Environmental Research Section A 82,60-80 (2000) Article ID enrs.1999.4003, available online a t http:llwww.idealibrary.com on 10 Ebl'

Acquisition and Retention of Lead by Young Children1 W. I. Ma~ i ton , "~ C. R. Angle,? K. L. StanekJ Y. R. Reese, *and T. J. Kuehnemann.1

'Dcpamnent of Geology. Universjty of Texas at Dallas, Richardson, Texas, 75083-0688; tDepartment ofPediatrics, University ofNebraska Medical Center, Omaha, Nebraska; and $Deperimeni ofNotrition Science, University ofNebraska at Omaha. Omaha. Nebraska

Received December 15. 1998

The concentrations and isotope ratios of lead in blood and urine, on the hands, and in duplicate diet samples were measured for children living in Omaha, Nebraska. One group consisted of 22 chil- dren followed from birth to between l and 2 years of agc and another group was 20 2. to 4-year-old chil- dren followed for l year, although some in each group were followed for periods between 3 and 4 years. At no time in life was a component of die- tary lead identified in blood by isotope ratios, and blood lead appears dominated by lead derived from the hands, which in turn appears derived from the floors. For some homes floor lead appeared to he a mixture of lead from window sills and from the exterior. Only 2 of the children appear to have in- gested lead directly from window sills. Several who lived in homes being remodeled were exposed to lead before the age of 2 years. For those who had been briefly exposed during professional remodel- ing the blood lead fell with a half-life of 10 months hut for those who had suffered prolonged exposure during remodeling by parents the apparent half-life was longer, between 20 and 38 months. a,zoooAcademic

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INTRODUCTION

In the 1960s so little was known of the conse- quences of environmental lead pollution that the architects of the Three- and Seven-City Surveys (Pub- lic Health Service. 1965; Tepper and Levin, 1975) did

The procedures and consent farms were reviewed and approved by the Institutional Revfew Board of the University of Nebraska Medical Center. "0 whom correspondence should be addressed a t Department

of Geology, Mall Drop FOZI, Univei.sity o f Texas a t Dallas. PO Box 830688. Richardson. TX 75083.0688. Fax: (972) 883-2537.

not include children in their sample. I t was Lin-Fu (1972, 1973) who first brought attention to the high blood lead of urban children and Sayre et a1 (1974) who first pointed to a correlation between the lead in their blood and that in the dust of their homes. a relationship borne out by many subsequent studies (Landrigan eta/.. 1975; Angle and McIntire, 1979; Charney et al., 1980; Bornschein eta]., 1987; Davies era]., 1990; Lanphear e t al., 1996, 1998a.b). Leaded gasoline and smelter emissions, which some years ago were major sources of lead particulate, are no longer of any consequence in the United States so that lead in house dust is presently regarded a s coming from two sources: one internal, presumed to be paint, and one external, usually claimed to be contaminated soil brought into the home on the feet of the occupants. Despite the simplicity of this model, i t has sometimes proved difficult to under: stand the relationships between blood lead and the putative source of the lead in house dust. Kilnbrough et a1. (1995), for example, found that soil lead ac- counted for only 3% of the variance in blood lead of children living in a n urban area surrounding a closed lead smelter. and Weitzman et al. (1993) found that children's blood lead did not fall by the expected amount after removal of lead-contaminated soil from around their dwellings. Variables such as race, family income, condition of the home, and mouthing activities may have effects large enough to obscure the contributions OF paint or soil to blood lead (Kimbrough et al.. 1995; Lanphear and Rogh- mann, 1997).

Another way to look for the sources of lead is to use isotope ratio tracing, which makes use of the prop- erty that lead, being to a large extent the product of the radioactive decay of uranium and thorium, va- ries in isotope ratio according to the geological age of the ore deposit from which it is mined. For the first clear enunciation OF the principle see Chow and Earl (1970). Not only does this method provide the

0013-9351100 $35.00 Copyright 63 2000 by Academic Press Ail righla of icproducfton in any form reserved.

62 MANTON ET AL.

Recruitment

In both parts of the study the subjects were re- cruited through newspaper advertisements and notices in health facilities. Exclusionary criteria in- cluded blood lead over 15 j~gldL, household members with known lead exposure, lead hazard in the house- hold identified by a health department inspection, anemia, chronic illness, or disability. An effort was made to recruit equal numbers of subjects in each dichotomized class: race (white and other), income (welfare assistance or not), plans for breast or bottle feeding, and sex of the children.

Training

At the initial visit, before signing the consent agreement, the mothers were told that they would be participating in a dietary lead study. They were informed that they would need to prepare, weigh, and record in a diary the contents of a 24-h duplicate diet 1 day per month. Much time was spent on this procedure, as it was the most difficult part of the research. The second most difficult area was collect- ing a urine specimen from the infants, and the mothers had to learn how to clean the genital area and how to affix a collection bag. Each family was told that a blood sample would be taken three times a year. This was another concern because of possible discomfort to the child. When told that handwipe samples would be taken a t each visit and that soil and dust samples would be periodically collected, very little discussion ensued because this sampling did not require the mother's compliance with a pro- cedure. Environmentalist visits were unannounced; otherwise the mother might have purposely cleaned and dusted. The mothers did not express concern about lead in dust or paint.

The training was surprisingly successful and the mothers learned to collect and record the diets and to collect clean urine samples in bags or in Teflon jars once the child got older. A technician visited each family once a month, measured the child's height and weight, took hand wipe samples, and picked up the monthly urine samples (collected that morning) and diet samples (collected over the previous 24 h). The visits of the phebotomist and the environ- mentalist were done in conjunction with that of the technician.

Sample Collection

Wherever possible, samples were collected in Tef- lon PFA vessels that were acid-cleaned in the Dallas

laboratory before shipped to Omaha. Exceptions were polyethlene jars used for food collection, which were acid-washed in Omaha, and polyethylene pediatric urine collection bags and polypropylene syringes used to draw blood and to transfer urine. which were shown to contain negligible amounts of lead.

Blood was taken at birth (if possible from the umbilical cord) and every 4 months therearter by a phlebotomist. Approximately 5 mL was drawn through a heparinized butterfly into a sealable Sar- stedt syringe in which it was shipped to Dallas. Urine was syringed out of the collection bags and transferred to Teflon bottles before shipping. A por- tion was retained for creatinine determination. Hand wipes were K-Mart Little Ones selected be- cause they contained less lead than other brands. To minimize the blank, only two were used to dean both hands of each child.

Floor, window sill, and carpet samples were col- lected by defined procedures (State of Minnesota. 1990). Surface dust was collected by wipe sample from a 1-square-foot area outlined by a template on the floor or from a measured area of window sill. The operator wore disposable gloves that were wiped clean, with the wipe being discarded. One wipe was sealed as a blank. Wiping was done in an S pattern over the entire area, the wipe was folded, and the area rewiped at 90 degrees to the first S. Carpet dust was aspirated through an air pump calibrated a t 3Llmin into an 0.8-pm filter cassette (Gelman Sciences, Ann Arbor. MI; GN-4 Membrane, Air Monitoring Cassette. 37-mm diameter). All analyses were converted to pg Pb/mz. The area sampled was the main play area of the child. If it was carpeted the nearest uncarpeted floor was sampled and vice versa. Doormats were bought for those families that did not own them and were shaken over a clean sheet of paper every 6 months.

Lead Spikes

A 78.9% enriched Zo"b spike was used. Because the isotope does not occur in nature, it may be used to obtain both the lead isotope ratios and the lead cocentration from the same analysis. A highly en- riched (99.98%) "O"Pb spike was used to measure blanks.

