal s mayals o occu r i n humans . Andrew s [1972 ] reporte d tha t 2.3 7 percen t o f nonsmokers ' childre n hav e congenita l abnormalities , whic h increase d t o 2.7 3 percen t fo r smokers ' offspring . Himmelberge r [1978 ] presente d the ris k o f thes e abnormalitie s fo r differen t smoking an d ag e levels , a s show

n i n Figur e 2.3 .

Below-Norma l Birt hWeight . I n laboratoryexperiments , moderat e materna l CO exposur e led t o decrease d infan t birt hweight s among rabbit s (Astru p e t al . [1972] ) an

d rat s (FeChte r an d Anna u [1976]) . Huma n smoking studie s sugges t tha t thi s CO-relate d even t mayals o occu r i n human s expose d t o ambien t C O levels .
Increasing level s o f materna l smoking ar e linke d wit hlowe r birt h weight s (Meredit h[1975] ) an d greate r risk s o f prematurit y(Meye r [1977]) . During childhood , progen yo f smoking mother s i n Finland wer e hospitalize d mor e ofte n an

d had mor e doctor' s visits , a s show n i n Tabl e 2. 2 (Rantakalli o [1969]) .

1 3P.1 7

2. 4 Healt hEffect s o n the Genera l Populac e

Th e majo r healt heffect s o f moderat e CO exposur e o n the genera l populac e ar e decrement s i n vigilanc e an d limitation s o n wor k capacity .

Decrement s i n Vigilance . Man yeffect s o f C O o n the centra l nervou s system hav e bee n studied , including altere d sleep pattern s (O'Donnel l e t al . [1971] , Groll-Knapp e t al . [1978] , an d Haide r e t al . [1976]) , time discrim

inatio n (Beard an

d Werthei m[1967]) , eye-han d coordinatio n (Johnson e t al . [1974]) , an

d driving task s (Wrigh t e t al . [1973]) . Th e studie s o f decre

ment s i n vigilanc e wil l b e summarize d her e a s representativ e o f centra l nervou s systemhealt heffects . Si xstudie s o f the relationshi p o f moderat e CO exposur e wit hvigilanc e performanc e ar e listed i n Tabl e 2.3 . Four studie s repor t decrement s i n vigilance , thoughtwo studie s foun d n o change .

Horvat he t al . [1971 ] expose d subject s t o 0 , 26 , an d 11 1 pp' mC O fo r ove r tw o hours . During exposure , performanc e o n a visua l vigilanc e tas k wa s monitored . Whe n expose d t o 11 1 ppmCO , initiall yther e wa s a signifi

can t decremen t i n vigilanc e performance , bu t thi s bega n improving afte r approximatel y3 7 minutes . Figur e 2. 4 fro mO'Hanlo n [1972 ] show s the vigil

anc e performanc e an d Tabl e 2. 4 fro

mHorvat he t al . [1971 ] contain s the mea n COH blevel s wit hthei r ranges . Fodo r an d Winnek e [1972 ] an d Groll-Knapp e t al . [1972 ] observe d decrement s i n vigilanc e thoughthe ydi d no t repor t act ua l COH blevels . Beard an d Grandstaf f [1975 ] foun d tha t end-of-vigilance

tes t mea n COH

bvalue s o f 1.8 , 5.2 , an d 7. 5 percen t wer e associate d wit h decrease s i n correc t number s o f response s o f 14 , 16 , an d 8 percen t respect ively .

1 4Decremen t i n Wor k Capacity . Moderat e C O exposur e impair s exercis e perfor

manc e (a s measure d b ymaxima l aerobi c power , V MAX ) i n health

ypeople . Horvat he t al . [1975 ] observe d statisticall ysignifican t decrease s i n maxima l aerobi c powe r whe n COH blevel s exceede d a threshol d o f 4. 3 percent . The relationshi p betwee n COH bleve l an

d decremen t i n nonsmokers ' maximu m aerobi c powe r (PDEC=percen t decreas e i n power ) i s modele d b y PDE C = 2. 2 + 0.9 1 (COHb) , wher e COH

bi s indicate d i n percent . Thi s linea r relationshi p i s plotte d i n Figur e 2. 5 an

d i s reproduce d fro mU.S . EPA[1979] . I t represent s the dat a fromHorvath' s grou p an d othe r simila r studies . A s state d i n U.S . EPA [1979],the relationshi p doe s no t appl yt o smoker s i n Horvath' s series , wh o had COH blevel s i n exces s o f 4 t o 5 percen t wit hn o decremen t i n thei r respectiv e V

MA Xvalues . A s can b e see n fromFigur e 2.5 , the linea r fi t i s no t accurat e indicating a considerabl e deviatio n among individua l patient s fromthi s model . Weise r e t al . [1978 ] repor t a simila r mode l base d o n thei r stud yan d others . Thi s mode l i s PDE C = 0.3 5 + 1.08(COHb) .

1 5P.1 9

Chapte r 3 . STRUCTUR E O F RIS K ASSESSMENT MODE L

Aris k assessmen t mode l fo r an ai r pollutan t i s intende d t o relat e ai r qualit ystandard s t o ris k outpu t measures . To evaluat e alternativ e stand

ards , the keyinformatio n i s the relationshi p betwee n a standard an d the healt heffect s tha t the publi c mayexperienc e i f thi s standard i s estab

lished . Simpl ystated , w e woul d lik e t o kno wfo r eac halternativ e C O standard , ho wman

ypeopl e ar e expecte d t o suffe r healt heffect s an d wha t i s the magnitud e o r seriousnes s o f thes e healt heffects .

3. 1 Overvie wo f the Ris k Assessmen t Mode l

A s indicate d i n Figur e 3.1 , the basi c inpu t t o the ris k assessmen t mode l i s an alternativ e standard fo r ambien t CO . Th e eigh t specifi c stand

ard s evaluate d i n thi s stud yar e liste d i n Tabl e 1.1 . Th e statu s qu o refer s t o the ai r qualit ya s i t currentl yexists . Th e othe r standard s ar e define d b

ythre e parameter s indicating the standard leve l i n part s pe r millio n (ppm) , the time perio d ove r whic hconcentration s shoul d b e average d t o examin e compliance , an d the expecte d numbe r o f exceedance s allowe d pe r year . Thus , fo r instance , on e standard examine d i n thi s stud ywa s 9 pp

m using an 8 hou r averag e wit hallowabl e exceedance s occurring o n a t mos t 5 day s pe r yea r o n the average . Thi s mean s tha t a pollutio n inciden t i s recorde d wheneve r the dail ymaximu m8-hour averag e ambien t CO leve l exceed s 9 ppm . I f the expecte d numbe r o f incident s i n a yea r i s si xo r more , the n the standard i s violated .

1 6P.2 0

Th e outpu t measure s fo r the ris k assessmen t mode l estimat e the numbe r o f case s tha t ma

yoccu r (including informatio n regarding the likelihoo d o f occurrence ) du e t o elevate d ambien t CO level s fo r the following healt h effects : angina attacks , nonfata l hear t attacks , fata l hear t attacks , prematur e births , vigilanc e impairment , an d aggravatio n o f angina , chroni c obstructiv e pulmonarydisease , an d periphera l vascula r disease . Some background informatio n concerning thes e healt heffect s a s a resul t o f exposur e t o CO wa s presente d i n Chapte r 2 , an d a detaile d discussio n o f suchhealt heffects , including the developmen t o f the specifi c ris k outpu t measures , i s foun

d i n Chapte r 5 . Thi s sectio n present s the overal l structur e o f the ris k assessmen t model . Mor e detail s abou t specifi c portion s o f the mode l ar e provide d i n Chapter s 4 through7 .

3. 2 Component s o f the Ris k Assessmen t Mode l

Th e relationshi p betwee n a specifi c ambien t C O standard an d ris k outpu t measure s involving advers e healt heffect s i s obviousl ya very comple xrelationship . Fo r example , conside r a typica l questio n abou t thi s relationship : Howman yadditiona l angin a attack s migh t b e expecte d t o occu r unde r a C O standard o f 3 5 ppmusing a 1 hou r averag e wit h1 expecte d exceedanc e pe r yea r than unde r a C O standard o f 2 5 ppmusing a 1 hou r averag e wit h1 expecte d exceedanc e pe r year ? No dat a bearing directl yo n thi s questio n ar e available , an d n o exper t coul d b e expecte d t o b e abl e t o provid e a reliabl e answe r t o the question . Informatio n (i.e. , data , expertise ) fro

msevera l field s suc ha s meteorology , physiology , an d medicin e woul d b e relevant . Thus , w e nee d t o decompos e the problemint o mor e manageabl e component s corresponding t o specifi c type s o f information .

1 7P.2 1

Thes e component s ar e the n analyze d an d logicall yintegrate d t o gai n insigh t an d informatio n abou t the overal l problem .

Th e decompositio n o f a comple xproblemint o mor e manageabl e part s i s base d o n the "divid e an d conquer " spiri t o f decisio n analysi s (se e Raiff a [1968]) . Th e natur e o f thi s decompositio n i s wha t w e refe r t o a s the structur e o f the ris k assessmen t model . I t i s dictate d t o a larg e exten t b ythe type s o f informatio n tha t ar e bot husefu l an d obtainable . Th e decomposition , show n i n Figur e 3.2 , illustrate s componen t model s t o conside r the following :

1 . the relationshi p betwee n a CO standard an d the ambien t ai r qualit yi n term s o f ambien t CO levels , 2 . Th e relationshi p betwee n ambien t CO level s an d the degre e o f exposur e o f peopl e t o differen t CO levels , 3 . the physiologica l response s o f peopl e t o thei r exposur e t o CO , 4 . the advers e healt heffect s relate d t o physiologica l responses , 5 . the relationshi p betwee n individua l advers e healt heffect s an d specifi c ris k outpu t measures . Admittedl ythes e relationship s ar e no t simple , bu t whe n considere d individ

uall ythe

yar e obviousl yles s comple xthan the overal l relationshi p betwee n standard s an

d ris k measure s show n i n Figur e 3.1 . Collectivel ythe yprovid e a reasonabl e manne r t o characteriz e the overal l relationship . W e wil l briefl ydescrib e eac hcomponen t mode l i n thi s section ; mor e detail s con cerning component s 1- 3 ar e give n i n Chapte r 4 an d mor e detail s concerning component s 4 an

d 5 ar e foun

d i n Chapter s 5 an d 6 .

1 8Th e firs t componen t mode l involve s the relationshi p betwee n a C O

standard an

d the ambien t level s o f CO . Th e standard i s simpl e (e.g. , 3 5 ppm , 1 hou r average , 1 expecte d exceedanc e pe r year ) an d i s no t sufficien t t o indicat e howofte n variou s level s o f C O belo wthe standard wil l occur . Fo r example , ho wofte n wil l the 1 hou r averag e excee d 2 0 pp mfo r a specifi c standard ? Th e ai r qualit ya t a give n locatio n depend s no t jus t o n the standard , bu t o n meteorologica l condition s an d the natur e o f th e location . Fo r example , the leve l o f CO nea r a bus ystree t i s usuall yhighe r than i n the middl e o f a larg e park . Th e basi c outpu t fromthe componen t mode l 1 i s a se t o f distribution s o f CO level s fo r differen t type s o f location s a t differen t times .

Give n distribution s o f ambien t CO levels , the exposur e o f individual s wil l stil l vary . A n individual' s exposur e depend s o n hi s o r he r activitie s an d movemen t fromlocatio n t o locatio n a t differen t times . Thus , the secon d componen t mode l depend s o n the activit ypattern s withi n the popu latio n o f interest . Someon e wh o commute s acros s a citydail ywil l hav e a differen t distributio n o f exposur e than someon e wh o stay s a t home mos t o f the time . Th e outpu t o f the componen t mode l 2 i s a distributio n o f CO exposur e level s among the member s o f a populatio n ove r time .

Wha t happen s whe n a perso n i s expose d t o a highconcentratio n o f C O i n the air ? Th e primaryphysiologica l respons e i s an increas e i n the leve l o f carboxyhemoglobi n (COHb ) i n the blood . Componen t mode l 3 relate s COH b level s t o C O exposure . Thi s provide s a distributio n o f COH blevel s acros s peopl e an

d acros s time .

1 9P.2 3

I n the fourt hcomponen t mode l w e ar e finall yread yt o conside r healt h effects . A

n elevatio n i n COH

bleve l i n the bloo d maylead t o the advers e healt heffect s indicate d i n Chapte r 2 . Fo r example , increase d COH btend s t o reduc e the time unti l the onse t o f an angina attac k an d ma ycaus e decre

ment s i n performanc e fo r peopl e doing task s tha t requir e vigilance . Com
ponen t mode l 4 concern s the 'relationship betwee n increase d COH blevel s an

d variou s advers e healt heffects . Fo r example , i f the COH bleve l i s increas

e d fromit s "normal " valu e t o a particula r higher-than-norma l level , wha t percentag e o f angina patient s wil l hav e additiona l attacks ? Componen t mode l 4 can b e though t o f i n term s o f probabilisti c dose-respons e relation

ships . Th e COH

bleve l represent s the dose , an d the respons e i s measure d i n terms o f the probabilit yo f variou s healt heffect s t o an individual . Finally , the fift hcomponen t mode l translate s individua l healt h effect s int o specifi c ris k outpu t measures . Combining informatio n fromthe earlie r component s wit hdat a regarding the numbe r o f peopl e suffering fro m angina wil l enabl e u s t o estimat e the additiona l numbe r o f angina patient s having additiona l attacks , using probabilitie s a s wel l a s poin t estimates .

The structur e o f the ris k assessmen t mode l show n i n Figur e 3. 2 repre sent s the decompositio n o f the ris k assessmen t tha t seem s mos t appropriat e t o examin e alternativ e ambien t CO standards . I t i s possibl e t o obtai n informatio n necessaryfo r the componen t model s i n thi s decompositio n using expertis e mos t pertinen t t o eac hcomponent . Fortunately , EPAhad previous

l ycollecte d an

d integrate d the informatio n necessaryfo r the firs t thre e componen t model s int o an overal l exposur e model . Thi s enable d u s t o expen d mor e time an

d effor t o n the othe r components . Model s corresponding t o com 2 0ponent s 4 an d 5 necessaryt o relat e COH blevel s t o the numbe r o f CO-induce d healt heffect s wer e no t previsoul yavailable . W e foun d tha t medica l expert s coul d provid e usefu l informatio n abou t healt heffect s associate d wit hdifferen t COH blevels . Thus , fo r eac hportio n o f the ris k assessmen t model , w e wer e abl e t o obtai n the mos t reliabl e informatio n availabl e give n the cos t an

d time constraint s o f thi s study .

Afte r the individua l component s o f the ris k assessmen t mode l ar e investigated , i t i s necessaryt o combin e themt o provid e insight s an d understanding abou t the relativ e impact s o f differen t standards . Briefly , thi s mean s tha t a standard result s i n a distributio n o f C O level s i n the air , whic hcan b e combine d wit hcomponen t mode l 2 t o yiel d a distributio n o f C O exposur e level s i n a 'population . This , i n turn , can b e combine d wit h componen t mode l 3 t o provid e an overal l distributio n o f COH blevels , whic h i s the n use d a s an inpu t t o componen t model s 4 an d 5 . Thi s provide s the desire d informatio n i n term s o f the selecte d ris k outpu t measures . B y going throughthi s proces s fo r differen t standards , w e can relat e the numbe r o f case s o f healt heffect s t o the standards , whic hi s the inten t o f the ris k assessmen t model .
Having provide d an overvie wo f the genera l structur e o f the ris k assessmen t model , w e turn t o mor e detaile d discussion s o f the individua l components . Th e standard/ai r quality/exposure/physiologica l respons e portio n o f the mode l (i.e. , component s 1 , 2 , an d 3 ) i s discusse d i n Chapte r 4 , informatio n abou t healt heffect s i s describe d i n Chapte r 5 , an d the developmen t o f dose-respons e relationship s i s covere d i n Chapte r 6 .

2 1Chapte r 4 . EXPOSUR E T O CARBO NMONOXID E

Th e Offic e o f Ai r Qualit yPlanning an d Standard s (OAQPS ) o f the EP A ha s develope d a genera l "Nationa l Ambien t Ai r Qualit yStandard (NAAQS ) Exposur e Model " (NEM ) t o estimat e populatio n exposure s associate d wit h possibl e standards . Th e structur e o f thi s mode l correspond s t o the firs t thre e component s o f the ris k assessmen t mode l presente d i n Chapte r 3 . Detail s abou t the NAAQ S exposur e mode l ar e foun d i n Bille r e t al . [1981 ] an d Johnso n an

d Pau l [1981] , Ou r stud yuse d the outpu t o f NE Mt o generat e exposur e estimate s associate d wit hthe variou s C O standard s unde r consider

ion . Hence , the genera l approac htake n i n NE Man d the natur e o f it s outpu t ar e discusse d briefl yi n thi s chapter . Th e discussio n addresse s the firs t thre e component s o f the ris k assessmen t mode l i n Figur e 3. 2 i n order .

4. 1 Ambien t C O Qualit y

Th e firs t componen t involve s the relationshi p betwee n a standard fo r CO an d the distributio n o f CO level s i n the air . O f course , i t i s no t feasibl e t o measur e distribution s o f C O level s unde r variou s hypothetica l standards . Actua l measurement s involv e the ai r qualit y"a s is, " an d suc h dat a hav e bee n collecte d a t selecte d monitoring sites . The.site s wer e chose n t o represen t specifi c "neighborhoo d types. " I n additio n t o the dat a collectio n stage , some emphasi s wa s give n t o dat a validation , including the us e o f time serie s model s t o fil l i n gap s i n dat a sets .
Sinc e the ai r qualit ydat a represen t the C O level s "a s is, " adjust

ment s ar e necessaryt o determin e the ai r qualit ytha t woul d b e expecte d

2 2P.2 6

unde r alternativ e C O standards . Thi s i s accomplishe d b yNE Mwit ha so-calle d "rollbac k model, " whic hadjust s C O level s i n relatio n t o background CO b

yproportionall yadjusting CO level s abov e a background leve l s o tha t the mos t pollute d monito r (neighborhoo d type ) jus t attain s the standard . Parameter s o f the rollbac k mode l wer e estimate d b yEPAt o simulat e the ai r qualit yexpecte d unde r differen t standards . Thi s provide s a distributio n o f CO level s a t differen t type s o f location s (e.g . center-cit yresidential , suburban commercial , center-cit yindustrial ) a t differen t times . Fo r purpose s o f the ris k assessment , i t i s assume d tha t the respectiv e standard i s jus t met . Thus , i f 5 exceedance s ar e allowed , i t i s assume d tha t exactl y5 exceedance s occur .

4. 2 Human Exposur e t o CO

Th e nex t step i s t o translat e ai r qualit ydat a int o exposur e data . W e mayknowho wofte n a certai n CO leve l tend s tf o occu r a t differen t loca-

- tions , bu t the relevan t questio n fo r a healt hris k assessmen t i s howofte n peopl e ar e actuall yexpose d t o tha t leve l o f CO . Th e answe r t o thi s questio n require s considerabl e informatio n abou t the activit ypattern s o f member s o f the populatio n o f interest . Suc hinformatio n i s provide d b ya huma n activitie s dat a bas e (Roddi n e t al . [1979] ) develope d fo r OAQPS . Th e dat a o n activit ypattern s wa s use d t o separat e the populatio n int o cohor t groups , whic har e group s o f peopl e wh o live i n the same typ e o f neighbor

hood , wor k i n the same typ e o f neighborhood , ar e member s o f the same age-occupatio n class , an d hav e simila r activit ypatterns . Asingl e cohor t can the n b e use d t o represen t an entir e group . Th e cohor t i s assigne d (o n a n hourl ybasis ) t o a neighborhoo d type , a microenvironmen t (e.g. , indoor s

2 3P.2 7

a t work , i n a vehicle , outdoors) , an d an activit yleve l (low , medium , o r high) . Th e informatio n o n activit yleve l doe s no t actuall yinfluenc e exposure , bu t i s necessaryt o estimat e the physiologica l respons e t o tha t exposur e a s indicate d i n the nex t subsection .

Th e exposur e mode l simulate s typica l movement s o f cohort s an d the distributio n o f C O level s a t differen t type s o f location s a t differen t times . Thes e ar e combine d t o produc e an overal l distributio n o f huma n exposur e t o CO . Thi s exposur e i s measure d i n severa l way s (e.g. , pollutan t encounters , numbe r o f peopl e exposed , numbe r o f peopl e a t pea k exposure ) fo r differen t averaging time s (e.g. , one-hour , eight-hour) . Example s o f the outpu t o f the exposur e mode l fo r CO ar e give n i n Table s 4.1-4.3 .

4. 3 Physiologica l Respons e t o CO

A s discusse d i n Chapte r 2 , exposur e t o CO lead s t o increase d COH b level s i n the blood . "The primaryfactor s determining the fina l leve l o f COH bi n individual s ar e the following : concentratio n o f C O inhaled , duratio n o f exposure , alveola r ventilatio n rate s (whichdepen d o n the leve l o f activity) , initia l COH blevel , endogenou s C O production , bloo d volume , hemoglobi n concentration , relative affinit yconstan t o f hemoglobi n fo r C O an d oxyge n (0„ ) barometri c pressure , an d relativ e diffusiv e capabilit yo f the lungs " (U.S . EPA[1980]) .

"Whe n individual s inhal e ai r containing a constan t concentratio n o f CO , severa l hour s ar e require d fo r themt o reac ha stat e o f equilibrium , a t whic hpoin t the COH bleve l i n the bod

yn o longe r increases . Fo r a give n CO

2 4P.2 8

level , the time require d t o reac hequilibriu mi s influence d b

ya numbe r o f factors , the mos t importan t fo r norma l individual s being the leve l o f activit ya s measure d b ythe alveola r ventilatio n rat e ( V ) . A t lowlevel s o f activit y(rest/intermitten t ligh t activity , V =5-1 0 L/min) , approxi

matel y8-1 2 hour s ar e neede d fo r equilibriu mt o b e achieved . Fo r moderat e exercis e (equivalen t t o 3 mp hwalkin g o n leve l ground o r ligh t industryo r housework) , V

=2 0 L/min , an

d the equilibriu

mleve l o f COH

bmayb e reache d i n hal f tha t time " (U.S . EPA[1980]) . Normally , individual s ar e no t expose d t o constan t concentration s fo r lon g period s o f time . Th e Cobur n mode l (Coburn e t al . [1965] ) permit s the calculatio n o f COH

bconcentratio n a s a functio n o f time , wit hthe physio

logica l factor s previousl ymentione d considered . EPAbelieve s the Cobur n mode l predict s wit hreasonabl e accuracythe typica l COH blevel s resulting fromspecifie d CO exposure s fo r non-equilibriu msituations . Thus , the Cobur n mode l allow s on e t o obtai n informatio n o n COH blevel s resulting from short-termCO exposures .

The fina l step performe d a s par t o f the "exposur e analysis " convert s the dat a regarding C O exposur e t o dat a regarding COH bexposur e using the Cobur n model . Example s o f the outpu t o f the exposur e mode l fo r COH bar e give n i n Table s 4.4-4. 6 an d Figure s 4.1-4.2 . I n words , the primary measure s o f interes t are : 1 . Th e annua l numbe r o f person-hour s wit ha COH bleve l greate r than x , fo r variou s value s o f x . 2 . Th e annua l numbe r o f person-day s wit ha t leas t on e hou r o f a COH bleve l greate r than x , fo r variou s value s o f x .

2 5P.2 9

3 . Th e annua l numbe r o f person-year s wit ha t leas t on e hou r o f a COH bleve l greate r than x , fo r variou s value s o f x . Thes e measure s wer e determine d fo r al l o f the standard s unde r consideratio n an d fo r four citie s (Lo s Angeles , Philadelphia , Chicago , an d St . Louis) .

I n an additiona l analysi s (called Specia l Group) , a particula r subse t o f the populatio n o f eac hcitywa s considered . Thi s subse t i s intende d t o represen t individual s wit hrestricte d activities . Parameter s wer e chose n t o limi t the cohort s t o thos e wit hthe characteristic s sucha s chroni c obstructiv e pulmonarydisease . Th e same typ e o f exposur e analysi s ru n fo r the entir e populatio n wa s ru n fo r thi s specia l group .
Disclaimer : Afte r completing the illustrativ e analysi s i n thi s report , w e wer e informe d b

ythe EP

Atha t the exposur e estimate s whic hwer e provide d t o u s systematicall yoverestimate d C O exposures . Thi s result s i n overesti

mate s o f the estimate d healt heffect s associate d wit hvariou s standards . I t doe s no t affec t the methdology , whic hcoul d utiliz e update d exposur e estimate s whe n the

ybecame available .

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Chapte r 5 . EXPERTS ' RIS K ASSESSMENT S O F HEALT H EFFECT S FROMLOW-LEVE L

EXPOSUR E T O CARBO

NMONOXID E

Th e problemo f relating COH blevel s t o specifi c healt heffect s i s exceedingl ycomplex . I t i s no t possibl e t o gathe r dat a directl yo n the healt heffect s o f CO exposur e i n the rea l worl d fo r severa l reasons . Th e C O exposur e i s o f cours e mixe d u p wit hexposur e t o othe r ai r pollutants . Healt heffect s relate d t o ai r pollutio n ar e probabl yaffecte d b ynumerou s othe r factor s suc ha s stress . Dat a i n the laboratorycan b e controlle d t o provid e usefu l information , bu t the n mus t b e "extrapolated " t o yiel d esti

mate d rea l worl d effects . An d some experiment s woul d simpl yb e rule d ou t becaus e o f ethica l (an d commo n sense ) consideration s suc ha s subjecting hear t patient s t o prolonge d highCO exposur e t o observ e whe n hear t attack s occur .

A s indicate d i n Chapte r 2 , ther e i s a significan t collectio n o f dat a concerning the healt heffect s o f CO exposure . T o interpre t the relevanc e o f thi s fo r determining the possibl e healt heffect s o f C O exposure , the professiona l judgment s o f medica l an d healt hexpert s ar e essential . Thi s sectio n describe s the result s o f the interview s wit hsevera l healt hexpert s conducte d t o asses s thei r estimate s o f healt hrisk s fro mlow-leve l C O exposures . Th e focu s o f our discussion s i s o n sensitiv e groups , sinc e the healt heffect s o n othe r peopl e i s considere d t o b e minima l b ymos t experts .

2 7P.3 1

5. 1 Selectio n o f Healt hExpert s an d Intervie wStyl e

Alis t o f 2 0 expert s wa s compile d i n consultatio n wit hthe EP At o represen t a crosssectio n o f variou s specialtie s i n the healt heffect s o f CO . Fourtee n o f thes e experts , liste d i n Tabl e 5.1 , wer e actuall yinter

viewed . Th e lengt ho f interview s range d from3 0 minute s t o two hours . Some expert s wer e personall yinterviewe d tw o o r thre e time s whil e onl y phon e conversation s wer e hel d wit hothers . Th e experts ' knowledg e an d experienc e pertaining t o the healt hris k assessment , willingnes s t o cooper ate , potentia l trave l cost s involve d t o conduc t some persona l interviews , an d timing consideration s wer e the mai n factor s causing variabilit yi n the lengt han

d dept ho f interviews . Th e trave l cos t an d time constraint s place d seriou s restriction s o n our interviewing o f experts . However , w e fee l tha t thes e interview s provide d valuabl e informatio n fo r the purpose s o f thi s study : t o develop the methodologyan d illustrat e it s us e wit hthe healt hris k assessment .

Preserving independenc e o f opinio n an d permitting ventilatio n o f divers e opinio n i s importan t i n the earl ystage s o f ris k assessment . Thus , eac hexper t wa s interviewe d independently . However , needles s t o say , thes e expert s shar e informatio n throughpublications , scientifi c meetings , etc. , an d thu s thei r response s ar e no t completel yindependent . W e merel ywis ht o poin t ou t tha t our ris k assessmen t proces s di d no t involv e dialogu e an d direc t sharing o f information .

I t i s our opinio n tha t a reasonabl e degre e o f agreemen t among expert s exist s o n the majo r healt heffect s o f CO . However , the magnitud e o f eac h

2 8P.3 2

healt heffec t an

d the level s o f exposure s a t whic hthes e effect s begi n diffe r somewha t fro mexper t t o expert . Hence , i f a complet e ris k assessmen t wer e t o b e conducte d i n suppor t o f standard setting , i t woul d b e desirabl e t o hav e repeate d interview s wit hexperts , providing feedbac k regarding the previou s iteratio n o f the ris k assessmen t model . I t woul d als o b e desirabl e t o hav e mor e in-dept hinterview s t o reduc e furthe r the likelihoo d an

d the effec t o f motivationa l o r hueristi c bia s o n the resulting assessments . Cos t an d time constraint s mad e thes e importan t extension s infeasibl e i n thi s study . I n addition , w e fee l tha t i t woul d b e desirabl e t o design a structure d grou p meeting i n whic hexpert s interac t wit hon e anothe r i n the ris k assessmen t process . Our results , whic h attemp t t o integrat e the collectiv e exper t judgments , coul d provid e on e foca l poin t fo r productiv e discussio n o f the healt heffect s o f CO exposure .

5. 2 The Healt hEffect s Assessmen t Procedur e

Eac hintervie wbega n wit ha brie f descriptio n o f the projec t an d the nee d fo r experts ' opinion s i n health-ris k assessment . Th e exper t wa s aske d t o qualitativel yidentif ythe healt heffect s o f low-leve l C O exposures . A descriptio n o f thes e healt heffect s i s give n i n Sectio n 5.3 . Subsequently , fo r a specifie d healt heffec t the exper t wa s aske d t o provid e specifi c informatio n abou t healt heffect s associate d wit hvariou s COH blevels . Fo r example , conside r reduce d time t o onse t o f pai n i n angina patient s a s a healt heffect . Th e exper t wa s aske d wha t percentag e o f angina patient s woul d b e expecte d t o experienc e thi s healt heffec t a t a COH bleve l o f 2 percent . Th e questio n wa s repeate d fo r severa l differen t level s o f COH b (e.g. , 1.5 , 2. 5 an

d 3 percent) . Severa l alternativ e questioning format s

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wer e use d t o elici t thi s information . Assuming a larg e population , sampling fluctuation s wil l b e negligible , an d a percentag e figur e give n b y an exper t can be interprete d a s a subjectiv e probabilit ytha t a randoml y selecte d individua l fromthe populatio n wil l suffe r the healt heffect . W e fee l tha t i t i s easie r fo r the expert s t o interpre t the question s i f the y ar e phrase d i n term s o f percentages .

Th e following i s a sampl e dialogu e i n whic hthe COH bleve l i s specifie d an

d a n expert' s estimat e o f the percentag e o f the populatio n suffering the healt heffec t (i.e. , o f the probabilit ytha t an individua l i n the populatio n wil l suffe r the healt heffect ) i s elicited . Analyst : EP

Aha s determine d tha t angin a patient s constitut e a sensitiv e grou p tha t mus t b e protecte d fro mthe advers e healt heffect s o f CO . Suppos e an experimen t i s conducte d o n 100 0 angina patients . Thes e patient s ar e representativ e o f the populatio n o f angin a patient s i n term s o f severit yo f the condition , age , sex , genera l healt hstatus , an

d s o on . Astud

yi s performe d o n thes e patient s t o evaluat e the effec t o f breathing CO , sufficien t t o raise , the COH bt o 2 percen t withi n tw o t o four hours . Le t u s defin e aggravatio n o f angina t o mea n ther e i s a decreas e o f a t leas t 1 0 percen t i n exercis e duratio n unti l onse t o f an angina attack . I n you r professiona l scientifi c judgment , ho wman ypatient s wil l experienc e aggravatio n o f thei r conditio n i n thi s hypothetica l experiment ? Wil l i t b e les s than o r greate r than 500 ? Expert : Answe r (assum e i t i s greate r than 500 ) Analyst : Wil l i t b e les s than o r greate r than 750 ?

