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Environmental Research Section A 82 60-80(2000)Article ID enrs 1999 4003 available online at http //www ideahbrary com on

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Acquisition and Retention of Lead by Young Children1

W I Manton * 2 C R Angle t K L Stanek J Y R Reese * and T J Kuehnemannt* Department of Geology University of Texas at Dallas Richardson Texas 750830688 ^Department of Pediatrics University of Nebraska

Medical Center Omaha Nebraska and ^Department of Nutrition Science University of Nebraska at Omaha Omaha Nebraska

Received December 15 1998

ll3js :" I1

The concentrations and isotope ratios of lead inblood and urine, on the hands and in duplicate dietsamples were measured for children living inOmaha Nebraska One group consisted of 22 children followed from birth to between 1 and 2 years ofage and another group was 20 2 to 4 year old children followed for 1 year, although some in eachgroup were followed for periods between 3 and4 years At no tune in life was a component of dietary lead identified in blood by isotope ratios andblood lead appears dominated by lead derived fromthe hands, which in turn appears derived from thefloors For some homes floor lead appeared to be

mixture of lead from window sills and from the'Xterior Only 2 of the children appear to have in

Rested lead directly from window sills Several wholived in homes being remodeled were exposed tolead before the age of 2 years For those who hadbeen briefly exposed during professional remodeling the blood lead fell with a half life of 10 monthsbut for those who had suffered prolonged exposureduring remodeling by parents the apparent half lifewas longer, between 20 and 38 months © 2000 A ademic

INTRODUCTION

In the 1960s so little was known of the consequences of environmental lead pollution that thearchitects of the Three and Seven City Surveys (Pubhe Health Service 1965 Tepper and Levin 1975) did

'This work was funded by the National Institute for Environmental Health Sciences through Grant ES 04762 to Carol AngleThe procedures and consent forms were reviewed and approvedby the Institutional Review Board of the University of NebraskaMedical Center

2To whom correspondence should be addressed at Department,of Geology Mail Drop FO21 University of Texas at Dallas POBox 830688 Richardson TX 75083 0688 Fax (972) 883 2537

0013 935iyOO $35 00Copyright © 2000 by Academic PressAll rights of reproduction in any form reserved

not include children in their sample It was Lin Fu(1972 1973) who first brought attention to the highblood lead of urban children and Sayre et al (1974)who first pointed to a correlation between the lead intheir blood and that in the dust of their homesa relationship borne out by many subsequent studies(Landngan et al 1975 Angle and Mclntire 1979Charney et al 1980 Bornschem et al 1987 Daviesetal 1990 LanpheareZaZ 1996 1998ab) Leadedgasoline and smelter emissions which some yearsago were major sources of lead particulate are nolonger of any consequence in the United States sothat lead in house dust is presently regarded ascoming from two sources one internal presumed tobe paint and one external usually claimed to becontaminated soil brought into the home on the feetof the occupants Despite the simplicity of thismodel it has sometimes proved difficult to understand the relationships between blood lead and theputative source of the lead in house dust Kimbroughet al (1995) for example found that soil lead accounted for only 3% of the variance in blood leadof children living in an urban area surroundinga closed lead smelter and Weitzman et al (1993)found that children s blood lead did not fall by theexpected amount after removal of lead contaminatedsoil from around their dwellings Variables such asrace family income condition of the home andmouthing activities may have effects large enough toobscure the contnbutions of paint or soil to bloodlead (Kimbrough et al 1995 Lanphear and Roghmann 1997)

Another way to look for the sources of lead is to useisotope ratio tracing which makes use of the property that lead being to a large extent the product ofthe radioactive decay of uranium and thorium vanes in isotope ratio according to the geological age ofthe ore deposit from which it is mined For the firstclear enunciation of the principle see Chow andEarl (1970) Not only does this method provide the

60

CHILDHOOD LEAD ACQUISITION 61

.5*

possibility of identifying particular sources but iflead in blood is measured the ratios may give information regarding past exposure because bloodlead is dominated by lead from bone (Manton 19771985) and especially so in children in which remodeling of the skeleton is continuously reapportiomnglead between blood and bone (OFlaherty 1995) TheUnited States is particularly well suited to performing isotope studies because it has mines that haveproduced lead covenng a wide range of isotope ratios from a 206Pb/207Pb ratio of 1 05 at Coeur d AleneIdaho to 1 4 in the Mississippi Valley deposits Dueto the mixing of ores dunng smelting and of themetal during refining the range encountered in theenvironment is somewhat less 1 12 to 1 30 but suchwas the manufacture and distribution of lead products half a century or more ago that one may find ina single old house lead with ratios close to eitherextreme Given that the isotope ratio of the lead inthe blood of the average resident of the UnitedStates lies somewhere m the middle of this rangeand that a difference in ratio of 0 002 is readilydistinguished by mass spectrometry it is clear thatisotope ratio tracing has the potential to identifyspecific sources of household lead in blood subject tothe probability that differences in isotope ratio existin the houses sampled It turns out in fact that ina prospective study such as this only about one caseout of five yields ratios far enough apart to be interpretable but this information cannot be obtained inany other way justifying the effort and expense Anassumption inherent in all isotopic studies is thatthe isotope ratios of bioavailable fractions of anyingested samples are identical to those measured mthe bulk sample This has never been confirmed onthe other hand there is no evidence from any studyto indicate that this assumption does not at leastapproximate the truth

In this study we have used the isotope tracingtechnique to investigate how a child first acquireslead and how early exposure may influence his bloodlead profile in later years The study consisted of twoparts Beginning in 1990 we measured for a period ofat least 2 years the blood urine diet and hand wipelead of 22 2 year old children living in pre 1955housing in Omaha Nebraska Environmental sampies were taken at the time of the initial visit to thehome The results of this study showed that theisotope ratios and blood lead concentrations of somehad been set by events that occurred during the first2 years of life We then began to follow another 22children from birth to 2 years and to find the sourceof the lead on their hands we took wipes twice a yearfrom floors and window sills and as a measure of the

lead earned into the houses on shoes we collectedshakings from doormats Of these children 6 dropped out of the study after 1 year the majority wereterminated at 2 years and some who were givingvaluable information pertaining to the clearance oflead were followed longer one for 43 months To givecontinuity to our narrative we report the results mthe reverse order first discussing the children studIBS from birth followed by those from 2 to 4 years ofage Some parts of the study have been reportedelsewhere Angle et al (1995) on a statistical analysis of the results of the 2 to 4 year old children andStanek et al (1998) on the implications of the leadcontent of their diets

METHODSSampling Design

The study was designed to minimize the numberof samples analyzed both to reduce the number ofisotopic analyses which are expensive and time consuming and to accommodate the principal shortcoming of studies using natural lead tracers whichis that they must be designed to investigate mixingbetween no more than two end members If morethan two are identified a unique solution cannot beobtained Therefore wherever possible compositeswere analyzed or samples were pooled For examplerather than having to analyze a number of soil sampies from each house we took a composite samplefrom a doormat Samples analyzed in the preliminary study had shown a large dispanty between theisotope ratios from doormats and those from housedust suggesting that exterior doormats sample theenvironmental lead outside the home with little contnbution from the interior That the amount of leadrecovered bears little relationship to the concentration of lead in the soil was immaterial, as the composite contains the isotopic information neededLikewise to avoid having to make separate analysesof lead in water we had the mothers include inthe duplicate diet containers all fluids that wereconsumed by the child over the period of collectionSamples of water from the homes contained anaverage of 0 22 jag Pb/L which is consideredlow and thus should not have contnbuted sigmficantly to the children s intakes None of the children were consuming diets that included largeamounts of tap water Reconstituted foods in whichwater was added durmg preparation accountedfor 18% of the dietary weight and only 11% of thetotal diet weight was calculated as plain tap waterconsumption

62

Recruitment

MANTON ET AL

In both parts of the study the subjects were recruited through newspaper advertisements andnotices in health facilities Exclusionary cntena ineluded blood lead over 15 ng/dL household memberswith known lead exposure lead hazard in the household identified by a health department inspectionanemia chrome illness or disability An effort wasmade to recruit equal numbers of subjects m eachdichotomized class race (white and other) income(welfare assistance or not) plans for breast or bottlefeeding and sex of the children