Sample Preparalion and Decomposition

Upon receipt, samples were handled under clean, Class 100 conditions. Initially, food was homogen- ized in a 4-L Waring blender but this was replaced

CHILDHOOD LEAD ACQUISITION 63

with a Brinkmann Polytron equipped with a 24-mm stainless steel generator having Teflon bearings. A 10% aliquot was taken for analysis. In the case of shakings from doormats, the fraction passing through a 100-mesh nylon sieve was analyzed. All samples were decomposed with distilled nitric acid in Teflon PFA vessels: blood, urine, and food on a hot plate and hand wipes and doormat shakings in a microwave. Blood and urine, which contained nanogram quantities of lead, were spiked before de- composition, whereas food and hand wipes, con- taining at least a hundred times more lead, were decomposed before being aliquoted and spiked.

Lead Separation

Lead in blood, urine, and food samples was separ- ated by anion exchange in dilute hydrobromic acid. A problem with this procedure is that nitric acid only partially decomposes the sample and large quantit- ies of organic matter follow lead through the separ- ation. To reduce the organics, samples were charred at 2OO"C after being evaporated to dryness and two ion exchange steps were used, a conventional col- umn followed by a single bead. Lead from hand wipe and doormat samples was coprecipitated with bar- ium nitrate added directly to an aliquot of the de- composed sample. It was then separated from the barium by electrodeposition on a platinum anode.

Mass Spectrometry

A Finnigan MAT 261 multicollector, thermal ion- ization mass spectrometer was used in this work. The ZnSPb spike, which was made from "'Pb, has a Z05PblZo'Pb of 6.05 and, as such, can yield accurate 206Pb/Z0'Pb ratios only if sample to spike ratios are large, which may not always obtain when samples of unknown lead content are analyzed. The ratio ZnGPb/207Pb, however, may be recovered for small sample to spike ratios and is the ratio reported here. Rabinowitz (1995) has pointed out that the correla- tion between 20'Pb/Z0@Pb and Zn'Pb/"07Pb in environ- mental lead is high. The reason is geological. All major ore deposits of lead formed during the last third of the Earth's history when Z3SU had already passed through [our half-lives, so that the produc- tion of ""Pb over this interval was small and its abundance in the Earthscarcely changed. The ratios mGPb/ZO'Pb and zo6Pb/2'"Pb are, therefore, essentially of the form d a and xlb, where a and b are constants. Thus, plots of either against time convey almost identical information (see also Manton, 1977) but if the highest accuracy is desired. "6Pb/Z07Pb must be

the ratio of choice because each isotope, having ap- proximately the same abundance, is measured with equal precision, an important consideration if sig- nals are small. The value of 20Tb1204Pb is, in con- trast, between 17 and 22. Another reason for using "Tb/Z07Pb is that the uncertainty introduced by mass fractionation in the thermal ionization source is half that affecting 206Pb/z04Pb.

Largely due to the longer half-life of '"Th (three times that of 238U), the 208Pb/20'Pb ratio of terrestrial lead changes a t half the rate of the "'PblZn4Pb ratio, which together with the coherence of uraniurn and thorium in the Earth diminishes the value of thorogenic '08Pb as an independent tracer, though some have attempted to use it. In this study the 20Tb/Z07Pb ratio was measured for all samples prin- cipally to monitor laboratory contamination with the '"'Pb spike, the rationale being that if contamination occurred it would be the Z06Pb/207Pb ratio rather than the "8Pb/"7Pb that would be affected.

Long-term stability of the mass spectrometer was monitored by routinely measuring the lead stan- dard SRM 981 but it must be pointed out that the changes being measured were many multiples of the long-term reproducibility of the instrument and even the uncertainty in applying the mass-depen- dent fractionation correction was less than the day to day variations in the isotope ratios of a subject's blood. Nonetheless, all ratios reported here have been corrected by a factor of 0.145% per atomic mass unit.

Blanks were routinely measured during the course of this work. We found that plasticware, such as urine collection bags, syringes, and zip-lock bags used to ship hand wipes, were essentially clean and that a t most tens of picograms of lead could be washed from them. Sodium heparin in contrast, con- tained 0.3 to 0.4 ngPb/mL: thus, a blood collection blank contained between 100 and 200 pg Pb. For the period September 1990 to May 1994 the hand wipes contained, on average. 100 ng Pb per wipe with iso- tope ratios ZO'Pb/ZoGPb = 0.0524. z07PblainiPb = 0.8219, and Zo8PblZ0Tb = 2.0277 but thereafter, due to some change in manufacture, their content drop- ped to 19 ng Pb with ratios Z0 'Pb/2n~b = 0.0534. z07Ph/206Pb = 0.8294, and 208PblZnGPb = 2.0372. If the amount of lead inherent in the handwipes was more than half of the lead analyzed, the value was re- ported as undetectable. The blank associated with the decomposition of the samples was essentially that of the acid used or about 10pg for blood or

64 MANTON ET AL

urine. For a diet sample more acid is required, mak- ing the blank about 0.5 ng. The blankcontributed by the ion exchange separation was about 12 pg Pb, negligible compared to that contributed by heparin to blood or that contained in aliquots of food samples. Small samples or urine contained as little as 1 ng Pb but even with these the total analytical blank of no more than 25 pg Pb constituted less than 1% of the lead processed, and for these and all other samples except the handwipes no correction to the isotope ratio was made.

Controls

The accuracy of the spike calibration and the cleanliness of the chemical separation was assessed by analyzing the whole blood standard SRM 955a.

When the quantity being measured is expected to vary smoothly with time, such as the isotope ratio of lead in urine, erratic values that stem from contami- nation of the sample during collection are easily recognized and the subject acts as his own control. This safeguard, however, fails to detect contamina- tion by lead identical in isotope ratio to the sample, which we monitored by estimating the 24-h urinary output of lead from the creatinine vs height tables of Viteri and Alverado (1970), rejecting samples in which the calculated output was more than three times the average calculated output. To monitor changes occurring in the environmental conditions of the home we measured the blood lead of the father until the child was born and then the mother's urine monthly and her blood every 6 months for as along as we followed the child. Such a technique is not ideal, because the sources to which each is exposed during the day may well be different, but it has the advantage that if both subjects change together a source affecting the whole household is indicated. To tie the two parts of the study together we used in the second part of the study some of the families who had participated in the first, so that we could com- pare the results from siblings living in the same house.

CHILDREN: BIRTH TO 2 YEARS

subjects

Initially, two pregnant women were recruited with a view to using their children as pilot subjects to evaluate the sampling plan and collection tech- niques. These children, subjects 5 1 and 53, are refer- red to as the pilot subjects. Both were white males and were bottle fed. Blood, urine, food. and hand wipes were collected from them but no environ-

mental samples were taken until the need for them became apparent. Angle et al. (1995) and Gulson et al. (1998a) have shown that the isotope ratios of spot urine closely correlate with those of simulta- neously drawn blood, which allows the isotopic in- formation in blood to be obtained without the need to bleed children frequently. Twenty-four other preg- nant women were then recruited but 4 dropped out before their children reached 1 year of age and are not reported here. The remaining 20 children, 7 of whom were breast fed, comprised 11 males (3 black. 8 white) and 9 females (4 black, 4 white). A further 6 dropped out after 1 year. Two that had been briefly exposed to lead while their homes were being re- modeled were continued beyond 2 years in order to provide estimates of the rate a t which the young child eliminates lead. Subject 51, one of the pilot children, was also briefly exposed to lead but as this was of distinct isotopic composition he was bllowcd for 3.5 years. Subject 101-3, who had a sister in the earlier study, was followed for 3 years.