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Expert : Answe r (assum e i t i s les s than 750 ) Analyst : Wha t i s you r bes t gues s (i.e. , median ) abou t the numbe r o f

patient s tha t wil l experienc e aggravation ? Tha t is , i f yo u gues s 650 , yo u shoul d fee l equall ycomfortabl e i n taking a be t tha t i t wil l b e abov e 65 0 o r belo w650 ? I n othe r words , i f I be t o n i t being belo w650 , an d yo u be t o n i t being abov e 65 0 (neithe r o f u s kno wwha t the tru e valu e i s unti l the result s o f the experimen t ar e known) , i t i s a fai r bet ? Expert : Answe r Th e genera l questio n i s the n repeate d fo r othe r level s o f COHb .

A n alternativ e questio n t o determin e the . expert' s estimat e o f the leve l o f COH

btha t wil l caus e the specifie d percentag e o f the populatio n t o experienc e a healt heffec t (i.e. , the leve l o f COH btha t wil l caus e a specifie d probabilit yo f suffering the healt heffect ) i s a s follows . Analyst : EPAha s determine d tha t angina patient s constitut e a sensitiv e

grou p wh o mus t b e protecte d fro mthe advers e healt heffect s o f CO . Base d o n you r professiona l scientifi c opinion , wha t leve l o f COH bwoul d protec t 9 9 percen t o f the angina patient s an d caus e n o mor e than on e i n a hundre d t o suffe r aggravatio n o f the condition ? Wil l i t b e les s than 5 percen t COHb ? Expert : Answe r (assum e yes ) Analyst : Wil l i t b e les s than 3 percen t COHb ? Expert : Answe r (assum e yes) . I t wil l probabl yb e aroun d 1. 8 percen t COHb .

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Simila r question s ar e the n pose d concerning the leve l o f COH b necessaryt o protec t othe r percentage s o f angina patient s fromaggravatio n o f the condition . I t shoul d b e emphasize d tha t al l o f thes e question s elici t experts ' subjectiv e probabilities , eve n thoughtheyar e no t phrase d specificall yi n term s o f probability .

Becaus e o f the complexit yo f the problem , i t i s usefu l a s indicate d t o elici t the sam

e informatio n fromdifferen t perspectives . Thi s produce s re dundan t informatio n an d sometime s indicate s inconsistencie s i n the expert' s responses . Thes e inconsistencie s ar e eas yt o detect . Theyar e pointe d ou t t o the exper t an

d reason s fo r the

mar e solicited . Assessment s ar e the n revise d t o produc e consisten t judgments . Procedure s fo r an d informatio n abou t the assessmen t an d quantificatio n o f professiona l judgmen t can b e foun d i n man

ysource s including Winkle r [1967 , 1969 , 1981] , Tversk yan d Kahnema n [1974] , Spetzle r an d StaS l vo n Holstei n [1975] , Sari n [1978] , an d Wallste n an

d Budesc u [1980] . I n a majorit yo f cases , the expert s initiall yhesitate d whe n providing numerica l estimates . A s the intervie wprogressed , the ybecame increasingl y willing t o quantif ythei r judgments . I n fact , check s a t the time o f the interviewreveale d remarkabl e consistencyi n the responses . I n some case s the same exper t wa s agai n interviewe d a t anothe r dat e an d i t wa s foun

d tha t the response s remaine d stable . (Simila r evidenc e fo r stabilit yan d con sistencyi s provide d i n Wallsten , Forsyth , an d Budescu , [1982]).Thi s show s tha t whil e scientist s ar e ofte n reluctan t t o quantif ythei r judgments , a prope r interrogatio n procedur e help s i n thi s quantification . Furthermore , whe n thei r judgment s ar e base d o n professiona l information , theyrevea l remarkabl e stabilit yan d consistency .

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5. 3 Summaryo f Healt hEffect s an d Ris k Measure s

Base d o n the surveyo f empirica l finding s reporte d i n Chapte r 2 an d the interview s wit hexperts , severa l possibl e healt heffect s associate d wit hlow-leve l CO exposur e hav e bee n identified . Thes e healt heffect s ar e divide d int o tw

o categories : majo r an d other . W e conside r case s o f majo r healt heffect s t o b e mor e seriou s than case s o f othe r healt heffects . Combine d wit hthe numbe r o f case s o f eac ho f thes e healt heffect s induce d b yexposur e t o CO , the majo r effect s woul d appea r mor e significan t fo r appraising appropriat e ambien t C O standards . Our estimate s o f C O risk s i n Chapter s 6 an

d 7 includ e bot hmajo r an d othe r healt heffects , althoughthe uncertaintie s abou t the probabilitisti c estimate s (i.e. , second-orde r probabilities ) ar e onl yinvestigate d fo r the majo r effects .

Ther e ar e thre e majo r healt heffect s o f exposur e t o CO . Thes e ar e additiona l angina attacks , additiona l hear t attacks , an d additiona l death s fromhear t attacks . Thes e ar e define d an d measure d i n the resulting ris k assessment s a s follows :

Additiona l Angin a Attacks : CO exposur e reduce s the exercis e tim e t o the onse t o f an angina attac k i n angina patients . I t i s therefor e believe d tha t a large r numbe r o f angina attack s occu r whe n angina patient s ar e expose d t o CO . Patient s wh o exercis e an d barel yavoi d a n angin a attac k (no t necessaril yconsciously ) i n "norma l air " woul d hav e a reduce d thres

hol d an d therefor e an attac k i n ai r wit ha highe r C O level . A s C O level s increase , the time t o onse t o f an attac k i s furthe r reduce d an d a large r numbe r o f patient s wil l hav e CO-induce d attacks . Thus , on e majo r healt h

3 3effec t measur e i s the annua l numbe r o f angina patient s suffering additiona l

attack s a s a resul t o f C O exposure .
Additiona l Hear t Attacks : B yreducing the oxygen-carrying capacit yo f the blood , C O increase s the discrepanc ybetwee n oxyge n demand an d suppl yt o hear t muscle . Thus , whe n expose d t o CO , some patient s wit hcardiovascula r diseas e ma

yhav e hear t attack s tha t woul d no t hav e occurre d withou t the C O exposure . Hence , a secon d majo r healt heffec t measur e i s the annua l numbe r o f additiona l hear t attack s suffere d b yhear t patient s a s a resul t o f C O exposure .

Death s fromHear t Attacks : Tw o separat e circumstance s mayresul t i n mor e death s fromhear t attack s i n highe r C O environments . First , simpl ybecaus e ther e ar e mor e hear t attacks , on e woul d expec t mor e death s i f the likeli

hoo d o f dying give n a hear t attac k remaine d constant . I n addition , how

ever , some patient s suffering a hear t attac k maydi e i f C O level s ar e high , wherea s the

ywoul d no t di e unde r lowC O levels . Th e las t majo r healt h effec t measur e i s the annua l numbe r o f additiona l hear t attac k death s a s a resul t o f CO exposure .

To interpre t the meaning o f the majo r healt heffects , i t i s importan t t o recogniz e the following . A n individua l mayhav e a hear t attac k induce d b yCO an d di e a s a result . Wit hthe measure s define d above , thi s even t i s counte d bot ha s an additiona l CO-induce d hear t attac k an d a s an additiona l CO-induce d death . W e chos e thes e measure s sinc e the ycorrespond t o the progressio n o f the severit yo f healt heffect s whic hmedica l expert s con sider . Fo r evaluatio n o f alternatives , i t mayb e necessaryt o distinguis h

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betwee n fata l an

d nonfata l hear t attack s t o avoi d the doubl e counting o f effects . I n thi s case , i t i s eas yt o determin e the additiona l numbe r o f nonfata l hear t attack s induce d b yC O b ysubtracting the numbe r o f addi

tiona l death s fro

mthe numbe r o f additiona l hear t attacks .

I n additio n t o the majo r healt heffects , the following five healt h effect s ar e als o quantifie d i n ou r ris k assessment . Sinc e thes e healt h effect s hav e bee n describe d i n Chapte r 2 , onl ythei r measure s fo r the ris k assessmen t ar e give n here . Aggravatio n o f Angina : Thi s healt heffec t i s measure d b ythe annua l numbe r o f angina patient s wh o experienc e a t leas t a 1 0 percen t reductio n i n tim e t o onse t o f angin a attacks . Aggravatio n o f Chroni c Obstructiv e PulmonaryDiseas e (COPD) : Thi s healt h effec t i s measure d b ythe annua l numbe r o f COP D patient s wh o wil l hav e a 1 0 percen t o r mor e reductio n i n the time t o onse t o f marke d dyspne a during exercise . Aggravatio n o f Periphera l Vascula r Disease : Thi s healt heffec t i s measure d b ythe annua l numbe r o f periphera l vascula r patient s wh o experienc e a t leas t a 1 0 percen t reductio n i n time t o onse t o f vascula r attacks . Impairmen t o f Vigilance : Thi s healt heffec t i s measure d b ythe annua l numbe r o f peopl e wh o experienc e some vigilanc e impairmen t du e t o C O exposure . Incidenc e o f Prematurity : Thi s healt heffec t i s measure d b ythe additiona l annua l numbe r o f babie s bor n prematurel ydu e t o frequen t C O exposure s during pregnancy .

3 5P.3 9

I t i s critica l t o recogniz e tha t al l o f our healt heffect s measure s indicat e the numbe r o f additiona l case s annuall yrelativ e t o wha t i s expecte d give n background CO levels . Fo r mos t o f the alternativ e standard s considered , the numbe r o f additiona l case s i s les s than tha t associate d wit hthe "statu s quo " alternative . Thus , w e woul d expec t fewe r case s o f the healt heffect s induce d b yCO i f the corresponding standard wer e established .

5. 4 Synopsi s o f the Healt hEffect s Assessment s

Thi s subsectio n provide s an overvie wo f the healt heffect s indicate d b ythe experts . I n Appendi xA , detail s o f interview s wit hDr . Arono wan d Dr . Kur t ar e give n i n orde r t o indicat e the manne r o f the assessments . Kindl ynot e tha t ther e i s no reporting o f response s fromDr . Tashki n an d Dr . Friedlander . Dr . Tashki n provide d onl ygenera l informatio n an d Dr . Friedlande r wa s primaril yconsulte d fo r the air-qualit yconsiderations .
Patient s wit hCardiovascula r Diseas e Angina . Al l expert s agree d tha t angin a patient s wil l suffe r aggravatio n o f thei r conditio n a t lowlevel s o f C O exposure . Al l expert s commenting o n the numbe r o f angin a attack s fel t mor e attack s woul d occu r a t highe r CO levels . Th e percentage s can b e interprete d a s probabilities . Fo r example , a t a COH

bleve l o f 2 percent , the probabilit ytha t an angina patien t wil l suffe r aggravatio n o f angina i s 0.90 .

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Aronow : Aggravatio n o f angin a Fina l COHb(percent ) Patient s wit haggravatio n o f angina (percent ) (10 % o r mor e reductio n i n time t o onse t o f pain ) 1. 0 5 1. 5 2 0 2. 0 >9 0 2. 5 9 9 CO-Induce d Angin a Attack s Fina l COHb(percent ) Patient s wit hCO-induce d angina attack s (percent ) 1. 0 0- 5 (2 % median ) 1. 5 5-2 0 (10 % median ) 2. 0 10-4 0 (25 % median ) 2. 5 4 0 (median ) 4. 0 6 0 (median ) 5. 0 8 0 (median ) Kurt : CO-Induce d Angin a Attack s Fina l COHb(percent ) Patient s wit hCO-induce d angina attack s (percent ) 1. 5 Some effec t bu t statisticall yundetectabl e 2. 0 2 0 2. 5 3 0 Mustafa : At 2 percen t fina l COHb , ther e woul d b e 10-2 0 percen t additiona l

angina attacks .

Thi s leve l indicate s the fina l COH bafte r on e t o four hour s o f exposur e t o CO . I t i s assume d tha t the patient s ar e engage d i n some exercis e an d ar e no t a t rest .

3 7P.4 1

Rokaw : Expec t 10-1 5 percen t mor e angin a attack s i f COH bleve l i s elevate d b

y2 percent .
Collier : Mor e angina attack s a t 2- 3 percen t fina l COH bleve l than a t lowe r COH blevels .

Horvath : At 2 percen t fina l COHb , on e shoul d expec t 10 0 percen t o f

patient s t o hav e aggravatio n o f angina base d o n the Arono wstudy .

Periphera l Vascula r Disease . Th e mechanis minducing bot hangin a an d periphera l vascula r attack s i s identical . Th e differenc e i s tha t angin a involve s ches t pai n an d a periphera l vascula r attac k involve s le g pain . Hence , the response s o f Drs . Aronow , Kurt , Mustafa , Rokaw , an d Collie r wer e the same a s thos e reporte d fo r angina an d therefor e ar e no t repeated .

Hear t Attacks . Al l expert s agree d tha t CO exposur e woul d caus e an increas e i n the likelihoo d o f a hear t attac k among thos e wh o alread yhav e hear t disease .

Aronow : Hear t Attack s Fina l COHb(percent ) Patient s wit hCO-induce d Hear t Attack s (percent ) 1. 5 1 2. 0 5 3. 0 1 0 4. 0 1 5 5. 0 2 0



### 3 8P.4 2

Ayres : At 3 percen t fina l COHb , ther e ma yb e a 5 percen t increas e i n hear t attacks .

Kurt : At 2 percen t fina l COHb , ther e migh t b e a 2 0 percen t increas e i n

hear t attacks .

Mustafa : A t 2 percen t fina l COHb , ther e woul d b e a 10-2 0 percen t increas e

i n hear t attacks .

Rokaw : W e migh t expec t a 1- 2 percen t increas e i n hear t attack s i f the

COH bleve l i s elevate d b y2 percent .

Coulson : I f an individua l i s abou t t o hav e a hear t attack , CO can tip hi m

t o a hear t attack . Benignus : Exposur e t o CO can caus e an increase d probabilit yo f hear t

attack .

Horvath : I t i s theoreticall ypossibl e tha t the probabilit yo f hear t attac k

wil l increas e wit hgreate r exposur e t o CO .
Additiona l Deaths . Mos t expert s believe d tha t CO exposur e wil l caus e a highe r deat hrat e among thos e wh o ar e having a hear t attack .

3 9P.4 3

Aronow : Fata l Hear t Attack s Fina l COHb(percent ) Increas e i n Death s fromHear t Attack s (percent ) 1. 5 1 2. 0 5 3. 0 1 0 4. 0 ' 1 5 5. 0 2 0

Ayres : Ther e mayb e a 3- 5 percen t increas e i n deat hrat e a t a 3 percen t

fina l COHb .

Kurt : Mor e death s wil l occur becaus e CO wil l precipitat e mor e hear t

attacks . But , the percentag e o f death s amongs t thos e wh o hav e hear t attack s wil l remai n abou t the same .

Mustafa : The increas e i n death s fromhear t attack s migh t b e 5 percen t a t a

COH bo f 2 percent .

Rokaw : Th e probabilit yo f deat hgive n a hear t attac k wil l increas e b y 10-1 5 percen t i f the COH bleve l i s elevate d b y2 percent . Benignus : Highe r COH blevel s woul d increas e the probabilit yo f deat hgive n tha t a hear t attac k occur s an d coul d increas e the expecte d severit yo f the attack .

Beard : Th e presenc e o f highe r COH blevel s impair s the chance s o f surviva l give n on e doe s hav e a hear t attack* .

4 0P.4 4

Progressio n o f Disease . Some expert s believe d tha t C O exposur e cause s an increas e i n the rat e o f progressio n o f cardiovascula r diseas e among thos e wh o alread

yhav e the disease .

Aronow : Lowlevel s o f CO precipitat e angina l pain , myocardia l

infarctions , an

d eve n death . Th e following judgment s relat e t o the increas e i n the probabilit ytha t a n individua l wit hstabl e angina wil l di e b

ythe en

d o f 1 , 5 , o r 1 0 year s du e t o COH b level s highe r than the background leve l o f les s than 1 percen t COHb .

Chanc e o f deat h(percent ) whe n expose d t o CO resulting i n B yen d o f Fina l C0Hb<l%(background ) Fina l COH b= 2 % Fina l COH b= 5 % Yea r 1 5 6 15-2 0 Yea r 5 2 5 3 0 Yea r 1 0 5 0 6 0

Collier : Ther e i s ever yreaso n t o suspec t tha t the progressio n o f cardiovascula r diseas e wil l b e accelerate d b yC O exposure .
Patient s wit hCOP D

Mos t expert s believ e tha t low-leve l C O exposur e o n a chroni c basi s doe s no t increas e the prevalenc e o f respiratorydiseas e bu t i t doe s increas e incidence s o f aggravatio n o f the pre-existing condition .

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Aronow : Aggravatio n o f COP D Fina l COHb(percent ) Patient s wit haggravatio n o f COP D (percent ) 1. 0 5 1. 5 2 0 2. 0 9 0 3. 0 9 9

Ayres : Seriousl yil l pulmonarypatient s wil l experienc e healt heffect s

betwee n 2- 4 percen t fina l COHb .

Kurt : At a 2 percen t fina l COH blevel , CO wil l precipitat e dyspne a bu t wil l no t caus e chroni c bronchitis . Similarly , i t wil l no t pre cipitat e an asthm

a attac k bu t wil l aggravat e i t i f an attac k i s alread ytaking place . Fo r example , i n an otherwis e mil d attack , CO coul d caus e worsening o f the symptom s t o mediu man d a mediu

m attac k coul d become a -serious attac k i n the presenc e o f CO .
Collier : A2 percen t fina l COH bleve l wil l adversel yaffec t the patient s b ylimiting thei r activity . Ther e i s n o stud ylinking C O a s the caus e o f COPD .

Mustafa : Te n t o twentypercen t o f emphysema patient s wil l hav e a 20-5 0

percen t reductio n i n activit ya t 2 percen t fina l COHb . Five t o ten percen t o f bronchiti s patient s wil l hav e a 20-5 0 percen t reductio n i n activit ya t 2 percen t fina l COHb . Th e chanc e o f dying during a seriou s asthma attac k wil l increas e b y5-1 0 percen t a t 2 percen t fina l COHb .

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Rokaw : Sever e emphysema patient s ar e mos t vulnerabl e t o CO . Lung

diseas e probabl ywil l no t respon d (e.g. , no t mor e mucou s formation ) t o CO . Presenc e o f lowlevel s o f CO during an asthm a attac k wil l no t aggravat e the breathing problem .

Crandall : COP D patient s ma yalread

yhav e lowbloo d oxyge n content , an d i f CO reduce s the oxyge n carrying capacity , the n aggravatio n o f thei r conditio n mayresult . I t i s unlikel ytha t sever e wide

spread effect s wil l b e see n belo w2. 5 percen t fina l COH bduring short-termexposures .

Pregnan t Wome n wit hthei r Fetuse s

Mos t expert s believe d tha t frequen t CO exposur e during pregnancycoul d resul t i n a lowe r weigh t o f the bab ya t birth . Sinc e ther e i s a highe r deat hrat e among lowe r weigh t babies , C O mayindirectl ycaus e a highe r deat hrat e among ne wbor n babies . D r Long o wa s the onl yexper t wh o wa s willing t o provid e quantitativ e estimate s relating COH bwit hincidence s o f prematurity . Thes e estimate s lik e othe r healt heffec t estimate s ar e base d o n hi s professiona l judgment .

4 3P.4 7 •^p^p^^r

Longo : Prematur e Birth s Fina l COHb(percent ) Incidence s o f Prematurit y(percent ) 1- 2 Difficul t t o detec t an increas e ove r norma l leve l o f 7 percen t 3- 4 ' 1 0 5 3 0 1 0 6 0 Horvath : Asmalle r growt ho f fetu s wil l b e observe d a t lowlevel s o f C O

exposure .

Kurt : CO wil l caus e lowe r weigh t o f the babie s a t birth .

Othe r Healt hEffect s Vigilanc e effect s

Beard : At 2- 3 percen t fina l COHb , impairmen t o f the abilit yt o

distinguis hthe lengt ho f shor t tim e segments , impairmen t o f visua l acuit yunde r lowillumination , reductio n o f performanc e regarding critica l flicke r fusio n frequency , an d increase d reactio n time t o stimulu s i n the fiel d o f visio n occur . Benignus : A t 4 percen t fina l COHb , 5 0 percen t o f populatio n o f health y young peopl e wh o ar e a t the limi t o f vigilanc e wil l b e affecte d i n a vigilanc e sens e (i.e. , theywil l no t b e abl e t o performan assigne d tas k i n a suitabl e fashion) .

4 4P.4 8

Aronow : At 2- 4 percen t fina l COHb , ther e i s a reductio n i n maxima l

exercis e time . I woul d als o b e concerne d abou t specia l group s suc ha s pilot s an

d drivers , becaus e o f a decreas e i n vigilance .

Mustafa : At a 2- 3 percen t fina l COHb , ther e i s an advers e effec t o n the

abilit yt o d o arithmatic , memory , an d the ocula r systemfo r 5 percen t o f people . A t 5 percen t fina l COHb , the percentag e o f individual s affecte d increase s t o 2 0 percent . At 2- 3 percen t fina l COHb , 5 percen t o f peopl e ar e affecte d b yheadache s causing bothe r bu t no t requiring-rest . At 2- 3 percen t fina l COHb , ther e ma yb e a 1- 5 percen t increas e i n traffi c accident s ove r fina l COH blevel s o f 1 percent . A

n adaptatio n ma

yoccur i f the motorist s ar e facing the highe r COH

blevel s ever

yday .
Atherosclerosi s

Kurt : Long ter

mexposur e t o lowlevel s o f CO (2- 3 percen t fina l COHb ) cause s atherosclerosis . Thi s leve l o f exposur e coul d caus e a 2 0 percen t increas e i n the prevalenc e o f coronaryhear t diseas e i n 1-2 0 years .

Rokaw : C O a s a co-facto r i n additio n t o diet , heredit yeffects , etc. ,

whic hcause s atherosclerosis .

4 5P.4 9

Chapte r 6 . DOSE-RESPONS E RELATIONSHIP S RELATIN GCOH bLEVEL S T O HEALT H EFFECT S

Th e EP Aexposur e mode l fo r CO provide s distribution s o f COH blevel s withi n the population , a s indicate d i n Chapte r 4 . To investigat e quanti

tativel ythe resulting healt heffect s w e nee d t o relat e COH blevel s t o our ris k outpu t measures . Thi s majo r step i n thi s i s t o develop dose-respons e relationships , wit hthe COH bleve l representing the dos e an d the likelihoo d o f variou s healt heffect s representing the responses . Ideally , w e woul d lik e t o hav e dat a fro mcarefull ycontrolle d experi

ment s wit hthe healt heffect s indicate d b ythe ris k outpu t measure s recorde d fo r variou s COH blevels . Suc hdat a coul d provid e numerou s point s fromwhic hdose-respons e curve s coul d b e estimated . However , experimenta l dat a o f thi s natur e ar e no t available . Variou s epidemiologica l an d clin

ica l studie s provid e usefu l informatio n fo r our stud yo f CO-relate d healt h effect s bu t do no t directl yyiel d point s o n a dose-respons e curve . Th e informatio n gathere d fromexpert s concerning CO-relate d healt heffect s use s the informatio n fromthos e epidemiologica l an d clinica l studie s a s wel l a s professiona l experienc e an d judgment s t o provid e the lin k necessaryfo r modeling o f the dose-respons e relationship s o f interest .

Assessment s o f the expert s give the dat a point s t o whic han expecte d dose-respons e relationshi p can b e fi t an d provid e quantitativ e informatio n abou t the degre e o f uncertaint yabou t the relationship . Th e point s sugges t potentia l model s tha t coul d b e use d t o represen t the dose-respons e curve . Fo r eac ho f the thre e majo r healt heffect s (i.e. , angina attacks ,

4 6P.5 0

hear t attacks , an

d hear t attac k deaths) , w e develop probabilit ydistribu

tion s on the response s associate d wit hdifferen t COH blevels , a s wel l a s an expecte d dose-respons e curve . Th e expecte d dose-respons e curve can b e interprete d i n terms o f probabilities , an d the probabilit ydistribution s on the response s can therefor e b e though t o f a s second-orde r probabilities . Fo r the othe r healt heffects , onl yexpecte d dose-response'curve s (i.e. , first-orde r probabilities ) ar e developed .

A s indicate d i n Chapte r 5 , the response s o f interes t ar e the numbe r o f additiona l case s o f the differen t healt heffects . Our dose-respons e func

tion s belo wrelat e COH blevel s t o the percentag e o f additiona l case s o f the healt heffec t fo r the populatio n o f interest . Thi s percentag e is , o f course , simpl ymultiplie d b ythe populatio n o f the appropriat e group s t o provid e the additiona l numbe r o f cases . Percentag e o f cases , rathe r than number , i s use d i n the dose-respons e relationship s fo r severa l reasons :

• Medica l expert s thin k i n terms o f the studie s the yhav e conducte d o r read an

d patient s the

yhav e seen . Theythin k abou t the per centage s o f thes e experiencing healt heffects , rathe r than th e implie d numbe r o f individual s i n societ yexperiencing thes e effects .

• Partiall ya s a resul t o f the above , the experts ' judgment s i n Chapte r 5 provide d percentage s experiencing effect s a t differen t COH blevels .

• Two separat e factors , percentag e o f the populatio n wit hthe effec t an

d siz e o f the population , determin e the numbe r o f case s o f a healt heffect . Ther e can b e uncertaintie s abou t each .

4 7P.5 1

Keeping thes e factor s separat e during the analysi s shoul d improve the qualit yo f information , facilitat e professiona l reviewan d appraisal , an

d provid e fo r mor e interesting sensitivit yanalysis .

6. 1 Dose-Respons e Relationship s fo r Majo r Healt hEffect s

First , conside r angina attacks . Th e dos e i s the COH bleve l i n the blood , expresse d a s a percentage . The response , denote d b yP , i s the percentag e o f angin a patient s suffering additiona l attack s du e t o the COH b level . Dose-respons e point s aggregate d fro mexper t assessment s ar e give n i n Tabl e 6. 1 an

d illustrate d i n Figur e 6.1 . The assessment s o f the expert s whic hdirectl yprovide d informatio n fo r thi s relationshi p ar e als o show n i n Tabl e 6. 1 A s can b e seen , fo r the P leve l associate d wit ha COH blevel , w e too k the mea n respons e whe n mor e than on e exper t provide d information . Thi s i s reasonabl e give n the similarit yo f the professiona l judgments .

Alinea r relationshi p coul d be use d a s a mode l fo r the dat a i n Figur e 6.1 , althougha mode l linea r i n transforme d variable s provide d a bette r fit . Th e dos e wa s expresse d i n logarithmi c terms , an d the respons e wa s expresse d i n log-odd s terms . Th e resulting mode l fo r the expecte d dose-respons e curve i s

ln ( 2_- ) = -3.65+3.1 1 ln(COHb) , (6-1 ) 100-P A A wher e COH

bi s measure d i n percen t an d the logarithm s ar e natura l logarithms . Th e correlatio n coefficien t fo r thi s mode l i s 0.99 , implying 2 an R=0.98 , whic hindicate s an excellen t fit . A n alternativ e wayt o expres s the mode l i s

4 8P.5 2

P A= 10 0 • 0.026(COHb) 3, U" "

. l+0.026(COHb) 3 ' U (6-2 ) Th e relationshi p expresse d alternatel yb y(6-1 ) an

d (6-2 ) i s the media n dose-respons e curve . However , i t woul d als o b e usefu l t o mode l the uncer taintyconcerning the dose-respons e curve fo r additiona l angina attacks . On e advantag e o f using log-odd s fo r the dependen t variabl e i n (6-1 ) i s that , i n thi s case , a constan t standard deviatio n i s consisten t wit hthe availabl e information . Conditiona l o n an yCOH blevel , w e chos e t o us e a norma l probabilit ydistributio n t o represen t the uncertainty . Thus , p w e tak e the log-odds , ln , A> , t o be normall ydistribute d wit ha mea n o f 

## UOO-PJ ! (-3.65+3.1 1 ln(COHb) ) an d standard deviatio n 0.50 . Thi s standard devia

tion i s reasonabl yconsisten t wit hthe quantitativ e estimate s o f Arono wan d the qualitativ e expression s o f othe r professional s abou t the uncertaint yo f the angina dose-respons e relationship . Th e dose-respons e mode l fo r additiona l angin a attack s implie s tha t a t a COH bleve l o f 3. 5 percent , the log-odd s ter mi s normall ydistribute d wit h mea n 0.24 6 an

d standard deviatio n 0.50 . I n terms o f P , w e expec t 56. 1 percen t o f angin a patient s t o suffe r additiona l attacks , an d a 9 5 percen t credibl e interva l range s fro m32. 1 percen t t o 77. 7 percen t o f angina patients . Th e media n dose-respons e curve an d the curve s o f uppe r an d lowe r limit s fo r 9 5 percen t credibl e interval s ar e show n i n Figur e 6.1 . O f course , curve s coul d b e generate d fo r an yfractile s o f P. ; the thre e curve s i n Figur e 6. 1 ar e the 0.025 , 0.50 , an d 0.97 5 fractiles .

The secon

d majo r healt heffec t i s the incidenc e o f additiona l hear t attack s among thos e wit hhear t disease . A s before , the dos e i s the COH b

4 9P.5 3

leve l i n the blood , expresse d a s a percentage . Th e response , denote d b y P , i s the percentag e increas e i n tota l hear t attacks , fata l an d nonfatal . Dose-respons e point s obtaine d throughexper t assessment , ar e give n i n Tabl e 6. 2 an d Figur e 6.2 . Her e a linea r mode l provide s a perfec t fi t

excep t fo r the firs t point , an d w e wil l us e sucha mode l fo r the media n dose-respons e curve ,



### f - 5 + 5 « 

## I 0 , _, . , • .(COHb) , fo r COHb^l , H A 1 " fo r C0Hb<l , (6-3 ) whic hi s illustrate d i n Figur e 6.2 .

I t shoul d b e note d tha t onl yDr . Arono wexpresse d judgment s abou t the relationshi p betwee n additiona l hear t attack s an d COH bfo r severa l differ

en t levels . Hence , the curve i n Figur e 6. 2 i s base d upo n thi s judgment . However , a s indicate d i n Chapte r 5 , the othe r expert s expresse d judgment s abou t the percentag e increas e i n hear t attack s a t a 2 percen t leve l o f COHb . Dr . Kur t estimate d thi s increas e a t 2 0 percent , Dr . Mustaf a sug geste d 10-2 0 percent , an d Dr . Rokawthough t a 1- 2 percen t increas e migh t b e observed . Thes e judgment s ar e reasonabl yconsisten t wit hthe media n esti

mat e i n Figur e 6. 2 (i.e. , som e estimate s fal l bot habov e an d belo wthe median) . Furthermore , theyindicat e something abou t the degre e o f uncer taintyconcerning additiona l hear t attacks .

