Bioavailability of Soilborne Lead in Adults,by Stable Isotope DilutionMark Maddaloni,l Nancy Lolacono,l William Manton,2Conrad BIum,3 John Drexler,4 and Joseph Grazianol1Columbia School of Public Health, Division of Environmental HealthSciences, New York, New York; 2University of Texas, Department ofGeosciences, Dallas, Texas; 3Columbia College of Physicians andSurgeons, Department of Medicine, New York, New York;4University of Colorado at Boulder, Boulder, Colorado

Using stable isotope dilution, we determined the bioavailability of soilborne lead (Pb) in humanadult volunteers. Soil from a residential yard at a mining-impacted federal Superfund site that hadnegligible amounts of other priority pollutants was dried and screened through a 25- pm meshsieve. The <250-pm fraction, which likely represents that ingested via hand-to-mouth activity,was then sterilized by exposure to radiation. Ten replicate samples yielded a mean (SD) soil Pbconcentration of 2924±36 ppm, and a mean 206Pb/207Pb ratio of 1.1083±0.0002, indicatingremarkable soil homogeneity. Six adults with 206Pb/207Pb ratios of > 1.190 were admitted to theclinical research center and fasted overnight prior to dosing with 250 pg Pb/70 kg bw (i.e., 85.5mg soilf70 kg) in a gelatin capsule. Blood for Pb and 206Pb/207Pb ratios was obtained at 14 timepoints through 30 hr. Results of the isotopic analyses from these subjects indicate that on

average 26.2% ±8.1 of the administered dose was absorbed. Six additional subjects were

subsequently studied but ingested soil immediately after a standardized breakfast. Bioavailabilityin this group was only 2.52% ± 1.7. Collectively, this study provides the first experimentalestimates of soil Pb absorption in humans, and should allow for more precise estimates of healthrisks due to Pb-contaminated soil. Environ Health Perspect 106(Suppl 6):1589-1594 (1998).http.//ehpnetl.niehs.nih.gov/docs/1998/Suppl-6/1589-1594maddaloni/abstract.html

Key words: lead, bioavailability, soil, stable isotopes

The regulation of environmental contami-nants such as lead (Pb) should reflect thepotential impact on human health and theenvironment. With respect to soilbornePb contamination, the bioavailability ofPb in that medium will to a great extentdetermine its capacity to adversely affecthuman health. The U.S. EnvironmentalProtection Agency (U.S. EPA) employsthe integrated exposure uptake biokinetic(IEUBK) model for lead to assess envi-ronmental Pb hazards in children (1) andhas developed an interim simplified

biokinetic model for use in adults (2)while the U.S. EPA explores expansion ofthe IEUBK model to accommodate all agegroups. In addition, there are a number ofbiokinetic models available (3-5) that areintended for use in adults. The output ofthese models is affected by a host ofexposure and kinetic factors, with thebioavailability of Pb in soil among themore prominent (6). Unfortunately, thisparameter is among the most poorlyunderstood and likely contains a highdegree of uncertainty.

This paper is based on a presentation at the Workshop on Model Validation Concepts and Their Application toLead Models held 21-23 October 1996 in Chapel Hill, North Carolina. Manuscript received at EHP 16 January1998; accepted 2 June 1998.

This study was funded by U.S. EPA Cooperative Agreement CR822793010 and Purchase Order8D137ONAEX, and National Institutes of Health grant RR00645. The authors thank the nurses and personnel ofthe Outpatient Clinic, Inpatient Unit, and the Nutrition Unit of the Irving Center for Clinical Research, ColumbiaPresbyterian Medical Center, New York, NY.

Address correspondence to J.H. Graziano, Columbia School of Public Health, Division of EnvironmentalHealth Sciences, 60 Haven Avenue B-1, New York, NY 10032. Telephone: (212) 305-1678. Fax: (212) 305-3857.E-mail: jg24@columbia.edu

Abbreviations used: CPMC, Columbia Presbyterian Medical Center; ICCR, (Columbia Presbyterian) IrvingCenter for Clinical Research; IEUBK, integrated exposure uptake biokinetic model for lead in children; PbB,blood lead; U.S. EPA, U.S. Environmental Protection Agency.