Blood Lead Concentrations

The blood lead concentrations, measured every 4 months, are plotted in Fig. 1 and are given in part in Table I . Although there is a tendency for the lead concentrations of children born with blood lead less than 1 pg/dL to rise over the first 4 months and those born with blood lead greater than 1 pgIdL to fall, the geometric mean blood lead values at birth and at 4 months were unchanged at 0.92 and 0.99 pgldL, respectively. After 4 months the blood lead concen- trations diverge. Two children, subjects 102-3 and 106-3, were exposed to lead while construction was being carried out a t their homes, and their blood lead concentrations briefly rose to values above 10 pgldL. Another two, subjects 5 1 and 112-3, showed subdued peaks rising above 6 pgldL, the causes of which are not apparent from their histories. Subjects 103-3 and 116-3 showed rapidly rising concentrations but dropped out of the study prematurely. The remain- der for the most part showed near constant or gently rising concentrations, with one child (subject 108-3). born with a blood lead of 0.63 &dL, not changing over 24 months.

Exposure to Lead from Food a n d Dust

The subjects' average monthly exposure to lead in the diet is plotted in Fig. 2 but it should be noted that the values for the first 3 to 6 months reflect only those who were bottle fed, it being impossibie to obtain duplicate diets for the breast-fed child. The

CHILDHOOD LEAD ACQUISITION 65

FIG. 1. Blood lead concentrations of children followed from birth to 2 years. (A) and (B) are bottle-fed children divided accord- ing to whether their blood rase or fell over the first 4 months o i life. (C) shows the breast-fed children.

U m 1 2 - 3 g 10 0 ' 8:

6

4

2

0

quantity of dietary lead rises steeply between 4 and 9 months, after which it shows no particular trend, varying erratically between 3 and 4 pg per day. In compiling the averages for the amount of lead on the hands, those cases in which no detectable lead was found were omitted, which causes the averages for the wipes in the early months to be larger than they really are. The amount of lead on hand wipes rises from birth to 9 months and then remains essentially constant at about 0.9 pg for the next 12 months before rising briefly to 1.4 pg between 20 and 24 months (Fig. 3). We therefore divided the exposure into three phases: (1) between birth and 4 months, when the child's intake of lead is small and in many cases insufficient to maintain his blood lead at the concentration with which he was born; (2) a transition from infancy to childhood between the 5th and the 8th month, when an adult type of diet replaces formula and baby food and when the child, spending more and more time out of the crib, gets increasing amounts of lead on his hands: and (3) the

C

- -

- - .

-

- , -, . , , . . , . .

period from the 9th month to 2 years, when his exposure to lead remains essentially constant.

0 4 8 12 16 20 24 Age In Months

Sources of Lead: Birlh to 4 Months

Over the first 4 months of life a child has little mobility and thus little contact with the lead in the dust on the floor and other surfaces of the home. In these circumstances in might be expected that lead from the diet will dominate blood. It turned out. however, that although the diets of some of the bottle-fed children had unusually high ratios (20GPbl '07Pb> 1.25) there was no corresponding shift in the ratios of their blood, implying that the dietary ab- sorption of lead is small. The high isotope ratios were traced to the Isomil brand of infant formula, of which a large stock was purchased and given to a woman who had elected to bottle feed her child. Her blood "VbIio7Pb ratio averaged 1.204 and changed little during her last trimester (Fig. 4). The child (subject 124-3) was born with a blood lead concentration of 1.2 pg/dL, which fell to 0.84 pgIdL a t 4 months. His dietary intake averaged 1.5 pglday, and between 0.13 and 1.2 pg of lead was wiped from his hands. He weighed 7.4 kg at 4 months and. assuming that the half-life of lead in his blood compartment had the adult value of 15 days (Chamberlain el a/.. 1978). an input of 0.46 pglday is required to sustain a blood lead concentration of 0.84 pg/dL. When the isotope ratios are plotted (Fig. 4) it is seen that his blood ratio moved away from his diet ratio and toward his hand wipe level, which must, therefore, be the greater contributor to his intake.

To calculate the contribution of dietary lead three sources must be considered because a flux from bone may not be ignored, especially as the child is in negative lead balance. The three-source problem does not yield an exact solution but a range of values lying between the limits of where the dietary and the bone contributions are in turn set to zero. To make the calculations, the following average 200Pb/Z"Pb ratios were used, with bone assumed to have the maternalvalue: food = 1.268, bone = 1,204, blood = 1.193, and wipe = 1.177. Some selected solutions are given in Table 2. The maximum possible figure For dietary absorption is 12% which occurs when the contribution of bone is zero. The presence of some lead from bone in a child's blood is to be expected but the amount is difficult to estimate. In adults the amount of bone lead in blood lies between 40 and 70% (Manton. 1985; Gulson et al., 1995: Smith eta/.. 1996). For an infant the mineralization of bone is less and the lead content of bone mineral is probably lower, against which must beset a much greater rate

66 MANTON ET AL.

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

Hand Wipes and 9- to 24-Month Arithmetic Means of thc Zo'Pblzo'Pb Ratios of Urine, Hand Wipes, and Diets of Children Followed from Birth to 2 Years

Subject Blood Pb Pb Sources ZmPblZo7Pb

N Racekev Birth 4 months 12 months 24 ,months Hand wipe Food Urine Hand wipe Food p~!dL pgldL j)ig!dL 1ig1dL its rlgiday

5 1 WIM 53 WIM

101-3 BIF 103-3 WIM 108-3 WIM 109-3 WIM 110-3 WIM 112-3 BIM 114-3 WIM 115-3 BIF - ~

119-3 BIF 120-3 WlM 122-3 BIF 124-3 BIM 126-3 BIF

102-3 WIF 104-3 WIF 105-3 WIF 106-3 W M 107-3 WIM 116-3 WIF 121-3 BiM

Overall arith, mean Overall aeom. mean

1.9 0.58

0.85 0.33 0.62 NIA 1.2 0.75 0.52 1.9 0.55 1.0 0.64 0.84 1.2

1.7 1.0 2.1 1.7 1.4 1.5 1.0

1.11 0.99

Pilot Study Children 4.8 4.1 1.2 2.2

Bottle-Fed Children 5.1 6.7 6.0 - 0.67 0.62 1.6 2.1

Breast-Fed Children 7.3 2.3

. . . . . . . . . Too Few Samples- - - 0.77 2.1 1.194

1.0 3.3 1.201 0.89 3.2 -

of bone turnover, perhaps as high as 300% of the skeleton per year (O'Flaherty, 1993). In this light, values between 10 and 59% do not seem unreason- able, which from Table 2 give dietary absorptions between 5 and 1 %.

Samples of milk were obtained from the breast feeders. Since milk is derived from plasma it may be expected to contain lead in the same ratio to blood as does plasma, or about 1 to 1.5% (Manton and Cook, 1984) in the subject eating ad libitum and less than 1% in the subject coming off a fast (Manton and Cook, 1984: Hernandez-Avila et al., 1998). All but one of the women produced samples that failed this criterion by having variable ratios that ranged up to 30% and are presumed to have contaminated their samples during collection. The mother of subject 107-3, however, gave milk with lead contents consis- tently between 0.6 and 1.8% of her blood lead, which

rose from 3.8 to 5.5 pgldL during lactation. Her child's blood lead decreased from 2.1 hig/dL at birth to 1.4 pg/dL a t 4 months, which would be sustained by an input of about 0.77 pg Pbiday. The average lead content of her milk was 0.06 pg/dL, and an average 0.3 pg of lead was wiped from his hands. His consumption of breast milk was approximately 1 Llday (he was fed six or eight times a day, each feeding averaging 123 g), of which 100% would have to be absorbed to maintain the concentration of lead in his blood. However, if lead from his hand wipes and from his skeleton are present in his blood, as was argued above, dietary absorption would have to be correspondingly reduced.