Th e informatio n availabl e fro mexpert s suggest s tha t the variabilit y o f the respons e increase s a s the dos e increases . Fo r example , the standard deviatio n o f the percentag e increas e i n hear t attack s i s greate r a t a COH b leve l o f 4 percen t than a t a COH bleve l o f 2 percent . To mode l thi s shif t

5 0P.5 4

in variability , w e represen t the 0.02 5 fractil e o f the dose-respons e relationshi p b

ythe line f -2. 5 + 2.5(COHb) , fo r C0Hb_>l , H A\ 0 , fo r C0Hb<l , (6-4 )

an d the 0.97 5 fractil e b ythe lin e p = f -1 0 + 10(COHb) , fo r COHb^.1 , " H A\ 0 , fo r COHb<l , (6-5 ) The media n dose-respons e curv e an d the curve s o f uppe r an d lowe r limit s fo r 9 5 percen t credibl e interval s ar e show n i n Figur e 6.2 .

Th e third majo r healt heffec t involve s death s associate d wit hhear t attacks . I f w e le t P denot e the probabilit yo f deat hfo r thos e wh o ar e having a hear t attack , the availabl e probabilisti c informatio n i n Chapte r 5 provide d b

yDr . Arono windicate s tha t the dose-respons e curve i s approximatel y pj?[l+0.05(C0Hb-l)] , fo r COH b_>1 , P D = { p £ fo r COH b<1 , (6 ' 6 ) wher e P i s the probabilit ytha t a hear t attac k i s fata l i n ai r wit h background level s o f CO (whichcorrespond s t o C0Hb<l) . I t i s wort h mentioning tha t the othe r experts ' judgments , no t use d i n constructing the dose-respons e curv e o f (6-6) , abou t the increasing rat e o f fatalitie s from hear t attack s wer e reasonabl yconsisten t wit hthe curve .

6. 2 Dose-Respons e Relationship s fo r Othe r Healt hEffect s

Thi s subsectio n develop s expecte d dose-respons e relationship s fo r the aggravatio n o f angina , COPD , an d PV D an d fo r vigilanc e effect s an d prema 5 1P.5 5

tur e births . Th e manne r i n whic hthi s i s don e i s simila r t o tha t fo r the majo r healt heffect s s o detail s ar e omitted . Also , becaus e thes e effect s ar e fel t t o b e les s importan t than the majo r effects , no model s o f the uncertaint yar e developed , althoughthe procedure s t o do thi s woul d corre spon d t o tha t fo r majo r effects .

Th e limite d experimenta l evidenc e concerning COH ban d angina involve s reductio n i n the time unti l the onse t o f an angin a attack . Thus , expert s seemt o fee l mor e comfortabl e wit hthi s concep t than wit hthe percentag e o f angina patient s suffering additiona l attacks . Some point s ar e presente d i n Tabl e 6. 3 an

d Figur e 6.3 , an

d the figur e als o include s the expecte d dose-respons e curv e tha t resulte d fromou r modeling :

100-P ^ 0.00019e ' ' A A ln ( •£•£- ) = -8.55 6 + 5.242(COHb) , (6-7 )

A A o r - 5.242(COHb ) P A A" 10 ° l+0.00019e 5

- 242(C0Hb ) (6-8 ) wher e the COH

bleve l i s indicate d i n percen t an d P represent s the per A A centag e o f angina patient s wit han aggravate d conditio n define d a s a t leas t a ten percen t reductio n i n tim e t o the onse t o f pain . From(6-7) , on e see s tha t the chose n mode l i s linea r whe n P. . i s transforme d t o log-odds . Anothe r healt heffec t involve s aggravatio n o f chroni c obstructiv e pulmonarydiseas e (COPD) . A s indicate d i n Chapte r 5 , w e defin e an aggravate d conditio n o f COP D a s a significan t reductio n (2 0 percen t o r more ) i n the time t o onse t o f marke d dyspne a during exercise . I f w e denot e the percentag e o f patient s wit haggravate d COP D a s P , the informatio n fro mthe expert s indicate s tha t the dose-respons e curve i s the same a s the

5 2P.5 6

dose-respons e curv e fo r reductio n i n time unti l the onse t o f an angin a attack . Thus ,

100-P , 0.00019e " ropn ln ( ^£i^ ) = _8.55 6 + 5.242(COHb) , (6-9 )

COP D ° r " 5.242(COHb ) P C0P D = 10 ° l+0.00019e 5 ' 242(COHb ) (6-10 )

Th e dose-respons e rat e fo r the percentag e (P pvn ) o f periphera l vascula r patient s wh o wil l hav e reduce d time t o the onse t o f a vascula r attac k i s als o identica l t o the dose-respons e curv e fo r reductio n i n tim e unti l the onse t o f an angina attack . Thi s seem s reasonable , sinc e the underlying mechanis mi s the same i n the two cases , wit hthe locatio n o f pai n differing . Thus ,

P PV D = 10 ° 0.00019e 5

- 242(COHb )

l+0.00019e 5

- 242(COHb ) (6-11 )

wher e the COH

bleve l i s i n percent .

Th e healt heffec t measur e relating t o vigilanc e i s define d a s the percentag e o f individual s wh o wil l experienc e some impairmen t i n vigilanc e (i.e. , inabilit yt o performan assigne d tas k suitably) . Denoting thi s measur e b

yP^ , w e estimate d the following dose-respons e relationshi p from the experts ' responses : 2. 5 (2 (COHb >- 2 ) fo r COH b>3 , P V 1 0 fo r COH b<3 . (6-12 ) Finally , w e conside r the increas e i n prematur e birth s relate d t o C O exposure . I f w e le t P p Rdenot e the increas e (in terms o f a percentag e o f al l babie s born ) i n prematur e birth s an d measur e the COH

bleve l i n percent , the expecte d dose-respons e curve i s

5 3P.5 7

ln(

- 

### P B 100- P - ) = -6.916 7 + 1.135(COHb) , or , equivalently , 

### PB

P P B = i0 ° 0.00019 e 1.135(COHb ) 1.135(COHb ) (6-13 ) l+0.00019 e A s i n the previou s case , the dependen t variabl e i s expresse d i n log-odd s form .



### 5 4P.5 8

Chapte r 7 . ESTIMATE S O F RIS K

Th e purpos e o f thi s chapte r i s t o provid e quantitativ e estimate s o f ris k t o huma n healt hi f differen t alternativ e standard s ar e adopte d (an d jus t met) . Fo r eac hstandard the exposur e dat a discusse d i n Chapte r 4 provide s an estimat e o f the numbe r o f peopl e expose d t o variou s level s o f COHb . Th e dose-respons e relationship s develope d i n Chapte r 6 indicat e the magnitude s o f differen t healt heffect s fo r eac hleve l o f COHb . Here , the exposur e dat a an

d dose-respons e relationship s ar e combine d t o estimat e the numbe r o f peopl e experiencing the healt heffect s o f interest , wit hprob

abilitie s a s wel l a s poin t estimate s fo r the majo r healt heffects . Result s ar e reporte d fo r eac ho f four citie s (Lo s Angeles , Philadelphia , St . Louis , an d Chicago) , the U.S . urba n population , an d group s particularl ysensitiv e t o CO .

7. 1 Combinatio n o f Exposur e Dat a an d Dose-Respons e Relationship s

Th e procedur e use d t o determin e ris k estimate s fo r the healt heffect s involve s the combinatio n o f exposur e dat a an d dose-respons e relationships . Fo r the majo r healt heffect s discusse d i n Sectio n 6. 1 an d the othe r healt h effect s discusse d i n Sectio n 6.2 , the procedur e can b e carrie d ou t i n five steps : Step 1 : Fo r eac hCOH blevel , determin e the numbe r o f peopl e expose d fromthe exposur e dat a o f Chapte r 4 , Step 2 : Fo r eac hCOH blevel , determin e the numbe r o f thes e individual s expose d wh o ar e i n a particularl ysensitiv e grou p (e.g. , angina patients) ,

5 5P.59 _

Ste p 3 : Fo r eac hCOH blevel , determin e the likelihoo d o f the particula r healt heffec t o f concern , Step 4 : Fo r eachCOH blevel , multipl ythe numbe r o f individual s i n the relevan t sensitiv e grou p (fro mStep 2 ) time s the like

lihoo d o f the particula r healt heffec t give n tha t COH bleve l (fro mSte p 3 ) t o determin e the numbe r o f case s o f the healt h effec t resulting fromthe give n COH blevel , Step 5 : Su

mu p the result s o f Step 4 ove r al l possibl e COH blevel s t o estimat e the tota l numbe r o f case s o f the healt heffec t induce d b

yCO .

I t i s importan t t o keep the following i n mind whe n interpreting the numbe r o f CO-induce d healt heffects . Thes e number s represen t an estimat e o f the additiona l case s o f the healt heffec t relativ e t o the numbe r o f case s expecte d wit hbackground C O level s (i.e. , pristin e ai r quality) . Thus , eve n a "strict " CO standard wil l resul t i n additiona l case s o f a healt heffect . However , thi s mayb e les s than the numbe r o f additiona l case s wit hthe statu s qu o circumstance s regarding CO ai r quality . Angin a Attack s

Th e numbe r o f CO-induce d angin a attack s i s compute d fo r bot h"people

days " an

d "people-hours " exposur e information . Th e underlying assumptio n i n using people-day s fo r exposur e i s tha t a perso n i s likel yt o hav e onl y one CO-induce d angina attac k pe r day , bu t the same perso n coul d hav e severa l ( a maximu

mo f 365 ) CO-induce d angin a attack s ove r the cours e o f a year . Th e us e o f people-hour s implie s tha t a perso n mayhav e attack s

5 6P.6 0

severa l time s i n a da yi f hi s o r he r COH bleve l reache s highenoughlevel s o n severa l occasion s during the same day .

I t i s reasonabl e t o expec t tha t ris k estimate s base d o n people-hour s provid e a n uppe r bound o n the numbe r o f CO-induce d angin a attack s pe r year . Th e reasoning i s a s follows . I f a perso n ha s had an attack , the COH bleve l i s likel yhighan

d h e o r she wil l likel yres t o r reduc e activity. ' Th e resulting COH

bleve l fo r thi s individua l wil l b e lowe r than wha t otherwis e woul d hav e bee n the case , whic htend s t o reduc e the chanc e o f additiona l attack s during the same day . The same argumen t migh t appl yt o people-day s dat a bu t wit hles s forc e a s highe r COH blevel s ma

yofte n no t occu r o n consecutiv e day s an d restricte d activit yan hou r afte r an angina attac k ma y b e mor e likel ythan a da yafterwards . W e di d no t us e people-year s fo r angina attack s sinc e clearl yi t provide s an unrealisticall ylowlowe r bound

- a perso n i s veryunlikel yt o hav e onl yon e angina attac k pe r year .

Fo r the initia l analysi s below , i t i s assume d tha t the distributio n o f angina patient s a t differen t level s o f COH bi s the same a s the distributio n o f exposur e fo r the overal l population . I n Sectio n 7.3 , w e provid e ris k estimate s unde r the assumptio n tha t the exposur e o f angina patient s follow s the exposur e patter n o f a specia l group . To obtai n CO induce d angina attack s the step s outline d abov e ar e conducte d a s follows :

Ste p 1 : Fo r eac hleve l o f COHb , the exposur e dat a provide s the numbe r N . o f people-day s (or people-hours ) expose d t o thi s COH bleve l i during a year .

5 7P.6 1

Step 2 : Base d o n availabl e data , w e estimat e tha. t 4 percen t (U.S .

Environmenta l Protectio n Agency[1981] ) o f the adul t populatio n ha s angin a an d tha t adult s compris e 68. 9 percen t o f the population . Thus , the numbe r A . o f angin a patient-day s (or patient-hours ) i n a yea r a t COH bleve l i i s give n b y A= (0.04)(0.689) N. (7-1 ) Step 3 : Fo r a give n COH blevel , the media n dose-respons e curv e give n i n (6-2 ) i s use d t o deriv e P (i) , percentag e o f angina A patient s suffering additiona l attack s du e t o the COH bleve l i . Th e likelihoo d tha t a patien t woul d suffe r tha t effec t i s the n P (i)/100 .

A Ste p 4 : No wthe numbe r o f CO induce d angina attack s fo r a give n COH b leve l i s give n b

ythe produc t o f A . an d P (i)/100 . 1 A Ste p 5 : Th e result s i n Sep t 4 ar e aggregate d ove r the possibl e COH b level s t o provid e the estimate d tota l numbe r No f angin a A attack s pe r yea r base d bot ho n people-day s an d people-hour s exposur e information . Thus , N

## A = Z

## V P 

## A (i)/100) 

## - (7 

## " 2 ) i Th e result s can als o b e represente d a s a percentag e o f tota l angina person-day s o r tota l angina person-hour s b ydividing b yEA . whic hyield s i N . EA( P (i)/100 )

_= i XA
. (7-3 ) EA . EA .

. 1 . 1 l l

5 8P.6 2

Th e compute d figure s indicat e the media n numbe r o f CO-induce d angin a attack s pe r yea r base d o n people-day s an d people-hour s o f exposure . Becaus e o f uncertaint yabou t the does-respons e relationship , the analysi s i s als o conducte d fo r the lowe r an d uppe r dose-respons e curve s (represent

in g the 0.02 5 an

d 0.97 5 fractile s o f P ) discusse d i n Sectio n 6.1 . A
Hear t Attack s

Th e computatio n o f the numbe r No f CO-induce d hear t attack s i s base d o n the people-yea r exposur e information . Thus , w e ar e assuming tha t a perso n wil l hav e a t mos t on e CO-induce d hear t attac k pe r year . Th e percentag e increas e i n hear t attack s i s als o reported . Th e step s o f the computatio n ar e simila r t o thes e describe d fo r angin a attacks : Step 1 : Us e people-yea r exposur e informatio n t o obtai n N. . Ste p 2 : Five percen t o f adult s hav e coronar yhear t diseas e (U.S . Environmenta l Protectio n Agency[1981]) . Sinc e 68. 9 percen t o f the populatio n ar e adults , the numbe r (HA) , o f coronary patient s expose d t o COH bleve l i i s (HA) . = (0.05)(0.689)N. . (7-4 ) Step 3 : Th e dose-respons e curv e (6-3 ) provide s the percentag e P (i ) H A increas e o f hear t patient s fo r COH bleve l i . Step 4 : Th e numbe r o f CO-induce d hear t attack s a s sociate d wit hCOH b leve l i i s the produc t o f (HA) , an d P (i)/100 . Ste p 5 : Th e result s i n Ste p 4 ar e aggregate d ove r the variou s COH b level s t o provid e the estimate d numbe r No f CO-induce d hear t attack s pe r yea r fo r eac hstandard : N ^ = E(HA) i (P RA (i)/100) . (7-5 ) i 5 9P.6 3

Th e procedur e i s repeate d fo r the lowe r an d uppe r dose

respons e curve s give n b y(6-4 ) an

d (6-5) , respectively .

Ther e wer e 1.2 5 millio n hear t attack s (se e Duva l [1972] ) i n 1972 , whe n the tota l populatio n o f the U.S . wa s estimate d b ythe U.S . Burea u o f th e Censu s t o b e 203.30 2 million . Thus* , w e assume the numbe r o f hear t attack s pe r yea r represent s 0.6 1 percen t o f th e population , a bas e fromwhic h percentag e increase s i n hear t attack s du e t o CO exposur e can b e calculated .

Death s among cardiovascula r patient s HighCOH

blevel s resul t i n a highe r incidenc e o f hear t attacks . Furthermore , thos e patient s wh o ar e having a hear t attac k (whethe r CO-induce d o r not ) hav e a highe r probabilit yo f deat hi f expose d t o a high COH bleve l a t the time o f the attack . Thes e two effect s ar e combine d t o deriv e additiona l death s du e t o C O exposur e a s follows : Step 1 : Us e people-year s exposur e informatio n t o obtai n N. . Ste p 2 : Th e sensitiv e individual s expose d t o hear t attack s a t COH b leve l i ar e the numbe r o f coronaryhear t diseas e patient s (HA) . give n b

y(7-4 ) an

d thos e wh o wil l hav e hear t attack s no t induce d b

yCO whic hnumbe r (0.61/100)Ni . Ste p 3 : Th e probabilit yP n (i ) o f a hear t attac k being fata l withi n a yea r a t COH

bleve l i i s give n b y(6-6) . I t i s furthermor e estimate d tha t 6 0 percen t o f hear t attac k victim s di e immediatel yo r withi n a year . Thi s estimate , provide d b y Dr . Aronow , i s highe r than publishe d estimate s whic hrang e fro m2 7 percen t fo r acut e myocardia l infarctio n t o 5 5

6 0P.6 4

percen t fo r coronar yhear t diseas e (U.S . Departmen t o f Healt han

d Huma n Service s [1977]) . Thus , a s a conservativ e estimate , the probabilit yP tha t a hear t attac k i s fata l a t background C O level s i s take n a s 0.6 . Ste p 4 : Additiona l death s associate d wit hCOH bleve l i fo r hear t attack s tha t woul d hav e occurre d anywa yar e give n b

y D. . = (0.61/100)N.P_(i) . (7-7 ) i l l D Also , highCOH

blevel s lead t o additiona l hear t attack s fo r individual s wit hCOH bleve l i . A s indicate d i n the previou s Step 4 fo r hear t attacks , the numbe r o f thes e case s i s (HA) . (P u .(i)/100) . The additiona l death s fo r thes e extr a hear t H A attack s i s give n b

y D 

### i 2 = 

### ( HA 

### ) i 

### ( p HA 

### ( i 

### )/ 1 

### 00 ) V-i)

- (7 

### " 8 ) Th e estimate d tota l numbe r o f CO-induce d death s D . fo r a l give n COH

bleve l i i s obtaine d fro m D . - D ± 1 + D. 2 . (7-9 ) Step 5 : Th e result s i n Step 4 ar e aggregate d ove r the differen t COH b level s t o provid e the estimate d numbe r o f CO-induce d hear t attac k death s pe r year . Thi s i s als o expresse d a s a percentag e increas e i n deaths , an d the analysi s i s repeate d fo r the lowe r an

d uppe r dose-respons e curves .

Aggravatio n o f Angin a

CO exposure s result s i n a reduce d time t o onse t o f pai n among exercising angina patients . W e sa ytha t an angina patien t i s aggravate d i f

6 1P.6 5

activit yi s limite d du e t o earlie r onse t o f an angina attack . Th e calculation s fo r the estimate d numbe r o f aggravate d case s o f angin a pe r yea r ar e simila r t o tha t fo r additiona l angina attack s wit hthe following modifications :

Ste p 1 : Us e people-day s fo r exposur e dat a N. . Ste p 2 : Th e numbe r o f angin a patient-day s expose d a t COH bleve l i i s give n b y(7-1) . Ste p 3 : The percentag e P (i ) o f angina patient s wit han aggravate d A A conditio n a t COH

bleve l i i s give n b y(6-8) . Step 4 : Th e numbe r o f aggravate d case s o f angina a t COH bleve l i i s A i (P M (i)/100) . Step 5 : Th e result s i n Step 4 ar e aggregate d t o provid e the esti

mate d tota l numbe r o f aggravate d case s o f angina pe r year . Aggravatio n o f COP D

Patient s wit hchroni c obstructiv e pulmonarydiseas e wil l experienc e reduce d time t o hypoxi a a t highe r level s o f C O exposure . Th e step s fo r the calculatio n o f th e estimate d tota l numbe r o f aggravate d COP D patient s du e t o CO exposur e ar e simila r t o tha t fo r aggravatio n o f angina : Step 1 : Us e people-day s fo r exposur e dat a N. . Step 2 : Th e populatio n o f patient s wit hCOP D i s estimate d t o b e

6. 9 percen t o f th e tota l populatio n (U.S . Environmenta l Protectio n Agency[1981]) . Thus , the numbe r o f COP D patient-day s expose d i s (COPD) . = 0.069N. . (7-10 )

6 2P.6 6

Step 3 : Th e percentag e P (i ) o f COP D patient s wit han aggravate d

conditio n a t COH

bleve l i i s give n b y(6-10) . Ste p 4 : Th e estimate d numbe r o f aggravate d case s o f COP D patient s a t

COH bleve l i i s (COPD ) (P(i)/100) . Ste p 5 : Th e result s i n Ste p 4 ar e aggregate d ove r COH blevel s t o provid e the estimate d tota l numbe r o f aggravate d case s o f COP D pe r year . Aggravatio n o f Periphera l Vascula r Diseas e

Exposur e t o CO cause s a reduce d tim e to onse t o f vascula r pai n i n muc h the same waya s i t reduce s the tim e t o onse t o f pai n fo r angina patients . The calculation s fo r the tota l numbe r o f aggravate d case s o f periphera l vascula r patient s ar e simila r t o thos e fo r aggravatio n o f angina . I n thi s case , however , i n Step 2 the numbe r o f patien t day s expose d i s calculate d b ymultiplying N . b y0.3/10 0 sinc e the percentag e o f periphera l vascula r patient s i n the populatio n i s 0. 3 percen t (U.S . Environmenta l Protectio n Agency[1981]) . Vigilanc e Effect s

A n exposur e t o CO reduce s the vigilanc e o f eve n the health ymember s o f society . Thus , thi s effec t relate s t o the tota l populatio n rathe r than t o a particula r segmen t sucha s cardiovascula r patients :

Step 1 : Us e people-day s fo r exposur e dat a N. . Ste p 2 : Th e numbe r o f peopl e expose d i s simpl yN. .
6 3P.6 7

Step 3 : Th e percentag e P v (i ) o f individual s experiencing impairmen t

o f vigilanc e a t COH bleve l i i s give n b y(6-12) . Ste p 4 : Th e numbe r o f peopl e wit hvigilanc e effect s a t COH bleve l i i s give n b

yN.( P (i)/IOO) . Ste p 5 : Th e result s i n Step 4 ar e aggregate d t o deriv e the estimate d numbe r o f peopl e wit hvigilanc e effect s pe r year .
Incidence s o f Prematurit y

I t i s believe d tha t a sustaine d CO exposur e during pregnanc ycause s an increas e i n the rat e o f prematur e babies . Th e exposur e dat a provid e an estimat e o f maximu

mdail yo r maximu

myearl yCOH

blevel s experience d b ya person . I t i s no t clea r whethe r a perso n i s expose d t o thes e highe r COH b level s o n a sustaine d basi s (e.g. , ove r the entir e day) . Ou r calculation s therefor e provid e an uppe r bound o n the numbe r o f prematur e babie s fo r eac h standard :

Step 1 : Us e people-year s fo r exposur e data . Ste p 2 : Th e numbe r o f babie s bor n pe r yea r i s approximatel y1. 5 percen t o f the tota l population . Thu s the tota l numbe r o f exposure s a t COH

bleve l i i s (PB) . = 0.015N. . Step 3 : From(6-13) , w e obtai n the percentag e increas e P (i ) i n P u prematur e birth s a s a functio n o f COH bleve l i . Step 4 : Th e additiona l numbe r o f prematur e babie s associate d wit h

COH bleve l i i s give n b y(PB ) . (P_ o (i)/100) . l P B Ste p 5 : Th e result s i n Ste p 4 ar e aggregate d t o provid e the estimate d uppe r bound fo r the numbe r o f CO-induce d prematur e

6 4P.6 8

babie s pe r yea r fo r eac hstandard . Th e percentage s reflec t the numbe r o f additiona l prematurit ycase s a s a percentag e o f the tota l numbe r o f births .

7. 2 Ris k Estimate s fo r Four Citie s

Th e procedur e describe d i n Sectio n 7. 1 wa s applie d fo r the eigh t C O standard s listed i n Tabl e 1.1 . Th e analysi s wa s conducte d fo r eac ho f four citie s - Lo s Angeles , Chicago , Philadelphia , an d St . Louis . Th e ris k estimate s fo r thes e four citie s ar e presente d i n Table s 7. 1 - 7.4 .

I n the ris k estimat e tables , the column s "ANALY1 " through"ANALY8 " represen t the eigh t standard s i n the same orde r a s the yar e presente d i n Tabl e 1.1 . Th e row s refe r t o differen t healt heffects , wit hresult s give n i n term s o f bot htota l numbe r o f CO-induce d case s relativ e t o the numbe r o f case s expecte d a t background CO level s an d a percentag e figur e describe d belo wfo r the separat e healt heffects . Angina Day s

Thi s healt heffec t estimate s the tota l numbe r o f additiona l CO-induce d angina attack s pe r yea r assuming tha t a t mos t on e attac k wil l occu r o n an y give n day . Th e LO , ME , an d H I estimate s correspon d t o the lower , median , an d uppe r dose-respons e curve s (i.e. , the 0.025 , 0.50 , an d 0.97 5 fractiles) . Fo r example , i f standard 2 , corresponding t o ANAL Y2 i n Tabl e 7.1 , i s adopte d an

d i s jus t met , the n w e estimat e tha t the n ther e i s a 0.02 5 chanc e tha t the numbe r o f CO-induce d angina attack s i n a yea r i n Lo s Angele s i s les s than 1.1 6 million , a 0.5 0 chanc e tha t the numbe r o f suc h

6 5P.6 9

attack s i s les s than 2.9 2 million , an d a 0.97 5 chanc e tha t the numbe r i s les s than 6.8 5 million . Thes e figure s (1.1 6 million , 2.9 2 million , an d 6.8 5 million ) represent , respectively , 1.4 9 percent , 3.7 6 percent , an d 8.8 2 percen t o f availabl e person-day s fo r angina patient s i n a one-yea r perio d i n Lo s Angeles . Angin a Hour s

Using angin a hours , the possibilit ytha t a perso n coul d hav e mor e than on e CO-induce d angina attac k i n a da yi s allowed . Onc e again , the LO , ME , an d H I figure s correspond t o the .025 , .50 , an d .97 5 fractile s o f the distribution . The percentage s ar e percentage s o f the availabl e person-hour s fo r angina patient s i n eac hcity .

Hear t Attack s

Th e numbe r o f additiona l hear t attack s pe r yea r i s represente d b ythi s estimate . Fo r example , wit hstandard 2 indicate d b yAnalysi s 2 , the media n numbe r o f additiona l hear t attack s i n Lo s Angele s i s 2100 , the 0.02 5 fractil e i s 105 0 hear t attacks , an d the 0.97 5 fractil e i s 420 0 hear t attacks . Th e percentage s ar e percentag e increase s i n hear t attacks ; e.g. , the media n estimat e o f 210 0 correspond s t o a 4.4 6 percen t increas e i n hear t attack s i n Lo s Angeles .

6 6P.7 0

Hear t Fatalitie s

I n estimating the tota l numbe r o f additiona l CO-induce d death s associate d wit hhear t attacks , bot hadditiona l death s fo r hear t attack s tha t ar e no t considere d a s CO-induce d an d death s fo r the additiona l CO-induce d attack s ar e included . Wit hAnalysi s 4 i n Lo s Angeles , fo r example , the media n estimat e i s 92 7 deaths , whic hrepresent s a 3.2 8 percen t increas e i n deaths . The lowe r an d uppe r estimate s ar e 42 6 an d 187 0 deaths . Angina Aggravatio n

Thi s estimat e involve s the estimate d numbe r o f additiona l incidence s o f aggravatio n among angina patient s pe r year , i n term s o f person-days . Tha t is , a patien t i s assume d t o hav e a t mos t on e incidenc e o f aggravatio n pe r day . Wit hAnalysi s 6 i n Lo s Angeles , w e expec t 6.2 2 millio n incidences , an

d thi s amount s t o 8.0 1 percen t o f the availabl e person-day s fo r angin a patients .

COP D Aggravatio n

Thi s estimat e i s identica l i n natur e t o the estimat e o f angin a aggravation , bu t i t pertain s t o COP D patient s instead o f angina patients .

PV D Aggravatio n Thi s estimat e i s als o identica l i n natur e t o the estimat e o f angin a aggravation , bu t i t pertain s t o periphera l vascula r diseas e patient s instead o f angin a patients .

6 7P.7 1

Vigilanc e Aggravatio n

Thi s ris k estimat e describe s the estimate d numbe r o f incidence s o f vigilanc e impairmen t pe r year . I t i s calculate d b yassuming tha t a n individua l canno t hav e mor e than on e suc hincidenc e pe r day .

Prematur e Birt hIncidenc e

Thi s estimat e indicate s the expecte d numbe r o f additiona l prematur e babie s bor n pe r year . Fo r example , wit hAnalysi s 8 , an uppe r bound fo r the expecte d numbe r o f additiona l prematur e babie s i n a yea r i n Lo s Angele s i s 2170 .

7. 3 Analysi s fo r Sensitiv e Group s

Fo r eac hstandard an d eac hmajo r healt heffect , w e hav e give n low , median , an

d highestimate s o f the additiona l numbe r (i n absolut e terms an d i n percentag e terms ) expecte d t o experienc e the healt heffect . Thes e thre e estimate s ar e the 0.025 , 0.50 , an d 0.97 5 fractile s o f the distributio n o f the numbe r expecte d t o experienc e the healt heffect . Th e population s i n questio n ar e i n fac t the sensitiv e group s - angina patient s fo r angina an d coronaryhear t diseas e patient s fo r hear t attacks .

T o provid e mor e informatio n abou t the percentag e o f a sensitiv e grou p tha t migh t suffe r CO-induce d advers e healt heffect s i n a year , w e fi t prob

abilit ydistribution s t o the numbe r o f suc hhealt heffects . Using the 0.025 , 0.5 , an

d 0.97 5 fractil e estimates , w e foun d tha t lognorma l distri

6 8P.7 2

bution s provide d veryclos e approximation s t o the data . Thi s i s partiall y du e t o the fac t tha t w e expec t the distribution s t o b e unimoda l an d skewe d t o the right . Th e resulting probabilit ydistributio n i s illustrate d i n Figur e 7. 1 fo r additiona l hear t attack s i n Lo s Angele s give n standard 8 . To fi t thi s curve , w e use d the informatio n i n Tabl e 7. 1 indicating tha t 0.02 5 fractil e fo r additiona l hear t attack s i n Lo s Angele s i n 1650 , the 0. 5 fractil e i n 3290 , an d the 0.97 5 fractil e i s 6590 .

Fromsuchdistributions , w e can fin d the probabilit ytha t a t leas t x percen t (fo r an

yx ) o f the sensitiv e grou p wil l suffe r a CO-induce d healt h effec t i n a give n year . I n orde r t o fin d thes e probabilities , w e firs t determin e howman

ypeopl e constitut e xpercen t o f the sensitiv e group . Th e right-hand cumulativ e probabilitie s fo r thes e value s ar e the desire d prob

abilities . Alternatively , w e can wor k directl ywit hpercentage s b yfitting lognorma l distribution s fo r percentages .

