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### REVIE WO F TH E NATIONA L AMBIEN T AI RQUALIT YSTANDARD S FO RLEAD :
ASSESSMEN T O F SCIENTIFI C AN D TECHNICA L INFORMATIO N

OAQP S DRAF T STAF F PAPE R

Strategie s an dAi r Standard s Divisio n Offic e o f Ai r Qualit yPlannin g andStandard s U.S . Environmenta l Protectio nAgenc y Researc hTriangl e Park , N.C . 2771 1

April , 198 5P. 3

1 1



### Thi s documen t i s anOAQP S staf f draf t tha t i s bein g circulate dfo r technica l revie wan dcomment . I t ha s no t bee nfull yreviewe dwithi nEP Aan ddoe s no t represen t Agenc ypolicy .P. 4

11 1 TABL E O F CONTENT S Pag e Lis t o f Figure s v Lis t o f Table s vi I . Purpos e 1- 1 I I . Backgroun d II- l II I . Approac hIII- l IV . Lea d Exposure : Multimedi a Consideration s IV- 1 A . Airborn e Lea d IV- 3 B . Lea d i n Soi l I V- 6 C . Lea d i n Dus t I V- 8 D . Lea d i n th e Die t I V-1 0 E . Lea d i n Wate r I V-1 2 V . Estimatin g Lea d Exposur e and Bloo d Lea d Level s V- l A . Integrate d Lea d Uptake/Metaboli c Mode l V- 2 B . Statistica l Relationship s betwee nBloo d Lea d and Airborn e Lea d V-1 0 V I

. Critica l Element s i n th e Revie wo fth e Primar yStandar d

. . . VI- 1 A . Mechanism s o f Toxicit yVI- 1 B . Effect s o f Concer nVI- 5 C . Sensitiv e Populatio nGroup s VI- 6 VII . Factors t o b e Considere d i n Selectin g a Primar yStandar d fo r Lea d VII- 1 A . Averagin g Tim e VII- 1 B . For mo f th e Standar d VII- 7 C . Leve l o f th e Standar d VII- 9 D . Summar yo f Staf f Conclusion s and Recommendation s VII-5 0PJ 5

IV

VIII . Critica l Element s i nth e Revie wo f th e Secondar yStandard . A . Terrestria l Ecosystem s B . Aquati c Ecosystem s , C . Staf f Conclusion s and Recommendation s Appendi xA . Lea d Metabolis m and Physiologica l Measurement . .. . Appendi xB . Estimate s o f Lea d Uptak e Appendi xC . Lea d Uptak e and Bloo d Lea d Concentration s Appendi xD . Healt hEffect s o f Lea d Reference s 

### Pag e VII I VII I VIII * VIII * 

## A-1 B- l C- l D- l - 1

- 1 

## -1 2 -1 4P. 6

V L I S T "OF FIGURE S
Numbe r Titl e Pag e 4- 1 Principa l Pathway s o f Huma nExposur e t o Lea d IV- 2 4- 2 Trend s i nMaximu mQuarterl yLea d Concentratio nfo r

Variou s Monito r Type s IV- 5 5- 1 Summar yo f Relationship s Betwee nLea d Uptak e and

Bloo d Lea d V- 8 C- l Relationshi p Betwee nDail yLea d Uptak e and Bloo d Lea d

i nAdul t Me nC- 3 C- 2 Schemati c Model s o f Lea d Metabolis mi nAdul t Me nC- 5 D- l Lea d Effect s o nHem e Biosynthesi s D- 2P. 7

V I LIS T O F TABLE S
Numbe r Titl e Pag e 4- 1 Typica l Lea d Concentration s i nVariou s Exposur e Medi a ... . IV- 2 4- 2 Frequenc yDistribution s o f Maximu m Quarterl yLea d Concentration s b

yTyp e o f Sit e I V- 5 5- 1 Mode l Balanc e Scheme s fo r Averag e Lea d Intak e and Uptak e

i n Childre n Unde r Alternativ e Ai r Lea d Level s V- 4 5- 2 Summar yo f Experimenta l Lea d Inhalatio n Studie s V-1 1 5- 3 Summar yo f Epidemiologica l Studie s o n Lead-Expose d Childre n . V-1 8 5- 4 Bloo d Lead/Ai r Lea d Slope s i nChildre n fo r Differen t Age s

and Exposure s V-2 0 7- 1 Monthly-to-Quarterl yAverag e Concentratio n Ratio s fo r

Differen t Site s VII- 5 7- 2 Summar yo f Lowes t Observe d Effec t Level s fo r Ke yLead

Induce d Healt hEffect s i nChildre nVII-1 0 7- 3 Summar yo f Lead' s Effect s o n th e Nervou s Syste mVII-1 2 7- 4 Summar yo f Lead' s Effect s o nHem e Biosynthesi s and

Relate d System s i n Childre n VII-1 7 7- 5 Staf f Assessmen t o f Ke yHealt hEffect s o f Lea d VII-2 2 7- 6 Populatio n Mea nBloo d Lea d Level s Require d t o Preven t 99.5 %

o f Childre nfro m

Exceedin g Specifie d Bloo d Lea d Level s . . . VII-2 8 7- 7 Averag e Bloo d Lea d Level s fo r Childre n Unde r Differen t

Ai r Lea d Level s Estimate d Usin g Integrate d Lea d Uptake / Biokineti c Mode l VII-2 9 7- 8 Ai r Lea d Level s Require d t o Protec t 99.5 % o f Childre n fro m

Exceedin g Alternativ e Maximu m Acceptabl e Bloo d Lea d Levels , Accordin g t o Aggregat e Epidemiologica l Model ; GS D fo r Populatio n Assume d t o b e 1 .3 9 VII-3 7 7- 9 Ai r Lea d Level s Require d t o Protec t 99.5 % o f Childre n fro m

Exceedin g Alternativ e Maximu m Acceptabl e Bloo d Lea d Levels , Accordin g t o Aggregat e Epidemiologica l Model ; GS D fo r Populatio n Assume d t o b e 1.3 4 .. . . - VII-3 7 7-1 0 Contribution s fro m Variou s Medi a t o Bloo d Lea d Level s o f U.S . Childre n (CD Disaggregat e Model ) VII-3 9P. 8

VI I Pag e
7-1 1 Maximu mIndividua l Bloo d Lea d Level s fo r 99.5 % o f Childre n

Unde r Differen t Ai r Lea d Levels , Base d o n Mea n Pb B Prediction s fro mC D Disaggregat e Mode l VII-4 1 7-1 2 Summar yo f Estimate d Bloo d Lea d Level s Unde r Differen t Ai r Lea d

Level s Usin g Thre e Modelin g Approache s VII-4 2 7-1 3 Result s o f Logisti c Regressio n Analysi s o f NHANE S I I Dat a . . . VII-4 8 7-1 4 Populatio n Mea n Bloo d Lea d Level s Require d t o Preven t 99.5 %

o f U.S . Childre n fro m Exceedin g Specifie d Bloo d Lea d Level s Estimate d fro mAlternat e Technique s VII-4 8 8- 1 Lead-Induce d Effect s i n Hydroponicall yGrow n Vascula r Plant s . . VI1 1 - 5 8- 2 Experimenta l Evidenc e o f Lead-Induce d Effect s Relatin g t o

Soi l Microbia l Activit yVIII- 8 8- 3 Effect s o f Waterborn e Lea d i n Aquati c Vertebrate s (Fish ) ... . VIII-1 5 B- l Summar yo f Environmenta l Lea d Measurement s fro mVariou s

Location s B- 7 B- 2 Generalize d Relationship s Betwee n Lea d Concentration s i n

Ai r and i n Dust s and Soi l B-1 0 C- 2 Predicte d Equilibrate d Bloo d Lea d Level s Ove r Tim e Amon g

Childre n wit hConstan t Lea d Uptake s C- 9 C- 3 Studie s Relatin g Bloo d Lea d Level s t o Dietar yIntake s C-l l C- 4 Estimate s o f th e Contributio n o f Soi l Lea d t o Bloo d Lea d ... . C-1 2 C- 5 Estimate s o f th e Contributio no f Housedus t t o Bloo d Lea d

i n Childre n C-1 2P. 9

REVIE WO F TH E NATIONA L AMBIEN T AI RQUALIT YSTANDARD S FORLEAD : ASSESSMEN T O F SCIENTIFI C AN D TECHNICA L INFORMATIO N

OAQP S STAF F PAPE R

I . PURPOS E Thi s pape r evaluate s and interpret s th e mos t relevan t scientifi c and technica l informatio nreviewe d i nth e draf t EP Adocumen t "Ai r Qualit y Criteri a fo r Lead " (EPA , 1984 ) i norde r t o bette r specif yth e critica l element s tha t EP Astaf f believe s shoul d b e considere d i nth e possibl e revisio no f th e primar yand secondar yNationa l Ambien t Ai r Qualit yStandard s (NAAQS ) fo r lead . Thi s assessmen t i s intende d t o hel p bridg e th e ga p betwee nth e scientifi c revie wcontaine d i nth e criteri a documen t and th e judgment s require d o f th e Administrato r i nsettin g ambien t standard s fo r lead . A s such , particula r emphasi s i s place d o nidentifyin g thos e conclusion s an d uncertaintie s i nth e availabl e scientifi c literatur e tha t th e staf f believe s shoul d b e considere d i nselectin g th e averagin g times , forms , and level s fo r th e primar yan d secondar ystandards . Whil e th e pape r shoul d b e o f us e t o al l partie s intereste d i nth e standard s review , i t i s writte n fo r thos e decisio nmakers , scientists , and staf f wh o hav e som e familiarit y wit hth e technica l discussion s containe d i nth e criteri a documen t (hereafte r reference d a s "CD") . II . BACKGROUN D Sinc e 197 0 th e Clea nAi r Act , a s amended , ha s provide d authorit y and guidanc e fo r th e listin g o f certai nambien t ai r pollutant s tha t ma y endange r publi c healt ho r welfar e and th e settin g and revisin g o f NAAQ S fo r thos e pollutants . Primar ystandard s mus t b e base d o nhealt heffect sP.1 0

11* . 2 criteri a and provid e a nadequat e margi n o f safet yt o ensur e protectio n o f publi c health . A s severa l recen t judicia l decision s hav e mad e clear , th e economi c and technologica l feasibilit yo f attainin g primar ystandard s ar e no t t o b e considere d i n settin g them , althoug hsuc hfactor s ma yb e considere d t o a degre e i n th e developmen t o f stat e plan s t o implemen t th e standard s (D.C . Cir. , 1980 , 1981) . Furthe r guidanc e provide d i n th e legislativ e histor yo f th e Ac t indicate s tha t th e standard s shoul d b e se t
a t "th e maximu mpermissibl e ambien t ai r leve l . . . whic hwil l protec t th e healt ho f an

y[sensitive ] grou p o f th e population. " Also , margin s o f safet yar e t o b e provide d suc htha t th e standard s wil l affor d " a reasonabl e degre e o f protectio n . . . agains t hazard s whic hresearc hha s no t ye t identified " (Committe e o n Publi c Works , 1974) . I n th e fina l analysis , th e EP AAdministrato r mus t mak e a polic ydecisio n i n settin g th e primar y standard , base d o nhi s judgmen t regardin g th e implication s o f al l th e healt heffect s evidenc e and o n th e requiremen t tha t a n adequat e margi n o f safet yb e provided . Secondar yambien t ai r qualit ystandard s mus t b e adequat e t o protec t th e publi c welfar e fro manyknown o r anticipate d advers e effect s associate d wit hth e presenc e o f a liste d ambien t ai r pollutant . Welfar e effects , whic har e define d i nsectio n302(h ) o f th e Act , includ e effect s o n vegetation , visibility , water , crops , man-mad e materials , animals , economi c value s and persona l comfor t and well-being . I nspecifyin g a leve l o r level s fo r secondar ystandard s th e Administrato r mus t determin e a t whic hpoin t th e effect s becom e "adverse " and bas e hi s judgmen t o nth e welfar e effect s criteria . Th e curren t primar ystandar d fo r lea d (t o protec t publi c health ) i s 1. 5 microgram s pe r cubi c mete r (ug/m^) , maximu marithmeti c mea nP.1 1

III- l

average d ove r a calendar quarter . Th e curren t secondar ystandar d fo r lea d (t o protec t publi c welfare ) i s identica l t o th e primar ystandard . Fo r bot hprimar yand secondar ystandards , lea d and it s compound s ar e measure d a s elementa l lea d and collecte d usin g a hig hvolum e ai r sampler . I nadditio nt o th e lea d NAAQS , severa l othe r federa l regulation s hav e bee nadopte d i norde r t o contro l huma nexposure s t o lead . Thes e includ e EPA' s schedul e fo r th e phase d reductio no f th e allowabl e lea d conten t i n gasolin e and th e nationa l primar ydrinkin g wate r standar d fo r lea d (5 0 pg / liter) , a s wel l a s th e Departmen t o f Housin g and Urba nDevelopment' s goal s t o eliminat e lead-base d pain t hazard s i nfederally-funde d housing , th e Foo d an d Dru g Administration' s regulation s o nth e lea d conten t o f food s and cerami c products , th e Consume r Produc t Safet yCommission' s limi t o nlea d conten t i npaints , toys , and furniture , and th e Occupationa l Safet yan d Healt hAdministration' s standard s fo r occupationa l exposur e t o lead . Inaddition , th e Center s fo r Diseas e Contro l hav e establishe d criteri a fo r healt hclassificatio no f childre nscreene d b ylea d poisonin g preventio nprograms . III . APPROAC H Th e approac huse d i nthi s pape r i s t o asses s and integrat e informatio n derive d fro mth e criteri a revie wi nth e contex t o f thos e critica l ele

ment s tha t th e staf f believe s shoul d b e considere d i nth e revie wo f th e primar yand secondar ystandards . Particula r attentio ni s draw nt o thos e judgment s tha t mus t b e base d o nth e carefu l interpretatio no f incomplet e o r uncertai nevidence . I nsuc hinstances , th e pape r state s th e staff' s evaluatio no f th e evidenc e a s i t relate s t o a specifi c judgment , set s fort happropriat e alternative s tha t shoul d b e considered , and recommend s a cours e o f action .P.1 2

III- 2
Th e principa l focu s o f thi s pape r i s o nth e effect s o f inorgani c lea d eithe r airborn e o r deposite d fro mth e ai r ont o dusts , soils , vegetation , food , and water . Th e impac t tha t lea d fro mnon-atmospheri c sources , suc h
a s pain t and solder , ha s o n huma nexposur e i s als o considered . Th e effect s o f organi c lea d vapor s whic har e no t commonl yfoun d i n th e atmospher e (se e Sectio n I V.A ) wil l no t b e addressed . Sectio n I V

present s relevan t feature s o f huma n exposur e t o atmospheri c an d non-atmospheri c source s o f lea d throug hvariou s pathways . Sectio n V present s differen t approache s t o estimat e th e impac t o f alternativ e ai r lea d level s o n lea d bodyburden s a s indicate d b ybloo d lea d levels . Sectio n V I addresse s othe r essentia l element s wit hregar d t o th e primar ystandards ; thes e includ e th e following : 1 ) identificatio n o f possibl e mechanism s o f toxicity ; 2 ) descriptio n o f healt heffect s and thei r relatio n t o exposur e levels ; and 3 ) identificatio no f th e mos t sensitiv e populatio n groups ; Drawin g fro mth e analyse s i nSection s IV , V , and V I o f th e criteri a documen t information , and th e associate d appendices , Sectio nVI I identifie s and assesse s th e factor s th e staf f believe s shoul d b e considere d i n selectin g a n averagin g time , form , and leve l o f th e primar ystandard . Selectin g a n appropriat e standar d leve l include s a determinatio n o f a n acceptabl e bloo d lea d leve l and th e impac t a give nai r standar d woul d hav e o nth e distributio n o f bloo d lea d level s i n th e populatio n o f concern . Preliminar ystaf f conclusion s regardin g alternativ e polic yoption s i n eac ho f thes e area s ar e als o presented . Sectio n VII I contain s a nexaminatio no f informatio ni n th e criteri a documen t th e staf f believe s i s mos t relevan t wit hrespec t t o th e secondar y standard . Thi s discussio n includes :P.1 3

III- 3 1 ) identificatio n o f th e level s a t whic hlead-induce d change s i n terrestria l an

d aquati c ecosystem s hav e bee n demonstrated ; 2 ) assessmen t o f th e availabl e dat a bas e (laborator yan d fiel d studies ) t o identif yquantitativ e relationship s necessar yfo r th e predictio n o f environmenta l impact ; and 3 ) preliminar ystaf f recommendation s concernin g a secondar ystandard .P.1 4

IV . LEAD EXPOSURE : MULTIMEDI ACONSIDERATION S Inorde r t o asses s th e risk s associate d wit halternat e lea d NAAQS , i t i s necessar yt o understan d th e influenc e exerte d b yatmospheri c lea d o n th e tota l lea d exposur e o f th e population(s ) o f concer nthroug hth e variou s exposur e pathways . Relevan t dat a o nthes e pathway s and th e relationship s betwee nai r lea d and lea d i nothe r medi a ar e summarize d i nthi s section . Sectio nV

present s methodologie s t o estimat e bloo d lea d level s associate d wit halternativ e ai r lea d levels . Th e source s and pathway s o f huma nlea d exposur e ar e diagramme d i n Figur e 4- 1 and typica l level s o f lea d i ndifferen t medi a t o whic hU.S . population s ar e expose d ar e presente d i nTabl e 4-1 . Betwee n85-90 % o f airborn e lea d i nth e U.S . originate s fro mgasolin e combustio nwit hth e remainde r fro mstationar yindustria l processe s suc ha s primar yand secondar y lea d smelting , batter yplants , lea d alky l production , iro nan d stee l produc

tion , or e pulverizing , coppe r smelting , and combustio no f oil , coal , and wast e oil . Atmospheri c emission s ca ninfluenc e huma nexposur e throug h direc t inhalatio no f lead-containin g particle s and throug hingestio no f lea d whic hdeposit s ont o soil , dusts , vegetation , and othe r environmenta l surfaces . Thi s depositio nca noccu r b yeithe r o r bot ho f tw o mechanisms : 1 ) continuou s dr ydepositio ndu e t o variou s mechanism s whic hma yinclud e gravitationa l settlin g o r wind-relate d deposition ; and 2 ) episodi c we t depostio ndu e t o eithe r washou t o f coars e mod e particle s (>2. 5 micrometer s i ndiameter ) whic har e foun d mainl ynea r emissio nsources , o r th e "rainout " (precipitatio nscavenging ) o f smalle r particle s whic har e mor e widel y dispersed . Huma nexposur e t o lea d ca nals o b e trace d t o lea d i npain t pigment s an d solde r i ncanne d food s and plumbing .P.1 5 

### IV- 2

SURFAC E AN O GROUN D WATE R

MA N Figur e 4-1 . Principa l pathway s o f huma n exposur e t o lead . Heavyarrow s ar e thos e pathway s discusse d i n greates t detail . Fro mCD , Figur e 7-1 .

Tabl e 4-1 . Typica l Lea dConcentration s i nVariou s Exposur e Medi a Mediu m Ambien t Ai r (ug/m3) b

I ndoo r A

i r (ug/m3) c

Soi l (ppm )

Stree t Ous t (ppm) d

Hous e Dus t (ppm) d
Typica l Food s (ppm ) Wate r (pg/ 1 ) Paint e Rura l Are a 0.0 1 - 0. 3 0.00 3 - 0. 2

5 - 3 0

8 0 - 13 0 (90 ) 5 0 - 50 0 (300 ) 0.00 2 - 0.9 8 < 1 - 18 0 pg/ 1

<1 - > 5 mg/cm 2 Urba nAre a 0.0 3 - 4. 4 0.0 1 - 0. 4

3 0 - 450 0

10 0 - 5,00 0 (1500 ) 5 0 - 3,00 0 (1000 )
Sam e Same
Same Nea r Poin t Source(s) a

0. 2 - 10. 2 0.0 7 - 3. 1

15 0 - 15,00 0

(25,000 )
7 0 - 100,00 0 (25,000 )
Same Same
Same Reference s Tyler , 1984 ; Yarn , 198 4 Yocum , 1982 ; Cohe nan d Cohen , 1980 ; Rabinowit z e t al. , 1984 b CD , Tabl e 7-11 ; Mielk e e t a l . ; 1983 ; Se e Table s C- l andC- 2 Nriagu , 1978 ; CD , Tabl e 7-2 6 U.S . EPA , 1977 ; Landriga ne t al. , 197 5 Angl e andMclntir e ( 1 _>7y ) CD , Tabl e 7D- 1 Sharret t e t al. , 1982 ; EPA , 1985 a Billic kandGray , 197 8

a Withi n2- 5 k

m o f source s includin gprimary an dsecondar y

leadsmelters , batter y plants . ^Represent s quarterl y average s monitore dbetwee nJul y 198 2 an

dJul y 1984 . c Rang e o f indoor/outdoo r ratio s use d(0. 3 - 0.8 ) fro m Yocum , 198 2 excep t nea r poin t source s wher e larg e particle s pre dominat e an

dinfiltratio nint o home s i s low , rati o appear s t o be close r t o 0. 3 (Cohe nan dCohen , 1980) . ^Value s i nparenthese s represen t estimate s provide di nC D(Table s 7-2 4 and7-26 ) a s typica l averages .
e Sinc e ther e may

b e severa l layer s o f lead-base dpain t o na give nsurface , absolut e concentratio no f leadi s les s usefu l tha nmg/cm 2 . Survey s b y HU Di nPittsburg hshowe dtha t mor e tha n70 % o f pre-194 0 dwellin gunit s and20 % o f post 196 0 unit s hada t leas t on e surfac e wit hmor e tha n1. 5 mg/cm 2 leadpain t (NAS , 1980) .P.1 6

IV- 3 A . Airborn e Lea d 1 . Physical , Chemica l and Spatia l Characteristic s I n general , abou t 50 % o f automotiv e lea d emission s deposit s withi n a fe whundre d meter s o f majo r roadway s (Daine s e t al. , 1970 ; Huntzicke r e t al. , 1975 ; Ingall s and Garbe , 1982 ) whil e th e remainin g particle s ar e smal l enoug ht o remai nairborn e and trave l hundred s o r thousand s o f kilometers . Thi s likel yaccount s fo r th e surfac e contaminatio n o f pola r glaciers , oceans , and othe r remot e location s aroun d th e glob e (Murozom i e t al. , 1969 ; Duc e e t al. , 1975 ; Davidso ne t al. , 1981b,c , 1982 ; Settl e and Patterson , 1982) . I n general , U.S . urba nand rura l airborn e lea d particle s hav e a mas s media n aerodynami c diameter * (MMAD ) consistentl ybetwee n 0. 3 and 0. 7 micrometer s (pm ) wit hmos t o f th e mas s associate d wit hsubmicro n particles , althoug ha distinc t pea k i s see ni n th e uppe r end o f manyo f th e particl e siz e distribution s betwee n 5 and 1 0 p m (Davidso n an

d Osborn , 1984) . Inorgani c lea d i s emitte d fro m automobile s a s lea d halides , hydroxides , an d oxide s an

d react s wit hatmospheri c ammoni a and aci d sulfate s t o for m principall ylea d sulfate (e.g. , [NH ^ SO^'PbSO^ ) wit hmino r amount s o f lea d carbonate s and halide s remainin g (Habibi , 1970 ; Te r Haa r and Bayard , 1971 ; Dzuba yand Stevens , 1973 ; Biggin s and Harrison , 1978 , 1979) . Smal l amount s o f lea d additive s use d i n gasolin e (tetraethyl

- and tetramethyl-lead ) ma y escap e t o th e atmospher e b yevaporatio n fro mfue l system s o r storage facilities . Relativel ylo wconcentration s o f thes e organi c lea d compound s hav e bee n typicall yfound i n atmospheri c sample s ( 1 - 6 % o f tota l lead ) excep t i n specia l situation s suc ha s gasolin e station s o r garage s (Skogerboe , 1975 ; Harriso n e t al. , 1979) . Becaus e thes e organi c lea d compound s decompos e b y

*MMAD i s use d a s an indicato r o f particl e siz e o f a lognormall ydistribute d aeroso l suc htha t hal f th e mas s lie s o n eithe r sid e o f th e MMAD .P.1 7

IV- 4 photoreactio n (Huntzicke r e t al. , 1975 ) and ar e readil yadsorbe d ont o atmospheri c particle s (Edward s e t al. , 1975) , thei r presenc e i n th e atmospher e i s transitory . Therefore , an yhealt hhazard s associate d wit h organi c lea d exposur e ar e mos t likel yt o occu r i n an occupationa l settin g and wil l no t b e assesse d here . I n contras t t o automobil e exhaust , atmospheri c lea d emission s fro m industria l plant s processin g lead and it s product s contribut e littl e t o th e overal l pollutio n load acros s large , regiona l area s althoug hfallou t fro m thes e source s ca n b e sever e o n a loca l scale . Th e hig hconcentratio n level s whic har e found aroun d lead smelter s i n particula r resul t mainl yfro m fugitiv e emission s predominatel ymad e up o f larg e (> 7 pm ) lea d particle s resultin g fro mmaterial s handling , furnac e upsets , and furnac e chargin g and tappin g operation s (Landriga ne t al. , 1975 ; Jennet t e t al. , 1977 ; GCA , 1984) . Beyon d th e immediat e are a (0.25- 1 km ) o f lea d stationar y sources , proces s emission s fro m stacks , predominatel ya s lea d sulfate s and oxide s wit ha siz e rang e betwee n 2 and 1 0 pm , becom e th e majo r sourc e o f lea d i n soil s and ai r nea r thes e source s (Dor n e t al. , 1976 ; Roel s e t al. , 1980 ; Davidso n and Osborn , 1984) . 2 . Ambien t Concentration s A s indicate d i n th e C D (Sectio n 7.2.1) , lea d level s i n urba n area s and nea r poin t source s hav e bee nmarkedl yreduce d sinc e 197 7 b yth e us e o f unleade d gasolin e i nne wcar s equippe d wit hcatalyti c converters , th e lead-in-gasolin e phasedow n program , and steadyreduction s i n emission s fro mal l type s o f industria l and commercia l source s i n complianc e wit hth e 197 8 lea d NAAQS . Recen t (1980-1983 ) ai r qualit ydat a fo r 41 4 stationar ysourc e sites , micro-scal e roadsid e sites , middl e scal e roadsid e sites , neighborhoo d scal e roadsid e sites , and othe r non-classifie d site s ar e summarize d i n Tabl e 4- 2 (Battye , 1985) . Th e monitorin g site s locate d nea r stationar ysource sP.1 8

IV- 5 Tabl e 4-2 . FREQUENC YDISTRIBUTION S O F MAXIMU M QUARTERL YLEADCONCENTRATION S BYTYP E O F SITE *

Sit e type/time frame 198 0 through198 3 Al l monitors 0 Stationar y

sourc e Microscal e roadside'* ' Middl e scal e Neighborhoo dscal e 198 3 onl y Al l monitors 0 Statlonar y

sourc e Microscal e roads1de d Middl e scal e Neighborhoo dscal e Percen t <0. 5

69 62 17 39 6 1

7 1 5 3 1 6 53 72 o f sit e 0.5-1. 0

22 1 6 40 42 3 2

1 9 24 47 3 3 28 year s in 1.0-1 .
5 8 27 18 5

5 9 3 2 1 3 0 concentratio n 5 1.5-2. 0

2 3 13 0 0

1 2 5 0 0 ranges 0 >2. 0

2 1 1 3 0 2

3 1 1 0 0 0 Mea n

0.5 3 0.9 5 0.9 9 0.6 8 0.5 1

0.5 1 0.8 8 0.8 3 0.6 0 0.4 0 Tota l

site year s

118 9 159 30 33 6 2

360 4 5 19 1 5 2 9 Tota l numbe r o f site s

414 5 6 18 1 5 29

360 4 5 1 9 1 5 29

a Dat a ar e fro

m th e SAROADsystem

an drepresen t the number s o f site-year s fo r whic hthe maximum quarterl y

concentration s fal l withi nth e designate dconcentratio nranges . T o be included , a site-yea r mus t have fou r vali dquarter s o f data . •""Concentratio

nrange s ar e 1 nunit s o f ug/m3 . •"•Includes site s previousl y classifie dint ocategorie s (e.g. , urban ) tha t do no t mee t an y o f th e curren t definitions . •"•Microscal e site s ar e withi n5-1 5 meter s fro m a majo r roadway

and2- 7 meter s abov e th e ground . Source : Battye , 198 4

P _* >

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- — i ri* ..'ARTE

O *•*= :