TrainingAt the initial visit before signing the consent

agreement the mothers were told that they would beparticipating in a dietary lead study They wereinformed that they would need to prepare weighand record in a diary the contents of a 24 h duplicatediet 1 day per month Much time was spent on thisprocedure as it was the most difficult part of theresearch The second most difficult area was collecting a urine specimen from the infants and themothers had to learn how to clean the genital areaand how to affix a collection bag Each family wastold that a blood sample would be taken three timesa year This was another concern because of possiblediscomfort to the child When told that handwipesamples would be taken at each visit and that soiland dust samples would be periodically collectedvery little discussion ensued because this samplingdid not require the mother s compliance with a procedure Environmentalist visits were unannouncedotherwise the mother might have purposely cleanedand dusted The mothers did not express concernabout lead in dust or paint

The training was surprisingly successful and themothers learned to collect and record the diets and tocollect clean urine samples in bags or in Teflon jarsonce the child got older A technician visited eachfamily once a month measured the child s heightand weight took hand wipe samples and picked upthe monthly urine samples (collected that morning)and diet samples (collected over the previous 24 h)The visits of the phebotomist and the environmentalist were done in conjunction with that of thetechnician

Sample CollectionWherever possible samples were collected in Tef

Ion PFA vessels that were acid cleaned in the Dallas

laboratory before shipped to Omaha Exceptionswere polyethlene jars used for food collection whichwere acid washed m Omaha and polyethylenepediatric urine collection bags and polypropylenesyringes used to draw blood and to transfer unnewhich were shown to contain negligible amounts oflead

Blood was taken at birth (if possible from theumbilical cord) and every 4 months thereafter bya phlebotomist Approximately 5 mL was drawnthrough a hepanmzed butterfly into a scalable Sarstedt syringe in which it was shipped to DallasUrine was syringed out of the collection bags andtransferred to Teflon bottles before shipping A portion was retained for creatmine determinationHand wipes were K Mart Little Ones selected because they contained less lead than other brands Tominimize the blank only two were used to clean bothhands of each child

Floor window sill and carpet samples were collected by defined procedures (State of Minnesota1990) Surface dust was collected by wipe samplefrom a 1 square foot area outlined by a template onthe floor or from a measured area of window sill Theoperator wore disposable gloves that were wipedclean with the wipe being discarded One wipe wassealed as a blank Wiping was done in an S patternover the entire area the wipe was folded and thearea rewiped at 90 degrees to the first S Carpet dustwas aspirated through an air pump calibrated at3 L/min into an 0 8 |am filter cassette (GelmanSciences Ann Arbor MI GN 4 Membrane AirMomtonng Cassette 37 mm diameter) All analyseswere converted to |ig Pb/m2 The area sampled wasthe mam play area of the child If it was carpeted thenearest uncarpeted floor was sampled and viceversa Doormats were bought for those families thatdid not own them and were shaken over a cleansheet of paper every 6 months

Lead SpikesA 78 9% enriched 205Pb spike was used Because

the isotope does not occur in nature it may be usedto obtain both the lead isotope ratios and the leadcocentration from the same analysis A highly enriched (99 98%) 206Pb spike was used to measureblanks

Sample Preparation and DecompositionUpon receipt samples were handled under clean

Class 100 conditions Initially food was homogenized m a 4 L Waring blender but this was replaced

^ f-

CHILDHOOD LEAD ACQUISITION 63

I If-

with a Brinkmann Polytron equipped with a 24 mmstainless steel generator having Teflon bearingsA 10% aliquot was taken for analysis In the case ofshakings from doormats the fraction passingthrough a 100 mesh nylon sieve was analyzed Allsamples were decomposed with distilled mtnc acidin Teflon PFA vessels blood unne and food on a hotplate and hand wipes and doormat shakings ina microwave Blood and urine which containednanogram quantities of lead were spiked before decomposition whereas food and hand wipes contaimng at least a hundred times more lead weredecomposed before being ahquoted and spiked

Lead SeparationLead in blood unne and food samples was separ

ated by amon exchange in dilute hydrobromic acidA problem with this procedure is that mtnc acid onlypartially decomposes the sample and large quantitIBS of organic matter follow lead through the separation To reduce the orgamcs samples were charredat 200 C after being evaporated to dryness and twoion exchange steps were used a conventional collimn followed by a single bead Lead from hand wipeand doormat samples was coprecipitated with barmm nitrate added directly to an aliquot of the decomposed sample It was then separated from thebanum by electrodeposition on a platinum anode

Mass SpectrometryA Fmmgan MAT 261 multicollector thermal ion

ization mass spectrometer was used in this workThe 205Pb spike which was made from 204Pb hasa205Pb/204Pbof605and as such can yield accurate206Pb/204Pb ratios only if sample to spike ratios arelarge which may not always obtain when samples ofunknown lead content are analyzed The ratio206Pb/207Pb however may be recovered for smallsample to spike ratios and is the ratio reported hereRabmowitz (1995) has pointed out that the correlation between 206Pb/204Pb and 206Pb/207Pb in environmental lead is high The reason is geological Allmajor ore deposits of lead formed dunng the lastthird of the Earth s history when 235U had alreadypassed through four half lives so that the production of 207Pb over this interval was small and itsabundance in the Earth scarcely changed The ratios206pb/204pb and 206pb/207pb are therefore essentiallyof the form x/a and x/b where a and b are constantsThus plots of either against time convey almostidentical information (see also Manton 1977) but ifthe highest accuracy is desired 206Pb/207Pb must be

the ratio of choice because each isotope having approximately the same abundance is measured withequal precision an important consideration if signals are small The value of 206Pb/204Pb is in contrast between 17 and 22 Another reason for using206pb/207pb lg that tbe uncertamty introduced bymass fractionation in the thermal lomzation sourceis half that affecting 206Pb/204Pb

Largely due to the longer half life of ^^h (threetimes that of 238U) the 208Pb/204Pb ratio of terrestriallead changes at half the rate of the 206Pb/204Pb ratiowhich together with the coherence of uranium andthonum in the Earth diminishes the value ofthorogemc 208Pb as an independent tracer thoughsome have attempted to use it In this study the208pb/2o?pb rat10 wag measured for all samples principally to monitor laboratory contamination with the206Pb spike the rationale being that if contaminationoccurred it would be the 206Pb/207Pb ratio rather thanthe 208Pb/207Pb that would be affected

Long term stability of the mass spectrometerwas monitored by routinely measunng the lead standard SUM 981 but it must be pointed out that thechanges being measured were many multiples of thelong term reproducibility of the instrument andeven the uncertainty in applying the mass dependent fractionation correction was less than the dayto day vanations in the isotope ratios of a subject sblood Nonetheless all ratios reported here havebeen corrected by a factor of 0 145% per atomic massunit

BlanksBlanks were routinely measured dunng the

course of this work We found that plasticware suchas unne collection bags syringes and zip lock bagsused to ship hand wipes were essentially clean andthat at most tens of picograms of lead could bewashed from them Sodium hepann in contrast contamed 0 3 to 0 4 ng Pb/mL thus a blood collectionblank contained between 100 and 200 pg Pb For theperiod September 1990 to May 1994 the hand wipescontained on average 100 ng Pb per wipe with isotope ratios 204Pb/206Pb = 0 0524 207Pb/206Pb =0 8219 and 208Pb/206Pb = 2 0277 but thereafter dueto some change in manufacture their content dropped to 19 ng Pb with ratios 204Pb/206Pb = 0 0534207pb/206pb = 0 g294 and 208pb/206pb = 3 Qgyg Jf fog

amount of lead inherent in the handwipes was morethan half of the lead analyzed the value was reported as undetectable The blank associated withthe decomposition of the samples was essentiallythat of the acid used or about 10 pg for blood or

f,

64 MANTON ET AL

urine For a diet sample more acid is required making the blank about 0 5 ng The blank contributed bythe ion exchange separation was about 12 pg Pbnegligible compared to that contributed by hepannto blood or that contained in aliquots of food samplesSmall samples of urine contained as little as 1 ng Pbbut even with these the total analytical blank of nomore than 25 pg Pb constituted less than 1% of thelead processed and for these and all other samplesexcept the handwipes no correction to the isotoperatio was made

ControlsThe accuracy of the spike calibration and the

cleanliness of the chemical separation was assessedby analyzing the whole blood standard SRM 955a