W e tabulate d the probabilitie s tha t a t leas t 1 , 5 , an d 1 0 percen t o f the sensitiv e grou

p wil l experienc e CO-induce d healt heffect s fo r angina attacks , hear t attacks , an d fatalitie s associate d fo r hear t attacks . Th e result s fo r Lo s Angeles , Chicago , Philadelphia , an d St . Loui s ar e give n i n Table s 7. 5 - 7.8 . Fo r example , i n Lo s Angele s wit hAnalysi s 8 , among coronarypatients ,
P(At leas t 1 percen t suffe r CO-relate d hear t attack s during a year ) = 0.731 , P(At leas t 5 percen t suffe r CO-relate d hear t attack s during a year ) = 0.00 ,
6 9P.7 3

an d P(At leas t 1 0 percen t suffe r CO-relate d hear t attack s during a year ) =

0.00 . Th e probabilit ytha t a t leas t 1 percen t suffe r hear t attack s i s illustrate d i n Figur e 7.1 . Th e EPAexposur e analysi s take s the populatio n o f Lo s Angele s a s 7.7 2 million . Fiv e percen t o f the adults , whic har e 68. 9 percen t o f the population , ar e coronarypatients . Thu s ther e ar e 0.22 6 millio n coronarypatient s i n Lo s Angeles , s o on e percen t represent s 2660 . On Figur e 7.1 , the probabilit yo f 266 0 o r mor e additiona l hear t attack s i s 0.731 . A s indicated , ther e i s essentiall yno chanc e tha t a s man ya s 5 percen t wil l b e affected .

7. 4 Analysi s fo r Specia l Exposur e Grou p

I n the analyse s presente d i n Section s 7. 2 an d 7.3 , i t i s assume d becaus e o f the exposur e dat a use d tha t individual s i n the sensitiv e group s had distribution s o f exposur e simila r t o the res t o f the population . However , the distribution s maydiffe r sinc e sensitiv e individual s ar e thos e suffering fro

msom e healt hproblem s suc ha s angina , cardiovascula r disease , o r chroni c obstructiv e pulmonarydisease . Peopl e wit hthes e healt h problem s migh t ten

d t o hav e differen t activit ypattern s an d henc e differen t distribution s o f exposure .
Give n the informatio n availabl e abou t the cohor t group s use d i n the EPAexposur e analysis , i t i s possibl e t o selec t a fewcohor t group s wit h physiologica l parameter s (e.g. , ventilatio n rate ) tha t seemroughl y characteristi c o f the sensitiv e groups . Thes e cohort s wer e chose n t o constitut e a specia l exposur e group . Analyse s corresponding t o thos e i n

7 0P.7 4

Section s 7. 2 an

d 7. 3 wer e ru

n using exposur e dat a fo r the specia l exposur e grou p instead o f fo r the entir e population . Risk s estimate s fo r thi s alternativ e analysi s ar e give n i n Table s 7. 9 - 7.12 , an d probabilitie s fo r 1 percent , 5 percent , an d 1 0 percen t o f the sensitiv e group s ar e presente d i n Table s 7.1 3 - 7.16 . A s expected , a compariso n o f Table s 7. 9 - 7.1 6 wit h Table s 7. 1 - 7. 8 indicate s tha t an individua l wit hthe exposur e patter n o f the specia l exposur e grou p woul d b e les s likel yt o suffe r advers e healt h effect s an

d woul d b e expecte d t o suffe r fewe r sucheffect s than an individua l wit hthe exposur e patter n o f the genera l population .

7. 5 Ris k Estimate s fo r the U.S . Urba n Populatio n

We hav e presente d result s fo r four citie s (Lo s Angeles , Chicago , Philadelphia , an

d St . Louis) , sinc e outpu t fromthe exposur e mode l wa s availabl e onl yfo r thos e cities . Withou t exposur e dat a fromothe r cities , i t i s difficul t t o provid e reasonabl e ris k estimate s fo r the entir e U.S . urba n population . T o provid e a veryroug hestimat e o f risk s fo r the U.S . urban population , w e hav e take n a weighte d averag e o f the result s fo r the four cities , wit hthe weight s reflecting populatio n size . Th e EPAexposur e analysi s too k the population s (i n millions ) o f thes e citie s t o b e 7.7 2 fo r Lo s Angeles , 2.3 6 fo r Chicago , 2.9 4 fo r Philadelphia , an d 1.2 1 fo r St . Louis . Muc ho f the urba n populatio n live s i n area s les s densel ypopulate d than the four citie s analyzed . T o the exten t tha t C O pollutio n level s ar e expecte d t o correlat e positivel ywit hpopulatio n densities , the estimate s fo r the urba n populatio n migh t b e considere d a s an uppe r bound .

7 1P.7 5

Th e estimate s o f the numbe r o f peopl e suffering eac hhealt heffec t o f interes t ar e give n i n Tabl e 7.1 7 fo r the entir e urba n populatio n using genera l exposur e data . Th e probabilitie s tha t 1 , 5 , an d 1 0 percen t o f the sensitiv e group s suffe r the healt heffect s ar e provide d i n Tabl e 7.18 . A simila r analysi s using exposur e dat a fo r the specia l exposur e grou p describe d i n Sectio n 7. 4 i s presente d i n Table s 7.1 9 an d 7.20 .

7. 6 Sensitivit yAnalysi s

Th e analyse s reporte d i n thi s chapte r provid e a goo d indicatio n o f the sensitivit yo f our result s t o change s i n the inputs . First , the analyse s fo r uppe r an

d lowe r dose-respons e curve s indicat e the sensitivit yo f the result s t o change s i n thes e functions . Th e numbe r o f peopl e expecte d t o b e affecte d b

yCO increase s a s w e mov e fromthe lowe r dose-respons e curv e t o the media n curv e an d finall yt o the uppe r curv e fo r a give n standar d an d .city . However , i n term s o f comparison s o f standards , the result s ar e simila r fo r the thre e dose-respons e curves . Fo r example , the standard associate d wit hAnalysi s 4 tend s t o provid e lowris k estimate s relativ e t o othe r standard s fo r al l situations , an d the standard s associate d wit h Analysi s 3 an

d Analysi s 8 ten

d t o provid e highris k estimate s relativ e t o othe r standards . I n thi s sense , the result s o f the ris k assessmen t appea r t o b e quit e robust .

Second , the consideratio n o f the specia l exposur e grou p provide s informatio n abou t the sensitivit yo f the result s t o variation s i n exposur e patterns . Onc e again , the result s chang e i n absolut e terms , wit hthe dat a fro mthe specia l exposur e grou p yielding lowe r ris k estimate s than the

7 2P.7 6

exposur e dat a fromthe genera l population . However , the relativ e compariso n o f standard s doe s no t chang e much , i f a t all . I n relativ e terms , the result s ar e onc e agai n quit e robust . Finally , the effec t o f varying some mode l parameter s can b e quit e straightforward . Fo r example , i t ha s bee n estimate d tha t 6 0 percen t o f al l hear t attac k victim s di e withi n a year , an d thi s figur e wa s use d i n the calculatio n o f ris k estimate s concerning death s associate d wit hhear t attacks . I f the 6 0 percen t figur e i s to o highan d shoul d b e reduce d b y some factor , thi s simpl yreduce s the ris k estimate s fo r heart-attac k death s b ythe same factor . Thus , the effec t o f varying thi s figur e can b e determine d i n a straightforwar d manner . Specifi c comment s o n desire d sensitivit yanalyse s ar e discusse d i n Section s 8. 2 an d 8.3 .

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Chapte r 8 . SUMMAR YAN D DISCUSSION

A s state d i n Chapte r 1 , the purpos e o f thi s repor t i s t o demonstrat e the developmen t an

d presentatio n o f an analysi s o f possibl e ambien t ai r qualit ystandard s fo r on e majo r pollutant , carbo n monoxide . Th e primary objectiv e o f the analysi s i s t o relate , vi a a ris k assessmen t model , advers e healt heffect s t o alternativ e carbo n monoxid e standards . I n thi s chapte r w e briefl ysummariz e the analysis , an d discus s way s i n whic hthe analysi s coul d b e furthe r refined .

8. 1 Summar

yo f the Analysi s

Give n the objectiv e o f relating advers e healt heffect s t o C O stand

ards , a keyissu e i s the developmen t o f an overal l structur e fo r the ris k assessmen t model . Tw o othe r majo r issue s involve the choic e o f healt h effect s an

d the modeling o f dose-respons e relationships . Finally , exposur e dat a an d dose-respons e model s mus t b e combine d t o arriv e a t the fina l quan titative ris k estimates . Th e manne r i n whic hthe analysi s addresse s thes e concern s i s summarize d below .

Structur e o f the Model . A n importan t aspec t o f the modeling proces s i s the decompositio n o f the problemint o manageabl e components . Thes e component s can the n b e separatel yanalyze d an d logicall yintegrate d t o provid e result s concerning the primaryobjectiv e o f the ris k assessmen t (i.e. , ris k esti

mate s fo r CO-induce d healt heffect s associate d wit hdifferen t CO stand

ards ) . Th e decompositio n o f the problem , o f course , i s dictate d t o a larg e exten t b

ythe type s o f informatio n tha t ar e bot husefu l an d obtainable .

7 4P.7 8

The componen t model s o f our decompositio n ar e 1 . the relationshi p betwee n a C O standard an d the actua l ambien t ai r qualit yi n term s o f ambien t C O levels , 2 . the relationshi p betwee n ambien t CO level s an d the degre e o f exposur e o f peopl e t o differen t CO levels , 3 . the physiologica l response s o f peopl e t o thei r exposur e t o CO , 4 . the advers e healt heffect s relate d t o physiologica l responses , an d 5 . the relationshi p betwee n individua l advers e healt heffect s an d specifi c ris k outpu t estimates . Th e structur e o f the ris k assessmen t show n i n Figur e 3.2 , involving thes e componen t models , wa s judge d t o b e the mos t appropriat e structur e give n th e informatio n availabl e an d give n the constraint s o n cos t an d time associate d wit hthi s study .
Exposur e t o Carbo n Monoxide . Th e Nationa l Ambien t Ai r Qualit yStandard Exposur e Mode l (NEM ) wa s use d t o generat e exposur e estimate s associate d wit hthe variou s CO standard s unde r consideration . Thi s mode l adjust s actua l dat a regarding measurement s o f CO level s a t a numbe r o f site s t o estimat e the ai r qualit ytha t woul d b e expecte d unde r alternativ e standard s (assumin

g eac hstandard i s jus t met) . Th e nex t step translate s ai r qualit y dat a int o exposur e data , using extensiv e empirica l result s regarding activit ypattern s o f the member s o f the populatio n i n the four citie s fo r whic hris k estimate s ar e generated . Sinc e CO-induce d healt heffect s occu r becaus e exposur e t o C O lead s t o increase d COH blevel s i n the blood , the las t step o f the exposur e analysi s involve s the conversio n o f dat a regard

in g CO exposur e t o informatio n concerning COH blevels . Thi s i s accomp 7 5P.7 9

lishe d vi a the Cobur n model . Th e outpu t o f the exposur e analysi s i s a se t o f distribution s o f COH bexposur e i n term s o f person-hours , person-day s (i.e. , the maximu

mCOH bexposur e during a day) , an d person-year s (i.e. , the maximu mCOH bexposur e during a year) .

Healt hEffects . Previou s empirica l an d epidemiologica l finding s indicat e severa l advers e healt heffect s relate d t o C O exposure . Th e group s tha t appea r t o b e quit e sensitive t o the increase d COH blevel s tha t resul t fro m CO exposur e includ e coronaryhear t diseas e patients , chroni c obstructiv e pulmonarydiseas e patients , an d pregnan t wome n wit hthei r fetuses . Unfor

tunately , i t ha s no t bee n judge d feasibl e t o gathe r dat a concerning the healt heffect s o f CO exposur e i n the rea l worl d (a s oppose d t o the labora

tory ) . Laboratorystudie s provid e usefu l informatio n bu t do no t addres s directl ythe question s o f primaryinteres t i n our ris k assessment . However , the professiona l judgment s o f medica l expert s abou t CO-induce d healt heffect s constitut e valuabl e information . Thus , w e interviewe d severa l healt hexpert s t o asses s thei r estimate s (in quantitativ e term s a s wel l a s i n qualitativ e terms ) o f healt hrisk s fromlow-leve l CO exposure . Afte r evaluating the previou s empirica l an d epidemiologica l finding s an d the informatio n fromexperts , w e decide d t o concentrat e on thre e majo r CO-induce d healt heffects : additiona l angina attacks , additiona l hear t attacks , an

d additiona l death s fro mhear t attacks . I n additio n t o thes e majo r healt heffects , w e als o analyz e five othe r effects : aggravatio n o f angina , aggravatio n o f chroni c obstructiv e pulmonarydisease , aggravatio n o f periphera l vascula r disease , impairmen t o f vigilance , an d incidenc e o f prematurity .

7 6P.8 0

Dose-Respons e Relationships . T o analyz e quantitativel yCO-induce d healt h effects , i t i s necessaryt o relat e COH blevel s t o thes e healt heffects . Informatio n use d t o selec t the healt heffect s include d i n the analysi s wa s als o use d t o estimat e dose-respons e relationships , wit hthe COH bleve l representing the dos e an d the percentage s o f additiona l CO-induce d case s o f the healt heffect s (additiona l a s compare d wit hwha t woul d b e expecte d give n COH

blevel s associate d wit hbackground-leve l CO occurring naturally ) representing the responses . Th e developmen t o f dose-respons e relationship s involve d some mode l building i n the sens e o f curve fitting , an d thi s wa s don e fo r al l o f the healt heffect s bein g considered . Fo r the thre e majo r healt heffects , uncertaint yconcerning the dose-respons e curve wa s modele d probabilistically , wit hdistribution s o f the fina l ris k outpu t estimate s conditiona l upo n COH blevels . Fo r the othe r healt heffects , onl yexpecte d dose-respons e relationship s wer e estimated .

Ris k Estimates . Th e fina l step i n the ris k assessmen t i s the combinatio n o f exposur e dat a an d dose-respons e model s t o arriv e a t the quantitativ e ris k estimate s presente d i n Chapte r 7 . Thi s wa s don e fo r the eigh t standard s liste d i n Tabl e 1. 1 fo r eac ho f four citie s - Lo s Angeles , Chicago , Philadelphia , an d St . Louis . Th e following estimate s wer e generate d fo r the majo r healt heffects : 1 . distribution s o f the fina l ris k outpu t estimate s (e.g. , the numbe r o f additiona l hear t attacks) , summarize d b ymedians , 0.02 5 fractiles , an

d 0.97 5 fractiles , 2 . probabilitie s tha t a t leas t 1 , 5 , o r 1 0 percen t o f the sensitiv e group s wil l suffe r advers e healt heffects .

7 7P.8 1

Fo r the othe r healt heffects , onl ypoin t estimate s o f the fina l ris k outpu t estimate s (e.g. , the annua l expecte d numbe r o f case s o f aggravatio n o f chroni c obstructiv e pulmonarydisease ) wer e found .

I n the mai n analysis , w e assume d tha t individual s i n the sensitiv e group s (e.g. , angina patients ) hav e distribution s o f exposur e similar * t o the res t o f the population . Becaus e o f thei r healt hproblems , thes e individual s mayten d t o hav e differen t activit ypattern s an d henc e differen t distribution s o f exposure . Asupplementaryanalysi s wa s conducte d wit ha specia l exposur e grou p consisting o f individual s wit h physiologica l parameter s mor e characteristi c o f the sensitiv e groups .

Th e mai n result s pertai n t o the four citie s fo r whic hexposur e informatio n wa s available . To provid e a roug hestimate s o f risk s fo r the entir e U.S . urba n population , w e foun d a weighte d averag e o f the result s fo r the four cities , wit hthe weight s reflecting populatio n size .

8. 2 Discussio n o f the Result s

Th e result s o f the analysi s ar e presente d i n twentytable s i n Chapte r 7 , an d i t i s difficul t t o provid e a brie f summar yo f al l o f thes e figures . Th e result s presen t an overal l pictur e o f the healt hrisk s associate d wit h eac hstandard tha t wa s analyzed . Perhap s the mos t striking poin t i s the insensitivit yo f the relativ e result s fo r the eigh t standards . Th e magni

tude s o f the ris k estimate s varyfro mcityt o city , fro mhighestimate s t o lowestimates , an

d fro mthe genera l populatio n exposur e t o the specia l exposur e group . Bu t the relativ e value s acros s standard s do no t vary

7 8P.8 2

greatly . Standard 4 ( 9 ppm , 8-hour average , 1 allowabl e exceedance ) consistentl ytend s t o lead t o the lowes t ris k estimates , an d standard s 6 ( 9 ppm , 8-hour average , 5 allowabl e exceedances ) an d 5 (1 2 ppm , 8-hour average , 5 allowabl e exceedances ) ar e lowrelativ e t o the others . At the othe r extreme , standard s 3 (3 5 ppm , 1-hou r average , 1 allowabl e exceedance ) an d 8 (2 5 ppm , 1-hou r average , 5 allowabl e exceedances ) ten d t o provid e the highes t (i.e. , the worst ) ris k estimates . Th e relativ e ordering o f standard s i n term s o f ris k estimate s appear s t o b e consisten t wit hwha t migh t hav e bee n anticipate d a priori .

Th e specia l exposur e grou p led t o lowe r ris k estimate s than the popu latio n exposur e group . Thi s i s no t surprising , sinc e individual s wit h healt hproblem s reflecte d b ythe physiologica l parameter s o f the specia l exposur e grou

p woul d b e expecte d t o hav e somewha t reduce d activit ylevel s an d henc e reduce d level s o f COH bexposure .

T o evaluat e the numerica l ris k estimate s i n an ydetai l shade s int o ris k evaluation . Th e objectiv e o f thi s stud ywa s t o develop a ris k assessment , no t a ris k evaluation . Next , w e wil l provid e some indicatio n a s t o ho wthe ris k assessmen t itsel f migh t b e refine d further .

8. 3 Potentia l Refinement s o f the Analysi s

Th e analysi s conducte d an d reporte d her e i s b yn o mean s the fina l wor d o n the subject . Th e assessmen t o f healt hrisk s associate d wit halternativ e standard s i s a verycomple xproblem , an d the informatio n availabl e i s cer 7 9P.8 3

tainl yles s than perfect . Give n the curren t stat e o f knowledg e concerning ambien t ai r quality , exposure , physiologica l responses , an d ultimat e healt h effect s an

d give n the constraint s o n time an d cos t impose d i n thi s study , w e fee l tha t the analysi s provide s a reasonabl e overal l pictur e o f the healt hrisk s associate d wit hvariou s CO standards . Relaxatio n o f the constraint s and/o r furthe r advance s i n the stat e o f knowledg e woul d permi t furthe r refinemen t o f the analysis . Ultimately , o f course , decision s regarding the degre e o f refinemen t o f a ris k assessmen t hing e upo n tradeoff s betwee n the anticipate d gain s froman d the additiona l cost s o f variou s refinements . Withou t making suchvalu e judgments , w e wil l attemp t t o lis t some potentia l refinements . Majo r change s i n the overal l structur e o f the mode l do no t seem necessaryo r desirable . W e fee l tha t the structur e i s soun d an d tha t muc h mor e i s t o b e gaine d b yrefining the individua l component s o f the model .
First , w e conside r the exposur e data . Th e NE Mmode l represent s a sig

nifican t attac k o n an extremel ycomple xproblem . Ther e are , however , man y possibl e improvement s t o the model . I n term s o f dat a collectio n regarding ambien t ai r quality , i t woul d b e desirabl e t o increas e the numbe r o f site s i n orde r t o reduc e the impac t o f purel yloca l effect s a t individua l sites . Site-to-sit e variabilit yi s surel ysufficien t t o mak e larg e sample s valu

able . Also , the rollbac k mode l use d t o relat e curren t ai r qualit yt o the ai r qualit yexpecte d give n tha t a standard i s impose d an d jus t me t deserve s furthe r attention . A s fo r activit ylevels , i t woul d b e helpfu l t o hav e dat a regarding activit ypattern s fo r the specifi c sensitiv e group s identi

fied i n our analysis . I n addition , the activit ypatter n i n time s o f par 8 0P.8 4

ticularl ypoo r ai r qualit y(e.g. , a smo g alert ) mayno t b e the same a s a t othe r time s fo r whic hactivit ydat a ar e availabl e an d utilize d a s i n the existing exposur e model .

Th e stud

yo f healt heffect s an d the developmen t o f dose-respons e rela

tionship s migh t b e improved . I f i t woul d b e possibl e t o conduc t laboratory experiment s t o collec t dat a bearing directl yo n the relationshi p betwee n COH blevel s an

d the majo r healt heffect s identifie d i n ou r analysis , the resulting dat a woul d hel p t o refin e the dose-respons e estimates . Furthe r informatio n concerning healt heffect s (e.g. , potentia l long-ter meffect s o f an increase d numbe r o f angina attacks ) woul d als o b e useful . I n the absenc e o f "hard data " o n thes e issues , mor e extensiv e assessmen t o f experts ' judgment s woul d b e desirable . I n particular , feedbac k regarding estimate d dose-respons e curve s coul d b e give n t o expert s an d additiona l assessment s coul d b e made . Thi s proces s coul d b e iterate d severa l times . I n thi s regard , i t would-appea r t o b e quit e valuabl e t o bring a grou p o f expert s togethe r t o interac t wit heac hothe r i n a structure d grou p meeting . Th e purpos e o f the meeting woul d b e t o provid e a state-of-current-knowledg e representatio n o f the probabilisti c dose-respons e functions .

On e refinemen t t o the analysi s i s t o mor e carefull ydefin e the sensitiv e groups . Th e curren t analysi s assume d tha t the same dose-respons e curve s pertaine d t o al l individual s withi n a sensitiv e group . I t mayb e tha t thes e group s can b e appropriatel ydivide d (i.e. , coronarypatient s wh o hav e had hear t attack s an d coronar

ypatient s wh o hav e no t had hear t attacks) . Differen t dose-respons e curve s ma yappl yt o the subgroups . Thi sP.8 5

migh t b e particularl yusefu l wit hrespec t t o improving paramete r estimate s suc ha s the probabilit ytha t a hear t attac k victi mdie s withi n a year .

The extrapolatio n o f the ris k estimate s fo r the four citie s t o estimat e healt heffect s t o the entir e U.S . urba n populatio n i s veryshaky . Mor e informatio n i s neede d abou t ho wrepresentativ e (or unrepresentative ) thes e four citie s ar e o f urban environment s an d urba n populations . Fo r example , ho wdoe s the ai r qualit yi n smalle r urba n area s compar e wit htha t i n larg e area s suc ha s the four citie s use d i n the study ?

Th e analysi s conducte d d e fact o assume s tha t member s o f sensitiv e group s ar e non-smokers , sinc e the exposur e mode l include s thi s assumption . The scop e o f thi s stud ywa s t o includ e thi s assumption . However , i f an adequat e wayt o includ e the characteristi c tha t member s o f the populatio n do smok e i s found , the resulting analysi s woul d b e useful . I t i s know n tha t regula r smoker s generall yhav e a muc hhighe r COH bleve l than non-smokers . Thus , i t mayb e the cas e tha t the ambien t CO leve l mayhav e a muc hsmalle r effec t o n CO-relate d healt heffect s fo r smoker s than non-smokers . I f thi s wer e the case , the estimate s provide d i n Table s 7. 1 - 7.2 0 woul d b e highe r than corresponding estimate s whic hinclude d the effect s o f smoking .

8 2APPENDI XA . Representativ e interview s wit hexperts .

Th e informatio n abou t healt heffect s i n Sectio n 5. 4 wa s gathere d i n individua l interview s wit hmedica l experts . Thi s Appendi xillustrate s the genera l natur e o f thos e interview s (no t al l o f the specifi c detail s o f the interviews ) b

ypresenting two representativ e examples . Th e informatio n her e i s base d o n the note s a t the time o f the interview s an d the recollection s o f the interviewer . I t represent s a condense d summar yo f the interactio n betwee n the interviewe r an d the experts , no t the verbati m question s an

d responses . Th e firs t cas e involve s tw o interview s wit hDr . Wilber t S . Aronow , Chief , Cardiovascula r Section , Veteran s Administratio n Hospital , Long Beach , California .

Th e Firs t Intervie wwit hDr . Arono w

Interviewer : Wha t ar e the healt heffect s o f low-leve l Carbo n Monoxid e (CO ) exposure s i n health ypeople ? Expert : Ver

yminimal . At 2 percen t COHb , health ypeopl e experienc e a reductio n i n maxima l exercis e time . Thi s coul d b e relevan t fo r athletes . A t highe r levels , o f course , suc ha s fo r nonsmoking foundry workers , the effect s hav e bee n demonstrate d t o b e serious . Interviewer : D o lowlevel s o f C O exposur e caus e cardiovascula r damag e i n norma l people ? Expert : I canno t sa y- w e kno wtha t the conditio n i s aggravate d i f a perso n alread

yi s a cornonaryhear t patient . Interviewer : A t wha t leve l o f COH bmigh t aggravatio n o f angina occur ? Expert : I t ha s bee n demonstrate d a t 2 percent .

8 3P.8 7

Interviewer : I f w e tak e a sampl e o f 100 0 angina patients , woul d yo u sa y tha t al l experienc e aggravatio n o f the conditio n a t 2 percen t COHb ? Expert : Mayb e no t al l 100 0 patients , bu t I gues s tha t 9 0 percen t o r mor e wil l experienc e aggravatio n o f the condition . Interviewer : At 1 percen t COHb , wha t percentag e o f angina patient s migh t experienc e aggravation ? Expert : I do no t know . Interviewer : Wil l yo u gues s les s than 1 percen t wil l experienc e

aggravation ? Expert : No ! Mor e than that . I woul d gues s 5 percent . Interviewer : At 1. 5 percen t COHb , ho wman ypeopl e wil l experienc e aggravation ? Expert : Mor e than 1 0 percent . Le t m e sa y2 0 percent . Interviewer : D o yo u agre e wit hthe following :

COHb(percent ) Percen t o f patient s experienc e aggravatio n 1. 0 5 1. 5 2 0 2. 0 >9 0 Expert : Yes ! But , I coul d b e wrong i f an experimen t i s conducted . Interviewer : Wil l yo u b e willing t o mak e a policybase d o n thes e numbers ? Expert : Yes ! I f no othe r stud ydat a i s available . Interviewer : Wha t i s the relationshi p o f angin a wit hcardiovascula r damag e an

d ultimatel ydeath ? Expert : O f peopl e wit hangina , 2 0 percen t hav e 1 vesse l disease , 4 0 percen t hav e 2 vesse l disease , an d 4 0 percen t hav e 3 vesse l disease . Further , o f the patient s wh o hav e 1 vesse l disease , 9 0 percen t wil l b e aliv e b ythe en

d o f 5 years ; o f the patient s wh o hav e 2 vesse l

8 4disease , 6 5 percen t wil l b e aliv e b ythe en

d o f 5 years ; an

d o f the patient s wh o hav e 3 vesse l disease , 4 5 percen t wil l b e aliv e b ythe en d o f 5 years . Interviewer : S o the averag e annua l mortalit yfo r coronaryhear t patient s wil l b e approximatel y8 percent . Expert : Yes , 6 0 percen t wil l b e aliv e a t the en d o f 5 years . Also , i f w e loo k a t the peopl e wh o hav e hear t attacks , 6 0 percen t wil l die : 5 0 percen t di e befor e reaching the hospita l (sudden death) ; an d anothe r 1 0 percen t di e during hospitalization . Interviewer : Howman ypeopl e wh o hav e periphera l vascula r diseas e wil l hav e reduce d tim

e t o onse t o f pai n a t 2 percen t COHb ? Expert : I woul d sa y9 0 percent . Interviewer : At 1. 5 percen t COHb ? Expert : Twent ypercent . Interviewer : A t 1 percen t COHb ? Expert : Fiv e percent . Interviewer : But , you r experimen t showe d aggravatio n o f thi s conditio n a t highe r level s o f COH ba s compare d wit hangina . Expert : Tha t i s becaus e the experimen t wa s conducte d a t somehwa t highe r levels . I woul d expec t thes e patient s t o b e no bette r of f than the angina patient s wit hC O exposures . Interviewer : Coul d a coronaryhear t patien t ge t myocardia l infarctio n o n an acut e basi s i f expose d t o CO ? Expert : I t depend s o n the severit yo f hi s disease . Peopl e wit hunstabl e angina o r i n distres s coul d b e tipped ove r t o myocardia l infarctio n b y a n exposur e t o CO . Ther e ar e a t leas t 1 0 percen t o f angin a patient s wit hunstabl e angina pectoris—actuall ymuc hmor e than 1 0 percent .

8 5Interviewer : At 3 percen t COH bho wman

ycoronaryhear t patient s coul d ge t a hear t attack ? Expert : I woul d gues s greate r than 1 0 percent . Interviewer : At a 1.5- 2 percen t COH blevel ? Expert : I woul d gues s 5 percent . Interviewer : I f a perso n i s having a hear t attack" , coul d highe r level s o f COH bdu e t o C O exposur e caus e death ? Expert : At 1.5- 2 percen t COHb , I woul d gues s 1- 5 percen t o f peopl e may di e an d a t 2- 3 percen t COHb , 1 0 percen t o f peopl e ma ydi e becaus e o f CO exposure . Interviewer : Coul d peopl e di e o f angina ? Expert : No , bu t thes e patient s develop othe r condition s an d eventuall ya majorit yo f themdi e o f hear t relate d causes . Interviewer : D o patient s wit hchroni c obstructiv e pulmonarydiseas e (COPD ) als o suffe r aggravatio n o f thei r condition s a t lowlevel s o f C O exposure ? Expert : Mos t certainly . Interviewer : Ho wwoul d yo u rank the following group s i n term s o f sensitivity ? Expert : Asthmatic s - mos t sensitiv e

Emphysem

a - nex t mos t sensitiv e Chroni c bronchiti s - sensitiv e Interviewer : At 3 percen t COHb , wha t percen t o f peopl e wit hCOP D suffe r aggravatio n o f thei r conditio n ( a significan t reductio n i n time t o onse t o f marke d dyspne a during exercise) ? Expert : I woul d gues s greate r than 9 0 percent . Interviewer : Ho wabou t a t 1. 5 percen t COHb ?

8 6P.9 0

Expert : Abou t 5 percent . Actually , I woul d gues s tha t thes e peopl e hav e the same o r mayeve n hav e a littl e wors e effect s a s the angina patients . S o w e coul d g o by : COHb(percent ) Percen t o f Patient s wit hAggravatio n 1. 0 5 1. 5 2 0 2. 0 >9 0 Interviewer : Ar e ther e othe r group s wh o ar e affecte d b ylow-leve l C O exposure ? Expert : Yes , anemi a patient s an d fetuses , bu t yo u shoul d tal k t o expert s i n thes e area s t o ge t bette r information .