In the cases discussed above the blood lead de- creased over the first 4 months of life. There is evidence that the increase of lead in some children's blood over the same period is due to ingestion of

CHILDHOOD LEAD ACQUISITION 67

Age in Months

FIG. 2. Quantity (geometric mean) of lead in the 24-h diet of children as a function of age. Solid line. the gmup followed from birth to 2 years. Dashcd line, the group of 2- to 3-year-oids followed for 12 months.

house dust rather than food. For example, the bottle- fed child, subject 115-3, was born with a blood lead of 0.87 pgldL, having a 20GPb/"7Pb ratio of 1.204, but a t 4 months his blood lead had increased to 1.9 &dL

0- 0 6 12 18 24 30 36 42 46

Age in Months

FIG. 3. Quantity (geometric mean) of lead wiped from the hands OF children a s a function of age. Solid line, the group followed from birth to 2 years. Dashcd line, the group of 2- to 3-year-olds followed for 12 months.

- Metern81 Biood --c Child's Oiel - - - C h i l d % W 1.28 -Child's Nandwipe

1 1 4 i " ' " ' " " i 4 4 4 -2 .? 0 i 2 3 4 5 6

Months from Parturition

FIG. 4. zM'Pb/Z"'Pb ralios of lead in maternal blood and in thaL of subject 124-3 a t birth and 4 months. The ratios measured in hand wipes and in his diet are also shown.

and its ratio had fallen to 1.189. The lead on his hand wipes throughout the study had low ratios, aver- aging 1.169 (Table I), and it seems likely that he was exposed to lead with this ratio in his first 4 months. even though little appeared on his hand wipes dur- ing this period. Likewise, the breast-fed child, sub- ject 106-3, was born with a blood lead of 0.66 pg/dL which rose to 1.7 a t 4 months. Over the same period the 206Pb/Z"Pb ratio of his blood fell from 1.206 to 1.193, while his mother's blood lead, and presumably also her milk. averaged 1.207. Lead on his wipes

TABLE 2 Rat io of Hand Wipe Lead t o Dietary Lead. Dietary Con-

t r ibut ion t o Blood, a n d Percentago of Dietary Lead Ah. so rbed b y Subjec t 124-3 a t 4 Months of Age Calculated for Various Percentages of Bone-Derived Lead i n Blood

Ratio of hand Dietary wipe Pb contribution

"A, Bone Pb to dietary Pb % to blood % Dietary Pb in blood in blood pg Pblday absorbed

68 MANTON ET AL.

taken over the course of the study averaged 1.181, and again it seems likely that he was exposed to such lead, even though no detectable amounts were found on his hands during his first 4 months.

Sources o f Lead; 5 to 8 Months

The period of transition occurring between the 5th and the 8th month is characterized by changes in blood lead concentration and increasing exposure to lead through the diet and hand wipes. Although the lead content of the diet changes three times more than that of the hand wipes no corresponding move- ment of the isotope ratios of blood and urine toward those of the diet was observed in any child over this period. As an example we show in Fig. 5 the isotope ratio profile of one of the pilot children, subject 53. He was born with a blood lead of 1.1 pgldL, which fell to 0.58 pg/dL a t 4 months and then rose to 1.2 a t 12 months (Table 1). Over this period he consumed food with high isotope ratios (Fig. 5) but the ratios of his urine between 4 and 12 months moved toward his hand wipes, indicating that they and not food were responsible for the rise in his blood lead.

Sources of Lead: 9 Months to 2 Years

To investigate the sources over this period we averaged (justified by the information in Fig. 2) each child's exposure, reporting amounts of lead as geo-

metric means and the isotope ratios, which we found to be normally distributed, as arithmetic means (see Table 1). The average amount of lead on hand wipes was 0.89 wg, and the average content of the diet was 3.2 pg. Individual ranges were small. With the ex- ception of one case of 44 pg of lead, no more than 8 pg was wiped from the hands of any child, and only eight diet collections contained more than 10 pg.

We use a simple correlation diagram to test for the presence of food or hand wipe lead in blood. If one source is predominant a plot of ZUGPb/Z07Pb in urine against 2oGPb/Z07Pb of that source will produce an array of points lying on a line of unit slope passing through the origin. In Fig. 6 the mean 2wPb/"7Pb ratio of each child's food is plotted against that of his urine and most of the points plot above the correia- tion line but when the hand wipe ratios are plotted against urine (Fig. 7) the points scatter about the line, suggesting that lead on the hands is the domi- nant source of lead in their blood.

Origin of Lead on Hand Wipes

It is seen from Table 3 that similar ranges in Z0GPb1207Pb ratio were found on the floors and in the carpets of each home and when the ratios are plotted against each other (Fig. 8) they closely correlate. If the lead found on the hand wipes (Table I) is plotted against that of the floor a fair correlation results (Fig. 9), and similarly with a plot against the ratios of the carpet (Fig. 10). so that for many of the chil- dren lead on the hands appears to originate either from contact with the floor or from the carpet or both. For those that fall off the line it is possible that the parts of the floor with which they were most commonly in contact were not sampled or that they were exposed to lead from another source but win- dow sill lead or door mat lead as sole sources are rejected because their ratios (Table 3) range far be- yond those found on the hand wipes.

-Urine Hand Wipe

. . . . . . . . .

Origin of Lead on Floor and Carpet

" " ' " " ' ~ ~ " ' " ' " " " " " ~ 0 4 8 12 16 20 24

Age in Months

FIG. 5. 'ooPb/20'Pb ratios OF lead in the blood, urine, hand wipes. and 24-h diets of the pilot study child subject 53 plotted against his age.

Table 3 lists the average loading and isotope ratio of lead onsurfaces in each child's home. Window sills are conspicuous for the amount of lead residing on them (up to 9.6 mglm2) and both they and door mat shakings for their wide range of 20~blz07Pb ratios, from 1.13 to 1.28. The range in ratio found on floors and carpets is narrower. from 1.18 to 1.22 (subject 103-3 excepted), which in itself implies that the lead that they harbor is not exclusively derived from either sill or door mat but for more than half the subjects the ratio for the floor falls outside the range

CHILDHOOD LEAD ACQUISITION 69

2"Pbf07Pb of Urine

FIG. 6. Correlation plot of the average Z"'%'bIZO'Pb ratios of lead In 24-h diets with those of lead in the urine of tire same children for the pcriad 9 to 24 months of age. The dashed line is a reference line of unit slope.

spanned by the mats and sills, implying that there are other sources of lead within or without the home that were not sampled. For three of the subjects, 101-3, 115-3, and 121-3, the ratios of window sills and door mats lie far apart and the samples from the

1.1s L 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23

206PbPn7Pb of Urine

FIG. 7. Correlation plot of the average "PbIzo'Pb ratios of lead In hand wipes with those of lead in the urine of the same children for the period 9 to 24 months of age. The dashed line Is a reference line of unit slope.

TABLE 3 Loading a n d Z"PhlZ"Ph Rat ios of Lead on Bare Floor,

Carpeted Floor, a n d Window Sills a n d Quantity and z"Ph/z07Ph of Lead in Door Mats a t Homes of Children Followed from Bir th t o 2 Years

Pb found "'Pbim'Pb

Floor Carpet Sill Mat Floor Carpet Sill Mat SubJect ligIrnZ li&d @rn2 ~6

101-3 102-3 103-3 104-3 105-3 106-3 107-3 108-3 109-3 110-3 112-3 114-3 115-3 116-3 119-3 120-3 121-3 122-3 124-3 126-3

Arlth mean G e m ,liean

floor fall in between. If i t is assumed that the lead on the floor is derived only from these two sources the ratio of sill lead to mat lead in these cases ranges from 0.8 to 1.8.