When the quantity being measured is expected tovary smoothly with time such as the isotope ratio oflead in urine erratic values that stem from contamination of the sample during collection are easilyrecognized and the subject acts as his own controlThis safeguard however fails to detect contammation by lead identical in isotope ratio to the samplewhich we monitored by estimating the 24 h urinaryoutput of lead from the creatimne vs height tables ofViten and Alverado (1970) rejecting samples inwhich the calculated output was more than threetimes the average calculated output To monitorchanges occurnng in the environmental conditionsof the home we measured the blood lead of the fatheruntil the child was born and then the mother s urinemonthly and her blood every 6 months for as alongas we followed the child Such a technique is notideal because the sources to which each is exposeddunng the day may well be different but it has theadvantage that if both subjects change togethera source affecting the whole household is indicatedTo tie the two parts of the study together we used inthe second part of the study some of the families whohad participated in the first so that we could compare the results from siblings living in the samehouse

CHILDREN BIRTH TO 2 YEARS

SubjectsInitially two pregnant women were recruited

with a view to using their children as pilot subjectsto evaluate the sampling plan and collection techmques These children subjects 51 and 53 are referred to as the pilot subjects Both were white malesand were bottle fed Blood unne food and handwipes were collected from them but no environ

mental samples were taken until the need for thembecame apparent Angle et al (1995) and Gulsonet al (1998a) have shown that the isotope ratios ofspot unne closely correlate with those of simultaneously drawn blood which allows the isotopic information in blood to be obtained without the need tobleed children frequently Twenty four other pregnant women were then recruited but 4 dropped outbefore their children reached 1 year of age and arenot reported here The remaining 20 children 7 ofwhom were breast fed comprised 11 males (3 black8 white) and 9 females (4 black 4 white) A further6 dropped out after 1 year Two that had been brieflyexposed to lead while their homes were being remodeled were continued beyond 2 years in order toprovide estimates of the rate at which the youngchild eliminates lead Subject 51 one of the pilotchildren was also briefly exposed to lead but as thiswas of distinct isotopic composition he was followedfor 3 5 years Subject 101 3 who had a sister in theearlier study was followed for 3 years

Blood Lead ConcentrationsThe blood lead concentrations measured every

4 months are plotted in Fig 1 and are given in partin Table 1 Although there is a tendency for the leadconcentrations of children born with blood lead lessthan 1 jig/dL to nse over the first 4 months and thoseborn with blood lead greater than 1 ng/dL to fall thegeometric mean blood lead values at birth and at4 months were unchanged at 0 92 and 0 99 ng/dLrespectively After 4 months the blood lead concentrations diverge Two children subjects 102 3 and106 3 were exposed to lead while construction wasbeing earned out at their homes and their blood leadconcentrations briefly rose to values above 10 |ig/dLAnother two subjects 51 and 112 3 showed subduedpeaks rising above 6 ng/dL the causes of which arenot apparent from their histones Subjects 103 3and 116 3 showed rapidly nsing concentrations butdropped out of the study prematurely The remainder for the most part showed near constant or gentlyrising concentrations with one child (subject 108 3)born with a blood lead of 0 63 ng/dL not changingover 24 months

Exposure to Lead from Food and DustThe subjects average monthly exposure to lead in

the diet is plotted in Fig 2 but it should be noted thatthe values for the first 3 to 6 months reflect onlythose who were bottle fed it being impossible toobtain duplicate diets for the breast fed child The

"W CHILDHOOD LEAD ACQUISITION 65

a>

co

Ic8

TJg 12

-ao_oCD

8 12 16Age in Months

20 24

FIG 1 Blood lead-Concentrations of children followed frombirth to 2 years (A) and (B) are bottle fed children divided according to whether their blood rose or fell over the first 4 months oflife (C) shows the breast fed children

quantity of dietary lead rises steeply between 4 and9 months after which it shows no particular trendvarying erratically between 3 and 4 \ig per day Incompiling the averages for the amount of lead on thehands those cases in which no detectable lead wasfound were omitted which causes the averages forthe wipes in the early months to be larger than theyreally are The amount of lead on hand wipes nsesfrom birth to 9 months and then remains essentiallyconstant at about 0 9 ng for the next 12 monthsbefore nsmg briefly to 1 4 fig between 20 and 24months (Fig 3) We therefore divided the exposureinto three phases (1) between birth and 4 monthswhen the child s intake of lead is small and in manycases insufficient to maintain his blood lead atthe concentration with which he was born (2)a transition from infancy to childhood between the5th and the 8th month when an adult type of dietreplaces formula and baby food and when the childspending more and more time out of the crib getsincreasing amounts of lead on his hands and (3) the

penod from the 9th month to 2 years when hisexposure to lead remains essentially constant

Sources of Lead Birth to 4 MonthsOver the first 4 months of life a child has little

mobility and thus little contact with the lead in thedust on the floor and other surfaces of the home Inthese circumstances in might be expected that leadfrom the diet will dominate blood It turned outhowever that although the diets of some of thebottle fed children had unusually high ratios (20BPb/207Pb> 1 25) there was no corresponding shift in theratios of their blood implying that the dietary absorption of lead is small The high isotope ratios weretraced to the Isomil brand of infant formula of whicha large stock was purchased and given to a womanwho had elected to bottle feed her child Her blood206pb/207pb ratlo averaged i 204 and changed littledunng her last trimester (Fig 4) The child (subject124 3) was born with a blood lead concentration of1 2 ng/dL which fell to 0 84 ng/dL at 4 months Hisdietary intake averaged 1 5 ng/day and between0 13 and 1 2 |ig of lead was wiped from his hands Heweighed 7 4 kg at 4 months and assuming that thehalf life of lead in his blood compartment had theadult value of 15 days (Chamberlain et al 1978) aninput of 0 46 ng/day is required to sustain a bloodlead concentration of 0 84 ng/dL When the isotopratios are plotted (Fig 4) it is seen that his bloodratio moved away from his diet ratio and toward hishand wipe level which must therefore be thegreater contributor to his intake

To calculate the contribution of dietary lead threesources must be considered because a flux from bonemay not be ignored especially as the child is innegative lead balance The three source problemdoes not yield an exact solution but a range of valueslying between the limits of where the dietary and thebone contributions are in turn set to zero To makethe calculations the following average 206Pb/207Pbratios were used with bone assumed to have thematernal value food = 1 268 bone = 1 204 blood =1 193 and wipe = 1 177 Some selected solutions aregiven in Table 2 The maximum possible figure fordietary absorption is 12% which occurs when thecontribution of bone is zero The presence of somelead from bone in a child s blood is to be expected butthe amount is difficult to estimate In adults theamount of bone lead in blood lies between 40 and70%(Manton 1985 GulsoneZaZ 1995 Smith etal1996) For an infant the mineralization of bone isless and the lead content of bone mineral is probablylower against which must be set a much greater rate

66 MANTON ET AL

TABLE 1Blood Lead Concentrations at Various Ages and 9 to 24 Month Geometric Means of the Amount of Lead in the Diets and

Hand Wipes and 6 to 24 Month Arithmetic Means of the 206Pb/207Pb Ratios of Urine Hand Wipes and Diets of ChildrenFollowed from Birth to 2 Years

Subject

N Race/sex BirthMg/dL

Blood Pb

4 months^g/dL

Pb Souices

12 months 24 months Hand wipeHg/dL ng/dL |ig

FoodHg/day

06Pb/207Pb

Urine Hand wipe Food

Pilot Study Children5153

101 31033108 310931103112311431153119 3120 3122312431263

102 3104310o 3106 310731163121 3

OverallOverall

W/MW/M

B/FW/MW/MW/MW/MB/MW/MB/FB/FW/MB/FB/MB/F

W/FW/FW/FW/MW/MW/FB/M

anth meangeom mean

121 1

15067063080061180760870401209112064

075—048066211 118

101092

19058

085033062N/A12075052190551006408412

17102117141510

1 11099

4812

Bottle5160067160901326501251121724

Breast7324365929

10638

3527

412 2

Fed Children67—0622109035176213—3034—

Fed Children23—242930——

292 4

15047

1212058140861007009603308706714073

230462012046

077

10089

4 732

56313239224925213846434 1223

2931213021Too Few21

3332

12311212

1 184121712051206120212091 19811851 1931 1941 19612091203

11911 191119411951202

Samples1194

1201—

12191210

118112011202121212001200120311691 1901211121712131193

11991 194119511861188

1190

1 199—

12071229

12001 191121512071239124512081206122211961 19712161218

12001202119012151210

1195

1210—

of bone turnover perhaps as high as 300% of theskeleton per year (O Flaherty 1993) In this lightvalues between 10 and 59% do not seem unreasonable which from Table 2 give dietary absorptionsbetween 5 and 1%