The Secon

d Interviewwit hDr . Arono w

Result s o f the secon d intervie wwit hDr . Arono war e summarize d b ythe following table s an d comments . Angin a patient s wh o mayexperienc e reduce d tim e t o onse t o f pai n COHb(percent ) Patient s (percent ) 1. 0 5 1. 5 2 0 2. 0 >9 0 2. 5 9 9

8 7P.9 1

Angin a Patient s wh o ma yexperienc e additiona l angina attack s Patient s wit hstabl e Patient s wit hunstabl e COHb(percent ) angina (percent ) angina (percent ) 1. 0 0- 5 (2 % median ) 1. 5 5-2 0 (10 % median ) 2. 0 10-4 0 (25 % median) ' 50-9 9 2. 5 4 0 (median ) 4. 0 6 0 5. 0 8 0 Th e rang e indicate s the 5t han d 95t hpercentile . Four t o five millio n peopl e hav e angin a an d mor e than 1 0 percen t hav e unstabl e angina . Th e caus e o f pai n i s a discrepancybetwee n oxyge n deman d an d suppl yt o the hear t muscl e whic hcause s angina attack . Fo r unstabl e angin a the discrepancyi s worse . Periphera l vascula r diseas e patient s wh o mayexperienc e reduce d time t o onse t o f pai n COHb(percent ) Patient s (percent ) 1. 0 5 1. 5 2 0 2. 0 >9 0 2. 5 9 9

8 8P.9 2

PV D patient s wh o experienc e additiona l attack s COHb(percent ) Patient s (percent ) 1. 0 2 1. 5 1 0 2. 0 2 0 2. 5 4 0

Additiona l case s o f hear t attack s among thos e wh o alread yhav e hear t diseas e COHb(percent ) Increas e i n hear t attack s (percent ) 1. 5 1 2. 0 5 3. 0 1 0 4. 0 1 5 5. 0 2 0

Additiona l death s among thos e wh o ar e having a hear t attac k COHb(percent ) Increas e (percent ) 1. 5 1 2. 0 5 3. 0 1 0 4. 0 1 5 5. 0 2 0

Lo wlevel s o f CO do no t caus e atherosclerosi s bu t theymayprecipitat e angina l pains , myocardia l infarctio n an d eve n death . I n the presenc e o f highe r COH

blevel s du e t o expsour e t o CO , the progres s o f angina l attack s

8 9P.9 3

an d movemen t t o unstabl e angina an d the n t o myocardia l infarctio n an d utlimatel yt o deat hi s faster . Approximatel yfiv e an d one-hal f millio n peopl e hav e angina , an d approximatel y1,250,00 0 peopl e hav e myocardia l infarctio n eac hyear . O f individual s wit hstabl e angina , 5 percen t di e withi n a year . Wit hunstabl e angina , 1 5 percen t di e withi n a year . Give n a myocardia l infarctio n (i.e. , hear t attack) , 6 5 percen t di e withi n a yea r (5 0 percen t di e befor e getting t o a hospital , 1 0 percen t di e i n the hospital , 5 percen t di e withi n a yea r afte r hospita l discharge) . I n eac h o f the abov e thre e categories , the chanc e o f dying increase s wit hfrequen t exposure s t o C O leading t o 2 percen t COHb . Fo r instance , wit hstabl e angina , the following increase s i n the probabilit yo f dying migh t resul t fromfrequen t C O exposure .

B yen d 1 5 1 0 o f the yea r Percen t

o f dyi n chs

%w i background

5 2 5 5 0 inc e th COH b <1 % Percen t chanc e o f dying wh < expose d t o CO resulting i n 2 % COH b 6 3 0 6 0 5-6 % COH

b 15-2 0

COP D patient s COHb(percent ) 1. 0 1. 5 2. 0 3. 0 Patient s wit haggravatio n (percent ) 5 2 0 9 0 9 9



### 9 0Aggravatio n o f COP D i s define d a s a significan t reductio n i n tim e t o onse t o f marke d dyspne a during exercise . Th e patient s wit hchroni c obstructiv e lun g diseas e als o hav e a highe r chanc e o f dying i f expose d t o 2 percen t COH blevels .

Author s Comment . Dr . Arono wrequeste d tha t w e mentio n i n the repor t tha t he provide d hi s estimate s base d o n hi s clinica l judgment . Hi s willingnes s t o shar e thes e professiona l judgment s i s greatl yappreciated .

Th e following summarize s an intervie wwit hDr . Thoma s L . Kurt , Clinica l Associat e Professo r o f Interna l Medicin e a t the Universit yo f Texa s Healt hScienc e Cente r a t Dalla s o n Octobe r 15 , 1981 .

Norma l Peopl e

Immediat e Healt hEffect s

At 2- 3 percen t COHb , n o immediat e healt heffects . Vigilanc e effect s occur a t abou t 4 percen t COH ban d hav e no t bee n verifie d a t lowe r levels .

Long TermHealt hEffect s

Ther e i s an overwhelming evidenc e tha t lowlevel s o f CO exposur e (2- 3 percen t COHb ) caus e atherosclerosi s i n nonsmoking norma l peopl e i n lon g run . Dr . Kur t mentione d tha t h e maintain s thi s vie wi n spit e o f the recen t Astru p study .
9 1P.9 5

Aquestio n wa s aske d abou t two hypothetica l citie s wit h100,00 0 populatio n eac hwher e al l othe r thing s excep t the level s o f C O ar e the same . Th e leve l o f CO i n cityB i s highenought o caus e 2- 3 percen t COH b level s i n it s resident s a s compare d wit hcityAwhic hha s extremel ylow level s o f C O (les s than 1 percen t COH blevel s i n the residents) . Wha t wil l the differenc e b e i n the healt heffect s experience d b ythe resident s o f the two cities ?

Dr . Kur t replie d tha t a t the en d o f 5-1 0 year s yo u wil l se e mor e atherogenesi s i f examine d unde r microscope . Yo u wil l no t se e clinica l manifestatio n o f the disease .
Wil l yo u se e mor e angina l cases ? No ! No t i n 5-1 0 year s bu t i n 15-2 0 year s yo u wil l observ e clinica l manifestatio n o f the disease , suc ha s peopl e having ches t pai n leading t o hear t attack s an d sudde n deaths . Prevalenc e o f coronaryhear t diseas e wil l increas e b y2 0 percent .
Wil l ther e b e an increas e i n respiratorydisease ?

No ! Exposur e t o CO o n a chroni c basi s doe s no t increas e the prevalenc e o f respiratorydiseas e bu t i t doe s increas e incidence s o f aggravatio n o f th e preexisting condition .

9 2P.9 6

Patient s wit hCardiovascula r Diseas e Angina Patient s
COHb(percent ) 1. 5 2. 0 2. 5 Additiona l dail yangina case s (percent ) Some effec t bu t statisticall yundetectabl e 2 0 3 0

Hear t Attack s COH b(percent ) 2 Additiona l case s o f hear t attacks(percent ) 2 0

Death s Mor e death s wil l occu r becaus e CO wil l precipitat e mor e hear t attacks . But , -th e percentag e o f death s among thos e wh o hav e hear t attack s wil l remai n abou t the same .

Patient s wit hRespiratoryDiseas e

Bronchiti s an

d Emphysem

a A2 percen t COH

bleve l wil l precipitat e dyspne a bu t wil l no t caus e chroni c bronchitis .

9 3P.9 7

Asthma

A2 percen t COH

bleve l wil l no t precipitat e an asthm a attack , bu t wil l aggravat e i t i f an attac k i s alread ytaking place . Fo r example , an other

wis e mil d attac k coul d caus e worsening o f the symptomt o mediu man d a mediu mattac k coul d become a seriou s attac k i n the presenc e o f CO .

Othe r Effect s

Lowe r weigh t o f the babie s a t birt han d therefor e a highe r likelihoo d o f prematur e babies . Sinc e ther e i s a highe r deat hrat e among prematur e babies , indirectl yC O ma ycaus e highe r deat hrate s among ne wbor n babies .

Level s a t whic hthe Healt hEffect s Begi n

A t 1. 5 percen t COHb , some healt heffect s begin . Th e threshol d i s abou t 1.7-1. 8 percen t COHb . Ther e wil l b e an increas e i n the incidenc e a s wel l a s seriousnes s o f the healt heffect s a s w e g o fro m1. 8 t o 3 percen t COHb . (Note : Thi s questio n wa s aske d sinc e Dr . Kurt' s stud yshowe d the presenc e o f threshol d bu t n o increas e i n the incidence s abov e the threshold) .

Othe r Issue s

1 . Base d o n Standardize d Mortalit yRates , the numbe r o f hear t attacks/year/100,00 0 populatio n varyfrom35 0 i n Denve r t o 80 0 i n a coasta l citysucha s Boston .

9 4P.9 8

2 . O f patient s wit hhear t attack s wh o g o t o a hospital , 15-3 0 percen t die . 3 . COH

bha s a half-lif e o f four hours . Tha t is , a 1 0 percen t CQH b leve l wil l decreas e t o 5 percen t i n four hour s i f a perso n i s i n CO fre e environment . 4 . Interactio n effect s wit hothe r pollutant s shoul d b e take n int o accoun t i n the stud yo f healt heffect s o f a pollutant . 5 . Healt heffect s varydepending o n howphysicall yactiv e the perso n is . Fo r example , resting individual s wil l no t experienc e som e healt heffect s a s compare d t o thos e wh o ar e moderatel y exercising . 6 . Beside s COHb , i f a perso n i s takin g certai n drug s o r i s working unde r circumstance s tha t reduc e oxyge n supply , the healt heffect s wil l b e mor e severe . 7 . Ther e ar e othe r mechanism s o f C O toxicit ysuc ha s combining wit h myoglobin , combining wit hcytochrome oxidase , an d interferenc e wit hthe electro n transfe r i n NA D system . 8 . Arono wwor k need s t o b e confirme d b yothe r researchers , eve n thoughI (Dr . Kurt ) believ e the result s sinc e the yar e corroborate d b

ysome othe r huma n an d anima l studies . 9 . Mos t studie s ar e don e o n norma l peopl e - studie s shoul d als o b e don e o n genera l population . Studie s o n specia l group s suc ha s fir e fighters , cok e ove n workers , an d foundr

yworker s coul d b e usefu l i n the constructio n o f a dose-respons e curv e sinc e they experienc e highe r level s o f CO exposures .

9 5P.9 9

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Winkler , R . L . Scoring rule s an d the evaluatio n o f probabilit yassessors . J . Amer . Statist . Assoc . 64_ : 1072-1078 , 1969 . Winkler , R . L . Combining probabilit ydistribution s fromdependen t informatio n sources . Managemen t Scienc e 27_ :/ +79-488 , 1981 . Winneke , G . Behaviora l effect s o f methylen e chlorid e an d carbo n monoxid e a s assesse d b

ysensor

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### 10 1P. 5

Lis t o f FIGURES : Figur e 2- 1 COH

bleve l an

d time unti l exercise-induce d angina . Figur e 2- 2 Perinata l mortalit yrate s an d materna l smoking level . Figur e 2- 3 Ris k o f congenita l abnormalit yaccording t o ag e an d smoking habit . (Himmelberger , 1978 . Figur e take n fromSurgeo n General' s 198 0 repor t o n "The Healt hConsequence s o f Smoking fo r Women." ) Figur e 2- 4 Mea n percentage s o f signal s correctl yidentifie d b ythe nonsmoker s i n the alerte d tes t an d a s a functio n o f tim e i n the vigil . (O'Hanlon , 1972. ) Figur e 2- 5 Relationshi p betwee n COH ban d decremen t i n maximu maerobi c power . (U.S . EPA , 1979. ) Figur e 3- 1 Overvie wo f the ris k assessmen t model . Figur e 3- 2 Th e structur e o f the ris k assessmen t model . Figur e 4- 1 Sampl e people-occurrence s fo r COH blevel s fromexposur e model . Figur e 4- 2 Sampl e peopl e expose d fo r COH blevel s fro

mexposur e model . Figur e 6- 1 Dose-respons e dat a an d curve fo r the percentag e o f additiona l angina attack s t o angina patients . Figur e 6- 2 Dose-respons e dat a an d curv e fo r the percentag e o f additiona l hear t attack s t o hear t attac k patients . Figur e 6- 3 Dose-respons e dat a an d expecte d dose-respons e curve o n relating COH

blevel s an

d the percentag e o f angina patient s wit haggravate d condition . Figur e 7- 1 Probabilit ydistributio n fo r annua l CO-induce d hear t attack s

i n Lo s Angele s unde r Standard 8 .
Lis t o f TABLES : Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e Tabl e 

### 1 2 2 2 2 4 4 4 4 4 4 5 6 6 6 7 7 7 7 1 1 2 3 4 1 2 3 4 5 6 1 1 2 3 1 2 3 4 ANALYZE D AMBIEN T CARBO NMONOXID E STANDARD S COH bLEVE L AND REDUCE D TIM E T O ONSE T O F ANGIN A MATERNAL SMOKIN

GLEVE L AN

D CHILDREN' S MEDICAL TREATMEN T COH bLEVE L AN

D DECREMENT S INVIGILANC E CARBOXYHEMOGLOBI NLEVEL S AFTE RVARIOU S EXPOSURE S SAMPL E POLLUTAN

T ENCOUNTE RDAT

AFROMEXPOSUR E MODE L SAMPL E PEOPL E EXPOSE D DATAFROMEXPOSUR E MODE L SAMPL E PEOPL E AT PEA K EXPOSUR E DATAFROMEXPOSUR E MODE L PEOPLE-OCCURRENCE S FORCOH bLEVEL S FROMEXPOSUR E MODE L PEOPL E EXPOSE D FORCOH bLEVEL S FROMEXPOSUR E MODE L PEOPL E A

T PEA K EXPOSUR E FORCOH

bLEVEL S FROMEXPOSUR E MODE L INTERVIEWE D HEALT H EXPERT S DOSE-RESPONS E RELATIONSHI P BETWEE NCOH bLEVEL S AN

D PERCENT
AG E O F ANGIN

APATIENT S SUFFERIN GADDITIONAL ATTACK S ( P ) DOSE-RESPONS E RELATIONSHI P BETWEE NCOH bLEVEL S AN

D PERCENT
AG E INCREAS E INHEART ATTACK S ( P ) DOSE-RESPONS E RELATIONSHI P BETWEE NCOH bLEVEL S AN

D PERCENT
AG E O F ANGIN

APATIENT S WIT H AGGRAVATE D CONDITION(P AA ) RIS K ESTIMATE S FORLO S ANGELE S RIS K ESTIMATE S FORCHICAGO RIS K ESTIMATE S FORPHILADELPHI A RIS K ESTIMATE S FORST . LOUI S



## 10 2P. 6

Tabl e 7. 5 PROBABILITYTHAT 1 , 5 , o r 1. 0 PERCENT O F SENSITIVE GROU P WIL L

SUFFE R ADVERS E HEALT H EFFECT S FORLO S ANGELE S Tabl e 7. 6 PROBABILITYTHA T 1 , 5 , o r 1 0 PERCEN T O F SENSITIVE GROU P WIL L SUFFE RADVERS E HEALT H EFFECT S FORCHICAGO Tabl e 7. 7 PROBABILITYTHA T 1 , 5 , o r 1 0 PERCENT Q F SENSITIVE GROU P WIL L SUFFE RADVERS E HEALTH EFFECT S FORPHILADELPHI A Tabl e 7. 8 PROBABILITYTHA T 1 , 5 , o r 1 0 PERCEN T O F SENSITIVE GROU P WIL L SUFFE RADVERS E HEALT H EFFECT S FORST . LOUI S Tabl e 7. 9 RIS K ESTIMATE S FORSPECIA L EXPOSUR E GROUP FORLO S ANGELE S Tabl e 7.1 0 RIS K ESTIMATE S FORSPECIA L EXPOSUR E GROU P FORCHICAGO Tabl e 7.1 1 RIS K ESTIMATE S FORSPECIA L EXPOSUR E GROU P FORPHILADELPHI A Tabl e 7.1 2 RIS K ESTIMATE S FORSPECIAL EXPOSUR E GROU P FORST . LOUI S Tabl e 7.1 3 PROBABILITYTHA T 1 , 5 , OR1 0 PERCENT O F SENSITIVE GROU P WIL L SUFFE R ADVERS E HEALT H EFFECT S FORLO S ANGELE S Tabl e 7.1 4 PROBABILITYTHA T 1 , 5 , OR1 0 PERCEN T O F SENSITIVE GROUP WIL L SUFFE R ADVERS E HEALT H EFFECT S FORCHICAGO Tabl e 7.1 5 PROBABILITYTHA T 1 , 5 , OR1 0 PERCEN T O F SENSITIVE GROU P WIL L SUFFE RADVERS E HEALT H EFFECT S FORPHILADELPHI A Tabl e 7.1 6 PROBABILITYTHA T 1 , 5 , OR1 0 PERCEN T O F SENSITIVE GROU P WIL L SUFFE RADVERS E HEALT H EFFECT S FORST . LOUI S Tabl e 7.1 7 RIS K ESTIMATE S FORU.S . URBA NPOPULATION Tabl e 7.1 8 PROBABILITYTHA T 1 , 5 , OR1 0 PERCEN T O F SENSITIVE GROU P WIL L SUFFE R ADVERS E HEALT H EFFECT S FORU.S . URBA NPOPULATION Tabl e 7.1 9 RIS K ESTIMATE S FORSPECIA L EXPOSUR E GROU P FORU.S . URBA N POPULATION Tabl e 7.2 0 PROBABILITYTHA T 1 , 5 , OR1 0 PERCEN T C F SENSITIVE GROU P WIL L SUFFE R ADVERS E HEALT H EFFECT S FORU.S . URBA NPOPULATION



### 10 3P. 7

10. 0



## 5 o O - L U 

# ^ ° fcO cr U J a. .a I O u 7.5 -

5.0 -

2.5 -

0. 0 •2 0 PDE C = 2.56+4.6 3 COH b

••

l ^ 6 0 8 0 PDEC : PERCEN TDECREAS E I N TIM E UNTI L EXERCISE-INDUCE D ANGIN A

Figur e 2-1
. COH b leve l an d tim e unti l exercise—induce d angina
.P. 8

5 -

£4 < c c > - l 3 -

< l - < * 2 c c L U a . S / y s / / / / / / ^ Meye retal
. (1975 ) / -Black s

/

Meye retal
. (1975)-White s Meye retal
. (1976 )

1 - •Dat a point s

I 0 Nonsmoker' s I I

1- 9 1 - mea n 3. 9 -1 0 I

1-2 0 (i.e
. les s tha n 1 pack ) I I

10 + 11 + mea n 12. 2 20" *

NUMBER S O F CIGARETTE S PE R DA Y

Figure 2-2
. Perinata l mortalit yrate s an d materna l smokin g level
.P. 9

0. 1

< <3 > Z h - ° Zl

•*•• - s > o t - z < m O tr a . 0.0 5 -

0. 0 • • .

• • Heav ySmoker :

"*•*•' •^ Moderat e Smoker : *^"«^. ^

1-1 9 Cigarettes/ d

^Nonsmoke r

2 0 ^ l I 3 0 4 0 MATERNA LAG E I 5 0

Figur e 2-3
. Ris k

o fcongenita l abnormalit yaccordin g t o ag e an d smokin g habit
. (Himmelberger , 1978
. Figur e take n fro m Surgeo n General' s 198 0 repor to n "Th e Healt h Consequence s o fSmokin g fo rWomen." )P.1 0

CO Z 

### g < i z 11 1 Q < Z ( J u U J 

## c tr O 

## o 9 0

80 *

7 0 -

6 0 -

5 0 -

Alerte d Tes t VIGI L(minutes )

Figur e 2-4
. Mea n percentage s o fsignal s correctl yidentifie d b yth e

nonsmoker s i n th e alerte d tes tan d a s a functio n o ftim e i n th e vigil
. (O'Hanlon , 1972 )P.1 1

X < O > z CO < L U c c o L U Q

Figur e 2-5
. Relationshi p betwee n COH b an d decremen ti n maximu m

aerobi cpower . (U.S
. EPA , 1979 )P.1 2

Basi cInput : Alternativ e Ambien tCO Standar d

Ris k Assessmen tMode l

Outpu tMeasures : Estimate s o fCO Induce d

Healt h Effect s

Figur e 3-1
. Overvie wo fth e ris k assessmen tmodel
.P.1 3



# c Basi cInput : Alternativ e

Ambien tC O Standar d 

# D

Componen tMode l 1 : Relate s C O Standar d an d Ambien t C O Level s 

# c Ambien tC O Qualit y 

# I 

# 3

Componen tMode l 2 : Relate s Ambien tC O Level s an d Huma n Exposur e t o Differen tLevel s 

# c Huma n Exposur e t o C O 

# 3

Componen tMode l 3 : Relate s C O Exposur e an d Resultin g COH b Level s

Physiologica l Response s 

# I 

# J

Componen tMode l 4 : Relate s COH b Level s an d Differen t Healt h Effect s 

# c Advers e Healt h Effect s 

# J

Componen tMode l 5 : Relate s Healt h Effect s t o Ris k Outpu tMeasure s 

# ( Outpu t Induce*
. Measures : Estimate s o fC O e d Healt h Effect s ) Figur e 3-2
. Th e structur e o fth e ris k assessmen tmodel
.P.1 4

Figur e 4- 1 SAMPL E PEOPL E - OCCURRENCE S FORCOH bLEVEL S FROMEXPOSUR E MODE L 

## Lo s Angele s Bes t

Estimat ewit hN o Additive s



# 02468 COH b Concentratio n(Percent ) 1 5 Oc t198 1P.1 5

Figur e 4- 2 SAMPL E PEOPL E EXPOSE D FORCOH bLEVEL S FROMEXPOSUR E MODE L 

## Lo s Angele s Bes t

Estimat ewit hN o Additive s 

# 1 0



# B O U

a ; C G 

# o 

# w * & . 

# S 1 0 1 0 6

# r

1 0 5

# -

1 0 4
_



# 0246 8 COH b Concentratio n(Percent ) 1 5 Oc t198 1P.1 6

t n •>-* 9 ~Z 0 1 ^ '— o C O C O •• * * * C D C O c —
—c a 5 -2 " o ** 5 » "2 &• * J S o > c = k

_** - 

### a 

### 2 o 5 100 - 8 0 - 6 0 - 4 0 - 2 0 - 0 L •Aggregated Oata fro m Tabl e 6- 1

1 Range s fro m Dr . Aronow J

_i n Tabl e 6- 1

0.97 5 Fractil e Curves* '

I I Media n Curv e •^^ ^
H).02 5 Fractil e Curv

e

I I I * COH b LEVE L (%

)

Figure 6-1
. Dose-response dat a an d curv e fo rth e percentag e o f

additiona l angin a attacks t o angin a patients
.P.1 7

4 0 - c a 

# s 3 

# ° - 03

2 0 - C O c O '— °* 5 * a 2 10 -

< I a. •Dat a fro m Tabl e 6- 2

•Anothe rPoin tEstimate d I Range s o fOthe rEstimate s

2 3 4 COHbLEVE L(%

)

Figure 6-2
. Dose-response data an d curve fo rth e percentag e o f

additiona l hear

tattacks t o hear

tattac k patients
.P.1 8

COH b (%

)

Figur e 6-3
. Dose-respons e dat a an d expecte d dose-respons e

curv e o n relatin g COH b level s an d th e percentag e o fangin a patient s wit h aggravate d condition
.P.1 9

C O Z

0.025 /

Fractil e / Estimate^^ r 1 i 0. 5 Fractil e

^^^*V,Estimat e

7 3 1 % fc o fAre a 1 1 Fi tLognorma l

Distributio n

1 0.97 5

Fractil e Estimate i i "• ' 200 0 266 0 400 0 ADDITIONA L HEAR TATTACK S 600 0 8000

Figure 7-1
. Probabilit ydistributio n fo rannua l CO-induce d

hear tattacks i n Lo s Angele s unde rStandard 8
.P.2 0

Tabl e 1. 1 ANALYZE D AMBIENT CARBO NMONOXID E STANDARD S

Allowabl e Averageing Exceedance s Alternativ e CO Standard Time (DailyMaximum ) Standard Leve l (ppm ) (hours ) (expecte d numbe r pe r year )

1 Statu s qu o (1981 ) 2 2 5 1 1 3 3 5 1 1 

### 4 9 8 1 5 1 2 8 1 

### 6 9 8 5 7 1 2 8 5 8 2 5 1 5Tabl e 2. 1 COH bLEVE L AN

D

Investigato r

Arono w[1978 J
Arono w[1981 ] Arono w[1978 ]
Aronow[1980 ] Anderso n an

d Isbel l [1973 ] Anderso n e t al . [1973 ] Anderso n e t al . [1973 ] Aronow , e t al . [1972 ] REDUCE D



## P e TIME TO ONSE T OF ANGIN A

rcen t Ca rboxyhemoglob i n Initia l Mean

1.2 5 1.0 9 1.3 0 1.7 3 1.0 3 1.4 0 

### 1. 6 1.1 2

a Adde d pollutant s i n freewa

yai r Fina l

Mean

1.7 7 2.0 2 2.2 8 5.3 7 2.6 8 2.9 0 

### 4. 5 5.0 8

o r tobacc o Measur e



### of Blood

Venou s
Venou s Venou s
Venou s
Venou s Venou s Venou s Arteria l

smok e ma

yhave

• Ambien t C O

Exposur e & Locatio n

2 hrs. , ventilate d room , wit htobacc o smok e 5 0 ppm , 1 hr . la

b 2 hrs. , unventilate d room , wit htobacc o smok e 10 0 ppm , i

n lab , unti l COH

b a t desire d leve l 5 0 ppm , 2 hrs . la

b 5 0 ppm , 4 hrs . la

b 10 0 ppm , 4 hrs . la

b 5 3 ppm , freewa

y

increased thes e figures . Mean Percentag e Reductio n in Time Unti l Exercise

Induced • Angina Pai n


### 22 a 

### 1 0 

### 38 a



### 3 5 1 6 1 6 1 7 

### 33 a -

Typ e 

### of Exercis e Bicycl e Bicycl e Bicycl e Bicycl e Bicycl e Treadmil l Treadmil l Bicycl e

jP.2 2

Tabl e 2. 2 MATERNAL SMOKIN GLEVE L AN

D CHILDREN' S MEDICAL TREATMENT

MATERNAL SMOKIN G LEVE L (Cigs./day ) INCREASE D DOCTO R VISIT S PE RCHIL D (Percen t relativ e t o nonsmoking mothers ) INCREASE D HOSPITALIZATION S PE RCHILD (Percen t relativ e t o nonsmoking mothers ) UNDE R AG E 1 AG E 1- 5

0 1-1 0 10 + 0. 0 8. 4 3 6 0. 0 21. 4 275. 0 0. 0 47. 7 47. 1

Source : Rantakalli o [1969 ]Tabl e 2. 3 COH bLEVE L AN

D DECREMENT S INVIGILANC E

Referenc e COH b(percent ) Measur e o f Vigilanc e Performanc e Result s

Fodo r an

d Winnek e [1972 ] Estimate d 2.3 , 3.1 , 4. 3 AuditoryVigilanc e decremen t i n vigilanc e a t first , the n i t increase d Groll-Knapp e t al . [1972 ] Estimate d 3. 0- 7. 6 Auditor yVigilanc e dose-relate ddecremen t i n vigilanc e Bear dan d Grandstaf f

[1975 ] Mea nValue s 1.8 , 5.2 , 7. 5 Visua lVigilanc e bigge r decrement s i nvigilanc e a t 1.8 % an d5.2 % COHb , tha n a t 7.5 % Horvat he t

al . [1971 ] At en d o f tes t 2.3 , 6. 6 Visua l Vigilanc e decremen t i n vigilanc e fo r the grou p wit h6.6 % a s fina l mea n COHb Winnek e [1974 ] 5.1 , 10. 0 AuditoryVigilanc e n o effec t Benignu s e t al . [1977 ] 4.61-12.6 2 Visua l Numeri c Monitoring Tas k n o effec tP.2 4

Tabl e 2. 4 CARBOXYHEMOGLOBI NLEVEL S AFTE RVARIOU S EXPOSURE S

(Source : CO an

d Huma n Vigilanc e - Horvat he t al . [1971] )

COH bSaturatio n Leve l (percent ) Afte r Exposur e Carbo n Monoxid e Inhaled(ppm ) 0 Minute s 6 0 t o 6 5 Minute s 13 5 t o 14 0 Minute s

0 2 6 11 1 0.8+0.35(0.4-1.6 )

0.8+0.57(0.4-1.2 ) 0.9+0.46(0.5-1.8 ) 0.8±0.23(0.5-1.3 ) 1.6±0.60(1.1-1.9 ) 4.2+1.15(3.3-6.7 ) 0.8+0.21(0.6-1.2 ) 2.3±0.55(1.9-2.4 ) 6.6+1.27(5.7-9.8 )
Figure s i n parenthese s represen t ranges . ~\Tabl e 4. 1 SAMPL E POLLUTAN T ENCOUNTE RDAT

AFROMEXPOSUR E MODE L

CO /B E ANALYSI S 1 (A ? X S ) FOP LO S ANGELE S

BES T eSTIf4T E CARBON MONOXIO E LO S ANGELE S

PL..LUTAN

T ENCOUNTER S FO R9 HOU

RAVERAGIN

GTIM E P.2 5

CONCENTRATIO N

1 EXCEEDE D1 (PP M ) 1

30. 0 1 65. 0 1 40. 0 1 33. 0 1 30. 0 1 25. 0 1 20. 0 1 15. 0 1 10. 0 1 5. 0 1 0. 0 1

MAX . CONCENTRATIO N 1 PEOPL E A T MAXIMU M 1 LO UEXERCIS E 1

132.00 0 1 1,670.00 0 1 6,060.00 0 1 53.600,00 0 1 754.000.00 0 1 10.700.000,00 0 1 62.500,000.00 0 1

32. 1 1 16.50 0 1 MEDIU M EXERCIS E

165.00 0 15.700,00 0 606.000,00 0 4,260.000.00 0

17. 6 9.20 0 HIG HEXERCIS E

592.00 0 94,700.00 0 943,000,00 0

10. 3 592,00 0 AN YEXERCIS E

132.00 0 1.970,00 0 9.060.00 0 53.900,00 0 770.000.00 0 11.400,000.00 0 67.600.000,00 0

32. 1 16.30 0 •*
- . . . . . - - + • .... . -• - ... .

'POLLUTAN T ENCOUNTERS ' I S TH E SAME AS PERSON HOUP S OF EXPOSUR E FO R1 HOU

RAVERAGINO TIME .

'AN YEXERCISE * MEASURE S EXPOSUR E INDEPENDEN T OF EXERCIS E LEVEL .Tabl e 4. 2 SAMPL E PEOPL E EXPOSE D DAT AFROMEXPOSUR E MODE L

O /B E ANALYSI S 1 (A S IS ) FO RLO S ANGELE S BES T ESTIMAT E CARBON MONOXID E LO S ANGELE S

PEOPL E EXPOSE O FO R0 HOU

RAVERAGIN

GTIME

CONCENTRATIO N EXCEEDE D ( PP M )

50. 0 i 45. 0 1 40. 0 1 35. 0 1 >0. 0 1 25. 0 1 20. 0 1 15. 0 1 10. 0 1 5. 0 1 0. 0

1 MAX . CONCENTHATIO' . 1 PEOPL E A T MAXIMU M LOW EXERCIS E 1

33.20 0 1 152,00 0 1 -.76,00 0 1 2.440.00 0 | 7.120,00 0 1 7,720.00 0 1 7,•'10,00 0 1

32. 1 1 16,30 0 1 MEDIU M EXERCIS E 1

61.60 0 1 3.590.00 0 1 6.940.00 0 1 7,200.00 0 1

17. 6 1 9,20 0 1 HIG HEXERCIS E 1

592,00 0 1 2.700,00 0 1 2.910.00 0 1

10. 3 1 592.00 0 1 AN YEXERCIS E

33,20 0 152.00 0 179,00 0 2,990,00 0 7,120.00 0 7,720,00 0 7,720,00 0

32. 1 16,50 0

'AN YEXERCISE ' MEASURE S EXPOSUR E INDEPENDEN T OF EXERCIS E LEVEL .P.2 7

Tabl e 4. 3 SAMPL E PEOPL E A T PEA K EXPOSUR E DAT

AFRO MEXPOSUR E MODE L

CO /B E ANALYSI S 1 (A S IS ) FO RLO S ANGELE S BES T ESTIMAT E CARBON MONOXID E LO S ANGELE S

PEOPL E A T PEA

KEXPOSUR E FO

R9 HOU

RAVERAGIN

GTIME

1 CONCENTRATIO N1 1 RANG E 1 I (PPM ) 1

1 50. 0 < 1 45. 0 < 1 40. 0 < 1 33. 0 < 1 30. 0 < 1 25. 0 < 1 20. 0 < 1 15. 0 < 1 10. 0 < 1 5. 0 < 1 0 . 0 < C < =

c < = C < s C < = C < = c < = c < = c < = C < s c < = c < = 100. 0 1

50. 0 1 45. 0 1 40. 0 1 35. 0 1 30. 0 1 25. 0 1 20. 0 1 15. 0 1 10. 0 1 5. 0 1

1 MAX . CONCENTRATIO N1 1 PEOPL E A T MAXIMU M1 LOW

2 4 EXERCIS E 1

33.20 0 1 119,00 0 1 25,90 0 1 ,720.00 0 1 ,230.00 0 1 597,00 0 1

32. 1 1 16.30 0 1 MEDIU MEXERCIS E 1

61,60 0 1 3,530,00 0 1 3.350.00 0 1 260,00 0 1

17. 6 1 0.20 0 1 HIG H EXERCIS E 1

502.00 0 1 2.110.00 0 1 114,00 0 1

10. 3 1 592,00 0 1 AN YEXERCIS E

33,20 0 119,00 0 25,00 0 2,720,00 0 4,230,00 0 597,00 0

32. 1 16,30 0 ..m..........*..m.m.-. . .^. ..... . ...... . + ...... . . .. . + .