An Illustralive Case: Subject 101-3

Figures 2 2 and 12 show the profiles of a child (sub- ject 101-3) who displays many of the characteristics of the group. Being the sister of a child in the earlier study (subject 23, Table 4). she was one of the linking subjects and was followed for 3 years rather than 2. She was bottle fed and her blood lead fell (Fig. 11) over her first 4 months before rising to a maximum of 6.7 pgidL a t 24 months, after which it fell to 6.2 pg1dL a t 36 months. After 6 months the amount of lead in her food varies erratically, showing no trend. No lead was detected on her hands for her first 8 months (as she had been recruited early in the study, a relatively large blank of 0.2 pg was asso- ciated with the wipes) but thereafter the amount of

70 MANTON

2 0 6 ~ b i 2 0 7 ~ b on Floor 206Pb/Z07Pb in Carpet

FIG. 8. Correlation plot of tho average ZoTbbiZU'Pb ratios of lead vaciwned from the carpet with those of lead wiped from the FIG. 10. Correlation plol of the average "PbbiZD'Pb mtios of floor of the same house. The dashed iine is a reference line of unit lead on hand wipes (from 9 lo 24 months) with those vacuumed

siope. from the carpet of the home. The dashed line is a reference ilne of unit slope.

lead on her hand wipes shows no trend. In the iso- tope ratio plot of Fig. 12 it is seen ( 1 ) that the ing infant formula with a high isotope ratio, and (3) 20~b/Z071'b ratio of her urine closely follows that of that her blood isotope ratio continues to Call to co- her blood. (2) that her blood lead falls in isotope ratio incide with the ratio of the lead first encountered on over her first 4 months even though she was consum- her hand wipes, and thereafter her blood and urine

track the ratio of her hand wipes. Figure 13 shows

1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24

206~bP07Pb on Floor

FIG. 9. Correialion piot of the average 2oVb/"'Pb ratios of lead on hand wipes (Crorn 9 to 24 months) with those wiped from the floor of the home The dashed iinc is a reference iine of unit s1opc.

+Blood - Handwipe . . . . . . . . . Food

FIG. 11. Blood lead concentrations and lead on hand wipes oC subject 101-3 From birth to 36 months and the concentration of lead in her diet from birth to 24 months.

CHILDHOOD LEAD ACQUISITION 7 1

s Blood - UO08 - Handwlp~ . , . . . . . . . Food

FIG. 12. 7ffiPb/ZU'Pb ratios of lead in the blood, urine, and hand wipes of subject 101-3 from birth to 36 months and the '"Pbbim7Pb ratio of her diet from birth to 24 months.

that the Z06Pb1207Pb ratios of the floor of the home consistently fall between those of the window sill and the door mat shakings and that the ratios of her hand wipes fall close to but do not coincide with those of the floor.

CHILDREN: 2 TO 4 YEARS

Subjects

The 20 subjects studied ranged in age from 19 to 39 months at the time or recruitment (Table 4). Of the boys 5 were white and 3 were black, including a pair of uniovular twins (subjects 20 and 21). Seven of the girls were white and the remaining 5 were black. Subjects 22 and 29 were cousins, as were subjects 7. 9. and 16. Most of the children had lived in the same houses since birth but subjects 17 and 24 had moved shortly before joining the study and sub- jects 23 and 29 during its course. Five were exposed to dust produced during long drawn-out remodeling projects: subjects 17 and 24 before they moved and subjects 25, 26, and 27 in the houses in which they had lived since birth.

Blood Lead Concentrations

The highest 'blood lead concentrations of I5 and 12 pg1dL were found in subjects 24 and 17, who had lived through remodeling projects. Subject 7's blood rose to above 10 pgldL over the period of observation, as did subject 29's after she went to live with her

cousin. The lowest average concentration of 2.7 pgldL was found in subject 20. The others showed small changes, generally less than 2 pgIdL, over the 12 months that they were followed.

Exposure to Lead from Food a n d Dust

Lead in 24-h duplicate diets ranged from 1.9 to 6.8 &day with a mean of 4.17pglday. There seems to be no trend with age (Fig. 2), and the amount found is 1 pglday higher than that found for the 9- to 24-month-old children. The amount of lead found on the hand wipes ranged from 1.2 pg (subject 23) to 12.9pg (subject 22) with a geometric mean of 3.97 pg. There is no trend with age (Fig. 3) but the quantities are 4.5 times greater than those found in the younger group of children. For the older group the ratios (1) of blood lead concentration to amount of lead in a 24-h diet and (2) of blood lead concentra- tion to amount of lead wiped from the hands provide an arbitrary but useful way of analyzing the results because they are close to unity for most of the chil- dren (Table 4) and plot in a close group (Fig. 14). Subjects 16 and 23 are displaced horizontally from the average by virtue of the relatively small amounts of lead wiped from their hands and subject 22 verti- cally by the relatively small amount of lead in her diet. This subject was the only one to show a strong seasonal variation in the amount of lead wiped from the hands, less than 10 pg in winter but as much as 40 pg in the summer. Empty battery cases were found stacked up against the house.

Anomalous Blood Lead Concentrations

Children who are displaced at 45 degrees away from the average group in Fig. 14 are anomalous in the sense that their blood lead concentrations ap- pear not to be commensurate with their measured exposure. Each is discussed below.

Subject 29 with a blood lead of 9.7 pg1dL initially plotted the farthest from the average but after she moved to live with her cousin (subject 22 discussed in the previous section) a t their grandmohr ' s home her hand wipe lead increased, causing her to plot close to the vertical axis. Visits to her grandmother would account for her being exposed to a source that we did not sample.

Subject 9 is similar tosubject 29 in that from birth to 6 months she spent 4 to 5 h a day a t the home of subject 7, and it is possible that her blood lead still reflects exposure to the relatively large amounts of lead in that home, reflected in subject 7's hand wipes (Table 4).

72 MANTON ET AL.

TABLE 4 Blood Lead Concentrations, Amount of Lead in Hand Wipes and Food, andZo'Pb12"Pb Ratios o f Lead i n Blood, Hand Wipes,

and Food for 2- t o 3-Year-Old Children

Subject Blood Pb Pb Sources Z"PblZo'Pb Blood Pb Blood Pi,

Age Start End Aver. Hand wipe Food -- N Racclscx (months) pgldL & d L wgldL pg pgi24h Blood Hand wipe Food Wipe Pb Food Pb

WIM WIM WIF B M WIF WIM WIF WIM WIM BIM BIM BIF B/F

WIF WIF WIF WIF BIF

WIM BIF

Arith. mean 26.3 6.6 6.4 5.1 5.1 4.2 1.198 Geom. mean - 6.0 5.8 4.0 4.0 3.9 -

'After 5 months changed residence. *"After 4 months moved to livo with subject 22