Samples of milk were obtained from the breastfeeders Since milk is derived from plasma it may beexpected to contain lead in the same ratio to blood asdoes plasma or about 1 to 1 5% (Manton and Cook1984) in the subject eating ad libitum and less than1% in the subject coming off a fast (Manton andCook 1984 Hernandez Avila et al 1998) All butone of the women produced samples that failed thiscriterion by having variable ratios that ranged up to30% and are presumed to have contaminated theirsamples during collection The mother of subject107 3 however gave milk with lead contents consistently between 0 6 and 1 8% of her blood lead which

rose from 38 to 55 (ig/dL during lactation Herchild s blood lead decreased from 2 1 pg/dL at birthto 1 4 ng/dL at 4 months which would be sustainedby an input of about 0 77 u.g Pb/day The averagelead content of her milk was 0 06 (ig/dL and anaverage 0 3 \ig of lead was wiped from his hands Hisconsumption of breast milk was approximately1 L/day (he was fed six or eight times a day eachfeeding averaging 123 g) of which 100% would haveto be absorbed to maintain the concentration of leadin his blood However if lead from his hand wipesand from his skeleton are present in his blood aswas argued above dietary absorption would have tobe correspondingly reduced

In the cases discussed above the blood lead decreased over the first 4 months of life There isevidence that the increase of lead m some children sblood over the same period is due to mgestion of

CHILDHOOD LEAD ACQUISITION 67

I,

T

6 -

CD

COc 3

12 18 24 30Age in Months

36 42 48

FIG 2 Quantity (geometric mean) oflead in the 24 h diet ofchildren as a function of age Solid line the group followed frombirth to 2 years Dashed line the group of 2 to 3 year oldsfollowed for 12 months

house dust rather than food For example the bottlefed child subject 115 3 was born with a blood lead of0 87 ug/dL having a 206Pb/207Pb ratio of 1 204 but at4 months his blood lead had increased to 1 9 ng/dL

en

tO

Ee

CD

12 18 24 30Age in Months

36 42 48

FIG 3 Quantity (geometric mean) of lead wiped from thehands of children as a function of age Solid line the groupfollowed from birth to 2 years Dashed line the group of 2 to3 year olds followed for 12 months

.QQ.

1 32

1 30

128

1 26

1 24

£- 1 22S

1 20

1 18

1 16

1 U

Maternal BloodChild s DietChild s BloodChild s Handwlpe

5 4 3 2 1 0 1 2 3 4 5 6Months from Parturition

FIG 4 206Pb/207Pb ratios oflead in maternal blood and in thatof subject 124 3 at birth and 4 months The ratios measured inhand wipes and in his diet are also shown

and its ratio had fallen to 1 189 The lead on his handwipes throughout the study had low ratios averaging 1 169 (Table 1) and it seems likely that he wasexposed to lead with this ratio in his first 4 monthseven though little appeared onjus hand wipes during this period Likewise the breast fed child subject 106 3 was born with a blood lead of 0 66 (ig/dLwhich rose to 1 7 at 4 months Over the same penodthe 206Pb/207Pb ratio of his blood fell from 1 206 to1 193 while his mother s blood lead and presumablyalso her milk averaged 1 207 Lead on his wipes

TABLE 2Ratio of Hand Wipe Lead to Dietary Lead Dietary Con

tribution to Blood and Percentage of Dietary Lead Absorbed by Subject 124 3 at 4 Months of Age Calculated forVarious Percentages of Bone Derived Lead in Blood

/ Bone Pbin blood

010203040505559

Ratio of handwipe Pb

to dietary Pbin blood

4752597195

1735

00

Dietarycontnbution/ to blood|ig Pb/day

0180075006700570044002500130000

/ Dietary Pbabsorbed

12504 43829160900

68 MANTON ET AL

taken over the course of the study averaged 1 181and again it seems likely that he was exposed to suchead even though no detectable amounts were found

on his hands during his first 4 months

Sources of Lead 5 to 8 MonthsThe period of transition occurring between the 5th

and the 8th month is characterized by changes inblood lead concentration and increasing exposure tolead through the diet and hand wipes Although thelead content of the diet changes three times morethan that of the hand wipes no corresponding movement of the isotope ratios of blood and unne towardthose of the diet was observed in any child over thisperiod As an example we show in Fig 5 the isotoperatio profile of one of the pilot children subject 53He was born with a blood lead of 1 1 ng/dL which fellto 0 58 ug/dL at 4 months and then rose to 1 2 at 12months (Table 1) Over this period he consumed foodwith high isotope ratios (Fig 5) but the ratios of hisurine between 4 and 12 months moved toward hishand wipes indicating that they and not food wereresponsible for the rise in his blood lead

Sources of Lead 9 Months to 2 YearsTo investigate the sources over this penod we

averaged (justified by the information in Fig 2) eachchild s exposure reporting amounts of lead as geo

1 45

1 40

1 35 -

130

1 25

1 20

1 15

m Blood—— Urine—— Hand Wipe

Food

e 12 isAge in Months

20 24

FIG 5 206Pb/207Pb ratios of lead in the blood unne handwipes and 24 h diets of the pilot study child subject 53 plottedagainst his age

metric means and the isotope ratios which we foundto be normally distributed as arithmetic means (seeTable 1) The average amount of lead on hand wipeswas 0 89 ng and the average content of the diet was3 2 ug Individual ranges were small With the exception of one case of 44 ug of lead no more than 8 ugwas wiped from the hands of any child and onlyeight diet collections contained more than 10 ug

We use a simple correlation diagram to test for thepresence of food or hand wipe lead in blood If onesource is predominant a plot of 206Pb/207Pb in unneagainst 206Pb/207Pb of that source will produce anarray of points lying on a line of unit slope passingthrough the origin In Fig 6 the mean 206Pb/207Pbratio of each child s food is plotted against that of hisunne and most of the points plot above the correlation line but when the hand wipe ratios are plottedagainst unne (Fig 7) the points scatter about theline suggesting that lead on the hands is the dominant source of lead in their blood

Origin of Lead on Hand WipesIt is seen from Table 3 that similar ranges in

206Pb/207Pb ratio were found on the floors and in thecarpets of each home and when the ratios are plottedagainst each other (Fig 8) they closely correlate Ifthe lead found on the hand wipes (Table 1) is plottedagainst that of the floor a fair correlation results(Fig 9) and similarly with a plot against the ratiosof the carpet (Fig 10) so that for many of the children lead on the hands appears to originate eitherfrom contact with the floor or from the carpet orboth For those that fall off the line it is possible thatthe parts of the floor with which they were mostcommonly in contact were not sampled or that theywere exposed to lead from another source but window sill lead or door mat lead as sole sources arerejected because their ratios (Table 3) range far beyond those found on the hand wipes

Origin of Lead on Floor and CarpetTable 3 lists the average loading and isotope ratio

of lead on surfaces in each child s home Window sillsare conspicuous for the amount of lead residing onthem (up to 9 6 mg/m2) and both they and door matshakings for their wide range of 206Pb/207Pb ratiosfrom 1 13 to 1 28 The range in ratio found on floorsand carpets is narrower from 1 18 to 1 22 (subject103 3 excepted) which in itself implies that the leadthat they harbor is not exclusively denved fromeither sill or door mat but for more than half thesubjects the ratio for the floor falls outside the range

CHILDHOOD LEAD ACQUISITION 69

i

.:

1 26

1 24

122

JD0.