AN YEXERCISE ' MEASURE S EXPOSUR E INDEPENDEN T OF EXERCIS E LEVEL .Tabl e 4. 4 PEOPLE-OCCURRENCE S FOR COH bLEVEL S FROMEXPOSUR E MODE L

C O /B E ANALYSI S 1 (A S IS ) FO RLO S ANGELE S BES T ESTIMAT E CARBON MONOXID E LO S ANGELE S

PEOPL E • OCCURRENCE S O F EXPOSUR E FO

RCARBOXYHEMOGLOBI N

1 CONCENTRATIO N 1 EXCEEDE D 1 (PERCENT )

1 5.0 0 1 4.5 0 1 4.0 0 1 3.5 0 1 3.0 0 1 2.5 0 1 2.0 0 1 1.5 0 1 1.0 0 1 0.5 0 1 0.0 0

1 MAX . CONCENTRATIO N 1 PEOPL E A T MAXIMU M 1 1 1 LOW

EXERCIS E 1

354.00 0 1 1.700.00 0 1 9,950.00 0 1 77,900.00 0 1 693.000.00 0 1 5,210.000,00 0 1 15.500.000.00 0 1 57,600.000.00 0 1 62.500.000.00 0 1

4.5 0 1 16.30 0 1 MEDIU M EXERCIS E 1

1.960.00 0 1 36.600,00 0 1 335.000.00 0 1 1.010,000,00 0 1 3.930,000,00 0 1 4.200.000,00 0 1

2.9 7 1 221.00 0 1 HIG HEXERCIS E

210.00 0 16,600,00 0 176,000.00 0 746.000.00 0 944,000,00 0

2.1 0 210.00 0 AN YEXERCIS E

354,00 0 1,700,00 0 9,950.00 0 79,900.00 0 730.000.00 0 5,570,000,00 0 16,700.000.00 0 62.200,000.00 0 67,600,000,00 0

4.5 0 16.30 0
.+..................+... .

'AN YEXERCISE ' MEASURE S EXPOSUR E INDEPENDEN T O F EXERCIS E LEVEL .Tabl e 4. 5 PEOPL E EXPOSE D FO R COH bLEVEL S FROMEXPOSUR E MODE L

CO /B E ANALYSI S 1 (A S IS ) FO RLO S ANGELE S BES T ESTIMAT E CARBON MONOXID E LO S ANGELE S

PEOPL E EXPOSE DFOB CARBOXYHEMOGLOBI N P.2 9

1 CONCENTRATIO N 1 1 EXCEEOE D1 1 (PERCENT ) 1

1 5.0 0 1 1 4.5 0 1 1 4.0 0 1 1 3.5 0 1 1 3.0 0 1 1 2.5 0 1 1 2.0 0 1 1 1.5 0 1 1 1.0 0 1 1 0.5 0 1 i o.o o ;

1 MAX . CONCENTRATIO N 1 1 PEOPL E A T MAXIMU M 1 LO UEXERCIS E 1

152.00 0 1 152.00 0 1 691.OC O1 1.60O.OC O1 6.620,OC O1 7.640,00 0 1 7,720,00 0 1 7,7?0.00 0 1 7.720.00 0 1

4.5 0 1 16,30 0 1 MEDIU M EXERCIS E 1

600.00 0 1 1.070.00 0 1 4.600,00 0 1 6,940,00 0 1 7,200.00 0 1 7.200,00 0 1

2.9 7 1 221.00 0 1 HIG HEXERCIS E 1

210.00 0 1 1.560,00 0 1 2,630,00 0 1 2.610,00 0 1 2.010.00 0 1

2.1 0 1 210.00 0 1 AN YEXERCIS E

152.00 0 152.00 0 691,00 0 1.660,00 0 6.620.00 0 7,660.00 0 7.720,00 0 7,720,00 0 7.720,OO O

4.5 0 16,50 0

. . ..........4.... . + ..... . ..« , . . . • .. .

'AN YEXERCISE ' MEASURE S EXPOSUR E INDEPENDEN T O F EXERCIS E LEVEL .P.3 0

Tabl e 4. 6 PEOPL E A T PEA K EXPOSUR E FOR COH

bLEVEL S FROMEXPOSUR E MODE L

C O /B E ANALYSI S 1 (AS IS ) FO RLO S ANGELE S BES T ESTIMAT E CARBON MONOXID E LO S ANGELE S

PEOPL E AT PEA

KEXPOSUR E FO

RCARBOXYHEMOGLOBI N

CONCENTRATIO N1 RANG E 1 (PERCENT ) 1

5.0 0 < 4.5 0 < 4.0 0 < 3.5 0 < 3.0 0 < 2.5 0 < 2.0 0 < 1.5 0 < 1.0 0 < 0.5 0 < 0.0 0 < C c c c c c c c c c c < = < :

< s

< 5 < : < =

< 2 < z < :

< * s

< s 10.0 0 1 5.0 0 1 4.5 0 1 4.0 0 1 3.5 0 1 3.0 0 1 2.5 0 1 2.0 0 1 1.5 0 1 1.0 0 1 0.5 0 1

MAX . CONCENTRATIO N1 PEOPL E A T MAXIMU M1 LO UEXERCIS E i

152.00 0 1

539,00 0 1 993,00 0 1 4,950,00 0 1 1.020.00 0 1 79,70 0 1

4.5 0 1 16.30 0 1 MEDIU MEXERCIS E 1

600.00 0 1 1,270.00 0 1 2.930.00 0 1 2.140.00 0 1 260.00 0 1

2.9 7 1 221.00 0 1 HIG H EXERCIS E 1

I •

210.00 0 1 1.350.00 0 1 1.070.00 0 1 179.00 0 1

2.1 0 1 210,00 0 1 AN YEXERCIS E

152,00 0

539.00 0 995,00 0 4.950.00 0 1,030.00 0 63.50 0

4.5 0 16.30 0

............... . •+---••--•- • .•..................+........ — —..+........ . ....- +

'AN YEXERCISE ' MEASURE S EXPOSUR E INDEPENDEN T OF EXERCIS E LEVEL .P.3 1

Tabl e 5. 1 INTERVIEWE D HEALT H EXPERT S

1 . Dr . Wilber t S . Arono w 2 . Dr . Steve n Ayre s 3 . Dr . RodneyBeard 4 . Dr . Verno n Benignu s 5 . Dr . Claranc e Collie r 6 . Dr . Ann Coulso n 7 . Dr . Edward Crandal l 8 . Dr . Sheldo n Friedlande r 9 . Dr . Steve n Horvat h 10 . Dr . Thoma s L . Kur t 11 . Dr . Laurenc e Long o 12 . Dr . Mohamme d Mustaf a 13 . Dr . StanleyRokaw 14 . Dr . Do n Tashki nP.3 2

Tabl e 6. 1 DOSE-RESPONS E RELATIONSHI P BETWEE NCOH bLEVEL S AN

D PERCENTAG E O F ANGIN APATIENT S SUFFERIN GADDITIONAL ATTACK S ( P )

Aggregate d Dat a Assesse d Exper t Dat a P COHb(percent )

1. 0 1. 5 2. 0 2. 5 4. 0 5. 0 P (percent )

2 1 0 2 0 3 5 6 0 8 0 Arono w

0-5( 2 median ) 5-20(1 0 median ) 10-40(2 5 median ) 4 0 6 0 Kur t

2 0 3 0 Mustaf a

10-2 0P.3 3

Tabl e 6. 2 DOSE-RESPONS E RELATIONSHI P BETWEE NCOH bLEVEL S AN

D PERCENTAG E INCREAS E INHEART ATTACK S ( P ) CI A

COHb(percent ) P(percent ) HA 1. 5 1 2. 05 3. 01 0 4. 01 5 5. 02 0P.3 4

Tabl e 6. 3 DOSE-RESPONS E RELATIONSHI P BETWEE NCOH bLEVEL S AND PERCENTAG E O F ANGIN APATIENT S WIT H AGGRAVATE D CONDITION( P ) Ax\.

COHb(percent ) P (percent )

1. 0 5 1. 5 2 0 2. 0 9 0 2. 5 9 9 3. 0 10 0P.3 5

Tabl e 7. 1 RIS K ESTIMATE S FOR LO S ANGELE S

(Usin g genera l exposur e data )

IMPAC T ANGINA HAYS(LO ) L A

ANAL Y1 0.154E+0 7 ( 1.98% ) ANAL Y2 ANAL Y3 ANAL Y4

0.116E+0 7 ( 1.49% ) 0.180E+0 7

( 2.31% ) 0.697E+0 6

< 0.90% ) ANAL YS

0.843E+0 6 < 1.09% ) ANAL Y6

0.796E+0 6 ( 1.02% ) ANAL Y7 ANAL Y8

0.106E+0 7 ( 1.362 ) 0.168E+0 7

( 2.16% ) ANGINA DAYS(ME ) 0.381E+0 7

( 4.91% ) 0.292E+0 7

< 3.76% ) 0.439E+0 7

( 5.66% ) 0.180E+0 7

( 2.32% ) 0.217E+0 7

< 2.79% ) 0.205E+0 7

( 2.64% ) 0.269E+0 7

( 3.47% ) 0.413E+0 7

< 5.32% ) ANGINA DAYS(HI ) 0.863E+0 7

(11.11% ) 0.685E+0 7

( 8.82% ) 0.975E+0 7

(12.56% ) 0.439E+0 7

( 5.65% ) 0.522E+0 7

( 6.73% ) 0.496E+0 7

( 6.39% ) 0.637E+0 7

( 8.20% ) 0.925E+0 7

(11.92% ) ANGINA HR S (LO ) 0.199E+0 8

( 1.07% ) 0.164E+0 8

( 0.88% ) 0.223E+0 8

( 1.19% ) 0.119E+0 8

( 0.64% ) 0.134E+0 8

( 0.72% ) 0.129E+0 8

< 0.69% ) 0.154E+0 8

( 0.83% ) 0.212E+0 8

( 1.14% ) ANGINA HR S (ME ) 0.509E+0 8

( 2.73% ) 0.423E+0 8

( 2.27% ) 0.565E+0 8

( 3.03% ) 0.310E+0 8

( 1.66% ) 0.348E+0 8

( 1.87% ) 0.335E+0 8

( 1.80% ) 0.399E+0 8

( 2.14% ) 0.539E+0 8

( 2.90% ) ANGINA HR S (HI ) 0.121E+0 9

( 6.52% ) 0.103E+0 9

( 5.52% ) 0.133E+0 9

( 7.15% ) 0.774E+0 8

( 4.15% ) 0.860E+0 8

( 4.62% ) 0.831E+0 8

( 4.46% ) 0.975E+0 8

( 5.23% ) 0.128E+0 9

( 6.87% ) HEAR T ATTA(LO ) 0.159E+0 4

( 3.37% ) 0.105E+0 4

( 2.23% ) 0.172E+0 4

( 3.66% ) 0.383E+0 3

( 0.81% ) 0.705E+03 '

( 1.50% ) 0.500E+0 3

( 1.06% ) 0.997E+0 3

( 2.12% ) 0.165E+0 4

( 3.50% ) HEAR T ATTA(ME ) 0.317E+0 4

( 6.74% ) 0.210E+0 4

( 4.46% ) 0.345E+0 4

( 7.32% ) 0.766E+0 3

( 1.63% ) 0.141E+0 4

( 3.00% ) 0.100E+0 4

( 2.13% ) 0.199E+0 4

( 4.23% ) 0.329E+0 4

( 6.99% ) HEAR T ATTA(HI ) 0.635E+0 4

(13.48% ) 0.420E+0 4

( 8.92% ) 0.689E+0 4

(14.64% ) 0.153E+0 4

( 3.25% ) 0.282E+0 4

( 5.99% ) 0.200E+0 4

( 4.25% ) 0.399E+0 4

( 8.47% ) 0.659E+0 4

(13.99% ) HEAR T FATA(LO ) 0.194E+0 4

( 6.85% ) 0.127E+0 4

( 4.51% ) 0.211E+0 4

( 7.45% ) 0.462E+0 3

( 1.63% ) 0.853E+0 3

( 3.02% ) 0.604E+0 3

( 2.14% ) 0.121E+0 4

( 4.28% ) 0.201E+0 4

( 7.12% ) HEAR T FATA(ME ) 0.394E+0 4

(13.93% ) 0.258E+0 4

< 9.12% ) 0.429E+0 4

(15.18% ) 0.927E+0 3

( 3.28% ) 0.172E+0 4

( 6.08% ) 0.121E+0 4

( 4.30% ) 0.244E+0 4

( 8.64% ) 0.409E+0 4

(14.48% ) HEAR T FATA(HT ) 0.813E+0 4

(28.78% ) 0.527E+0 4

(18.64% ) 0.888E+0 4

(31.42% ) 0.187E+0 4

( 6.61% ) 0.349E+0 4

(12.34% ) 0.245E+0 4

( 8.68% ) 0.499E+0 4

(17.65% ) 0.846E+0 4

(29.94% ) ANGINA AGGRAVA 0.131E+0 8

(16.82% ) 0.967E+0 7

(12.45% ) 0.153E+0 8

(19.72% ) 0.542E+0 7

( 6.98% ) 0.665E+0 7

( 8.56% ) 0.622E+0 7

( 8.01% ) 0.876E+0 7

(11.27% ) 0.143E+0 8

(18.40% ) COP D AGGRAVA 0.327E+0 8

(16.82% ) 0.242E+0 8

(12.45% ) 0.383E+0 8

(19.72% ) 0.136E+0 8

( 6.98% ) 0.166E+0 8

( 8.56% ) 0.156E+0 8

( 8.01% ) 0.219E+0 8

(11.27% ) 0.358E+0 8

(18.40% ) PU D AGGKAU A 0.142E+0 7

(16.82% ) 0.105E+0 7

(12.45% ) 0.167E+0 7

(19.72% ) 0.590E+0 6

( 6.98% ) 0.724E+0 6

( 8.56% ) 0.678E+0 6

( 8.01% ) 0.953E+0 6

(11.27% ) 0.156E+0 7

(18.40% ) VICTl . AGGRAVA 0.241Et*0 6

( 0.01% ) 0.434E+0 5

( 0.00% ) 0.499E+0 6

( 0.02% ) 0. 0

( 0. 0 % ) 0. 0

( 0. 0 % ) 0. 0

( 0. 0 % ) 0.170E+0 5

( 0.00% ) 0.3A9E+0 6

( 0.01% ) PREMA r INC I DE N 0.193Kf0 4

( 1.67% ) 0.11AE+0 4

( 1.00% ) 0.233E+0 4

( 2.01% ) 0.550E+0 3

( 0.47% ) 0.765E+0 3

( 0.66% ) 0.639E+0 3

( 0.55% ) 0.106E+0 4

( 0.91% ) 0.217E+0 4

( 1.87% )Tabl e 7. 2 RIS K ESTIMATE S FOR CHICAGO (Usin g genera l exposur e data ) P.3 6

CHICAG O IMPAC T ANAL Y1 ANAL Y2 ANGIN A 0.319E+0 6 0.320E+0 6 DAYS(LO ) ( 1.34% ) ( 1.35% ) ANGIN A 0.807E+0 6 0.810E+0 6 DAYS(ME ) ( 3.39% ) ( 3.40% ) ANGIN A 0.189E+0 7 0.190E+0 7 DAYS(HI ) ( 7.96% ) ( 7.98% ) ANGIN A 0.309E+0 7 0.310E+0 7 HR S (LO ) ( 0.54% ) ( 0.54% ) ANGIN A 0.807E+0 7 0.811E+0 7 HR S (ME ) ( 1.41% ) ( 1.42% ) ANGIN A 0.202E+0 8 0.203E+0 8 HR S (HI ) ( 3.54% ) ( 3.56% )

HEAR T FATA(LO )

HEAR T FATA(HI ) ANAL Y3 ANAL Y4 0.565E+0 6 ( 2.38% ) 0.135E+0 7 ( 5.66% ) 0.289E+0 7 (12.16% ) 0.478E+0 7 ( 0.84% ) 0.121E+0 8 ( 2.12% ) 0.287E+0 8 ( 5.03% ) 0.160E+0 6

( 0.67% ) 0.422E+0 6 ( 1.77% ) 0.107E+0 7 ( 4.49% ) 0.128E+0 6 ( 0.02% ) 0.342E+0 6 ( 0.06% ) 0.866E+0 6 ( 0.15% ) ANAL Y5

0.220E+0 6 ( 0.93% ) 0.572E+0 6 ( 2.40% ) 0.141E+0 7 ( 5.92% ) 0.233E+0 7 ( 0.41% ) 0.618E+0 7 ( 1.08% ) 0.159E+0 8 ( 2.78% ) ANAL Y6

0.195E+0 6 ( 0.82% ) 0.509E+0 6 ( 2.14% ) 0.127E+0 7 ( 5.34% ) 0.212E+0 7 ( 0.37% ) 0.563E+0 7 ( 0.99% ) 0.145E+0 8 ( 5% ) ANAL Y7

0.286E+0 6 ( 1.20% ) 0.730E+0 6 ( 3.07% ) 0.174E+0 7 ( 7.31% ) 0.284E+0 7 ( 0.50% ) 0.746E+0 7 ( 1.31% ) 0.188E+0 8 ( 3.30% ) ANAL Y8

0.430E+0 6 ( 1.81% ) 0.106E+0 7 ( 4.44% ) 0.237E+0 7 ( 9.98% ) 0.390E+0 7 ( 0.68% ) 0.100E+0 8 ( 1.76% ) 0.245E+0 8 ( 4.29% ) HEAR T 0.311E+0 3 0.314E+0 3 0.563E+0 3 0.125E+0 3 0.222E+0 3 0.179E+0 3 0.2B9E+0 3 0.453E+0 3 ATTA(LO ) ( 2.16% ) ( 2.18% ) ( 3.91% ) < 0.87% ) ( 1.54% ) ( 1.25% ) ( 2.01% ) ( 3.15% ) HEAR T 0.623E+0 3 0.629E+0 3 0.113E+0 4 0.250E+0 3 0.444E+0 3 0.359E+0 3 0.577E+0 3 0.906E+0 3 ATTA(ME ) ( 4.33% ) ( 4.37% ) ( 7.82% ) ( 1.74% ) ( 3.08% ) ( 2.49% ) ( 4.01% ) ( 6.29% ) HEAR T 0.125E+0 4 0.126E+0 4 0.225E+0 4 0.500E+0 3 0.888E+0 3 0.718E+0 3 0.115E+0 4 0.181E+0 4 ATTA(HI ) ( 8.65% ) ( 8.74% ) (15.64% ) ( 3.48% ) ( 6.17% ) ( 4.99% ) ( 8.02% ) (12.58% )

0.378E+0 3 0.381E+0 3 < 4.37% ) ( 4.42% ) 0.688E+0 3 ( 7.97% ) 0.151E+0 3

( 1.75% ) 0.268E+0 3

( 3.11% ) 0.217E+0 3

( 2.51% ) 0.350E+0 3

( 4.05% ) 0.552E+0 3

( 6.39% ) HEAR T 0.764E+0 3 0.771E+0 3 0.140E+0 4 0.303E+0 3 0.541E+0 3 0.436E+0 3 0.707E+0 3 0.112E+0 4 FATA(ME ) ( 8.84% ) ( 8.93% ) (16.25% ) ( 3.51% ) < 6.26% ) ( 5.05% ) ( 8.18% ) (12.98% )

0.156E+0 4 0.158E+0 4 (18.06% ) (18.23% ) 0.291E+0 4 (33.72% ) 0.611E+0 3

( 7.07% ) 0.110E+0 4

(12.72% ) 0.883E+0 3

(10.22% ) 0.144E+0 4

(16.69% ) 0.231E+0 4

(26.75% ) ANGIN A 0.258E+0 7 0.259E+0 7 0.457E+0 7 0.917E+0 6 0.152E+0 7 0.126E+0 7 0.224E+0 7 0.358E+0 7 AGGRAV A

(10.83% ) (10.87% ) (19.21% ) ( 3.85% ) ( 6.41% ) ( 5.30% ) ( 9.41% ) (15.03% ) COP D0.645E+0 7 0.647E+0 7 0.114E+0 8 0.230E+0 7 0.382E+0 7 0.316E+0 7 0.560E+0 7 0.895Ef0 7 AGGRAV A

(10.83% ) (10.87% ) (19.21% ) ( 3.85% ) ( 6.41% ) ( 5.30% ) ( 9.41% ) (15.03% ) PU D0.281E+0 6 0.281E+0 6 0.497E+0 A 0.998E+0 5 0.166E+0 6 0.137E+0 6 0.244E+0 6 0.389E+0 6 AGGRAV A

(10.83% ) (10.87% ) (19.21% ) ( 3.85% ) ( 6.41% ) ( 5.30% ) ( 9.41% ) (15.03% ) VIGI L 0.331E+0 5 0.382E+0 S 0.446E+0 6 0. 0 0. 0 0. 0 0.250E+0 5 0.120E+0 6 AGGRAV A

( 0.00% ) ( 0,00% ) ( 0.05% ) (0.0% ) (0.0% ) (0.0% ) ( 0.00% ) ( 0.01% ) PREMA I 0.372E+0 3 0.375E+0 3 0.941E+0 3 0.169E+0 3 0.241E+0 3 0.211E+0 3 0.325E+0 3 0.612E+0 3 INC I DE N

( l.-05% ) ( 1.06% ) ( 2.667.) < 0,4H% ) ( 0.68% ) < 0.60% ) ( 0.92% ) ( 1.73% )Tabl e 7. 3 RIS K ESTIMATE S FOR PHILADELPHI A (Usin g genera l exposur e data )

IMPAC T PHIL A

ANAL Y1 ANAL Y2 ANAL Y3 ANAL Y4 ANAL Y5 ANAL Y6 ANAL Y7 ANAL Y8 ANGINA DAYS(LO ) 0.230E+0 6

( 0.78% ) 0.305E+0 6

( 1.03% ) 0.493E+0 6

( 1.67% ) 0.164E+0 6

( 0.56% ) 0.197E+0 6

( 0.67% ) 0.209E+0 6

( 0.71% ) 0.283E+0 6

( 0.96% ) 0.495E+0 6

( 1.68% ) ANGINA DAYS(ME ) 0.584E+0 6

( 1.98% ) 0.758E+0 6

( 2.57% ) 0.117E+0 7

< 3.96% ) 0.428E+0 6

( 1.45% ) 0.508E+0 6

( 1.72% ) 0.536E+0 6

< 1.82% ) 0.709E+0 6

( 2.40% ) 0.117E+0 7

( 3.98% ) ANGINA DAYS(HI ) 0.140E+0 7

( 4.75% ) 0.177E+0 7

( 5.99% ) 0.258E+0 7

( 8.73% ) 0.107E+0 7

( 3.61% ) 0.124E+O 7

< 4.21% ) 0.130E+0 7

( 4.41% ) 0.167E+0 7

( 5.65% ) 0.259E+0 7

( 8.76% ) ANGINA HR S (LO ) 0.283E+0 7

( 0.40% ) 0.349E+0 7

( 0.49% ) 0.499E+0 7

( 0.70% ) 0.214E+0 7

( 0.30% ) 0.157E+0 7

( 0.22% ) 0.266E+0 7

( 0.38% ) 0.331E+0 7

( 0.47% ) 0.500E+0 7

( 0.71% ) ANGINA HR S (ME ) 0.737E+0 7

( 1.04% ) 0.895E+0 7

( 1.26% ) 0.124E+0 8

< 1.75% ) 0.5A4E+0 7

( 0.80% ) 0.412E+0 7

( 0.58% ) 0.695E+0 7

( 0.98% ) 0.853E+0 7

( 1.20% ) 0.125E+0 8

( 1.76% ) ANGINA HR S (HI ) 0.183E+0 8

( 2.58% ) 0.218E+0 B

( 3.07% ) 0.291E+0 8

< 4.11% ) 0.143E+0 8

( 2.02% ) 0.105E+0 8

( 1.48% ) 0.173E+0 8

( 2.45% ) 0.209E+0 8

( 2.95% ) 0.291E+0 8

( 4.11% ) HEAR T ATTA(LO ) 0.424E+0 3

< 2.36% ) 0.655E+0 3

( 3.65% ) 0.965E+0 3

( 5.38% ) 0.216E+0 3

( 1.21% ) 0.331E+0 3

( 1.85% ) 0.365E+0 3

( 2.04% ) 0.613E+0 3

( 3.42% ) 0.967E+0 3

( 5.39% ) HEAR T ATTA(ME ) 0.847E+0 3

( 4.72% ) 0.131E+0 4

( 7.31% ) 0.193E+0 4

(10.76% ) 0.433E+0 3

( 2.41% ) 0.663E+0 3

( 3.70% ) 0.730E+0 3

( 4.07% ) 0.123E+0 4

( 6.83% ) 0.193E+0 4

(10.79% ) HEAR T ATTA(HI ) 0.169E+0 4

( 9.45% ) 0.262E+0 4

(14.61% ) 0.38AE+0 4

(21.52% ) 0.866E+0 3

( 4.83% ) 0.133E+0 4

( 7.39% ) 0.146E+0 4

( 8.14% ) 0.245E+0 4

.(13.67% ) 0.387E+0 4

(21.58% ) HEAR T FATA(LO ) 0.514E+0 3

( 4.78% ) 0.801E+0 3

( 7.44% ) 0.119E+O 4

(11.05% ) 0.261E+0 3

< 2.43% ) 0.401E+0 3

( 3.73% ) 0.442E+0 3

( 4.11% ) 0.748E+0 3

( 6.95% ) 0.119E+0 4

(11.08% ) HEAR T FATA(ME ) 0.104E+0 4

( 9.67% ) 0.163E+0 4

(15.1-5% ) 0.244E+0 4

(22.68% ) 0.526E+0 3

( 4.89% ) 0.810E+0 3

( 7.53% ) 0.894E+0 3

( 8.31% ) 0.152E+0 4

(14.13% ) 0.245E+0 4

(22.74% ) HEAR T FATA(HI ) 0.213E+0 4

(19.79% ) 0.338E+0 4

(31.37% ) 0.513E+0 4

(47.67% ) 0.106E+0 4

( 9.89% ) 0.165E+0 4

(15.33% ) 0.182E+0 4

(16.94% ) 0.314E+0 4

(29.20% ) 0.514E+0 4

(47.81% ) ANGINA AGGRAVA 0.157E+0 7

( 5.31% ) 0.216E+0 7

( 7.32% ) 0.360E+0 7

(12.20% ) 0.107E+0 7

( 3.62% ) 0.134E+0 7

( 4.53% ) 0.142E+0 7

( 4.82% ) 0.199E+0 7

( 6.75% ) 0.362E+0 7

(12.27% ) COP D AGGRAVA 0.393E+0 7

( 5.31% ) 0.541E+0 7

( 7.32% ) 0.901E+0 7

(12.20% ) 0.267E+0 7

( 3.62% ) 0.334E+0 7

( 4.53% ) 0.356E+0 7

( 4.82% ) 0.-499E+0 7

( 6.75% ) 0.907E+0 7

(12.27% ) PVI i AGGRAVA 0.171E+0 6

( 5. 3 1% ) 0.235E+0 6

( 7.32% ) 0.392F+0 6

(12.20% ) 0.116E+0 6

( 3.62% ) 0.145E+0 6

( 4.53% ) 0.155E+0 6

( 4.82% ) 0.217E+0 6

( 6.75% ) 0.394E+0 6

(.12.27% ) V I G. [ I.. . AGGRAV A 0.512Et*0 5

( 0.00% ) 0.188E+0 6

( 0.02% ) 0.743E+0 6

( 0.07% ) 0.350E+0 4

( 0.00% ) 0.161E+0 5

( 0.00% ) 0.286E+0 5

( 0.00% ) 0.137E+0 6

( 0.01% ) 0.748E+0 6

( 0.07% ) PREM AI' INCIDE N 0.629L* : + 0 3

( 1.43% ) 0.134E+0 4

( :s.o:r/.) 0.327E+0 4

( 7.427. ) 0.2A9E+0 3

( 0.61% ) 0.434E+0 3

( 0.98% ) 0.518E+0 3

( 1.17% ) 0.113E+0 4

( 2.35% ) 0.328E+0 4

( 7.44% )Tabl e 7. 4 RIS K ESTIMATE S FOR ST . LOUI S (Usin g genera l exposur e data )

IMPAC T ANGINA DAYS(LO ) ANGINA DAYS(ME ) S T LOUI S

ANAL Y1 ANAL Y2 0.135E+0 6 0.116E+0 6 ( 1.11% ) ( 0.95% ) 0.345E+0 6 0.299E+0 6 < 2.85% ) ( 2.46% ) ANAL Y3 0.146E+0 6 ( 1.20% ) 0.371E+0 6 ( 3.05% ) ANAL Y4