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## § 1 . 9 1 . 8 1 . 7 1 . 6 1 . 5 1 .4 - 1 . 3 1 . 2 1 , 1 1 , 0 O. 9 0. 8 0. 7 0. 6 0. 5 0.4 - 0. 5 0. 2 - 0, 1 - MICROSCAL E \ + - \ STATIONARY"SOURCE S

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### 198 0 198 1 198 2 

# T5i T Yea r Figur e 4-2

. Trend s i n maximu m quarterl ylea d concentratio n fo r

variou s monito rtypes
. Source : Battye,198 4P.1 9

IV- 6

and majo r roadway s (i.e. , microscale ) reporte d th e majorit yo f concentration s ove r 1. 5 ug/m^ . Onl yon e population-oriente d o r neighborhoo d sit e ha d a quarterl yaverag e greate r tha n1. 5 ug/m*- * betwee n 198 0 an d 1983 , wherea s 14 % an d 16 % o f quarterl yaverage s i n source-oriente d and microscal e site-years , respectively , exceede d thi s value . Trend s i n maximu m

quarterl yaverage s betwee n 198 0 and 198 3 ar e illustrate d i n Figur e 4-2 . Becaus e o f recen t change s i n lea d monito r sitin g guidelines , th e lea d monito r networ k currentl yi s bein g expande d and changed . I n orde r t o avoi d biase s relatin g t o change s i n th e monitorin g network , th e trend s analysi s include d onl ysite s wher e vali d dat a wer e availabl e fo r thre e o f th e fou r year s studie d (Battye , 1985a) . I t shoul d b e noted , therefore , tha t thes e trend s data , wit hth e exceptio n o f thos e fo r "all " monitorin g site s whic h includ e currentl yunclassifie d site-types , ar e base d o n a limite d numbe r o f availabl e monitorin g site s tha t remaine d i n servic e sinc e 198 0 (e.g. , 2 7 stationar ysourc e sites , 9 neighborhoo d scal e sites) . Despit e th e ne w sitin g guidelines implemente d i n 198 2 tha t adde d site s close r t o traffi c emissions , microscal e reading s hav e bee n declining , correspondin g t o th e phasedow n o f th e lea d conten t i ngasolin e and reduction s i n leade d gasolin e usag e du e t o th e gradua l phase-ou t o f olde r lead-burnin g cars . Similarly , annua l and maximu mquarterl yaverag e lea d level s nea r poin t source s hav e als o decrease d sinc e 1980 , partl ydu e t o increase d control s b ylead-emittin g source s i n complianc e wit hstat e implementatio n plan s a s wel l a s t o decrease d industria l productio n a t lead-emittin g facilitie s (Silvasi , 1985) . B . Lea d i n Soi l Th e natura l occurrenc e o f lea d i n th e earth' s crus t average s 5-5 0 pg lead/ g soi l [on e ug/ g i s equivalen t t o on e par t pe r millio n o r 1 ppm ] lea d i n variou s soil s (Shacklett e e t al. , 1971 ; McKeagu e and Wolynetz , 1980) . Muc ho f th e lea d i nth e atmospher e deposit s o n terrestria l surface sP.2 0

I V - 7 wher e i t i s retaine d i norgani c complexe s nea r th e soi l surfac e (CD , p . 7-28) . Th e abilit yo f soi l t o immobiliz e lea d largel ydepend s o nsoi l pH
and organi c conten t (i.e. , fulvi c and humi c substances) . Man yU.S . soil s appea r t o hav e a larg e capacit yt o bin d lea d wit honl ya smal l fractio n dissolve d i nsoi l moistur e wher e i t i s availabl e fo r plan t uptak e (se e Sectio nVIII) . Th e environmenta l impac t o f lea d o nth e biot a o f terrestria l
and aquati c ecosystem s i s discusse d i nSectio nVIII . Th e uppe r laye r o f roadsid e soil s ma ycontai natmospheri c lea d fro m 3 0 t o 200 0 pp m

i nexces s o f natura l level s withi n2 5 meter s o f th e roadbe d beyon d whic hconcentration s declin e abruptl yi nrelatio nt o traffi c densit y and vehicl e spee d (Pag e and Ganje , 1970 ; Quarle s e t al , 1974 ; Wheele r an d Rolfe , 1979 ; Pierso nand Brachaczek , 1976) . Incontrast , soi l lea d concentration s aroun d variou s lea d poin t source s generall ydecreas e exponentiall ywithi n a 3-1 0 k

m radiu s fro m100-60,00 0 ppmdow nt o backgroun d level s (CD , Appendi x 7-C) . However , elevate d soi l lea d level s hav e eve nbee nfoun d a t distance s exceedin g 20-2 5 k

mfro msom e smelter s (Wixson , 1978) . Limite d dat a indicat e tha t lea d i nsoi l nea r primar yan d secondar ylea d smelter s occur s a s lea d oxides , sulfide , sulfate , and elementa l lea d (Olso nand Skogerboe , 1975 ; Corri nand Natusch , 1977) . Urba nsoil s ar e contaminate d b ylea d fro ma combinatio no f automotiv e an d poin t sourc e depositio na s wel l a s fro mpain t chip s fro mindoo r and outdoo r surfaces . Elevate d soi l concentration s (a s hig ha s 200 0 ppm ) hav e bee nfoun d withi n1 0 fee t o f woo d fram e house s painte d wit hlead-base d pain t (Te r Haa r and Aronow , 1974) . Accumulation s o f lea d i nsoil s (and dusts ) aroun d bric k o r ston e structure s hav e als o bee nfound , and ca nb e partiall yattribute d t o washof f lea d collecte d o nroofs , ledges , and exterio r wall s (Wheele r and Rolfe , 1979) . Vegetabl e garde nsoi l sample s collecte dP.2 1

IV- 8 i n a 30-mil e radiu s o f downtow n Baltimor e ha d lea d level s up t o 10,90 0 pp m wit ha media n valu e o f 10 0 ppm(Mielk e e t al. , 1983) . Muc ho f thi s lea d
wa s attribute d t o automotiv e exhaus t and industria l emission s becaus e o f th e nea r absenc e o f lea d painte d house s and th e clustere d patter n o f lea d level s aroun d downtown . Soi l lea d concentration s i n a sampl e o f cit ypark s hav e als o bee nreporte d t o b e quit e high , rangin g fro m20 0 t o 330 0 ppm (Cho we t al. , 1975 ; Zimdah l an d Hassett , 1977) . Th e contributio n tha t lea d i nsoi l ca n mak e t o tota l lea d exposur e unde r alternativ e ai r lea d level s i s addresse d i nth e modelin g approache s presente d i n Sectio nV . C . Lea d i nDus t Dus t i s a norma l componen t o f th e hom e (i.e. , "hous e dust" ) a s wel l a s th e outdoo r environmen t wher e i t ca n b e found o n sidewalks , playgrounds , driveways , and othe r har d surfaces . Anthropogeni c material s deposite d o n thes e outdoo r surface s wil l b e referre d t o a s "stree t dusts" . I n addition , th e ver yto p laye r o f soil s (includin g lea f litter ) t o whic hpeople , particlarl y children , com e i n direc t contact , ar e considere d i n th e criteri a documen t t o b e "soi l dusts" . Bot hhous e dus t and street/soi l dus t contai n lea d fro matmospheri c deposition , "natural " soil , and pain t chips . A s wit hroadsid e soil , significan t correlation s betwee n lea d concentration s i nstree t dus t and th e proximit y and densit yo f traffi c hav e bee nfoun d (Rolf e e t al. , 1977 ; La u an d Wong , 1982) . A s summarize d b yNriag u (1978) , stree t dust s fro mdifferen t U.S . citie s containe d betwee n 30 0 and 18,00 0 ppmlead . Asurve yo f stree t dust s i n 7 7 midwester n citie s showe d a naverag e lea d conten t o f 1,63 6 ppmi n residentia l neighborhood s an d 2,41 3 pp m i n commercia l and industria l area s (NAS , 1980) . Limite d chemica l analyse s o f roadsid e soil s and dust s fro mP.2 2

IV- 9 U.S . citie s found lea d predominatel ya s sulfate , alon g wit hmino r amount s o f oxid e and halid e salt s (Olso nand Skogerboe , 1975 ; Corri nand Natusch , 1977) . Gutte r debri s i n Dearborn , Michiga n containe d mostl ylarg e lead particle s rangin g betwee n4 0 and 100 0 pm(Pierso n and Brachaczek , 1976) . Airborn e lea d deposite d o n streets , sidewalk s and driveway s i s subjec t t o furthe r distributio nb ywin d and water . Windblow n particle s associate d wit hdus t ar e ap t t o b e redeposite d withi n th e urba n environmen t becaus e o f th e comple xwin d current s cause d b ybuilding s and stree t canyons . Ther e i s somewha t conflictin g evidenc e o n th e persistenc e o f lea d i n stree t dust . Laxe n and Harriso n (1977 ) foun d tha t onl ya ligh t rainfal l ( 2 t o 3 mm ) i s sufficien t t o remov e 9 0 percen t o f th e lea d fro mth e roa d surface , mainl y t o surroundin g soi l and t o waterways . Asurve yo f rainwashe d area s i n th e U.K . an d Ne wZealan d concluded , however , tha t th e acidit yo f rai n (pH betwee n 4 and 5 ) wa s insufficien t t o completel ydissolv e and transpor t lea d particles , and tha t residu e nea r street s pos e a healt hhazar d t o childre n wh o ar e pron e t o inges t stree t dust s (Da ye t al. , 1979) . Th e rat e o f remova l o f lea d fro mdust s i s als o dependen t o n th e frequenc yand efficienc yo f stree t cleanin g operations . In th e absenc e o f empirica l dat a regardin g thi s mechanism , i t i. s reasonabl e t o assum e tha t lea d concentration s i n urba n street , curb , and sidewal k dus t wil l ris e betwee n precipitatio n and stree t cleanin g episodes , and dro p thereafter . Lea d level s i nhous e dus t ca nb e expecte d t o varyconsiderabl ydependin g o n hous e cleanin g practices , th e presenc e and conditio n o f lead-base d paint , th e presenc e o f cigarett e smoke , th e amoun t o f dus t and soi l blow n int o o r carrie d int o th e hous e o n clothin g and shoes , (especiall yo n thos e occupationall yexpose d t o lead) , indoo r source s o f lea d othe r tha n pain t (e.g. , soldering) , th e permeabilit yo f th e hom e t o outdoo r ai r (whic hca nP.2 3

IVrl O

varywit hseason) , and th e outdoo r concentration s o f ai r lead . Survey s o f
a divers e se t o f home s indicat e a wid e rang e o f hous e dus t lea d level s betwee n 1 8 and 16,00 0 pp m(EPA , 1977 ; Harrison , 1979 ; Angl e an d Mclntire , 1979 )
and a s hig ha s 100,00 0 ppmwithi n2 k mo f smelte r (Landriga n e t al. , 1975) . I t i s wel l establishe d tha t childre n wh o pla yi ndus t an d soil , especiall y i n urba n area s and o n site s pollute d b ylong-ter mfallou t fro mindustria l emissions , inges t lea d i nthes e medi a throug hnorma l mouthin g behavior . Significan t correlation s hav e bee n found betwee n bloo d lea d level s and lea d i n soil , househol d and stree t dusts , and o n children's hand s (Lepo we t al. , 1975 ; Sayr e e t al. , 1974 ; Angl e and Mclntire , 1982 ; Qua he t al. , 1982 ; Brunekree f e t al. , 1983) . I n orde r t o asses s th e impac t o f atmospheri c lea d o n children' s tota l exposure , i t i s necessar yt o estimat e th e contribution s o f differen t ai r lea d level s t o outdoo r and indoo r soil/dus t lea d level s a s wel l a s th e amoun t o f dir t a chil d mayingest , bot hinadvertantl yand deliberately . Thes e issue s are

addresse d i n th e modelin g approache s presente d i n Sectio n V . D . Lea d i n th e Die t Th e ingestio n o f foo d appear s t o b e a majo r componen t o f mos t individuals ' tota l lea d uptake , althoug hth e exac t amoun t i s a functio no f th e siz e and typ e o f diet . Th e occurrenc e o f lea d i nth e die t mayb e a resul t o f a ) natura l
source s o f lead ; b ) depositio no f airborn e lea d particle s ont o vegetation , soils , and water ; and c ) th e harvesting , processing , transportation , packaging , preparation , and storag e o f foo d durin g whic hlea d ca n b e introduce d a t ever y stag e eithe r b

yatmospheri c depositio n o r throug hmetalli c contamination , particularl yfro m

solder . A s woul d b e expecte d fro mth e difference s i n th e handlin g o f variou sP.2 4

IV-1 1 foods , lea d content s var yconsiderably , rangin g fro m0.00 2 t o 0.9 8 pp m(CD , Tabl e 7D-1) . Lea d i n unprocesse d food s suc ha s fres hfruit s and vegetable s come s fro matmospheri c depositio n o n vegetatio n surface s an d uptak e fro m soi l throug hroot s (Schuc k and Locke , 1970 ; Mott o e t al. , 1970) . Th e potentia l fo r lea d uptak e throug hth e root s i s determine d primaril yb y th e soil' s organi c conten t and pH ; a t norma l soi l pH level s (4. 5 t o 8 ) an d wit hsufficien t organi c content , lea d i s boun d t o organi c complexe s i n preferenc e t o othe r metal s tha t ar e plan t nutrients , e.g. , zinc , calcium , manganese , magnesiu m(CD , p . 6-32) . Wit hchange s i n soi l propertie s suc h
a s reduce d organi c conten t and lowe r pH , a greate r fractio n o f tota l soi l lea d ma ybecom e mobilize d and it s potentia l fo r uptak e b yplan t root s enhance d (CD , p . 6-38) . Severa l studie s hav e showntha t lea d o nth e surfac e o f leave s (an d bark ) i s closel yrelate d t o traffi c densit yand distanc e fro mth e highway , (o r mor e specificall yt o ai r lea d concentratio n and particl e siz e distribu

tion) , and tha t no t al l o f th e lea d particle s deposite d o n plan t surface s ca n b e washe d of f (Mott o e t al. , 1970 ; Schuc k and Locke , 1970 ; Lagerwerf f
e t al. , 1973 ; Pilegaard , 1978 ; Gart yand Fuchs , 1982 ; Tanak a and Ichikuni , 1982) . Leaf yabovegroun d vegetable s whos e edibl e portion s ar e expose d t o atmospheri c lea d (e.g. , spinach , lettuce ) ten d t o hav e th e highes t lea d level s (Spittle r and Feder , 1978 ) whil e fo r manycrops , th e edibl e interna l portion s (e.g. , cor n an d whea t kernels ) hav e considerabl yles s lead tha n th e oute r expose d part s suc ha s stems , leaves , and husk s (Te r Haar , 1970) . Belowgroun d crop s suc ha s potatoe s and onion s ar e onl ypartiall yprotecte d fro matmospheri c depositio n sinc e thei r root s accumulat e lea d fro mth e soi l (CD , p . 7-34) . Mea t product s tha t ente r ou r foo d chai n ma yals o b e affecte d b yatmospheri c lea d vi a th e depositio nand accumulatio n o f lea d o n forag eP.2 5

IV-1 2 subsequentl yeate nb ylivestoc k (Graha man d Kalman , 1974 ; Crump an d Barlow , 1982) . Recen t studie s o nlea d conten t o f variou s food s expose d t o and protecte d fro matmospheri c lea d an d lea d solder , and o ndietar ypattern s i nth e U.S. , provid e informatio no ndietar ylea d intake s fo r differen t population s (Wolni k e t al. , 1983 ; Nationa l Foo d Processor s Associations , 1982 ; Pennington , 1983 ; U.S . FDA , 1983 , 1984) . Base d o nthes e data , th e C D ha s apportione d lea d i n"typical " chil d and adul t diets ' t o fou r sources : natura l lead , atmospheri c lead , lea d i nsolder , and lea d whos e origi ncanno t b e determine d
a t present . Thes e estimate s and thei r associate d uncertaintie s ar e discusse d i nterm s o f thei r applicatio nt o estimatin g lea d exposur e discusse d i n i nSectio nV . E . Lea d i nWate r Lea d i s a natural , usuall yminor , constituen t o f surfac e and groun d waters . Atmospheri c lea d ca nente r th e aquati c syste mthroug hdirec t fallou t o r i nsurfac e runof f a s suspende d particle s o r adsorbe d t o soi l particles . Unde r mos t condition s (pH , temperature , alkalinity) , lea d form s insolubl e salt s and precipitate s t o sediments , whic hprobabl yaccount s fo r th e lo wlea d conten t o f U.S . sourc e wate r supplies ; th e averag e concentratio n rangin g betwee n3 and 4 microgram s P bpe r lite r wate r (pg/1) . I ncontrast , lea d level s i nhousehol d drinkin g wate r ca nb e muc h highe r du e t o plumbin g corrosio nand subsequen t leachin g o f lead , rangin g betwee n1 0 and 3 0 pg/ 1 o naverage . Th e combinatio no f corrosiv e (i.e. , sof t o r acidic ) wate r and lea d pipe s o r soldere d joint s i ndistributio n system s creat e localize d zone s o f hig hlea d concentration s (Wort he t al. , 1981 ) a s hig ha s 38 0 pg/1 . Ingeneral , level s ar e highes t i nsample s o f ho t and/o r stagnan t "firs t draw " water .P.2 6

IV-1 3 Drinkin g wate r i s a majo r sourc e o f lea d exposur e amon g manyinfant s whil e the yar e dependen t o n babyformula s durin g thei r firs t year . EPA' s Offic e o f Drinkin g Wate r i s currentl yreviewin g th e degre e o f protectio n afforde d b

yth e existin g lea d standar d o f 5 0 pg/ 1 agains t healt hrisk s i n thi s sensitiv e population . Th e CD' s estimate s o f th e contribution s tha t atmospheri c and solde r lea d mak e t o youn g children' s tota l lea d exposur e vi a drinkin g wate r ar e addresse d i nth e modelin g approache s presente d i nSectio n V .P.2 7

V . ESTIMATIN GLEA D EXPOSURE S AN D BLOO D LEAD LEVEL S

I norde r t o asses s th e healt hrisk s associate d wit halternativ e ai r lea d levels , i t i s necessar yt o estimat e th e bloo d lea d (PbB ) level s tha t woul d b e distribute d i nth e population(s ) o f concer nunde r variou s ai r lea d concentrations . [Th e amoun t o f lea d measure d i nwhol e bloo d i s aninde xo f lea d absorptio nand i s generall yuse d a s th e dosage , o r inde xo f exposure , i ninvestigatin g th e variou s huma nhealt heffect s associate d wit hlead. ] Thre e approache s ar e examine d tha t ca nb e use d t o estimat e o r predic t th e impac t o f inhale d and ingeste d lea d aerosol s and compound s o nth e body burde no f lea d a s indexe d b ybloo d lead . Thes e approache s ar e presente d fo r consideratio ni npossibl yusin g one , two , o r al l thre e (wit han ynecessar y modification s usin g improve d data ) i nassessin g th e protectio nafforde d b y alternativ e lea d NAAQS . Th e firs t approac hi s t o us e measure d rate s o f "uptake " o f lea d throug h differen t pathway s (e.g. , inhalation , ingestion ) fro mexperimenta l studie s togethe r wit havailabl e mathematica l model s fro mlea d balanc e studie s t o projec t eithe r tota l bodyburde no r th e amoun t o f lea d i nanyo f th e presume d "physiological " kineti c compartment s (e.g. , blood , sof t tissue , bone ) a t
anytim e (Hammon d e t al. , 1981) . Thi s "uptake/biokinetic " modelin g approac h attempt s t o accoun t fo r th e following : a ) th e amoun t o f lea d i nth e bodya t
an yon e tim e i s th e produc t o f dynami c interaction s o f partiall yoffsettin g processe s o f absorption , distribution , storage , mobilization , and excretion ; b ) thes e processe s var ywit hth e rout e and rat e o f exposure , a person' s age , nutritiona l an d healt hstatus , an d baselin e exposure ; an d c ) uptak e fro mal l source s b

yal l absorptio nroute s ca nb e modeled , thu s providin g an estimat e o f th e relativ e importanc e o f atmospheri c lea d exposure , eithe r directl yo r indirectly , t o tota l bodyburden .P.2 8

V- 2 Th e leve l o f lea d i non e tissu e (e.g. , blood ) an d it s relationshi p t o level s o f lea d i nothe r tissue s respond s t o manyexterna l and interna l factors . Adiscussio no f lead' s absorption , excretion , retention , and distributio nwithi na child' s bodyunde r differen t exposur e and physiologica l condition s i s provide d i nAppendi xA . Anyapplicatio no f thi s model' s outputs , shoul d however , recogniz e th e limitation s o f th e dat a and th e significan t variabilit yamon g population s i nthei r behavioral , exposure , and physiologica l characteristics . Th e secon d modelin g approac hi s t o estimat e separat e empirica l relationship s betwee naverag e level s o f lea d i nair , food , water , dust , soi l and i nblood , whic har e availabl e fro mexperimenta l exposur e and observational , o r epidemio

logical , studie s o f differen t population s (i.e. , "disaggregate " approach ) (CD , Sectio n11.4) . Th e thir d i s referre d t o a s th e "aggregate " approac h whereb ya relationshi p betwee nbloo d lea d and ai r lea d i s derive d tha t reflect s bot hdirec t inhalatio nexposur e and indirec t exposure s vi a secondar y depositio nprocesses . Th e validit yo f thes e latte r tw o approaches , whic h rel yprimaril yo nepidemiologica l data , require s tha t th e inpu t o f lea d fro mal l source s mus t hav e bee nreasonabl yconstan t lon g enoug hfo r virtua l equilibratio nt o occu r betwee nbloo d lea d an d environmenta l lea d level s (Hammon d e t al. , 1981) . Th e natur e o f th e relationship s detecte d betwee n lea d concentration s i nbloo d and variou s environmenta l media , and th e merit s and limitation s i nusin g empirica l relationship s t o represen t lea d exposur e throug hmultipl e pathways , wil l b e discusse d i nSectio nV.B . A . Integrate d Lea d Uptake/Biokineti c Mode l Ther e hav e bee nsevera l studie s measurin g th e intake , uptake , and metabolis m

o f lea d i nvolunteers , fro mwhic hbalanc e scheme s hav e bee n constructe d (Kehoe , 1961 ; Chamberlai ne t al. , 1978 , Rabinowit z e t al. ,P.2 9

V- 3 1976 , 1977) . Thes e balanc e scheme s ar e derive d fro mlimite d dat a obtaine d unde r experimenta l condition s and thei r applicatio nthu s fa r ha s bee n restricte d t o adul t males . I t i s als o possibl e t o construc t balanc e scheme s b ymakin g estimate s abou t lea d intake s and variou s metaboli c factors . Thi s approac hsuffer s fro m th e fac t tha t th e dat a and assumption s employe d
ar e base d o nth e result s o f manyseparat e piece s o f research , and therefor e importan t variable s ma yb e omitted . However , provide d th e dat a exist , balanc e scheme s ca nb e constructe d fo r differen t group s wit hdifferen t exposure s t o lead , and fo r assessin g th e importanc e o f specifi c exposur e factor s unde r variabl e condition s (e.g. , alternativ e lea d NAAQS , phaseou t o f lea d i nsoldere d can s and i ngasoline) . Th e staf f ha s attempte d t o devis e mode l balanc e scheme s fo r U.S . childre n a t and unde r 6 year s o f ag e unde r alternativ e ai r lea d levels . Becaus e th e analysi s assume s tha t th e variou s ai r lea d level s ar e maintaine d constantly , averagin g tim e (considere d i nSectio nVII ) wil l no t affec t th e uptak e estimates . Th e reason s fo r specifyin g thi s ag e group ar e discusse d i n Sectio nVI.C . Th e result s summarize d i nTabl e 5- 1 giv e a broa d outlin e o f th e actua l and relativ e magnitude s o f averag e intake s an d uptake s o f lea d b ydifferen t pathway s and fro mdifferen t sources . I t i s importan t t o recogniz e th e limitation s o f thi s exercise , whic hinvolve s manyuncertaintie s and assumption s du e t o a lac k o f sufficien t data . Thes e limitation s alon g wit h detail s o f th e availabl e dat a and calculations ar e provide d i nAppendi xB . Th e group s o f childre nconsidere d i nth e mode l d o no t includ e th e whol e U.S . population ; the ycompris e group s wit hdifferen t exposure s t o lead , som e o f the m

extreme , i norde r t o illustrat e th e variation s i nlea d exposur e and absorptio ni ndifferen t situations . Sectio nV.A. 2 present s methodologie s t o relat e estimate s o f averag e lea d uptak e unde r alternativ e ai r lea d level sTabl e 5-1 . Mode l Balanc e Scheme s for Averag e Lea d Intak e an

d Uptak e in Childre n Unde r Alternative Ai r Lead Levels 1

1 . Outdoo r ai r lea d (pg/m** ) 2 . Indoo r ai r lea

d (pg/m-* ) 3 . Tim e spen t outdoor s (hours/day ) 4 . Tim e weighte d averag e (pg/m 3 ) 5 . Volum

e o f ai r respired (m 3 /day ) 6 . Lea d Intak e fro

mai r (pg/day ) 7 . % deposition/absorption in lung s 8 . Tota l lea

d uptak e fro

mlung s (pg/day ) 9 . Dietar

yLea d Consumption (pg/day ) a ) fro msolder , undetermined source s b ) atmospheri c lea

d 10 . %absorption i

n gut 11 . Dietar

ylea d uptak e (pg/day ) 12 . Stree t dust/soi l lea d (pg/g ) 13 . Indoo r dus t lea d (pg/g ) 14 . Tim e weighted averag e (pg/g ) 15 . Amoun t o f dir t ingested (g/day ) 16 . Lea d intake fro

mdir t (pg/day ) 17 . % dir t lea

d absorption i

n gu t 18 . Lea d uptak e fro

mdir t (pg/day ) 19 . Tota l lea

d uptak e fro

mlun g an d gut (pg/day ) 0. 5 ug / General* ^ 

### 0. 5 0.15-0. 4 

### 2- 4 .18-.4 2 5-1 0 0.9-4. 2 25-5 0 0.23-2. 1 

### m 3

Point Source 3 

### 0. 5 0.1 5 

### 2- 4 .18-.2 1 5-1 0 0.9-2. 1 45-7 5 0.41-1. 6 0.7 5 pg/m 3 1. 0 pg/m 3

Genera l 0.7 5 0.23-0. 6 

### 2- 4 .27-.6 3 5-1 0 1.4-6. 3 25-5 0 0.35-3. 2 Poin t

Sourc e 0.7 5 0.2 3 

### 2- 4 .27-.3 2 5-1 0 1.4-3. 2 45-7 5 0.63-2. 4 Genera l



### 1. 0 0.3-0. 8 

### 2- 4 .36-.8 3 5-1 0 1.8-8. 3 25-5 0 0.45-.4 2 Poin t

Sourc e 

### 1. 0 0. 3 2- 4 .36-.4 2 5-1 0 1.8-4. 2 45-7 5 0.81-3. 1

10. 1 

### 1. 0 42-5 3 2.7-5. 9 100-45 0 220-30 0 210-32 5 

### 0. 1 21.0-32. 5 

### 3 0 6.3-9. 8 9.2-17. 8 10. 1



### 1. 0 42-5 3 2.7-5. 9 350-80 0 450-70 0 442-71 6 

### 0. 1 44.2-71 . 

### 3 0 13.2-21 . 16.3-2 9 

### 6 5 0 10. 1 

### 1. 0 42-5 3 2.7-5. 9 275-80 0 375-65 0 366-67 5 

### 0. 1 36.6-67 . 

### 3 0 11.0-20 . 14.1-29 . 

### 5 3 4 10. 1 

### 1. 0 42-5 3 2.7-5. 9 600-125 0 625-85 0 623-91 7 

### 0. 1 62.3-91. 7 

### 3 0 18.7-27. 5 22.0-35. 8 10. 1



### 1. 0 42-5 3 2.7-5. 9 500-115 0 525-87 5 523-92 1 

### 0. 1 52.3-92. 1 

### 3 0 15.7-27. 6 18.9-33. 9 10. 1



### 1. 0 42-5 3 2.7-5. 9 750-145 0 800-115 0 796-120 0 

### 0. 1 79.6-120. 0 

### 3 0 23.9-36. 0 27.4-45. 0
^Assumption s an

d calculation s ar e described i n Appendi xB b yro wnumber . ^Refer s t o children livin g i n typica l urba

n o r rura l environments . 3 Refer s t o children livin g nea r one o r mor e lea d poin t sources .Tabl e 5-1 . Mode l Balanc e Scheme s fo r Averag e Lea dIntak e andUptak e i nChildre nUnde r Alternativ e Ai r Lea dLevels 1 (Continued )

1 . Outdoo r ai r lead(pg/m 3 ) 2 . Indoo r ai r lead(pg/m 3 ) 3 . Time spen t outdoor s (hours/day ) 4 . Time weighte daverag e (pg/m 3 ) 5 . Volume o f ai r respire d(m 3 /day ) 6 . Lea dIntak e fro m ai r (pg/m 3 ) 7 . % deposition/absorptio ni nlung s 8 . Tota l leaduptak e fro m lung s (Mg/day ) 9 . Dietar y

Lea dConsumptio n(pg/day ) a ) fro m solder , undetermine dsource s b ) atmospheri c lead 10 . % absorptio ningu t 11 . Dietar y

leaduptak e (pg/day ) 12 . Stree t dust/soi l lead(pg/g ) 13 . Indoo r dus t lead(pg/g ) 14 . Time weighte daverage (pg/g ) 15 . Amoun t o f dir t ingeste d(g/day ) 16 . Lea dintak e fro

m dir t (pg/day ) 17 . % dir t leadabsorptio ni ngut 18 . Lea duptak e fro

m dir t (pg/day ) 19 . Tota l leaduptak e fro m lungan

d gu t (pg/day ) 1.2 5 Genera l 1.2 5 0.38-1. 0 

### 2- 4 0.45-1. 0 5-1 0 2.3-10. 0 25-5 0 0.58-5. 2 

## wg

/ m 3 Poin t Sourc e 1.2 5 0.3 8 

### 2- 4 .45-.5 4 5-1 0 2.3-5. 3 45-7 5 1.0-3. 9 

### 1. 5

Genera l 1. 5 .45-1. 2 

### 2- 4 0.54-1.2 5 5-1 0 2.7-12. 5 25-5 0 0.68-6. 3 pg/m 3

Poin t Sourc e 

### 1. 5 0.4 5 

### 2- 4 .54-.6 3 5-1 0 2.7-6. 3 45-7 5 1.2-4. 7 1.7 5



### Genera l 1.7 5 .53-1. 4 

### 2- 4 0.63-1.4 6 5-1 0 3.2-14. 6 25-5 0 0.8-7. 3 

### yg / m 3

Poin t Sourc e 1.7 5 0.5 3 

### 2- 4 .63-.7 3 5-1 0 3.2-7. 3 45-7 5 1.4-5. 5

10. 1 

### 2. 0 42-5 3 5.1-6. 4 600-125 0 625-100 0 623-104 1 

### 0. 1 62.3-104. 1 

### 3 0 18.7-31. 2 24.4-42. 8 10. 1



### 2. 0 42-5 3 5.1-6. 4 850-100 0 1050-140 0 1033-133 3 

### 0. 1 103.3-133. 3 

### 3 0 31.0-40. 0 37.1-50. 3 10. 1



### 2. 0 42-5 3 5.1-6. 4 700-140 0 750-115 0 746-119 2 

### 0. 1 74.6-119. 2 

### 3 0 22.4-35. 7 28.2-48. 4 10. 1



### 2. 0 42-5 3 5.1-6. 4 1000-175 0 1200-170 0 1183-170 8 

### 0. 1 118.3-170. 8 

### 3 0 35.5-51. 2 41.8-62. 3 10. 1



### 2. 0 42-5 3 5.1-6. 4 775-145 0 800-120 0 798-124 1 

### 0. 1 79.8-124. 1 

### 3 0 23.9-37. 2 29.8-50. 9 10. 1



### 2. 0 42-5 3 5.1-6. 4 1075-195 0 1350-190 0 1327-190 8 

### 0. 1 132.7-190. 8 

### 3 0 39.8-57. 2 46.3-69. 1
Assumption s an

dcalculation s ar e describe di nAppendi xB b y ro w number . ^Refer s t o childre nlivingi ntypica l urba no r rura l environments . 3 Refer s t o childre nlivingnea r on e o r mor e leadpoin t sources .