In the past, investigators have employedanimal models to study the bioavailability ofPb in soil (7,8). These studies, however,have primarily focused on predictingbioavailability in children rather than inadults. For example, using immature swineas a surrogate for young children, Casteelet al. (7) conducted a bioavailability studyof soils from the Smuggler MountainSuperfund site in Aspen, Colorado. Twosoils were tested at three different doses andwere administered in daily feed material for15 days. The average absolute bioavailabilityin all six test groups was 28%. Employing arat model, Freeman et al. (8) studied thebioavailability of Pb-contaminated miningwaste from the Butte, Montana, Superfundsite. Soils with high (3908 ppm) and low(810 ppm) Pb concentrations were mixedwith varying amounts of feed material tomimic the soil ingestion pattern of childrenwith pica. Relative bioavailability was meas-ured against a Pb acetate standard that wasadded as a solution to the feed material. Thedietary feeding study was conducted over 39days. Analysis of blood Pb (PbB) datayielded a relative bioavailability of20%.

Until now, however, there have been nocontrolled studies assessing the bioavailabil-ity of soilborne Pb in humans. Past humandietary studies employing solubilized Pb inan aqueous vehicle (9-11) may providesome insight regarding the extent of Pbabsorption from soil. However, the Pb/soilmatrix is believed to influence absorptionthrough factors such as Pb speciation, parti-cle size distribution, and organic/mineralcontent of the soil (12). Steele et al. (12)and Mushak (13) have reviewed the influ-ence of soil characteristics on Pb absorptionusing epidemiologic studies, in vitro tests,and animal bioassays. For example, particlesize affects both the dissolution of Pb in invitro systems (14) and the bioavailability ofPb in animal models (15). The dissolutionrate of Pb is proportional to the Pb-bearingsurface area. As particle size decreases, thereis a corresponding increase in surface areaper unit weight of material.

Medlin (14) developed a method forestimating the bioavailability of soilbornePb through use of an in vitro test for meas-uring the dissolution of Pb from variousPb-bearing minerals. Among six mineralsstudied (galena [PbS], slag, cerussite,pyromorphite, Pb oxide, and anglesite[PbSO4]), an average 5-fold increase insolubility occurred when the <38-pparticle size was compared to the 150- to

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250-p size range. Barltrop and Meek (15)observed a nonlinear inverse relationshipbetween particle size and PbB when ratswere administered metallic Pb particlesranging in size from 5 to 200 p in theirdiet over a 48-hr period.

The chemical species of Pb influences itssolubility. Ruby et al. (16) have demon-strated a direct relationship between Pb sol-ubility, as measured by a physiologicallybased extraction test and bioavailability inanimal models. Additional evidence of theimpact of speciation on bioavailability canbe illustrated by the relationship betweensoil Pb concentration and PbB in communi-ties impacted by either smelting or miningwaste. Pb associated with mining waste con-sists primarily of PbS altered to PbSO4 inthe surficial waste piles, whereas the preva-lent forms of Pb at smelter sites are the moresoluble oxides (lead monoxide [PbO] andlead dioxide [PbO9]) (17). Steele et al. (12)reviewed epidemiologic studies that relatedPbB to soil Pb concentration (i.e., slopestudies) and derived an average slope of 1.7pg/dl PbB per 1000 ppm Pb in soil frommining-impacted soilborne Pb, as opposedto 4.6 pg/dl PbB per 1000 ppm Pb in soilfrom smelting-impacted waste.

In addition, Pb uptake in the gastro-intestinal tract is affected by the presence ofsuch nutrients as calcium, iron, phosphate,vitamin D, fats, and fiber, as they occurwith meals or snacks. In adults, it is wellknown that Pb uptake is markedly lowerwhen ingested with meals than under

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fasting conditions (9-11). Human data, inthe aggregate, indicate that calcium, iron,and other cations interact stronglv as com-petitors of Pb uptake so that Pb absorptionigenerally increases as dietary levels of thesenutrients decrease (13, 18).

This study is the first of its kind todirectly measure the absorption of soil-borne Pb in humans. It included extensivecharacterization of soil matrix factors thatimpact bioavailability. The results of thisstudy are intended to improve biokineticmodeling of soilborne Pb hazards at sites(i.e., indtistrial) in which adults rather thanchildren are the primaiy targets of exposure.