0.115E+0 6 ( 0.95% ) 0.298E+0 6 ( 2.46% ) ANAL Y5 ANAL Y6

0.203E+0 6 ( 1.67% ) 0.499E+0 6 ( 4.11% ) 0.148E+0 6

< 1.22% ) 0.377E+0 6 ( 3.10% ) ANAL Y7

0.989E+0 5 ( 0.81% ) 0.256E+0 6 ( 2.11% ) ANAL Y8

0.223E+0 6 ( 1.83% ) 0.541E+0 6 ( 4.46% ) ANGINA DAYS(HI ) 0.828E+0 6 0.726E+0 6

( 6.82% ) < 5.99% ) 0.881E+0 6 ( 7.26% ) 0.725E+0 6

( 5.97% ) 0.113E+0 7

( 9.34% ) 0.893E+0 6

( 7.36% ) 0.630E+0 6

( 5.19% ) 0.121E+0 7

( 9.99% ) ANGINA HR S (LO ) 0.175E+0 7 0.183E+0 7

( 0.60% ) ( 0.63% ) 0.226E+0 7 ( 0.77% ) 0.151E+0 7

( 0.52% ) 0.161E+0 7

( 0.55% ) 0.161E+0 7

( 0.55% ) 0.185E+0 7

( 0.63% ) 0.242E+0 7

( 0.83% ) ANGIN A HR S (ME ) 0.457E+0 7 0.476E+0 7

( 1.56% ) < 1.63% ) 0.580E+0 7 ( 1.98% ) 0.397E+0 7

( 1.36% ) 0.422E+0 7

( 1.45% ) 0.422E+0 7

( 1.44% ) 0.480E+0 7

( 1.64% ) 0.615E+0 7

( 2.11% ) ANGINA HR S (HI ) 0.114E+0 8 0.118E+0 8

< 3.89% ) ( 4.03% ) 0.140E+0 8 ( 4.80% ) 0.100E+0 8

( 3.42% ) 0.106E+0 8

( 3.62% ) 0.106E+0 8

( 3.62% ) 0.119E+0 8

( 4.07% ) 0.148E+0 8

( 5.05% ) HEAR T 0.182E+0 3 0.210E+0 3 0.323E+0 3 0.818E+0 2 0.136E+0 3 0.132E+0 3 0.214E+0 3 0.348E+0 3 ATTA(LO ) ( 2.46% ) ( 2.85% ) ( 4.37% ) ( 1.11% ) ( 1.84% ) ( 1.79% ) ( 2.89% ) ( 4.72% ) HEAR T ATTA(ME ) 0.363E+0 3 0.421E+0 3

< 4.92% ) ( 5.70% ) 0.646E+0 3 ( 8.75% ) 0.164E+0 3

( 2.22% ) 0.272E+0 3

( 3.69% ) 0.264E+0 3

( 3.58% ) 0.427E+0 3

( 5.79% ) 0.696E+0 3

( 9.44% ) HEAR T 0.726E+0 3 0.842E+0 3 0.129E+0 4 0.327E+0 3 0.544E+0 3 0.528E+0 3 0.854E+0 3 0.139E+0 4 ATTA(HI ) ( 9.84% ) (11.40% ) (17.50% ) ( 4.43% ) ( 7.37% ) < 7.15% ) (11.57% ) (18.87% ) HEAR T 0.221E+0 3 0.256E+0 3 0.396E+0 3 0.987E+0 2 0.165E+0 3 0.160E+0 3 0.260E+0 3 0.428E+0 3 FATA(LO ) ( 4.98% ) ( 5.78% ) ( 8.94% ) < 2.23% ) ( 3.72% ) ( 3.61% ) ( 5.87% ) ( 9.66% ) HEAR T 0.446E+0 3 0.519E+0 3 0.809E+0 3 0.199E+0 3 0.333E+0 3 0.322E+0 3 0.527E+0 3 0.875E+0 3 FATA(ME ) (10.08% ) (11.73% ) (18.26% ) ( 4.48% ) ( 7.51% ) ( 7.28% ) (11.91% ) (19.76% ) HEAR T 0.914E+0 3 0.107E+0 4 0.169E+0 4 0.401E+0 3 0.677E+0 3 0.656E+0 3 0.108E+0 4 0.183E+0 4 FATA(HI ) (20.64% ) (24.11% ) (38.05% ) ( 9.06% ) (15.29% ) (14.81% ) (24.49% ) (41.30% ) ANGINA AGGRAVA 0.105E+0 7 0.884E+0 6

( 8.64% ) ( 7.29% ) 0.114E+0 7 ( 9.37% ) 0.881E+0 6

( 7.26% ) 0.159E+0 7

(13.09% ) 0.116E+0 7

( 9.53% ) 0.735E+0 6

( 6.05% ) 0.174E+0 7

(14.37% ) COP D AGGRAVA 0.262E+0 7 0.221E+0 7

( 8.64% ) ( 7.29% ) 0.285E+0 7 ( 9.37% ) 0.221E+0 7

( 7.26% ) 0.398E+0 7

(13.09% ) 0.290E+0 7

( 9.53% ) 0.184E+0 7

( 6.05% ) 0.437E+0 7

(14.37% ) PVD AGGRAVA 0.114E+0 6 0.963E+0 5

( 8.64% ) ( 7.29% ) 0.124E+0 6 ( 9.37% ) 0.959E+0 5

( 7.26% ) 0.173E+0 6

(13.09% ) 0.126E+0 6

( 9.53% ) 0.800E+0 5

( 6.05% ) 0.190E+0 6

(14.37% ) VIG.II . 0.773 E + 0 4 0.232EI-0 4 0.207 E t-0 5 0.232E+0 4 0.118E+0 6 0.219E+0 5 0. 0 0.158 E + 0 6 AGGRAV A( 0.00% ) ( 0.00% ) ( 0.00% ) ( 0.00% ) ( 0.03% ) ( 0.00% ) ( 0. 0 % ) ( 0.04% ) PREMA T 0.235E+0 3 0.306EfO 3 0 . 779 E + 0 3 0.993 E + 0 2 0.154E+0 3 0.150E+0 3 0.310 E + 0 3 0.905E+0 3 INCIDE N( 1.29% ) ( l.o8% ) ( 4.29% ) ( 0.55% ) ( 0.85% ) ( 0.82% ) ( 1.71% ) ( 4.99% ) 12.56.1 :P.3 9

Tabl e 7. 5 PROBABILITYTHA T 1 , 5 , o r 1 0 PERCEN T O F SENSITIV

E GROU P WIL L SUFFE R ADVERS E HEALTH EFFECT S FORLO S ANGELE S (Usin g genera l exposur e data )

PRO P CALCULA

T L A IMPAC T ANG(.1% ) ANG<5% > ANG(10% ) HEA(1% ) HEA(5% ) HEA(10% ) FAT(1% ) FAT(5% ) FAT(10% ) ANAL Y1

99.99 % 45.59 % 4.26 % 69.46 % 0.00 % 0. 0 % 99.43 % 2.53 % 0.01 % ANAL Y2

99.83 % 24.36 % 1.21 % 24.79 % 0. 0 % 0. 0 7. 91.32 % 0.08 % 0.00 % ANAL Y3

100.00 % 58.59 % 7.72 % 77.25 % 0.00 % 0. 0 7. 99.71 % 4.36 % 0.01 % ANAL Y4

96.30 % 4.36 % 0.06 % 0.02 % 0. 0 % 0. 0 % 6.04 % 0. 0 7. 0. 0 7. ANAL Y5

98. 6 2 % 9.25 %

. 0.22 % 3.36 % 0. 0 7. 0. 0 7. 58.56 % 0.00 % 0. 0 % ANAL Y6

98.11 % 7.49 % 0.16 % 0.24 % 0. 0 % 0. 0 •/ . 21.87 % 0. 0 % 0. 0 % ANAL Y7

99.67 % 19. 2 4 % 0.78 % 20.24 % 0. 0 % 0. 0 % 88.69 % 0.04 % 0.00 % ANAL Y8

99.99 % 52.96 % 6.02 % 73.11 % 0.00 % 0. 0 % 99.58 % 3.25 % 0.01 % Tabl e 7. 6 PROBABILITYTHA T 1 , 5 , o r 1 0 PERCEN T O F SENSITIV

E GROUP WIL L SUFFE R ADVERS E HEALT H EFFECT S FORCHICAGO (Usin g genera l exposur e data )

PRO B CALCULA

T CHICAGO IMPAC T ANG(1% ) ANG(5% ) ANG(.L0% ) HEA(1% ) HEA(5% ) HEA(10% ) FAT(1% ) FAT(5% ) FAT(10% ) ANAL Y1

99.64 % 17.71 % 0.65 % 22.08 % 0. 0 % 0. 0 % 89.85 % 0.05 % 0.00 % ANAL Y2

99.65 % 17.89 % 0.66 % 22.89 % 0. 0 % 0. 0 % 90.32 % 0.06 % 0.00 % ANAL Y3

100.00 % 58.69 % 6.94 % 82.57 % 0.01 % 0. 0 % 99.84 % 6.47 % 0.03 % ANAL Y4

88.15 % 1.35 % 0.01 % 0.03 % 0. 0 % 0. 0 % a . 69 % 0. 0 7. 0. 0 % ANAL Y5

96.80 % 5.29 % 0.09 % 4.03 % 0. 0 % 0. 0 7. 61.77 % 0.00 % 0. 0 % ANAL Y6

94.41 % 3.27 % 0.04 % 0.91 % 0. 0 % 0. 0 % 37.66 % 0 . 00 % 0. 0 % ANAL Y7

99.25 % 12.87 % 0.38 % 16.15 % 0. 0 % 0. 0 % 85.45 % 0.02 % 0. 0 % ANAL Y8

99.97 % 36.44 % 2.43 % 62.19 % 0.00 % 0. 0 % 99.03 % 1 . 55 % 0 . 0 0 7.P.4 0

Tabl e 7. 7 PROBABILITYTHA T 1 , 5 , o r 1 0 PERCEN T O F SENSITIV

E GROU P WIL L SUFFE R ADVERS E HEALT H EFFECT S FORPHILADELPHI A (Usin g genera l exposur e data )

PRO B CALCULAT PHIL A IMPAC T ANG(1% > ANG(5% ) ANGU0% > HEA(1% ) HEA(5% ) HEA(10% ) FAT(1% ) FAT(5% ) FAT(10% ) ANAL Y1

92.88 % 1.83 % 0.01 % 30.30 % 0.00 % 0. 0 % 93.63 % 0.13 % 0.00 % ANAL Y2

98.21 % 5.91 % 0.08 % 77.11 % 0.00 % 0. 0 % 99.71 % 4.31 % 0.01 % ANAL Y3

99.95 % 26.70 % 1.07 % 96.35 % 0.27 % 0.00 % 99.99 % 28.17 % 0.66 % ANAL Y4

77.64 % 0.37 % 0.00 % 0.71 % 0. 0 % 0. 0 % 34.15 % 0.00 % 0. 0 % ANAL Y5

87.26 %
* 0.93 % 0.01 % 11.03 % 0. 0 7. 0. 0 % 79.41 % 0.01 % 0. 0 % ANAL Y6

89.66 % 1.22 % 0.01 % 17.21 % 0. 0 % 0. 0 % 86.39 % 0.03 % 0. 0 % ' ANAL Y7

97.31 % 4.45 % 0.05 % 70.84 % 0.00 % 0. 0 % 99.49 % 2 . 78 % 0.01 % ANAL Y8

99.95 % 27.00 % 1 . 10 % 96.90 % 0.28 % 0.00 % 99.99 % 28.43 % 0.68 % Tabl e 7. 8 PROBABILITYTHA T 1 , 5 , o r 1 0 PERCEN T O F SENSITIV

E GROUP WIL L SUFFE R ADVERS E HEALTH EFFECT S FORST . LOUI S (Usin g genera l exposur e data )

PRO B CALCULA T IMPAC T ANG ( 17.) ANG(5% ) ANG(10% ) HEA(1% ) HEA(5% ) HEA(10% ) FAT(1% ) FAT(5% ) FAT(10% ) S T LOUI S

ANAL Y1 98.81 % 9.85 % 0.24 % 34.47 % 0.00 % 0. 0 7. 94.94 % 0 . 20 % 0.00 % ANAL Y2

97.26 % 5.64 % 0.10 % 51.07 % 0.00 % 0. 0 % 98.03 % 0.72 % 0.00 % ANAL Y3

99.25 % 12.61 % 0.36 % 89.64 % 0.04 % 0. 0 % 99.94 % 11.79 % 0 . 10 % ANAL Y4

97.21 % 5.57 % •0.10 % 0.35 % 0. 0 % 0. 0 % 25.64 % 0.00 % 0. 0 % ANAL Y5

99.94 % 30.25 % 1 .667. 10.90 % 0. 0 % 0. 0 % 79.20 % 0.01 % 0. 0 % ANAL Y6

99.33 % 13.30 % 0.39 % 9.34 % 0. 0 % 0. 0 % 76.60 % 0.01 % 0. 0 7. ANAL Y7

94.26 % 2.88 % 0.03 % 52.77 % 0.00 % 0. 0 % 98.22 % 0.81 % 0 . 00 % ANAL Y8

99.97 % 36.95 % 2.44 % 93.06 % 0.08 % 0 . 00 % 99.97 % 16.78 % 0 .20 %P.4 1

Tabl e 7. 9 RIS K ESTIMATE S FOR SPECIA L E-XPOSUR

E GROU P FOR LO S ANGELE S

SPE C ESTIMAT E LA IMPAC T ANAL Y1 ANAL Y2 ANAL Y3 ANAL Y4 ANAL Y5 ANAL Y6 ANAL Y7 ANAL Y8 ANGINA0.755E+0 6 0.565E+O 6 0.893E+0 6 0.327E+0 6 0.376E+0 6 0.360E+0 6 0.490E+0 6 0.821E+0 6 DAYS(LO ) ( 0.97% ) ( 0.73% ) ( 1.15% ) ( 0.42% ) ( 0.48% ) ( 0.46% ) ( 0.63% ) < 1.06% ) ANGINA0.196E+0 7 0.149E+0 7 0.229E+0 7 0.877E+0 6 0.101E+0 7 0.963E+0 6 0.130E+0 7 0.212E+0 7 DAYS(ME ) ' ( 2.52% ) ( 1.91% ) ( 2.95% ) ( 1.13% ) ( 1.30% ) ( ' 1.24% ) ( 1.67% ) ( 2.73% ) ANGINA0.480E+0 7 0.375E+0 7 0.552E+0 7 0.233E+0 7 0.264E+0 7 0.254E+0 7 0.331E+0 7 0.514E+0 7 DAYS(HI ) ( 6.18% ) ( 4.83% ) ( 7.11% ) ( 3.00% ) ( 3.41% ) ( 3.27% ) ( 4.27% ) ( 6.62% ) ANGINA0.917E+0 7 0.731E+0 7 0.105E+0 8 0.533E+0 7 0.583E+0 7 0.567E+0 7 0.680E+0 7 0.988E+0 7 HR S <L0 ) ( 0.49% ) < 0.39% ) ( 0.56% ) (.0.29% ) ( 0.31% ) < 0.30% ) ( 0.36% ) ( 0.53% ) ANGINA0.243E+0 8 0.195E+0 8 0.277E+0 8 0.144E+0 8 0.157E+0 8 0.153E+0 8 0.182E+0 8 0.260E+0 8 HR S (ME ) ( 1.30% ) ( 1.05% ) ( 1.48% ) ( 0.77% ) ( 0.84% ) ( 0.82% ) < 0.98% ) < 1.40% ) ANGINA0.622E+0 8 0.510E+0 8 0.699E+0 8 0.384E+0 8 0.418E+0 8 0.407E+0 8 0.478E+0 8 0.663E+0 8 HR S (HI ) ( 3.34% ) ( 2.74% ) ( 3.75% ) ( 2.06% ) ( 2.24% ) ( 2.18% ) ( 2.57% ) ( 3.56% ) HEAR T 0.11SE+0 4 0.589E+0 3 0.118E+0 4 0.147E+0 3 0.294E+0 3 0.294E+0 3 0.589E+0 3 0.118E+0 4 ATTA(LG ) ( 2.50% ) ( 1.25% ) ( 2.50% ) ( 0.31% ) ( 0.62% ) ( 0.62% ) ( 1.25% ) ( 2.50% ) HEAR T 0.235E+0 4 0.118E+0 4 0.235E+0 4 0.294E+0 3 0.589E+0 3 0.589E+0 3 0.118E+0 4 Q.235E+0 4 ATTA(ME ) ( 5.00% ) ( 2.50% ) ( 5.00% ) ( 0.62% ) ( 1.25% ) ( 1.25% ) ( 2.50% ) ( 5.00% ) HEAR T 0.471E+0 4 0.235E+0 4 0.471E+0 4 0.589E+0 3 0.118E+0 4 0.118E+0 4 0.235E+0 4 0.471E+0 4 ATTA(HI ) (10.00% ) ( 5.00% ) (10.00% ) ( 1.25% ) ( 2.50% ) ( 2.50% ) ( 5.00% ) (10.00% ) HEAR T 0.143E+0 4 0.711E+0 3 0.143E+0 4 0.177E+0 3 0.354E+0 3 0.354E+0 3 0.711E+0 3 0.143E+0 4 FAIA(LO ) ( 5.06% ) ( 2.52% ) ( 5.06% ) ( 0.63% ) ( 1.25% ) ( 1.25% ) ( 2.52% ) ( 5.06% ) HEAR T 0.290E+0 4 0.143E+0 4 0.290E+0 4 0.354E+0 3 0.711E+0 3 0.711E+0 3 0.143E+0 4 0.290E+0 4 I-ATA(ME ) (10.25% ) ( 5.06% ) (10.25% ) ( 1.25% ) ( 2.52% ) ( 2.52% ) ( 5.06% ) (10.25% ) HEAR T 0.593E+0 4 0.290E+0 4 0.593E+0 4 0.711E+0 3 0.143E+0 4 0.143E+0 4 0.290E+0 4 0.593E+0 4 FATA(HI ) (21.00% ) (10.25% ) (21.00% ) ( 2.52% ) ( 5.06% ) ( 5.06% ) (10.25% ) (21.00% ) ANGINA0.509E+0 7 0.335E+0 7 0.639E+0 7 0.993E+0 6 0.135E+0 7 0.123E+0 7 0.255E+0 7 0.570E+0 7 AGGRAV A( 6.56% ) ( 4.32% ) ( 8.22% ) ( 1.28% ) ( 1.74% ) ( 1.58% ) ( 3.29% ) ( 7.34% ) COP D 0.127E+0 8 0.840E+0 7 0.160E+0 8 0.249E+0 7 0.338E+0 7 0.308E+0 7 0.640E+0 7 0.143E+0 8 AGGRAVA( 6.56% ) ( 4.32% ) ( 3.22% ) ( 1.28% ) ( 1.74% ) ( 1.58% ) ( 3.29% ) ( 7.34% ) PVD 0.554E+0 6 0.365E+0 6 0.695E+0 6 0.108E+0 6 0.147E+0 6 0.134E+0 6 0.278E+0 6 0.621E+0 6 AGGRAV A( 6.56% ) ( 4.32% ) ( 3.22% ) ( 1.28% ) ( 1.74% ) ( 1.58% ) ( 3.29% ) ( 7.34% ) VIGI L 0. 0 0. 0 0. 0 0. 0 0. 0 0. 0 0. 0 0. 0 AGGRAVA( 0. 0 7.) ( 0. 0 % ) ( 0. 0 7.) ( 0. 0 7.)

( 0. 0 7.)

( 0. 0 % ) ( 0. 0 % ) ( 0. 0 % ) PREhA T 0.I1SE+0 4 0.654E+0 3 0.115E+0 4 0.371E+0 3 0.475E+0 3 0.475E+0 3 0.654E+0 3 0.115E+0 4 INC I DE N( 0.99% ) ( 0.56% ) ( 0.99% ) ( 0.32% ) ( 0.41% ) ( 0.41% ) ( 0.56% ) ( 0.99% )Tabl e 7.1 0 RIS K ESTIMATE S FOR SPECIA L EXPOSUR E GROU P FOR CHICAGO P.4 2

SPE C ESTIMAT E CHICAG O IMPAC T ANAL Y1 ANAL Y2 ANGINA0.101E+0 6 0.101E+0 6 DAYS(LO ) ( 0.42% ) ( 0.42% ) ANGINA0.270E+0 6 0.270E+0 6 •DAYS(ME ) ( 1.14% ) ( 1.14% ) ANAL Y3 0.134E+0 6 ( 0.56% ) 0.354E+0 6 ( 1.49% ) ANAL Y4

0.817E+0 5 ( 0.34% ) 0.220E+0 6 ( 0.92% ) ANAL Y5

0.886E+0 5 ( 0.37% ) 0.238E+0 6 ( 1.00% ) ANAL Y6 ANAL Y7 ANAL Y8

0.839E+0 5 ( 0.35% ) 0.226E+0 6 < 0.95% ) 0.978E+0 5

( 0.41% ) 0.262E+0 6 ( 1.10% ) 0.114E+0 6

( 0.48% ) 0.302E+0 6 ( 1.27% ) ANGINA DAYS(HI ) 0.711E+0 6 0.711E+0 6

< 2.99% ) ( 2.99% ) 0.905E+0 6 ( 3.80% ) 0.S88E+0 6

( 2.47% ) 0.632E+0 6

( 2.66% ) 0.603E+0 6

( 2.54% ) 0.691E+0 6

( 2.90% ) 0.786E+0 6

( 3.30% ) ANGINA HR S (LO ) 0.111E+0 7 0.112E+0 7

( 0.20% ) ( 0.20% ) 0.144E+0 7 ( 0.25% ) 0.469E+0 6

( 0.08% ) 0.904E+0 6

( 0.16% ) 0.831E+0 6

( 0.15% ) 0.105E+0 7

( 0.18% ) 0.128E+0 7

( 0.22% ) ANGINA HR S (ME ) 0.300E+0 7 0.301E+0 7

( 0.53% ) < 0.53% ) 0.386E+0 7 ( 0.68% ) 0.128E+0 7

( 0.22% ) 0.244E+0 7

( 0.43% ) 0.225E+0 7

< 0.39% ) 0.283E+0 7

( 0.50% ) 0.344E+0 7

( 0.60% ) ANGINA HR S (HI ) 0.800E+0 7 0.802E+0 7

( 1.40% ) ( 1.41% ) 0.101E+0 8 ( 1.78% ) 0.346E+0 7

( 0.61% ) 0.6S6E+0 7

( 1.15% ) 0.605E+0 7

( 1.06% ) 0.757E+0 7

( 1.33% ) 0.912E+0 7

( 1.60% ) HEAR T 0.180E+0 3 0.180E+0 3 0.360E+0 3 0.450E+0 2 0.900E+0 2 ATTA(LO ) ( 1.25% ) ( 1.25% ) ( 2.50% ) ( 0.31% ) ( 0.62% ) HEAR T 0.360E+0 3 0.360E+0 3 0.720E+0 3 0.900E+0 2 0.180E+0 3 ATTA(ME ) < 2.50% ) ( 2.50% ) < 5.00% ) < 0.62% ) ( 1.25% ) 0.900E+0 2 ( 0.62% ) 0.180E+0 3 ( 1.25% ) 0.180E+0 3

( 1.25% ) 0.360E+0 3 ( 2.50% ) 0.360E+0 3

( 2.50% ) 0.720E+0 3 ( 5.00% ) HEAR T ATTA(HI ) 0.720E+0 3 0.720E+0 3

( 5.00% ) ( 5.00% ) 0.144E+0 4 (10.00% ) 0.180E+0 3

( 1.25% ) 0.360E+0 3

< 2.50% ) 0.360E+0 3

( 2.50% ) 0.720E+0 3

( 5.00% ) 0.144E+0 4

(10.00% ) HEAR T FATA(LO ) 0.217E+0 3 0.217E+0 3

( 2.52% ) ( 2.52% ) 0.437E+0 3 ( 5.06% ) 0.541E+0 2

( 0.63% ) 0.108E+0 3

( 1.25% ) 0.108E+0 3

( 1.25% ) 0.217E+0 3

( 2.52% ) 0.437E+0 3

( 5.06% ) HEAR T FATA(ME ) 0.437E+0 3 0.437E+0 3

( 5.06% ) ( 5.06% ) 0.885E+0 3 (10.25% ) 0.108E+0 3

( 1.25% ) 0.217E+0 3

< 2.52% ) 0.217E+0 3

( 2.52% ) 0.437E+0 3

( 5.06% ) 0.885E+0 3

( 10.25% ) HEAR T FATA(HI ) 0.885E+0 3 0.885E+0 3

(10.25% ) (10.25% ) 0.181E+0 4 (21.00% ) 0.217E+0 3

( 2.52% ) 0.437E+0 3

( 5.06% ) 0.437E+0 3

( 5.06% ) 0.885E+0 3

(10.25% ) 0.181E+0 4

(21.00% ) ANGINA AGGRAVA 0.353E+0 6 0.353E+0 6

( 1.48% ) ( 1.48% ) 0.652E+0 6 ( 2.74% ) 0.214E+0 6

( 0.90% ) 0.263E+0 6

( 1.10% ) 0.222E+0 6

( 0.93% ) 0.334E+0 6

( 1.40% ) 0.459E+0 6

( 1.93% ) COP D AGGRAVA 0.884E+0 6 0.884E+0 6

( 1.48% ) ( 1.48% ) 0.163E+0 7 ( 2.74% ) 0.536E+0 6

( 0.90% ) 0.658E+0 6

( 1.10% ) 0.556E+0 6

( 0.93% ) 0.835E+0 6

( 1.40% ) 0.115E+0 7

( 1.93% ) PVD AGGRAVA 0.384E+0 5 0.384E+0 5

( 1.48% ) ( 1.48% ) 0.709E+0 5 ( 2.74% ) 0.233E+0 5

( 0.90% ) 0.286E+0 5

( 1.10% ) 0.242E+0 5

( 0.93% ) 0.363E+0 5

( 1.40% ) 0.499E+0 5

( 1.93% ) VIGI L AGGRAVA 0. 0 0. 0

( 0. 0 % ) ( 0. 0 7.) 0. 0 ( 0.07.) 0. 0

( 0. 0 % ) 0. 0

( 0. 0 % ) 0. 0

( 0. 0 7.) 0. 0

( 0. 0 % ) 0. 0

( 0. 0 % ) PREMA T INCIDE N 0.200E+0 3 0.200E+0 3

( 0.56% ) ( 0.56% ) 0.350E+0 3 ( 0.99% ) 0.113E+0 3

( 0.32% ) 0.145E+0 3

( 0.41% ) 0.145 E + 03 '

( 0.41% > 0.2OOE+0 3

( 0.56% ) 0.350E+0 3

( 0.99% )Tabl e 7.1 1 RIS K ESTIMATE S FOR SPECIA L EXPOSUR E GROU P FOR PHILADELPHI A

SPE C ESTIMAT E PHIL A IMPAC T ANGINA DAYS(LO ) ANGINA DAYS(ME ) ANGINA DAYS(HI ) ANGINA HR S (LO ) ANGINA HR S (ME ) ANGINA HR S (HI ) HEAR T * ATTA(LO ) HEAR T ATTA(ME ) HEAR T ATTA(HI ) HEAR T FATA(LO ) HEAR T FATA(ME ) HEAR T FATA(HI ) ANGINA AGGRAVA COP D AGGRAVA PVD AGGRAVA VIGI L AGGRAVA PREMA T INC I DE N ANAL Y1

0.160E+0 6 ( 0.54% ) 0.407E+0 6 ( 1.38% ) 0.997E+0 6 ( 3.38% ) 0.170E+0 7 ( 0.24% ) 0.451E+0 7 ( 0.64% ) 0.117E+0 8 ( 1.65% ) 0.560E+0 3 ( 3.12% ) 0.112E+0 4 ( 6.25% ) 0.224E+0 4 (12.50% ) 0.683E+0 3 ( 6.35% ) 0.139E+0 4 (12.89% ) 0.286E+0 4 (26.56% ) 0.766E+0 6 ( 2.60% ) 0.192E+0 7 ( 2.60% ) 0.834E+0 5 ( 2.60% ) 0.885E+0 5 ( 0.01% ) 0.931E+0 3 ( 2.11% ) ANAL Y2

0.265E+0 6 ( 0.90% ) 0.641E+0 6 ( 2.17% ) 0.148E+0 7 ( 5.03% ) 0.728E+0 7 ( 1.03% ) 0.184E+0 8 ( 2.60% ) 0.430E+0 8 ( 6.07% ) 0.897E+0 3 ( 5.00% ) 0.179E+0 4 (10.00% ) 0.359E+0 4 (20.00% ) 0.110E+0 4 (10.25% ) 0.226E+0 4 (21.00% ) 0.473E+0 4 (44. OOX ) 0.148E+0 7 ( 5.02% ) 0.371E+0 7 ( 5.02% ) 0.161E+0 6 ( 5.02% ) 0.390E+0 6 ( 0.04% ) 0.258E+0 4 ( 5.85% ) ANAL Y3

0.479E+0 6 ( 1.62% ) 0.110E+0 7 ( 3.73% ) 0.241E+0 7 ( 8.18% ) 0.415E+0 7 ( 0.59% ) 0.102E+0 8 ( 1.44% ) 0.242E+0 8 ( 3.41% ) 0.123E+0 4 ( 6.87% ) 0.247E+0 4 (13.75% ) 0.493E+0 4 (27.50% ) 0.153E+0 4 (14.22% ) 0.316E+0 4 (29.39% ) 0.673E+0 4 (62.56% ) 0.311E+0 7 (10.53% ) 0.778E+0 7 (10.53% ) 0.338E+0 6 (10.53% ) 0.127E+0 7 ( 0.12% ) 0.639E+0 4 (14.49% ) ANAL Y4

0.946E+0 5 ( 0.32% ) 0.251E+0 6 ( 0.85% ) 0.656E+0 6 ( 2.22% ) 0.108E+0 7 ( 0.15% ) 0.291E+0 7 ( 0.41% ) 0.777E+0 7 ( 1.10% ) 0.280E+0 3 ( 1.56% ) 0.560E+0 3 ( 3.13% ) 0.112E+0 4 ( 6.25% ) 0.339E+0 3 ( 3.15% ) 0.683E+0 3 ( 6.35% ) 0.139E+0 4 (12.89% ) 0.359E+0 6 ( 1.22% ) 0.898E+0 6 ( 1.22% ) 0.390E+0 5 ( 1.22% ) 0. 0 ( 0. 0 % ) 0.329E+0 3 ( 0.74% ) ANAL Y5

0.130E+0 6 < 0.44% ) 0.338E+0 6 ( 1.15% ) 0.848E+0 6 ( 2.87% ) 0.144E+0 7 ( 0.20% ) 0.383E+0 7 ( 0.54% ) 0.101E+0 8 < 1.42% ) 0.448E+0 3 ( 2.50% ) 0.897E+0 3 ( 5.00% ) 0.179E+0 4 (10.00% ) 0.545E+0 3 ( 5.06% ) 0.U0 E + 0 4 (10.25% ) 0.226E+0 4 (21.00% ) 0.607E+0 6 ( 2.05% ) 0.152E+0 7 ( 2.05% ) 0.660E+0 5 ( 2.05% ) 0. 0 ( 0. 0 % ) 0.576E+0 3 ( 1.30% ) ANAL Y6

0.149E+0 6 ( 0,51% ) 0.379E+0 6 ( 1.28% ) 0.928E+0 6 ( 3.14% ) 0.155E+0 7 ( 0.22% ) 0.412E+0 7 ( 0.58% ) 0.108E+0 8 ( 1.52% ) 0.448E+0 3 ( 2.50% ) 0.897E+0 3 ( 5.00% ) 0.179E+0 4 (10.00% ) 0.545E+0 3 ( 5.06% ) 0.110E+0 4 (10.25% ) 0.226E+0 4 (21.00% ) 0.699E+0 6 < 2.37% ) 0.175E+0 7 ( 2.37% ) 0.761E+0 5 ( 2.37% ) 0.885E+0 5 ( 0.01% ) 0.576E+0 3 ( 1.30% ) ANAL Y7