C OP.3 2

V- 6
t o bloo d lea d levels . Althoug hthi s approac hpredict s hypothetica l outcome s and th e absolut e number s shoul d no t b e use d uncritically , th e mode l doe s striv e t o us e th e availabl e data , wit hal l it s limitations , t o th e fulles t exten t possibl e and t o provid e a usefu l too l i neventuall ydistinguishin g th e healt himpact s o f alternativ e lea d NAAQS . 1 . Estimate s o f Lea d Uptak e Th e metho d employe d t o estimat e th e degre e t o whic heac henvironmenta l
sourc e o f lea d contribute s t o a child' s tota l dail ylea d uptak e i s base d
o nth e maximu mambien t ai r lea d leve l allowabl e fo r eac hleve l considered , probabl e exposur e condition s wit hrespec t t o othe r exposur e medi a suc ha s foo d and dust , and averag e biologica l absorptio nrate s fo r eac hexposur e route . Th e metho d consist s o f a four-ste p process : 1 ) definitio no f ambien t concentration s o f lea d fo r majo r exposur e source s (i.e. , air , food , soil , dust) ; 2 ) determinatio no f dail ylea d intak e accordin g t o th e relationship : I i = C i • CPb] i wher e I i i s th e dail ylea d intak e fro msourc e i , C i i s th e consumptio npe r da yo f eac hlea d sourc e i and [Pb] i i s th e concentratio no f lea d i neac h
sourc e i'i ; 3 ) calculatio no f th e amoun t o f lea d absorbe d fro meac hexposur e sourc e i :

^ =I i ' A i wher e U-

j i s lea d uptak e fo r eac hexposur e sourc e i , l i i s th e dail ylea d intak e fro m

eac hsourc e i , and A ^ i s th e percen t absorptio no f lead , vi a th e appropriat e exposur e rout e fo r th e particula r source ; an d 4 ) calculatio no f th e tota l lea d uptak e fro mal l sources , U u : U u= Z (1 ^ ' Ai )P.3 3

V- 7 Certai nassumption s ar e require d t o calculat e th e averag e dail yintak e and uptak e o f lea d fo r childre nlivin g i nth e tw o genera l area s specifie d - - urban/rura l and nea r (withi n2- 5 km ) on e o r mor e poin t sources . Th e assumption s an d estimate s use d i nth e calculation s presente d i nTabl e 5- 1 ar e discusse d i nAppendi xB . 2 . Uptak e and Bloo d Lea d Concentratio n T o estimat e children' s bloo d lea d (PbB ) level s unde r differen t exposur e scenarios , severa l differen t kind s o f studie s ca nb e use d t o deriv e a relationshi p betwee nabsorbe d lea d (o r lea d uptake ) and bloo d lead . Availabl e studie s includ e populatio nsurvey s i nwhic hth e bloo d lea d concentratio no f individual s o r group s i s correlate d wit hmeasure d lea d concentration s i n air , food , water , soil , o r dust ; experiment s i nwhic hvolunteer s ar e expose d t o controlle d ai r lea d concentration s and thei r Pb B level s measured ; and lea d balanc e studie s o f individual s wit hmeasure d lea d intakes . Th e mos t relevan t o f thes e studie s ar e discusse d i nAppendi xC alon g wit hdescription s o f th e analyse s use d t o deriv e uptake/Pb B relationships . Dat a o nchildre n fro mpopulatio nsurvey s ar e discusse d i nSectio nV.B . Becaus e o f significan t metaboli c differences , experimenta l dat a o nadult s ar e use d fo r comparativ e purpose s only . Figur e 5- 1 compare s th e relationship s derive d fro mth e Ryu e t al . (1983 ) dietar yintak e studyo ninfants , th e Chamberlai nan d Hear d (1981 ) analysi s o f th e adul t epidemiologica l data , and th e metaboli c lead balance / compartmenta l model s o f Rabinowit z e t al . (1976 ) and Harle yand Knei p (1985) . Despit e th e divers e natur e o f th e populations , studydesigns , and methodologies , ther e i s a fai r degre e o f consistenc yi nth e relationships . Eac hstudy foun d tha t a linea r functio nprovide d a s goo d a fit , i f no t better , tha n othe r non-linea r form s a t th e relativel ylo wexposur e level s investigated . Som e experimenta l and epidemiologica l evidenc e suggest s however , tha t th eV- 8 P.3 4

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V- 9 relationshi p betwee nlea d concentration s i ntissu e and cumulativ e lea d intak e i s onl yapproximatel ylinea r a t lo wlevel s o f intake , an d tha t successiv e increment s i nintak e o r exposur e resul t i nprogressivel ysmalle r contribution s t o bloo d lea d concentration s (Aza r e t al. , 1975 ; Moore , 1977 ; Gross , 1981 ; DeSilv a 1981 ; Sherloc k e t al. , 1982) . Thi s curvilinea r relationshi p ma yb e du e t o increase d rena l clearanc e wit hhighe r bloo d lea d (Gross , 1981) , distributiona l non-linearitie s du e t o difference s i nlea d bindin g site s i ndifferen t tissue s (Hammon d e t al. , 1981) , and/o r t o a sizeabl e poo l o f mobil e lea d i nbon e maintaine d mor e o r les s independentl yo f uptak e (Rabinowit z e t al. , 1977 ; Chamberlain , 1983) . I t appear s however , tha t
non e o f th e mechanism s introduc e significant non-linearitie s a t bloo d lea d level s belo w3 0 pg/d l (Marcus , 1984 , 1985 ; Chamberlain , 1983 ) and tha t a linea r mathematica l mode l i s vali d fo r relativel ylo wt o moderat e lea d exposure s (CD , p . 10-31 , Appdx . 11A-2) . A s discusse d i nAppendi xA , abov e 30-4 0 pg/dl , bloo d lea d mayb e a ninadequat e inde xfo r tissu e lea d burden s i nmanychildre n(Piomell i e t al. , 1984 ) an d linea r model s ar e likel yt o los e thei r predictiv e power . Fo r thi s reason , th e relationship s depicte d i nFigur e 5- 1 ar e truncate d a t 3 0 pg/dl . T o estimat e Pb B level s abov e 3 0 pg/dl , whic hi s no wabov e th e maximu mPb B leve l o f health-relate d
concer nfo r childre n(se e Sectio nVII.C) , woul d requir e us e o f non-linea r model s whic har e discusse d i nth e criteri a documen t (Appendi xII.B) . Th e compartmenta l biokineti c mode l o f lea d metabolis mdevelope d b yMallo n (1983 ) and Knei p e t al . (1983 ) and revise d fo r childre nb yHarle yand Knei p (1985 ) relie d o na broa d arra yo f experimenta l and observationa l measurement s o f mammalia nmetabolis mand growt hpatterns , and ha s bee nsuccessfull y validate d usin g availabl e huma nexperimenta l and autops ydata . A s i s th e cas e fo r an

ymathematica l model , ther e ar e inheren t limitation s an d un -P.3 6

V-1 0 certaintie s associate d wit hit . Becaus e thi s mode l howeve r i s base d o nth e mos t comprehensiv e dat a availabl e an d ha s bee ndevelope d specificall yt o predic t orga nlea d concentration s ove r tim e i nyoun g childre nwit hcontinuou s lea d uptake , i t appear s tha t th e output s o f th e Harle yand Knei p (1985 ) biokineti c mode l mayb e th e mos t appropriat e t o predic t Pb B level s i n childre nusin g th e integrate d lea d uptak e estimate s presente d i nTabl e 5- 1
and Appendi xB . Pb B level s calculate d fro mth e conjunctio no f th e integrate d lea d uptak e and biokineti c model s ar e presente d i nSectio nVII.C. 2 (alon g wit hestimate s usin g othe r modelin g approache s tha t ar e discusse d later ) i norde r t o estimat e potentia l healt himpact s amon g childre nunde r alternativ e ai r lea d levels . B . Statistica l Relationship s betwee nBloo d Lea d and Airborn e Lea d Thi s sectio naddresse s tw o othe r method s o f determinin g th e contributio no f ai r lea d t o tota l exposur e and th e potentia l healt himpact s associate d wit halternativ e ai r lea d levels . Th e previou s sectio nexamine d th e relationship s betwee nbloo d lea d i nchildre nand estimate d level s o f lea d uptak e fro mth e air , housedust , outdoo r soi l and dust , and diet . Th e approache s presente d her e wil l b e t o develo p a direc t relationshi p betwee n ai r lea d and bloo d lea d i nchildre nand t o 1 ) conside r ho wai r lea d alon e ca nserv e a s a ninde xfo r lea d exposur e throug hothe r medi a affecte d b y atmospheri c lea d depositio na s wel l (i.e. , "aggregate " modelin g approach) , and 2 ) ho wthes e othe r environmenta l medi a ca nb e take nint o accoun t separatel y(i.e. , "disaggregate " modelin g approach) . Variou s experimenta l and communit ystudie s provid e quantitativ e relation

ship s betwee nai r lea d and bloo d lead . Experimenta l studies , summarize d i n Tabl e 5-2 , includ e thos e i nwhic hadul t volunteer s hav e bee nexpose d t o con trolle d level s o f laborator ygenerate d lea d aerosols , i nsom e case s wit hTabl e 5-2 . SUMMARYO F EXPERIMENTAL LEADINHALATION STUDIE S

Study/Subject s Exposur e Othe r Controlle d LeadExposure s Sourc e o f Analysi s Estimate dMea n

Inhalatio nSlop e (ug/d l pe r pg/m 3 ) Griffi ne t al. , 197 5 1 4 adul t male s 1 7 adul t male s

6 adul t male s (controls ) 3. 2 Mg/m 3 - Die t 10. 9 pg/m 3 - Die t submicro nleadoxid e aeroso l fo r 4-1 4 weeks , 2 3 hrs/day Ambien t ai r (0.1-0. 2 .g/m 3 ) Die t C D Snee , 198 1 Hammonde t al , 198 1 C D
CO 3.0 0 2. 3 1. 9 0.65-2.1 7 mea n> * 1.5 7 _ + 0.2 6 0.2 0 + 1.4 8 Rabinowit z e t al. , 197 7 5 adul t male s Ambien t ai r ( • 4 pg/m 3 ) ! , roo m wit hunfiltere dair , (0.4-2. 1 ug/m 3 ) , and roo m wit hfiltere dai r Die t supplemente d wit hIsotopi c lead trace r

Ambien t ai r (2. 1 pg/m 3 ) 2 Othe r exposure s identica l C D
Snee , 198 1 C D 1.59-3.5 6 mea n« • 2.1 4 1.7-3. 9 2.63-5.8 8 mea n= 3.5 1 Chamberlai ne t al. , 197 8 1 0 adul t male s P blabele dsubmicro nca r exhaust , lea doxide , an d leadnitrat e aerosol s fo r severa l minute s C D 2.2-2.7 3 3.0-3.5 4

Kehoe , 196 1 6 adul t male s

9 adul t male s 0.6-0. 9 ug/m 3 submicro nDie t lea dsesquioxid e aeroso l fo r variou s dail y

interval s ove r three-fiv e year s 0.6-3. 6 pg/m 3 ove r simila r Die t perio d C D
Gross , 198 1 Hammonde t al. , 198 1 -0.3 4 t o 2.6 0 mea n» 1.2 5 0.5 7 0.5 9

ifiase donstationar y

monito r reading s no t representativ e o f persona l exposure s whil e outsid e (1 0 hrs/day ) (CD , p . 11-47) . 2 C D(p . 11-48 ) estimate s outdoo r exposur e mos t likel y t o be 2. 1 pg/m 3 resultin gi nestimate dleadintak e an dp t o b e significantl y

different . 3 Depend s o

nassumption s regardin gresidenc e tim e o f leadandvolume o f bloo d(CD , p . 11-4 9 t o 11-50) . '"'Afte r adjustmen t fo r long-term bon e resorptio no f leadwit hchroni c exposur e (Chamberlai ne t al. , 1978) .

c oP.3 8

V-1 2 isotopi c lea d tracer . Dat a fro mth e mos t relevan t studie s hav e bee nre-analyze d i nth e C D t o yiel d bloo d lead-ai r lea d "slopes " (B) , wher e g measure s th e chang e i nbloo d lea d tha t i s expecte d fo r a uni t chang e i nai r lead . Becaus e intak e o f ai r lea d throug hth e die t and dus t wa s probabl yminima l fo r th e adul t subject s i nthes e experiments , thes e studie s ma yunderestimat e th e dos e respons e tha t woul d b e see namon g childre nt o environmenta l change s i nai r lea d (Angl e e t al. , 1985) . Epidemiologica l (i.e. , community ) studie s provid e correlation s betwee nai r lea d and bloo d lea d i ndifferen t population s o f childre nand adult s unde r varyin g condition s o f lead , fro mcurren t o r previou s atmospheri c fal l ou t
and othe r sources , and ma yyiel d estimate s o f dos e respons e tha t ar e biological

l ymor e relevant . Tw o modelin g approache s usin g th e bes t availabl e epidemio

logica l dat a ca nb e applie d t o estimat e quantitativel yth e relationshi p betwee n ai r lea d and bloo d lea d i nchildren : 1 ) a disaggregat e mode l i nwhic htota l exposur e t o ai r lea d i s assesse d b yseparatel yanalyzin g th e relationshi p betwee nbloo d lea d and inhale d ai r lea d versu s th e associate d change s i n bloo d lea d a s a resul t o f surfac e depositio no f lea d ont o soil , dust , food , and water ; and 2 ) a naggregat e mode l i nwhic hbloo d lead/ai r lea d relationship s ar e analyze d suc htha t integrate d environmenta l lea d exposur e i s represente d b ya singl e variable . Befor e discussin g thes e approaches , severa l importan t limitation s i ninterpretin g th e epidemiologica l studie s shoul d b e noted . a ) Measurement s o f lea d i nth e environmen t wer e generall ylimite d
and take nfro m

sample s separate d i ntim e and spac e fro mactua l populatio n exposure s (a s indexe d b ybloo d lead) . Consequently , reporte d ai r lea d concentration s i noutdoo r ai r (measure d a t centralized , stationar ymonitors) , fo r example , hav e differen t relationship s t o th e tru e persona l airborn e lea d exposur e o f th e targe t populatio ni ndifferen t studies ;P.3 9

VT1 3 b ) I n orde r fo r th e relationship s betwee nbloo d lea d and environmenta l lea d t o hav e genera l predictiv e valu e fo r othe r populations , steadystat e o r nea r steadystat e condition s mus t hav e prevaile d wherei nth e amoun t o f lead inhale d and ingeste d pe r uni t tim e wa s reasonabl yconstan t lon g enoug h fo r virtua l equilibratio n t o occu r betwee n lea d i n air , food , dust , etc. , and bloo d lea d (Hammon d e t al. , 1981) . A s discusse d below , i n situation s wher e lea d concentration s i n differen t medi a ar e onl ymoderatel ycorrelated , environmenta l exposur e canno t simpl yb e characterize d b yth e lea d concentratio n i n on e medium , lik e ai r o r dust . (Brunekreef , 1984) ;
c ) Th e blood/ai r lea d relationship s generall yar e limite d i ntha t
a t mos t tw o o r three , bu t frequently , onl yon e environmenta l sourc e o f lead i s measure d i n eac hstudy . Becaus e o f th e simultaneou s presenc e o f lea d i n multipl e media , suc hrelationship s underestimat e o r otherwis e confoun d ai r lead' s effec t o n tota l exposur e unles s lea d intak e fro mth e othe r source s remain s approximatel yconstan t and lea d concentration s i n differen t medi a ar e wel l correlated . I nsituation s wher e th e latte r conditio n doe s no t hold , environmenta l exposur e canno t b e simpl ycharacterize d b yth e lea d level s i nai r (fo r example , nea r poin t source s wher e th e accumulatio n o f lea d i n soi l i s relate d mor e t o historical , rathe r tha n present , emissions , especiall ywhe n contro l measure s ar e bein g o r hav e bee ntaken) . Thes e difficultie s ca n b e partl yovercom e bu t unfortunately , longitudina l assessment s o f simultaneou s exposur e t o al l medi a hav e no t bee n mad e and onl ylimite d informatio nexist s fro mstudie s measurin g lead isotop e ratio s i n bloo d and i n th e environment , a metho d whic hha s emerge d a s a valuabl e too l t o apportio n lead exposur e amon g differen t source s (Facchett i and Geiss , 1982 ; Yaff e e t al. , 1983) ; d ) A s wit hth e uptake/biokineti c approach , th e importanc e o f specifi cP.4 0

V-1 4

source s o f exposur e varie s widel yfro mon e individua l t o th e next , and relianc e o na blood/ai r relationshi p fro man"average " cas e ma yb e inap

propriat e t o predic t differen t individua l risk s bu t ca nprovid e reasonabl e estimate s o f possibl e population-wid e impacts . e ) Again , simila r t o th e uptake/biokineti c approach , environmenta l
and bloo d lea d sampling , analytica l techniques , an d qualit ycontro l (i f any ) diffe r amon g studie s and ma yexplai npar t o f th e variabilit yo f th e results ; and f ) Possibl e confoundin g variable s tha t influenc e Pb B level s bu t whic har e no t relate d t o ai r lea d measurement s (e.g. , lea d i npaint , canne d foo d and plumbing , socioeconomi c status , parenta l care , housin g and pla y conditions , calciu m intake ) canno t alway s b e disentangled . Contro l fo r confounder s ca nb e achieve d b ycomparin g population s tha t diffe r onl yi n thei r exposur e t o airborne-derive d lead . However , identifyin g suc hgroup s ha s bee ndifficult . Anothe r possibilit yi s t o perfor ma multivariat e statistica l analysi s i nwhic hadjustment s ar e mad e fo r som e o r al l o f th e confounder s befor e calculatin g th e bloo d lead/ai r lea d relationship . Thi s require s informatio no nth e valu e o f eac hconfounde r fo r eac hindividual , whic hi s als o ver ydifficul t t o estimate . I nth e cas e o f lead , severa l confounder s ten d t o wor k i nth e sam e directio na s ai r lead . Fo r example , elevate d exposur e and unfavorabl e socia l condition s ofte nar e bot hconcentrate d i ncentra l cities . Consequently , whe nstatistica l adjustmen t i s incomplete , th e relationshi p betwee nai r lea d and bloo d lea d wil l likel yb e inflated . Th e situatio ni s complicate d whe nmor e tha non e exposur e variabl e beside s ai r lead i s entere d int o th e analysis . Adjustmen t fo r a confoundin g variabl e usuall yimplie s tha t al l o f th e share d varianc e betwee nconfounde r an d exposur eP.4 1

V-1 5 variabl e i s attribute d t o th e confounder ; thi s ca ninevitabl ylea d t o underestimatio no f th e "true " impac t o f th e exposur e variabl e (Rutter , 1983) . Thus , adjustin g fo r environmenta l exposure s suc ha s soi l o r dus t lead , whic har e determine d t o a larg e exten t b yai r lea d levels , ca n resul t i nanunderestimatio no f th e tota l impac t o f airborne-derive d lea d
o nbloo d lea d (Brunekreef , 1984) . 1 . Blood/Ai r Lea d Relationshi p Usin g Disaggregat e Mode l Th e C D conclude s tha t experimenta l inhalatio nstudie s (se e Tabl e 5-2 )
and epidemiologica l studie s o nadult s (Aza r e t al. , 1975 ) expose d t o relativel y lo wai r lea d level s (<3. 0 pg/m*-* ) produc e linea r inhalatio nbloo d lead/ai r lea d slope s o f 1.6 4 an d i nth e rang e o f 1.08-2.5 7 respectivel y(CD , Table s 11-38 , 11-40) . Inhalatio nslope s fo r childre nwer e estimate d i nth e C D fro mth e populatio nstudie s o f Angl e and Mclntir e (1.9 2 +_.60) , Roel s e t
a l . (2.4 6 +

_0.58) , an d Yanke l e t al . (1.5 3 +

_0.064) , yieldin g anunweighte d
mea nslop e o f 1.9 7 +^0.3 9 (CD , p . 11-76) . Thes e studie s wer e chose nfo r analysi s and emphasi s i nth e C D becaus e the ywer e judge d t o addres s severa l ke yfactor s sufficientl ywel l t o establis hmeaningfu l relationships . Thes e factor s includ e a well-define d studypopulation , a goo d measur e o f individua l exposure , measuremen t o f bloo d lea d wit hadequat e qualit ycontrol , a statistica l analysi s mode l tha t i s biologicall yplausibl e and consisten t wit hth e data , and contro l o r measuremen t o f importan t covariate s (CD , p . 11-63) . I n addition , the ywer e selecte d s o that , wit hth e exceptio no f som e childre n i nth e Yanke l e t al . study , attentio nca nb e restricte d "t o thos e individual s withou t know nexcessiv e occupationa l o r persona l exposures " (CD , p . 11-65) .P.4 2

V-1 6 Th e relationshi p betwee nbloo d lea d an d direc t inhalatio no f airborn e lea d provide s informatio nusefu l fo r change s i nai r lea d o na tim e scal e o f onl ysevera l month s (CD , p . 11-186) . Ove r time , suspende d lea d deposit s and i s incorporate d int o soil , dust , and water , and enter s th e foo d chain . Sinc e prio r an d curren t atmospheri c fallou t directl ymodif yth e dail yburde no f ingeste d lead , large r change s i nbloo d lea d woul d b e predicte d b yth e associate d change s i nth e surfac e depositio no f lea d (Angl e e t al. , 1985) . T o accoun t fo r th e simultaneou s presenc e o f lea d i nmultipl e environmenta l media , th e C D ha s analyze d th e separat e relationship s betwee nchildren' s bloo d lea d an d dietary , soil , an d dus t lead . Thes e analyse s ar e summarize d i nth e table s include d i nAppendi xC and ar e describe d i ndetai l i n Chapte r 11. 4 o f th e CD . Ase t o f th e mos t reliabl e relationship s derive d fro mthes e analyse s ar e applie d i na furthe r analysi s presente d i nth e C D (CD , Tabl e 13-6 ) and reproduce d i nthi s pape r (Tabl e 7-10 ) a s a wa y t o characteriz e averag e tota l lea d exposur e amon g U.S . childre nunde r alternativ e ai r lea d levels . Asimila r disaggregat e mode l wa s develope d b yAngl e and Mclntir e (1979 ) an d Angl e e t al . (1985 ) i nformin g anintegrate d lea d exposur e functio nfro mmeasurement s o f lea d i nair , soil , and hous e dus t
an d relatin g tha t t o Pb B level s o f childre nlivin g i nvariou s area s o f Omaha . 2 . Blood/Ai r Lea d Relationshi p Usin g Aggregat e Mode l I nth e disaggregat e modelin g approach , "inhalation " lea d slope s ar e derive d b

ystatisticall yadjustin g bloo d lead/ai r lea d slope s b ywhateve r non-ai r exposur e variable s (e.g. , hous e dus t lead ) tha t wer e measure d i n th e individua l epidemiologica l studies , and the ncombinin g separat e slope s availabl e fo r othe r exposur e medi a (e.g. , dust , food , water ) t o arriv e a t anintegrate d lea d exposur e function . Wit hth e exceptio no f Angl e and Mclntir e (1979) , th e communit ystudie s fro mwhic hinhalatio nslope s hav eP.4 3

V-1 7 bee nderive d hav e no t simultaneousl ymeasure d lea d i nmor e tha ntw o o r thre e medi a and consequently , th e integrate d lea d exposur e functio ni s necessaril y base d o ndat a fro mmultipl e studie s involvin g differen t populations , exposur e conditions , measuremen t techniques , etc . Analternativ e metho d o f calculatin g th e effec t o f change s i nai r lea d o nchildren' s bloo d lea d i s t o analyz e individua l communit ystudie s i nwhic hreliabl e "unadjusted " bloo d lead/ai r lea d relationship s ca nb e derive d suc htha t th e impac t o f bot hdirec t (inhaled ) and indirec t (vi a dust , soil , etc. ) contribution s o f ai r lea d ar e combined , o r aggregated , i non e variabl e (i.e. , ai r lead )
a t a time . T o simpl yus e an"adjusted " bloo d lead/ai r lea d slop e (i.e. , inhalatio nslope ) woul d b e t o underestimat e th e impac t o f atmospheri c lea d o nchildren' s tota l exposur e sinc e ai r lea d levels , i ngeneral , ar e significantl ycorrelate d wit hothe r importan t exposur e variable s suc ha s hand and househol d dus t lea d (Brunekreef , 1984) . Th e populatio nstudie s wit hidentifiabl e ai r monitorin g method s an d reliabl e bloo d lea d dat a ar e summarize d i nTabl e 5-3 . A s i s th e cas e fo r th e dat a i neac ho f th e experimenta l studies , differen t statistica l analyse s o f th e studie s hav e resulte d i na rang e o f possibl e value s fo r th e bloo d lead/ai r lea d relationshi p (p) . Unadjuste d (i.e. , aggregate ) relationship s ar e presente d i nadditio nt o adjuste d relationship s derive d fro mregressio n analyses , th e latte r whic hrefe r t o th e bloo d lead/ai r lea d relationship s du e t o direct inhalatio nexposure . Not e tha t i nth e majorit yo f thes e studie s adjustmen t fo r confoundin g factor s ha s bee nabsent o r incomplete . I nTabl e 5-4 , th e calculate d 6 value s liste d i nTabl e 5- 3 fo r eac hstudy ar e presente d accordin g t o th e bloo d lea d levels , ages , and typ e o f locatio n o f th e investigate d children . Relativel ywid e range s o f 3 value s ar e observe d fo r industria l and urba narea s a t lo wand hig hPb B level s and fo rTabl e b-3 . SUMMAR YOF EPIDEMIOLOGICAL STUDIE S U N LEAD-EXPOSE DCHILDRE N