Stable Isotope Dilution:Principles and ApplicationsLead has four stable isotopes, 04Pb, 2`6Pb,207Pb, and 208iPb, of which the last three arecontinually being produced by radioactivedecay. Thus, Pb in industrial use can varygreatly in its stable isotope ratios accordinigto the geologic age of the Pb deposit. Forexample, the ratio of 2tiGPb/ir)7Ib in theBroken Hill, Australia, Pb deposit is 1.03;in the younger U.S. deposits of theMississippi Valley it is as high as 1 .42 (19).

An individual's bodv buriden of I'bpossesses an isotopic fingerprint reflectingthe sources of Pb exposure in that person'senvironment. We previously reported fre-quency distributions of blood 20icPb/2(07IPbratios for huiman populations in threedifferent geographic locations; Americansubjects had higher 206Pb/2017Pb ratios than

14

12

10

4

1.09 1.1.05 1.15 1 .125 1.135 1.145 1.155. 1.1655

Lead isotope rati midpoint

90 Soil sampleM Subject

.:1 1.1-5. 1.1- 6t.175 1.185 1.19G 1.205 1.215

Figure 1. Frequency distribution of 206Ph/207Pb isotope ratios in normal volunteers recruited for this study comparedto the 2ttPh/207Pb isotope ratio of the Bunker Hill soil sample.

subjects from Australia or Scotland (20).The sensitivity of the stable isotope dilu-tion technique as an analytical tool tostudy bioavailability is driven by the differ-ence between the blood 2()6Pb/20i7Pbisotopic ratio and that of the exogenous Pbsource (i.e., in this case, soil) (Figure 1).

Soil samples from U.S. EPA Superfundsites arotind the United States wereobtained to find a soil that contained a2`J6Pb/2ii7Pb isotopic ratio strikingly differ-ent from the blood 20i6Pb/207Pb isotopicratios previously established for Americansubjects in New York. Soil 2t)6Pb/2(T7Pbratios ranged from a low of 1.057 atBunker Hill, Idaho, to a high of 1.253 atTriumph, Idaho (Table 1). Sample calcula-tions were performed to test analytical sen-sitivity by matching soils with low'()Pb/2iiTPb ratios to American subjects,anid soils with high 20)6Pb/207Pb ratios toScottish and Australian subjects. Thus, weestimated that if American subjects withblood 20)6Pb/207Pb ratios > 1.190 were toingest soil (250 pg Pb/70 kg bw) fromBunker Hill, we would be able to preciselyestimate bioavailability even if it wereextraordinarily low.

Preparation andCharacterization of theBunker Hill Soil SampleA 2.5-kg surface soil sample was obtainedfrom a residential yard at the Bunker HillSuperfund site. Historical informationindicated that mine tailings had been uti-lized extensively as fill material in this area(21). After mixing, a subsample wasscreened for priority pollutants by the U.S.EPA Region II's Edison, New Jersey, labo-ratory (22). Lead and arsenic were the onlycontaminants found above trace or non-detectable levels. At 34 ppm, the calculateddose of arsenic to be administered in thisstudy (approximately 3 pg) would be wellbelow the 340 pg typically found in 8 oz oflobster meat (23). In contrast, the concen-tration of Pb in the gross soil sample was2240 ppm.

Soil drying was accomplished by airdrying in a filtered incubator at room tem-perature for 8 days. The soil contained

Table 1. Lead isotope ratios from various sites.

Location Superfund site 206Pb/207PbBunker Hill, Idaho Bunker Hill 1.057Butte, Montana Silver Bow Creek 1.148Leadville, Colorado California Gulch 1.170Buffalo, New York Bern Metal 1.205Triumph, Idaho Triumph Mine 1.253

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BIOAVAILABILITY OF SOILBORNE LEAD IN ADULTS

2.4% residual moisture. The soil was thenmanually sieved through a 250-pm mesh;the yield was 24% by weight. Relative to thebulk soil sample, the concentration of Pb inthe sieved fraction increased from 2240 to2924 ppm. The resultant sieved soil fractionwas then sterilized by y irradiation (MedicalSterilization Inc., Syosset, NY).

Ten replicate soil samples were analyzedfor Pb concentration and 206Pb/207Pb ratio.Soil Pb was extracted by leaching in hotconcentrated nitric acid for 8 hr. Themean ± SD Pb concentration was 2924 ± 36ppm and the mean ± SD 206Pb/207Pb ratiowas 1.1083 ± 0.0002, indicating remarkablesoil homogeneity (Table 2).