Q_CD

S

1 19

1 17

1 15

. I

1 15 117 1 19206pb/207pb

1 22 1 24 1 26

FIG 6 Correlation plot of the average 206Pb/207Pb ratios oflead in 24 h diets with those of lead in the urine of the samechildren for the period 9 to 24 months of age The dashed line isa reference line of unit slope

spanned by the mats and sills implying that thereare other sources of lead within or without the homethat were not sampled For three of the subjects10F3 115 3 and 121 3 the ratios of window sillsand door mats he far apart and the samples from the

1 23

1 22 -

121 -8-5•O 1 20CO

cO.aQ.

i1 19

1 18

1 16

1 151 15 1 16 1 17 118 119 1 20 1 21

206pb/207pb Qf Unne

1 22 1 23

FIG 7 Correlation plot of the average 206Pb/207Pb ratios oflead m hand wipes with those of lead in the urine of the samechildren for the penod 9 to 24 months of age The dashed line isa reference line of unit slope

TABLESLoading and 206Pb/207Pb Ratios of Lead on Bare Floor

Carpeted Floor and Window Sills and Quantity and2oopb/2<>7pb of Lead m Door Mats at Homes of ChildrenFollowed from Birth to 2 Years

Pb found 206pb/207pb

Subject

101102103104105106107108109110112114115116119120121122124126

33333333333333333333

FloorHg/m2

94882045212365191120202126594041525144421836

Carpet

1332449534815874926131413242170739396—3834

SillHg/m2

5490218040oO37408040o9810704682750473967028883417201873256252318710178

MatMg

29683266627196122619241249422

19705222882441158

Floor

1111

188191236206

11901 18112101111111111111

207214196196215194197206197194202207195

Carpet

11111111111111111

11

179192226196195196214201218195202208194205214200198—209198

Sill

1128120012501 18911261 1761201123812471 17912811 1971 162120712111 1901 173120312131 189

Mat

1 1491186123211781 17311951208122112241 1911233122412531205122811971225120512151239

ArithmeanGeommean

77 9 33 8 2581 181 1 201 1 202 1 198 1 209

454 159 1187 45 0 — — — —

floor fall in between If it is assumed that the lead onthe floor is denved only from these two sources theratio of sill lead to mat lead in these cases rangesfrom 0 8 to 1 8

An Illustrative Case Subject 101 3Figures 11 and 12 show the profiles of a child (sub

ject 101 3) who displays many of the characteristicsof the group Being the sister of a child in the earlierstudy (subject 23 Table 4) she was one of the linkingsubjects and was followed for 3 years rather than 2She was bottle fed and her blood lead fell (Fig 11)over her first 4 months before nsmg to a maximumof 6 7 g/dL at 24 months after which it fell to6 2 (ig/dL at 36 months After 6 months the amountof lead in her food vanes erratically showing notrend No lead was detected on her hands for herfirst 8 months (as she had been recruited early in thestudy a relatively large blank of 0 2 ng was associated with the wipes) but thereafter the amount of

70 MANTON ET AL

1 24

1 122rtOcX)t?~ 1 20§

Q.tos

1 16

1 16

——— I ———— I ———— I ———— 1 ———— I ———— i ———— 1 ——— i ————

-

.

-

* *• ,

•• * -

9 * 9

*• **

-

-

i 1 1 1 \ 1 I 1

il5TJcCDICOrta.<LQ.

u>OCM

1 16 1 18 12 1 22 1 24206pb/207pb on Roor

1 24

1 23

1 22

1 21

1 20

1 19

1 18

1 17

, | . , . , . , . , . , . , .

-

-

**

.. •.« *

*•*

• •

•

.

-

1 16 1 17 118 1 19 1 20 1 21 1 22 1 23 1 !

206pb/207pb m c ,

FIG 8 Correlation plot of the average 206Pb/207Pb ratios oflead vacuumed from the carpet with those oflead wiped from thefloor of the same house The dashed line is a reference line of unitslope

FIG 10 Correlation plot of the average 206Pb/207Pb ratios oflead on hand wipes (from 9 to 24 months) with those vacuumedfrom the carpet of the home The dashed line is a reference line ofunit slope

lead on her hand wipes shows no trend In the isotope ratio plot of Fig 12 it is seen (1) that the206pb/207pb ratlQ of her urme closely f0nows that of.er blood (2) that her blood lead falls in isotope ratio

Wer her first 4 months even though she was consum

ing infant formula with a high isotope ratio and (3)that her blood isotope ratio continues to fall to coincide with the ratio of the lead first encountered onher hand wipe's and thereafter her blood and urinetrack the ratio of her hand wipes Figure 13 shows

1 23

0 1 22Q.

•O 1 21ca

§ 120

1 17

1 161 16 1 17 1 18 1 19 1 20 1 21 1 22 1 23 1 24

206pb/207pb 0

FIG 9 Correlation plot of the average 206Pb/207Pb ratios oflead on hand wipes (from 9 to 24 months) with those wiped from

I the floor of the home The dashed line is a reference line of unitslope

20

15

io 10

.oQ.

- Blood- Handwipe

Food

12 18 24Age in Months

30 36

FIG 11 Blood lead concentrations and lead on hand wipes ofsubject 101 3 from birth to 36 months and the concentration oflead in her diet from birth to 24 months

1W

El

CHILDHOOD LEAD ACQUISITION 71

1 30

I

I

1 25

joQ.

120

1 15

Blood- Urine- Handwipe

Food

12 18 24Age in Months

30 36

FIG 12 206Pb/207Pb ratios of lead in the blood urine andhand wipes of subject 101 3 from birth to 36 months and the206Pb/207Pb ratio of her diet from birth to 24 months

that the 206Pb/207Pb ratios of the floor of the homeconsistently fall between those of the window silland the door mat shakings and that the ratios of herhand wipes fall close to but do not coincide withthose of the floor

CHILDREN 2 TO 4 YEARS

SubjectsThe 20 subjects studied ranged in age from 19 to

39 months at the time or recruitment (Table 4) Ofthe boys 5 were white and 3 were black includinga pair of umovular twins (subjects 20 and 21) Sevenof the girls were white and the remaining 5 wereblack Subjects 22 and 29 were cousins as weresubjects 7 9 and 16 Most of the children had livedin the same houses since birth but subjects 17 and 24had moved shortly before joining the study and subjects 23 and 29 dunng its course Five were exposedto dust produced during long drawn out remodelingprojects subjects 17 and 24 before they moved andsubjects 25 26 and 27 in the houses in which theyhad lived since birth

Blood Lead ConcentrationsThe highest blood lead concentrations of 15 and

12 ng/dL were found in subjects 24 and 17 who hadlived through remodeling projects Subject 7 s bloodrose to above 10 ng/dL over the period of observationas did subject 29 s after she went to live with her

cousin The lowest average concentration of2 7 jag/dL was found in subject 20 The othersshowed small changes generally less than 2 ng/dLover the 12 months that they were followed

Exposure to Lead from Food and Dust

Lead in 24 h duplicate diets ranged from 1 9 to6 8 ng/day with a mean of 4 17^g/day There seemsto be no trend with age (Fig 2) and the amountfound is 1 ng/day higher than that found for the 9 to24 month old children The amount of lead found onthe hand wipes ranged from 1 2 (ig (subject 23) to12 9 ng (subject 22) with a geometric mean of3 97 \ig There is no trend with age (Fig 3) but thequantities are 4 5 times greater than those found inthe younger group of children For the older groupthe ratios (1) of blood lead concentration to amountof lead in a 24 h diet and (2) of blood lead concentration to amount of lead wiped from the hands providean arbitrary but useful way of analyzing the resultsbecause they are close to unity for most of the children (Table 4) and plot in a close group (Fig 14)Subjects 16 and 23 are displaced horizontally fromthe average by virtue of the relatively small amountsof lead wiped from their hands and subject 22 vertically by the relatively small amount of lead in herdiet This subject was the only one to show a strongseasonal variation in the amount of lead wiped fromthe hands less than 10 ng in winter but as much as40 \ig in the summer Empty battery cases werefound stacked up against the house

Anomalous Blood Lead ConcentrationsChildren who are displaced at 45 degrees away

from the average group in Fig 14 are anomalous inthe sense that their blood lead concentrations appear not to be commensurate with their measuredexposure Each is discussed below

Subject 29 with a blood lead of 9 7 ug/dL initiallyplotted the farthest from the average but after shemoved to live with her cousin (subject 22 discussedin the previous section) at their grandmother s homeher hand wipe lead increased causing her to plotclose to the vertical axis Visits to her grandmotherwould account for her being exposed to a source thatwe did not sample

Subject 9 is similar to subject 29 in that from birthto 6 months she spent 4 to 5 h a day at the home ofsubject 7 and it is possible that her blood lead stillreflects exposure to the relatively large amounts oflead in that home reflected in subject 7 s hand wipes(Table 4)