Stud y Roel s et al. , 1976,1978,198 0 Population 3 Ai r Lead 0 (pg/m 3 ) BloodLead (pg/dl ) Statistica l Mode l (Analyst ) Covariate s Measure d bloodLead / Ai r LeadSlop e <lkin : 10-1 5 yr s n=21 4 2.5km : 10-1 3 yr s n=16 8 Urban : 10-1 4 yr s n=5 5 Rural : 10-1 3 yr s n=22 3 Livin gnea r leadsmelte r (Antwerp , Belgium ) 2.68-4.0 6 24.6-30. 1 0.54-1.0 0 13.3-21. 1 0.45-0.5 6 10.4-12. 7 0.29-0.3 7 9.0-10. 7 ( 9 mont havgs ; lo w volum e sampler) 0 Multipl e regressions : Roel s e t al. , 198 0 ( 8 groupmeans ) C D(14 8 subjects ) Age , drinkin gwater , income 5. 3 plu s han ddus t P badjustmen t 0.00 7 -plu s han

ddus t P badjustmen t 2.4 6

Yanke l e t al. , 1977 ; Walte r e t al. , 198 0 1- 9 yr s n=114 9 (1974 )

1-1 0 yr s n=78 1 (1975 ) livinga t varyin g distance s fro

m lea d smelte r (Kellogg ) 0-1.6k m 1.6-4k m 4-10k m 10-24k m 24-32k m » 75km : 18. 0

14. 0 6. 7 3. 1 1. 5 1. 2 (monthl y avgs . 65. 9

47. 7 33. 8 32. 2 27. 5 21. 2 21. 2 Multipl e regressions : Yanke l e t al . (1977 ) Sne e (1982b ) Sne e (1982a ) C D(linear ) C D(non-linear ) Walte r e t al . (1980 ) Grou pcomparison s (Brunekreef , 1984 ) Aye , drinkin gwater , paint , SES , hous e dus t -plu s soi l « dus t P b occupatio nadjustmen t -plu s soi l Pb , occupation , cleanliness , pic a adjustmen t -same a s abov e -same a s abov e -sam e a s abov e No adjustmen t fo r soi l o r dus t P b
Angl e an d Mclntire , 197 9 1-1 8 yr s n=83 1

livinginindustria l urban , suburba n area s o f Omah a industrial : 0;37-1.6 6 24. 8 urban : 0.32-1.4 4 22. 0 suburban : 0.22-0.7 3 18. 0 (annua l avgs . 1970 - 1977 ) Regressio nAnalyses : Angl e andMclntir e (1979 ) (6-18yr . olds ) C D(Tabl e 11-33 ) (1-1 8 yr . olds ) CD-(Tabl e 11-33 ) Brunkreef , 1984 ; (al l children ) (1- 5 yr . olds ) (6-1 8 yr . olds ) Age , drinkin gwater , food -plu s soi l &

hous e dus t P badjustmen t -same a s abov e -sam e a s abov e N o adjustmen t fo r soi l o r dus t lead At 1. 0 py / 197 4 dat a 1.1 6 1.1 3 1.U 7 l.bi ! 1.1 b 1.2 6 2.4-3. 3 dependiny 1. 4 0. 6 1.9 2 4.4 0 O.b b 2.6 3 2.1 0 m-* ;

\

onaye

< i 0 0

Brunekree f e t al. , 1981 ; Zielhui s et al. , 197 9 1976:2- 3 yr s n=10 8

1977:1- 7 yr s n=69 0 1978:1- 3 yr s n=9 5 living<2k

m and2-5k

m fro m secondary

smelte r (Arnheim ) 0.5-2.5(0.4km ) 0.4-1.6(0.4km ) 0.28-0.51(<lkm ) ( 2 mont havg. ) 11.8(2-5km)-19.7(.4-lkm ) 14.6(l-2km)-18.2(.4-lkm ) 16.1(.4-lkm ) Grou pcompariso n (Brunekreef , 1984 ) Multipl e regressio n (Brunekreef , 1984 ) Age , parenta l educatio n an dexposure , drinkin gwater , food , ag e o f home , mouthin g behavior/han ddirt , hous e dus t

- plu s adjustmen t fo r parenta l educatio n 4. 0 (1976 ) 3. 6 (1977 ) 3. 6 (1976 ) Landriga n1972:1-1 8 yr s n=25 9 (exposed ) et al. , 1975 ; 1977:1-1 8 yr s n=49 9 (control ) Mors e e t al . 1-1 8 yr s n=14 0 (exposed ) 197 7 livingnea r primary

smelte r (El Paso ) <.8k m ,8-1.6k

m o a — 10. 0 6 . 5. 5 3.0 d ( 4 mont havg. ) <.8k m 41. 4 17.7 e .8-1.6k

m 31. 2 20. 2 Grou pcompariso n

(Brunekreef , 1984 ) Aye , drinkiny water , mil k2. 6 (1972 ) consumption , parenta l income , 3. / (1977 ) home pain t statu sTabl e b-3 . SUMMAR YO F EPIDEMIOLOGICA

L STUDIE S O

N LEAD-EXPOSEDCHILDRE N (CONTINUED )

Stud y Population 3 Ai r Lead 0 (py/m 3 ) Bloo dLea d (py/dl ) Statistica l Mode l (Analyst ) Covariate s Measured Billicke

t al. , 0- 6 yr s n=178,53 3 1979 , 1980 ; livin g i nNY C Nathanso n& Nudleman , 198 0 0.8-2. 5 (quarterly

averages , 1970-1974 ) 20-3 3 Regressionanalysi s (Brunekreef , 1984 ) Bloo dLead / Ai r Lea dSlope Season , location , plu s adjustmen t fo

r age 4 rac e 2. 9

Brunekree f e t al. , 198 3 4- 6 yr s n=19 5

livin g i ncit y center o r i nsuburba

narea (Rotterdam ) .2 5 cit y .1 3 suburba

n (6-monthavg. , lo w volum e sampler 0 ) 13. 1

8. 2 Grou pmeancomparison s Regressionanalysi s (Brunekreef , 1984 ) Regressionanalysi s (Brunekree f e

t al. , 1983 , 1984 ) Age , drinkin y water , hous e paint , SES , parenta l exposure , locatio n -plu s adjustmen t fo r Pb depositionoutdoors , age of home , mil kconsumption , number o f rooms , han

ddirt , mouthing behavior , pet s 24. 5 18. b 3.0-8. 5

aRefer s t o age of childrensample dan dsampl e size s (n) . DRepresent s average level s measuredeithe r a t variou s location s specifiedi n"population " colum nor a t variou s distance s fro

m specifiedpoint sources .

c Ai r lea

dlevel s sample

db y lo w volum e method s likely

underestimatedlevel s tha t woul dhav e bee nmeasuredb

y hi-vol um e sampler s use

di nother studies , especiall y near smelte r wher e larger lea dparticle s predominate . Thi s coul dre sul t i ninflatedblood/ai r lea dratios . Estimate db

y interpolationof ai r quality dat a presented .

e Base do

nonly 3 sample s - blood/ai r lea dslope for 197 7 base do nreductio

nof ai r an

dbloo dlea da t 0.8-1,6k

m fro m source . i t — A U DTabl e 5-4 . BLOO D LEAO/AI R LEA

D SLOPES 1 I NCHILDRE NFO R DIFFEREN

T AGE S AN

D EXPOSURE S

Blood Lea

d (ug/dl) / Ag e (years )
_ <25/0- 9 Typ e o f Location (Study ) Urba n Nea r Poin t Source(s ) 8.5 a > D (Brunekree f e t al. , 1983 ) 3.6-4.0 a (Zielhui s e t al. , 1979 ; Brunekree f e t al. , 1981 ) <25/0-9 , 10 + 0. 6 (Angl e an d

1.4 aMclntire ; 1.9 2 1979 , CD

) 4.4 0 0.66 a(Brunekreef , 198 4 -2.63 afro m Angl e an d 2.10 aan d Mclntire , 1979 ) <25/10 +

>25/0- 9 2.4 6 (C D fro mRoel s e t al . 1976 ) 5.3 a (Roel s e t al . 1980 ) « 5.9-9.8 a » bBrunekreef , 198 4 fro mRoel s e t al. , 1976 , 1978 , 1980 )
2. 9 (B i Hic k e t al. , 1979 , 1980 ; Nathanson an

d Nudleman , 1980 ) 1.07-1.5 2 (Yanke l e t al. , 1977 ; Walte r e t al. , 1980 ; Snee , 1982b ; CD ) 2.4-3.3 a (Brunekreef , 198 4 fro mYanke l e t al. , 1977 ) i r o o

>25/0-9 , 10 + 2.6-3.7 a (Landriga n e t al . 1975 ; Mors e e t al. , 1977 ) 4.6 a (Brunekreef , 198 4 fro mRoel s e t al. , 1976 , 1978 , 1980 )

^Slope s ar e in unit s o f p g lead/d l blood pe r p g lead/m*- * air .
a "Aggregate " slope s derived fro mgrou p comparison s or multipl e regression analyse s tha t wer e unadjuste d fo r soi l o r dus t lead , thereb

yattemptin

g t o accoun t for influenc e o f deposite d atmospheri c lea d throug

hthes e exposur e routes . Remainin

g slope s represen t relationship s between blood lea d an d ai r lea

d du e solelyt o direc t inhalatio n whic hhave been calculated b

yadjustin

g for the influenc e o f soi l and/o r dus t lead . D Us e o f low-volum

e particulat e sampler s likelyunderestimated ai r lea d exposures , an

d overestimate d the 3 value , especiall ynear point sourc e wher e larg e particle s predominate .P.4 7

V-2 1 al l age s o f children . Th e apparen t tren d toward s lowe r slope s wit hincreasin g Pb B level s i s consisten t wit hfinding s withi n som e studie s (Angl e and Mclntire , 1979 ; Roel s e t al. , 1980 ) and othe r observation s o f curvilinea r bloo d lead/exposur e relationship s (Aza r e t al. , 1975 ; Moor e e t al. , 1977 ; Gross , 1981 ; DeSilva , 1981 ; Sherloc k e t al. , 1982 ; Hammon d e t al. , 1981) . A s discussed , th e C D determine d tha t th e inhalatio n slope s derive d fro mth e studie s b

yAngl e an d Mclntire , Roel s e t al. , and Yanke l e t al . ar e th e mos t reliabl e give nthei r overal l quality . I t i s importan t t o not e severa l additiona l studie s and analyse s tha t ma yprovid e equall yrelevan t
and usefu l informatio n fo r purpose s o f estimatin g a n aggregat e bloo d lead/ai r lea d slope . Table s 5- 3 and 5- 4 identif ysurvey s beside s thos e o f Angl e and Mclntir e and Roel s e t al . whic hstudie d childre n (0-1 0 yrs ) whos e bloo d lea d level s wer e belo w2 5 pg/dl . Thes e studie s (Brunekree f e t al. , 1983 ; Zielhui s e t al . 1979 ; Brunekree f e t al. , 1981 ) reporte d well-define d study populations , employe d availabl e qualit ycontro l procedure s fo r bloo d lea d analysis , and measure d o r controlle d fo r importan t covariate s (se e Tabl e 5-3) . Severa l specifi c comment s shoul d b e mad e regardin g thes e studies : 1 . Th e serie s o f studie s reporte d b yZielhui s e t al . (1979 ) and Brunekree f e t al . (1981 ) include d manyenvironmenta l measurement s (lea d i n ambien t and indoo r air , lea d i n dustfal l indoor s and outdoors , soil , streetdust , floordust , tapwater , and dustines s o f homes ) and regressio n analyse s t o determin e th e impac t o n Pb B level s o f differen t variable s (i.e. , th e abov e environmenta l indice s a s wel l a s distanc e fro mth e smelter , parenta l education , ag e o f th e child , mouthin g activity , cleanlines s o f th e child) . Venou s bloo d lea d sample s wer e analyze d b ystandar d technique s and althoug hinformatio no n interlaborator ycomparison s i s no t give ni n th e origina l study , qualit ycontro l participatio ni s reporte d b yon e o f th eP.4 8

V-2 2 investigator s i na subsequen t revie w(Brunekreef , 1984) . Ai r lea d wa s measure d a t tw o site s i n1976 , and presumabl yi n1977 , 0. 2 an d 0. 4 k mfro m th e smelter . Th e level s i nTabl e 5- 3 wer e take nfro mBrunekree f (1984 ) an d represen t thos e measure d a t 0. 4 k mfro mth e smelter . Si xmonitor s measure d ai r lea d a t 6 site s continuousl yfo r 2 month s i n1978 . Brunekree f (1984 ) estimate s 3 fo r 197 6 b yassumin g a differenc e o f 2. 0 ug/m ^ i naverag e ai r lea d exposur e level s betwee nth e 2- 3 yea r ol d childre nwit hth e highes t and lowes t Pb B levels . Th e bloo d lea d differenc e o f abou t 8 ug/d l decrease d t o 7. 2 ug/d l afte r adjustmen t fo r parenta l education , resultin g i na slightl ylowe r 3 estimat e (3.6) . Fo r 1977 , a differenc e o f 1. 0 yg/m ^ wa s assume d fo r ai r lea d exposur e level s betwee nexpose d an d contro l childre n o f 2- 3 year s wh o ha d Pb B level s o f 18. 2 and 14. 6 yg/dl , respectively , agai n resultin g i na 3 o f 3.6 . I n1978 , onl ychildre nlivin g betwee n0. 4 and 1. 0 k mo f th e smelte r wer e sample d and ai r level s di d no t correlat e wit hbloo d lea d withi nthi s population . Thus , n o direc t estimat e o f 3 ca nb e derived , althoug hsoi l lea d and indoo r and outdoo r dus t lead , and therefore , accumulate d lea d deposition , accounte d fo r a significan t fractio no f th e varianc e i n Pb B level s (Brunekree f e t al. , 1981) . Base d o nth e aforementione d criteri a use d t o determin e ke ystudie s i nth e C D (p . 11-63) , i t appear s tha t thi s serie s o f studie s nea r Arnhei mand th e subsequen t analyse s i nBrunekree f (1984 ) i s o f sufficien t qualit yt o provid e reliabl e aggregat e relationship s betwee nbloo d lea d and ai r lead . 2 . Th e mor e recen t studyb yBrunekree f e t al . (1983 ) o nDutc hcit yand suburba nchildre nals o measure d venou s bloo d (whic hwa s analyze d a s par t o f th e Europea nCommunit ylaborator yqualit ycontro l program ) and man y environmenta l and socia l variable s an d potentia l confounder s (lea d i n drinkin g water , soil , stree t and playgroun d dust , hand dust , indoo r dust ,P.4 9

V-2 3 mouthin g behavior , dietar yintakes , parenta l educatio nand occupation , ag e o f home , etc) . Th e ver yhig h3 valu e (8.5 ) derive d b yBrunekree f (1984 )
eve nafte r adjustmen t i na multipl e regressio nanalysi s fo r si xo f th e confounders , ma yb e relate d t o anunderestimatio no f ambien t ai r lea d level s du e t o th e fac t tha t lo wvolum e Britis hSmok e ai r monitor s wer e employed , i ncontras t t o th e hi-vo l sampler s use d i nmos t othe r studies . Th e exten t o f inflatio ni nth e estimate d slop e a s a resul t o f an yunderestimate d ai r lea d leve l i s uncertain . Brunekree f (1984 ) note s howeve r tha t eve ni f thi s bia s i s accounte d for , th e differenc e i nurba nand suburba nai r lea d level s wa s probabl yno t large r tha n0. 2 ug/m-* . Th e contras t i nlea d depositio nbetwee nth e area s wa s significan t (i.e. , 64 3 vs . 22 0 ug/m^/day) , indicatin g tha t ongoin g lea d pollutio naccounte d fo r a goo d dea l o f th e difference s i nPb B levels , althoug hvariation s i nhistorica l emission s ca n no t b e entirelyrule d out . Th e relativel ylo wPb B level s i nthi s study ( a 8-1 3 ug/dl ) coul d b e anothe r partia l explanatio no f th e hig h3 estimates , give ntha t othe r studie s use d t o deriv e 3 include d childre nwit hPb B level s o naverag e close r to , and above , 3 0 ug/dl , a t whic hpoin t th e bloo d lead/lea d intak e relationshi p i s estimate d t o b e non-linea r and level s off ; belo w3 0 ug/dl , thi s relationshi p appear s t o b e approximatel ylinea r (CD , p . 11-104) . Despit e th e uncertaintie s i nth e ai r monitorin g data , thi s study appear s t o hav e bee ncarefull ydesigne d and conducte d and thoug hth e precis e valu e o f th e bloo d lead/ai r lea d relationshi p i s no t certain , th e estimate d 3 valu e appear s t o b e significantl yhighe r tha nth e mea ninhalatio nslop e derive d fro m

othe r studie s o f comparabl e qualit yand relevance . I nadditio nt o thes e studies , th e availabl e statistica l aggregat e analyse s o nth e criteri a document' s thre e "ke yinhalatio nslope " studie sP.5 0

Vr.2 4

o n childre nrequir e brie f discussion . 3 . Th e thre e inhalatio n 3 value s (0.6 , 1.92 , and 4.40 ) attribute d t o regressio n analyse s performe d b yAngl e and Mclntir e (1979 ) (CD , Tabl e 11-39 ) al l include d adjustment s fo r soi l and hous e dus t lead . A nunadjuste d regressio n analysi s found a 3 o f 1. 4 fo r 6-1 8 yea r old s (Angl e and Mclntire , 1979) . Unadjuste d coefficient s o f 0.6 6 (al l children) , -2.6 3 (1- 5 y r olds )
and 2.1 0 (6-1 8 yea r olds ) wer e obtaine d b yBrunekree f (1984) . Th e surprisin g 3 fo r th e 1- 5 yea r old s coul d b e du e t o th e fac t tha t thi s ag e group wa s onl y sample d durin g on e year , wherea s samplin g o f olde r childre n wa s performe d
ove r 6 years . Brunekreef' s reanalysi s illustrate s tw o points : 1 ) anyslop e derive d fo r al l childre ni n th e study(1-1 8 yrs ) likel yi s deflate d b y includin g th e discrepan t result s o f th e 1- 5 yea r olds ; and 2 ) b yadjustin g fo r soi l and hous e dus t lea d i nth e analysis , th e slop e fo r ai r lea d decrease d three-fol d fro m2.1 0 t o 0.6 9 i nth e 6-1 8 yea r olds . 4 . Th e inhalatio n 3 valu e o f 2.4 6 fro m Roel s e t a l . (1976 ) wa s estimate d i n th e C D b

yadjustin g fo r dus t lea d level s measure d o n th e children' s hands . A

n unadjuste d regressio nanalysi s b yth e author s o f th e combine d dat a (197 6 throug h1980 ) yielde d a 3 valu e o f 5. 3 (Roel s e t al. , 1980) . Brunekree f (1984 ) segregate d th e dat a and compare d group s wit hlarg e difference s i n exposur e (i.e. , < 1 k mfro m smelte r vs . urban/rural ; 3 » 5.9 ) group s wit h smal l difference s i n exposur e a t hig hexposur e level s (i.e. , < 1 k m vs . 2. 5 k mfro msmelter ; 3 = * 4.6 ) and group s wit hsmal l difference s i n exposure s a t lo wlevel s (i.e. , 2. 5 k mfro m smelter/urba nvs . urban/rural ; 3 •**• * 13.7) . Th e hig hestimat e a t th e lowe r exposur e leve l i s influence d b ytw o extrem e values ; removin g the mleave s a slop e o f approximatel y9.8 . A s i n th e Brunekree f e t al . (1983 ) study , th e us e o f low-volum e sampler s likel y underestimate d ai r lea d exposures , and overestimate d th e 3 value , especiall yP.5 1

V.2 5 fo r thos e childre n nea r th e smelte r wher e larg e particle s predominate . Th e slop e ma yb e underestimate d fo r youn g children , however , sinc e thi s study onl ysample d childre n olde r tha n10 . Give nthes e differen t factor s and analyses , i t i s difficul t t o estimat e a "true " aggregat e slop e fro mRoel s e t al . (1976 , 1980) . I t i s clea r tha t a rang e o f possibl e slope s fo r thi s studyha s bee n calculate d tha t ar e dependen t o n exposur e level s and adjustment s fo r dus t lead , and whic har e al l greate r tha n th e slop e fo r inhale d ai r lea d alon e (2.46 ) cite d i n th e criteri a document . 5 . Similarly , analyse s o f th e Yanke l e t al . (1977 ) dat a adjuste d fo r soi l lead , cleanliness , dust , education , and/o r pic a hav e yielde d inhalatio n 3estimate s rangin g betwee n 1.0 1 and 1.5 3 a t an ai r lea d leve l o f 1. 0 pg/m* * (Yanke l e t al. , 1977 ; Snee , 1982 ; Walte r e t al. , 1980 ; CD , Tabl e 11-39) . Brunekree f (1984 ) estimate d 3 value s betwee n 2. 4 and 3. 3 dependin g o nag e afte r comparin g th e highes t and lowes t expose d children' s unadjuste d Pb B level s fro m1974 . Th e remainin g slope s liste d i n Tabl e 5- 4 ar e base d o n dat a fro mchildre n whos e Pb B levels , a s som e i n Yanke l e t al . (1977) , exceede d 2 5 pg/dl . A s discusse d i n th e CD , th e relationshi p betwee n lea d uptak e and Pb B level s abov e abou t 3 0 pg/d l appear s t o b e non-linea r (CD , p . 10-31 ; Marcus , 1985) . Becaus e Pb B level s abov e 25-3 0 pg/d l ar e abov e th e maximu mPb B leve l o f health-relate d concer n (se e Sectio nVII.C) , however , thes e slope s ar e les s relevan t t o th e presen t review . I n summary , th e abov e analyse s usin g th e aggregat e approac hassum e th e sam e sourc e fo r mos t lea d i n air , soil , and housedust , and tha t adjustmen t o f Pb B level s fo r soi l o r dus t lea d tha t yield s an inhalatio n slop e under

estimate s th e "true " impac t o f atmospheri c lea d o n Pb B levels . Arang e o f value s ca n b e estimate d fro ma ) additional , and apparentl yrelevant , studie sV-2 6

no t use d t o deriv e inhalatio n slope s (i.e. , Zielhui s e t al. , 1979 ; Brunekree f
e t al. , 1981 , 1983 ) and b ) aggregat e analyse s tha t includ e bot hdirec t (inhalation ) an d indirec t (vi a soil , dust , etc. ) ai r lea d contribution s i n th e ke y"inhalatio n slope " studie s cite d i nth e criteri a document . Although fa r fro mconclusive , thes e studie s and analyse s sugges t a rang e o f possibl e bloo d lead/ai r lea d aggregat e slope s i nth e rang e o f 2 t o 1 0 fo r young , moderatel yexpose d childre n wit hth e mos t reliabl e slope s fallin g betwee n3
and 5 (CD , p . 11-104) . Becaus e th e blood/air lea d relationship s wer e derive d fro mstudie s whic hmeasure d ai r lea d concentration s average d ove r period s rangin g betwee n on e mont hand on e yea r (Se e Tabl e 5-3) , and becaus e long-ter maverage s (e.g. , annual ) ma yno t reflec t short-ter m (e.g. , monthly ) pea k averages , i t i s possibl e tha t applyin g thes e slope s t o estimat e th e impact s o f differen t ai r lea d level s woul d yiel d overestimate s o f Pb B level s i f th e ai r lea d standar d considere d i s a one-mont haverag e (Se e Sectio n VII.A) . Any overestimation , however , i s likel yt o b e smal l give n th e long-ter mpatter n o f lea d accumulatio ni n th e environmenta l medi a t o whic hchildre n ar e predominantl yexpose d (i.e. , soils , dust , food ) and th e resultin g modulatio n b yth e environmen t o f potentia l short-ter m pea k exposur e levels . Therefore , i t ca n b e assume d tha t thes e slope s ar e applicabl e i n estimatin g Pb B level s associate d wit hdifferen t monthly , a s wel l a s calenda r quarterly , averag e ai r lea d levels . I t i s importan t t o add , a s discusse d i nAppendi xA , tha t som e o f th e absorbe d lea d tha t accumulate s i n th e skeleto n deposit s i n th e spong y trabecula r bone s (e.g. , rib , vertebrae ) wher e i t ma yb e resorbe d int o th e bloo d stream . Becaus e air-bloo d slope s ar e derive d fro mepidemiologica l studie s i n whic hexposur e t o ai r lea d wa s assesse d ove r days , weeks , o rP.5 3

V-2 7 • months , anadditiona l facto r mus t b e allowe d fo r possibl e re-entr yo f lea d int o th e bloo d transferre d fro m bon e o r othe r long-ter mstorag e (Chamberlain , 1983) . Base d o nisotopi c rati o and radiolabe l trace r studie s o n adults , Chamberlai n e t al . (1978 ) estimate d thi s facto r t o b e 1.3 , althoug hi t i s likel yt o b e highe r i nchildre n becaus e o f th e rapi d growt hand hig hrat e o f turnove r i n thei r skeleta l systems . Applyin g thi s facto r t o th e bloo d lead/ai r lea d aggregat e slop e rang e discusse d abov e (3- 5 pg/m** ) yield s a rang e o f abou t 4 t o 6 . Us e o f thes e slope s t o evaluat e alternativ e ai r lea d level s i s discusse d i n Sectio n VII.C. 2 alon g wit hth e tw o othe r modelin g approache s introduce d i nthi s section .P.5 4

V I

. CRITICA LELEMENT S I N THE REVIE

WO F THE PRIMAR

YSTANDAR

D A

. Mechanism s o fToxicit y Th e toxicologica l impac to fenvironmenta l lea d ca n eithe rb e th e cumulativ e produc to fcontinuou s low-leve l exposure , o ro fsingl e o rrepeate d acut e exposures . Advers e effect s ar e du e essentiall yt o th e mobil e fractio n o fabsorbe d lea d withi n th e body

. Thus , a majo rdeterminan to ftoxicit y i s th e distributio n o flea d among bindin g protein s an d compartment s tha t contai n susceptibl e enzym e system s o rothe rtarge tsite s (Raghava n e tal. , 1981 ; Silbergeld , 1983)

. Th e effect s o flea d o n subcellula rstructure s an d processe s resul ti n biochemica l derangement s commo n t o an d affecting , man ytissue s an d orga n systems
. Thes e biochemica l alteration s ca n b e linke d t o th e divers e type s o flead-base d functiona l disruption s o forga n system s tha toperat e i n a coordinated , interdependen tway .