Duplicate samples of the sterilizedmaterial were characterized for Pb specia-tion and particle size distribution. A 10-galiquot of the soil was divided in two andparticle mineralogy was identified using anelectron microprobe, according to themethod of Davis et al. (24).

Particle size distribution was determinedusing an electrozone sensor in an Elzone 280PC System (Particle Data Laboratories,Elmhurst, IL). The particle size distributionindicated that 79.5% of the particles were< 20 pm (Figure 2). The Pb speciation pro-file was dissimilar between the split samples.Because the variability in the speciation pro-file was inconsistent with the homogeneitydemonstrated via Pb concentration, isotopicratio, and particle size distribution, a repeatPb speciation profile was performed. Therepeat analysis resulted in a more homoge-nous profile, suggesting a possible "nuggeteffect" in one of the original duplicatesamples. A nugget effect occurs when a parti-de with a heavily concentrated predominantPb form skews the species profile. In anycase, mean values from the four speciationprofiles are presented in Figure 3.

Clinical and LaboratoryMethodsThe soil ingestion study was approved bythe Columbia Presbyterian Medical Center(CPMC) Institutional Review Board andwritten informed consent was obtainedfrom all subjects. The subjects, healthyadults between 21 to 40 years of age, werescreened prior to study to assure that theyhad normal urinalyses, blood chemistries,blood counts, and physical exams, and thattheir PbB was <5 pg/dl and blood206Pb/207Pb ratio was > 1.190. All werewithin 10% of their ideal weight for heightbased on the Metropolitan Life tables.Subjects were admitted to the ColumbiaPresbyterian Irving Center for Clinical

Table 2. Soil homogeneity.

Sample no. Weight, g Lead, ppm 206Pb/207Pb1 0.1091 2858 1.10842 0.0968 2952 1.10823 0.0944 2928 1.10834 0.1037 2965 1.10835 0.0963 2931 1.10806 0.1003 2914 1.10847 0.0919 2912 1.10878 0.0988 2942 1.10819 0.0921 2967 1.1083

10 0.0988 2876 1.1084Mean SD 0.0982 ± 0.0053 2924 ± 36 1.1083 ± 0.0002

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Figure 2. Frequency distribution of the soil grain size in the Bunker Hill residential soil sample.

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Figure 3. Distribution of the lead speciation profile of the Bunker Hill soil sample. Values are the mean results offour separate analyses.

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Research (ICCR) on day 1 at 5:00 P.M.and remained in the ICCR for the dura-tion of the study (until 1:00 P.M. on day3). Following admission, they received aregular hospital dinner and then fastedovernight except for water. At 6:00, 6:30,and 7:00 A.M. on day 2, baseline PbB and206Pb/207Pb samples were taken. A baselineurine sample was also collected fromadmission until 7:00 A.M. on day 2.

Immediately following the 7:00 A.M.blood drawing on day 2, subjects ingestedsoil that contained 250 pg Pb/70 kg bw.This dose was chosen as the maximum dosethat could be safely administered with thefollowing safety considerations in mind. Anindividual weighing 70 kg has approximately5 liters of blood. A 70-kg subject with a PbBof 5 pg/dl (the maximum eligible PbB forthis study) would therefore have approxi-mately 250 pg Pb in the blood compart-ment. Even if Pb absorption was complete(i.e., bioavailability = 100%) and instanta-neous, this dose of Pb would increase thePbB from 5 to 10 pg/dl (the currentlyaccepted upper limit of normal PbB).

The soil was ingested in a No. 6gelatin capsule, with 240 cc of water.Blood and urine were collected over thenext 30 hr and analyzed for Pb and206Pb/207Pb ratio. Blood samples werecollected in Becton Dickinson trace ele-ment vacutainer tubes (Becton Dickinson,East Rutherford, NJ) with sodiumheparin. Urine samples were collected inacid-washed plastic bottles. All tubes andbottles were purchased in one lot prior tothe start of the study and were randomlysampled to check for contamination.

The concentration of Pb in soil was2924 ppm and in the fasted group (group

1) the mean subject weight was 59.7 kg,resulting in an average administered soildose of 72.9 mg (Table 3). In the non-fasted group (group 2), the mean subjectweight was 67.9 kg, resulting in an averagesoil dose of 82.9 mg.