Subject 17 moved shortly before the study began into a home that his parents had been converting from a warehouse since the time he was 6 months old. He frequently accompanied them and was al- lowed to crawl a t will on the floor. Over the first 12 months that he was sampled, his blood lead concen- tration steadily decreased from 12 to 8.5 pgldL. while the M'Tb/207Pb ratio of his blood and urine did not deviate from the unusually low value of 1.171. He was followed for a further 24 months during which his blood lead concentration continued to de- cline, ending a t a value of 4.5 pg/dL (Table 5). There was, however, no change in his blood lead isotope ratio, which continued to remain lower than that observed in his Food and on his hands. It is clear that his blood lead was dominated by lead from another source but, given his decreasing blood lead concen- trations, it is likely that this source is endogenous and is lead stored in his skeleton. This interpreta- tion is consistent with the possibility of exposure to lead during a period of renovation and construction

occurring before we first sampled him a t age 2 years. Subject 24 lived from birth to 4 months before she

moved into her current home in a 100-year-old house in which her Father had done sanding and painting among other refurbishing projects. Her blood lead concentration (initially 15 pgIdL) was the highest encountered il l the study, and a t the outset of samp- ling there was the greatest disparity between the Z"Pb/Z07Pb ratio of her blood and urine (1.158) and that of her food and hand wipes (1.200-1.210). She was followed for 3 years. Lead concentrations are shown in Fig. 15. Except for a subsidiary peak a t age 37 months her blood lead concentration steadily de- clined. passing through 10 pgIdL a t 56 months and ending a t 8.9 pg/dL a t age 64 months. Duplicate diets and hand wipes were taken from her until she started attending kindergarten a t 54 months. Over the period sampled, the amount of lead in her food declined, while the amount of lead wiped from her hands shows no trend despite some occasions when more than 10pg was found. The isotopic profile

CHILDI-IDOD LEAD ACQUISITION 73

I) Floor

116

114

112 0 6 12 18 24 30 36

Age in Months

FIG. 13. ZoTpi20'Pb ratios of lead on thc window sill, on the floor, and in dust shaken from the doormat or the home of subjecl 101-3 plotted as a function of her age. The ralios for her hand wipes are also piolted. See Fig. 12

(Fig. 16) shows the 206Pb/207Pb ratio in her food and hand wipes varying about a n average value of 1.205. The abrupt rise in the Z0??b/207Pb ratio of her blood and urine corresponds to the change in blood lead concentration occurring a t age 37 months but, apar t

i 2 3 4 5 6

Blood PbiHand Wipe Pb

FIG. 14. The ratio, for the 2- to 3-year-old children, of blood lead concentration Lo lead on hand wipes plotted against the ratio of blood lead concentration to lead in 24-h diet. Those subjects shown by number are discussed in the text.

from this, their ratios slowly trend toward those of her food and hand wipes. The declining blood lead concentrations of this subject and the absence of any lead sources with low isotope ratios in her home point to much of the lead in her blood having been acquired in her first home and stored in her skeleton before she reached the age of 2 years. I t turned out from her history tha t the excursion in blood lead concentration and isotope ratio occurring at 37 months corresponds to a remodeling project in the new home.

Other Children Exposed to Lead during Remodeling

Subjects 25. 26. and 27. who had lived since birth in houses being remodeled, do not plot anomalously in Fig. 14. With a blood lead concentration averaging 4.2 pg/dL, subject 25 does not appear to have been affected to any great extent and is not considered further. Subjects 26 and 27's blood lead concentra- tions were initially 8.2 and 8.7 pg/dL and fell over the first 12 months of observation. The zo"Pb/""Pb ratio of subject 26's blood and urine did not deviate from 1.170, and this value was almost identical to tha t found in her hand wipes. She was not followed any longer. The 20Tb/m7Pb ratio of subject 27 with a value of 1.230 was consistently higher than that of her hand wipes. She was then followed for a further 22 months over which her blood lead fell steadily to 4.4 &dL (Table 5), with its 20@l'b1207Pb ratio remain- ing a t its high value, a s if the lead in her blood was dominated by lead acquired before we began samp- ling her. In the cases of the two subjects 26 and 27 and of subject 17 the ratios fall outside of the range most frequently encountered in the United States environment (Jaeger et al., 1998) and suggest deri- vation from a restricted source, such a s a batch of paint containing lead with a distinct isotopic com- position.

The Twins: Subjects 20 and 21

The twins are of interest because each acts a s the control of the other, and, indeed, their exposure to lead in food and hand wipes was almost identical both in quantity and in isotope ratio. Despite this similarity in exposure the blood lead concentration of subject 21 was initially 4.6 g / d L as compared to his brother's 2.8 &dL (Fig. 17). I t progressively de- creased for 12 months before attaining a constant value 0.4 pg/dL higher than his brother's, which had remained constant over the 3 years of observation. The isotope ratio plot (Fig. 18) shows a similar pat- tern. Subject 20 is normal in tha t the 2 0 ~ b / m 7 P b

74 MANTON ET AI..

TABLE 5 Blood Lead Concent ra t ions (PbB) of Chi ldren Withdrawn f rom Exposure t o Lead a t Various Ages

Subject 17 Subject 24 Subject 27 Subject 51 Subject 102-3 Subject 106-3

Age PbB Age PbB Age PbB Age PbB Age PbB Age PbB months pgldL months pddL months $@dL months pgldL months pg/dL months pg/dL.

27.6 12.0 34.0 15.0 31.0 8.7 18.2 7.3 8.3 11.0 7.9 12.1 30.3 10.2 37.0 13.8 34.5 8.2 23.8 4.1 12.0 7.3 12.0 5.9 32.7 10.1 43.7 12.8 37.2 7.3 29.3 3.1 18.2 3.0 17.9 4.6 34.8 8.5 48.9 13.2 39.3 8.0 24.4 2.3 24.0 3.1 37.3 7.8 55.9 10.2 41.0 7.0 30.6 1.5 29.9 2.9 42.2 6.4 61.1 8.6 46.9 6.1 54.3 4.1 63.7 8.9 52.9 5.9 57.4 4.5 57.7 5.2

60.2 4.4 (20 months) (38 months) (33 months) (8.9 months) (7.8 months) (1 1.4 months)

Nole. The last row contains the apparent half-lives of iead in the blood of each child.

ratios of his blood and urine are similar to those of his hand wipes. His brother's blood and urine have initjally much lower ratios, which move toward his over a 12-month period. Over the following 14 months their ratios parallel each other's with subject 21's ratio being slightly less than his brother's. It seems that subject 21 was briefly exposed to lead before age 21 months, which was largely excreted over the following 12 months, but part of this lead

was retained and only slowly makes its way into blood, still contributing about 0.4 pgldL a t least 3 years after his initial exposure.

DISCUSSION

Lead in Blood

The average concentration of lead in the blood of the 2- to 4-year-olds (4.0 pgldL; Table 4) is almost

--3-- Blood -Wand Wipe . . . . . . . . . Food h

- . .- 30 36 42 46 54 60

Age in Months

FIG. 15. Blood lead concentrations and the amount of iead on hand wipes and in the diet of subject 24 as a function of age. No hand wipe or food samples were taken once she started attending kindergarten a t 51 months.

iB blood -Urine

Hand Wipe ......... Food

1.141 . , . . . . , , . . . . . , . . . . , ,--- . . . 30 36 42 48 54 60

Age in Months

FIG. 16. 'ooPb/2"'Pb ratios of lead in thc blood. uvine. and hand wipes ofsubject 24 as a fiinction ofage. No hand wipcoi (bod samples were taken once she sfarted attending kindergal-ten at 54 months.

CHILDHOOD LEAD ACQUISITION 75

FIG. 17. Blood lead concentrationsand the average amount of lead wiped from the hands of the unlovular twins, subjects20 and 21, plotted a s a function of their age.

5

i e o 4~ 2 0 0) i d 3 - a

2

1

identical to the national average of 4.1 pgldL for 3- to 5-year-olds reported for the period 1988 to 1991 (Brody et al.. 1994). The value for those followed

+U20 Blood -0-#21 Slood

- . . . . . . . . . Hand Wipes -

.