Th e majo rmolecula rbasi s underlyin g lead' s toxicit yi n variou s human orga n system s an d tissue s i s believe d t o be it s abilit ya s a metalli c catio n t o bin d wit h specifi cbiochemica l ligands , suc h as sulfhydryl , amino , an d carboxy l groups , presen ti n biomolecula rsubstance s crucia l t o norma l physiologica l function s (Moore e tal. , 1980)

. Thi s bindin g interfere s wit h physiologica l processe s throug h th e followin g mechanisms : 1

. Inhibitio n o fenzym e activit y Lea d inhibit s a tleas ttw o enzymes i n th e hem e biosyntheti cpathway , delta-aminolevulinat e dehydras e (ALA-D ) an d ferrochelatas e (Chisolm , 1981) , a s wel l a

s enzymes an d cofactor s involve d i n maintainin g th e structura l integrit yo fre d bloo d cel l an d protectin g the m agains toxidatio n — Na + , K + -activate d adenosin e triphosphatas e (Na + , K + - ATPase) , pyrimidine 5'-nucleotidas e (Py-5-N) , superoxid e dismutase , an d glutathion e (Hasa n e t al. , 1967 ; Secch i e tal. , 1973 ; Raghava n e tal. , 1981 ; Pagli a e tal. , 1975 ;P.5 5

VI- 2 Valentin e e t al. , 1976 ; Levande r e t al. , 1980 ; Gelma ne t al. , 1978) . Th e synthesi s o f tetrahydrobiopteri n ( a cofacto r i nbrai nneurochemistry ; se e below ) and th e activit yo f brai nadeny l cyclas e (associate d wit hneurochemica l receptors ) ar e als o inhibite d b ylea d i nvitr o and i nviv o a t lo wconcentration s (Purdye t al. , 1981 ; Sauerhof f and Michaelson , 1973 ; Nathanso nand Bloom , 1975) . I t i s importan t t o not e tha t althoug hcatalyti c activit yo f thes e susceptibl e enzyme s ma yb e diminishe d acros s a wid e rang e o f lea d exposur e dow nt o very

lo wlevels , sometime s withou t anobservabl e threshold , th e physiologica l o r functiona l consequence s o f suc hinhibition s depen d o nth e reserv e capacit yo f th e enzymes , th e healt han d nutritiona l statu s o f th e individual , and subsequen t exposure s t o lea d and othe r environmenta l stres s factors . Thes e issue s a s wel l a s dose-respons e relationship s ar e addresse d i nSectio nVII.C . and Appendi xD . 2 . Altere d cellula r energ ymetabolis mand io ntranspor t Energ ymetabolis moccupie s a centra l positio ni nal l biologi c processe s an d substantia l interferenc e wit hon e o r mor e step s i ncellula r energetic s ca nhav e immediat e and sever e effect s o nth e usua l functiona l output s o f a cell , tissue , o r organ . Mitochondria l structur e an d a variet y o f it s function s i nenerg ymetabolis mar e ver ysensitiv e t o lead , particularl y i nrapidl ydevelopin g tissue s i nth e youn g (Holtzma n and She nHsu , 1976 ; Bul l e t al. , 1979 ; Holtzma ne t al. , 1978) . Effect s includin g uncouple d oxidativ e phosphorylatio n(Goye r and Moore , 1974) , inhibite d substrat e oxidatio n(Bul l e t al. , 1975) , and change s i nmitochondria l membran e permeabilit y and transpor t o f ions , especiall ycalciu m(Ca ++ ) (Holtzma ne t al . 1977 ; Bull , 1980) , occu r a t level s a s lo wa s 1 0 micromole s ( p moles ) i nintac t cellula r systems . Becaus e o f th e pervasiv e rol e calciumplay s i nregulatin g cellula rP.5 6

VI- 3 function , a wid e rang e o f linkage s betwee nlead' s impact s o nCa + + and energ ymetabolism , and altere d functiona l activit yand developmenta l delay s i nth e kidney , liver , brai nand smoot hmuscl e hav e bee npropose d (Bul l e t al. , 1975 , 1979 ; Bull , 1980 ; McCaule ye t al. , 1979 ; Silbergeld , 1983 ; Pound s e t al. , 1982 ) and ar e discusse d below . 3 . Competitio nwit hion s fo r essentia l bindin g site s and altere d neurochemistr y Lea d absorption , distribution , and retentio ni s know nt o vary dependin g o ndietar yintak e o f calcium , iron , copper , an d zinc , a s wel l a s othe r nutrient s (e.g. , protein , fat , vitami nD ) (Mahaffe yand Michaelson , 1980) . Inaddition , increase d susceptibilit yt o th e toxi c effect s o f lea d
o nhem e synthesi s and o nneurologica l functio nha s bee nassociate d wit h deficiencie s i ncalcium , iron , copper , an d zin c (Mahaffey-Si xand Goyer , 1970 , 1972 ; Klaude r and Petering , 1977 ; Cerklewsk i an d Forbes , 1976) . Thes e metaboli c interaction s ca nb e expecte d 'amon g element s tha t shar e commo nchemica l propertie s and compet e fo r commo nmetaboli c bindin g sites , suc ha s th e mucosa l protein s responsibl e fo r absorptio nand transpor t
acros s th e intestina l wall , an d o nspecifi c intracellula r enzymes . Lead-induce d alteratio no f cellula r calciu mhomeostasis , a t level s a s lo wa s 1 0 p moles , eithe r b ydirec t competitio na t recepto r bindin g site s (Barto ne t al. , 1978 ; On g an d Lee , 1980 ; Haberman n e t al. , 1983 ) o r indirectl yb

yreducin g energ yproductio nand impairin g mitochondria l an d cel l membran e transpor t "pumps " (Pound s e t al. , 1982a ) coul d distur bmultipl e cel l function s o f differen t tissue s tha t depen d upo ncalciuma s a messenge r o f hormona l an d electrica l stimul i o r a s a modulato r o f cycli c nucleotid e metabolis m(Rasmusse n and Waisman , 1983 ; Rosen , 1983) . Fo r example , lo w level s o f lea d inhibi t th e calcium-mediate d regulatio no f pyruvat e kinas e activit yessentia l t o hepati c glycolysi s (Pound s e t al. , 1982b) , and som eVI- 4

calcium-dependen t neurotransmissio n tha t regulate s th e propagatio no f
nerv e impulse s i nth e brai n(Silbergel d e t al. , 1977 ; Silbergel d and Adler , 1978) . Beside s competitio nwit hcalciuma t synapti c bindin g sites , othe r mechanism s b

ywhic hlea d a t lo wdose s ma yalte r th e functionin g o f neurotrans
mitte r pathway s (se e CD , Tabl e 12-7 ) include : 1 ) inhibitio ni nth e brai n o f th e enzyme s (Na,K)-ATPas e whic hhelp s maintai nth e iondistributio nabou t th e cellula r membran e require d fo r neurona l activit y(Valle e and Ulmer , 1972) , and adeny l cyclase , whic hregulate s cycli c AM P metabolis mand synapti c transmissio n(Nathanso nand Bloom , 1975) ; 2 ) inhibitio no f sodium-dependen t neurotransmitte r uptak e (Silbergel d an d Goldberg , 1975) ; 3 ) impairmen t o f cerebella r and cerebra l energ ymetabolis m(Holtzma ne t al. , 1978 ; Bul l e t al. , 1979) ; 4 ) inhibitio no f tetrahydrobiopterin , whic hhelp s contro l th e synthesi s o f th e neurotransmitter s dopamin e and norepinephrin e (Purd ye t al. , 1981) ; an d 5 ) inhibitio no f hem e synthesi s resultin g i na ) a naccumulatio no f AL Ai nth e brai ntha t disrupt s th e synthesi s and functio no f th e neurotransmitte r GAB A(Sass a e t al. , 1979 ; Silbergel d and Lamon , 1980) , and b ) reduce d hem e level s i nth e live r tha t appea r t o alte r th e activit yi nth e brai no f th e amin o acid , tryptophan , and th e transmitte r t o whic hi t contributes , serotoni n (Litma n and Correia , 1983) . I nadditio nt o th e abov e mechanisms , lea d mayexer t it s toxicit yb yit s abilit yt o rapidl ycleav e messenge r RN A(a t concentration s i nsolutio na s lo wa s 0.00 1 millimoles ) and disrup t protei nsynthesi s (Farkas , 1975 ; Brow n e t al. , 1983) . I t i s uncertai nwhethe r a commo nunderlyin g mechanismi s involve d i n th e divers e functiona l impairment s produce d b ylead . I t doe s appea r however , tha t lead affect s biologica l system s directl yrathe r tha nthroug hmetaboli c transformation , an d tha t ther e ma yb e n o biologica l threshol d fo r it sP.5 8

VI- 5 effect s a t subcellula r o r cellula r site s o f action . Externa l exposur e level s o r interna l circulatin g level s (bloo d lea d concentrations ) o f lea d sufficien t t o achiev e subcellula r o r cellula r concentration s associate d wit hth e bio

chemica l change s describe d abov e remai n t o b e defined . B . Effect s o f Concer n Lea d mayproduc e physiological , and ultimately , pathologica l effect s i n a variet yo f tissu e and orga n system s acros s a broa d rang e o f exposur e levels . Evidenc e fo r suc heffect s i s draw n fro mi n vitro , anima l toxicological , and huma n clinica l and epidemiologica l studies ; Base d o n thes e data , summarize d i n th e C D (Chapte r 12) , effect s i n th e followin g area s ar e o f primar yinterest : 1 ) hem e biosynthesi s and relate d function s 2 ) neurobehaviora l functio n 3 ) cardiovascula r functio n 4 ) kidne yfunctio n 5 ) reproductio nand developmen t 6 ) possibl e carcinogenesis/mutagenesi s 7 ) immunologica l functio n 8 ) liver , gastrointestinal , and endocrin e functio n Th e majo r implication s o f th e availabl e literatur e relate d t o eac ho f thes e effec t area s ar e discusse d i n Appendi xD and summarize d i n Sectio n VII.C . a s the yrelat e t o assessin g th e risk s associate d wit halternativ e lea d NAAQS . C . Sensitiv e Populatio n Group s Tw o populations , pre-schoo l ag e childre n(_ < 6 year s old ) and pregnan t women , ar e define d i n th e C D a s particularl ysensitiv e t o lead . Severa l factor s predispos e youn g childre n t o lead-relate d risks : 1 ) greate r lea dP.5 9

VI- 6

conten t o f thei r diet s whic hinclud e larg e portion s o f processe d foods , canne d milk , and drinkin g water ; 2 ) norma l mouthin g behavio r (e.g. , finge r lickin g and immatur e dietar yhabits ) whic hca n transfe r lead-contaminate d soi l and dus t fro mthei r hand s int o th e gastrointestina l (GI ) tract ; 3 ) greate r lea d intak e int o th e respirator yand G I tract s o n a bodyweigh t basis ; 4 ) greate r lea d absorptio n and retentio n rates ; 5 ) greate r prevalenc e o f nutrien t deficiencie s whic henhanc e lea d G I absorptio n rate s and toxicologica l effects ; 6 ) relativel ygreate r proportio no f thei r lea d bodyburde n i n sof t tissue s an

d othe r labil e pool s rathe r tha ni nslo wexchang e pool s (e.g. , dens e bon e matrix ) a s compare d t o adults ; 7 ) a les s develope d blood-brai n barrie r tha t ca n allo wgreate r entr yo f lea d int o th e brain ; and 8 ) an inherentl ygreate r physiologica l sensitivit yo f developin g tissue s and organs , a s indicate d b ylowe r thresholds , and greate r severit yfo r lead-induce d effect s i n th e hematologica l and neurologica l systems . I n addition , dietar yand metaboli c imbalances , and period s o f physiologica l stress , no t unusua l i nyoun g children , ca ncaus e variation s i n th e leve l o f toxicologicall yactiv e lead throug hbone-lea d mobilizatio n and change s i n lea d absorptio n rate s (Chisol mand Harrison , 1956 ; Rose n and Markowitz , 1980 ; Arak i and Ushio , 1982) . Physiologica l sensitivit yt o lead ma yb e a t a maximu n durin g feta l developmen t whe n th e centra l nervou s syste m i s undergoin g it s mos t pronounce d growth . Persisten t effect s o nneurologica l functio n hav e bee n observe d followin g i n uter o lea d exposur e i n experimenta l animal s and hav e bee n suggeste d b

ysom e preliminar yresult s fro m huma n longitudina l studies . Th e pregnan t woma n i s considere d sensitiv e insofa r a s sh e i s th e exposur e vehicl e fo r he r unbor n child , sinc e lea d i s transferre d acros s th e placenta . However , ther e i s som e evidenc e tha t indicate s a greate r ris k o f materna lP.6 0

VI- 7 deliver ycomplication s a t relativel ylo wPb B level s a s wel l (Appendi xD.5) . Ther e wer e abou t 23. 3 millio npre-schoolag e childre ni nth e U.S . i n 198 2 (U.S . Burea u o f th e Census , 1982) ; som e 14. 2 millio nlive d i nurba n area s an d approximatel y240,00 0 liv e nea r poin t source s wher e lea d exposur e i s generall yhighe r (CD , Tabl e 13-10 ; Battye , 1985c) . Th e C D estimate s tha t abou t 4. 4 millio nchildre nbetwee nage s 3 an d 5 year s ar e particularl y sensitiv e t o lea d becaus e o f iro ndeficienc y(CD , p . 13-47) . Th e tota l numbe r o f wome no f child-bearin g ag e (betwee n1 5 an d 4 4 years ) i s estimate d t o b e abou t 5 4 million , wit habou t 3 3 millio nlivin g i nurba narea s (CD , Tabl e 13-10) ; o f these , approximatel y7 percen t ar e pregnan t a t anygive n tim e (CD , p . 13-47) . Level s o f ris k ar e no t unifor mthroughou t thes e population s bu t ar e likel yt o b e distribute d according t o individua l exposur e conditions , behaviora l patterns , and physiologica l sensitivit yt o lead .P.6 1

VII . FACTOR S T O B E CONSIDERE D I NSELECTIN GAPRIMAR YSTANDAR D FO RLEA D Thi s section , drawin g upo nth e previou s evaluatio n o f scientifi c informatio n fro m

th e criteri a document , outline s th e ke yfactor s tha t shoul d b e considere d b yth e Administrato r i n designatin g an appropriat e averagin g tim e and samplin g frequenc ycriteri a and i n establishin g th e leve l o f th e lea d primar ystandard . Preliminar ystaf f conclusion s and recommendation s regardin g th e mos t appropriat e polic yoption s i neac ho f thes e area s ar e presented . A . Averagin g Tim e T o b e protectiv e o f huma n health , th e averagin g perio d fo r th e lea d standar d shoul d b e chose n suc htha t variation s o f exposur e tha t coul d resul t i n advers e effect s d o no t occu r unles s th e standar d i s exceeded . Th e curren t averagin g tim e fo r th e lea d primar yNAAQ S i s a calenda r quarte r ( 3 months) . Whe n th e lea d standar d wa s propose d i n 1977 , th e averagin g tim e fo r th e primar ylea d NAAQ S wa s specifie d a s a calenda r mont hwhic hi s somewha t shorte r tha n th e approximatel y6 0 day s befor e steadystat e Pb B level s i n adult s adjus t t o change s i n ai r lea d concentratio n(Rabinowit z e t al. , 1973 ; Griffi n e t al. , 1975) . Amont haveragin g tim e wa s considere d appropriat e becaus e o f th e greate r ris k o f exposur e o f youn g childre n (4 2 FR63076) . Subsequently , EP Apromulgate d th e curren t NAAQ S wit ha calenda r quarte r averagin g tim e base d o nth e conclusio n tha t an ai r leve l o f 1. 5 ug/m* *
a s a ceilin g woul d b e saf e fo r indefinit e exposur e o f youn g childre n and tha t th e slightl ygreate r possibilit yo f elevate d ai r lea d level s withi n th e quarterl yperio d wa s no t significan t fo r healt h(4 3 F R46246) . Th e followin g assessmen t o f additiona l healt hand exposur e informatio n availabl e sinc e 197 8 and othe r evidenc e suggests , however , tha t a shorte r averagin g tim e tha n a calenda r quarte r ma yb e mor e appropriate .P.6 2

VIIr 2
1 . Equilibratio n Perio d fo r Bloo d Lea d i n Childre n N o direc t measurement s hav e bee nmad e o n thi s parameter , althoug hth e highe r metaboli c rate s i n childre n woul d b e expecte d t o produc e a mor e rapi d turnove r rat e o f re d bloo d cells , alon g wit hlead , i n thei r bloo d compare d t o adult s (Chamberlai ne t al. , 1978) . Dugga n(1983) , base d
o n limite d lea d balanc e dat a i n infants , ha s preliminaril yestimate d a considerabl yshorte r half-lif e o f bloo d lea d i nchildre n( < 1 week ) tha ni n adult s (18-2 8 days ; Griffi ne t al. , 1975 ; Rabinowit z e t al. , 1976 ; Chamberlai n e t al. , 1978) . I t i s o f interes t t o not e tha t regressio n analyse s o f NHANE S I I and nationa l gasolin e consumptio ndat a foun d tha t averag e bloo d lea d level s i nchildre n wer e mos t closel ycorrelate d wit hgasolin e lea d us e whe n a mont hla g wa s introduce d (EPA , 1985c) . Perhap s a mor e importan t consideratio n i s th e tim e i t take s fo r th e ver y smal l fractio no f "active " lea d t o b e transporte d i nplasm a and extracellula r flui d t o th e variou s targe t bodyorgan s and tissues . I t appear s tha t lea d level s i nplasm a ris e wit hlevel s i nwhol e bloo d (PbB ) i nadult s (Everso n an d Patterson , 1980 ; DeSilva , 1981 ; Cavaller i e t al. , 1978 ) and tha t lea d i s remove d fro m

plasm a wit ha half-lif e o f les s tha n on e hour ; indeed , ingeste d lea d appear s withi n urin e i n les s tha n an hou r (Chamberlai n e t al. , 1978) . Thes e finding s sugges t tha t th e rat e b ywhic hlea d i s transferre d t o sof t tissue s vi a th e plasm a i s fas t enoug htha t exces s lea d enterin g th e bloo d strea mwoul d b e rapidl ytransporte d vi a plasm a t o tissues . I naddition , a s illustrate d i n Figur e 10- 2 o f th e C D (p . 10-18 ; Manto n and Cook , 1984) , th e relationshi p betwee n plasm a lea d and bloo d lea d i s curvilinea r upward s suggestin g tha t transien t shift s i n bloo d lea d woul d resul t i n plasm a value s greate r tha ntha t predicte d o n th e basi s o f equilibrate d percentage s a t lowe r Pb B values . Thi s curvilinearit ybecome s manifes t i n adul t subject sP.6 3

VII- 3

a t 50-6 0 ug/d l (DeSilva , 1981 ; Manto nand Cook , 1984) , bu t ma ywel l appl y a t relativel ylowe r Pb B level s i nchildren . Furthe r suppor t come s fro mdat a o nexperimenta l animal s whos e level s o f lea d i nbrain , kidney , and femu r followe d mor e o f a direc t proportionalit y wit hth e leve l o f dosing tha nwit hbloo d lead , whic hma yrelat e t o th e fac t tha t plasm a lea d rise s proportionall yfaste r tha nwhol e bloo d lea d (Aza r e t al. , 1973 ; Gran t e t al. , 1980) . Base d o nthes e data , i t appear s reasonabl e t o assum e tha t increase d lea d exposur e ma yproduc e increase s i nsteadystat e Pb B level s i nchildre n soone r tha nth e 6 0 day s observe d i nadults , and tha t suc hchange s ma yno t reflec t thos e occurrin g i nth e level s o f toxicologicall yactive , o r mobile , lea d throughou t th e body , particularl yi f exposur e i s i nth e for mo f intermitten t pulses .

2 . Healt hImpact s Associate d wit hShort-ter mPeak s i nLea d Concentration s Mos t anima l and huma nstudie s o f lea d toxicit yus e measure s o f lea d exposur e whic hreflec t accumulation s ove r tim e (suc ha s bloo d and toot hlead ) and thu s d o no t readil yallo weffect s o f differen t exposur e pattern s t o b e distinguished . I t i s generall yaccepted , however , tha t acut e exposure s t o very hig hlea d level s ca nresul t i nimmediat e change s i n bloo d lea d and over t toxicity . Littl e informatio ni s availabl e o nth e effect s o f acut e exposure s t o lowe r level s o f lead tha t ar e relevan t t o ambien t ai r condition s althoug h ther e ma yb e som e caus e fo r concern . Fo r example , consisten t wit hth e fac t tha t lea d i s rapidl ytransporte d vi a bloo d plasm a int o targe t tissue s suc h
a s bon e marrow , singl e experimenta l lea d exposure s wer e followe d b ya rapi d (< 2 weeks ) alteratio ni nth e hem e productio ncycle , a s indicate d b yP.6 4

VII- 4 significantl yelevate d E P i nadul t me nand wome n(Stuik , 1974 ; Cool s e t al. , 1976) . Despit e limite d quantitativ e healt heffect s dat a o nhumans , i t appear s appropriat e i ndecidin g whethe r t o retai nth e calenda r quarte r averagin g tim e t o conside r th e exten t o f short-ter mpeak s i nai r lea d level s tha t ca nb e anticipate d a s a resul t o f th e implementatio no f suc ha standard . Th e risk s o f shorte r ter mexposure s t o lea d elevate d abov e a quarterly-average d standar d tha t migh t g o undetecte d wer e considere d i nth e 197 8 standar d decisio nt o b e minimize d becaus e 1 ) base d o nth e ambien t dat a availabl e a t tha t time , th e possibilitie s fo r significant , sustaine d excursion s wer e considere d small , and 2 ) i t wa s determine d tha t direc t inhalatio no f ai r lea d i s a relativel y smal l componen t o f tota l airborn e lea d exposur e (4 3 FR46246) . Mor e recen t dat a o nshort-ter mai r lea d level s ar e considere d below . Ai r qualit yanalyse s wer e performe d o nal l availabl e SAROA D dat a (10,71 2 monitor-quarters ) collecte d fro mstationar ysource , microscal e (fo r mobil e sourc e emissions) , and neighborhoo d scal e monitor s betwee n198 0 and 198 4 (Battye , 1984) . Maximu mmonthl yaverag e lea d concentration s wer e highe r tha n quarterl yaverage s b yanaverag e facto r o f 1.35 . Monthly-to-quarterl yaverag e concentratio nratio s fo r poin t sourc e monitor s wer e highe r tha nroadsid e and neighborhoo d monitor s wit hpea k ratio s fo r poin t sourc e site s a s hig ha s 2.8 6 (Se e Tabl e 7-1) . Thes e ratio s wer e largel yindependen t o f averag e lea d concentration . Thes e result s sugges t tha t i norde r t o protec t agains t maximu m monthl yaverag e concentration s o f 1. 5 pg/rn^ , fo r example , a quarterl yaverag e o f approximatel y1. 1 pg/m* * woul d b e required , whil e a quarterl yaverag e o f 1. 5 pg/m* * woul d allo wmonthl ymaximu maverage s a s hig ha s 2. 1 pg/rn*^ . Dail y maximu mlevel s wer e greate r tha nquarterl yand monthl yaverage s b yanaverag e facto r o f 2.0 8 an d 1.47 , respectively . Dail yt o quarterl yand dail yt o monthl yratio s nea r poin t source s wer e 2.5 9 and 1.72 , respectively ; a tTABL E 7-1 . MONTHLY-TO-QUARTERLY AVERAGE CONCENTRATIO NRATIO S FO

R DIFFEREN

T SITE S

Distributio n property Al l monitor s

1.3 5 1 .2 8 1.2 0 Point

sourc e monitor s

1.4 0 1 .31 1.2 5 Microscal e

roadsid e monitor s

1.2 7 1.2 3 1.2 0 Neighborhoo d

scal e roadsid e monitor s

1.2 7 1.2 b 1.2 0 Mean rati o Median Distributio n pea

k Uppe r limit s (on

e tailed ) 8 0 percen t 9 0 percen t 9 5 percen t 9 8 percen t 9 9 percen t 1.5 0 1.6 8 1.8 9 2.2 4 2.6 2 1.6 0

1.8 2 2.0 9 2.4 3 2.8 6 1.3 0

1.5 6 1.7 9 1.8 0 2.0 0 1.3 9

1.5 0 1.6 7 1.8 9 2.0 9 I c n

Source : Battye (1984 )P.6 6

VII- 6
microscal e and neighborhoo d scal e site s thes e ratio s wer e 2.0 8 t o 2.15 , an d 1.5 7 t o 1.61 , respectively . Th e magnitud e o f suc hexcursion s i nai r lea d level s ove r a give nquarterl y averag e standar d ar e clearl yo f concern , especiall yi f the yar e repeated . Th e healt hsignificanc e o f thes e variations , however , i s difficul t t o determin e a t present . I nsummary , althoug hth e frequenc yand healt hrisk s associate d wit h repeated , short-ter m increase s i nchildren' s lea d exposur e abov e tha t allowe d unde r an

ygive nstandar d i s difficul t t o quantif ya t thi s time , ther e doe s appea r t o b e som e caus e fo r concer ngive nthat : 1 ) lea d accumulate s i nth e bodyand i s onl yslowl yremoved , therefor e repeate d exposure s t o smal l amount s ove r manymonth s mayproduc e elevate d Pb B level s (CDC , 1985) ; 2 ) th e mean-lif e o f lea d i nbloo d i s approximatel y3 0 day s and th e toxicologicall yactiv e fractio no f bloo d lea d appear s t o respon d quickl yt o change s i nexposure ; and 3) ' base d o nlimite d studies , short-ter mincrease s t o moderat e level s o f lea d exposur e ma yresul t i nsignifican t interferenc e i nhem e biosynthesis . Effect s o nothe r physiologica l processe s associate d wit hsimila r short-ter mexposure s remai nt o b e studied . Base d o nth e abov e discussion , th e staf f recommend s tha t consideratio n b e give nt o a monthl yaverag e sinc e i t woul d b e mor e protectiv e o f children' s healt htha nth e curren t quarterl ystandard , especiall yaroun d poin t source s wher e emission s ma yb e mor e sporadic . Guidanc e i s requeste d fro mCASA C o n whethe r th e adde d protectio nprovide d b ya chang e t o a monthl ystandar d woul d warran t a revisio no f th e curren t quarterl yaveragin g period . Th e staf f als o request s commen t o nwhethe r th e availabl e informatio nsuggest s th e nee d fo r anaveragin g tim e les s tha na month . Give nth e norma l operatio no f th e on e i nsi xdaylea d samplin g schedule , th e numbe r o f sample s tha t ar e collecte d i nth e cours e o f a mont hwoul dP.6 7

VII- 7

no t provid e a statisticall yvali d estimat e o f th e actua l ai r qualit yfo r th e perio d (Thral l e t al. , 1984) . Consequently , shoul d a monthl yaverag e lea d NAAQ S b e chosen , i t woul d b e necessar yt o increas e th e ai r lea d samplin g fro mon e i nsi xdays , especiall ydurin g period s and i narea s o f maximu m concentration . Analyse s ar e underwa yt o determin e th e mos t appropriat e samplin g schedule s unde r a monthl ystandard . B . For m

o f th e Standar d Th e staf f recommend s tha t th e primar ylea d NAAQ S b e state d i na statisti

ca l for mrathe r tha nth e curren t deterministi c form . Unde r th e curren t standard , th e maximu m arithmetic mea naverag e ove r a calenda r quarte r i s no t t o excee d 1. 5 pg/m** . Th e statistica l for mca noffe r a mor e stabl e targe t fo r contro l program s and , wit hreasonabl ycomplet e data , i s les s sensitiv e t o trul yunusua l meteorologica l condition s tha ni s th e deterministi c form . Ingeneral , monthl yo r quarterl ymea nconcentration s o f lea d wil l varyfro mon e mont h
o r quarte r t o th e next , eve ni f emission s remai nconstant , du e t o th e rando mnatur e o f meteorologica l condition s tha t affec t th e dispersio n o f lea d particle s i nth e atmosphere . Thus , unde r a deterministi c form , complianc e wit hth e standard , an d consequentl yemissio ncontro l requirements , mayb e determine d o nth e basi s o f a mont ho r quarte r wit hunusuall y advers e weathe r conditions . Th e genera l limitation s o f th e deterministi c for mar e discusse d mor e full yelsewher e (Bille r and Feagans , 1981) . Recognitio no f thes e limitation s ha s mos t recentl yle d EP At o propos e statistica l form s fo r th e particulat e matte r standards . Conceptually , assumin g eithe r a monthl yo r quarterl yaveragin g time , a simpl e approac hwoul d b e t o expres s th e statistica l for ma s anexpecte d maximu mmonthl yo r quarterl yarithmeti c mea ndetermine d b yaveragin g th e annua l maximu mmonthl yo r quarterl yarithmeti c average s ove r a 3-yea rP.6 8

VII- 8

period . Specifi c adjustment s t o th e computation s necessar yfo r analyzin g lea d dat a ma yb e require d t o accoun t fo r possibl e change s i nth e frequenc y o f sampling . Analternativ e approac hwoul d b e t o directl yrecogniz e th e statistica l variabilit yassociate d wit hth e estimate d maximu mmonthl yo r quarterl y averag e an d develo p a toleranc e interva l s o tha t a sit e woul d no t b e classifie d a s i nattainmen t unles s th e estimate d exceedanc e rat e i s belo w th e standar d leve l b ymor e tha nthi s toleranc e interval . Similarly , th e toleranc e interva l approac hmigh t also.b e applie d i nth e othe r direction , s o tha t a sit e woul d no t b e considere d a s non-attainmen t unles s th e maximu m

monthl yo r quarterl yaverag e plu s th e toleranc e limi t i s greate r tha nth e standar d level . Th e magnitud e o f thi s toleranc e interva l coul d b e determine d b ydevelopin g a statistica l mode l t o accoun t fo r th e underlyin g variabilit yo f th e dat a and coul d incorporat e factor s suc ha s autocorrelation . Th e Agenc yha s solicite d comment s o nthi s genera l typ e o f statistica l standar d i nth e proposa l fo r th e particulat e matte r NAAQ S issue d o n Marc h20 , 198 4 (4 9 FR10408) . Thes e comment s wil l b e examine d b ystaf f
a s i t assesse s thes e alternativ e statistica l forms . Becaus e th e leve l o f protectio nafforde d b ya standar d varie s significantl ywit hth e averagin g period , form , and samplin g frequency , thes e interaction s mus t b e explicitl yconsidere d i nsettin g th e standar d level . Rathe r tha nattemptin g t o addres s thes e variable s simultaneously , i t mayb e easie r t o firs t selec t anacceptabl e standar d leve l unde r on e se t o f conditions , and the nadjus t th e leve l s o a s t o provid e roughl y equivalen t protectio nunde r alternativ e averaging periods , forms , and samplin g schedules .P.6 9