On day 2, the subjects in group 1received no breakfast, a standardized liquidlunch at noon, and a standardized dinnerat 5:00 P.M. They received a standardizedbreakfast and lunch on day 3. The protocolwas identical for group 2, except that thisgroup received a standardized high-fatbreakfast at 6:45 A.M. on day 2 immedi-ately prior to the soil Pb administration.Breakfast consisted of 25 g of wheat cereal,130 g of whole milk, 1 large hard-boiledegg (approximately 48 g), 50 g of firmwhole wheat bread, 6 g of butter, 5 g ofjam/preservatives, and 6 g of white sugar.The total calories consumed with this mealwas 430, with 15% coming from protein,51% from carbohydrates, and 33% fromfat. The breakfast contained 255 mg of cal-cium and 418 mg of phosphorus. All mealswere prepared in duplicate and analyzedfor Pb content, which was unremarkable at< 0.5 ppm Pb dry weight.

The ratio of 206Pb/207Pb and total Pbcontent were simultaneously measured inthe blood. An appropriate quantity of 205Pbwas added as an internal standard to eachblood sample, which was then decomposedby boiling in concentrated HNO3. Thesolution was evaporated to dryness and theresidue charred at 250°C. Pb was thenextracted by anion exchange chromato-graphy and isotopically analyzed on aFinnigan MAT 261 multicollector massspectrometer (Finnigan Instruments,Bremen, Germany) (25). Pb blanks for the

method were consistently < 25 pg Pb. Theaccuracy of the spike calibration was verifiedby analysis of standard SRM 955a, Lead inBlood (National Institute of Standards andTechnology). Accuracy of the isotopicanalyses was monitored by analyzing SRM981, Common Pb. All other blood andurine analyses were performed by theCPMC clinical laboratories.

ResultsThe demographic characteristics of thestudy subjects are presented in Table 3.Prior to ingestion of the soil, the mean PbBin the fasted group was 1.59 pg/dl and themean 206Pb/207Pb ratio was 1.195. Thirtyhours after soil administration, the PbBrose to a mean value of 2.6 pg/dl (p= 0.02)and the 206Pb/207Pb ratio fell to a meanvalue of 1.166 (p = 0.0001). In contrast, thePbB in the fed group rose by only 0.3pg/dl, whereas the 206Pb/207Pb ratio fell byonly 0.004 These changes were essentiallycomplete by 24 hr. Typical absorptionprofiles from subjects in the fed and fastedgroups are presented in Figure 4A and B,respectively. The absorption profile pre-sented in Figure 4, for example, demon-strates the remarkable sensitivity of thestable isotope dilution technique. This sub-ject had both the lowest baseline PbB (0.7pg/dl) and the smallest increase in PbBamong fasted subjects (0.5 pg/dl) followingingestion of the soil, yet soil and nonsoil Pbsources could readily be distinguished.

On average, at 24 hr, we could accountfor 14.4% ± 4.5 of the administered Pbdose in the blood compartment of thefasted subjects. Bioavailability is tradition-ally estimated by comparing the kinetics ofan oral dose to those of an intravenous

Table 3. Subject demographics and study findings.

PbB, pg/dl 206Pb/207PbSubject Age, years Race Gender Weight, kg Pb dose, pg Soil dose, pg Start 24 hr Start 24 hr Bioavailability, %

Group 1, fasted 1 26 White F 56.5 202 69.0 1.94 3.34 1.193 1.165 35.62 27 Asian M 57.8 206 70.5 1.52 2.16 1.193 1.169 22.63 30 Hispanic F 53.2 190 65.0 2.04 2.81 1.191 1.173 19.04 24 Asian F 59.0 211 72.1 0.71 1.28 1.199 1.160 18.05 26 Hispanic F 65.5 234 80.0 1.57 2.82 1.194 1.158 36.66 33 Hispanic M 66.0 236 80.6 1.77 2.75 1.200 1.175 25.4

Mean 28 59.7 213 72.9 1.59* 2.53* 1.195** 1.167** 26.2Group 2, fed 7 28 Hispanic M 79.2 283 96.7 4.60 5.10 1.196 1.195 1.8

8 30 White M 78.5 280 95.9 2.12 2.37 1.201 1.195 5.29 26 White F 64.0 229 78.2 1.02 1.06 1.201 1.194 2.310 25 White F 60.2 215 73.6 2.55 2.59 1.186a 1.186 0.2a11 27 White F 63.5 227 77.6 1.22 1.31 1.190 1.185 2.312 29 White F 61.7 220 75.4 1.92 2.12 1.195 1.191 3.3

Mean 28 67.9 242 82.9 2.24 2.42 1.195 1.191 2.52Abbreviations: F, female; M, male. aThis subject's 206Pb/207Pb ratio dropped from 1.194 at the initial screening to 1.186 just prior to administration of the soil capsule. Thecause of this change is unknown but likely had an effect on this value. When this value is deleted, the mean bioavailability in group 2 is 2.98%. *p= 0.0268; **p= 0.0001.