0.234E+0 6 ( 0.79% ) 0.574E+0 6 < 1.94% ) 0.134E+0 7 ( 4.55% ) 0.220E+0 7 ( 0.31% ) 0.571E+0 7 ( 0.81% ) 0.144E+0 8 ( 2.03% ) 0.785E+0 3 ( 4.37% ) 0.157E+0 4 ( 3.75% ) 0.314E+0 4 (17.50% ) 0.962E+0 3 ( 8.94% ) 0.197E+0 4 (18.27% ) 0.410E+0 4 (38.06% ) 0.124E+0 7 ( 4.21% ) 0.311E+0 7 ( 4.21% ) 0.135E+0 6 ( 4.21% ) 0.302E+0 6 ( 0.03% ) 0.160E+0 4 ( 3.62% ) ANAL Y8

0.488E+0 6 ( 1.65% ) 0.111E+0 7 ( 3.76% ) 0.243E+0 7 ( 8.22% ) 0.416E+0 7 ( 0.59% ) 0.103E+0 8 ( 1.45% ) 0.243E+0 8 ( 3.43% ) 0.123E+0 4 ( 6.87% ) 0.247E+0 4 (13.75% ) 0.493E+0 4 (27.50% ) 0.153E+0 4 (14.22% ) 0.316E+0 4 (29.39% ) 0.673E+0 4 (62.56% ) 0.312E+0 7 (10.56% ) 0.781E+0 7 (10.56% ) 0.339E+0 6 (10.56% ) 0.139E+0 7 ( 0.13% ) 0.639E+0 4 (14.49% )Tabl e7.1 2 RIS K ESTIMATE

S FO RSPECIA

LEXPOSUR

EGROU PFO RST . LOUIS

SPE C ESTIMAT E S TLOUI S IMPAC TANAL Y1 ANAL Y2 ANAL Y3 ANAL Y4 ANAL Y5 ANAL Y6 ANAL Y7 ANAL Y8 ANGINA DAYS(LO ) ANGINA DAYS(ME ) ANGINA DAYS(HI ) ANGINA HR S (LO ) ANGINA HR S (ME ) ANGINA HR S (HI ) HEAR T ATTA(LO ) HEAR T ATTA(ME ) HEAR T ATTA(HI ) HEAR T FATA(LO ) HEAR T FATA(ME ) HEAR T FATA(HI ) ANGINA AGGRAVA COP D AGGRAVA PVD AGGRAVA VIGI L AGGRAVA PREMA T INC I DE N 0.648E+0 5

( 0.53% ) 0.171E+0 6 ( 1.41% ) 0.436E+0 6 ( 3.59% ) 0.798E+0 6 ( 0.27% ) 0.213E+0 7 < 0.73% ) 0.562E+0 7 ( 1.92% ) 0.185E+0 3 ( 2.50% ) 0.369E+0 3 ( 5.00% ) 0.738E+0 3 (10.00% ) 0.224E+0 3 ( 5.06% ) 0.454E+0 3 (10.25% ) 0.930E+0 3 (21.00% ) 0.294E+0 6 ( 2.42% ) 0.736E+0 6 ( 2.42% ) 0.320E+0 5 ( 2.42% ) 0. 0 ( 0. 0 % > 0.237E+0 3 ( 1.30% ) 0.552E+0 5

( 0.45% ) 0.147E+0 6 ( 1.21% ) 0.382E+0 6 ( 3.15% ) 0.839E+0 6 ( 0.29% ) 0.224E+0 7 ( 0.77% ) 0.586E+0 7 ( 2.01% ) 0.185E+0 3 ( 2.50% ) 0.369E+0 3 ( 5.00% ) 0.738E+0 3 (10.00% ) 0.224E+0 3 ( 5.06% ) 0.454E+0 3 (10.25% ) 0.930E+0 3 (21.00% ) 0.212E+0 6 ( 1.75% ) 0.532E+0 6 ( 1.75% ) 0.231E+0 5 ( 1.75% ) 0. 0 ( 0. 0 % ) 0.237E+0 3 ( 1.30% ) 0.740E+0 5

( 0.61% ) 0.192E+0 6 ( 1.58% ) 0.483E+0 6 < 3.98% ) 0.108E+0 7 ( 0.37% ) 0.283E+0 7 ( 0.97% ) 0.718E+0 7 ( 2.46% ) 0.277E+0 3 ( 3.75% ) 0.554E+0 3 ( 7.50% ) 0.111E+0 4 (15.00% ) 0.338E+0 3 ( 7.64% ) 0.689E+0 3 (15.56% ) 0.143E+0 4 (32.25% ) 0.349E+0 6 ( 2.87% ) 0.873E+0 6 ( 2.87% ) 0.379E+0 5 ( 2.87% ) 0. 0 ( 0. 0 % ) 0.630E+0 3 ( 3.47% ) 0.549E+0 5

( 0.45% ) 0.146E+0 6 ( 1.20% ) 0.381E+0 6 ( 3.14% ) 0.693E+0 6 ( 0.24% ) 0.187E+0 7 ( 0.64% ) 0.500E+0 7 ( 1.71% ) 0.692E+0 2 ( 0.94% ) 0.138E+0 3 ( 1.88% ) 0.277E+0 3 ( 3.75% ) 0.834E+0 2 ( 1.88% ) 0.168E+0 3 ( 3.79% ) 0.338E+0 3 ( 7.64% ) 0.211E+0 6 ( 1.73% ) 0.527E+0 6 ( 1.73% ) 0.229E+0 5 ( 1.73% ) 0. 0 < 0. 0 % ) 0.862E+0 2 ( 0.47% ) 0 . 105E+0 6

( 0.86% ) 0.262E+0 6 ( 2.16% ) 0.627E+0 6 ( 5.17% ) 0.731E+0 6 ( 0.25% ) 0.197E+0 7 < 0.67% ) 0.524E+0 7 < 1.79% ) 0.115E+0 3 ( 1.56% ) 0.231E+0 3 ( 3.13% ) 0.461E+0 3 ( 6.25% ) 0.139E+0 3 ( 3.15% ) 0.281E+0 3 ( 6.35% ) 0.571E+0 3 (12.89% ) 0.540E+0 6 ( 4.45% ) 0.135E+0 7 ( 4.45% ) 0.588E+0 5 ( 4.45% ) 0.878E+0 5 ( 0.02% ) 0.13SE+0 3 ( 0.74% ) 0.759E+0 5

( 0.63% ) 0.197E+0 6 ( 1.62% ) 0.493E+0 6 ( 4.06% ) 0.731E+0 6 ( 0.25% ) 0.197E+0 7 ( 0.67% ) 0.523E+0 7 ( 1.79% ) 0.115E+0 3 ( 1.56% ) 0.231E+0 3 ( 3.13% ) 0.461E+0 3 ( 6.25% ) 0.139E+0 3 ( 3.15% ) 0.281E+0 3 ( 6.35% ) 0.571E+0 3 (12.89% ) 0.361E+0 6 ( 2.98% ) 0.904E+0 6 ( 2.98% ) 0.393E+0 5 ( 2.98% ) 0. 0 ( 0. 0 % > 0.135E+0 3 ( 0.74% ) 0.478E+0 5

( 0.39% ) 0.128E+0 6 ( 1.06% ) 0.340E+0 6 ( 2.81% ) 0.850E+0 6 ( 0.29% ) 0.226E+0 7 ( 0.78% ) 0.592E+0 7 ( 2.03% ) 0.185E+0 3 ( 2.50% ) 0.369E+0 3 ( 5.00% ) 0.738E+0 3 (10.00% ) 0.224E+0 3 ( 5.06% ) 0.454E+0 3 (10.25% ) 0.930E+0 3 (21.00% ) 0.145E+0 6 ( 1.20% ) 0.364E+0 6 ( 1.20% ) 0.158E+0 5 ( 1.20% ) 0. 0 ( 0. 0 % ) 0.237E+0 3 ( 1.30% ) 0.118E+0 6

( 0.97% ) 0.287E+0 6 ( 2.36% ) 0.673E+0 6 ( 5.55% ) 0.118E+0 7 ( 0.40% ) 0.305E+0 7 ( 1.04% ) 0.764E+0 7 ( 2.61% ) 0.277E+0 3 ( 3.75% ) 0.554E+0 3 ( 7.50% ) 0.111E+0 4 (15.00% ) 0.338E+0 3 < 7.64% ) 0.689E+0 3 (15.56% ) 0.143E+0 4 (32.25% ) 0.599E+0 6 < 4.94% ) 0.150E+0 7 < 4.94% ) 0.652E+0 5 ( 4.94% ) 0.161E+0 6 ( 0.04% ) 0.630E+0 3 ( 3.47% )P.4 5

Tabl e 7.1 3 PROBABILITYTHA T 1 , 5 , OR1 0 PERCEN T O F SENSITIVE GROU P WIL L SUFFE R ADVERS E HEALTH EFFECT S FORLO S ANGELE S (Usin g specia l exposur e grou p data )

PRO B CALCULA

T L A IMPAC T ANG(1% ) ANG(5% ) ANG(10% ) HEA(1% ) HEA(5% ) HEA(10% > FAT(1% ) FAT(5% ) FAT(10% ) ANAL Y1

97.50 % 6.42 % 0.13 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 % ANAL Y2

91.02 % 1.99 % 0.02 % 0.93 % 0. 0 % 0. 0 % 37.95 % 0.00 % 0. 0 % ANAL Y3

99.01 % 11.45 % 0.32 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 % ANAL Y4

59.47 % 0.12 % 0.00 % 0. 0 % 0. 0 % 0. 0 % 0.00 % 0. 0 % 0. 0 % ANAL Y5

69.83 % 0.27 % 0.00 % 0.00 % 0. 0 7. 0. 0 % 1.03 % 0. 0 % 0. 0 % ANAL Y6

66.64 % 0.21 % 0.00 % 0.00 % 0. 0 % 0. 0 % 1.03 % 0. 0 % 0. 0 % ANAL Y7

85.26 % 1.02 % 0.01 % 0.93 % 0. 0 % 0. 0 % 37.95 % 0.00 % 0. 0 % ANAL Y8

98.40 % 8.62 % 0.20 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 %

Tabl e 7.1 4 PROBABILITYTHA T 1 , 5 , OR1 0 PERCEN T O F SENSITIV

E GROU P WIL L SUFFE R ADVERS E HEALT H EFFECT S FORCHICAGO (Usin g specia l exposur e grou p data )

PRO B CALCULA

T CHICAG

O IMPAC T ANG(IX ) ANG(5% ) ANG(10% ) HEA(1% ) HEA(5% ) HEA(10% ) FAT(1% ) FA T (5% ) FAT(10% ) ANAL Y1

59.84 % 0.12 % 0.00 % 0.93 % 0. 0 % 0. 0 % 37.95 % 0.00 % 0. 0 % ANAL Y2

59.84 % 0.12 % 0.00 % 0.93 % 0. 0 % 0. 0 % 37.95 % 0.00 % 0. 0 % ANAL Y3

79.18 % 0.52 % 0.00 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 % ANAL Y4

43.47 % 0.03 % 0.00 % 0. 0 % 0. 0 % 0. 0 % 0.00 % 0. 0 % 0. 0 % ANAL Y5

49.73 % 0.05 % 0.00 % 0.00 % 0. 0 % 0. 0 % 1.03 % 0. 0 % 0. 0 % ANAL Y6

45.62 % 0.04 % 0.00 % 0.00 % 0. 0 % 0. 0 % 1.03 % 0. 0 % 0. 0 % ANAL Y7

• 57.42 % 0.10 % 0.00 % 0.93 % 0. 0 % 0. 0 % 37.95 % 0.00 % 0. 0 % ANAL Y8

68.49 % 0.22 % 0.00 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 %Tabl e 7.1 5 PROBABILITYTHA T 1 , 5 , OR1 0 PERCENT O F SENSITIVE GROU P WIL L SUFFE R ADVERS E HEALTH EFFECT S FORPHILADELPHI A (Usin g specia l exposur e grou p data )

PRO B CALCULA

T PHIL A IMPAC T ANG(1% ) ANG(5% ) ANG(10% ) HEA(1% ) HEA(5% ) H£A(10% ) FAT(1% ) FAT(5% ) FAT(10% ) ANAL Y1

74.95 % 0.23 % 0.00 % 61.46 % 0.00 % 0. 0 % 98.98 % 1.47 % 0.00 % ANAL Y2

96.16 % 2.44 % 0.02 % 95.03 % 0.14 % 0.00 % 99.99 % 21.41 % 0.35 % ANAL Y3

99.94 % 22.31 % 0.66 % 99.49 % 1.89 % 0.00 % 100.00 % 55.36 % 4.10 % ANAL Y4

36.53 % 0.01 % 0.00 % 4.38 % 0. 0 % 0. 0 % 63.22 % 0.00 % 0. 0 % ANAL Y5

60.52 % 0.08 % 0.00 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 % ANAL Y6

69.85 % 0.14 % 0.00 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 % ANAL Y7

93.12 % 1.41 % 0.01 % 89.66 % 0.04 % 0. 0 % 99.94 % 11.81 % 0.10 % ANAL Y8

99.95 % 22.90 % 0.67 % 99.49 % 1.89 % 0.00 % 100.00 % 55.36 % 4.10 %

Tabl e 7.1 6 PROBABILITYTHA T 1 , 5 , OR1 0 PERCEN T O F SENSITIVE GROUP WIL L SUFFE R ADVERS E HEALT H EFFECT S FORST . LOUI S (Usin g specia l exposur e grou p data )

PRO B CALCULA T IMPAC T ANG(1% ) ANG(5% ) ANG(10% > HEA(1% ) HEA(5% ) HEA(10% ) FAT(1% ) FAT(5% ) FAT(10% ) S T LOUI S

ANAL Y1 75.60 % 0.37 % 0.00 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 % ANAL Y2

64.74 % 0.16 % 0.00 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 % ANAL Y3

83.07 % 0.67 % 0.00 % 79.32 % 0.01 % 0. 0 % 99.77 % 5.06 % 0.02 % ANAL Y4

64.40 % 0.16 % 0.00 % 0.07 % 0. 0 % 0. 0 % 12.72 % 0. 0 % 0. 0 % ANAL Y5

95.44 % 2.82 % 0.03 % 4.38 % 0. 0 % 0. 0 % 63.22 % 0.00 % 0. 0 % ANAL Y6

84.35 % 0.75 % 0.00 % 4.38 % 0. 0 % 0. 0 % 63.22 % 0.00 % 0. 0 % ANAL Y7

54.21 % 0.08 % 0.00 % 36.22 % 0.00 % 0. 0 % 95.41 % 0.23 % 0.00 % ANAL YU

97.40 % 4.04 % 0.04 % 79.32 % 0.01 % 0. 0 % 99.77 % 5.06 % 0.02 %Tabl e 7.1 7 RIS K ESTIMATE S FOR U.S . URBA NPOPULATION (Usin g genera l exposur e data )

IMPAC T ANAL Y1 ANAL Y2 ANAL Y3 ANAL Y4 ANAL Y5 ANAL Y6 ANAL Y7 ANAL Y8 ANGINA0.217E+0 8 0.200E+0 8 0.314E+0 8 0.123E+0 8 0.131E+0 8 0.157E+0 8 0.180E+0 8 0.311E+0 8 DAYS(LO ) ( 1.30% ) ( 1.21% ) ( 1.89% ) ( 0.77% ) ( 1.09% ) ( 0.94% ) ( 1.09% ) ( 1.87% ) ANGINA0.545E+0 8 0.507E+0 8 0.761E+0 8 0.332E+0 8 0.4S3E+0 8 0.403E+0 8 0.459E+0 8 0.756E+0 8 DAYS(ME ) ( 3.28% ) ( 3.05% ) ( 4.58% ) ( 2.00% ) ( 2.76% ) ( 2.43% ) ( 2.76% ) ( 4.55% ) ANGI'N A0.127E+0 9 0.120E+0 9 0.169E+0 9 0.820E+0 8 0.109E+0 9 0.976E+0 8 0.109E+0 9 0.169E+0 9 DAYS(HI ) ( 7.66% ) ( 7.20% ) (10.18% ) ( 4.93% ) ( 6.55% ) ( 5.38% ) ( 6.59% ) (10.16% ) ANGINA0.260E+0 9 0.253E+0 9 0.350E+0 9 0.147E+0 9 0.189E+0 9 0.198E+0 9 0.242E+0 9 0.334E+0 9 HR S (LO ) ( 0.65% ) ( 0.64% ) ( 0.88% ) ( 0.37% ) ' ( 0.48% ) ( 0.50% ) ( 0.61% ) ( 0.84% ) ANGI'N A0.673E+0 9 0.656E+0 9 0.886E+0 9 0.387E+0 9 0.496E+0 9 0.520E+0 9 0.628E+0 9 0.849E+0 9 HR S (ME ) ( 1.69% ) ( 1.65% ) ( 2.22% ) ( 0.97% ) ( 1.24% ) ( 1.30% ) ( 1.57% ) ( 2.13% ) ANGINA0.165E+1 0 0.161E+1 0 0.210E+1 0 0.972E+0 9 0.125E+1 0 0.130E+1 0 0.155E+1 0 0.203E+1 0 HR S (HI ) ( 4.13% ) ( 4.05% ) ( 5.27% ) ( 2.44% ) ( 3.12% ) ( 3.27% ) ( 3.39% ) ( 5.08% ) HEAR T 0.261E+0 5 0.275E+0 5 0.436E+0 5 0.101E+0 5 0.170E+0 5 0.154E+0 5 0.263E+0 5 0.422E+0 5 ATTA(LO ) ( 2.59% ) ( 2.73% ) ( 4.33% ) ( 1.00% ) ( 1.68% ) ( 1.53% ) ( 2.61% ) ( 4.19% ) HEAR T 0.522E+0 5 0.550E+0 5 0.873E+0 5 0.201E+0 5 0.339E+0 5 0.309E+0 5 0.526E+0 5 0.844E+0 5 ATTA(ME ) ( 5.18% ) ( 5.46% ) ( 8.66% ) ( 2.00% ) ( 3.37% ) ( 3.07% ) ( 5.22% ) ( 8.38% ) HEAR T 0.104E+0 6 0.110E+0 6 0.175E+0 6 0.403E+0 5 0.678E+0 5 0.618E+0 5 0.105E+0 6 0.169E+0 6 ATTA(HI ) (10.36% ) (10.92% ) (17.32% ) ( 4.00% ) ( 6.73% ) ( 6.13% ) (10.43% ) (16.76% ) HEAR T 0.317E+0 5 0.335E+0 5 0.535E+0 5 0.12*E+0 5 0.205E+0 5 0.187E+0 5 0.320E+0 5 0.518E+0 5 FATA(LO ) ( 5.25% ) ( 5.54% ) ( 8.85% ) ( 2.01% ) ( 3.39% ) ( 3.09% ) ( 5.29% ) ( 8.56% ) HEAR T 0.643E+0 5 0.679E+0 5 0.109E+0 6 0.244E+0 5 0.414E+0 5 0.377E+0 5 0.648E+0 5 0.106E+0 6 FATA(ME ) (10.63% ) (11.23% ) (18.09% ) ( 4.04% ) ( 6.85% ) ( 6.23% ) (10.72% ) (17.49% ) HEAR T 0.132E+0 6 0.140E+0 6 0.22SE+0 6 0.493E+0 5 0.842E+0 5 0.766E+0 5 0.133E+0 6 0.220E+0 6 FATA(HI ) (21.82% ) (23.09% ) (37.72% ) ( 8.16% ) (13.92% ) (12.67% ) (22.01% ) (36.45% ) ANGINA0.362E+0 9 0.383E+0 9 0.625E+0 9 0.135E+0 9 0.231E+0 9 0.210E+0 9 0.365E+0 9 0.604E+0 9 AGGRAVA(10.40% ) ( 9.48% ) (15.12% ) ( 5.43% ) ( 8.15% ) ( 6.92% ) ( 8.37% ) (15.02% ) COP D 0.433E+0 9 0.394E+0 9 0.629E+0 9 0.226E+0 9 0.339E+0 9 0.288E+0 9 0.348E+0 9 0.625E+0 9 AGGRAVA(10.40% ) ( 9.48% ) (15.12% ) < 5.43% ) ( 8.15% ) ( 6.92% ) ( 8.37% ) (15.02% ) PVD 0.395E+0 8 0.418E+0 8 0.682E+0 8 0.148E+0 8 0.252E+0 8 0.229E+0 8 0.398E+0 8 0.659E+0 8 AGGRAVA(10.40% ) ( 9.48% ) (15.12% ) ( 5.43% ) ( 8.15% ) ( 6.92% ) ( 8.37% ) (15.02% ) VIGI L 0.285E+0 7 0.363E+0 7 0.216E+0 8 0.129E+0 6 0.426E+0 7 0.115E+0 7 0.246E+0 7 0.200E+0 8 AGGRAVA< 0.00% ) ( 0.01% ) ( 0.04% ) ( 0.00% ) ( 0.01% ) ( 0.00% ) ( 0.00% ) ( 0.03% ) PREMA T 0.123E+0 8 0.153E+0 8 0.370E+0 8 0.477E+0 7 0.717E+0 7 0.711E+0 7 0.138E+0 8 0.362E+0 8 INC I DE N( 1.36% ) ( 1.69% ) ( 4.10% ) ( 0.53% ) ( 0.79% ) ( 0.79% ) ( 1.52% ) ( 4.01% )Tabl e 7.1 8 PROBABILITYTHA T 1 , 5 , OR1 0 PERCEN T O F SENSITIVE GROU P WIL L SUFFE R ADVERS E HEALT H EFFECT S FORU.S . URBA NPOPULATION (Usin g genera l exposur e data )

PRO B CALCULA T IMPAC T ANG(1% ) ANG(5% ) ANG(10% ) HEA ( 17.) HEA(5% ) HEA(10% ) FAT(1% ) FAT(5% ) FAT(10% ) TOTA L

ANAL Y1 99.57 % 15.70 % 0.50 % 40.06 % 0.00 % 0. 0 % 96.30 % 0.32 % 0.00 % ANAL Y2

99.27 % 12.34 % 0.34 % 46.07 % 0.00 % 0. 0 % 97.37 % 0.51 % 0.00 % ANAL Y3

99.98 % 39.14 % 2.7.1 % 89.12 % 0.03 % 0. 0 % 99.94 % 11.31 % 0.09 % ANAL Y4

92.72 % z*» ^*"~* % 0.02 % 0.14 % 0. 0 % 0. 0 % 17.02 % 0. 0 % 0. 0 % ANAL Y5

98.64 % 8.46 % 0.18 % 6.75 % 0. 0 % 0. 0 % 70.94 % 0.00 % 0. 0 % ANAL Y6

97.09 % 5.21 % 0.08 % 3.89 % 0. 0 % 0. 0 % 61.25 % 0.00 % 0. 0 % ANAL Y7

98.63 % 8.63 % 0.19 % 40.89 % 0.00 % 0. 0 % 96.47 % 0.34 % 0.00 % ANAL Y8

99.98 % 38.62 % 2.68 % 37.22 % 0.02 % 0. 0 % 99.91 % 9.61 % 0.06 %Tabl e 7.1 9 RIS K ESTIMATE S FOR SPECIA L EXPOSUR E GROU P FOR U.S . URBA

NPOPULATION

SPE C ESTTMAT E IMPAC T ANAL Y1 ANAL Y2 ANAL Y3 ANAL Y4 ANAL Y5 ANAL Y6 ANAL Y7 ANAL Y8 ANGINA0.103E+0 8 0.104E+0 8 0.164E+0 8 0.638E+0 7 0.878E+0 7 0.809E+0 7 0.926E+0 7 0.173E+0 8 DAYS(LO ) ( 0.62% ) ( 0.63% ) ( 0.99% ) ( 0.38% ) ( 0.54% ) ( 0.49% ) ( 0.56% ) ( 1.04% ) ANGINA0.268E+0 8 0.267E+0 8 0.405E+0 8 0.171E+0 8 0.233E+0 8 0.212E+0 8 0.240E+0 8 0.421E+0 8 DAYS(ME ) ( 1.61% ) ( 1.61% ) ( 2.44% ) ( 1.03% ) ( 1.40% ) ( 1.27% ) ( 1.44% ) ( 2.53% ) ANGINA0.671E+0 8 0.665E+0 8 0.958E+0 8 0.450E+0 8 0.586E+0 S 0.540E+0 8 0.604E+0 8 0.9S4E+0 8 DAYS(HI ) ( 4.04% ) ( 4.00% ) ( 5.77% ) ( 2.71% ) < 3.53% ) ( 3.25% ) ( 3.63% ) ( 5.92% ) ANGIN A0.120E+0 9 0.190 E + 0 9 0.177E+0 9 0.756 E + 0 8 0.922 E + 0 8 0.917 E + 0 8 0.U5 E + 0 9 0..174E+0 9 HR S (LO ) ( 0.30% ) ( 0.48% ) ( 0.44% ) ( 0.19% ) ( 0.23% ) ( 0.23% ) ( 0.29% ) ( 0.44% ) ANGINA0.319E+0 9 0.492E+0 9 0.456E+0 9 0.204E+0 9 0.248E+0 9 0.246E+0 9 0.305E+0 9 0.448E+0 9 HR S (ME ) ( 0.80% ) ( 1.23% ) ( 1.14% ) ( 0.51% ) ( 0.62% ) ( 0.62% ) ( 0.76% ) ( 1.12% ) ANGINA0.829E+0 9 0.122E+1 0 0.114E+1 0 0.546E+0 9 0.658E+0 9 0.654E+0 9 0.793E+0 9 0.112E+1 0 HR S (HI ) ( 2.08% ) ( 3.06% ) ( 2.85% ) ( 1.37% ) ( 1.65% ) ( 1.64% ) ( 1.99% ) ( 2.80% ) HEAR T 0.236E+0 5 0.252E+0 5 0.394E+0 5 0.787E+0 4 0.134E+0 5 0.134E+0 5 0.236E+0 5 0.394E+0 5 ATTA(LO ) ( 2.34% ) ( 2.50% ) ( 3.91% ) ( 0.78% ) ( 1.33% ) ( 1.33% ) ( 2.34% ) ( 3.91% ) HEAR T 0.472E+0 5 0.504E+0 5 0.787E+0 5 0.157E+0 5 0.268E+0 5 0.268E+0 5 0.472E+0 5 0.787E+0 5 ATTA(ME ) ( 4.69% ) ( 5.00% ) ( 7.81% ) ( 1.56% ) ( 2.66% ) ( 2.667.) ( 4.69% ) ( 7.81% ) HEAR T 0.945E+0 5 0.101E+0 6 0.157E+0 6 0.315E+0 5 0.535E+0 5 0.535E+0 5 0.945E+0 5 0.157E+0 6 ATTA(HI ) ( 9.37% ) (10.00% ) (15.62% ) ( 3.12% ) ( 5.31% ) ( 3.31% ) ( 9,37% ) (15.62% ) HEAR T 0.287E+0 5 0.307E+0 5 0.483E+0 5 0.950E+0 4 0.162E+0 5 0.162E+0 5 0.288E+0 5 0.483E+0 5 FAIAd-O ) ( 4.75% ) ( 5.09% ) ( 8.00% ) ( 1.57% ) ( 2.68% ) ( 2.68% ) ( 4.76% ) ( fl.00%) HEAR T 0.581E+0 5 0.625E+0 5 0.989E+0 5 0.191E+0 5 0.327E+0 5 0.327E+0 5 0.584E+0 5 0.989E+0 5 FATA(ME ) ( 9.61% ) (10.34% ) (16.36% ) ( 3.16% ) ( 5.41% ) ( 5.41% ) ( 9.66% ) (.16.36% ) HEAR T 0.119E+0 6 0.129E+0 6 0.207E+0 6 0.386E+0 5 0.665E+0 5 0.665E+0 5 0.L20E+0 6 0.207E+0 6 FATA(HI ) (19.70% ) (21.37% ) (34.20% ) ( 6.39% ) (1.1.00% ) (1.1.00% ) (19.89% ) (34.20% ) ANGINA0.327E+0 9 0.354E+0 9 0.567E+0 9 0.106E+0 9 0.182E+0 9 0.182E+0 9 0.330E+0 9 0.567E+0 9 AGGRAVA( 3.27% ) ( 3.14% ) ( 6.09% ) ( 1.28% ) ( 2.34% ) ( 1.97% ) ( 2.52% ) ( 6.19% ) COP D 0.136E+0 9 0.131E+0 9 0.253E+0 9 0.533E+0 8 0.972E+0 0 0.8.18E+0 8 0.105E+0 9 0.258E+0 9 AGGRAVA( 3.27% ) ( 3.14% ) ( 6.09% ) ( 1.28% ) ( 2.34% ) ( 1.97% ) ( 2.52% ) ( 6.19% ) PVD 0.356E+0 8 0.387E+0 8 0.619E+0 8 0.116E+0 8 0.199E+0 8 0.199E+0 8 0.3A0E+0 8 0.619E+0 8 AGGRAVA( 3.27% ) ( 3.14% ) ( 6.09% ) ( 1,28% ) ( 2.34% ) ( 1.97% ) ( 2.52% ) < 6.1.9% ) VIGI L 0.125E+0 7 0.S50E+0 7 0.178E+0 8 0. 0 0.301E+0 7 0.125E+0 7 0.425E+0 7 0.251E+0 8 AGGRAVA( 0.00% ) ( 0.01% ) ( 0.03% ) ( 0. 0 % ) ( 0.00% ) ( 0.00% ) ( 0.01% ) ( 0.04% ) PREMA T 0.112 E + 0 8 0.137E+0 8 0.451 E + 0 8 0.421 E + 0 7 0.649 E + 0 7 0.649 E + 0 7 0.137 E + 0 8 0.45.I. E + 0 8 INC. ! DE N( 1.24% ) ( 2.07% ) ( 4.99% ) ( 0.46% ) ( 0.72% ) ( 0.72% ) ( 1.51% ) ( 4.99% )Tabl e 7.2 0 PROBABILITY THA T 1 , 5 , O

R 1 0 PERCEN

T O F SENSITIVE GROU P WIL L SUFFE R ADVERS E HEALT H EFFECT S FOR U.S . URBA NPOPULATION (Usin g specia l exposur e grou p data )

PROB CALCULA

T TOTA

L IMPAC T ANG(1% ) ANG(5% ) ANG(10% ) HEA(1% ) HEA(5% ) HEA(10% ) FAT(1% ) F A1(5% ) FAT(10% ) ••AL Y1 83.84 % 0.73 % 0.00 % 29,51 % 0.00 % 0. 0 % 93.39 % 0.13 % 0.00 % ANAL Y2

84.18 % 0.68 % 0.00 % 36.22 % 0.00 % 0. 0 % 95.54 % 0.27 % 0.00 % ANAL Y3

97.65 % 4.86 % 0.06 % 82.52 % 0.01 % 0. 0 % 99.84 % 6.91 % 0.03 % ANAL Y4

51.80 % 0.06 % 0.00 % 0.01 % 0. 0 % 0. 0 % 4.93 % 0. 0 7. 0. 0 % ANAL Y5

75.75 % 0.31 % 0.00 % 1 .47 % 0. 0 % 0. 0 % 45.38 % 0.00 % 0. 0 % ANALY * 6

68.88 % 0.19 % 0 .00 % 1 . 4 7 % 0. 0 % 0. 0 % 45.38 % 0.00 % 0. 0 % ANAL Y7

77.69 % 0.38 % 0.00 % 29.51 % 0.00 % 0. 0 % 93.49 % 0.14 % 0.00 % ANAL Y8

98.23 % 5.54 % 0.07 % 82.52 % 0.01 % 0. 0 % 99.84 % 6.91 % 0.03 %