VII- 9

Fo r purpose s o f thi s paper , alternativ e ai r lea d level s presente d late r wil l assum e a constan t averag e (regardles s o f averagin g period) , deterministi c form , wit h1 i n6 da ysampling . Analyse s ar e underwa yt o bette r characteriz e th e distributio no f quarterl yo r monthl yambien t lea d concentration s and t o examin e whethe r adjustment s woul d b e necessar yunde r th e alternativ e statistica l for mapproaches , wit hpossibl ymor e frequen t sampling , t o provid e equivalen t protection . C . Leve l o f th e Standar d T o asses s th e degre e o f healt hprotectio ntha t woul d b e afforde d b y alternativ e lea d NAAQS , i t i s necessar yt o predic t th e bloo d lea d (PbB ) level s associate d wit hvariou s concentration s o f ai r lea d fo r th e sensitiv e population s and t o determin e th e toxicologica l consequence s associate d wit hdifferen t Pb B level s amon g youn g children . 1 . Summar yo f Healt hRisk s Associate d wit hDifferen t Pb B Level s Tabl e 7- 2 summarize s th e lowes t observe d effec t level s (i nterm s o f Pb B levels ) tha t th e C D conclude s t o b e thu s fa r credibl yassociate d wit h "unacceptabl e risk " fo r particula r healt heffect s o f concer noccurrin g amon g a t leas t som e childre n(CD , p . 13-32) . Manyothe r individual s ma y no t experienc e th e state d effec t unti l distinctl yhighe r Pb B level s ar e reache d (CD , p . 13-32) , o r conversel yrespon d t o eve nlowe r Pb B level s du e t o wid e range s o f individua l biologica l susceptibility , variation s i nnutritiona l status , and othe r factors . I t i s clear , a s discusse d i nSectio nVI an d i nAppendi xD , tha t lea d affect s manydifferen t orga nsystem s and biochemical/physiologica l processe s acros s a wid e rang e o f exposur e levels . Thes e effect s rang e fro mbiochemica l change s i nenerg ymetabolis mand synapti c neurotransmission , wit hn o apparen t threshol d o na subcellula r molecula r level , a s wel l a s alteration s i nbloo dP.7 0

VII-1 0

Tabl e 7-2 . SUMMAR YO FLOWES

TOBSERVE D EFFEC TLEVEL S FO R KE YLEAD-INDUCE

D HEALT

H EFFECT S I N CHILDRE N Lowes t Observe d Effec t Leve l (PbB ) Heme Synthesi s an d Hematologica l Effect s Neurologica l Effect s Rena l System Effect s Gastrointestina l Effect s 80-10 0 pg/d l
7 0 pg/d l 6 0 pg/d l 5 0 pg/d l 4 0 pg/d l Fran kanemi a

Reduce dhemoglobi n synthesi s Elevate dcoproporphyri n Increase durinary

ALA 3 0 pg/d l
I S pg/d l
1 0 pg/d l Erythrocyt e protoporphyi n A elevatio n ALA- 0 inhibitio n 1 Py-5- N activit y inhibitio n 

### 1

•> Encephalopath y sign s an

dsymptoms Periphera l neuropathie s 4 *

•> CN S cognitiv e effect s (I Qdeficits , etc. ) Periphera l nerve dysfunctio n (slowe dNCV's )

Altere dCNS'electrophysiologica l response s Chroni c nephropathy Colic , othe r over t (aminoaciduria , etc. ) gastrointestina l symptom s

Vitami n0 metabolis m interferenc e

Abbreviations : PbB = bloodleadconcentrations ; Py-S- N = pyrimidine-5'-nucleotidase . Source : CD , Tabl e 13-8 .P.7 1

VII-1 1

enzym e activit ydetectabl e a t Pb B level s a t o r belo w10-1 5 ug/d l (e.g. , ALA-D , pyrimidine-5-nucleotidase ) (CD , Tabl e 12-9 ; Angl e e t al. , 1982 ) t o severe , irreversibl e centra l nervou s syste mdamag e manifeste d b ymenta l retardation , encephalopathy(degenerativ e brai n disease) , and possibly , deat h
a t Pb B level s startin g betwee n 8 0 an d 10 0 ug/d l (CD , p . 12-62) . Othe r over t neurologica l damag e suc ha s periphera l neuropathie s hav e bee n observe d
a t Pb B level s a s lo wa s 40-6 0 ug/d l (CD , p . 12-95) . Clearl yadvers e effect s occu r i n othe r orga nsystem s a t thes e elevate d level s (60-10 0 pg/dl ) includin g chroni c nephropathy , gastrointestina l symptoms , and fran k anemia , representin g a n extrem e manisfestatio n o f reduce d hemoglobi n synthesi s whic hha s bee n observe d a t Pb B level s a s lo wa s 4 0 ug/d l (CD , p . 12-47) . Les s sever e bu t importan t sign s o f impairmen t i n norma l physiologica l functio n ar e eviden t a t simila r and lowe r exposur e level s tha n thos e associate d wit hover t intoxication . Th e nervou s syste mi s a critica l targe t fo r low-leve l lea d effects , whic har e summarize d i n Tabl e 7-3 . Indication s o f sensor yand periphera l moto r nerv e dysfunction , suc ha s slowe d nerv e conductio n velocitie s (NCV) , hav e bee nobserve d i n adult s wit hPb B level s a s lo wa s 30-5 0 ug/d l (CD , p . 12-61) . Significan t delay s i n neurologica l developmen t and persisten t alteration s i n neurobehavio r hav e bee nfound i nyoun g animal s expose d t o relativel ylo wlevel s o f lea d (Se e Appendi xD.2) . Determinin g th e subtl e interactiv e effect s o f lo wleve l lea d exposur e o n children' s neuropsychologica l developmen t i n relatio n t o socia l (especiall ycaregiving) , genetic , nutritional , and othe r influentia l variable s ove r tim e and controllin g fo r experimenta l
and analytica l biase s ha s prove d t o b e difficult , however , and ha s generate d contrastin g interpretations . Problem s encountere d i n th e conduc t and interpretatio n o f childhoo d lea d studie s ar e discusse d i n th e criteri a documen t and i nAppendi xD.2 .Effec t

Biochemica l Tabl e 7-3 . SUMMAR YU F LEAD' S EFFta s U N TH E NERVOU S SYSTE

M

_Exposur e Referenc e

I nvitro impairment of : synthesi s of tetrahydrobiopteri nU. l - 5 p M lea d Tneurotransmitte r cofactor ) i nra t brain ; adeny

l cyclas e solutio n an dNa,K-ATPas e activity i nra t brai nhomogenates ; enery y metabolism

i nra t brai nmitochondri a Purd y e t al. , 1981 ; Godardan dRobin son , 1976 ; Taylor e t al. , 1978 ; Umereket al. , 1981 ; Holtzmane t al. , 197 8 Delayeddevelopmen t o f ra t brai nenerg

y metabolism an drespiratio

n(i nvivo ) Alteredsynthesis , release , and/or uptake o f severa l neurotransmitter s i nviv o (dopamine , norepinephrine , serotonin , GABA ) 0.02 % lea dsal t i ndrinking wate r 0.00 4 - 2.0 % lea

d sal t i ndrinkin

g wate r McCaule y e t al. , 1979 ; Bul l et al . Bull , 198 3 1979 ,

Morphologica l an

dFunctiona l Developmen t Impaire dmyelin , glia l cel l developmen t i nra t brai n0. 1 - 4.0 % lea di ndie t Govon l e

t al. , 1978 , 1984 ; Mem o e t al. , 1980a,b , 1981 ; Lucch i e t al. , 1981 ; Sil bergel det al. , 1979 ; 1980a ; Duba s et al. , 1978 ; Goldmanet al. , 1980 ; Lit ma nan dCorreia , 198 3

Delayedsynaptogenesi s an dneurona l developmen t i n young , ra

t brai n

Delayeddevelopment o f explorator y an dlocomotor activity ; persistent learnin g an dbehavio r deficit s i

nanimal s expose

djm uter o or sinc e birth 0. 2 - 4.0 % lea di ndie t

>0.005 % lea

di ndie t Reyner s e t al. , 1979 ; Windeban ket al. , 1980 ; Stephen s an

dGerber , 198 1 McCaule y et al. , 1979 , 1982 ; Peti t an d LeBoutillier , 1979 ; Averil l an dNeedle man , 1980 ; Campbel l et al. , 1982 ; Al fan o an dPetit , 1982 ; Peti t e t al. , 1983 ; Cost a an

dFox , 198 3 Brown , 1976 ; Overmann , 1977 ; Overman net al. , 1981 ; Winnek e e t al. , 1977 ; Hasting s e t al. , 1979 ; Bul l et al. , 1979 , 1983 ; McCaule y e t al. , 1979 , 1982 ; Bushnel l an d Bowman , 1979 ; Ric e an dMilles . 1979 ; Croftone t al. , 1980 ; Jasonan dKellogg , 1981 ; Gross-Selbec kan dGross-Selbeck , 1981 ; Peti t et al. , 1983 ; Levi nan dBow man , 198 3 Conflictin

g preliminar

y findings ; possibl e smal l deficit s i

nearly sensorimotor an

dmenta l development i

ninfant s <1 5 pg/dl Pb B Dietrichet al . e t al. , 198 4 1984 ; Bellinge r Electrophysiologica l Altere delectrica l activity of isolate

d neuron s (i_n

_vitro ) Alteredvisua l an

delectrica l evokedresponses , visua l acuity , an

dspatia l resolutio ni n young rats , monkeys Subtle , persistent alteration s o f brai nelectrica l activity

(EE Gpatterns , brainste m an dauditor

y evokedpotentials ) i nyoung children Depressedconductio nvelocitie s i

nsensor

y an dmotor nerve s o f adult s an dchildren >1 p m lea dsolutio

n >1 % lea di ndrinking wate r 0.2 % lea

di ndie t

N o apparent threshol d dow nt o 15-3 0 pg/dl Pb B an dpossibl y

belo w >30-S 0 pg/dl Pb

B Fo

xan dSillman , 1979 ; Sillmanet al . 1982 ; Taylor e

t al. , 1978 ; Palme r et al. , 1981 ; Olsone

t al. , 198 1 Bushnel l e

t al. , 1977 ; Fo

xet al. , 1977 , 1979 , 1982 ; Winneke , 1980 ; Coope r et al. , 1980 ; Impelma

net al. , 198 2 Ott o et al. , 1981 , 1982 , 1984 ; Beningnu s e t al. , 1981 ; Burchfie l et al. , 198 0 Seppalainenet a\., 197S ; Arak i an d Honma , 1976 ; Melgaardet al. , 197b , Ashby , 1980 ; Bordo e t al. , 1982 ; John so ne t al. , 1980 ; Seppalainenan dHern berg , 1980 , 1982 ; Singe r et al. , 1983 ; Triebi g an

dNottbohm , 1983 ; Feldmane t al. , 197 7 i r o

r

oTabl e 7-3 . SUMMAR YO F LEAD' S EFFECT S O N TH E NERVOU S SYSTE

M (CONTINUED ) EJ_fec t Motor Nerv

e Functio

n Exposur e Referenc e

Smal l deficit s i

nperceptual-moto r integratio nan d fin e motor coordinationi nyoun y children

Conflictin

g result s at simila r exposur e level s 5U-6 0 pg/dl PbB , possibl y

a s lo w as 30 - 4 0 pg/dl or lower d e la Burde an

dChoate , 1972 , 1975 ; Landriganet al. , 1975 ; McBrid e et al. , 1982 ; Needlemanet al. , 1979 ; 1984 ; Winneke et al. , 1982a , 198 3 Rummo , 1974 ; Rumm

o e t al.,1979 ; Perino an dErnhart , 1974 ; Koto ket al. , 1977 ; Winnek e e

t al. , 198 4 Behaviora l Disorder s Symptom s associatedwit hhyperactivity i nchildren Attentio

n(reactio

ntime ) deficit s an ddistractability i nyoun g children Effec t leve l not adequatel y

define d >30-6 0 pg/dl Pb

B an dpossibl y

a s lo w as 15-2 0 pg/dl Balo he t al. , 1975 ; Gittlemanan dEskena zi , 1983 ; Davi det al. , 1976 , 198 3 Winneke e

t al. , 1983 , 1984 ; Needleman e t al. , 1979 , 1984 ; Yul e an dLandsdown , 1983 ; Hunte r e

t al. , 198 3 Auditor y an dLanguag e Processin g Deficit s i

nmotor speechbehavior , language compre hension , formulatio nbehaviors , auditor y processin

g >30-5 0 pg/dl Pb B d

e la Burde an

dChoate , 1975 ; Needleman e t al. , 1979 , 198 4 Cognitiv

e Functio

n Smal l deficit s i

nI Q score s o

nverba l performance , visual-motor perception , short-ter m memory , genera l intelligenc e amon g youn g children

Conflictin

g result s a

t similar exposur e level s >30-5 0 pg/dl PbB ; [possibly

as lo w as 15-3 0 pg/dl i

n sociall y

disadvantaged children ]

Over t Toxicity Periphera l nerv

e damag e amon

g chronicall y

exposed adult s an

dchildren

Encephalopathy , menta l retardation , possibly death amon g children >4 0 pg/dl

>80-10 0 pg/dl d e la Burde an

dChoate , 1972 , 1975 ; Rummo , 1974 ; Rumm o e t al. , 1979 ; Perin o an dErnhart , 1974 ; Ernhar t e t al. , 1981 ; Ernhart , 1983 , 1984 ; Needle ma ne t al. , 1979 , 1984 ; [Smithet al. , 1983 ; Harve

y et al. , 1983 , 1984 ; Yul e e t al. , 1984 ; Winnek e e t al. , 1983 , 1984J Yul e e t al. , 1983 ; Yul e an dLandsdown , 1983 , Winnek e e t al. , 1983 , 198 4

Lilli s e t al. , 1977 ; Spive y et al. , 1979 , Haenninene

t al. , 1979 ; Zimmerman Tansell a et al. , 1983 ; Erenberg et al. , 197 4 Gant e t al. , 1938 ; Smithe t al. , 1938 ; Bradle y et al. , 1956 ; Chisolm an dHarri son , 1966 ; Chisolm , 1965 ; Bradle y an dBaumgartner , 1958 ; Cumings , 1959 ; Rumm

o e t al. , 197 9 i

c oP.7 4

VII-1 4 Th e criteri a documen t conclude s that : "non e o f th e availabl e studie s o n th e subject , individually , ca n b e sai d t o prov e conclusivel ytha t significant cognitiv e (IQ ) o r behaviora l effect s occu r i nchildre na t Pb B level s < 3 0 ug/dl . Rather , th e collectiv e neurobehaviora l studie s ca n probabl yno wb e mos t reasonabl y interprete d a s bein g clearl yindicativ e o f likel yassociation s betwee n neuropsychologi c deficit s and lo wleve l lea d exposure s i n youn g childre n resultin g i n Pb B level s rangin g t o a s lo wa s 30-5 0 ug/dl . Th e magnitud e o f average observe d I Q deficit s appear s t o b e approximatel y 5 point s a t mea n Pb B level s o f 50-7 0 ug/d l and abou t 4 point s a t mea n Pb B level s o f 30-5 0 ug/d l (CD , p . 13-35) . Althoug hsuc hI Q deficit s ar e relativel ysmal l o naverage , suc hshift s i n th e mea n ca n mak e a substantia l differenc e i n th e percentag e o f childre n wit hIQ' s i n th e extreme s o f th e populatio n distribution(i.e. , belo w8 0 and abov e 125 ) and ma yimpac t th e intellectua l development , schoo l achievement , and socia l developmen t o f th e affecte d childre nsufficientl ys o a s t o b e regarde d a s adverse " (CD , p . 13-36) . I n childre n estimate d t o hav e Pb B level s betwee n 1 5 and 3 0 ug/dl , smal l deficit s i nI Q and attentivenes s hav e bee nobserved , althoug hn o consisten t statisticall ysignifican t association s hav e bee n found (Smit he t al. , 1983 ; Harve ye t al. , 1983 , 1984 ; Yul e e t al. , 1984 ; Hunte r e t al. , 1984 ; Winnek e e t al. , 1983 , 1984) . Because th e mos t reliabl e o f thes e studie s found 1- 2 poin t I Q deficit s remainin g afte r correctio n fo r confoundin g factors , th e criteri a documen t conclude s tha t "lea d canno t b e totall yrule d
ou t a s a possibl e etiologica l facto r contributin g t o th e inductio n o f suc h effect s i n th e 15-3 0 ug/d l range , base d o nexistin g publishe d studies " (CD , p . 13-36) . I n additio n t o I Q decrements , Pb B level s i n th e 30-5 0 ug/d l rang e ma yb e associate d wit hdeficit s i n auditor yand languag e processing , moto r coordination , appropriat e socia l behavior , and th e abilit yt o focu s attentio n (a e l a Burd e and Choate , 1972 , 1975 ; Needlema ne t al. , 1979 ; Winneke e t al. , 1983) . Th e degre e t o whic hlead' s effect s o n neuropsychologica l performanc e a t thes e level s persis t int o late r lif e remain s t o b e established . Altere d electrica l activit yi nth e brai nha s als o bee n associate d wit h Pb B level s i nchildre n (alon g wit hI Q decrements ; Burchfie l e t al. , 1980 )P.7 5

VII-1 5

i n th e rang e o f 30-5 0 ug/dl , wit hn o eviden t threshol d downt o 1 5 ug/d l
o r somewha t lowe r (Benignu s e t al. , 1981 ; Ott o e t al. , 1981 , 1982 , 1984) . Th e functiona l significanc e o f manyo f th e electrophysiologica l change s observe d belo w3 0 ug/d l (i.e. , slo wwav e potentials , synchronize d EE G amplitudes , visua l evoke d potentials ) ha s no t bee n established , althoug h
som e change s persiste d fo r a t leas t tw o year s (Ott o e t al. , 1982) . However , slowe d nerv e conductio n i nth e auditor ypathwa yha s bee n relate d t o pathologica l lesion s and t o non-specifi c demyelinatin g disease s suc ha s multipl e sclerosis ; thu s th e effect s o n auditor ybrainste mevoke d potential s observe d acros s th e rang e o f Pb B level s betwee n 6 and 5 9 ug/d l ma yb e indicativ e o f subtl e neurologica l impairmen t (Ott o e t al. , 1984) . Alteration s i n neurochemistr y(e.g. , neurotransmission , brai n mitochondria l function ) ar e eviden t withi n minute s o f exposur e t o submicromola r concentration s o f lea d i n vitr o and i nvivo . Althoug hth e functiona l significanc e i s difficul t t o asses s and n o estimate s ca n b e mad e o f Pb B level s a t whic hsuc h effect s occu r i n humans , thes e neurochemica l change s (e.g. , inhibitio n o f acetylcholin e releas e and Na,K-ATPas e activity ) exhibi t continuou s dose

respons e relationship s whic hma yfor m th e base s o f delaye d brai n development
and disrupte d neurobehaviora l functio n (Silbergeld , 1983) . Fo r example , effect s hav e bee n found o ncertai nbehaviora l (e.g. , reactio n tim e deficits) , and electrophysiologica l (e.g. , altere d EE Gpatterns , nerv e conductio n velocities ) measure s indicativ e o f CN S an d periphera l nerv e functio npertur
bations , supportin g a continuou s dose-effec t gradien t betwee n lea d and neurotoxicit ydown t o exposur e level s a s lo wa s 15-3 0 ug/d l PbB , o r perhaps , somewha t lowe r (CD , p . 12-137) . I n summary , althoug hther e hav e bee n inconclusiv e finding s and contrastin g interpretation s regardin g lead' s effect s o n specifi c neurobehaviora l indicator sP.7 6

VII-1 6

and function s (e.g. , verba l performance , emotiona l reactivity , perceptual-moto r integration , short-ter mmemory , attentio nelectrica l activit yi nth e brain )
and th e mechanism s involved , th e overal l evidenc e indicate s tha t lea d i s associate d wit hneurologica l impairmen t i nsom e childre nwit hPb B level s betwee n3 0 an d 5 0 ug/d l and tha t possibl ylowe r level s o f exposur e (i.e. , dow nt o 1 5 ug/dl ) ma yhav e som e small , bu t potentiall yimportan t and persisten t effect s o nneurologica l function . Th e impact s o f lea d o nhem e synthesi s and relate d system s ar e summarize d i nTabl e 7-4 . Becaus e hem e synthesi s i s a continuou s process , mos t o f thes e effect s ar e reversibl e upo nremova l o r reductio no f lea d fro mth e organis mo r cellula r system s involved . However , given : a ) tha t ther e ma yb e long-ter m effect s o f eve ntransitor ychange s i ndevelopin g tissue s in,children ; b ) heme' s pervasiv e rol e i nman yorga nsystem s and physiologica l processes ; and c ) th e sensitivit yo f hem e productio nt o lead , lead' s .interferenc e i n th e hem e syntheti c pathwa ymus t b e carefull yconsidered . A s discusse d i nAppendi xD , lea d interfere s wit hhem e synthesi s a t severa l point s i nit s metaboli c pathway : 1 ) Activityo f th e enzym e ALA-D , whic hcatalyze s th e conversio no f AL A t o porphobilinogen , i s inhibite d i nre d bloo d cell s a t Pb B level s belo w 10-1 5 ug/d l wit hn o clea r threshold . ALA- D activit yi nsof t tissue s suc h
a s liver , brain , and kidney , appear s t o b e inhibite d t o th e sam e degre e a t simila r Pb B levels ; 2 ) Accumulation s o f ALA , whic hresul t fro minhibite d ALA- D activity , hav e bee nnote d i nplasm a and urin e a t Pb B level s o f 4 0 ug/dl , and possibl y a s lo wa s 1 8 ug/dl . Increase s i nnon-utilize d AL Alikel yoccu r i nbrain , kidney , an d othe r tissue s a t roughl yth e sam e Pb B level s associate d wit h AL Aaccumulation s i nplasma ;Pb B

(ug/dl) 1 <1 0

>1 2
«1 5
>2 0 2 5 - 3 0

>3 3

1 8 - 4 0

»4 0 Effec t Tabl e 7-4 . SUMMAR YO F LEAD' S EFFECT S O NHEM E BIOSYNTHESI S AN D RELATE D SYSTEM S I NCHILDRE N Reference s Inhibitio n o f ALA-D , Py-5-N , red cel l ATPas e activit y Reductio n i n vitami n D hormon e synthesi s Accumulatio n o f E P indicatin g impaire d hem e synthesi s Impaire d globi n synthesi s Significan t E P elevatio n abov e norma l Significan t interferenc e wit hvitami n D hormon e synthesi s comparabl e t o tha t see n i n rena l disease s Accumulatio n o f underutilize d ALA ; possibl e interferenc e wit hneuro transmissio n Significan t reductio n i n hemo

globi n level s (anemia ) Impairmen t o f cytochrom e synthesi s and functio n (e.g. , dru g metabolism , cellula r energ ymetabolism ) Alteration s i n heme-base d neurochemica l synthesi s and neurologica l tissu e developmen t Hernber g an d Nikkanen , 1970 ; Secch i e t al. , 1973 ; Wad a e t al. , 1976 ; Angl e an d Mclntire , 1978 ; Valentin e and Paglia , 198 0 Rose n e t al. , 198 0
Roel s e t al. , 1976 ; Piomell i e t al. , 1977; , 1982 ; Hammon d e t al. , 1984 ; Rabinowit z e t al. , 198 5 Whit e and Harvey , 1972 ; Dresne r e t al. , 198 2 Roel s e t al. , 1976 ; Piomell i e t al. , 198 2

Rose n and Chesney , 1983 ; Chesne ye t al. , 198 3

Meredit he t al. , 1978 ; O'Flahert ye t al. , 1980 ; Nicoll , 1976 ; Brenna n an d Cantrill , 1979 ; Silber

gel d e t al. , 1980 , 198 2 Bett s e t al. , 1973 ; Rose n e t al. , 1974 ; Adenbojo , 1974 ; Puesche l e t al. , 197 2 Alvare s e t al. , 1975 ; 1976 , Meredit he t al. , 1977 ; Saenge r e t al. , 1984 ; Holtzma n and She n Hsu , 1976 ; Bul l e t al. , 197 9 Litma n and Correia , 1983 ; Whetsel l and Kappas , 1981 ; Whetsel l e t al. , 198 4 i

•~J

1 Thes e level s represen t lowes t observe d effec t level s i n a significan t fractio n o f childre n studied . I n som e cases , n o threshol d ha s bee n detected , a s note d b y< o r > signs .P_78 ^

VII-1 8 (3 ) Lea d impair s th e transmitochondria l transpor t o f iro n and instea d
o f producin g heme , th e mitochondri a accumulat e it s precursor , protoporphyri n which , lackin g iron , i s incapabl e o f performin g it s essentia l respirator y function . A s a resul t o f lea d intoxicatio n i n newl yformin g erythrocytes , protoporphyri n (referre d t o a s erythrocyt e protoporphyri n o r EP ) take s th e plac e o f hem e i n th e specifi c pocke t o f th e hemoglobi n molecule . A s th e re d cell s remai n i n th e circulation , zin c i s rapidl ychelate d a t th e cente r o f th e molecul e i nth e sit e normall yoccupie d b yiro n (Piomell i e t al. , 1982) . Th e resultin g zin c protoporphyri n (ZPP ) i s tightl yboun d i n th e availabl e hem e pocke t fo r th e lif e o f th e erythrocyte , normall y120-13 0 day s (Lamol a e t al. , 1975) . Th e Pb B threshol d fo r elevate d E P i n childre n i s approximatel y 1 5 ug/d l i n childre nwit hsignifican t elevation s (> 1 and 2 standar d deviation s abov e norma l E P mea n levels ) occurrin g i n 5 0 percen t o f childre n studie d a t Pb B level s o f betwee n 2 5 and 3 5 pg/d l (Roel s e t al. , 1976 ; Piomell i e t al. , 1982) . Th e healt hsignificanc e o f E P o r ZP P accumulatio n i s tha t i t indicate s tha t hem e o r hemoprotei n synthesi s i n manytissue s ha s bee n impaire d a s a resul t o f lead' s entr yint o mitochondri a (CD , p . 12-46) . Previously , E P elevation s a t Pb B level s aroun d 3 0 ug/d l wer e o f concer n base d o n functiona l disruption s i n hemoglobi n synthesi s a t 4 0 ug/d l and neurobehaviora l effect s abov e 5 0 ug/d l (EPA , 1977) . I nsettin g th e curren t lea d NAAQ S i n 1978 , 3 0 ug/d l wa s adopte d a s a maximu msaf e PbB , allowin g som e margi n o f safet yrelativ e t o level s associate d wit hinhibition s o f hemoglobi n synthesi s o r neuropsychologica l deficits . Thi s Pb B leve l wa s identica l t o th e Cente r fo r Diseas e Control' s (CDC ) previou s criteri a leve l fo r undu e lea d exposur e fo r youn g children . Recen t data , however , hav e provide d mor e informatio n o n th e extensiv e impac t o f lea d o n th e bod yhem e poo l and associate d disruption s o f manyP.7 9