-

. . . . . , . . . . . , . . . . . , . , , , . , . , , . , q . . , , , , I - 18 24 30 36 42 48 54

18 24 30 36 42 48 54 Age in Months

Age in Monlhs

FIG. 18. "TbIzo'Pb ratios of lead in the blood, urine. and avcragod hand wlpcs of the uniovuiar twins. subjects 20 and 21, plotted as a function of their age. At month 42 the curves for their urincs touch but do not cross. Symbols are the same as those of Fig. 17 but with wines of each plotted as solid lines.

from birth for the period 12 to 24 months is some- what less (2.4 to 2.8 pgldL: Table 1) but is consistent with the continuous decline in lead in the blood of the population. Although these values are less than those reported in earlier time-continuous studies, the overall patterns are similar. Thus, the curves shown in Fig. 1 have the same form as those in Fig. 1 of Clark et al. (1985). and the decrease in blood lead concentration in the first 4 months of life was ob- served by Ryu et al. (1983).

Lead in Food and Hand Wipes

During the 1980s the concentrations of lead in the diets of infants and toddlers living in the United States declined rapidly, converging to a value of about 5 pglday in 1988 (Bolger et al., 1991). The concentrations of lead in the 24-h duplicate diets of both our groups of children (3.2 pglday for the 9- month- to 2-year-olds and 4.2 pglday for the 2- to 4-year-olds) are consistent with this trend and again indicate that the population that we sampled was representative of the average child of the early 19;9os.

-

The 4.0 pg of lead wiped from the hands of the 2- to 4-year-olds is comparable to the amounts reported for Cincinnati children living in post World War I1 private housing in satisfactory condition (4.3 pg) and in public housing (4.8 pg) during the 1980s (Clark el a/., 1991) but the 0.93 pg found for the group that we followed from birth to 2 years is lower than any figure reported to date.

With regard to the large,'difference between the amounts of lead in hand wipes taken from the two groups of children, we first considered the possibility that lead recovered from the hands was a function or hand size or. as reviewed by Finley er al. (1994). an age-related difference in soil-to-skin adherence. Ap- plying the calculations of Finley et al. to the increase in surface area and hand surface area of children (0.047-0.057% of total body surface area). the pro- gressive plot of hand surface area from birth through 48 months does not predict the observed values. The 4.0 pg wiped from the hands of 2- to 4-year-olds with hand surface area 26.3-42.6cm2 is equivalent to 0.094-0.136 mglcm? Applying this concentration to the hands of a 12-month-old (22-27 cm2) would pre- dict 2.10-3.7 pg Pb recovery. In sum, the recovery of only 0.93 pg Pb from birth to 24 months cannot be attributed solely to the smaller hand size.

We next considered the possibility that it was an artifact, because three field technicians were employed over the course of the study, the first of whom was the only one to get samples from the 2- to 4-year-old

76 MANTON ET Al..

children. We are, however, confident that each was wiping the hands a s effectively a s the other because the sampling of the pilot study child subject 5 1 span- ned the employment of all three. The first technician wiped his hands from birth to 11 months, the second from 12 to 21 months, and the third from 22 to 42 months. I t is seen in Fig. 19 that, although each obtained a different average amount of lead, the effect being sought, namely that the second and third technicians were wiping the hands less effi- ciently, is absent. Another test is to compare the results from siblings, one of whom was sampled only by the first technician. Subject 51 is the brother of subject 2 who had a blood to wipe ratio close to unity (Table 4), which value subject 51 exhibited for the last year in which he was sampled (Fig. 19). Like- wise, subject 25 (Table 1) and her sister subject 102-3 when 24 months old (Table 4) had blood to wipe ratios close to one, although the quantities of lead for the older child were twice a s high. The two sisters, subjects 23 and 101-3, have comparable amounts of lead on their hands, and their blood to wipe ratios of 3.3 and 4.5 are similar and character- istically both higher than average. These results suggest that we sampled two different populations. one of which, the 2- to 3- year-olds and their siblings, lived in homes with a greater lead loading on surfa- ces, whether due to remodeling, more lead in the paint of the home, or poorer housekeeping practices. But this explanation is not entirely satisfactory be- cause the wipe to blood ratios are not a same for each

--r91-- Blood . . . , . . . . . Hand Wipe

FIG. 19. Blood lead concentrations and the arnounl of lead on handwipes and in the diet of subject 51 as a function of age.

group. For the younger group the ratio a t 24 months is 0.37 and for those of the older children who plot in the closely spaced group of Fig. 14 the ratio is 0.89 [or an average age of 25 months. Some other factor seems to be involved, possibly different bioavailabili- ties of the lead in the homes of the two groups, arid even the likelihood of some of the mothers washing their children's hands prior to visits cannot be en- tirely discounted. Even if the last occurred, our in- terpretations would still be valid because washing would not materially alter the isotopic character of lead on the hands.

Uptake olLead from Food a n d H a n d Wipes

A commonly used value for the gastrontestinal absorption of dietary lead in the infant is 53"% taken from the work of Alexander el al. (1974) and sup- ported by the studies of Ziegler el a1 ((1978). Our finding of much lower uptake was made on a child whose diet contained one tenth the amount of lead in the diets of Alexander et al.'s (1974) subjects and may be reconciled with their work if the absorption of lead is a nonlinear function tha t rises steeply a s the PbiCa ratio of the diet increases. Given the cur- rent levels of lead in food, i t seems inappropriate to continue to use Alexander et al.'s (1974) value for infants. and from the work of Gulson el a/. (1997) similarly high values currently used for the older child also appear to be unrealistically high. In con- trast, the dominance of the blood lead isotope ratios by those of the hand wipes indicates that the absorp- tion of lead in dust and dirt ingested in the absence of dietary calcium is high. How high cannot be deter- mined from the present work, except to say that the absorption probably differs a t least by the factor of 10 found by James et al. (1 985) for 203Pb-labeled lead acetate administered to adults.

Gulson el al. (1998b) have used the isotope ratios of lead in blood to determine the dietary absorption of lead by infants. For breast-fed children born in Australia to immigrant inothers they report values between 36 and 80%. and for formula-fed children they report 24 to 68% which is far larger than our estimates for a formula-fed child (see Table 2). They used a two-source model with breast milk or formula as one end member and the infant's blood (presum- ably the cord blood) as the other and, without measuring hand wipes, assumed the contribution from dust to be negligibly small. I t is clear from our work, however, that the contribution from dust can- not be ignored and that their failure to check for lead on the children's hands casts doubt on the validity of their calculations.

CHILDHOOD LEAD ACQUISITION 77

Applicability of Dietary Lead Uptakes to Other Populations

Since certain nutrient deficiencies, specifically cal- cium, iron, and zinc, may enhance lead absorption (Chisholm, 1980; Mahaffey, 1980; Coyer, 1997), the diets of the children was analyzed for adequacy by both direct chemical analyses and by computer-gen- erated estimates based on the mothers' diaries. For the chemical analyses, aliquots of homogenates of 84 diets (quarterly collections) were shipped to Midwest Laboratories of Omaha where they were analyzed for calcium, iron, and zinc by inductively coupled plasma mass spectrometry after digestion in nitric and hydrochloric acids. Estimates of concentrations of these same metals in 249 additional diets were generated with the Minnesota Nutrient Data Sys- tem Version 2.3 software (Nutrition Coordinating Center, 1991). All values were then compared to the Recommended Dietary Allowances (RDA). Mean in- takes of calcium were 58% (estimated) and 57% (actual) of the RDA; zinc was 47% (estimated) and 46% (actual); and iron a s estimated was 89%. Actual determinations of iron were not reported since the blender used for homogenization added iron to the samples. From these values i t seems that our find- ings of low dietary absorption are applicable to diets both adequate and inadequate with respect to cal- cium and zinc.

Our findings do not apply, however, to those cities and other localities where tap water may contain a s much a s 15 pg PbIL and constitutes a major source of lead intake, perhaps a s much a s 20% of the average resident's total exposure (Warlaw, 1999). Here. the lead content of infant formula reconstituted with such water would be considerably greater than what we measured, and the uptake of lead from tap water taken between meals might be comparable to that ingested from the hands.