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BIOAVAILABILITY OF SOILBORNE LEAD IN ADULTS

A B1.4 -*1.2-

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Figure 4. Change in blood lead concentration after ingestion of a soil containing 250 pg Pb/70 kg bw in a fasted (A) and a nonfasted (B) subject. , total blood lead concen-tration. By the technique of stable isotope dilution, we were able to differentiate the relative contribution of soil lead (e) and endogenous lead (o) to total lead.

dose. Previous studies of intravenous 203Pb(26-28) indicate that at 24 hr, 55% of anadministered dose is still in the blood com-partment. In this manner, we estimated themean fraction of Pb absorbed from the soilsample to be 26.2% ± 8.1, with a range of18.0 to 36.6%. In the six fed subjects,1.4% ± 0.9 of the administered Pb dose waspresent in the blood compartment at 24hr. Consequently, the estimated mean frac-tion of Pb absorbed in this group is2.52% ± 1.7 (range 0.2-5.2%).

DiscussionThe hazard posed by Pb-contaminated soilshas and continues to be of great interest toorganizations, such as the U.S. EPA, withpublic health and regulatory mandates. Theintent of this research project is to provideexperimental data that will better enable theU.S. EPA and similar agencies to assess andregulate the widespread soilborne Pb conta-mination in nonresidential areas throughoutthe United States.

Biokinetic models that assess the impactof Pb-contaminated soil have had toestimate the bioavailability of soilborne Pbby extrapolating from dietary exposurestudies in humans and/or soil-feedingstudies in animals. The strength of thecurrent study is that it directly examineshuman Pb bioavailability in a contaminatedsoil sample obtained from a hazardouswaste site. In addition, the soil samplecontains a Pb concentration (2924 ppm)that is commonly encountered at sitesundergoing remedial investigation, and theamount of soil administered (72.9 and 82.9mg) approximates the range estimated[20-80 mg (29)] for normal daily soilingestion by adults.

Although the study design strived tomimic an actual exposure scenario, it isunlikely that the daily soil ingested by anadult occurs as a bolus. Estimates of inci-dental daily soil ingestion in adults, thoughpoorly defined, are associated withmouthing activities. The repetitive nature ofthese activities (e.g., smoking, eating, etc.)leads to soil ingestion throughout the day.Ideally, experimental soil administrationshould occur in a pattern that simulates real-life exposure; however, practical considera-tions make this an extraordinarily difficulttask. Therefore, as a concession to practical-ity, we administered the soil as a bolus andrecognized the possible limitations of thisdosing regimen. However, the compara-tively small tracer dose of Pb administered,even as a bolus, seems unlikely to result insaturable kinetics (8,30).

The lack of speciation homogeneitybetween duplicate soil samples raised aconcern regarding the results of the soilbioavailability study. Possible differences inthe Pb speciation profile across the adminis-tered soil samples introduces the possibilitythat the variance in absorption fractionwithin each of the test groups could haveincluded variance due to Pb speciationrather than simply variance due tointerindividual variability. Also, a lack ofhomogeneity in soil Pb speciation reducesthe confidence in projecting the results ofthe soil bioavailability study as beingrepresentative of a particular profile of phy-sicochemical soil/Pb characteristics.Nevertheless, this type of microhetero-geneity in speciation likely occurs at manysites around the world.

Various investigators (9-11) havedemonstrated absorption in the range of

30 to 70% when solubilized Pb wasadministered to fasted subjects. Thesesame investigators (9-11) demonstratedsignificantly reduced absorption (range3.5-9%) when solubilized Pb was admin-istered with a meal. The results of our soilbioavailability study are consistent withthat trend, in that absorption was approx-imately an order of magnitude different(2.5% vs 26.1%) between the fasted andfed states, respectively.

In conclusion, we believe that thisexperimental model provides importantnew information that supplements thatobtained from observational epidemiologicstudies of soil Pb/PbB relationships. Thegeneralizability of these findings to othersoils or to remediated sites is not knownbut can be determined experimentallyusing this in vivo model.