VII-1 9 physiologica l processe s (se e Figur e 7-1) . Wit hincreasin g lea d exposure , impairmen t o f hem e and hemoprotei n synthesi s intensifies i ndifferen t orga nsystem s resultin g i nreduction s i noxyge ntransport , change s i n cellula r energetics , neurotransmitte r function , and i ndetoxificatio no f drug s and othe r foreig nagents , and impairments i nth e biosynthesi s o f importan t substance s suc ha s 1,25-dihydroxyvitami n D (1,25-0H2~D) . Inspectio no f Figur e 7- 1 reveal s effect s tha t ca nb e viewe d a s intrinsicall yadvers e a s wel l a s thos e tha t reduc e th e body' s abilit yt o cop e wit hothe r form s o f toxi c stress , e.g. , reduce d hepati c detoxificatio no f certai ndrug s and othe r xenobiotic s (a s a resul t o f lead-induce d impairmen t o f hepati c enzym e systems) , and possibl yimpairmen t o f th e immun e syste m(CD , p . 13-30) . O f th e functiona l consequence s associate d wit hhem e reduction s and lead' s interactio nwit hthos e processes , perhap s th e bes t quantitativ e dat a i s availabl e o nth e negativ e correlatio nbetwee nPb B level s (beginnin g a t 1 2 ug/dl ) and circulatin g level s o f th e vitami nD hormone , 1,25(0H) 2 D (Rose ne t al. , 1980) . Highl ysignifican t and profoun d depression s i n circulatin g 1,25(0H) g D level s wer e foun d i nchildre nwhos e Pb B level s range d fro m3 3 t o 12 0 pg/dl , wit hth e mos t strikin g decrease s abov e 6 2 pg/dl . Th e criteri a documen t conclude s tha t i t appear s likel ytha t lead-induce d reduction s i nhem e underli e thi s association , and tha t impaire d productio no f 1,25(0H) 2 D ca nhav e profoun d and pervasiv e effect s o ntissue s and cell s o f divers e typ e and functio nthroughou t th e body(CD , p . 12-49) : (1 ) Altere d level s o f 1,25(0H) 2 D ma yimpac t calciumhomeostasi s and thu s calcium-dependen t processe s essentia l t o severa l enzym e systems , th e transpor t o f and respons e t o variou s hormona l and electrica l stimuli , and cycli c nucleotid e metabolism . I naddition , lea d ma ydirectl yaffec t th e rol e o f 1,25(0H) 2 D i ncel l differentiation/maturation , immunoregulation , pancreati cP.8 0

VII-2 0

functio n(e.g. , insuli nsecretion) , an d mediatio no f tumorigenesi s (Se e Appendi x D.l(c) ; CD , pp . 12-4 0 t o 12-42) ; (2 ) Th e effec t o f lea d o n1,25(0H) 2 D i s a particularl yrobus t one , wit hPb B level s o f 30-5 0 pg/d l resultin g i ndecrease s i nth e hormon e tha t overla p comparabl e decrease s observe d i nchildre nwit hsever e kidne y injur ylackin g two-third s o f norma l rena l function , a s wel l a s i nthos e wit hvariou s geneti c disorder s suc ha s vitami nD-dependen t ricket s and hypoparathyroidis m(Rose ne t al. , 1980 ; Rose nand Chesney , 1983 ; Chesne y e t al. , 1983) . A t highe r levels , lead' s interferenc e wit hhem e synthesi s and othe r re d bloo d cel l function s (e.g., inhibitio no f Py-5- Nactivit ywhic haffect s membran e stability ) ma yresul t i nanemia . Althoug hthi s i s a seriou s clinica l manifestation , th e inhibitio no f hem e synthesi s a t lowe r lea d level s ha s muc hwide r implication s fo r a multitud e o f organ s and systems , a s describe d above , especiall yi nth e growin g child . Th e C D conclude s that : "Give nth e availabl e evidenc e indicativ e o f significan t effect s o n neurologica l functionin g and othe r importan t physiologica l processe s a s Pb B level s increas e abov e 15-2 0 pg/d l an d approac ho r excee d 30-4 0 pg/dl , th e rational e fo r continuin g t o vie w3 0 pg/d l a s a "maximumsafe " Pb B leve l i s calle d int o questio nan d substantia l impetu s i s provide d fo r revisin g th e criteri a leve l downward , i.e. , t o som e Pb B belo w3 0 pg/dl . A t thi s time , i t i s difficul t t o identif yspecificall ywha t blood-P b criteri a leve l woul d b e appropriat e i nvie wo f th e existin g medica l information . Clearly , 3 0 pg/d l ca nn o longe r b e see na s affordin g an ymargi no f safet ybefor e Pb B level s are reache d tha t ar e associate d wit hunacceptabl e ris k o f notabl e advers e healt heffect s occurrin g i n som e children . Thi s i s base d o na t leas t tw o grounds : (1 ) Pb B level s i nth e 30-4 0 pg/d l rang e ar e no wknow nt o "mask " fo r som e childre n markedl yelevate d chelatabl e bodylea d burden s tha t ar e comparabl e t o lea d burden s see ni nothe r childre ndisplayin g over t sign s and symptom s o f lea d intoxication ; and (2 ) Pb B level s i nth e 30-4 0 pg/d l rang e ar e als o associate d wit hth e onse t o f deleteriou s effect s i nsevera l orga nsystem s whic har e eithe r individuall yo r collectivel ysee na s bein g adverse .P.8 1

VII-2 1

"A t level s belo w3 0 ug/dl , man yo f th e differen t smalle r effect s reporte d a s bein g associate d wit hlea d exposur e migh t b e argue d a s separatel yno t bein g o f clea r medica l significance , althoug heac hi s indicativ e o f interferenc e b ylea d wit hnorma l physiologica l processes . O n th e othe r hand , th e collectiv e impac t o f al l o f th e observe d effect s (representin g potentiall yimpaire d functionin g an d deplete d reserv e capacitie s o f manydifferen t tissue s and organs ) may , a t som e poin t distinctl ybelo w3 0 ug/dl , b e see n a s representin g an advers e patter n o f effect s worthyo f avoidanc e wit hsom e adde d margi n o f safety . Th e onse t o f sign s o f detectabl e hem e synthesi s impairmen t i n manydifferen t orga n system s a t Pb B level s startin g aroun d 10-1 5 ug/dl , alon g wit h indication s o f increasin g degree s o f pyrimidin e metabolis minterferenc e and sign s o f altere d nervou s syste mactivity , coul d b e viewe d a s suc h a point . Or , alternatively , th e collectiv e impac t o f suc heffect s migh t b e argue d a s becomin g sufficientl yadvers e t o warran t avoidanc e (wit ha margi no f safety ) onl ywhe n th e variou s effect s com e t o represen t marke d deviations fro mnorma l a s Pb B level s excee d 20-2 5 ug/d l and begi n t o approac hth e mor e -clearl yadvers e 3 0 ug/d l level . Lastly , othe r argument s hav e bee n advance d t o th e effec t tha t an ydeviatio n fro mnorma l biochemica l level s o r physiologica l functionin g i n an y orga n syste mshoul d b e viewe d a s advers e healt heffect s t o b e avoided , eve n a t Pb B level s belo w1 0 ug/dl. " (CD , p . 13-40 ) Tabl e 7- 5 present s a preliminar ystaf f assessmen t o f th e dat a i n th e C D tha t ar e mos t usefu l i n determinin g a saf e Pb B fo r protectio n o f th e sensitiv e populations . Th e tabl e focuse s o nthos e effect s associate d wit hPb B level s a t and belo w4 0 ug/dl . Th e clearl yadvers e effect s a t highe r exposure s ar e liste d i nTabl e 7-2 . Base d o nth e abov e discussion , th e staf f conclude s tha t multi-orga n effect s resultin g fro mimpairment s i n hem e synthesi s and vitami n D metabolis m ar e likel ybetwee n25-3 0 ug/dl , and tha t potentiall ysignifican t effect s o n thes e processes , a s wel l a s o nth e centra l nervou s syste mma yb e possibl e a t th e lowe r Pb B level s indicated , bu t th e evidenc e and risk s ar e les s certain . I n evaluatin g th e healt heffect s i n th e contex t o f decision-makin g o n an appropriat e Pb B leve l o f concern , th e followin g consideration s ar e important . 1 ) Ther e i s considerabl e uncertaint yand controvers yregardin g th e natur e and degre e o f lead' s impac t o nneuropsychologica l functio n althoug h th e weigh t o f th e evidenc e suggest s a smal l bu t significan t associatio nP.8 2

Tabl e 7-5 . VII-2 2

STAF FASSESSMEN TO F KE YHEALT H EFFECT S O F LEA D Pb B Observe dEffect s Implication s 4 0 pg/d l Reduce dhemoglobi nsynthesis ; anemi a i nsome children 1

Possibl e I Q (4- 5 poin t avg. ) andbehaviora l deficits 2 Significan t reduction s i nvitami nDhormon e synthesis 3 Possibl e slowe dnerv e conductio nvelocities 4 Subtl e alteration s 1 nbrai nelectrophysiology ' Stron gevidenc e fo r significan t andpersisten t effect s o nhema tological , neurological , immunologica l anddetoxifica tio nsystems . 3 Uyg/d l Significantl y elevate dEP 6 Possibl e I Q ( 4 poin t avg. ) andattentiona l deficits 7 Significan t reduction s i nvitami nDhormon e synthesis 3 Possibl e slowe dNCVs 3 Subtl e alteration s i nbrai nelectrophysiology ^ Significan t Py-5- N

activit y

inhibition 8 Likely multi-orga neffect s resultin gfrom

hem e andvitami n Dimpairment . Some ris ko f behavioral/sensor y

disturbanc e an

d effec t o ncognitiv e functio no r academi c capacity . 2 5 ug/d l Significantl y elevate dEP 5 Possibl e I Q (1- 2 poin t avg. ) andattentiona l deficits 9 Reduce dvitami nDhormon e synthesis 3 Subtl e alteration s inbrai nelectrophysiology 1 " Likel y multi-orga neffect s resultin gfrom

hem e an

dvitami n Dimpairment . Som e ris ko f behavioral/sensor y

disturbanc e an deffec t o

ncognitiv e functio n o r academi c capacity . 2 Upg/d l Elevate dEP 6

Possibl e I Q (1- 2 poin t avg ) andattentiona l deficits 9 Reduce dvitami nDhormon e synthesis 3 Subtl e alteration s i nbrai nelectrophysiology 1 ^ Som e ris ko f multi-orga neffect s resultin gfrom

hem e andvitami nD impairment . Som e ris ko f behavio ral/sensor y

disturbanc e an

deffec t oncognitiv e functio no r academi c capacity . 1 5 pg/d l Lowes t leve l o f elevate dEP 6

Possibl e I Q andattentiona l deficits 9 Reduce dvitami nDhormon e synthesis 3 Subtl e alteration s inbrai nelectrophysiology 1 0 Reduce dALA- Dactivity 1 1 Smal l ris ko f multi-orga nimpair ment s resultin gfrom hem e an

dvita mi nDimpairment , behavioral/sen sor y disturbanc e andeffec t on cognitiv e functio no r academi c capacity . 5-1 0 pg/d l Reduce dALA- Dactivity, 1 1 Py-5- N synthesis 8 Subtl e alteration s inbrai nelectrophysiology 1 ^ Significan t functiona l effect s unlikely . Experimenta l alteration s i nneurochemistr y andcellula r energ y metabolism 1 2 Effect s detectabl e a t lo w invitr o level s o r experimenta l dosages ; correspondin ghuma nPbB level s an d functiona l significanc e difficul t t o determin e
ibett s e t al. , 1973 ; Rose ne t al. , 1974 ; Adenbojo , 1974 ; Puesche l e t al. , 197 2 2 D e la Burd e andChoate , 1972 , 1975 ; Perin o an dErnhart , 1974 ; Ernhar t e t al. , 1981 ; Ernhart , 1983 ; Needlema ne t al. , 197y Needleman , 198 4 3 Rose net al. , Iy80 ; Mahaffe y e t al. , 1982 ; Rose nandChesney , 198 3 4 Seppalaine ne t al. , 1979 ; Seppalaine nandHember g1980 , 1982 ; Feldma ne t al. , 197 7 5 Ott o e t al. , 1981 , 1982 , 1984 ; Beningnu s e t al. , 1981 ; Burchfie l e t al. , 198 0 6 Piomell i e t al. , 1977 ; 1982 ; Roel s e t al. , 1976 ; Hammon de t al. , 1984 ; Rabinowit z e t al. , 198 5 7 Needlema ne t al. , 1979 , 1982 ; Needleman , 198 2 8 Valentin e andPaglia , 1980 ; Angl e andMclntire , 1978 ; Angl e e t al. , 198 2 9 Smit he t al. , 1983 ; Harve y e t al. , 1983 , 1984 ; Yul e e t al. , 1984 ; Hunte r e t al. , 1983 ; Winnek e e t al. , 1983 , 198 4 1 0 0tt o e t al. , 1982 , 198 4 ^Hernber gandNikkanen , 1970 ; Granic ke t al. , 1973 ; Roel s e t al. , l»75b ; Wad a e t al. , 197 6 12 6ul l e t al. , 1975 , 1979 ; Holtzma nandShe nHsu , 1976 ; McCaule y e t al. , 1979 ; Holtzma ne t al. , 1978 ; Silbergel dand Adler , 1978 ; Silbergel de t al. , 1979 , 1982 ; Purdy e t al. , 1981 ; Litma nandCorreia , 198 3P.8 3

VII-2 3 betwee nlead , IQ , an d disturbance s i nsensory/attentio nprocesse s a t level s betwee n3 0 an d 5 0 pg/d l and possibl ydow nt o 1 5 ug/dl . I t i s hope d tha t improve d informatio nwil l resul t fro mongoin g researc ha s wel l a s fro mth e ongoin g EP A"ris k assessment " tha t wil l elici t probabilisti c exper t judgmen t o nth e existin g dat a bas e regardin g lead' s relationshi p t o I Q i nchildren . 2 ) Similarly , ther e i s incomplet e informatio no nth e medica l significanc e o f elevation s i nE P and th e dose-respons e relationshi p betwee nlea d an d hemoglobi ndecrements . Th e ongoin g ris k assessmen t wil l hopefull yprovid e usefu l informatio no nthes e issue s a s well . 3 ) Th e risk s associate d wit hreduction s i nvitami nD hormon e synthesi s an d altere d brai nwav e activit ya t Pb B level s _ < 3 0 ug/d l ar e difficul t t o determin e a t present . I t i s fel t tha t th e collectiv e impac t o f thes e change s alon g wit hothe r lead-induce d effect s a t lo wPb B level s shoul d b e considere d sufficientl yimportan t t o warran t avoidance . 4 ) A s par t o f thei r lea d poisonin g screenin g program , th e CD C ha s revise d thei r definitio no f lea d toxicit yfo r individua l childre nfro m 3 0 ug/d l t o 2 5 ug/d l PbB , accompanie d b yanelevate d E P leve l (>

_3 5 pg / dl ) (CDC , 1985) . Detectin g thes e level s identifie s a chil d a s requirin g immediat e medica l and environmenta l intervention . Th e revision s wer e base d o nth e recen t evidenc e o f neurobehavioral , hematological , and vitami nD metabolis meffect s o f lea d cite d above , and o nevidenc e tha t a bloo d lea d concentratio nma yunderestimat e th e bodyburde no f lea d i na child . CD C argue d tha t 3 0 ug/d l provide s littl e o r n o margi no f safety , and tha t th e biologi c threshol d fo r lea d toxicit ya s indicate d b yincreasin g E P levels , i s belo w2 0 ug/d l (CDC , 1985) . However , CD C acknowledge s tha t practica l consideration s mus t b e take nint o accoun t i nsettin g thi s level . A

ninterventio nleve l o f 2 5 ug/d l therefor e represent s anP.8 4

VII-2 4
accommodatio nbase d o na pragmati c decisio no nth e limit s o f effectivel y implementin g th e existin g screenin g progra mand ho wmuc hris k i s tolerable . 5 ) Th e Clea nAi r Ac t require s tha t th e ai r standar d b e precautionar y i nnatur e and tha t th e leve l shoul d no t b e base d o neconomi c o r technologica l considerations . Whil e th e lea d NAAQ S and CDC' s progra mshar e th e commo n goa l o f reducin g children' s lea d exposure , ther e i s animportan t distinction . Th e screenin g progra m i s a for mo f secondar ypreventio nan d i s necessar y t o preven t lea d toxicit yamon g susceptibl e children , bu t i s base d i n part , o npractical , technological , and cos t considerations . I ncontrast , th e lea d NAAQ S i s a for mo f primar ypreventio nt o contro l lea d emission s a t th e source , befor e opportunitie s fo r huma nuptak e and undu e risk s arise , and i s no t t o b e base d o ncost . Th e staf f conclude s o nth e basi s o f th e abov e consideration s tha t th e CD C interventio nleve l i s no t directl yanappropriat e surrogat e fo r th e lea d NAAQ S and tha t a Pb B leve l o f 2 5 ug/d l contain s littl e o r n o margi no f safet yfro mpotentiall yadvers e effect s o nhem e synthesis , vitami nD metabolism , and possibl yneurologica l and behaviora l functions . 2 . Predictin g Bloo d Lea d Level s unde r Alternativ e Ai r Lea d Level s Thre e approache s ar e examine d her e tha t ca nb e use d t o estimat e th e impac t o f alternativ e ai r lea d level s onPb B level s amon g children . Th e firs t i s t o combin e th e estimate s o f dail ylea d uptak e fro mal l route s o f exposur e fo r give nai r lea d concentration s wit hth e derive d lea d uptake-to

bloo d lea d relationships , a s presente d i nSectio nV.A . Th e secon d approac h i s t o directl yappl ymathematica l relationship s betwee nai r lea d and bloo d lea d derive d fro mpopulatio nstudie s and appropriat e statistica l analyse s tha t accoun t fo r children' s exposur e t o atmospheri c lea d throug h pathway s othe r tha ninhalatio nsuc ha s ingestio no f dus t and soi l (Sectio nP.8 5

VII-2 5 V.B.2) . Finally , a hybri d o f th e firs t tw o approache s i s provide d i nth e criteri a documen t i nwhic hmathematica l relationship s derive d fro mpopulatio n studie s ar e applie d t o estimate s o f lea d concentratio ni nindividua l medi a (Sectio nV.B.I) . Thes e thre e modelin g approache s ar e discusse d belo wand th e result s ar e presente d (i nTabl e 7-12 ) fo r consideratio ni n th e possibl e us e o f one , two , o r al l thre e approache s (wit han ynecessar y modification s usin g improve d data ) i nassessin g th e protectio nafforde d b yalternativ e lea d NAAQS . Al l thre e model s estimat e Pb B level s i nterm s o f populatio nmea n levels . Fo r purpose s o f settin g a lea d NAAQS , i t i s necessaryt o determin e th e bloo d lea d distributio ncorrespondin g t o a give nmea nPb B fo r th e populatio no f childre nsuc htha t a specifie d percentag e i s protecte d fro m exceedin g a maximu m acceptabl e Pb B level . I ndeterminin g suc ha distribution , i t i s importan t t o recogniz e tha t ther e i s significan t biologica l variabilit y withi nan

ypopulation , and i t i s thos e individual s wit hth e greates t advers e respons e t o anygive nlea d exposur e tha t ar e o f greates t concer n i nestablishin g a primar ylea d NAAQS . Ametho d t o conside r th e mos t susceptibl e segmen t o f th e populatio no f childre ni s discusse d here . Severa l epidemiologica l studie s hav e indicate d tha t th e lo g value s o f
measure d individua l Pb B level s i na uniformlyexpose d populatio nar e normall ydistribute d wit ha variation , includin g analytica l variation , rangin g betwee n1. 3 and 1.4 , whe nexpresse d a s a geometri c standar d deviatio n(GSD ) (Teppe r and Levin , 1975 ; Aza r e t al. , 1975 ; Billic k e t al. , 1979) . Usin g standar d statistica l techniques , i t i s possibl e t o us e th e geometri c standar d deviatio nt o calculat e th e mea npopulatio nbloo d lea d leve l tha t woul d plac e a give npercentag e o f th e populatio nbelo w anacceptabl e maximu m Pb B fo r anindividua l child . Th e NHANE S I I study , whic hprovide s th e bes t availabl e dat a i nterm s o f qualit ycontro l andP.8 6

VII-2 6 sampl e size , yield s estimate s o f GSD s i nth e rang e o f 1.3 4 t o 1.39 , un correcte d fo r analytica l variation , fo r variou s subgroup s o f youn g childre n wit hcomparabl e sex , age , income , an d plac e o f residenc e (i.e. , degre e o f urbanization ) (CD , p . 11-2 9 t o 11-30) . Byusin g thes e GSD s fo r separat e homogeneous population s identifie d i nth e NHANE S I I survey , i t i s possibl e tha t th e mos t sensitiv e segmen t (i.e. , highl yexposed ) o f th e populatio n i s no t bein g accuratel ycharacterize d sinc e fo r tha t grou p ther e i s likel yt o b e a differen t distributio no f exposure s fro mth e homogenou s NHANE S I I subgroups . Thi s i s indicate d b yth e fac t tha t th e GS D fo r al l blac k childre nlivin g i ncentra l citie s wa s 1.4 6 and fo r al l childre nsample d i nNHANE S II , th e GS D wa s 1.47 , no t adjuste d fo r age , income , o r degre e o f urbanizatio n(DHHS , 1984) . Th e rang e o f GSD s presente d abov e whic har e assume d t o b e constan t fo r th e entir e distributio nshoul d therefor e b e interprete d a s preliminar yattempt s t o characteriz e th e mos t appropriat e sub-population s o f childre ngive nth e availabl e dat a i nth e CD . Th e calculation s o f bloo d lea d distribution s unde r variou s ai r lea d level s usin g th e thre e model s presente d belo wshoul d als o b e considere d a s preliminar yunti l furthe r commen t an d CASA C guidanc e i s receive d o n thi s issue . Analytica l variatio nwhic hexist s i nanymeasuremen t ha s a nimpac t
o nth e bia s and precisio no f statistica l estimate s suc ha s th e GSD s derive d fro m

NHANE S II . Fo r thi s reason , i t i s importan t t o recogniz e th e magnitud e o f analytica l variatio ni nbloo d lea d measurement s du e t o measuremen t variatio n(i.e. , betwee nmeasurement s runa t th e sam e time )
and variatio ncreate d b yanalyzin g bloo d sample s a t differen t time s (CD , p . 11-26) . Correctin g thes e GSD s fo r th e overal l estimat e o f analytica l variatio nfo r th e NHANE S I I study(0.02083 ) yield s estimate d GSD s i nth e rang e o f 1.2 9 t o 1.34 . Usin g GSD s correcte d i nsuc ha way , althoug hprovidin gVII-2 7

a mor e accurat e characterizatio no f a give nbloo d lea d distribution , ma y no t b e appropriat e fo r thi s assessmen t becaus e th e healt heffect s studie s use d t o defin e a maximu m acceptabl e Pb B di d no t correc t thei r Pb B measurement s fo r analytica l variance . Thes e studies , lik e NHANE S II , generall yemploye d th e bes t availabl e measuremen t technique s and qualit ycontrol . Usin g "corrected " GSD s o non e hand t o predic t percentage s o f childre nwit hvariou s Pb B level s give na targe t mea npopulatio nPbB , and the nmatchin g thos e predicte d Pb B level s wit h"uncorrected " Pb B level s derive d fro mhealt h studie s i norde r t o asses s th e risk s associate d wit htha t populatio nmea n PbB , woul d resul t i na somewha t biase d assessment . Therefore , th e rang e o f GSD s presente d i nth e C D fro mNHANE S I I tha t ar e no t correcte d fo r analytica l varianc e wil l b e use d i nfurthe r calculations . Th e staf f encourage s an

ycommen t o r additiona l informatio no nthi s issue . I n settin g th e curren t lea d NAAQ S i n1978 , EP Aestimate d tha t i n orde r t o protec t 99.5 % o f U.S . childre nfro mattainin g a Pb B o f 3 0 ug/dl , a targe t populatio nmea nPb B woul d b e approximatel y1 5 ug/d l assumin g a GS D o f 1.3 . Simila r calculation s ca nb e mad e fo r othe r percentage s o f th e population , e.g. , 99. 9 o r 99.0% . Ther e ar e approximatel y2 5 millio n childre nunde r 7 year s o f ag e i nth e U.S. , som e 1 4 millio ni nurba n areas , and approximatel y240,00 0 livin g nea r poin t source s wher e atmospheri c lea d exposure s ma yb e hig h(CD , p . 13-47 ; Battye , 1985c) . Tabl e 7- 6 present s th e populatio nmea nPb B level s tha t woul d b e require d t o protec t 99.5 % o f U.S . childre nfro mreachin g variou s Pb B level s give nth e rang e o f uncorrecte d GSD s derive d fro mNHANE S I I fo r homogeneou s subpopulations . (Mea nPb B level s necessar yt o provid e 99.9 % protectio n woul d b e somewha t lower ; conversely , the ywoul d b e highe r fo r 99.0 % protection) . Thes e value s wer e calculate d usin g th e formul a give nt o describ e aP.8 8

VII-2 8 lognorma l distribution(Yanke l e t al. , 1977) : M g • GSD n= D n wher e Mg = geometri c mea n Pb B GS D = geometri c standar d deviatio n n = th e numbe r o f standar d deviation s D n = valu e o f Pb B a t a standar d deviation . Tabl e 7-6 . POPULATIO NMEANBLOO D LEAD LEVEL S (pg/dl ) REQUIRE D T O PREVEN T 99.5 % O F U.S . CHILDRE NFRO MEXCEEDIN GSPECIFIE D BLOO D LEAD LEVEL S (Assumin g GSD s o f 1.3 4 - 1.39 )



### GS D
1.3 9 1.3 4 MaximumAcceptabl e Bloo d Lea d Leve l (pg/dl )

2 5 2 0 1 5 1 0
10. 7 11. 8 

### 8. 6

9. 4 6. 4

7. 1 4. 3

4. 7

I t shoul d b e note d tha t i f th e GS D o f 1.4 7 calculate d fo r al l childre n sample d b

yNHANE S I I (no t adjuste d fo r age , sex , income , o r degre e o f urbanization ) i s used , th e populatio nmea n Pb B level s require d t o protec t 99.5 % o f childre n fro mexceedin g 25 , 20 , 15 , and 1 0 pg/d l woul d b e 9.3 , 7.4 , 5.5 , and 3. 7 pg/dl , respectively . a ) Integrate d Lea d Uptake/Biokineti c Mode l Tabl e 7- 7 present s th e uppe r and lowe r boun d estimate s o f average dail ylea d uptak e derive d i n th e Integrate d Lea d Uptak e Mode l i n Sectio n V.A. I fo r poin t source s and genera l urban/rura l area s unde r differen t averag e ai r lead concentrations , alon g wit hth e correspondin g Pb B level s predicte d fo r 2 yea r ol d childre nb yth e biokineti c mode l presente d i n Sectio n V.A. 2 (Harle yand Kneip , 1985) . Severa l uncertaintie s associate d wit hthes e estimate s ar e discusse d i n Sectio nV.A. I and Appendi xB . I t i s importan t t o emphasiz e tha t becaus e ai r lea d (an

d associate d dietary , soil , and dus t lead ) level s wer e assume d t o b e constan t a t whateve r ai r leve l wa s analyzed , th e uppe r end s o fP.8 9 VII-2 9 Tabl e 7-7 . AVERAG E BLOO D LEAD LEVEL S FO RCHILDRE NUNDE RDIFFEREN T AI RLEAD LEVEL S

(ESTIMATE D USIN GINTEGRATE D LEAD UPTAKE/BIOKINETI C MODEL ) Averag e Averag e Averag e Ai r Lea d Lea d Uptak e Bloo d Lea d (ug/m 3 ) 1 Typ e o f Are a (ug/day) ? (ug/d l ) 3

0.2 5

0.5 0

0.7 5



### 1. 0

1.2 5



### 1. 5

1.7 5 Genera l 4.8-11. 1 1.9-4. 4

Pt . Sourc e 7. 0 - 21. 3 2. 8 - 8. 6

Genera l 9. 2 - 17. 8 3. 7 - 7. 2 Pt . Sourc e 16. 3 - 29. 0 6. 6 - 9. 3

Genera l 14. 1 - 29. 4 5. 7 - 11. 9 Pt . Sourc e 22. 0 - 35. 8 8. 9 - 14. 5

Genera l 18. 9 - 33. 9 7. 7 - 13. 7 Pt . Sourc e 27. 4 - 45. 0 11. 1 - 18. 2

Genera l 24. 4 - 42. 8 9. 9 - 17. 3 Pt . Sourc e 37. 1 - 50. 3 15. 0 - 20. 3

Genera l 28. 2 - 48. 4 11. 4 - 19. 6 Pt . Sourc e 41. 8 - 62. 3 16. 9 - 25. 2

Genera l 29. 8 - 50. 9 12. 0 - 20. 6 Pt . Sourc e 46. 3 - 69. 1 18. 7 - 27. 9

*Ai r lea d level s tha t wer e use d t o calculat e dail yuptak e level s wer e assume d t o b e constan t and therefor e ca nrepresen t eithe r monthl yo r calenda r quarterl y averages . ^Uptak e estimate s derive d i nTabl e 5-1 . Rang e unde r eac hai r lea d leve l and locatio nreflect s uppe r and lowe r bound set s o f estimate s use d t o calculat e uptak e levels . 3 Pb B level s fo r 2 yea r ol d childre n derive d fro m lea d biokineti c mode l (Harle yand Kneip , 1985 ) discusse d i n Sectio n V.A.2 . Rang e unde r eac hai r lea d leve l and locatio n reflect s uncertaintie s i n uptak e estimates .P.9 0

VII-3 0 thes e range s i nparticula r ma yrepresen t "wors t case " populatio nmea n uptak e an d Pb B estimate s fo r eac hai r lea d concentration . Furthermore , estimate d Pb B level s a t 2 year s o f ag e wer e selecte d i norde r t o predic t th e maximu mimpact s o nyoun g children . A t thi s age , Pb B level s woul d b e highest , assumin g constan t exposure , accordin g t o th e biokineti c mode l (consisten t wit hth e NHANE S I I data) . Th e staf f believes , therefore , tha t give nth e availabl e dat a and necessar yassumption s use d i nthi s model , th e lowe r end s o f th e range s o f Pb B level s fo r th e differen t ai r lea d level s reflec t th e bes t estimate s o f lea d exposure , uptake , and metabolis mamon g individual s i ndifferen t location s withi nth e population . Th e lowe r boun d estimate s fo r 2 yea r ol d childre nwil l thu s b e use d a s th e predicte d mea nPb B level s unde r eac hai r leve l i nlate r calculations . Finally , usin g standar d statistica l technique s and identifie d character

istic s o f th e Pb B distributio nwithi nth e populatio n(discusse d previously) , i t i s possibl e t o calculat e fo r an ymea nPbB , th e individua l Pb B a t a specifie d standar d deviation . Thi s calculatio ni s illustrate d belo wfo r th e othe r tw o modelin g approache s and th e result s ar e late r summarize d i n Tabl e 7-12 . b ) Applicatio no f "Aggregate " Bloo d Lead/Ai r Lea d Relationship s fro mEpidemiologica l Studie s i ) Blood/Ai r Lea d Slop e Th e epidemiologica l studie s discusse d i nSectio nV.B . provid e quantitativ e estimate s o f th e relationshi p betwee nai r lea d exposure s and Pb B level s i nvariou s population s o f children . I nassessin g th e tota l impac t tha t atmospheri c lea d make s o ntota l exposure , th e aggregat e modelin g approac hdiscusse d i nSectio nV.B. 2 attempt s t o recogniz e th e simultaneou s presenc e o f lea d i nmultipl e environmenta l media . Thus , th e media nblood/ai r lea d inhalatio nslop e fo r childre n(s ) i s estimate d i nth e C D t o b e 1.9 2 fro mthre e majo r studie s (Yanke l e t al. , 1977 ; Roel sP.9 1

VII-3 1

e t al. , 1980 ; Angl e and Mclntire , 1979) , and aggregat e slope s tha t includ e bot hdirec t (inhalation ) and indirec t (vi a soil , dust , etc. ) ai r lea d contribution s typicall yyiel d value s i nth e rang e 3- 5 (CD , p . 11-108) . T o acoun t fo r possibl e re-entr yo f lea d int o th e bloo d transferre d fro mbon e o r othe r long-ter mstorage , Chamberlai n(1983 ) estimate s tha t blood/ai r lea d relationship s fo r adult s mus t b e multiplie d b ya facto r o f 1.3 , yieldin g a rang e o f aggregat e slope s betwee n4 and 6 fo r tota l ai r lea d exposure . I t i s possibl e tha t th e rapi d growt hand hig h rat e o f turnove r i nchildren' s skeleta l system s woul d requir e aneve n highe r adjustment . Assumin g tha t thes e slope s ar e reasonabl yaccurate , and tha t a t lowe r level s o f exposur e ( < 3 0 ug/dl ) a linea r relationshi p applie s (Chamberlain , 1983 ; CD , p . 11-64) , a 1 ug/m 3 chang e i nth e averag e ai r lea d concentratio n woul d produc e a correspondin g increas e o f betwee n4 an d 6 ug/d l i nth e averag e equilibrate d bloo d lea d leve l o f youn g children .