Lead Loadings on Window Sills

The high loadings of lead that occur on window sills probably originate from dust produced by fric- tion along lead painted surfaces. It seems from our work that some of this dust settles on the floor where it is mixed with lead tracked into the house and that this mixture is then ingested by the child. Such ingestion constitutes indirect exposure to window sill lead. An interesting question is how often a child touches a window sill and is thereby directly exposed to the lead deposited on it. The plot in Fig. 13 may reveal a pattern of behavior. Up to 23 months of age the isotope ratios of the lead on this child's hand

wipes were less than those of the floor, as if she was getting more into areas contaminated with lead brought in from the exterior, but from 23 months her hand wipe ratios were higher than those of the floor. as if she was more frequently touching the sill. What is clear, however, is tha t few of the children that we followed had potentially dangerous encounters with lead on window sills because, of the 40, only 2 appear to have ingested a bolus of lead from a concentrated source such a s a sill. One of these is subject 52, whom we followed from birth to 43 months. I-Iis blood lead concentrations (Fig. 19), measured every 4 months, passed through a peak a t 12 months that was not reflected in his hand wipes. The isotope ratios of his urine (Fig. 20), taken monthly, narrowly define his exposure to a brief period when he was 14 months, which according to his history is when he began to walk. I t then took 36 months for the isotope ratios of his blood and urine to attain the ratios of his hand wipes, which had also failed to show any sus- tained exposure to lead with a high isotope ratio. As this child was one of the pilot study children, we were not simultaneously getting environmental samples from his home but a survey conducted when he was 36 months old found lead on a window sill with a ratio of 1.270. The other case is the twin. subject 21, who some time before we began to follow him had been exposed to some source of lead to which his brother had not. The question of how one and not the other could be exposed when their

Age in Months 0 6 12 18 24 30 36 42 48

FIG. 20. Z"Pbi2"Pb ratios u l lead in the blood, urine, hand wipes, and diet of subjccl 51 as a function of age.

78 MANTON ET AL.

subsequent exposures were nearly identical is an- swered by invoking a n encounter with lead on a win- dow sill, and the initial survey of the home found lead with a 2oGPb/207Pb ratio of 1.164 on a sill. The loading was 4900 d m Z .

Rate of Lead Loss after Exposure

In this study we have observed changes in blood lead concentration following two types of exposure to lead: one brief resulting from contact with some highly contaminated source, such a s a window sill or from dust produced during professional remodeling, and the other prolonged resulting from some long drawn-out project carried out by the parents on weekends or other times available to them. Subjects 51, 102.3, and 106-3 fall in the first group and sub- jects 17. 24, and 27 in the second. Their blood lead concentrations and ages are given in Table 5. The approximations to straight lines in the semi-logar- ithmic plot of Fig. 21 indicate that the decline of blood lead in these children can be expressed by an exponential function whose rate constant, which is the sum of all rate constants in and out of the blood compartment, yields a n apparent half-life of lead in blood. The slopes of the lines indicate that the clear- ance of lead from the children who had prolonged exposure over the first 2 years of life is longer than that of the children who were briefly exposed. The apparent half-life of the briefly exposed group lay between 8 and 11 months while that of the group

FIG. 21. Piot of the logarithm of blood lead Concentration against age for children who had abnormal exposure to concen- trated sources of lead.

with prolonged exposure lay between 20 and 38 months (Table 5). These values are much longer than the 15 day half-life of lead in the blood compart- ment of the adult (Chamberlain et al., 1978) and are manifestations of the greater rate of turnover of the skeleton of the young child (Leggett, 1993: O'Flaherty. 1995). If the blood lead concentration of subject 24 continued to decline with a 38-month half-life i t would in 10 years have reached 1 1 % of its value a t 34 months. Likewise, the blood lead of sub- ject 27 with a half-life of 33 months would in 10 years be 8% of its value a t 33 months. These values are in fair agreement with O'Flaherty's (1995) calculation predicting that a t age 12 years the blood lead concen- tration of a girl who had been removed from expo- sure to lead a t age 2 years would have fallen to 14% of its starting value. With a half-life of 20 months, however, subject 17's projected blood lead concentra- tion falls far short of O'Flaherty8s (1995) predictions.

There are two principal implications of these lon- ger apparent half-lives. First, if a child is found to have a blood lead in excess of the CDC guideline of 10 &dL (Centers for Disease Contl-01. 1991) it may be futile to attempt to find the source of lead in the child's immediate surroundings because the expo- sure may have occurred many months before, even in another residence. Second, experiments should be designed with these long apparent half-lives in mind. Thus, if i t is desired to examine the effects of soil lead abatement it would be more meaningful to compare the blood leads of the exposed group with those of a new generation of children growing up on the abated soil rather than to attempt to assess the post-abatement decrease in the blood lead of the exposed group. The Boston Lead-in-Soil Demonstra- tion Project is a case in point (Weitzman eta%. 1993; Aschengrau et al., 1994).

Isotopic Studies vs Statistics-Based Studies

The traditional way of investigating the pathways by which children acquire lead is to correlate by statistical methods concentrations of lead in blood with the amounts of lead associated with the various surfaces and materials with which the child !nay have contact. There have been many such studies (some are listed in the Introduction) of which the most recent is the Rochester study described in sev- eral papers by Lanphear and his co-workers (Lan- phear et al., 1995, 1996, 1997, 1998a). I t is of interest to compare the findings of their work to those of our study to see to what extent the fundamentally differ- ent statistical and isotopic approaches to the same problem complement each other.

CHILDHOOD LEAD ACQUISITION 79

Comparing the Omaha children followed from birth to the Rochester children, we find that the Omaha children had a t 12 months a lower blood lead (2.7 vs 7.7 pg PbIdL) and correspondingly lower loadings on floors (45 vs 160 pg Pb/m2) and carpeted floors (16 vs 110 pg Pb/mz). The relatively smaller fraction of car- pet lead measured for the Omaha houses may result from sampling technique (Lanphear eta/. , 1995). The loadings on window sills were closer, 1190 pg PWm2 for Omaha and 1660 pg Pb/m2 for Rochester. No hand wipes were taken from the Rochester children, and no soil was measured in Omaha.

Lanphear et al." (1996) principal conclusion that lead-contaminated house dust is the major contribu- tor to children's blood lead is supported by our work but we would go further and state that i t is the only contributor, having found the amount of dietary lead in blood to be negligible. They identified all surfaces measured, i.e., bare floors, carpeted floors, window sills, and window wells, a s significant contributors to blood lead. As bare floors and carpeted floors had the same isotope ratio, we cannot state which contrib- utes more lead to blood. We found that lead on win- dow sills contributes to floor dust and so to blood lead but that only 2 of 40 children ingested large amounts of lead directly from what could have been a window sill. If doormat shakings are representative of the soil around a house, we have shown that soil contrib- utes to house dust, a point that Lanphear el a1. (1996) could not decide upon.

What is surprising in the light of our findings is that the statistical correlations between house dust and blood lead are not stronger and, in particular, how weak was the correlation found by Bornschein eta/. (1987) between hand wipe lead and blood lead: however, a s Lanphear and Roghmann (1997) point out, if the child iscontinuously putting its hands into its mouth the amount of lead on its hands will never be measured accurately. Other factors that may weaken a statistical correlation are different forms of lead in dust, different gastrointestinal absorp- tions, and the apparent long half-life in the blood of children, so that a blood lead concentration always to some extent reflects past exposure. All in all, the two approaches lead to similar conclusions, with the iso- topic, by virtue of its independence of concentration measurements, providing insights into the processes that bring about the acquisition and retention of lead by children.

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