72 MANTON ET AL

TABLE 4Blood Lead Concentrations Amount of Lead in Hand Wipes and Food and 206Pb/207Pb Ratios of Lead in Blood Hand Wipes

and Food for 2 to 3 Year Old Children

N

26789

101316172021222323*242526272929 *3031

ArithGeom

Subject

Race/sex

W/MW/MW/FB/MW/FW/MW/FW/MW/MB/MB/MB/FB/F

W/FW/FW/FW/FB/F

W/MB/F

meanmean

Blood Pb

Age(months)

20282439282227272421213931

3022272819

2524

263—

StartHg/dL

4 14 5867858375550

1202846563838

15054828797

1066539

6660

EndHg/dL

4435

1077 25845355085303974—4 2

153455880—

1194 237

6458

AverHg/dL

4337947557484 251

1012740623841

loO4 2688097

117494 1

5140

Pb Sources

Hand wipe FoodHg ng/24h

4 052856427482o13183743

12912124 248

1108516

1185138

5140

26336752254437333637393036545468555519283948

4239

206pb/207pb

Blood Hand wipe Food

12021 1931209119811941 19911981202117012001184120812051 1991 1701 196117012301 2061 20812081208

1198—

1 1961 185122012011 187119912031200118312051206121212071 19812051195117312191207120812021217

1201—

121612131201120012081197120812131208121312141 1991210121512031208120412161220120412121224

1209—

Blood Pb

Wipe Pb

1 1071 112211017395607090533

360906096110101 1_—

Blood Pb

Food Pb

17111414231 11 1152807102 109

280612155 14 21309__

—

* After 5 months changed residence** After 4 months moved to live with subject 22

v i

1 irM

fH

Subject 17 moved shortly before the study beganinto a home that his parents had been convertingfrom a warehouse since the time he was 6 monthsold He frequently accompanied them and was allowed to crawl at will on the floor Over the first 12months that he was sampled his blood lead concentration steadily decreased from 12 to 85 ng/dLwhile the 206Pb/207Pb ratio of his blood and urine didnot deviate from the unusually low value of 1171He was followed for a further 24 months duringwhich his blood lead concentration continued to declme ending at a value of 4 5 ng/dL (Table 5) Therewas however no change in his blood lead isotoperatio which continued to remain lower than thatobserved in his food and on his hands It is clear thathis blood lead was dominated by lead from anothersource but given his decreasing blood lead concentrations it is likely that this source is endogenousand is lead stored m his skeleton This mterpretation is consistent with the possibility of exposure tolead during a period of renovation and construction

occurring before we first sampled him at age 2 yearsSubject 24 lived from birth to 4 months before she

moved into her current home in a 100 year old housein which her father had done sanding and paintingamong other refurbishing projects Her blood leadconcentration (initially 15 ug/dL) was the highestencountered in the study and at the outset of sampling there was the greatest disparity between the2o6pb/207pb ratlQ of her Wood and unne (1 15g) and

that of her food and hand wipes (1 200-1 210) Shewas followed for 3 years Lead concentrations areshown in Fig 15 Except for a subsidiary peak at age37 months her blood lead concentration steadily declmed passing through 10 |ig/dL at 56 months andending at 8 9 ^g/dL at age 64 months Duplicatediets and hand wipes were taken from her until shestarted attending kindergarten at 54 months Overthe period sampled the amount of lead in her fooddeclined while the amount of lead wiped from herhands shows no trend despite some occasions whenmore than 10 \j.g was found The isotopic profile

CHILDHOOD LEAD ACQUISITION

JD0.

126

1 24

122

1 20

1 18

1 16

1 14

1 12

Mat

12 16 24Age in Months

FIG 13 206Pb/207Pb ratios of lead on the window sill on thefloor and in dust shaken from the doormat of the home of subject101 3 plotted as a function of her age The ratios for her handwipes are also plotted See Fig 12

(Fig 16) shows the 206Pb/207Pb ratio in her food andhand wipes varying about an average value of 1 205The abrupt rise in the 206Pb/207Pb ratio of her bloodand unne corresponds to the change in blood leadconcentration occurring at age 37 months but apart

6-

S.oom

3-

2-

1 -

29

29

24 17

22

16

23

0 1 2 3 4 5 6 7Blood Pb/Hand Wipe Pb

FIG 14 The ratio for the 2 to 3 year old children of bloodlead concentration to lead on hand wipes plotted against the ratioof blood lead concentration to lead in 24 h diet Those subjectsshown by number are discussed m the text

from this their ratios slowly trend toward those ofher food and hand wipes The declining blood leadconcentrations of this subject and the absence of anylead sources with low isotope ratios in her homepoint to much of the lead in her blood having beenacquired in her first home and stored in her skeletonbefore she reached the age of 2 years It turned outfrom her history that the excursion, in blood leadconcentration and isotope ratio occurring at 37months corresponds to a remodeling project in thenew home

Other Children Exposed to Lead during RemodelingSubjects 25 26 and 27 who had lived since birth

in houses being remodeled do not plot anomalouslyin Fig 14 With a blood lead concentration averaging4 2 \ig/dL subject 25 does not appear to have beenaffected to any great extent and is not consideredfurther Subjects 26 and 27 s blood lead concentrations were initially 8 2 and 8 7 ng/dL and fell overthe first 12 months of observation The 206Pb/207Pbratio of subject 26 s blood and unne did not deviatefrom 1 170 and this value was almost identical tothat found in her hand wipes She was not followedany longer The 206Pb/207Pb ratio of subject 27 witha value of 1 230 was consistently higher than that ofher hand wipes She was then followed for a further22 months over which her blood lead fell steadily to4 4 ng/dL (Table 5) with its 206Pb/207Pb ratio remaining at its high value as if the lead in her blood wasdominated by lead acquired before we began sampling her In the cases of the two subjects 26 and 27and of subject 17 the ratios fall outside of the rangemost frequently encountered in the United Statesenvironment (Jaeger et al 1998) and suggest denvation from a restncted source such as a batch ofpaint containing lead with a distinct isotopic composition

The Twins Subjects 20 and 21The twins are of interest because each acts as the

control of the other and indeed their exposure tolead in food and hand wipes was almost identicalboth in quantity and in isotope ratio Despite thissimilarity m exposure the blood lead concentrationof subject 21 was initially 4 6 ng/dL as compared tohis brother s 2 8 ng/dL (Fig 17) It progressively decreased for 12 months before attaining a constantvalue 0 4 g/dL higher than his brother s which hadremained constant over the 3 years of observationThe isotope ratio plot (Fig 18) shows a similar pattern Subject 20 is normal in that the 206Pb/207Pb

MANTON ET AL

TABLESBlood Lead Concentrations (PbB) of Children Withdrawn from Exposure to Lead at Various Ages

Subject 17 Subject 24 Subject 27 Subject 51 Subject 102 3

Note The last row contains the apparent half lives of lead in the blood of each child

Subject 106 3

Agemonths

276303327348373422543574

(20

PbBug/dL

1201021018578644 145

months)

Age PbBmonths ug/dL

340370437489559611637

(38

1501381281321028689

months)

Age PbBmonths Hg/dL

310345372391410469529577602(33

878273807061595244

months)

Agemonths

182238293

PbBHg/dL

734131

(8 9 months)

Age PbBmonths ug/dL

83120182244306

(78

11073302315

months)

Agemonths

79120179240299

PbBHg/dL

12159463 129

(114 months)

ratios of his blood and urine are similar to those ofhis hand wipes His brother s blood and urine haveinitially much lower ratios which move toward hisover a 12 month penod Over the following 14months their ratios parallel each other s with subject21s ratio being slightly less than his brothers Itseems that subject 21 was briefly exposed to leadicfore age 21 months which was largely excretediver the following 12 months but part of this lead

25

.0Q.