"ii ) Contribution s fro mNon-Ai r Source s o f Lea d T o predic t Pb B level s associate d wit halternativ e ai r lea d level s usin g thes e aggregat e slopes , i t i s necessar yt o estimat e th e contributio nt o tota l lea d exposur e fro memissio nsource s no t subjec t t o contro l b yimple

mentin g anai r qualit ystandard . Thes e source s ma yinclud e lead-soldere d foo d cans , lea d plumbing , lead-base d paint , and indirec t occupationa l exposure s (i.e. , fro mclothin g and shoe s o f parent s wh o wor k i nlead-relate d industries) . I t shoul d b e note d tha t b yusin g observe d lea d concentration s i ndus t fro m

a wid e rang e o f location s and conditions , th e integrate d uptak e mode l discusse d i nth e previou s sectio nattempte d t o implicitl y accoun t fo r averag e contribution s t o tota l exposur e fro mlead-base d paint . I naddition , th e estimate s provide d i nth e criteri a documen t base d o nP.9 2

VII-3 2

recen t FD Aan d industr ydat a directl yprovid e estimate s fo r non-ai r source s o f lea d i nth e die t whic hwer e use d i nth e model . I nattemptin g t o explicitl yestimat e exposure s fro mnon-ai r source s o f lead , whic hi s necessar yi napplyin g th e aggregat e blood/ai r lea d slope s t o determin e a nappropriat e lea d NAAQS , severa l difficultie s arise : 1 ) Wit hth e exceptio no f non-ai r lea d i ndiet , fe wstudie s provid e detaile d informatio no nth e relativ e contributio no f variou s source s t o children' s Pb B level s i nth e U.S . Estimate s mus t b e mad e b yinferenc e fro mearlie r surve ydat a and theoretica l calculations ; and 2 ) Becaus e non-ai r contribution s t o Pb B level s probabl yvar ywidel y i nspac e and tim e amon g children , a singl e estimat e fo r th e averag e cas e ma yresul t i na lea d NAAQ S tha t i s no t protectiv e fo r al l children . Thi s ca nb e expected , fo r example , fo r childre nwh o regularl yinges t lead-base d paint . Conversely , th e ai r standar d wil l b e overprotectiv e i narea s wher e lea d fro mnon-ai r source s i s belo wth e average . I nsettin g th e 197 8 lea d NAAQS , th e Agenc yestimate d tha t non-ai r source s o f lea d contribute d o naverage , 1 2 ug/d l t o children' s Pb B levels . Sinc e then , significan t reduction s i nPb B level s hav e occurred , attributabl e no t onl yt o decline s i natmospheri c lea d emission s bu t t o th e gradua l conversio nb

ymanufacturer s t o non-lea d soldere d cans , th e reductio no f old , lead-painte d homes , cleane r workin g conditions , a s wel l a s effort s b yparent s and publi c healt hagencie s t o minimiz e children' s lea d exposure . I t i s no t surprising , therefore , tha t th e non-ai r lea d contributio nt o averag e Pb B level s appear s t o b e lowe r today . I nchildre nsample d i n NHANE S I I betwee n197 6 and 198 0 livin g i nrura l area s wher e ai r emission s ca nb e expecte d t o b e minimal , th e measure d geometri c mea nPb B wa s approximatel y 1 2 ug/d l (Mahaffe ye t al. , 1982) . Afte r thre e adjustment s ar e mad e t o th e NHANE S I I data , a tru e "non-air " Pb B i nth e rang e o f 5. 9 t o 6. 6 ug/d lP.9 3

VII-3 3
i s estimate d fo r childre nlivin g i nth e U.S . today . Th e rational e fo r th e adjuste d valu e i s describe d below . 1 ) Althoug hautomobil e and industria l emission s ma yb e low , rura l population s i nth e U.S . ar e stil l expose d t o atmospheri c lea d throug hlong-rang e transpor t fro murba nand poin t sourc e area s and indirectl yfro matmospheri c depositio no f lea d o n crop s grownaroun d th e countr ytha t enter s thei r diet . N o dat a ar e availabl e o nU.S . children , althoug hpreliminar yanalyse s o f th e Isotopi c Lea d Experiment , whic hmanipulate d th e isotopi c compositio no f gasolin e sol d i nand aroun d Turin , Italy , foun d tha t betwee n1 1 and 14 % o f th e bloo d lea d i nadul t me nlivin g i nth e countrysid e ca nb e directl yand indirectl ytrace d t o gasolin e lea d locall yconsume d ove r 7 year s (Facchett i and Geiss , 1982 ; Colomb o an d Fantechi ; 1983) . I t ca nb e reasonabl yassume d tha t th e contributio n o f tota l atmospheri c (no t onl ygasoline ) lea d t o activ e childre nwh o ar e regularl yexpose d t o dir t and dus t i s likel yt o b e significantl y highe r compare d t o adults . I nth e absenc e o f direc t data , th e rang e o f 11-14 % fo r rura l Turi nme ni s multiplie d b ytwo , yieldin g a rang e o f 20-30 % fo r Pb B relate d t o gasolin e lea d and industria l source s i n rura l U.S . children . Thus , th e remainin g 70-80 % o f children' s bloo d lea d i s assume d t o b e attributabl e t o non-atmospheri c sources . 2 ) Th e NHANE S I I dat a ar e base d o nbloo d lea d measurement s mad e betwee n197 6 and 1980 . Sinc e then , i nadditio nt o th e phasedow no f gasolin e lead , effort s b yth e foo d industr yt o remov e source s o f lea d consume d b

yyoun g childre nhav e continued . Th e us e o f lead-soldere d
can s i nth e cannin g industr yha s decrease d fro m90 % i n197 9 t o 63 % i n198 2 an d a s th e switchove r continues , lea d i ncanne d food s fo r childre nshoul d decreas e b ya s muc ha s 70 % (CD , p . 7-48) . Sinc eP.9 4

VII-3 4

lea d fro msolde r and othe r metal s i s estimate d t o accoun t fo r approxi

matel y21 % o f a typica l child' s backgroun d lea d exposur e (Tabl e 7-25) , i t i s estimate d tha t th e averag e child' s tota l Pb B level s wil l declin e b

y(0.2 1 x0.7 ) o r 14% . 3 ) Th e staf f estimate s tha t ongoin g effort s t o reduc e occupationa l exposure s and t o preven t childhoo d lea d poisoning , and th e gradua l reductio n o f lea d exposur e t o lead-base d pain t i n ol d home s hav e resulte d i n a 20 % reductio n i nth e averag e Pb B leve l i n U.S . childre n sinc e th e 1976-198 0 tim e period . Base d o n thes e thre e considerations , th e NHANE S I I mea n valu e o f 1 2 ug/d l fo r rura l childre nsample d betwee n197 6 and 198 0 i s adjuste d i n th e followin g calculation : 1 2 ug/d l x(0. 7 t o 0.8 ) x(0.86 ) x(0.8 ) = 5. 8 t o 6. 6 ug/d l Thi s rang e represent s th e mea n Pb B level s tha t woul d b e expecte d toda y i n U.S . childre n no t expose d t o atmospheri c lea d directl yo r indirectly , base d o n th e dat a and assumption s presente d above . Anothe r metho d t o estimat e children' s mea n"non-air " Pb B i s t o us e availabl e dat a o n typica l backgroun d level s o f lea d i n food , water , dust , and soi l ingeste d b yU.S . childre nand th e relationshi p betwee n lea d take n u p throug hthes e medi a and children' s Pb B levels . Tabl e 13- 6 o f th e criteri a document use s suc hdat a i ncalculatin g a mea nPb B o f 4.4 2 ug/d l t o b e expecte d a t an ai r lea d leve l o f zero . Becaus e thi s estimat e i s base d o nobservation s limite d t o a fe wstudie s no t necessaril yrepresentativ e o f al l U.S . children , i t wil l b e use d wit hand adde d t o th e estimate s derive d fro mth e NHANE S I I surve yt o construc t a rang e o f Pb B level s (4. 4 t o 6. 6 pg/dl ) predicte d fo r U.S . childre n no t expose d t o atmospheri c lea d emissions , eithe r directl yo r indirectly .P.9 5

VII-3 5

I t mus t b e emphasize d tha t thes e estimate s fo r non-ai r contribution s t o averag e Pb B level s represen t averag e values . Manychildre nma yb e a t ris k fo r significantl yhighe r lea d exposure s tha t canno t b e prevente d b yatmospheri c emissio ncontrols . I nparticular , thes e includ e childre n wh o inges t pain t chip s and othe r non-foo d item s containin g leade d paint , childre nexpose d t o hig hdrinkin g wate r lea d level s fro merodin g lea d pipe s o r solder s i nplumbin g o r distributio nsystems , thos e livin g i n deteriorate d o r recentl yresurface d lead-painte d housin g wh o inadvertantl y tak e up pain t dus t throug hnorma l mouthin g activities , childre no f parent s wit hhig hoccupationa l exposure s t o lea d dus t tha t i s carrie d hom e o n clothing , o r childre nlivin g nea r lea d smelter s and othe r poin t source s wher e historica l soi l and dus t lea d accumulation s ar e excessive . Th e staf f urge s tha t othe r regulator yagencie s and publi c healt hprograms , includin g othe r EP Acomponents , responsibl e fo r minimizin g children' s lea d exposure s fro mnon-ai r sources , o r fro mhistorica l atmospheri c lea d deposition , maintai no r increase , wher e necessary , thei r efforts . ' iii ) Calculatio no f Alternativ e Lea d NAAQ S Base d o nth e conclusion s reache d i nth e preceedin g sections , alternativ e targe t ai r lea d level s ca nb e derive d usin g th e "aggregate " modelin g approac hby : 1 ) determinin g a maximu macceptabl e Pb B leve l fo r individua l childre n (n o greate r tha n2 5 ug/dl ) t o protec t agains t effect s discusse d i n Section s V. B and VI.A. l wit hanadequat e margi no f safety ; 2 ) calculatin g a targe t geometri c mea nPb B leve l fo r U.S . childre n base d o nplacin g a specifie d percentag e o f the mbelo wth e maximu m acceptabl e PbB : fo r purpose s o f th e presen t discussio nth e goa l i s assume d t o b e 99.5 % (Tabl e 7-6) ;P.9 6

VII-3 6

3 ) estimatin g th e Pb B leve l attribute d t o non-ai r source s suclra s leade d pain t and canne d foo d (4. 4 -6. 6 ug/dl) . 4 ) subtractin g th e non-ai r contribution s fro mth e targe t geometri c mea n Pb B level ; and 5 ) dividin g th e remainin g allowabl e contributio n t o bloo d lea d fro m ai r source s b

yth e aggregat e bloo d lead/ai r lea d slope s (4- 6 ug/d l pe r ug/m 3 ) discusse d i n Sectio n V.B . Table s 7- 8 an d 7- 9 presen t th e alternativ e ai r lea d level s derive d fro mthes e calculation s assumin g a goa l o f protectin g 99.5 % o f th e populatio n and GSD s o f 1.3 9 an d 1.3 4 respectively . Fo r purpose s o f thi s analysis , n o distinctio n i s mad e betwee n monthl yo r quarterl yaveragin g time s becaus e eac hai r lea d leve l i s assume d t o b e constant . Fo r eac hpossibl e Pb B tha t coul d b e accepte d a s th e leve l o f concern , differen t targe t ai r lea d value s aris e dependin g o nwhic hblood/ai r lea d slope , whic hnon-ai r bloo d lea d contribution , and whic hGS D i s ultimatel ytaken . Fo r example , i n orde r t o protec t 99.5 % o f th e populatio no f childre n fro mexceedin g a Pb B leve l o f 2 0 ug/dl , and assumin g a GS D o f 1.34 , a non-ai r bloo d contributio n o f 4.4 , and a bloo d lead/ai r lea d slop e o f 5 , a n ai r lea d leve l o f 1. 0 ug/m 3 woul d b e adequate . A t thi s time , th e staf f doe s no t attemp t t o distinguis h th e validit yo f th e value s presente d fo r eithe r o f thes e parameter s (i.e. , GSD , blood/ai r lea d slope , non-ai r PbB ) and await s commen t onthes e issue s befor e discussin g th e margin s o f safet yassociate d wit halternativ e lea d NAAQS . I t i s clear , however , tha t unles s 2 5 ug/d l i s determine d t o b e a n acceptabl e Pb B fo r an individua l child , and th e non-ai r contributio n t o bloo d lea d i s take n a s 4. 4 ug/d l and th e aggregat e blood/ai r lea d slop e i s assume d t o b e les s tha n 5 , al l o f th e ai r lea d alternative s predicte d b y th e aggregat e epidemiologica l mode l ar e belo wth e curren t standar d leve l o fTabl e 7-8 . Ai r Lea d Level s (ug/m 3 , monthl yo r quarterl yaverage ) Require d t o Protec t 99.5 % o f Childre n

fro mExceedin g Alternativ e Maximu m Acceptabl e Bloo d Lea d Levels,Accordin g t o Aggregat e Epidemiologica l Model , fo r Differen t Non-Ai r Lea d Contribution s and Blood/Ai r Lea d Slopes ; GS D fo r Populatio n Assume d t o b e 1.3 9

Blood/Ai rLea d Slop e 4 5 6 1 0 ug/d l

Non-Ai rPb

B 4. 4 6. 6

-

- Maximu m 1n d 1 5 ug/d l Non-Ai rPb

B 4. 4 6. 6 0. 5 0. 4 0. 3 ividua l 2 0 Non 4. 4 1. 1 0. 8 0. 7 PbB ug/d l Ai r Pb B 6. 6 0. 5 0. 4 0. 3 25

No n 4. 4 1. 6 1. 3 1. 1 ug/d l -Ai rPbB 6. 6 1. 0 0. 8 0. 7

Tabl e 7-9 . Ai r Lea d Level s (pg/m 3 , monthl yo r quarterl yaverage ) Require d t o Protec t 99.5 % o f Childre n fro m Exceedin g Alternativ e Maximu mAcceptabl e Bloo d Lea d Levels , Accordin g t o Aggregat e Epidemiologica l Model , fo r Differen t Non-Ai r Lea d Contribution s and Blood/Ai r Lea d Slopes ; GS D fo r Populatio n Assume d t o b e 1.3 4 i 0 0

B l ood/A i r Slop e 4 5 6 Lea d 1 0

Non 4. 4 0.0 8 0.0 6 0.0 5 ug/d l Ai rPb B 6. 6

-

-

- 1 5

Non 4. 4 0. 7 0. 5 0. 5 Maximu m ug/d l -Ai rPb B 6. 6 0. 1 0. 1 0.0 8 Individua l

2 0 Non 4. 4 1.2 5 1. 0 0. 8 PbB yg/d l Ai r Pb B 6. 6 0. 7 0. 6 0. 5 25

Non 4. 4 1.8 5 1. 5 1. 2 ug/d l •Ai rPbB 6. 6 1. 3 1. 0 0. 9VII-3 8

1. 5 ug/m 3

. I t i s als o clea r tha t accordin g t o thi s model , eve na nai r lea d leve l clos e t o zer o woul d no t b e full yprotectiv e fo r childre nfro m exceedin g Pb B level s o f 1 0 ug/dl , and assumin g a non-ai r contributio no f 6. 6 ug/dl , fro m

exceedin g 1 5 ug/dl . Thes e result s ar e compare d i n Tabl e 7-1 2 wit hPb B level s predicte d unde r variou s ai r lea d level s b yth e othe r tw o models . I naddition , i t onc e agai nshoul d b e note d tha t non e o f thes e ai r lea d level s ca nfull yprotec t childre nwh o ar e excessivel yexpose d t o non-ai r source s o f lead , suc ha s pain t chip s an d heavil ycontaminate d soil s and dusts . c ) Predictin g Bloo d Lea d Level s Usin g "Disaggregated " Slope s fo r Individua l Medi a Jus t a s mathematica l relationship s hav e bee nderive d betwee nbloo d lea d
and ai r lea d level s amon g differen t populations , variou s studie s hav e investigate d th e relationshi p betwee nbloo d lea d level s i nchildre nand concentration s o f lea d i nfood , water , soil , an d dus t t o whic hthe yar e exposed . Th e C D ha s applie d th e mos t reliabl e and relevan t o f thes e relationship s t o currentl yrepresentativ e concentration s o f lea d i nthes e individua l medi a i norde r t o estimat e proportiona l input s t o tota l Pb B level s i nU.S . childre n(CD , Sectio n13.4.3) . Tabl e 7-1 0 (CD , Tabl e 13-6 ) present s estimate s fo r th e direc t and indirec t contribution s o f ai r lea d t o 2-yea r ol d children' s bloo d lea d a t differen t ai r lea d level s and typica l backgroun d level s o f lea d i nfood , wate r and dust . Calculation s and assumption s use d i nderivin g th e estimate s ar e summarize d i nfootnote s t o th e tabl e and ar e reference d t o specifi c section s o f th e criteri a document . Thi s disaggregate d analysi s share s similaritie s t o bot happroache s presente d earlie r i nthi s pape r tha t wer e use d t o estimat e Pb B level s unde r alternativ e ai r lea d levels . Fo r example , th e integrate d lea d uptake/bio

-P.9 9



### VII-3 9
TABL E 7-10 . CONTRIBUTION S FROMVARIOU S MEOI AT O BLOO D LEA D LEVEL S (pg/dl ) O F U.S . CHILDRE N(AG E = 2 YEARS) : BACKGROUND LEVEL S AND INCREMENTA L CONTRIBUTION S FROMAI R

Sourc e Background-no n ai r Food 1 Water 2 Dust 3 Subtota l Background-ai r Food 4 Water 5 Subtota l Ingeste d Dus t (wit hPb deposite d fromair) 6 Inhale d air 7 Tota l 0
1.5 5 .9 4 .3 0 2.7 9
1.4 7 .1 6 1.6 3
0.0 0 0.0 0 4.4 2 .2 5

1.5 5 .9 4 .3 0 2.7 9
1.4 7 .1 6 1.6 3 1.5 7 .5 0 6.4 9 .5 0

1.5 5 .9 4 .3 0 2.7 9
1.4 7 .1 6 1.6 3
3.0 9 1.0 0 8.5 1 Ai r Lea d

.7 5
1.5 5 .9 4 .3 0 2.7 9
1.4 7 .1 6 1.6 3
4.7 0 1.5 0 10.6 2 (ug/m 3 )

1. 0
1.5 5 .9 4 .3 0 2.7 9
1.4 7 .1 6 1.6 3 6.2 7 2.0 0 12.6 9 1.2 5

1.5 5 .9 4 .3 0 2.7 9
1.4 7 .1 6 1.6 3 7.8 4 2.5 0 14.7 6 1. 5

1.5 5 .9 4 .3 0 2.7 9
1.4 7 .1 6 1.6 3 9.4 0 3.0 0 16.8 2 "•Fro mTabl e 7-25 , (18. 9 - 9.2 ) pg/da yx(0.1 6 fromRy u e t al. , 1983 ) = 1.5 5 ug/dl . 2 Fro mTabl e 7-25 , (6. 9 - 1.0 ) pg/da yx(0.1 6 fromRy u e t al. , 1983 ) = 0.9 4 pg/dl . Alternatively , Table s 7-20 , 7-2 1 giv e a weighte d mea n concentratio n o f liquid s a s 0.01 2 pg/g . 1/ 7 i s atmospheric , leavin g 0.0 1 pg/ g (1 0 pg/1 ) non-atmospheric . 1 0 x (0.0 6 fromPococ k e t al. , 1983 ) =0. 6 pg/dl . 3 Fro mChapte r 7 , 1/1 0 dus t no t atmospheric . Usin g Angl e e t al . (1984 ) loware a (Are a S ) fo r soi l and hous e dus t and thei r regressio n equation , w e have : (1/10 ) x(9 7 pg/ g x 0.0068 1 + 32 4 pg/ g x0.00718 ) = 0.3 0 pg/dl . Alternatively , th e consumptio n fromno n ai r woul d b e (1/10 ) x(9 7 pg/ g soi l dus t + 32 4 pg/ g hous e dust ) x0.0 5 gram s ingeste d o f eac h= 2. 1 p g ingested . Usin g Ry u e t al . (1983) , 2. 1 x0.1 6 = 0.3 4 pg/d l adde d t o blood . 4 A s i n 1 above , bu t usin g 9. 2 instea d o f (18. 9 - 9.2 ) yield s 1.4 7 pg/dl . Value s ar e derive d fo r componen t o f backgroun d Pbi n foo d frompas t depositio n fromai r ont o soi l and int o othe r medi a leadin g int o huma n foo d chai n (no t expecte d t o chang e muc hexcep t ove r long-term) . s A s i n 2 above , bu t usin g 1. 0 instea d o f (6. 9 - 1.0 ) yield s 0.1 6 pg/dl . Value s ar e derive d fo r componen t o f backgroun d Pbi n foo d from pas t depositio n fromai r ont o soi l and int o othe r medi a leadin g int o huma n foo d chai n (no t expecte d t o chang e muc hexcept.ove r long-term) . 6 Th e regressio n equation s o f Angl e e t al . (1984 ) ar e used , a s wel l a s level s o f soi l dus t and hous e dus t i n th e loware a (S ) and highare a (C ) o f tha t study . Fo r example , th e increas e a t 1. 0 pg/m 3 i n ai r woul d resul t i n increase s i n soi l a s follows :



# orHr U X(519 

# • 97 ) = 52

6 M9/ 9 Similarl yth e increas e i n hous e dus t woul d be : 0;8 6 - gil l * (625-324 ) = 37 4 pg/ g Th e effec t o n bloo d lead woul d b e (52 6 x0.00681 ) + (37 4 x0.00718 ) = 6.2 7 pg/dl . Th e effec t o n bloo d lead woul d b e (52 6 x0.00681 ) + (37 4 x0.00718 ) 7 Usin g th e 2. 0 slop e fromAngl e e t al . (1984) , i.e. , 1.9 3 rounde d up . 

### Source : CD , Tabl e 13-6 .P.10 0

VII-4 0
kineti c mode l estimate d th e rang e o f contribution s tha t bot hatmospheri c and non-atmospheri c lea d mak e t o tota l exposure , directl yand indirectly , vi a th e individua l medi a pathways . Th e secon d "aggregate " bloo d lead/ai r lea d approac hrelie d o n mathematica l relationship s derive d fro m som e o f th e sam e populatio n studie s betwee n bloo d lea d and lea d i n th e environment . I t i s o f interes t t o not e tha t afte r adjustin g th e estimate d Pb B i n Tabl e 7-1 0 fo r childre n expose d t o 1.2 5 ug/m 3 ai r lea d t o a leve l tha t woul d b e expecte d give n th e dietar yand backgroun d lea d condition s durin g 1976-198 0 whe nNHANE S I I wa s conducted , th e resul t i s roughl ycomparabl e t o th e mea nPb B measure d b yth e NHANE S I I surve yfo r childre n livin g i n U.S . urba n area s whic hthe nha d a naverag e ai r leve l o f approximatel y1.2 0 ug/m 3 (15. 6 vs . 16. 8 ug/dl ) (CD , p . 13-2 6 t o 13-28) . Th e Pb B level s liste d unde r eac hai r lea d leve l i n Tabl e 7-1 0 represen t th e predicte d populatio nmea n Pb B level s fo r 2-yea r olds . Usin g th e equatio n presente d previousl yi nthi s section , i t i s possibl e t o estimate , give n a geometri c mea n Pb B leve l and knowndistributio n characteristic s o f th e population , th e individua l Pb B a t a specifie d standar d deviation . Tabl e 7- 6 fo r example , indicate s tha t give n a geometri c mea n Pb B leve l betwee n 8. 6 and 9. 4 ug/dl , 99.5 % o f th e populatio n woul d hav e Pb B level s belo w2 0 ug/d l (dependin g o nwhic hgeometri c standar d deviatio n i s chosen) . Similarly , a populatio n mea n Pb B o f 8.5 1 fo r exampl e (predicte d unde r an ai r lea d leve l o f 0.5 0 ug/m 3 i n Tabl e 7-10) , woul d preven t 99.5 % o f th e populatio nfro mexceedin g a Pb B o f eithe r 18. 1 o r 19. 8 ug/d l (fo r GSD' s o f 1.3 4 and 1.39 , respectively) . Tabl e 7-1 1 list s th e maximu mindividua l Pb B predicte d i n 99.5 % o f th e populatio nfo r eac hestimat e o f mea n Pb B predicte d b yth e criteri a documen t i n Tabl e 7-10 . Thes e result s ar e presente d i n Tabl e 7-1 2 fo r compariso n wit hthos e o f th e othe r tw o modelin g approaches .