REFERENCES AND NOTES

1. U.S. EPA. Guidance Manual for theIntegrated Exposure Uptake BiokineticModel for Lead in Children. EPA540/R-93/081. Washington:U.S. Envi-ronmental Protection Agency, 1994.

2. Unpublished recommendations ofthe U.S. EPA Technical ReviewWorkgroup for Lead for an InterimApproach to Assessing Risks Associatedwith Adult Exposures to Lead in Soil.Technical Review Workgroup for Lead,1996.

3. O'Flaherty EJ. Physiologically basedmodels for bone-seeking elements. IV:Kinetics of lead deposition in humans.Toxicol Appl Pharmacol 118:16-29(1993).

4. Leggett RW. An agc-specific kineticmodel of lead meta olism in humans.

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Environ Health Perspect 101:598-616 (1993).5. Bowers TS, Beck BD, Karam HS. Assessing the relationship

between environmental lead concentration and adult bloodlead levels. Risk Anal 14:183-189 (1993).

6. Unpublished U.S. EPA Review of a Methodology forEstablishing Risk-Based Soil Remediation Goals forCommercial Areas of the California Gulch Site. TechnicalReview Workgroup for Lead, 1995.

7. Casteel SW, Cowart RP, Weis CP, Henningsen GM, HoffmanE, Brattin WJ, Guzman RE, Starost MF, Payne JT, StockhamSL, et al. Bioavailability of lead to juvenile swine dosed withsoil from the Smuggler Mountain NPL Site of Aspen,Colorado. Fundam Appl Toxicol 36:177-187 (1997).

8. Freeman GB, Johnson JD, Killinger SC, Liao, SC, Feder PI,Davis AO, Ruby MV, Chaney RL, Lovre SC, Bergstrom PD.Relative bioavailability of lead from mining waste soil in rats.Fundam Appl Toxicol 19:388-398 (1992).

9. James HM, Hilburn JA, Blair JA. Effects of meals and mealtimes on uptake of lead from the gastrointestinal tract inhumans. Hum Toxicol 4:401-407 (1985).

10. Rabinowitz MB, Kopple JD, Wetherill GW. Effect of foodintake and fasting on gastrointestinal lead absorption inhumans. Am J Clin Nutr 33:1784-1788 (1980).

11. Blake KHC, Barbezat GO, Mann M. Effect of dietary con-stituents on the gastrointestinal absorption of 203Pb in man.Environ Res 30:182-187 (1983).

12. Steele MJ, Beck BD, Murphy BL. Assessing the contributionfrom lead in mining waste to blood lead. Regul ToxicolPharmacol 11:158-190 (1990).

13. Mushak P. Gastro-intestinal absorption of lead in children andadults: overview of biological and biophysico-chemical aspects.Chem Speciat Bioavailab 3:87-104 (1991).

14. Medlin EA. An in vitro method for estimating the relativebioavailability of lead in humans. Master's Thesis. Boulder,CO:University of Colorado at Boulder, 1997.

15. Barltrop D, Meek F. Effect of particle size on lead absorptionin the gut. Arch Environ Health 34:280-285 (1979).

16. Ruby MV, Davis A, Schoof R, Eberle S, Sellstone C. Estimationof lead and arsenic bioavailability using a physiologically basedextraction test. Environ Sci Technol 30:422-430 (1996).

17. Foster RL, Lott PF. X-ray diffractometry examination of air

filters for compounds emitted by lead smelting operations.Environ Sci Technol 14:1240-1244 (1980).

18. U.S. EPA Air Quality Criteria for Lead. EPA 60018-83-028ad.Research Triangle Park, NC;U.S. Environmental ProtectionAgency 1986.

19 Chow TJ, Earl JL. Lead aerosols in the atmosphere: increasingconcentrations. Science 169:577-580 (1970).

20. Graziano JH, Blum CB, Lolacono NJ, Slavkovich V, MantonWI, Pond S, Moore MR. A human in vivo model for the deter-mination of lead bioavailability, using stable isotope dilution.Environ Health Perspect 104:176-179 (1996).

21. Unpublished U.S. EPA Risk Assessment Data EvaluationReport for the Populated Areas of the Bunker Hill SuperfundSite, 1990.

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1594 Environmental Health Perspectives * Vol 106, Supplement 6 * December 1998