20-

15-

10-

5-

- Blood- Hand Wipe

Food

30 36 42 48 54Age in Months

60 66

FIG 15 Blood lead concentrations and the amount of lead onhand wipes and in the diet of subject 24 as a function of age No

and wipe or food samples were taken once she started attendingndergarten at 54 months

was retained and only slowly makes its way intoblood still contributing about 0 4 ug/dL at least3 years after his initial exposure

DISCUSSION

Lead in BloodThe average concentration of lead in the blood of

the 2 to 4 year olds (4 0 ng/dL Table 4) is almost

1 26

1 24-

1 22-

1 20-

1 18-

1 16-

1 14

s blood—— Urine—— Hand Wipe

Food

30 36 42 48 54Age in Months

60 66

FIG 16 206Pb/207Pb ratios of lead in the blood urine andhand wipes of subject 24 as a function of age No hand wipe or foodsamples were taken once she started attending kindergarten at54 months

CHILDHOOD LEAD ACQUISITION 75

a>

#20 Blood#21 BloodHand Wipes

181 i '24

' i '30

1 i '36 42 48 54

Age in Months

FIG 17 Blood lead concentrations and the average amount oflead wiped from the hands of the umovular twins subjects 20 and21 plotted as a function of their age

identical to the national average of 4 1 ng/dL for 3 to5 year olds reported for the period 1988 to 1991(Brody et al 1994) The value for those followed

1 23

1 22

1 21

£ 1 20

1 18

1 17

1 1618

1 i <24

' I i30

1 ' ' I '36

Age in Months

T1"42 48 54

FIG 18 206Pb/207Pb ratios of lead in the blood urine andaveraged hand wipes of the umovular twins subjects 20 and 21plotted as a function of their age At month 42 the curves for theirurines touch but do not cross Symbols are the same as those ofFig 17 but with urines of each plotted as solid lines

from birth for the penod 12 to 24 months is somewhat less (2 4 to 2 8 |ig/dL Table 1) but is consistentwith the continuous decline in lead in the blood ofthe population Although these values are less thanthose reported in earlier time continuous studiesthe overall patterns are similar Thus the curvesshown in Fig 1 have the same form as those in Fig 1of Clark et al (1985) and the decrease in blood leadconcentration in the first 4 months of life was observed by Ryu et al (1983)

Lead in Food and Hand WipesDuring the 1980s the concentrations of lead in the

diets of infants and toddlers living in the UnitedStates declined rapidly converging to a value ofabout 5 ug/day in 1988 (Bolger et al 1991) Theconcentrations of lead in the 24 h duplicate diets ofboth our groups of children (3 2 |ag/day for the 9month to 2 year olds and 4 2 ng/day for the 2 to4 year olds) are consistent with this trend and againindicate that the population that we sampled wasrepresentative of the average child of the early1990s

The 4 0 |ig of lead wiped from the hands of the 2 to4 year olds is comparable to the amounts reportedfor Cincinnati children living in post World War IIprivate housing in satisfactory condition (4 3 ng) andirfpubhc housing (4 8 g) during the 1980s (Clark etal 1991) but the 0 93 \ig found for the group that wefollowed from birth to 2 years is lower than anyfigure reported to date

With regard to the large difference between theamounts of lead in hand wipes taken from the twogroups of children we first considered the possibilitythat lead recovered from the hands was a function ofhand size or as reviewed by Fmley et al (1994) anage related difference in soil to skin adherence Applying the calculations of Fmley et al to the increasein surface area and hand surface area of children(0 047-0 057% of total body surface area) the progressive plot of hand surface area from birth through48 months does not predict the observed values The4 0 |ig wiped from the hands of 2 to 4 year olds withhand surface area 26 3-42 6 cm2 is equivalent to0 094-0 136 mg/cm2 Applying this concentration tothe hands of a 12 month old (22-27 cm2) would prediet 2 10-3 7 jag Pb recovery In sum the recovery ofonly 0 93 |*g Pb from birth to 24 months cannot beattributed solely to the smaller hand size

We next considered the possibility that it was anartifact because three field technicians were employedover the course of the study the first of whom was theonly one to get samples from the 2 to 4 year old

76 MANTON ET AL

children We are however confident that each wasviping the hands as effectively as the other becausene sampling of the pilot study child subject 51 span

ned the employment of all three The first technicianwiped his hands from birth to 11 months the secondfrom 12 to 21 months and the third from 22 to 42months It is seen m Fig 19 that although eachobtained a different average amount of lead theeffect bemg sought namely that the second andthird technicians were wiping the hands less efficiently is absent Another test is to compare theresults from siblings one of whom was sampled onlyby the first technician Subject 51 is the brother ofsubject 2 who had a blood to wipe ratio close to unity(Table 4) which value subject 51 exhibited for thelast year in which he was sampled (Fig 19) Likewise subject 25 (Table 1) and her sister subject102 3 when 24 months old (Table 4) had blood towipe ratios close to one although the quantities oflead for the older child were twice as high The twosisters subjects 23 and 101 3 have comparableamounts of lead on their hands and their blood towipe ratios of 3 3 and 4 5 are similar and characteristically both higher than average These resultssuggest that we sampled two different populationsone of which the 2 to 3 year olds and their siblingslived in homes with a greater lead loading on surfa:es whether due to remodeling more lead in thelamt of the home or poorer housekeeping practices

But this explanation is not entirely satisfactory because the wipe to blood ratios are not a same for each

9

s -

7 -

6 -

5O% 4

J2°- 3

2

1

- BloodHand Wipe

12 18 24 30 36 42 48Age in Months

FIG 19 Blood lead concentrations and the amount of lead onlandwipes and in the diet of subject 51 as a function of age

group For the younger group the ratio at 24 monthsis 0 37 and for those of the older children who plot inthe closely spaced group of Fig 14 the ratio is 0 89for an average age of 25 months Some other factorseems to be involved possibly different bioavailabihties of the lead in the homes of the two groups andeven the likelihood of some of the mothers washingtheir children s hands pnor to visits cannot be entirely discounted Even if the last occurred our interpretations would still be valid because washingwould not materially alter the isotopic character oflead on the hands

Uptake of Lead from Food and Hand WipesA commonly used value for the gastrontestinal

absorption of dietary lead in the infant is 53% takenfrom the work of Alexander et al (1974) and supported by the studies of Ziegler et al (1978) Ourfinding of much lower uptake was made on a childwhose diet contained one tenth the amount of lead inthe diets of Alexander et al s (1974) subjects andmay be reconciled with their work if the absorptionof lead is a nonlinear function that nses steeply asthe Pb/Ca ratio of the diet increases Given the current levels of lead in food it seems inappropriate tocontinue to use Alexander et al s (1974) value forinfants and from the work of Gulson et al (1997)similarly high values currently used for the olderchild also appear to be unreahstically high In contrast the dominance of the blood lead isotope ratiosby those of the hand wipes indicates that the absorption of lead in dust and dirt ingested in the absenceof dietary calcium is high How high cannot be determined from the present work except to say that theabsorption probably differs at least by the factor of10 found by James et al (1985) for 203Pb labeled leadacetate administered to adults

Gulson et al (1998b) have used the isotope ratiosof lead in blood to determine the dietary absorptionof lead by infants For breast fed children born mAustralia to immigrant mothers they report valuesbetween 36 and 80% and for formula fed childrenthey report 24 to 68% which is far larger than ourestimates for a formula fed child (see Table 2) Theyused a two source model with breast milk or formulaas one end member and the infant s blood (presumably the cord blood) as the other and withoutmeasuring hand wipes assumed the contributionfrom dust to be negligibly small It is clear from ourwork however that the contnbution from dust cannot be ignored and that their failure to check for leadon the children s hands casts doubt on the validity oftheir calculations * k

t

/ff

CHILDHOOD LEAD ACQUISITION 77

k Applicability of Dietary Lead Uptakesto Other PopulationsSince certain nutrient deficiencies specifically cal

cium iron and zinc may enhance lead absorption(Chisholm 1980 Mahaffey 1980 Goyer 1997) thediets of the children was analyzed for adequacy byboth direct chemical analyses and by computer generated estimates based on the mothers diaries Forthe chemical analyses ahquots of homogenates of 84diets (quarterly collections) were shipped to MidwestLaboratories of Omaha where they were analyzedfor calcium iron and zinc by inductively coupledplasma mass spectrometry after digestion in nitricand hydrochloric acids Estimates of concentrationsof these same metals in 249 additional diets weregenerated with the Minnesota Nutnent Data Systern Version 2 3 software (Nutntion CoordinatingCenter 1991) All values were then compared to theRecommended Dietary Allowances (RDA) Mean intakes of calcium were 58% (estimated) and 57%(actual) of the RDA zinc was 47% (estimated) and46% (actual) and iron as estimated was 89% Actualdeterminations of iron were not reported since theblender used for homogemzation added iron to thesamples From these values it seems that our findings of low dietary absorption are applicable to dietsboth adequate and inadequate with respect to calcium and zinc

Our findings do not apply however to those citiesand other localities where tap water may contain asmuch as 15 ug Pb/L and constitutes a major source oflead intake perhaps as much as 20% of the averageresident s total exposure (Warlaw 1999) Here thelead content of infant formula reconstituted withsuch water would be considerably greater than whatwe measured and the uptake of lead from tap watertaken between meals might be comparable to thatingested from the hands

Lead Loadings on Window SillsThe high loadings of lead that occur on window

sills probably originate from dust produced by fhction along lead painted surfaces It seems from ourwork that some of this dust settles on the floor whereit is mixed with lead tracked into the house and thatthis mixture is then ingested by the child Suchmgestion constitutes indirect exposure to windowsill lead An interesting question is how often a childtouches a window sill and is thereby directly exposedto the lead deposited on it The plot in Fig 13 mayreveal a pattern of behavior Up to 23 months of agethe isotope ratios of the lead on this child s hand

wipes were less than those of the floor as if she wasgetting more into areas contaminated with leadbrought in from the exterior but from 23 months herhand wipe ratios were higher than those of the flooras if she was more frequently touching the sill Whatis clear however is that few of the children that wefollowed had potentially dangerous encounters withlead on window sills because of the 40 only 2 appearto have ingested a bolus of lead from a concentratedsource such as a sill One of these is subject 52whom we followed from birth to 43 months His bloodlead concentrations (Fig 19) measured every4 months passed through a peak at 12 months thatwas not reflected in his hand wipes The isotoperatios of his urine (Fig 20) taken monthly narrowlydefine his exposure to a bnef period when he was 14months which according to his history is when hebegan to walk It then took 36 months for the isotoperatios of his blood and urine to attain the ratios of hishand wipes which had also failed to show any sustamed exposure to lead with a high isotope ratio Asthis child was one of the pilot study children wewere not simultaneously getting environmentalsamples from his home but a survey conducted whenhe was 36 months old found lead on a window sillwith a ratio of 1 270 The other case is the twinsubject 21 who some time before we began tofollow him had been exposed to some source of leadto which his brother had not The question of howone and not the other could be exposed when their

1 27

1 26 -

1 25

1 24

Is 123Q.u>8 , 22

1 21

1 20

1 19

BloodUrineHand Wipe

6 12 18 24 30 36 42Age in Months

48

FIG 20 206Pb/207Pb ratios of lead in the blood urine handwipes and diet of subject 51 as a function of age

•VDS

78 MANTON ET AL

subsequent exposures were nearly identical is answered by invoking an encounter with lead on a window sill and the initial survey of the home foundlead with a 206Pb/207Pb ratio of 1 164 on a sill Theloading was 4900 (ig/m2

Rate of Lead Loss after ExposureIn this study we have observed changes in blood

lead concentration following two types of exposure tolead one bnef resulting from contact with somehighly contaminated source such as a window sill orfrom dust produced during professional remodelingand the other prolonged resulting from some longdrawn out project earned out by the parents onweekends or other times available to them Subjects51 102 3 and 106 3 fall in the first group and subjects 17 24 and 27 in the second Their blood leadconcentrations and ages are given in Table 5 Theapproximations to straight lines in the semi logarithmic plot of Fig 21 indicate that the decline ofblood lead in these children can be expressed by anexponential function whose rate constant which isthe sum of all rate constants in and out of the bloodcompartment yields an apparent half life of lead inblood The slopes of the lines indicate that the clearance of lead from the children who had prolongedexposure over the first 2 years of life is longer thanthat of the children who were briefly exposed Theapparent half life of the briefly exposed group laybetween 8 and 11 months while that of the group

100

JOo>JDQ-•oom

1 oo

511023

Sub 106 3

12 24 36 48Age in Months

60 72

FIG 21 Plot of the logarithm of blood lead concentrationagainst age for children who had abnormal exposure to concentrated sources of lead

with prolonged exposure lay between 20 and 38months (Table 5) These values are much longerthan the 15 day half life of lead in the blood compartment of the adult (Chamberlain et al 1978) andare manifestations of the greater rate of turnoverof the skeleton of the young child (Leggett 1993O Flaherty 1995) If the blood lead concentration ofsubject 24 continued to decline -with a 38 monthhalf life it would in 10 years have reached 11% of itsvalue at 34 months Likewise the blood lead of subject 27 with a half life of 33 months would in 10 yearsbe 8% of its value at 33 months These values are infair agreement with 0 Flaherty s (1995) calculationpredicting that at age 12 years the blood lead concentration of a girl who had been removed from exposure to lead at age 2 years would have fallen to 14%of its starting value With a half life of 20 monthshowever subject 17 s projected blood lead concentration falls far short of 0 Flaherty s (1995) predictions

There are two principal implications of these Ionger apparent hah0 lives First if a child is found tohave a blood lead in excess of the CDC guideline of10 ng/dL (Centers for Disease Control 1991) it maybe futile to attempt to find the source of lead m thechild s immediate surroundings because the exposure may have occurred many months before evenin another residence Second experiments should bedesigned with these long apparent half lives inmind Thus if it is desired to examine the effects ofsoil lead abatement it would be more meaningful tocompare the blood leads of the exposed group withthose of a new generation of children growing up onthe abated soil rather than to attempt to assess thepost abatement decrease in the blood lead of theexposed group The Boston Lead in Soil Demonstration Project is a case m point (Weitzman et al 1993Aschengrau et al 1994)

Isotopic Studies us Statistics Based StudiesThe traditional way of investigating the pathways

by which children acquire lead is to correlate bystatistical methods concentrations of lead in bloodwith the amounts of lead associated with the varioussurfaces and materials with which the child mayhave contact There have been many such studies(some are listed m the Introduction) of which themost recent is the Rochester study descnbed in several papers by Lanphear and his co workers (LanpheareZaZ 1995 1996 1997 1998a) It is of interestto compare the findings of their work to those of ourstudy to see to what extent the fundamentally different statistical and isotopic approaches to the sameproblem complement each other

CHILDHOOD LEAD ACQUISITION 79

f

Comparing the Omaha children followed from birthto the Rochester children we find that the Omahachildren had at 12 months a lower blood lead (2 7 vs7 7 (ig Pb/dL) and correspondingly lower loadings onfloors (45 vs 160 ugPb/m2) and carpeted floors (16 vs110 ng Pb/m2) The relatively smaller fraction of carpet lead measured for the Omaha houses may resultfrom sampling technique (Lanphear et al 1995) Theloadings on window sills were closer 1190 ngPb/m2

for Omaha and 1660 ng Pb/m2 for Rochester No handwipes were taken from the Rochester children and nosoil was measured in Omaha

Lanphear et al s (1996) principal conclusion thatlead contaminated house dust is the major contributor to children s blood lead is supported by our workbut we would go further and state that it is the onlycontributor having found the amount of dietary leadin blood to be negligible They identified all surfacesmeasured i e bare floors carpeted floors windowsills and window wells as significant contributors toblood lead As bare floors and carpeted floors had thesame isotope ratio we cannot state which contnbutes more lead to blood We found that lead on window sills contributes to floor dust and so to blood leadbut that only 2 of 40 children ingested large amountsof lead directly from what could have been a windowsill If doormat shakings are representative of thesoil around a house we have shown that soil contnbutes to house dust a point that Lanphear et al(1996) could not decide upon

What is surprising in the light of our findings isthat the statistical correlations between house dustand blood lead are not stronger and in particularhow weak was the correlation found by Bornscheinet al (1987) between hand wipe lead and blood leadhowever as Lanphear and Roghmann (1997) pointout if the child is continuously putting its hands intoits mouth the amount of lead on its hands will neverbe measured accurately Other factors that mayweaken a statistical correlation are different formsof lead in dust different gastrointestinal absorptions and the apparent long half life in the blood ofchildren so that a blood lead concentration always tosome extent reflects past exposure All in all the twoapproaches lead to similar conclusions with the isotopic by virtue of its independence of concentrationmeasurements providing insights into the processesthat bring about the acquisition and retention oflead by children

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